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

ALLERGENS A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

ii

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., 1960Allergens: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-497-00045-8 1. Allergens-Popular works. I. Title.

iii

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.

iv

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 allergens. 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.

v

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.

vi

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

vii

Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON ALLERGENS ............................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Allergens ..................................................................................... 11 E-Journals: PubMed Central ....................................................................................................... 69 The National Library of Medicine: PubMed ................................................................................ 71 CHAPTER 2. NUTRITION AND ALLERGENS ................................................................................... 117 Overview.................................................................................................................................... 117 Finding Nutrition Studies on Allergens.................................................................................... 117 Federal Resources on Nutrition ................................................................................................. 119 Additional Web Resources ......................................................................................................... 120 CHAPTER 3. ALTERNATIVE MEDICINE AND ALLERGENS ............................................................. 123 Overview.................................................................................................................................... 123 National Center for Complementary and Alternative Medicine................................................ 123 Additional Web Resources ......................................................................................................... 131 General References ..................................................................................................................... 138 CHAPTER 4. DISSERTATIONS ON ALLERGENS ............................................................................... 139 Overview.................................................................................................................................... 139 Dissertations on Allergens......................................................................................................... 139 Keeping Current ........................................................................................................................ 140 CHAPTER 5. PATENTS ON ALLERGENS ......................................................................................... 141 Overview.................................................................................................................................... 141 Patents on Allergens .................................................................................................................. 141 Patent Applications on Allergens .............................................................................................. 166 Keeping Current ........................................................................................................................ 196 CHAPTER 6. BOOKS ON ALLERGENS ............................................................................................. 199 Overview.................................................................................................................................... 199 Book Summaries: Federal Agencies............................................................................................ 199 Book Summaries: Online Booksellers......................................................................................... 200 Chapters on Allergens................................................................................................................ 201 CHAPTER 7. PERIODICALS AND NEWS ON ALLERGENS ............................................................... 207 Overview.................................................................................................................................... 207 News Services and Press Releases.............................................................................................. 207 Newsletter Articles .................................................................................................................... 209 Academic Periodicals covering Allergens .................................................................................. 212 CHAPTER 8. RESEARCHING MEDICATIONS .................................................................................. 213 Overview.................................................................................................................................... 213 U.S. Pharmacopeia..................................................................................................................... 213 Commercial Databases ............................................................................................................... 214 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 219 Overview.................................................................................................................................... 219 NIH Guidelines.......................................................................................................................... 219 NIH Databases........................................................................................................................... 221 Other Commercial Databases..................................................................................................... 223 APPENDIX B. PATIENT RESOURCES ............................................................................................... 225 Overview.................................................................................................................................... 225 Patient Guideline Sources.......................................................................................................... 225 Finding Associations.................................................................................................................. 232 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 235 Overview.................................................................................................................................... 235

viii Contents

Preparation................................................................................................................................. 235 Finding a Local Medical Library................................................................................................ 235 Medical Libraries in the U.S. and Canada ................................................................................. 235 ONLINE GLOSSARIES................................................................................................................ 241 Online Dictionary Directories ................................................................................................... 242 ALLERGENS DICTIONARY....................................................................................................... 243 INDEX .............................................................................................................................................. 319

1

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 allergens 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 allergens, 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 allergens, 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 allergens. 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 allergens, 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 allergens. The Editors

1

From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

3

CHAPTER 1. STUDIES ON ALLERGENS Overview In this chapter, we will show you how to locate peer-reviewed references and studies on allergens.

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

Allergic Contact Dermatitis in Dental Professionals: Effective Diagnosis and Treatment Source: JADA. Journal of the American Dental Association. 134(2): 185-194. February 2003. Contact: Available from American Dental Association. ADA Publishing Co, Inc., 211 East Chicago Avenue, Chicago, IL 60611. (312) 440-2867. Website: www.ada.org. Summary: Dental professionals are at risk of developing allergic contact dermatitis (ACD) after exposure to allergenic chemicals. Common allergens include antimicrobials, preservatives, rubber additives, and methacrylates. In this article, the authors describe an orthodontic assistant with severe skin disease, whose symptoms included redness, cracking and bleeding that persisted for 10 years. The patient had

4

Allergens

previously received an incomplete diagnosis. After performing patch testing, assessing symptoms, and evaluating the patient's medical history, the authors diagnosed ACD resulting from exposure to several dental allergens. The patient received appropriate treatment and counseling to better manage her allergies; this resulted in resolution of all symptoms and averted permanent occupational disability. The authors conclude that not all skin reactions are related to gloves or natural rubber latex. Dental professionals should be aware of common chemical allergens, symptoms of ACD, and the appropriate treatment of occupational skin disease. 3 figures. 3 tables. 26 references. •

Forbidden Foods Source: Digestive Health and Nutrition. p. 16-19. January-February 2000. Contact: Available from American Gastroenterological Association. 7910 Woodmont Avenue, 7th Floor, Bethesda, MD 20814. (877) DHN-4YOU or (301) 654-2055, ext. 650. Email: [email protected]. Summary: For the 5.2 million Americans suffering from food allergies, one wrong food choice could trigger a host of reactions ranging from abdominal cramps to hives and swelling and, in extreme cases, even death. This article reviews the problem of food allergies, first defining the differences between food allergy and food intolerance. A true food allergy triggers the immune system; with food intolerances, the problem arises from the metabolism (the body may not be able to adequately digest some components of the foods). For example, people with lactose intolerance have trouble digesting lactose (the sugar in milk) and therefore may have cramping and diarrhea after drinking or eating dairy products. Whereas people with food allergies must totally avoid certain foods, those with intolerances can sometimes eat small quantities of offending foods without any side effects. Food allergies are classically diagnosed with a thorough health history; sometimes a food diary is also used. The next step is to institute a diet that eliminates suspected allergens. Only a few foods account for most allergic reactions (soy products, fish, shellfish, nuts, eggs). The author considers the role of food additives (aspartame, MSG, sulfites, food coloring) as possible food allergens. Food labeling requirements make it easier to readily identify offending ingredients. The author also reviews the difficulties inherent in eating at restaurants, the problems of cross reactivity (being sensitive to foods similar to the primary offending food), and exercise induced food allergies (probably triggered by the rise in body temperature that accompanies exercise). A brief concluding section discusses what to do for food allergy reactions. An information resource noted is the Food Allergy Network (800 929 4040, www.foodallergy.org).

•

What to Do About Pruritus Scroti Source: Postgraduate Medicine. 88(6): 95-96, 99, 100. November 1, 1990. Summary: Pruritis scroti is a common clinical disorder with many causes. It has received little attention in the literature compared with its counterpart in women, pruritis vulvae. This article reviews the various causes of pruritis scroti and discusses diagnostic techniques and therapy. Causes of the condition discussed include various inflammatory disorders, infections, infestations, and neoplasms. The author notes that laboratory evaluation, including bacterial and fungal cultures, microscopic examination, skin biopsies, and measurement of blood glucose levels, is useful in establishing the diagnosis. Management of pruritis scroti includes avoidance of irritants, allergens, and restrictive clothing, and use of topical and systemic agents that provide both symptomatic relief and specific treatment of the underlying cause. 10 figures. (AA-M).

Studies

•

5

Burning Mouth Syndrome: A Possible Etiologic Role for Local Contact Hypersensitivity Source: Journal of the American Academy of Dermatology. 26(6): 935-940. June 1992. Summary: The pathogenesis of burning mouth syndrome (BMS) is not yet understood. This article reports on a study of 22 patients (19 women, 3 men) classified with BMS, in which clinical and laboratory investigations were performed with particular emphasis on the role of contact hypersensitivity. Twenty of the 22 patients wore a complete or partial denture. Folate, iron, pyridoxine deficiency, and Candida infections were found, but correction of the deficiency or treatment of the infections were of no benefit. Contact allergy to allergens used in the production of acrylate-based dentures was observed in six (27 percent) of the cases. In six cases (27 percent), a possible relevant sensitization was seen to dental metals and, in particular, to gold chloride (four cases). The authors conclude that the possible role of local hypersensitivity reactions to denture or dental components must be considered as etiologic factors in BMS. 1 figure. 2 tables. 33 references. (AA-M).

•

Dental Metal Allergy in Patients with Oral, Cutaneous, and Genital Lichenoid Reactions Source: American Journal of Contact Dermatitis. 12(3): 146-150. September 2001. Contact: Available from American Journal of Contact Dermatitis. W.B. Saunders Company, Periodicals Department, P.O. Box 628239, Orlando, FL 32862-8239. (800) 6542452. Summary: The subject of lichen planus (LP) and dental metal allergy has long been debated. An overwhelming majority of the existing literature focuses on mercury and gold salts in relation to oral lichen planus. This article reports on a study undertaken to expand current knowledge regarding LP and lichenoid lesions (LL) and dental metal allergy by investigating more metals and investigating cutaneous (skin) and genital disease in addition to oral disease. The study included 51 patients with known LP or LL who were patch tested to a series of dental metals. Patients chose to replace their dental metals or make no revision. A telephone survey was conducted after 1 year to determine disease state. The results showed that 38 of 51 patients (74.5 percent) had at least 1 positive reaction; 25 of 51 patients (49 percent) showed sensitivity to at least 1 mercurial allergen. Prevalence data for patients patch tested by the North American Contact Dermatitis Group (NACDG) from 1996 to 1998 was available for chromate, cobalt, gold, nickel, and thimerosal. The prevalence of positive reactions was higher in this study group than in the NSCDG group for all 5 of these allergens; statistical significant was achieved for chromate, gold, and thimerosal. Of patients who had a positive patch test reaction to 1 or more metals, 100 percent (9 of 9 patients) reported improvement after metal replacement, whereas 62.5 percent (15 of 24 ) reported improvement without metal replacement. The authors conclude that sensitization to dental metals is more common among LP and LL patients than in routinely tested patients, and might be an etiologic or triggering factor in the disease. 2 figures. 4 tables. 25 references.

•

Allergies and Vocal Fold Edema: A Preliminary Report Source: Journal of Voice. 13(1): 113-122. March 1999. Contact: Available from Singular Publishing Group, Inc. 401 West 'A' Street, Suite 325, San Diego, CA 92101-7904. (800) 521-8545 or (619) 238-6777. Fax (800) 774-8398 or (619) 238-6789. E-mail: [email protected]. Website: www.singpub.com.

6

Allergens

Summary: This article describes different tools that can be used to determine the etiology of vocal fold edema. The authors report on the complete voice assessment that is used in their Voice Center. This includes patient history, acoustic analysis, laryngeal videostroboscopy, otolaryngology consultation, allergy testing (from a companion Allergy Clinic), and gastroenterology consultation as appropriate. Inhalant allergy can be a hidden, yet very common cause of chronic laryngitis. Respiratory allergies can also cause decreased pulmonary function; excessive secretions in either the lower airway, trachea, bronchi, or in the upper airway of the pharynx; edema of the vocal folds themselves; and unusual resonance characteristics of the pharynx or nasal cavity due to congestion of the membrane in those areas. Voice patients with a history of seasonal hay fever, a history of allergic reactions around cats or dogs, or a strong family history of allergies should be allergy tested. Screening tests for allergies are available. Once specific allergens are identified, recommendations for therapy or other intervention can be made. Straining the voice, in combination with the above conditions, can increase the voice problem. The authors describe the histories, allergy test results, and voice laboratory evaluations of several patients. Identifying these voice patients and treating their allergies are important in keeping these patients healthy and maintaining a clear, good voice quality. The authors conclude that the multidisciplinary approach in voice disorders is indispensable in diagnosis and treatment of these disorders. •

Emergency Medicine: Beyond the Basics Source: JADA. Journal of American Dental Association. 128(7): 843-854. July 1997. Summary: This article describes the appropriate management of two common emergency situations that may arise in the dental office: allergy and chest pain. The author stresses that preparedness for medical emergencies depends on the ability to rapidly recognize a problem and to effectively institute prompt and proper management. In all emergency situations, management is based on implementation of basic life support, as needed. The author begins with an overview of general emergency preparedness, including an outline of the roles of the emergency team and emergency drugs and equipment to have available. The author then addresses allergic reactions, including delayed reactions (localized and systemic) and emergency reactions that can include anaphylaxis, which is immediately life-threatening. The next section reviews in detail the in-office management of a patient with chest pain. Charts outline common allergens in dentistry, chemical mediators of allergy, the usual progression of anaphylaxis, dosages of injectable emergency drugs, cardiac versus noncardiac chest pain, the etiology of acute anginal episodes, and patient activity at the onset of clinical signs of myocardial infarction. The author concludes that both allergy and chest pain, though usually readily recognized and easily managed without significant sequelae, may prove to be situations that can lead to morbidity or even death. 1 figure. 6 tables. 27 references. (AA-M).

•

Sleep Apnea in End Stage Renal Disease Source: ANNA Journal. American Nephrology Nurses Association Journal. 24(6): 645654. December 1997. Contact: Available from American Nephrology Nurses Association. Box 56, East Holly Avenue, Pitman, NJ 08071. (609) 256-2320. Summary: This article familiarizes nephrology nurses with the sleep apnea syndrome, a disorder that is characterized by repetitive episodes of the cessation of breathing (apneas) or diminished airflow (hypopneas) that occur during sleep, and is usually,

Studies

7

although not always, associated with a reduction in the oxygen saturation of the blood. The author reviews risk factors, clinical features, diagnostic strategies, and treatments. The author also discusses recent research linking sleep apnea with end-stage renal disease (ESRD). In diagnosing sleep apnea syndrome, the total number of apneas and hypopneas that occur during a sleep period are usually added together and then divided by the number of hours spent sleeping to obtain a respiratory disturbance index (RDI). While disrupted sleep and daytime sleepiness are significant problems, cardiopulmonary abnormalities are also important complications associated with sleep apnea. Risk factors for sleep apnea include obesity, craniofacial abnormalities, male gender, certain medical illnesses, lifestyle factors (use of alcohol and central nervous system depressants, smoking, exposure to allergens), and cardiovascular diseases. The author reviews nine studies of ESRD and sleep apnea, all of which demonstrated that sleep apnea has a prominent presence in ESRD, that both hemodialysis and peritoneal dialysis patients are vulnerable to it, and that dialysis itself seems to have little effect on its clinical expression. These studies showed that the incidence of sleep apnea is most likely much higher in this group than in the general population, but they did not succeed in determining the exact prevalence of sleep apnea in chronic renal failure because of subject selection bias and small sample sizes. The author concludes that patients with ESRD who have symptoms related to sleep-wake problems should be evaluated. Treatment of a sleeping disorder thus revealed is likely to have a drastic impact on the quality of life experienced by these patients. 4 figures. 2 tables. 26 references. (AA-M). •

Allergic Management of Meniere's Disease: An Outcome Study Source: Otolaryngology-Head and Neck Surgery. 122(2): 174-182. February 2000. Contact: Available from Mosby-Year Book, Inc. Subscription Services, 11830 Westline Industrial Drive, St. Louis, MO 63146-3318. (800) 453-4351 or (314) 453-4351. Fax (314) 432-1158. E-mail: [email protected]. Summary: This article reports on a study in which the effect of allergy immunotherapy and elimination of suspected food allergens was evaluated in patients with Meniere's disease. A total of 137 patients with Meniere's disease for whom allergy treatment had been recommended were identified and were mailed and returned a symptoms questionnaire. One hundred thirteen had received allergy treatment; 24 did not have treatment and served as a control group. Information regarding history, signs and symptoms, allergy test results, and audiologic data were obtained by chart review. The 113 patients treated with desensitization and diet showed a significant improvement from pretreatment to posttreatment in both allergy and Meniere's symptoms. Ratings of frequency, severity, and interference with everyday activities of their Meniere's symptoms also appeared better after allergy treatment (compared to controls). Hearing was stable or improved in 61.4 percent. The author concludes that patients with Meniere's disease can show improvement in their symptoms of tinnitus and vertigo when receiving specific allergy therapy. The inner ear may be the target, directly or indirectly, of an allergic reaction. 4 figures. 4 tables. 26 references.

•

Food Allergies Source: Nutrition Action Healthletter. 28(3): 10-13. April 2001. Contact: Available from CSPI. 1875 Connecticut Avenue, NW, Suite 300, Washington, DC 20009. Fax (202) 265-4954. E-mail: [email protected]. Website: www.cspinet.org.

8

Allergens

Summary: This article reviews food allergies and food intolerances. Food allergies occur when the immune system overreacts to certain proteins in food. Although more than 200 food ingredients can provoke an allergic reaction, the vast majority are caused by eight ingredients: nuts (like walnuts and almonds), peanuts (which are legumes), milk, eggs, fish, shellfish, soybeans, and wheat. Typical symptoms are nausea, hives, skin rash, nasal congestion, and wheezing. For most people with food allergies, allergic reactions to food are a temporary discomfort, but for many the result is anaphylactic shock, a quick reaction in which their throats may swell enough to cut off breathing. The author reviews the typical pattern of a study of 32 fatal reactions; all but two reactions were triggered by peanuts or nuts. Most of the victims were teenagers or young adults who had asthma, and most knew that they suffered from food allergies; 27 ate the food away from home, and only three were carrying emergency self injectable epinephrine. Most reactions to food are caused not by allergies but by intolerances, which are less severe. The author reviews intolerances to lactose (milk sugar), sulfites, monosodium glutamate (MSG), red wine, chocolate, and food colors. The article concludes with a discussion of four reminders regarding food allergies: offending foods may show up where they are not expected; trace amounts can trigger a reaction; foods can be contaminated with allergens; and labels do not have to disclose allergens in flavors. Appended to the article is a list of websites and resource organizations for readers wishing to obtain additional information. 1 figure. 6 references. •

Latex Allergy: Everyone's Concern Source: Journal of the Michigan Dental Association. 80(5): 30-42. June 1998. Contact: Available from Michigan Dental Association. 230 North Washington Square, Suite 208, Lansing, MI 48933-1392. (517) 372-9070. E-mail: [email protected]. Summary: This article reviews the problem of latex allergy, particularly in the health care setting. The author emphasizes that all health care professionals need to know about latex allergy, the potential hazards it poses, and how to manage it effectively if encountered. The article begins with a series of questions to elicit information from the patient about potential latex allergy; the author notes that merely asking if the person is allergy to latex is not sufficient. The author then briefly considers the many theories that have been posed to explain the increasing prevalence of latex allergies. The main theory states that the cause is increased exposure to latex gloves, due to the increased demand for personal protection in response to the AIDS crisis. Other topics include the types of latex reactions, including irritant contact dermatitis, delayed hypersensitivity, and immediate hypersensitivity; risk factors; latex allergens and diagnosis; how to treat the latex allergic patients; consumer products that often contain latex; items used in dentistry that may contain latex; treating the latex-allergic dental worker; proper hand care; glove selection; and potential legislation, Federal guidelines, and research in this area. One chart summarizes reactions to natural rubber latex, including the cause, intervention strategies, percentage of population affected (prevalence), time to onset of symptoms, potential for respiratory involvement, facial involvement, systemic involvement, and recommended action. 3 tables. 34 references.

•

When Your Food Bites Back: Food Allergies and Intolerances Source: Diabetes Self-Management. 16(4): 106, 108, 110, 112. July-August 1999. Contact: Available from R.A. Rapaport Publishing, Inc. 150 West 22nd Street, New York, NY 10011. (800) 234-0923.

Studies

9

Summary: This article, written for people who have diabetes, describes food allergies and intolerances. The author notes that the obvious treatment for food allergies and sensitivities is to avoid the food in question. However, eliminating a food or entire group of foods from one's diet without making appropriate dietary substitutions can create nutrient or calorie imbalances or deficits. A food allergy, also known as a food hypersensitivity, is a reaction by the immune system to a substance that is generally regarded as harmless. Symptoms of a food allergy often involve the skin, respiratory system, and intestinal tract. A food intolerance, in comparison, does not involve the immune system. Food intolerance is generally described as a metabolic disorder in which the body has difficulty digesting or tolerating a certain food or food group. The physical symptoms of food intolerance usually involve the gastrointestinal tract and may include abdominal pain or diarrhea. There is no evidence to suggest that people with diabetes have a higher incidence of food allergy than the general population, although people with type 1 diabetes are at greater risk for developing an intolerance to gluten, a protein in wheat and other grains. The author reviews the diagnostic tests that may be used to confirm a food sensitivity or allergy, and offers basic strategies for coping with a food allergy. The author stresses that people with a food allergy should work with a nutrition professional to learn how to eat healthfully and avoid food allergens that cause symptoms. The article is appended with a list of resource organizations that can offer more information about food allergies, gluten intolerance, and related issues. •

Allergy Tests For Milk Source: Newsletter for People with Lactose Intolerance and Milk Allergy. 1992. p. 6. Contact: Available from Newsletter for People with Lactose Intolerance and Milk Allergy. P.O. Box 3129, Ann Arbor, MI 48106-3129. (313) 572-9134. Summary: This brief article reviews the current thinking about allergy testing in children, particularly those used for identifying food allergens. The author conveys the information that, while allergy testing for food allergens is unreliable, testing for environmental allergies is both reliable and useful. Identifying and treating environmental allergies, thereby reducing sensitivity to known allergens, will have a very positive effect on general health that will strengthen the immune system.

•

Is Your Skin A Little, Uh, Sensitive? Source: Healthy Skin and Hair. p. 9-10. Winter 2001. Contact: Available from Quadrant HealthCom, Inc. 26 Main Street, Chatham, NJ 079282402. (973) 701-8900. Fax: (973) 701-8892. Summary: This journal article discusses sensitive skin. Sensitive skin is easily irritated by perfumes, soaps, weather conditions, and chemicals. Other irritants of sensitive skin include poison ivy and oak, wool, rough towels, and cosmetics. Some people are born with sensitive skin and others develop sensitivity after being exposed to allergens or chemicals. People who develop rashes easily or have itching after exposure to irritants should use mild products without added perfumes, bar soaps, products that contain petroleum jelly, sunscreen, and avoid chemical fragrances.

•

Nail Psoriasis Often Misdiagnosed as Onychomycosis Source: Skin and Allergy News. 28(10):32; October 1997.

10

Allergens

Summary: This journal article for health professionals reports on the misdiagnosis of nail psoriasis as onychomycosis. Nail psoriasis is difficult to diagnosis, and it may be caused by reactions to various irritants and allergens. A method of treating limited nail psoriasis is to inject triamcinolone acetonide into the proximal and lateral nail folds every four weeks until the nails are clear. In addition, other inflammatory nail conditions, such as alopecia universalis, can improve with intralesional injections. 1 photograph. •

Acute and Chronic Urticaria: Challenges and Considerations for Primary Care Physicians Source: Postgraduate Medicine. 109(2): 107-108,111-114,119-123. February 2001. Summary: This journal article provides health professionals with information on the classification, diagnosis, and management of urticaria. This common dermatologic problem may be classified as either acute or chronic. Lesions that last less than 6 weeks are referred to as acute urticaria. They are usually caused by exposure to food allergens, food additives, certain medications, or radiocontrast media. Chronic urticaria occurs most frequently in middle aged women, and it is likely to coexist with the physical urticarias. Before a diagnosis of chronic idiopathic urticaria is made, several specific urticarial syndromes need to be considered and excluded, including autoimmune mast cell disease, urticarial vasculitis, physical urticaria, and exercise induced urticaria. Urticaria is fairly easy to diagnose, and its symptoms include raised, erythematous wheals accompanied by intense pruritus. Laboratory tests should be performed to exclude systemic disease. Specific allergy or provocative tests may be needed to further clarify the diagnosis. Punch biopsy of an urticarial lesion often provides useful information that can help guide patient management. Management involves patient education, avoidance of known triggers, and pharmacotherapy. Patients need to be educated about their disease and given specific instructions on crisis management. When a specific trigger has been identified, the patient must avoid any exposure to it. Drugs that may be beneficial include traditional antihistamines such as hydroxyzine, cyproheptadine hydrochloride, and azatadine. The newer generation antihistamines, such as cetirizine hydrochloride, loratadine, and fexofenadine hydrochloride, have a rapid onset of action, are very effective, and have minimal side effects. Patients who have an angioedema component should be provided with an epinephrine autoinjector for use in case of respiratory distress. Drugs that may be used to treat patients with urticarial vasculitis syndrome include prednisone, azathioprine, and cyclophosphamide. 5 figures, 2 tables, and 23 references.

•

Managing Atopic Dermatitis in Children and Adults Source: Nurse Practitioner. 25(4): 58-59,63-64,69-70,73,76,79-81. April 2000. Summary: This journal article provides nurse practitioners with information on the epidemiology, pathogenesis, clinical features, diagnosis, complications, and treatment of atopic dermatitis. This common skin inflammation, which is characterized by intense pruritus, is most common in children. The prevalence of atopic dermatitis has tripled in the past 30 years, and the condition affects about 10 percent of the U.S. population at some point in their lifetime. Although the etiology of atopic dermatitis is not well understood, it appears to be linked to a combination of genetic and environmental factors, and it is usually associated with other atopic diseases such as asthma and hay fever. The initial clinical feature of atopic dermatitis is skin dryness and roughness. Erythema, papules, and pruritus may develop after additional irritation. The pattern of atopic dermatitis lesions varies by age. A definitive diagnosis in children and adults

Studies

11

depends on identifying the nature and distribution of the lesions and on eliciting a personal or family history of the disease. Although no cure exists, atopic dermatitis often resolves spontaneously and can be controlled through proper management. Avoiding factors that precipitate or exacerbate inflammation, including aeroallergens, food allergens, and irritants, is key to preventing disease flares. In children and adults, hydration and topical corticosteroids are the mainstays of therapy. Recalcitrant disease may be treated with ultraviolet light therapy or psoralen phototherapy and cyclosporin. Current advances in understanding the immunologic basis of the disease have led to the development of highly effective new treatments. Using patient education and support, the clinician can help adults and children successfully manage their disease. The article includes a continuing education test. 2 figures, 4 tables, and 42 references. (AA-M). •

Diagnosis and Management of Chronic Nonspecific Mucosal Lesions Source: CDA Journal. Journal of the California Dental Association. 27(4): 290-297, 299. April 1999. Contact: Available from California Dental Association (CDA). 1201 K Street, Sacramento, CA 95814. (916) 443-0505. Summary: This journal article reviews the diagnosis and management of chronic nonspecific mucosal lesions. The author notes that chronic lichenoid or leukoplakic oral mucosal lesions are a common cause of morbidity and concern. Many of these are reactive or inflammatory lesions, but they can also represent other disorders, including dysplasia. These lesions are caused by a variety of irritants and allergens such as systemic drugs, dental restorations and prostheses, oral health care products, foods, habits, and candida (which causes thrush). Indiscriminate use of steroids to treat these lesions empirically is contraindicated; management should be aimed at discovery and removal of the cause. The proposed sequence of investigation is initially intended to eliminate any obvious etiology and, if that is unsuccessful, to rule out candida or determine a histologically diagnosable disease. If a biopsy shows nonspecific or lichenoid mucositis and the lesions are symptomatic, the investigation is directed to the more obscure and speculative causes that require expensive and time consuming trial and error elimination of various agents. 9 figures. 2 tables. 21 references. (AA-M).

Federally Funded Research on Allergens The U.S. Government supports a variety of research studies relating to allergens. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to allergens.

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).

12

Allergens

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 allergens. The following is typical of the type of information found when searching the CRISP database for allergens: •

Project Title: ADULT ASTHMA: BIOLOGY, SOCIETY AND ENVIRONMENT Principal Investigator & Institution: Blanc, Paul D.; Professor of Medicine; Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 30-JUN-2006 Summary: (provided by applicant): Environmental, biological, and psychosocial factors can all separately influence the disease burden in asthma. As yet, no studies have taken into account all three categories of factors together, to examine their relative contributions to the disease burden and investigate whether their cumulative effects can explain the health disparities of at-risk populations, either additively or synergistically. Asthma is an ideal chronic condition in which to delineate the potential linkages among biological mechanisms, social factors, and physical environments and, more specifically, to show how these linkages may lead to health disparities. Study Hypotheses: 1) There are socioeconomic status (SES) differentials in the disease burden of asthma; 2) Environmental, biological, and psychosocial factors are linked to the asthma disease burden additively, if not synergistically; and 3) The variance in SES differentials of disease burden will be substantially explained by modeling that takes specific environmental, biological, and psychosocial factors into account. Methods: This proposed study will make use of an established panel of 590 adults with asthma of varying severity. We propose to supplement these survey data with 500 home site visits in which we will directly gather environmental, biological, and psychosocial data. Specific environmental risk factors we will quantify include: allergen sensitization, home allergens, ETS exposure, and indoor air quality. We will also assess perceived stress and social support. In addition, we will link subjects to other potential exposures through external data sets. We will also administer a follow-up survey to investigate the combined influence of environmental, biological, and psychosocial exposures in explaining SES disparities in the disease burden of asthma. This study combines a multidisciplinary team of researchers with expertise in clinical medicine, social sciences, epidemiology, psychology, endocrinology, asthma treatment and prevention, and biostatistics. Anticipated Results and Significance: The proposed investigation will have sufficient power to detect differences in the proportions of outcomes between two groups in the range of 10-15 percent at the 0.05 level for dichotomous outcomes. This project addresses a major research need and can be a basis for the development of public policies to address environmentally related and other health disparities in adult asthma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: AIRWAY-CENTRAL NERVOUS SYSTEM CONTROL Principal Investigator & Institution: Haxhiu, Musa A.; Physiology and Biophysics; Howard University Washington, Dc 20059 Timing: Fiscal Year 2004; Project Start 01-JAN-1995; Project End 31-MAR-2009 Summary: (provided by applicant): Chronic airway diseases such as bronchial asthma and chronic obstructive bronchitis share the salient features of inflammation, hyperresponsiveness to various inhalants, and airway narrowing. Although these two conditions result in enormous morbidity and social cost, the central nervous system mechanisms involved in airway hyperreactivity remain poorly understood. In the prior

Studies

13

funding cycle of this proposal we have characterized the primary neurochemical(s) and receptor subtypes involved in transmission of excitatory inputs from the respiratory tract to the nucleus tractus solitarius (NTS) neurons; from these second order sensory cells to airway-related vagal preganglionic motor neurons (AVPNs); and from AVPNs back down to the airways. As a natural continuation of this work, we now focus on inhibitory pathways that regulate cholinergic drive to the airways. Neuroanatomical studies will define the normal neural circuitry between inhibitory GABAergic, catecholaminergic, or serotonergic cell groups and AVPNs. In these studies, retrograde tracing will be used to define AVPNs projecting to the trachea. Dual or triple labeling immunocytochemistry will be used to simultaneously locate neurotransmitters, their receptors, and AVPNs. Tissues will be examined using light microscopy, confocal microscopy, and electron microscopy. Protein levels will be measured by Western blotting. In physiological studies, we will microinject uptake inhibitors, specific agonists, or antagonists into the rostral nucleus ambiguus (rNA, where AVPNs are abundant), to define the functional roles of specific inhibitory neurotransmitters and their receptors on basal and reflex-induced changes in tracheal tone and airway resistance. Subsequently, we will test the hypothesis that repeated exposure to allergens in sensitized animals induces morphological and physiological changes in central inhibitory influences, resulting in a shift from inhibitory to excitatory transmission. These changes lead to a hyperexcitable state of AVPNs and to airway hyperreactivity. The results of these studies will provide necessary knowledge in the neural control of the airways and will support the development of novel pharmaceutical strategies which target the central nervous system for the treatment of airway disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AIRWAYS EOSINOPHILS AS ANTIGEN-PRESENTING CELLSASTHMA Principal Investigator & Institution: Weller, Peter F.; Professor; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-MAY-2006 Description (provided by applicant): Studies will investigate the ability of eosinophils to serve as antigen-presenting cells that contribute to propagating lymphocyte-dependent, IgE-mediated response to inhaled antigens in the respiratory tract. Eosinophils are prominent cellular components of allergic airway responses. While many cells function as antigen-presenting cells, eosinophils have distinct capabilities within the airway. First, eosinophils are present in the airway lumina of asthmatics; and these eosinophils in vivo express requisite class II MHC proteins and critical lymphocyte costimulatory proteins. Second, eosinophils contain preformed stores of cytokines that may be rapidly mobilized for extra cellular release to modulate lymphocyte-dependent responses. Third, unlike B cells and dendritic cells that are capable of presenting soluble protein antigens, eosinophils, like macrophages, are especially able to degrade particulate antigens. Alveolar macrophages are poor antigen-presenting cells. In contrast, eosinophils could present peptides derived from particulate inhaled allergens. Fourth, antibodies of several classes, by Fc receptor-mediated mechanisms, can dramatically enhance antigen uptake and presentation by antigen-presenting cells. Eosinophils with their IgE, IgA, and IgG antibodies receptors are well suited to internalize and present allergens recognized by allergen-specific IgE, IgA, and IgG antibodies present in the respiratory tract. Fifth, eosinophil trafficking from the airway lumen into lymphocytes provides a mechanism for antigens inhaled into the airways to be processed and transported into tissues for presentation to lymphocytes. Hypotheses are that

14

Allergens

eosinophils are effective at presenting inhaled antigens to lymphocytes, that this eosinophil antigen processing and trafficking occur in vivo within the airways, that eosinophil high affinity IgE receptors function to enhance eosinophil antigen presentation of allergens, and that antigen presentation by eosinophils, perhaps based on their release of preformed, cytokines, skews Th2-mediated responses to inhaled antigens. Studies aim to define the capacity of human eosinophils in vitro to function as antigen-presenting cells and to define the role of eosinophil IgE receptors in facilitating antigen presentation by eosinophils. These studies of eosinophils active in asthma focus on the roles of eosinophils in propagating the chronic airway inflammation of asthma. Roles for eosinophils as antigen-presenting cells in sustaining allergic responses to inhaled particulate allergens would provide insights into the characteristically chronic nature of allergic diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ALLERGY PEPTIDE(ECP)VACCINE

PREVENTION

BY

LGE

CYTOTOXIC

Principal Investigator & Institution: Chen, Swey-Shen A.; Ige Therapeutics, Inc. 6827 Nancy Ridge Dr San Diego, Ca 92121 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-AUG-2003 Summary: (Provided by the applicant): IgE-mediated allergic asthma, rhinitis, food allergy, atopic dermatitis, anaphylaxis cost annual 18 billions in medical costs and loss of productivity in this country. Regulation of IgE production by B cells is orchestrated by Th2 cytokines. This paradigm dictates a treatment modality of IgE-mediated hypersensitive diseases that diminishes endogenous levels of IL-4, thereby IgE production by IgE-committed B cells. Alternatively, studies initiated by PI indicated that following IgE immunization, CD8 T cells play an important role in inhibiting IgE production by IgE-committed B cells, and profound IgE deficiency ensued and is maintained in IgE-immunized mice. This observation leads to the current passive antiIgE therapeutic product concept. However, this treatment modality suffers drawbacks in failing to inhibit IgE synthesis as well as to remove circulating IgE-anti-IgE complexes, which accumulates to levels 10 fold higher, compared to the levels prior to treatment. And it is yet to be determined whether patients may be given a second heavy dose without eliciting neutralizing antibodies, including internal image-type of antibodies that potentially can cause mast cell degranulation. It is imperative to design alternative therapeutic modality based on active IgE immunization with higher safety standards. Herein, we provide a long-term strategy of reducing IgE levels by active immunization with IgE cytotoxic peptides (ECP) that are independent of requirement of conformation. Since B cells and plasma cells of the IgE lineage exhibiting natural ECP onto the binding site pocket of MHC class I, these targets are Iysed by ECP-specific CTL due to active vaccination. The advantages of this commercial vaccine are: (i) ECP is sequence-dependent, and does not elicit anti-IgE; (ii) ECP is economic and its effect long-lasting. To achieve this immediate goal, our two Aims are: Aim I: To Determine the Structure of Natural Human IgE (huIgE) CTL Epitopes Restricted To HLA-A2.1 and Ascertain Their Efficacies with huIgE-Producing Cells. Aim II: To Determine Whether ECP-specific CTL Elicited By Active Immunization Inhibit Human IgE Production In A Pre-clinical Model of huIgE/HLA-A2.1 Transgenic Mice. PROPOSED COMMERCIAL APPLICATION: IgE cytotoxic peptide (ECP) vaccine aims at an open market of active allergy immunization. Unlike the conventional allergen-desensitization, ECP technology based on targeting the universal IgE epitope can desensitize allergic syndromes caused by a myriad of allergens with a booser dose. Furthernore, unlike the current passive

Studies

15

anti-IgE therapy, ECP is economic for one or two injections; risk-free since it is directed to linear sequence not recognize by anti-IgE, as compared to the current anti-IgE therapy that may actually cause mast cell degranulation due to induction of anti-idiotype. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANTIGEN IMMUNOSUPPRESSION BY KILLER LANGERHANS CELLS Principal Investigator & Institution: Takashima, Akira; Professor; Dermatology; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 01-JUN-2000; Project End 31-MAY-2005 Summary: Langerhans cells (LC) ordinarily deliver activation signals to T cells. We hypothesized that LC genetically modified to over-express CD95L (Fas ligand) termed "killer" LC, would deliver apoptotic signals to T cells upon antigen-specific interaction. To test this, we introduced CD95L cDNA into our LC line XS106 (derived from A/J mice) and selected a stable clone (XS 10-6-CD95L) that expressed abundant surface CD95L. This killer LC clone, when pulsed with ovalbumin (OVA), triggered apoptosis of OVA-reactive CD4+ T cells in vitro by an antigen-specific and CD95L-dependent mechanism. OVA-pulsed killer LC, when injected into A/J mice before or after sensitization, suppressed ear swelling responses to DNFB. Importantly, OVA-pulsed killer LC suppressed OVA responses, but not responses to the irrelevant antigen HEL, whereas HEL- pulsed killer LC inhibited only the HEL responses, establishing antigenspecificity. We will define mechanisms, under the new hypothesis that killer LC suppress diverse immunological responses by triggering apoptosis of putative effector T cells that recognize respective antigens. Specifically, we will study the impact of killer LC using five-established animal models: 1) Delayed type hypersensitivity: We will inject OVA- pulsed killer LC before or after sensitization to study the impact of CD4+ effect T cells and memory T cells, the fate of effector cells (adoptive transfer of OVAreactive, naive CD4+ T cells from the D011.10 transgenic mice), and the critical timing for cytotoxic interaction of killer LC with T cells (drug-inducible suicide system). 2) Contact hypersensitivity. We will inject DNFB-pulsed killer LC before or after sensitization to study the impact of CD8+ effector T cells and on Th2-like regulatory T cells, killer LC interaction with CD8+ T cells and antigen- specificity. 3) Th2-biased immune responses. Mice will be sensitized epicutaneously with an OVA-absorbed "patch" to produce OVA-specific IgE and IgG1 antibodies and atopic dermatitis-like skin lesions. We will inject OVA-pulsed killer LC to study the impact on Th2-biased effector and helper T cells and "therapeutic" efficacy for skin lesions. 4) Experimental autoimmune myocarditis. Mice will be sensitized with cardiac myosin (CM) to produce autoimmune myocarditis. We will inject CM-pulsed killer LC to study the impact on CD4+ pathogenic T cells that recognize tissue-specific autoantigen, the fate of pathogenic T cells, and therapeutic efficacy and safety. 5) Skin graft rejection. We will study the impact of killer LC and "killer LC hybrids" on allo-reactive CD4+ and CD8+ T cells, which are ordinary activated via "direct" and "indirect" pathways. These studies will form the framework for establishing an entirely new immunosuppressive therapy for inflammatory skin diseases, the therapy designed to eliminate selectively the effector T cells that recognize pathogenic antigens (e.g., haptens, allergens, autoantigens, and alloantigens). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

16

•

Allergens

Project Title: ANTIGEN PRESENTATION--MODEL OF ALLERGIC EYE DISEASE Principal Investigator & Institution: Benichou, Gilles A.; Schepens Eye Research Institute Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 01-APR-1999; Project End 31-MAR-2003 Summary: Immediate hypersensitivity or allergy is the most widespread immunological disorder in humans. We have recently developed a mouse model of allergic conjunctivitis to cat dander (Fel dl), and characterized the T helper responses in susceptible animals. Approximately 25% of the world's population suffer from allergies; with ocular symptoms contributing a significant proportion of the discomfort and patient care costs associated with allergic disease. There is considerable interest among ophthalmologists for the development of new anti-allergic and anti-inflammatory compounds that can be used safely in the eye. A novel and promising approach to management of ongoing allergic disease is that of peptide immunotherapy. Identification of defined T cell epitopes containing peptides, based on the primary structure of major allergens may provide an effective tool for modification of human immediate hypersensitivity to allergens. Since functional and biochemical studies have demonstrated that the generation of T cell responses depends upon antigen receptors on T cells (TCR) recognizing peptide fragments of foreign proteins associated with products of the major histocompatibility complex (MHC), that are expressed on the membranes of accessory cells, any examination of T cell epitopes must also include MHC analysis. Therefore, the goal of this proposal is to use our mouse model of allergic conjunctivitis to clearly define the molecular interaction in the ternary complex of immunodominant peptide, the MHC on the antigen presenting cell (APC), and the T cell receptor. After we have define the specific T cell/peptide/APC interaction, we will use this information to develop a novel T cell vaccine my making an antigenized MHC-Ig chimera, and then to test this T cell vaccine in our mouse model of allergic conjunctivitis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: ASTHMA AND LEAD PREVENTION IN CHICAGO PUBLIC HOUSING Principal Investigator & Institution: Knight, John Q.; Senior Program Associate; Safer Pest Control Project 25 E Washington St, Ste 1515 Chicago, Il 60602 Timing: Fiscal Year 2002; Project Start 15-SEP-2001; Project End 30-JUN-2005 Summary: (provided by applicant) African Americans, Puerto Ricans, and persons living in low income neighborhoods have at least five times the death rates from asthma as non- Hispanic whites. Many environmental variables have been shown to increase symptoms in persons predisposed to the disease, including exposure to cockroach allergens, furry/feathered pets, dust mites, rodents, endotoxins, and pesticide sprays. The purpose of the current study is to examine the effects of peer education and modification of the home environment on the incidence and severity of asthma, lead dust exposure, and lead poisoning in Chicago public housing residents over a four-year period. The project will build upon a network of community groups, healthcare providers, specialists, and Chicago Housing Authority (CHA) personnel committed to improving public health in Chicago public housing. A total of six peer educators will be recruited from Ogden Courts, Henry Homer, and Robert Taylor developments who will work with a total of 600 families with asthmatics from the three developments to assess and modify pest problems and other asthma triggers and lead hazards. A total of fifteen residents from the three developments will additionally be recruited to carry out small unit repairs (caulking and sealing of cracks and crevices) for cockroach and rodent

Studies

17

management in all 600 units. The specific aim of this study is to reduce the incidence and severity of asthma and lead poisoning in Chicago Public Housing. Long-term objectives are to implement and formalize Integrated Pest Management (effective pest control while minimizing the use and hazards of pesticides) Authority-wide, to improve the self-sufficiency of CHA residents, and to enable CHA residents to direct environmental improvements in their own developments leading to better health. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ASTHMA COALITION ON COMMUNITY, ENVIRONMENT AND STRESS Principal Investigator & Institution: Piltch, Cynthia; Ctr for Community Health Educ Res & Srv Education Research and Service Boston, Ma 02120 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Our proposed Center for Reducing Asthma Disparities involves partnership between researchers at Harvard University (Charming Laboratory, BWH and HSPH) and a network of Boston-area Community Health Centers (CHCs) affiliated with the non-profit community-based organization CCHERS (Center for Community Health Education, Research and Service). Broad specific aims are (see Section D for more detailed aims):I. Conduct a community needs assessment to assess differences in perceptions about asthma etiology, disparities, and effective treatment between community representatives, CHC patients, and CHC providers. 2. Determine the role of socio/environmental exposures (psychosocial stress, indoor allergens, cigarette smoking and diesel-related air pollutants) on asthma onset through study of a prenatally enrolled birth cohort. 3.Determine the role of genetics in modifying the risk of the social/physical environment by concurrent assessment of the following genetic factors thought to influence immune development and airway inflammation in early life: stress (corticosteroid regulatory genes, adrenergic system regulatory genes), diesel exhaust and smoking (biotransformation genes), indoor allergens (cytokine pathway genes). 4. Use a quasiexperimental design to evaluate the effectiveness of the research, training, and outreach components of our project in leading to significant changes in the ability of particular stakeholders to design and implement sound asthma intervention strategies. 5. Development of training programs at Harvard that provide masters and predoctoral students as well as postdoctoral fellows with experience and expertise in Community-Based Participatory Research (CBPR) focused on reducing asthma disparities. 6. Develop training and information dissemination materials for health center staff and community members (especially caregivers of children with asthma). CCHERS will take the lead in implementing Specific Aims 1, 4 and 6, while the Harvard group will take the lead on Aims 2, 3 and 5. In addition to building needed infrastructure to support partnership-based research and interventions aimed at reducing health disparities, this proposal has the potential to make significant contributions to the scientific literature with respect to health disparities and asthma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: ASTHMA INDUCTION BY DENDRITIC CELLS AND TH2 CELLS Principal Investigator & Institution: Sung, Sun-Sang J.; Associate Professor; Internal Medicine; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 30-NOV-2007 Summary: (provided by applicant): Asthma is an important disease that afflicts 5% of the general population. Atopic asthma is caused by biased-T helper 2 (Th2) responses to

18

Allergens

allergens. In a mouse model, mice primed intratracheally with Ag-pulsed dendritic cells and challenged with Ag developed airway hyperresponsiveness, and lung eosinophilia and inflammation. Lungs have a more Th2-biased environment and primed T cells seem to divide faster in the lungs than lymph nodes in Ag-challenged mice, although the lymph node is believed to be the site of T cell activation and development. In this study, lung DC have been found to be composed of multiple subset. Studies on DC migration suggest that secondary lymphoid chemokine (SLC/CCL21) may be a key chemokine for DC migration to draining LN. In the lung but not lymph nodes of lung-immunized mice, large numbers of interferon-gamma-producing CD8+ T cells (Tc1) were present, resulting in a more Th2-baised environment in the lungs. These results support the hypothesis that: "a DC subset that presents antigen in lungs and mediates a Th2-biased response occurs in lungs. For T lymphocyte and DC migration to lymph nodes, SLC is a major mediator. Because Th1 and Tc1 cell numbers are very low in the inflammatory lungs, activated T cells readily develop into Th2 cells." In this proposal, experiments are designed to support this hypothesis. The aims consist of: (1) the isolation and functional studies of DC subsets in lungs; (2) the studies of CCR7/SLC interaction as a key chemokine receptor/chemokine interaction for lung DC and T cell migration to lymph nodes. The roles of other important candidate chemokine receptors such as CCR2 in mediating DC migration will also be examined; and (3) the studies of the migration of IFN-gamma-producing CD8+ T cells away from lungs during asthma pathogenesis. These studies will clarify the roles of DC and CD8+ T cells in the biased-Th2 lung response in asthma and provide a novel mechanism for Th2-biased responses during asthma pathogenesis. The results may provide additional therapeutic strategies in asthma by the interference of SLC functions and by regulating the migration of DC, Th1, and IFN-gamma-producing CD8+ T cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CALCIUM SIGNALING IN DENDRITIC CELL FUNCTION Principal Investigator & Institution: Ahern, Gerard P.; Pharmacology; Georgetown University Washington, Dc 20057 Timing: Fiscal Year 2003; Project Start 15-FEB-2003; Project End 31-JAN-2007 Summary: (provided by applicant): Dendritic cells (DC) are a heterogeneous population of rare leukocytes highly specialized for immune-surveillance, and the induction and regulation of primary immune responses. This unique capacity reflects their ability to continuously sample the microenvironment and ingest foreign and self-antigens. After encountering a "danger" stimulus in the form of microbes, inflammatory molecules or allergens, DC transform into potent stimulatory cells and migrate to secondary lymphoid tissues, where they trigger the activation of antigen-specific effector T cells. The signaling pathways that underlie these processes are undoubtedly complex, but intracellular calcium appears to play a crucial role. We have recently characterized two novel calcium signaling pathways in DC. First, we have identified the skeletal muscletype ryanodine receptor (RyR1) in DC. RyR1 is a massive intracellular channel that can amplify small calcium transients within a cell to produce much larger, sustained calcium rises. Second, we have demonstrated that calcium fluxes trigger rapid secretion by DC. Such pathways enable DC to respond rapidly to external stimuli, and release autocrine and paracrine signaling factors including exosomes and leaderless secretory proteins. The goal of this proposal is to determine the RyRl-calcium regulated pathways in DC. We hypothesize that RyR1 integrates diverse cellular stimuli, and mediates the calcium pathways that drive DC function. An inter-disciplinary approach is outlined to investigate the properties of these calcium signaling mechanisms and understand how

Studies

19

they participate in DC biology. We will accomplish the objectives of this proposal by pursuing the following specific aims: Aim 1 is designed to determine the role of RyR1 during DC development and function. Aim 2 tests the impact of endogenous and pharmacologic activators of RyR1 on DC. In Aim 3, we will elucidate the role of calcium-triggered secretion in DC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CARDIOVASCULAR LUNG, AND BLOOD IMMUNOBIOLOGY IN HEALTH Principal Investigator & Institution: Corry, David B.; Assistant Professor of Medicine; Medicine; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-JUL-2005 Summary: (provided by applicant): The long- term objectives of this laboratory are to elucidate the immunopathologic basis of airway obstruction in a murine model of asthma. This proposal will investigate the role the epithelium plays in allergic lung inflammation and focus specifically on an epithelium- derived immunoregulatory molecule, Clara cell secretory protein (CCSP), that potentially limits deleterious allergic inflammation of the airway. Work from this laboratory has identified proteases derived from fungi and pollen as critical regulators of T helper activation and allergic inflammation. The dominant role played by proteases raises the intriguing possibility that the lung immune system has evolved mechanisms that limit tissue injury in the setting of allergic inflammation. Clara cells are non- ciliated respiratory epithelial cells that secrete one of the most abundant proteins contained in the respiratory lining fluid, CCSP. Although the biological functions of CCSP remain unclear, it is an antiprotease potentially capable of neutralizing exogenous proteases implicated in allergic airway disease. CCSP may also regulate adaptive immune responses of the airway by influencing epithelium-derived factors necessary for growth and survival of T and B cells. Studies from this laboratory provide preliminary evidence that CCSP downregulates airway Th2 responses provoked by exogenous proteases. Thus, CCSP is immunosuppressive with regard to allergic lung inflammation but its precise mechanisms of action remain uncertain. Aim 1 of this proposal will define the allergic settings relevant to CCSP- dependent regulation. We will investigate whether the potency of both protease- containing and protease- deficient (ovalbumin/alum) allergens is inhibited by CCSP in vivo. The role of CCSP will be evaluated using mice overexpressing CCSP in the airway and CCSP-deficient mice. In part based on the results of Aim 1, we will dissect in Aim 2 the major mechanism by which CCSP attenuates allergic inflammation. We will focus specifically on T cell-dependent effects and explore, with and without CCSP, T helper effector differentiation in vitro and in vivo, Th2 homing to lung and Th2 activation and cytokine production in vitro. Where effects are observed, we will correlate immunosuppressive activities with the antiprotease potential of CCSP. Finally, we will explore the potential of CCSP in the prevention and amelioration of allergic lung disease. Mice will be challenged intranasally with recombinant CCSP during immune induction with proteasecontaining allergens and following established allergic lung inflammation to evaluate these two endpoints. Efficacy of CCSP will be compared to a specific protease inhibitor, streptomyces subtilisin inhibitor (SSI). Together, these data will elucidate an epitheliumdependent immunomodulatory mechanism of the lung mediated through CCSP, and potentially identify novel means for the therapy of allergic lung disorders such as asthma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

20

•

Allergens

Project Title: CHEMOKINES AND LYMPHOID TISSUE ORGANIZATION AND FUNCTION Principal Investigator & Institution: Cyster, Jason G.; Associate Professor; Microbiology and Immunology; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2004; Project Start 01-APR-1999; Project End 31-MAR-2009 Summary: (provided by applicant): Secondary lymphoid organs promote cell-cell and cell-antigen interactions that are necessary for the initiation of adaptive immune responses. Chemokines have recently been established to have a central role in the development and organization of secondary lymphoid tissues. The long-term objective of this proposal is to define how secondary lymphoid organs become organized and to determine how this organization fosters the cell-cell encounters that are necessary for adaptive immunity. The first of three aims seeks to determine the role of CXCR5 in guiding helper T cells to B cell areas, and to determine the importance of this chemokine receptor for T helper cell function. A second part of this aim will use 2-photon microscopy to study interactions between B cells and T cells within viable lymphoid tissue. B-cell derived chemokine(s) involved in promoting encounters between activated T and B cells will also be characterized. Lymphoid chemokine induction in the spleen is lymphotoxin (LT) dependent and occurs during the first few weeks after birth. In aim 2 the major cell types functioning as sources of LT within the neonatal spleen will be characterized. The role of lymphoid chemokines in organizing the developing whitepulp will be investigated, including an analysis of newly generated ELC knockout mice. In addition, a BLC reporter mouse strain will be generated to permit the appearance of BLC expressing cells to be tracked. Many of the cells within lymphoid organs are in a state of continual motility, a behavior that facilitates their surveillance for antigen. The third aim will explore the role of chemokines and integrins in promoting cell motility within lymphoid organs. By improving our understanding of the factors that promote lymphoid tissue development and organization and by further developing understanding of how B and T lymphocytes interact to mount antibody responses, these studies should lead to approaches to augment immune responses against pathogens and vaccine antigens, and to thwart unwanted responses against allergens or autoantigens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: CHICAGO INNER CITY ASTHMA STUDY Principal Investigator & Institution: Evans, Richard; Children's Memorial Hospital (Chicago) Chicago, Il 606143394 Timing: Fiscal Year 2001; Project Start 01-AUG-1996; Project End 31-JUL-2004 Summary: Data from NCICAS indicate that a multiplicity of risk factors interact to increase the severity of asthma in poor, urban minority children. Any intervention to reduce morbidity in this Medicaid-dependent population should not only be multifaceted but also reasonably priced. Therefore, the Chicago Inner-City Asthma Study (CICAS) proposes to identify a cost- effective intervention that will reduce asthma morbidity in 4- to 12-year- old minority/low-income urban children with severe/moderately severe asthma. Primary outcome measures are reduction in mean symptom days and cost-effectiveness. Secondary measures include other morbidity measures (reductions in hospitalization, unscheduled acute-care visits including to ER, and school absences); improved patient/caretaker knowledge of asthma management, medications, and use of delivery devices/peak flow meters; increased primary-care physicians' practice effectiveness and asthma-care knowledge (including written asthma

Studies

21

management plans); improved communication between physician and patient/caretaker leading to greater adherence; decrease in indoor allergens; and a reduction in behavior problems. The CICAS will evaluate three HMO-based interventions and compare them to a control group (Group I) in which patients receive usual care. The intervention groups are designed on an add-on principle. Each succeeding group receives all the interventions of the previous group(s) plus one additional intervention. Eight physician-provider clinic sites affiliated with United Health Care of Illinois (an HMO that serves a large proportion of Chicago's Medicaid population) will be randomized to one of the four groups. Children/families from these sites will be screened and recruited for the study. Patients will receive skin testing and spirometry, and they/caretakers will complete various written assessments of asthma risk and asthma knowledge. Groups II-IV will receive patient education taught by a clinic-based asthma mentor, including the proper use of medications and devices. Primary-care physicians in these groups will participate in a case-based physician education program that will also stress use of asthma-care guidelines and written management plans. An inspector will visit homes of patients in Groups III and IV to assess environmental risk factors. Targeted interventions will be provided for patients who are dust-mite (e.g., pillow, mattress covers) or cockroach (extermination) sensitive. Selected patients in Group IV (those with behavioral or other intractable problems) will receive intensive case management. Throughout the interventions, patients will be monitored bimonthly by telephone. The asthma mentor will also play a key role in problem-solving in each clinic. A successful cost-effective intervention that reduces morbidity among inner-city minority children would be a significant health benefit, and it would provide economic relief to the overburdened urban healthcare system. The CICAS believes that its study design permits the determination of the most effective intervention that is also cost-effective. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHITOSAN IFNGAMMA-PDNA NANOSPHERE THERAPY AND IMMUNOPATHOLOGY OF ALLERGIC ASTHMA Principal Investigator & Institution: Mohapatra, Shyam S.; Professor of Medicine; Internal Medicine; University of South Florida 4202 E Fowler Ave Tampa, Fl 33620 Timing: Fiscal Year 2003; Project Start 25-SEP-2003; Project End 31-AUG-2007 Summary: (provided by applicant): With an intent to develop effective prophylaxis or treatment of allergic diseases including allergic asthma, our goal is to examine the safety and efficacy of chitosan IFN-gamma-pDNA nanosphere (CIN) Therapy and the cellular and molecular mechanisms underlying its effectiveness in a mouse model of asthma. Deviation of immune response to allergens from a pathogenic T helper-2 type response to T helper-1 type may provide a practical approach to modifying the course of disease. Administration of IFN-gamma, and IL-12 DNA plasmids significantly decreased airway inflammation and airway hyperresponsiveness in a mouse model of grass allergic asthma. In addition, Adenoviral-mediated IFN-gamma, gene transfer effectively reversed established asthma in BALB/c mouse model. While these studies aid in the mechanistic understanding of IFN-gamma, action in the lung, acute inflammation and immunogenicity to virus remains the major obstacle for the application of viralmediated gene transfer for treating human asthma. We therefore developed a non-viral strategy that involves the development of chitosan nanospheres containing IFN-gamma, pDNA (CIN), intranasally (i.n.) delivered to the lung, as a strategy for asthma treatment. Our working hypothesis is that i.n. CIN therapy provides for effective prophylaxis or treatment of asthma by inducing changes in expression of cytokine and chemokine

22

Allergens

genes which result in altered antigen presentation, decreased migration of effector cells into the lung, and apoptosis of inflammatory cells, leading to a global decrease in inflammation and airway remodeling. The specific aims of this research program are as follows: Aim #1. Evaluate chitosan-IFN-gamma-pDNA nanospheres (CIN) as a prophylactic or a therapeutic modality for allergic disease in BALB/c mice. We plan to evaluate the role of CIN in prophylaxis/therapy of allergic asthma in BALB/c mice with respect to magnitude of acute inflammation, duration of protection from asthma and its potential in a chronic asthma model. We will analyze different asthma phenotypes, such as immune deviation of allergic response revealed by a change in T-cell cytokine secretion and antibody response profiles, the airway hyperreactivity and eosinophils in broncho-alveolar lavage, and lung pathology. Aim #2. Elucidate the cellular/molecular mechanism of CIN-induced immunomodulation. We plan to examine the role of T cells, CIN modulation of specific T cell response in the lung including apoptosis of Th2 cells and modulation of the number and activity of dendritic cells in the lung. Aim #3. Elucidate the anti-inflammatory mechanism of CIN-induced protection. We plan to examine the genes, which mediate the effects of CIN, whether CIN affects airway inflammation and airway remodeling in lungs of mice, and whether CIN induces apoptosis of mucus producing goblet cells. It is anticipated that the results of these studies will contribute significantly to our knowledge of asthma and CIN therapy may provide a major breakthrough in management of asthma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COLLABORATIVE STUDIES ON THE GENETICS OF ASTHMA (CSGA) Principal Investigator & Institution: Blumenthal, Malcolm N.; Professor; Medicine; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 30-SEP-1992; Project End 31-AUG-2002 Summary: Asthma is a respiratory disease characterized by variable airways obstruction, airways inflammation and bronchial hyperresponsiveness (BHR). There are increases in asthma mortality and prevalence in the US, especially in AfricanAmericans. Multiple studies suggest that both genetic and environmental factors are important in asthma susceptibility. The aim of the Collaborative Study of the Genetics of Asthma (CSGA) is to identify asthma susceptibility loci. The CSGA is composed of four centers (Johns Hopkins University, university of Chicago, University of Maryland, University of Minnesota, and a data coordinating center at Bowman Gray). At each center, families were ascertained through two siblings with asthma. All family members were characterized with spirometry, bronchial responsiveness to methacholine or reversibility testing, skin-tests and questionnaire data. The initial genome screen has been completed on the first 237 sib pairs from three racial groups (African-American, Caucasian, and Hispanic), and genotyping on the remaining family members and families will be completed before the start of the renewal proposal. Therefore, the initial aim of the CSGA to map susceptibility regions has been completed, with detection of several novel chromosomal regions, and replication of several regions previously linked to associated phenotypes. In order to determine the importance of these regions in asthma susceptibility, and the impact of environmental risk factors, we propose to 1) evaluate the evidence for linkage in the complete CSGA data using 2-point, multipoint and multilocus approaches for asthma and associated phenotypes (including BHR, total serum IgE and skin test reactivity to standardized allergens); 2)perform fine mapping studies of regions using additional genetic markers to obtain a <2 cM map; 3) identify candidate genes and novel sequence variants; and 4) characterize a patient population

Studies

23

with asthma to study identified variants with respect to asthma severity and bronchial inflammation. These studies will allow US to identify asthma susceptibility genes and their variants, interactions with other genes and environmental risk factors, as well as provide insight for the development of improved treatment and ultimate prevention of asthma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COLLECTIN DEFICIENCY IN THE MOUSE Principal Investigator & Institution: Hawgood, Samuel; Professor of Pediatrics; Pediatrics; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-JUL-1997; Project End 30-JUN-2005 Summary: A complex immune system protects the mucosal surfaces of the respiratory tract from the constant exposure to pathogenic microorganisms and environmental allergens. The collectin proteins (collagen-like lectins) are components of this multifaceted system. Two of the 6-member collectin family, surfactant protein A (SP-A) and surfactant protein D (SP-D), are present in the lining fluids of the respiratory tract, in good position to provide immunological surveillance against both microbes and allergens. The long-term objectives behind this proposal are to determine the mechanisms of collectin action in pulmonary host defense and the relative importance of the collectins in maintaining human health. To best focus on specific mechanisms a single model organism, influenza virus (IAV), will be studied in several transgenic mouse models of altered collectin expression. The hypothesis to be tested in this proposal is that SP-A and SP-D limit lung injury from IAV infection by distinct and complementary mechanisms, specifically SP-D acts primarily as a direct viral neutralizing molecule blocking infection of the epithelium while SP-a reduces the viral load primarily by enhancing macrophage phagocytosis. The proposal also tests the idea that the collectins present IAV to the cells of the adaptive immune response and modify the cellular and humoral response to infection. These hypotheses will be tested by four specific aims. Aim 1: To determine the respective role of SP-A and SP-D during strain specific IAV infection in vivo. Aim 2: To characterize the effects of SP-A and SP-D on the response of macrophages to IAV. Aim 3: To determine if SP-A or SP-D influences the humoral and cellular immune response to IAV infection. Aim 4: To characterize the critical functional domains of the collectins in mediating the mouse response to influenza virus. Although our studies are focused on a specific organism, we expect the mechanisms underlying collectin-IAV-host interactions will pertain more generally to the action of collectins in respiratory immune responses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: COLUMBIA CENTER FOR CHILDREN'S ENVIRONMENTAL HEALTH Principal Investigator & Institution: Perera, Frederica P.; Assistant Professor; Environmental Health Sciences; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2004; Project Start 01-NOV-1998; Project End 31-OCT-2008 Summary: (provided by applicant) The overall theme of the Columbia Center for Children's Environmental Health (CCCEH) is the identification and prevention of risks of neurodevelopmental impairment and childhood asthma from prenatal and postnatal exposure to urban pollutants. Since it was established in 1998, the Center has forged a

24

Allergens

successful partnership with West Harlem Environmental Action, Inc. (WE ACT), and nine other community organizations to identify and prevent environmental causes of childhood disease in Northern Manhattan and the South Bronx. The Center has enrolled and retained a unique cohort of mothers and children of color who belong to one of the most at-risk urban populations in this country with respect to environmental exposures, social adversity, and childhood health problems. Using molecular epidemiologic approaches, Center investigators have developed a rich body of knowledge about this vulnerable and disadvantaged urban population. They have documented substantial prenatal exposure to indoor and outdoor urban pollutants, including the combustion byproduct polycyclic aromatic hydrocarbons (PAH), environmental tobacco smoke (ETS), pesticides, and pest allergens. The research has demonstrated significant associations between prenatal exposures to those pollutants and adverse birth outcomes and/or neurodevelopmental, immunological, and respiratory health outcomes in children studied through age two. Building on its achievements of the past five years, the Center proposes several important new initiatives. These include follow-up of the mother and child cohort through ages five to seven, as the children enter school, with links to school performance data at age eight. Additional exposure, biomarker, and outcome assessments will allow testing of new etiologic hypotheses in the community based participatory research (CBPR) projects on asthma and growth and development. A new laboratory-based mechanistic research project will elucidate possible mechanisms of in utero sensitization by co-exposure to PAH/diesel exhaust particles and allergens, directly complementing the CBPR asthma project. A CBPR Intervention project on integrated pest management and health-related housing improvements will be conducted in partnership with the New York City Departments of Health and Mental Health and the New York City Housing Authority. A new Community Outreach, Translation, and Application Core (COTAC) will ensure that the Center's findings have local and national public health impact. COTAC initiatives will include: education of medical students, medical residents, and pediatricians about children's environmental health; a new community campaign to improve air and housing quality in New York City, co-led by WE ACT; and risk assessment, cost, and risk prevention analyses on the Center's findings regarding the health effects of environmental exposures and the costeffectiveness of IPM. In summary, it is important that the Center as an institution be continued as an established and valued resource to the community, scientific researchers, and policymakers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COMMUNITIES ORGANIZED AGAINST ASTHMA AND LEAD (COAL) Principal Investigator & Institution: Ward, Jonathan B.; Professor & Director; Preventive Medicine and Community Health; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 30-JUN-2007 Summary: (provided by applicant) Communities Organized Against Asthma and Lead: Project COAL (Communidades organizadas contra asthma y plomo) will be a partnership between De Madres a Madres, Inc. in Houston, TX, The University of Texas Medical Branch in Galveston, Casa de Amigos Health Center, and the Environmental Justice Clinic at Texas Southern University School of Law. The partnership will bring together a well-established and respected community based organization in the Near North Side community of Houston, with Environmental Toxicologists in the NIEHS Center at UTMB, health care providers at the Harris County Hospital District Clinic

Studies

25

serving the Near North Side, and attorneys and law students with a history of response to environmental health problems in disadvantaged communities. This partnership will address two pressing environmental problems in the homes of this community: exposure of children to lead, from paint, and to agents that can trigger asthma. We will address these issues first through a novel approach to communication using theater as a means to educate and to elicit responses from the community. This approach will inform the community about Project COAL and provide local knowledge from the community to the partners in this project. The second focus of the project will be to serve the needs of residents in the community by making assessments of their homes to identify sources of lead and agents that can trigger asthma. Paint samples will be tested for lead. Levels of allergens (dust mites, mold spores, pollen) in the air will be determined, irritant chemicals and allergens from insects and rodents will be measured. UTMB will train local resident home assessment teams and perform the laboratory tests. Residents will be given training to enable them to reduce or eliminate these hazards from their homes and they will receive consistent follow-up from the home assessment teams. The medical clinic and environmental justice clinic will serve in an advisory capacity and provide data about the community, and assist in specific situations when the need arises. The primary purpose of Project COAL is to give De Madres a Madres the means to provide services to reduce the exposure of children in their community to agents that can result in lead exposure and asthma exacerbation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COMMUNITY PREVENTION INTERVENTIONS FOR URBAN DEMOLITION Principal Investigator & Institution: Farfel, Mark R.; Kennedy Krieger Research Institute, Inc. Baltimore, Md 21205 Timing: Fiscal Year 2002; Project Start 15-SEP-2000; Project End 31-MAR-2004 Summary: (Taken from the Applicant's Abstract) As part of ongoing urban redevelopment efforts, aging U.S. cities are razing thousands of abandoned and derelict houses in aging neighborhoods. Baltimore, for example, has initiated a campaign to demolish 22,000 vacant, aging and deteriorating row houses by the year 2008. Such housing is likely to contain multiple environmental hazards, including lead-containing paint and dust, asbestos, rats, cockroaches, allergens and molds. Demolition activities can increase risks to human health as a result of the dispersion of multiple housingrelated hazards into the ambient environment including neighboring houses, streets, sidewalks, yards, gardens and schools. During the course of their ongoing study of the fate of lead during demolition, Baltimore residents of minority and low-income neighborhoods expressed concerns about the hazards of usual demolition practices. Such concerns have included inadequate control of dust, rodents, insects, waste water, the public's access to the demolition site, and a lack of advance notice and educational/safety information to residents. Preliminary results from this ongoing study indicate that usual demolition practices are associated with increased lead levels in dust fall near the demolition site and that, remarkably, urban redevelopment activities are often undertaken with little knowledge and understanding of how to address and prevent human exposures to multiple housing-related health hazards. Their research goal is to develop culturally appropriate, community-based prevention interventions which are field tested and then incorporated into urban redevelopment activities in minority and low-income communities to improve the prevention and control of environmentally-related diseases and to enhance environmental justice. Specific aims are: (1) to develop, with input from community organizations, health and

26

Allergens

housing agencies, and public health experts, a package of preventive interventions at the house and block level to control exposure to the multiple environmental hazards potentially generated by residential demolition and; (2) to assess the costs and effectiveness of the intervention package by conducting longitudinal field based research on two city blocks slated for demolition which includes measurement of lead and allergens (cockroach and mouse) in entryway mat dust; and (3) to assess the level of community acceptance and satisfaction by conducting in-home interviews. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--CLINICAL Principal Investigator & Institution: Sundy, John S.; Assistant Professor; Duke University Durham, Nc 27710 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: The primary objective of Core B (Clinical Core) is to collect high quality clinical information and biologic specimens from subjects which will allow accurate phenotype-genotype associations necessary for the success of Projects 1-4. A key to the success of the core is a highly experienced investigator team with a proven track record in subject recruitment, phenotype determination, and collection of biologic specimens in asthma. Using these resources and expertise we will complete the following specific aims: Aim 1. Recruit subjects and obtain clinical data and biologic specimens for Project 1. Specifically, we will: 1) screen approximately 150 subjects to determine their asthma/atopy status; and 2) perform subsegmental bronchial challenge with lipopolysaccharide (LPS) and dust mite allergen, and obtain bronchial cells for gene expression analysis in 40 characterized on the basis of asthma and atopy phenotypes (10 subjects with atopic asthma, 10 subjects with atopy but not asthma, 10 non-atopic asthmatics, and 10 non-atopic, non-asthmatics). Aim 2. Establish and characterize an African-American asthma cohort for genetic analysis studies in Project 2. We will identify and characterize the phenotype of 200 probands with childhood asthma, 2-3 first-degree relatives of each proband, and 200 age- and sex-matched non-asthmatic controls (total n=900). Aim 3. Perform allergen skin testing on subjects enrolled in Project 3. 250 subjects tmdergoing inhaled ozone challenge will be skin tested with a panel of allergens to establish their atopy status. Aim 4. Obtain human bronchoalveolar lavage cells and fluid for Project 4. Bronchoalveolar lavage cells and fluid will be obtained from 40 subjects undergoing research bronchoscopy in Project 1. A portion of BAL cells and fluid, and phenotype data will be transferred for use in Project 4. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: CORE--IMMUNE FUNCTION AND INFLAMMATION Principal Investigator & Institution: Stephensen, Charles B.; Research Scientist; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 956165200 Timing: Fiscal Year 2003; Project Start 15-JAN-2003; Project End 31-DEC-2007 Summary: (provided by applicant): Background And Significance: Immune Function And Inflammation Core: Co- Directors: Charles B. Stephensen, PhD. Mark Shigenaga, PhD A 1. Asthma and other chronic diseases are linked to obesity in minority youth The epidemic of obesity that is currently sweeping the U.S. is affecting adolescents as well as adults, and is particularly evident in African American and Hispanic youth (Popkin and Udry 1998; Dwyer, Stone et al. 2000). This unprecedented increase in body mass index (BMI) in adolescents is an unhealthy trend since high BMIs increase the risk of

Studies

27

developing chronic disease, including asthma, type 2 diabetes and cardiovascular disease. Recent studies in urban African American and Hispanic children and adolescents have documented this association of obesity with asthma risk (Gennuso, Epstein et al. 1998; Luder, Melnik et al. 1998; von Mutius, Schwartz et al. 2001). This association is in addition to the increased burden of asthma that inner city children may face as a result of increased exposure to allergens in substandard housing (Eggleston, Rosenstreich et al. 1998). Type 2 diabetes, long considered an adult-onset disease associated with obesity, is now being diagnosed in adolescents, particularly African Americans and Hispanics (Bourgeois 2002). Poor health behaviors (e.g., high dietary cholesterol, increased body fat) that are risk factors for cardiovascular disease are also more prevalent in African American and Hispanic adolescents than in their European American counterparts (Fardy, Azz.ollini et al. 2000). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DETERMINANTS OF ASTHMA MORBIDITY IN AN URBAN POPULATION Principal Investigator & Institution: Wisnivesky, Juan P.; Medicine; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2007 Summary: (provided by the applicant): Despite advances in asthma therapy, asthma morbidity has increased dramatically in the past decade, especially among inner-city minority populations. While epidemiological studies have highlighted the sociodemographic groups most at risk for illness and death, the underlying reasons for these disparities in health are not well understood. The overall objective of this project is to evaluate the factors contributing to asthma morbidity in inner-city minority populations. The specific aims are to: (1) develop an instrument to measure patient adherence to asthma control medications; (2) determine the relative contribution of low adherence to medications, inadequate patient-provider communication, and poor access to care to poor asthma outcomes; (3) test if sensitization and indoor exposure to cockroach allergen result in increased asthma morbidity; and (4) develop the protocol and perform pilot testing of an intervention to improve the outcomes of adult inner-city asthmatics. The proposed study will enroll 420 adults with persistent asthma from the Primary Care Clinic of the Mount Sinai Hospital, located in East Harlem, a community in the epicenter of the asthma epidemic. The protocol will include a comprehensive baseline interview followed by telephone questionnaires at 4- and 12-weeks. The domains covered by the baseline interview will include sociodemographics, comorbidities, access to care, past utilization, current medications, adherence, knowledge, beliefs, psychological symptoms, quality of patient-provider communication, environmental exposure to indoor allergens, and metered dose inhaler technique. Allergen specific IgE antibodies will be used to document allergic sensitization. At 4 and 12 weeks following the baseline assessment, telephone interviews will be conducted to obtain data on asthma symptoms, quality of life, peak flow measurements, hospitalizations, emergency department visits, and unscheduled outpatient visits. In the final 11/2 years of the project, the data collected from the initial phase of this proposal will be used to develop and pilot a self-management intervention to improve the outcome of inner-city asthmatics. During the five-year project, the candidate will pursue advanced graduate work in clinical epidemiology and health services research to further develop his scientific skills. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

28

•

Allergens

Project Title: DIESEL, ALLERGENS AND GENE INTERACTION AND CHILD ATOPY Principal Investigator & Institution: Lemasters, Grace K.; Professor; Environmental Health; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 30-JUN-2006 Summary: (provided by applicant): Allergic disorders affect over 40 million children, resulting in two million missed school days and costing society more than 10 billion/year. Atopy, defined as immediate hypersensitivity to specific allergens, is the strongest risk factor for child-onset asthma. The reported increasing incidence of atopic respiratory disorders is exaggerated in urban children living in westernized countries. There is intriguing scientific evidence demonstrating that diesel exhaust particles (DEP), a constituent of truck exhaust, promote expression of Th2 cytokines and production of IgE antibodies. The concern is that these exposures enhance clinical expression of IgE mediated respiratory disorders. Hence, children residing near interstate highways are at potentially high risk for exposures to truck emissions and resultant atopic respiratory disorders. In the Cincinnati metropolitan region, three interstate corridors intersect creating one of the busiest U.S. north/south and east/west commercial truck routes converging on a population of 1.9 million. The proposed investigation will follow two groups of children from birth through early childhood. The first group are children living within 400 m of interstate highways. This group will be matched by birth date, race and income to a second group living beyond 1 km. There are two study purposes. The first is to measure DEP exposure levels and to determine if children with higher levels of exposure are at an increased risk for atopy and atopic respiratory disorders. The second is to determine if these effects are magnified in a genetically at risk subpopulation. The proposed study is a prospective cohort and nested case control design. The cohort of newborns will be evaluated prospectively for positive skin prick tests (SPT), allergic rhinitis and asthma. Residential exposures to DEP and aeroallergens also will be characterized longitudinally.The children who develop positive SPT will be matched by race and gender to controls having negative but the same number of SPT. The case control study will evaluate potential susceptiblity as measured by cytokine polymorphisms and to determine if exposure to DEP promotes the phenotypic expression of atopy and atopic respiratory disorders. This study design is optimum for determining if young children exposed to DEP have enhanced sensitization to aeroallergens and for dissecting gene-environment interactions. Results of this study may ultimately result in finding a preventable cause of atopic disorders in children. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: DIET, IMMUNE MODULATION, AND ASTHMA IN EARLY LIFE Principal Investigator & Institution: Weiss, Scott T.; Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 30-SEP-1998; Project End 31-AUG-2003 Summary: Asthma is the most common chronic disease of childhood in the developed world, affecting about 10 million U.S. children under the age of sixteen. Asthma prevalence in Western industrialized countries is increasing at an alarming rate, and this increase is coincident with an increase in type I hypersensitivity (allergy). Eighty percent of childhood asthmatics exhibit hypersensitivity to indoor aeroallergens. Maternal diet represents an important exposure that has significant potential to modify immune function and, hence, the development of allergy. To study the evolution of the asthmatic immune response, focusing on the cellular response to allergens and foods, this

Studies

29

application proposes a collaborative study involving pulmonary and dietary epidemiologists (Drs. Weiss, Colditz, and Gold), experts in lipid biochemistry (Dr. Sacks) and immunologists specializing in the role of T- and B-cells in the asthmatic response (Drs. Finn and Perkins). The application proposes to utilize a prospective longitudinal cohort study of children of asthmatic mothers to examine the role of maternal dietary fat intake (N-3 polyunsaturated fat) in the development of (1) nonspecific and specific cellular immune responses by age 2-3; (2) asthma/wheeze, atopic dermatitis, food allergy, and allergic rhinitis by age 3. In a subset of 50 five year old children with asthmatic mothers, 25 with high and 25 with low N-3 fatty acid intake during pregnancy, studies will assess lymphocyte proliferation and cytokine production (IL-4, IL-5, and interferon-gamma [IFN-gamma]) to nonspecific (PHA) and representative specific antigenic stimulation: beta-lactoglobin (food), cockroach (Bla g2) and dust mite (Der fI) (indoor allergen). Additional potentially influential host and environmental factors to be examined include: parental asthma history, maternal age, perinatal history, acute lower respiratory illness history, day care, environmental tobacco smoke, birthweight, head circumference, sex, and race. The application proposes to test the following hypotheses: 1. At birth, maternal dietary N-3 fatty acid levels assessed in the second and third trimester of pregnancy with a semiquantitative food frequency questionnaire will be correlated with N-3 fatty acid levels in cord blood. 2. At birth, infants with high cord blood levels of N-3 fatty acids will have reduced lymphocyte proliferative responses to cockroach, dust mite (indoor allergen), and betalactoglobin and reduced levels of inflammatory cytokines (IL-4, IL-5) and increased levels of interferon-gamma. 3. High cord blood levels of N-3 fatty acids and reduced lymphoproliferative responses to cockroach, dust mite and beta-lactoglobin will independently predict decreased development of allergic disease (asthma/wheeze, atopic dermatitis, food allergy, and allergic rhinitis) at age 3. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DOMAINS FOR FCERI SIGNALING & INTERNALIZATION Principal Investigator & Institution: Wilson, Bridget S.; Associate Professor; Pathology; University of New Mexico Albuquerque Controller's Office Albuquerque, Nm 87131 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2008 Summary: (provided by applicant): Allergens stimulate release of mast cell inflammatory mediators by crosslinking IgE bound to the high affinity IgE receptor, FcepsilonRI. By immunogold electron microscopy of native membrane sheets, we have recently shown that multiple, distinct microdomains mediate signaling and receptor internalization in mast cells. Receptors cluster together with Lyn in resting cells, are phosphorylated by Lyn very rapidly after stimulation in the signal initiation step, and then segregate from Lyn as receptors accumulate in osmiophilic regions of membrane. For signal propagation, these dark patches of membrane also accumulate Syk, PLCgamma2, p85, Gab2 and Grb2, identifying the osmiophilic patch as a primary site of FcepsilonRI signaling. Recruitment of AP-2, Eps15 and clathrin to receptors in osmiophilic patches, and the budding of clathrin-coated vesicles there, also define it as the primary site of FceRI internalization. Secondary signaling domains include p85 and PLCgamma1 and may be organized around the palmitoylated transmembrane adaptor protein, LAT. We hypothesize that these distinct microdomains perform separate tasks in mast cell signaling and receptor trafficking. To do so, they require unique lipid and protein compositions. We further propose that, after the initial segregation of receptors from Lyn, receptors go through a series of interaction and segregation steps with signaling and internalization machinery. The "segregation model" predicts that these

30

Allergens

successive association/dissociation steps are ordered in part by features of the osmiophilic patch. To test these hypotheses, we propose to use a combination of electron microscopy, recombinant protein expression, biochemical assays and mass spectrometry to map the distribution of proteins and lipids in primary and secondary domains. We will test roles for acylation or prenylation of key signaling proteins in their targeting to either primary or secondary domains. We will also define the requirement for ubiquitin ligases and multiubiquitination in receptor endocytosis. This work will define roles for microdomains in the processes of signal initiation, signal propagation and receptor internalization. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENDOTOXIN EXPOSURE ALTERS ANTI-TETENUS IGE IN INFANTS Principal Investigator & Institution: Ownby, Dennis R.; Head; Pediatrics; Medical College of Georgia 1120 15Th St Augusta, Ga 30912 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2005 Summary: (provided by applicant): Recent studies have suggested that high levels of endotoxin exposure during infancy are associated with a reduced risk of subsequent allergic sensitivity. Learning more about the relationship between environmental endotoxin exposure and subsequent allergic disease is potentially important given the increasing prevalence of allergic diseases in the United States. The goal of this application is to evaluate the hypothesis that high levels of environmental endotoxin exposure will be associated with reduced anti-tetanus IgE responses following routine immunizations with tetanus toxoid in infancy. This study will utilize the structure of the ongoing WHEALS Study (AI/ES 50681, a study to evaluate the hygiene hypothesis in a multi-racial birth cohort of 3000 children in and around Detroit, MI). In home endotoxin assessements will be increased from 1 to 5 locations (the floor beside the infant's crib, the infant's bed, the parent's bed, the floor beside the parent's bed, and the floor in the living/family room) during both the 1 and 6-month home visits. Endotoxin will be measured using a commercial kinetic Limulus assay. Relationships between endotoxin measurements by location, month of year, and household characteristics (e.g., animals in the home) will be examined. These analyses will provide a better understanding of variations in endotoxin exposure within homes and allow an assessment of whether measurements from certain locations are more closely related to altered IgE production. All infants in this cohort are expected to receive routine immunizations with DtaP (diphtheria, tetanus and acellular pertussis) vaccine at 2,4, 6-7 and 15-18 months of age. In addition to measuring IgE specific for common allergens at 6 and 24 months of age, IgE specific for tetanus toxoid will be measured in the same blood samples using the commercial Pharmacia CAP assay. The anti-tetanus IgE measurements will be analyzed to learn whether IgE production is influenced by endotoxin exposure. Important advantages of measuring anti-tetanus IgE are the likelihood that most infants will receive all immunizations with identical doses at the same ages. The well standardized tetanus immunizations contrast with the highly variable and difficult to measure exposures to natural allergens. Anti-tetanus IgE responses are also likely to be measureable much earlier in infancy than are responses to other allergens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: ENVIRONMENTAL AND GENETIC DETERMINANTS OF ASTHMA INCIDENCE Principal Investigator & Institution: Mcconnell, Rob S.; Associate Professor; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033

Studies

31

Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant): Asthma is the most common chronic disease of childhood, and asthma prevalence and incidence have been increasing over the past several decades. This population-based cohort study of risk factors for asthma in schoolaged children offers an opportunity to address this important, poorly understood chronic childhood disease. The results from the CHS provide leads for reducing the burden of asthma. In high ozone communities, physician diagnosis of asthma in the CHS was associated with time spent outside and with playing team sports, factors which increase exposure and ventilation rates. Obesity was associated with new onset asthma; pets accounted for a substantial proportion of the attributable risk; and interaction was observed between a prototype air pollutant, cigarette smoke, and GSTP1, an enzyme involved in the metabolism of oxidants present in air pollution. To expand on these findings, the investigators propose to establish a new cohort of 6,000 kindergarten, first, and second grade children, enriched with children who play team soccer. The diagnosis of incident asthma cases in each of the 12 communities will be confirmed by a standardized clinical examination. Information on physical activity will be obtained from team sport participation and pedometry. The extensive air pollution monitoring system in each of the 12 communities will be enhanced by measurement of N02, 03, PM2.5 and CO at homes, schools and areas where children exercise. Individual exposures will be assigned using spatial mapping techniques and micro-environmental models. A case-control study of new asthmatics will provide an opportunity to: (1) replicate associations between asthma and genes involved in the response to reactive oxygen species; (2) clarify the temporal association between asthma onset and exposure to pets and other indoor allergens; and (3) evaluate interactions between air pollution and indoor allergens, and between exposure to ambient air pollution and polymorphisms in genes involved in the response to reactive oxygen species. This proposal presents innovative approaches to defining the asthma phenotype in large epidemiologic studies, physical activity assessment, exposure assessment, and genetic epidemiology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EPIDEMIOLOGY Principal Investigator & Institution: Correa-Villasenor, Adolfo; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-NOV-2001; Project End 31-OCT-2002 Summary: Asthma morbidity is high among inner city children. The factors responsible for this public health problem remain unclear but are probably related to genetics, psychosocial factors, and exposures to allergens and air pollutants, including environmental tobacco smoke, particles, ozone and nitrogen dioxide. The proposed epidemiologic project aims to elucidate the relationship between exposures to allergens and air pollutants and asthma morbidity among inner city children with asthma. The specific aims are: (1) to characterize exposure to allergens and air pollutants among inner city children with asthma; (2) to determine the prevalence of respiratory morbidity among inner city children with asthma; and (3) to assess whether exposure to higher levels of both air pollutants and allergens results in more asthma morbidity than expected based on the effects from independent exposures to air pollutants and allergen. This community-based epidemiologic project will enroll children who currently have symptomatic asthma in an asthma education program in 25 elementary schools and invite them participate in a study of the relationship of asthma to air pollution. Participants (expected n= 300) will be recruited over a 3 year period. Children

32

Allergens

and their families will undergo a clinic visit with interviews on demographics, psychosocial, past and current asthma health status, exposure to passive smoking, and time-activity patterns. Children will receive allergy skin tests, and provide spirogram, urine for cotinine and serum for total IgE. Children's homes will be visited to ascertain the physical condition, and measure allergens in settled dust, airborne PM/2.5 and PM/10, ozone, NO2 and cotinine. Data on ambient measurements of pollutants will be obtained from the State of Maryland (ozone and NO2 and a USA EPA monitoring station (particles) in the study community. A sample of study children (n=200) will be interviewed six months after baseline to assess asthma status. Analysis will examine whether asthma morbidity is associated with exposure to allergens, pollutants or a combination, and whether apparent seasonal variations in asthma morbidity are associated with seasonal variations in allergens and pollutants. The goal of this effort is to identify environmental factors associated with asthma morbidity that may help in the development of cost-effective community-based interventions in urban environments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MEETINGS

EXPERIMENTAL

AND

CLINICAL

CONTACT

DERMATITIS

Principal Investigator & Institution: Cooper, Kevin D.; Professor; University Hospitals of Cleveland Lksd 1400 Cleveland, Oh 441065000 Timing: Fiscal Year 2002; Project Start 20-SEP-2002; Project End 31-DEC-2002 Summary: (provided by applicant): This proposal requests support for the third meeting of the Experimental Contact Dermatitis Research Group (ECDRG). The ECDRG was founded in 1997 to provide a forum for North American scientists and physicians to discuss issues concerning irritant and allergic contact dermatitis. The first meeting was held in Cincinnati in May 1999 and the second in Dallas in Nov. 2000. The first two meetings have been useful in bringing together parties from academic medicine, university and research institute labs, industry, and government. This will be the second meeting held in conjunction with the American Contact Dermatitis Society (ACDS). The inclusion of the ACDS at the Dallas meeting brought together for the first time on a large scale a coalition of basic scientists and clinicians who have special expertise in contact dermatitis, which helped provide a translational research element in each segment of the meeting. This format was popular with the attendees and the meeting in Cleveland will follow the same combined format. In addition, a satellite meeting will be held on Skin Equivalents immediately prior to the ECDRG, which will help bring in scientists who use such technology to predict contact dermatitis, further enriching the meeting interactions. Three goals of the meeting are to provide an interdisciplinary forum: 1) To discuss: a) predictive methods that identify irritants and sensitizers before human exposure, b) methods to distinguish irritants from allergic responses with current tests, c) pathogenic mechanisms of dermatitis and possible interventions, d) factors that modify expression of dermatitis e) variables in sensitization that affect tolerance and disease expression, and translating these concepts into interventions that reduce or modify sensitization and elicitation and to induce tolerance. 2) To update attendees regarding: a) allergens that are newly recognized or increasingly recognized in clinical practice b) new technology as it applies to data analysis and epidemiology of dermatitis and c) opportunities arising from patient--centered interactions between clinicians, industry and government colleagues. 3) To enable participants to plan collaborative research projects and to introduce young scientists to the field. The proposed meeting will allow exchange not only among researchers in the various lab

Studies

33

and clinical research settings, and clinicians but also between researchers interested in this field who see the practical outcomes in patients with diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EXPOSURE INTERVENTION IN A RURAL PEDIATRIC ASTHMA COHORT Principal Investigator & Institution: Thorne, Peter S.; Professor; Prev Med & Environmental Hlth; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-JUL-2006 Summary: (provided by applicant): Recent studies have provided evidence to support a causal relationship between asthma exacerbations and exposure to inflammatory agents such as endotoxin and fungal glucans. Investigators have also begun to assess what changes to the environment can reduce the severity of asthma. This project is a community- based, participatory, environmental intervention study in an established cohort of asthmatic children who reside in a rural, medically underserved, and ethnically diverse Iowa county. The cohort is currently serving as the control group for a medical intervention in the adjacent county. This project recognizes that interventions that are effective for urban residents may not apply to children living on farms and in rura1 communities. Thus, this project will test the efficacy of an intervention that includes a household hygiene educational intervention, professional super cleaning, booster cleaning, and integrated pest control against a minimal intervention in the control group. This randomized controlled study with repeated measures has the following specific aims: Aim 1. Develop and validate reproducible, quantitative methods for assessing airborne and settled dust exposures to inflammatory agents and rural allergens in homes and schools. Aim 2. Perform a pilot study to establish the time course for changes in environmental concentrations of etiologic agents before and at various times after an extensive "Super Cleaning." Aim 3. Perform a controlled, targeted environmental intervention in homes and schools of 132 rural child asthmatics and determine the effectiveness of these measures for reducing exposures to etiologic agents for asthma. Aim 4. Determine the effectiveness of the asthma intervention measures for reducing asthma symptoms, school absenteeism, and utilization of medical services; and improving pulmonary function and quality of life. Aim 5. Through analysis of preintervention and post-intervention exposure data and health status data, examine exposure-response relationships between endotoxins, glucans, and other exposure and indicators of health status. Environmental sampling in the homes will occur at baseline and 6, 14, and 26 weeks. Home hygiene education will occur at 2 weeks, the professional super cleaning will take the place at 4 weeks, follow-up home hygiene educations at 6 and 14 weeks, and the booster cleaning at 16 weeks. Detailed health and home hygiene questionnaires and home inspections will be conducted at baseline and one year later, as will child spirometry. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: EXPRESSION, REGULATION, FUNCTION OF MICE/HUMAN IA GENES Principal Investigator & Institution: David, Chella S.; Professor of Immunology; Mayo Clinic Coll of Medicine, Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 01-SEP-1977; Project End 31-MAY-2005 Summary: (Adapted from the Investigator's abstract): The HLA class II molecules play a pivotal role in most immune responses. Thus, while the HLA class II molecules are

34

Allergens

critical for protection against infection and cancer, they are also implicated in susceptibility to various autoimmune diseases and immune deficiencies. Considerable knowledge has been generated on the MHC class II molecules through studies with the mouse as well as the human system. During the past few years, transgenic mice expressing HLA-DQ and -DR genes have provided us with an additional tool to dissect the role of class II molecules in various human immune responses. As part of this research proposal, the available transgenic mice will be generated to fill the gaps in the information and to complement studies. The genes are introduced into mice lacking endogenous class II such that human class II antigens are the sole restricting element for CD4. In selected mice, human CD4 gene will replace the deleted mouse CD4 gene to further humanize these mice. HLA-DQ and -DR restricted epitopes on known human allergens, house dust mite and ragweed will be identified, and antagonist peptides will be generated to test their efficacy in desensitization in an in vivo model of allergy. An HLA-DR/DQ restricted experimental autoimmune encephalomyelitis disease model for Multiple Sclerosis will be studied to identify epitopes on potential human autoantigens such as MBP, PLP, and MOG, and to understand how the gene complementation between the HLA-DQ and -DR genes determine predisposition, onset, and the severity of the disease. A spontaneous insulitis model in the HLA-DQ/DR transgenic mice would be utilized to understand the events which lead from insulitis to full-blown diabetes. This model can also be used to understand the role of potential autoantigens such as GAD and insulin in human diabetes. Finally, this set of transgenic mice will be a resource for investigators studying various aspects of the role of HLA class II molecules in human immune responses and to generate DQ/DR restricted mouse models for human diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ALLERGENS

FUNCTIONAL

ANALYSIS

OF

MAIZE

GROUP-1

POLLEN

Principal Investigator & Institution: Cosgrove, Daniel J.; Biology; Pennsylvania State University-Univ Park 110 Technology Center University Park, Pa 16802 Timing: Fiscal Year 2002; Project Start 15-DEC-2000; Project End 30-NOV-2004 Summary: (from the application): When grass pollen lands on the receptive surface of the stigma, it begins to hydrate and secrete various proteins. Among these is an antigenic protein known as the group-I grass pollenallergen. This protein is a major cause of hay fever and asthma, afflicting ca. 25 percentof the US population. We recently discovered that the group-I allergen from maize pollen (called Zea ml) loosens the extracellular matrix (wall) of the grass stigma. In this proposal, we outline several experimental approaches to elucidate the structure, function, and evolutionary distribution of the group-I allergens and related proteins, which we hypothesize aid pollen tube penetration of the stigma and style. RNA and protein analyses will be used to determine the temporal and spatial pattern of Zea ml expression and secretion. Using a reverse genetics approach we have identified four maize lines with transposon insertions in the Zea ml gene; these lines will be studied to learn the phenotypic consequences of Zea ml gene disruption. We will take advantage of the unusual physical properties of Zea ml to study how it acts to loosen the cell wall, still an enigmatic problem. By X-ray analysis of Zea ml crystals, we propose to solve its structure and to use this structure to investigate how the protein interacts with the polymers of the extracellular matrix. By binding assays we will define the substrates to which this protein binds. We will test these ideas by site-directed mutagenesis of recombinant protein. We will also attempt to identify peptides, monoclonal antibodies

Studies

35

and oligosaccharides that interfere with Zea ml activity, to be used as inhibitors of the biological function of these proteins. To date, it appears that group-I grass pollen allergens are found only in grasses. To evaluate the evolutionary distribution of this protein, we will test pollen extracts from grasses, close relatives, and more distant plant groups by means of activity and immunoblot assays. Finally, we will leverage the insights gained from analysis of Zea ml to study the function of group-Il and group-Ill grass pollen allergens, which show significant sequence similarity with the carboxy terminus of group-I allergens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENERATION OF ANTIGEN SPECIFIC REGULATORY T CELLS Principal Investigator & Institution: Vasu, Chenthamarakshan; Assistant Research Professor; Surgery; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2006 Summary: (provided by applicant): Immunosuppressive drugs result in global attenuation of the immune response with potential fatal side effects, thus, limiting their utility in treating autoimmune diseases. A more effective approach would involve antigen specific inactivation of autoreactive T cells. The role of the costimulatory molecule CTLA-4 in tolerance induction has been well documented. In spite of the significant tolerogenic response that was observed in our earlier, there are two potential limitations to the targeted delivery of CTLA-4 signaling. The first is a limited accessibility to certain large target tissues second is the need necessary to link antiCTLA-4 antibody to different tissue specific antibodies for different targets. Further, this strategy may not be effective in treating systemic autoimmune conditions. To overcome these potential limitations, we have recently designed a novel strategy by using matured dendritic cells (DCs) as APCs and manipulating the interaction at the immunological synapse through a DC bound cross-linking anti-CTLA-4 antibody to induce regulatory T cells and tolerance to a specific antigen presented by DCs. The major advantages of this system are 1) one BiAb can be used to induce tolerance to any number of antigens; 2) it can be used to tolerize T cells against autoantigens of systemic as well as organ specific autoimmune diseases and also can induce tolerance to allergens, allo- and xenoantigens, etc; 3) in vivo injected DCs could migrate into lymphoid structures and target organs throughout the body and inactivate antigen specific T cells; 4) use of the exceptional antigen presenting capability of DCs that could induce a much stronger regulatory T cell expansion and tolerance. Here, we propose to determine the therapeutic potential of an anti-CTLA-4 antibody coated dendritic cells and in inducing regulatory T cells. In aim-l, we will test the efficacy of BiAb in inducing regulatory T cells in vivo and in vitro. In aim-2, we will test the ability of these regulatory T cells in down modulating EAT and CIA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: HOME BASED ENVIRONMENTAL ADHERENCE TRIAL Principal Investigator & Institution: Eggleston, Peyton A.; Professor of Pediatrics; Pediatrics; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 05-AUG-1998; Project End 31-DEC-2003 Summary: Allergen avoidance is a risk-free therapy for asthma that has been shown repeatedly in clinical trial to reduce asthma symptoms and bronchial hyperresponsiveness. We propose to conduct the first trial of the effectiveness of this

36

Allergens

important adjunct therapy, comparing a home-based allergen control education program to customary education program. We will recruit 240 children aged 6-17 years who have asthma that is currently active. Each child and their family will undergo a baseline evaluation that will include questionnaires, allergy skin tests, spirometry and a home visit to evaluate allergen control behaviors and to collect dust from the child's bedroom to measure concentrations of house dust mite, cat, dog and cockroach allergens. After receiving traditional allergen control education in the clinic, participants will be randomized to receive either usual care in a pediatrician's office or a home-based behavioral educational and support program provided by trained Evironmental Control counselors. Support will include identification of environmental risk factors for the family, modeling and teaching control behaviors, problem solving with the family, and encouraging self-efficacy. Both office-based control and homebased intervention groups will be offered discounted environmental control supplies and cockroach extermination. Children and families will be assessed in clinic visits by a separate evaluation team at 6 to 12 months post randomization. Home visits will be repeated by the evaluation team at 6 to 12 months. Primary outcome will be changes in changes in Asthma-related Quality of Life measures and target environmental allergen levels in the home. Secondary outcomes include adherence with environmental control recommendations, changes in Rhinoconjunctivitis-related Quality of Life measures, FEV1, changes in environmental allergens other than the targeted allergen, self efficacy for environmental allergy control and healthcare utilization. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HYGIENE HYPOTHESIS: GENETIC ASPECTS Principal Investigator & Institution: Beutler, Bruce; Professor; University of California San Diego La Jolla, Ca 920930934 Timing: Fiscal Year 2002; Project Start 01-DEC-2002; Project End 30-NOV-2007 Summary: Both genes and environment and determine who will develop asthma. While genome-wide linkage screens and focused analysis of specific candidate loci have made inroads into the question of which genes are culpable in asthma, the preponderance of the genetic effect remains unexplained. A large number of low-frequency codominant mutations are believed to be responsible for most complex genetic diseases, and such mutations are not readily isolated through a genome-wide screen of the population at large. The environmental influence is complex, and in some respects paradoxical. On the other hand, asthma is provoked by environmental allergens. However, in accordance with the Hygiene Hypothesis, heavy exposure to environmental agents that induce an innate immune response can effectively prevent asthma. The physical basis for this effect has come into sharp focus with the finding that ligands such as lipopolysaccharides (LPS) and immunostimulatory oligodeoxyribonucleotides (ISSODN), which signal via the Toll-like receptors (TLRs), are able to attenuate airway hyper-reactivity. Hence, a discrete collection of genes has been found to contribute to innate immune sensing, and a practical assay for innate immune sensing has emerged. This proposal is designed to probe the repertoire of genes that link environmental immunostimulants (specifically ISS-ODN) and asthma. We will rely upon N-ethyl-Nnitrosourea (ENU) mutagenesis to identify genes that disrupt signaling initiated by ISSODN, and thereby block its ability to prevent airways hyper-reactivity. Mutations are found to have this effect will be isolated through positional cloning, and the genes involved will be characterized to determine the level at which they contribute to signaling. The human orthologs of these genes will be analyzed by DNA sequencing in asthma patients and in ethnically matched controls without asthma. Hence, we will first

Studies

37

identify loci wherein isolated mutations clearly producer airways disease in mice. We will then directly measure the effect of genetic load at these loci in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HYGIENE HYPOTHESIS: THE IMPACT OF ADAPTIVE IMMUNITY Principal Investigator & Institution: Corr, Mary P.; Assistant Professor; University of California San Diego La Jolla, Ca 920930934 Timing: Fiscal Year 2002; Project Start 01-DEC-2002; Project End 30-NOV-2007 Summary: Allergic diseases such as asthma are research epidemic proportions in the industrialized and developing world. Major factors driving these rising trends are increased exposure to sensitizing allergens and reduced stimulation of the immune system during critical periods of development. In allergic disease, reduced stimulation of the immune system during critical periods of development. In allergic disease, there is a polarization of T-lymphocyte responses, and enhanced secretion of cytokines involved in regulation of immunoglobulin E, mast cells, basophils and eosinophils, ultimately leading to inflammation and disease. The hygiene hypothesis suggests that early exposure to microorganisms stimulates the immune system to prevent this type of polarization and thereby inhibits the development of allergies. The central hypothesis of this proposal is that triggering the immune response through the Toll-like receptors, which bind to microbial products, establishes an immunologic window that preferentially differentiates T cells to a non-allergic phenotype and maintains this memory. We propose 1) to evaluate the role of TLR signaling in priming of the adaptive immune responses; 2) to determine the role of TLRs in the effector phase of the immune response; and 3) to evaluate the immunologic function of mice generated in Project 1 with novel germline mutations in rendering them resistant to ISS and/or LPS treatment. A clear understanding of the cellular and molecular mechanisms of allergic disease and the complex interplay between genetic and environmental factors may potentially identify new molecular targets for therapeutic interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: IMMUNE DYSREGULATION IN ALLERGIC ASTHMA Principal Investigator & Institution: Lipscomb, Mary F.; Professor and Chair; Pathology; University of New Mexico Albuquerque Controller's Office Albuquerque, Nm 87131 Timing: Fiscal Year 2002; Project Start 01-DEC-1996; Project End 30-NOV-2006 Summary: (Applicant's Abstract) The guiding hypothesis of this SCOR renewal is that allergic asthma results from a dysregulated immune response to allergens. The dysregulated immune response sets in motion a cascade resulting in the accumulation of IgE-sensitized mast cells and allergen-specific Th2 cells in airway mucosa, airway hyperreactivity, eosinophilic inflammation and airway remodeling with mucous cell metaplasia. The proposal consists of four projects, each with a clinical component, and three supporting cores, including a clinical core. Dr. Lipscomb's project proposes to study the role of lung antigen presenting cells, particularly lung dendritic cells (DCs), in pulmonary immune responses to allergens. Lipscomb will adoptively transfer T cell clones and lung DCs in a murine allergic pulmonary inflammation model and use human monocyte-derived DCs, human bronchoalveolar lavage fluids and bronchial biopsies in these studies. Dr. Oliver's project will exploit her laboratory's observation showing that basophils that don't release histamine following high affinity IgE receptor (FceRI) crossing-linking are deficient in the tyrosine kinase, Syk. Oliver proposes to determine whether people with such "non-releaser" basophils are protected from

38

Allergens

asthma. She will also explore the mechanisms for loss of Syk activity in non-releaser basophils and assess whether decreased serum IgE induced by anti-IgE therapy leads to a decrease in FceRI expression on human lung mast cells. Dr. Sklar's project will examine the molecular mechanisms involved in the preferential recruitment of eosinophils and basophils into the bronchial mucosa in asthma. Sklar will use novel technology to quantify changes in affinity and avidity of the molecules involved in the cell-cell interactions that model leukocyte adhesion to the endothelium. Dr. Tesfaigzi's project proposes to study the role of mediators generated in asthmatic lungs in causing mucous cell metaplasia. Specifically, Tesfaigzi win seek a role for suppression of normal apoptosis by the pro-apoptotic regulator, Bax, in mucous cell metaplasia. He will use an innovative mouse bronchiolar explant model, cytokine receptor and Bax knockout mice, human bronchial brushings, and autopsy tissues from asthmatics and controls. Collectively, the four projects will identify mechanisms involved in critical pathways that lead to asthmatic lung inflammation and bronchial remodeling with the goal of identifying possible targets for prevention or treatment of asthma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMMUNOGENETIC ANALYSIS OF IMMUNE RESPONSE TO ALLERGENS Principal Investigator & Institution: Huang, Shau-Ku; Associate Professor; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-DEC-2007 Summary: (provided by applicant): The genetic basis of IgE responsiveness leading to the expression of atopic diseases remains elusive. This is due, in part, to the multigenetic nature of the disease involving a complex array of molecular genetic networks and environmental factors. Recent consistent evidence has suggested that chromosome 5q, 11q and 12q regions contain susceptibility gene(s) regulating IgE responsiveness and/or asthma. The overall objective of our continuing effort is, therefore, to determine the nature of the susceptibility gene(s) and its functional relevance. In this new grant application, we will target specifically the candidate genes associated with the regulation of Th2 cell responses on these three critical chromosomal regions, for which the evidence of association with and linkage to atopic phenotypes have been significant and consistent. We will continue to focus on the analysis of well-defined and previously studied populations. Systematic analysis of allelic polymorphisms within these candidate gene loci and their functional correlates will be pursued, with initial emphasis on recently identified sequence variants. Multiple statistics will be used to increase the power for linkage/association detection, including the Transmission Disequilibrium Test (TDT) and haplotype analysis. This proposal presents a continuing effort built upon our past accomplishments, with the aim being to identify susceptibility gene(s) regulating IgE responsiveness and/or asthma. It is anticipated that the accomplishment of these studies will greatly facilitate the efforts to uncover the genetic basis of IgE responsiveness and atopic diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: IMMUNOLOGIC HYPERSENSITIVITIES

BASIS

OF

COW

MILK

INDUCED

Principal Investigator & Institution: Sampson, Hugh A.; Professor; Pediatrics; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2002; Project Start 01-AUG-1999; Project End 31-JUL-2003

Studies

39

Summary: Cow mil is one of the major causes of food hypersensitivity in children. Based on 4 prospective studies, 2.5% of infants develop cow milk allergy in the first year of life [100,000 babies/year in the U.S.] Although exclusive breast feeding reduces the incidence of cow milk allergy, 0.5% of infants exclusively breast fed through the first 6 months of life develop cow milk allergy due to cow milk antigen passed in maternal breast milk. Long-term follow-up indicates that about 80% of these infants "outgrow" [become "tolerant"] their milk allergy by 3 years. However, 15% of infants with milkspecific IgE antibodies at 1 year of age remained milk allergic at 10 years of age and 35% were allergic to other foods at the age of 10 years. Cow milk allergy is associated with a broad spectrum of both IgE- and non-IgE-hypersensitivity disorders: IgE-mediated [urticaria, eczema, rhinoconjunctivitis, asthma, colic, vomiting, diarrhea and hypotension; and non-IgE-mediated [milk-induced enterocolitis syndrome, benign eosinophilic proctocolitis, enteropathy syndrome, allergic eosinophilic gastroenteritis, eosinophilic eosophagitis, and gastroesopha-geal reflex]. The immunologic mechanisms responsible for these hypersensitivities, and the subsequent development of tolerance are poorly understood, and will be addressed in this program project. The combined resources of this program project provide a unique opportunity to define the immunologic bases for four common forms of cow milk hypersensitivity. The first project will identify four distinct patient groups with cow milk allergy [both IgE- and non-IgE-mediated] and non-allergic control group, establish the relative allergenicity of cow milk proteins and map allergenic epitopes [B cell and/or T cell] in these four forms of mil hypersensitivity, investigate basic immunologic mechanisms associated with these hypersensitivities and determine the changes that occur when milk allergy is "outgrown". The second project will seek to define whether pathway(s) employed by intestinal epithelial cells [IELs] to handle cow milk proteins differ from those of nonallergens [e.g. tetanus toxoid] and whether IECs from milk allergic patients handle antigen differently compared to normal controls. Since most patients "outgrow" their milk allergy, IEC function will be re-evaluated once clinical tolerance has developed to determine whether antigen processing of cow milk protein changed [normalized], contributing to the loss of hypersensitivity. The third project provides a unique opportunity to address the issue of oral tolerance induction in normal children and those with distinct forms of cow milk hypersensitivity. Finally the fourth project provides an opportunity to dissect basic immunologic mechanisms of IgE-mediated food hypersensitivity not possible in man. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMMUNOTHERAPY FOR PATIENTS WITH PEANUT ANAPHYLAXIS Principal Investigator & Institution: Burks, A. Wesley.; Professor; Arkansas Children's Hospital Res Inst Research Institute Little Rock, Ar 72202 Timing: Fiscal Year 2002; Project Start 15-SEP-1999; Project End 31-AUG-2003 Summary: The applicant is a Professor in the Department of Pediatrics at the University of Arkansas for Medical Sciences. This grant application addresses the qualifications of the applicant, the mentoring plan, and the patient-oriented research plan as detailed below. This grant will be utilized t provide additional protected time to be used mentoring other individuals who are pursuing patient-oriented research and working with our Departmental Clinician Scientist mentoring program. Food allergy, an IgEmediated disease, is a significant health problem affecting 6-8% of children and 1% of adults. Peanut hypersensitivity is one of the most common and severe of the food allergies, and the only therapeutic option currently available is food avoidance. Peanuts and peanut products are used in many different processed foods, increasing the

40

Allergens

possibility of an inadvertent ingestion. Like any other allergic disease, the events that initiate and promote peanut hypersensitivity in a susceptible individual center around the response of T cells to peanut allergens The T-cell response is mediated through the T-cell receptor (TCR) which communicates with the nucleus via a complicated array of signaling pathways. It is believed that when the TCR is occupied by an allergen in susceptible individuals the signaling pathways lead to the activation of cytokine genes that promote the synthesis of IgE. Our hypothesis for this proposal is that the cascade of events that leads to T- cell activation and promotion of IgE production can be disrupted by modifying the allergen-receptor interaction. While conventional immunotherapeutic approaches have been successful for other types of allergic diseases, these approaches have not been safe or efficacious alternatives for the treatment of peanut hypersensitivity. Some problems with standard peptide immunotherapy in the treatment of peanut hypersensitivity include severe problems with standard peptide immunotherapy in the treatment of peanut hypersensitivity include severe anaphylactic reactions, lack of detailed information about the allergens, and insufficient information about the T-cell response to peanut allergens. We propose to utilize our extensive knowledge of the allergens involved in peanut hypersensitivity to design an immunotherapeutic approach that would lower the risk of anaphylactic reactions in patients with life threatening allergic reactions to peanuts. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMPROVED HOUSING AND PRODUCTION OF TRANSGENIC MICE AT VU Principal Investigator & Institution: Richerson, Joan T.; Medical Administration; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2005 Summary: (provided by applicant): Funds provided by the NCRR Grant 1C06RR7400-01 have facilitated the build out of the seventh floor shell space in the MCN II Animal Facility. This new space will provide housing for an additional 10,000 cages of mice and for expansion of the Transgenic Mouse/ES Cell Shared Resource. This growth is essential for the continued success of the research enterprise at Vanderbilt University (VU). For three years, the mouse census has increased by 2000 cages annually; currently the actual mouse census is ahead of the July 2003 projections. To accommodate the expanding mouse population, additional ventilated cage and rack units must be purchased. Compared to a static system, ventilated cage and rack units offer the advantage of housing a larger number of mouse cages in the same floor space. This application requests funding to purchase 25 single sided and 12 double-sided ventilated cage and rack units. VU is committed to converting all housing of mice to ventilated cage and rack units. These ventilated cages will ease the overcrowding in other existing animal facilities, improve the microenvironment of the mice, and reduce personnel exposure to mouse allergens. The research programs of 57 PHS funded investigators will directly benefit from the availability of these ventilated units. Many investigators (including the 57 mentioned above) utilize germ-line altered mice in their research. The Transgenic Mouse and ES Cell Shared Resource has been instrumental in providing services to produce and maintain these unique mouse strains. Expansion of the services offered by this resource will be enhanced by the availability of additional equipment. Funding is requested to purchase two Vertical Flow Stations, two Taylor Wharton Liquid Nitrogen small tank dewars, two roller bases for dewars, two low level battery alarms, a Xenoworks Automatic Transjector with Manipulators, and a Labconco Freeze Dry System. This equipment is important to VU's continuing effort to provide new

Studies

41

services such as Intracytoplasmic Sperm Injection (ICSI) and maintain the cryopreservation of sperm and embryos. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IN VITRO APPROACH TO PROBLEMS OF CLINICAL ALLERGY Principal Investigator & Institution: Lichtenstein, Lawrence M.; Professor; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-APR-1976; Project End 31-MAY-2006 Summary: (provided by applicant): For 35 years, this grant has supported studies involving the treatment of allergic diseases. For the last 25 of these, our focus has been on insect allergy. In 1976, we showed that the then standard treatment immunotherapy, with whole body extract, was no different than placebo, whereas treatment with venoms eliminated the reaction to sting. Venom immunotherapy rapidly became standard. Guidelines call for all history positive, skin test positive patients to receive venom immunotherapy, but this involves fully 3% of all United States citizens. European workers reported, about 8 years ago, that fully 75% of vespid allergic individuals with positive skin tests would not react to sting. We have confirmed that work. Our present goals build on the fact that we have very recently, developed laboratory tests which predict 98% of those patients who will not react. We would like to continue that work to develop laboratory tests, which identify who will react on sting. We are limited by the low reaction rate and so have joined forces with a colleague in rural Pennsylvania to obtain additional patients. We will also try to more closely approximate the field sting which usually takes place when patients are exercising. Even better, we will try to see if we can mimic a sting using very high concentrations of venom together with the vasodialators which are in venoms, such as histamine and kinins. We have recently found that the current diagnostic methods, that is the venom skin test and RAST, are not adequate. History positive, skin test positive and negative patients have the same rate of reactions to sting. We will tempt to improve the skin test material by dialysis and/or working with the purified major allergen of yellow jackets, Ves v 5. We hope to extend our studies into large local reactions, which occur 3-5 times more commonly than systemic reactions. In about one-third of such patients, the reactions are sufficiently painful to require medication with steroids. We intend to demonstrate that immunotherapy will ablate this type of reaction. Finally, we are collaborating with a company, Dynavax Technologies Corporation*, which has shown that allergens linked to bacterial oligonucleotides containing the CpG mot have decreased allergenicity and changed a Th2- to a Th1-like response. Since there is a 50% systemic reaction rate ring venom immunotherapy, we would like less harmful and more effective materials for immunotherapy. Finally, our most recent studies have shown that not all patients can discontinue venom immunotherapy after 5 years, which is the current recommendation, and that not all children outgrow insect allergy. We need to continue to study these patients to develop the most useful clinical guidelines. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: IN VIVO REGULATION OF IGE PRODUCTION Principal Investigator & Institution: Lafaille, Juan J.; Assistant Professor; Skirball Institute; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2002; Project Start 01-JAN-2001; Project End 31-DEC-2005 Summary: (Adapted from the Investigator's abstract): Exacerbated immune responses to environmental airborne non-pathogenic antigens (allergens) are one of the main factors

42

Allergens

for the development of asthma. Allergic reactions in the airways are triggered by antigen crosslinking of IgE molecules on mast cells, leading to degranulation and release of active mediators of smooth muscle constriction and inflammation. It has been shown that one of the essential determinant of allergic responses is the stimulation of T helper lymphocytes of the type 2 (Th2), which, through cognate T/B interaction and IL-4 secretion mediate B lymphocyte switch to IgE production, and through the secretion of IL-5, regulate the recruitment, differentiation and activation of eosinophils. This application is focused on the in vivo regulation of IgE production. Using homologous recombination, we have inserted a rearranged VDJ heavy chain gene as well as a rearranged VJ light chain gene from an influenza hemagglutinin-specific B cell hybridoma into the genome of mice. B cells from these mice maintain the physiological elements controlling somatic hypermutation and isotype switching, but, contrary to normal mice, the fate of antigen-specific cells can be easily followed. These mice will enable us to assess the relative importance of the different signals which promote isotype switching to IgE, thus defining ways in which the generation of IgE could be prevented or downregulated. Specifically, we will: 1) determine the conditions which favor the generation of antigen-specific IgE in vivo; 2) assess the importance of the affinity of the B cell receptor for its antigen on immunoglobulin class switch; 3) determine whether non-IgE antibodies expressing the same antigen-specificity of IgE antibodies can modulate the response in the airways, and 4) determine whether T cells are involved in the downregulation of IgE responses. We believe that the proposed experiments will enhance our knowledge on the regulation of IgE production in response to antigen, and will open new avenues for therapy of atopic disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INDUCIBLE DOMINANT NEGATIVE OF STAT 6 IN MEMORY IGE Principal Investigator & Institution: Miller, Rachel L.; Medicine; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 01-AUG-1998; Project End 31-JUL-2003 Summary: (Adapted from applicants' abstract) The cross-linking of immunoglobulin E (IgE) bound to high affinity Fc receptors on the surface of mast cells or basophils triggers much of the inflammatory responses and symptomatology in allergic reactions and extrinsic asthma. The cytokine interleukin 4 (IL-4) mediates primary IgE responses by inducing class switching to IgE, via the transcription factor Stat6. The binding of IL-4 to its receptor on B cells initiates the dimerization, activation, and nuclear translocation of Stat6 so that it binds to IL-4 response elements in the promoter of IL-4 inducible genes. Germline E transcription follows and permits deletional recombination upstream of the heavy chains that encode for IgE. Knockout models have confirmed in vivo that primary IgE class switching depends upon the activation of the transcription factor Stat6. However, the mechanism for IL-4-mediated secondary or memory IgE remains obscured. Understanding this mechanism is important to comprehending the pathophysiology of human clinical allergic disease because it is characterized by repeated exposures to allergens, resulting in even greater IgE production. The overall aim is to determine whether or not the role of IL-4 signaling though Stat6 is an established or memory IgE allergic immune response. The applicant proposes to develop an inducible dominant negative system in order to study the importance of Stat6 the memory IgE response. Dominant negative Stat6 molecules will be generated by either a carboxy terminus truncated Stat6 mutant molecule or a chimeric Stat6/KRAB protein each possessing the hCMV regulatory minimal promoter with upstream tetoperators regulated by the rtTA-encoding gene that becomes activated in the presence of

Studies

43

doxycycline. The efficacy of the system will be evaluated in vitro and in vivo in transgenic mice and employed to determine if the expression and induction of dominant negative Stat6 can alter a secondary IgE response. Both the memory allergic response to antigenic stimulation and the polyclonal IgE response will be studied. In addition, the components of the memory response that are affected by Stat6 activity will be analyzed. (End of Abstract) Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INFLAMMATORY CYTOKINES IN THE ALLERGIC RESPONSE Principal Investigator & Institution: Finkelman, Fred D.; Professor; Internal Medicine; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-DEC-2007 Summary: (provided by applicant): This proposal will test three related hypotheses that attempt to explain how and why inhalation of some, but not all, antigens stimulates an allergic response. These hypotheses suggest that the adaptive immune system will respond to stimulation with a foreign protein plus an inflammatory cytokine, such as IL1Beta, GM-CSF, or TNF-alpha, with a Th2 cytokine response, while the same stimuli, plus a cytokine that promotes IFN-gamma production, such as IL- 12 or type 1 IFN, will induce a Thl response. As a corollary, we hypothesize that allergens share the property of inducing the innate immune system to produce inflammatory cytokines, but not cytokines that promote IFN-gamma production, while conventional protein antigens (non-allergens) fail either to stimulate inflammatory cytokine production or stimulate production of both inflammatory and Th1-promoting cytokines. Results of studies of cytokine production in worm-infected mice support the additional hypothesis that Th2 cytokine responses, but not Th1 responses, are self-sustaining (i.e., a Th2 response will persist in the absence of continued inflammatory cytokine production, while a Th1 response will switch to a Th2 response in the absence of continuing Th1-promoting cytokines). These hypotheses will be tested with a series of studies in which: 1) mice are inoculated either tracheally or intraperitoneally with allergens, conventional antigens +/- inflammatory and/or IFN-gamma-inducing cytokines, or toll-like receptor ligands that induce distinct patterns of cytokine production; 2) cytokine responses are measured by a novel in vivo cytokine capture assay and/or real-time RT-PCR; 3) pulmonary allergic responses are evaluated by quantitating IgE, IgG1, and IgG2a antibody responses, eosinophilia, goblet cell hyperplasia, and mouse mast cell protease 1 levels; 4) "knockout" mice and neutralizing anti-cytokine antibodies are used to evaluate the ability of allergens to induce an allergic response in the absence of inflammatory cytokines; and 5) a gene chip approach is used to determine whether allergens rapidly induce the expression of characteristic set of genes, other than or in addition to inflammatory cytokine genes, that are not activated by conventional antigens. Results of these studies may explain why some protein antigens are allergens, improve our understanding of why some pathogens induce a Th1 response while others induce a Th2 response, and promote new and better strategies for vaccination procedures that would induce the optimal cytokine response to prevent or control infection by a particular pathogen. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: INNOVATIVE DEVICE FOR INDOOR AIR DISINFECTION Principal Investigator & Institution: Yalamanchili, Rattaya C.; Senior Res Scientist; Lynntech, Inc. College Station, Tx 77840

44

Allergens

Timing: Fiscal Year 2003; Project Start 15-FEB-2003; Project End 30-NOV-2003 Summary: (provided by applicant): Accumulation of organic contaminants and allergens (e.g., spores, bacteria, mold) in indoor air poses a threat to people with wide ranging health sensitivities from allergies to immune system disorders. Currently, the majority of technologies rely on particulate filtration that may or may not be coupled with an absorptive matrix. Such technologies suffer from drawbacks including absorbent saturation, off gassing, secondary waste generation, catalyst replacement and/or regeneration. On the other hand, contaminant destruction methods, such as thermal catalytic oxidation, require high temperatures and generate waste heat and toxic compounds, and the catalyst may become deactivated by certain secondary gas phase compounds. Lynntech proposes the development of an innovative air cleaner catalytic system for the oxidation of organic contaminants and allergens and the reduction of ozone to oxygen from indoor air. The benefits of this approach are its low cost, longevity, diverse flow rate capacity, size and performance. Phase I will involve the evaluation of the device in a custom designed flow loop under various catalyst loadings, humidity, and airborne contaminants for its effectiveness, reliability, cost of operation and ease of use. At the end of Phase I we will have established a sound rationale for the technical and commercial viability of the device and technology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IRRITANTS EFFECTS ON EPIDERMAL ANTIGEN PRESENTATION Principal Investigator & Institution: Gaspari, Anthony A.; Professor; Dermatology; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2002; Project Start 30-SEP-1998; Project End 31-AUG-2004 Summary: (Adapted from the Investigator's Abstract) Irritant contact dermatitis (ICD) is a common and clinically important type of inflammatory skin disorder, and is thought to be the result of non-immunologic inflammation resulting from chemical injury to the skin. This is in contrast to allergic contact dermatitis (ACD), in which hapten specific CD4+ T-lymphocytes are thought to be critical in the immunopathogenesis of this type of dermatitis. However, previous clinical, histologic and immunologic research studies comparing irritant to allergic contact dermatitis indicated that in most assays, these two types of dermatitis are similar, if not identical. We hypothesize that irritant and allergic contact dermatitis share common pathways of immune-mediated skin damage, resulting in the common phenotype of the two kinds of contact dermatitis. Irritants and allergens damage the epidermis, resulting in the release of self-antigens. We hypothesize that these self-antigens are presented to auto-reactive T-lymphocytes by epidermal antigen presenting cells (APC), which are central to the pathogenesis of both irritant and allergic contact dermatitis. To test our hypothesis, we will study the direct effects of irritants on human keratinocytes (KC) and Langerhans cell (LC)-like dendritic cells (DC) in their expression of adhesion molecules and cytokines that are known to be critical for regulating APC-functions or T-lymphocyte growth. Antigen presentation by normal or irritant-treated epidermal KC or LC-like DC cells to skin homing Tlymphocyte populations will be studied. The autologous mixed lymphocyte reaction will be used a model for presentation of self-antigens to autoreactive T-lymphocytes by irritant-stressed epidermal APC. The following T-lymphocyte populations will be studied for autoreactivity against irritant-treated APC: Skin homing T-cell populations (Cutaneous leukocyte antigen+) (CLA) derived from the peripheral blood; Tlymphocytes that infiltrate into irritant skin challenge sites; or non-classical Tlymphocytes (CD4-CD8-, T-cell receptor y/8 bearing) derived from normal human epidermis. These studies will define novel immunologic mechanisms of ICD, and will

Studies

45

lead to a better understanding of the effects of irritants on the regulation of APC function and the subsequent interactions with skin homing T-lymphocytes. Some of these assays may be useful as an in vitro to identify individuals at risk for irritancy. Since ICD can be a debilitating skin problem that potentially affects millions of Americans, the identification of individuals at risk for irritancy using in vitro tests would be of utility in preventing this common and potentially disabling condition. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: KDR MUTATIONS IN THE COCKROACH Principal Investigator & Institution: Dong, Ke; Entomology; Michigan State University 301 Administration Bldg East Lansing, Mi 48824 Timing: Fiscal Year 2002; Project Start 01-JAN-1999; Project End 31-DEC-2002 Summary: The long-term goal of this research is to understand the molecular basis of insecticide resistance in the cockroach. The cockroach is a major threat to human health as a carrier of human pathogens and a major source of indoor allergens and cause of acute asthma. Strategies for the control of cockroaches and other insect pests rely heavily on the application of insecticides. Pyrethroids are a large class of insecticides that possess high insecticidal activity and relative low mammalian toxicity. The heavy use of pyrethroids, however, led to rapid selection of resistant strains in many insect pest populations. Previous studies with the pyrethroid-resistant German cockroach strain, Ectiban- R, suggest that the pyrethroid resistance mechanism (kdr) in this strain is likely due to a mutation(s) in the para sodium channel gene. Recently cDNAs encoding para genes from Ectiban-R and a genetically related pyrethroid-susceptible strain, CSMA, have been cloned and sequenced. Sequence comparison reveals a single amino acid change, from L993 in ParaCSMA to F993 in ParaEctiban-R. The F993 mutation was found in most pyrethroid-resistant cockroach strains, some of which also possess additional kdr-associated para gene mutations. To characterize the effects of these kdr-associated para gene mutations on sodium channel properties and sodium channel interaction with pyrethroid insecticides, the following three specific aims are proposed: 1) Characterization of the responses of wild-type and mutant Para sodium channels to pyrethroids and site 2 neurotoxins; 2) Examination of functional properties of wild-type and mutant Para sodium channels; and 3) Characterization of pyrethroid binding to wild-type and mutant Para sodium channels. Knowledge gained from this project will have significant implications for preserving a whole class of pest control chemicals for the control of major urban insect pests and for further enhancing its efficacy through a better understanding of the molecular interactions between sodium channels and pyrethroids. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: LUNG IMMUNE RESPONSE TO COMPLEX EXPOSURES Principal Investigator & Institution: Holian, Andrij; Professor; Biomedical & Pharmaceutical Scis; University of Montana University Hall 202 Missoula, Mt 598124104 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-AUG-2004 Summary: Asthma is a chronic lung disorder that continues to increase in prevalence, cost and mortality despite improved treatments. Although the association of allergens with asthma has been extensively investigated, the cellular and molecular mechanisms involved in the development of asthma remain to be fully elucidated. Furthermore, even though there is good epidemiological evidence indicating that both particulate matter (PM) and ozone can exacerbate existing asthma, even less is known regarding the

46

Allergens

potential mechanisms that are involved. Preliminary data are presented indicating that PM by itself can generate a Th2-like response and airway hyperresponsivenes, which is enhanced by ozone exposure. Additional data support the notion that the effects of PM may be mediated through alveolar macrophages (AM) by apoptotic elimination of immune suppressor AM allowing immune active AM to stimulate T helper cells and cause airway hyperresponsiveness. Consequently, in this proposal the hypotheses will be tested that exposures to PM plus/minus ozone can produce asthma-like symptoms and exacerbate asthma-like inflammation in a well-established murine model (allergen sensitization) by altering AM populations and functional activity. Furthermore, these airborne contaminants target AM to disrupt the normal Th1: Th2 cytokine balance in the lung leading to the airway hyperresponsiveness. The following Specific Aims will be used to test these hypotheses: 1) characterize the lung response (functional, morphological, cellular, humoral and molecular) to exposures of PM plus\minus ozone; 2) characterize the exacerbation of the lung response (functional, morphological, cellular, humoral and molecular) to exposures of PM and/or ozone in ovalbuminsensitized mice; and 3) confirm the role of AM apoptosis, AM antigen presentation activity, as well as, Th1 and Th2 pathways in the regulation of lung inflammation caused by exposures to PM and/or ozone. Consequently, it will be possible to define the immune alterations caused by PM plus\minus ozone and the requirements of different steps in the hypothesized pathway (AM apoptosis greater than increased APC activity greater than activation of Th2 pathway) leading to airway hyperresponsiveness caused by PM plus\minus ozone. These studies will be most effectively conducted using the murine models described in this application and then extrapolated to humans, since similar studies can not be directly performed in humans. Furthermore, the information obtained from these studies will significantly improve our understanding of the role of the various immune cells in the regulation of lung inflammation and characterize the mechanisms by which ozone and PM mediate lung inflammation. In addition, this information may be ultimately used in improving prevention and treatment for asthma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MATURATION OF NON-SPECIFIC AIRWAYS REACTIVITY Principal Investigator & Institution: Grunstein, Michael M.; Professor; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, Pa 191044399 Timing: Fiscal Year 2004; Project Start 01-JUL-1988; Project End 31-MAR-2008 Summary: (provided by applicant): Clinical evidence supports the notion of agedependent differences in the acquisition of airways hyperreactivity in response to proasthmatic conditions such as atopy, allergen exposure, and viral respiratory infections. Based on our recent evidence that under certain conditions of airway sensitization the smooth muscle (ASM) itself is induced to express proinflammatory cytokines that autologously elicit changes in its constrictor and relaxant responsiveness, the interrelated hypotheses are raised that: I: The induction of altered ASM responsiveness under pro-asthmatic conditions of airway sensitization varies in an age-dependent manner; II: Maturational differences in induced altered ASM responsiveness are attributed to age-related changes in intrinsic Fc receptor-mediated proinflammatory cytokine release and autocrine action; and III: Age-dependent differences in induction of altered ASM responsiveness reflect maturational differences in induced perturbations of the receptor/G protein-coupled transmembrane signaling mechanisms that regulate ASM contraction and relaxation. In addressing these hypotheses, experiments are proposed to examine age dependent mechanisms of induction of altered agonist responsiveness in sensitized maturing rabbit ASM tissues. A: To investigate the

Studies

47

maturation of mechanisms regulating induction of altered ASM responsiveness in the sensitized state, we will examine whether ontogenetic differences exist in: 1) the effects of ASM sensitization under atopic (IgE-mediated) conditions alone and in the presence of either viral pathogen inoculation with RV and RSV, or exposure to the dust mite allergens, Der p1 and Der p3; 2) the evoked release and autocrine actions of specific proinflammatory cytokines under these sensitizing conditions; and 3) the expression and activation of specific Fc receptors, cellular adhesion molecules (CAMs) and proteaseactivated receptors (PARs) in the sensitized ASM. B: To investigate age-related mechanisms of altered receptor/G protein-coupled transmembrane signaling in sensitized ASM, we will examine whether induced changes in ASM responsiveness are attributed to: 1) altered constrictor agonist-mediated receptor/G protein coupled accumulation, metabolism, and receptor binding of the key calcium-mobilizing second messenger, inositol 1,4,5-trisphosphate (Ins(1,4,5)P3 in ASM; and 2) altered betaadrenoceptor-mediated modulation of constrictor agonist-induced accumulation, metabolism, and receptor binding of Ins(1,4,5)P3. It is anticipated that the results generated by these proposed studies will yield significant new insights into the maturation of interplaying mechanisms regulating the acquisition of pro-asthmatic changes in ASM responsiveness in sensitized airways. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF AIRWAY OBSTRUCTION AFTER VIRAL INFECTION Principal Investigator & Institution: Sorkness, Ronald; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: The inception and exacerbations of childhood asthma may be the result of a dysregulated airway inflammation/repair process that occurs in individuals having genetic, developmental, or acquired imbalances in their immune response to environmental airway challenges such as viral infections and allergens. We have developed a rat model of chronic airway dysfunction that shares many features with childhood asthma, and we are employing this model to study mechanisms that are potentially important to defining the host factors that make airways vulnerable to asthma pathogenesis, and the mechanisms that ultimately link immune dysregulation with airflow obstruction. Peripheral airway instability and closure may be important to the airway obstruction of asthma, but the characteristics and the mechanisms of airway closure are poorly understood. It is the overall hypothesis of this project that airway closure is a pivotal component of airway obstruction in asthma, and is the result of an interaction of pathophysiological mechanisms in the airways. The objectives of this project are to determine, using detailed physiologic and morphometric analyses in rats having an asthma-like phenotype, the relative contributions of 4 principal mechanisms to airway closure: reduced lung elastic recoil; altered airway smooth muscle dynamics; altered airway wall morphology; altered airway luminal secretions. In the first Specific Aim, studies are designed to quantify the contribution of each of the airway closure mechanisms, and determine the morphologic correlates with physiological dysfunction. In the second Specific Aim, the same mechanisms of airway closure will be characterized in the context of alterations during, and after withdrawal of, systemic corticosteroid treatment. These studies will increase our understanding of the mechanisms of airway obstruction in asthma, and will provide information that complements parallel studies in children with asthma, as well as identify hypotheses for future translational studies in children with asthma.

48

Allergens

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

Project Title: MUCINS OF THE OCULAR SURFACE Principal Investigator & Institution: Gipson, Ilene K.; Senior Scientist; Schepens Eye Research Institute Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 01-AUG-1979; Project End 31-JUL-2005 Summary: The mucus of the tear film is responsible for maintenance of fluid on the surface of the eye and for providing a microbe barrier to protect the eye from infection. Ocular surface diseases such as those of the dry eye type, vitamin A deficiency, ocular surface infections as well as allergic conjunctivits may involve mucus deficiency, disruption of the mucus layer, or discharge of large amounts of mucus. During the previous funding period, we demonstrated that three mucin genes are expressed by the ocular surface epithelium, two prevalent ones being the membrane- spanning mucin MUC4 and the goblet cell-specific mucin MUC5AC. We sequenced portions of MUC4 and developed probes, antibodies, and assay methods for both mucins that we now propose to use in four specific aims toward understanding aspects of the function and regulation of expression of these mucins on the ocular surface in normal and pathologic states. Aim I: Characterize two aspects of the membrane-spanning mucin MUC4 on the ocular surface. A. determine whether the mucin remains associated with the apical membrane glycocalyx or whether its extracellular domain is shed into the tear film. b. Test candidate inducers of MUC4 gene expression, based on presence of putative transcription factor binding sites identified from sequencing the MUC4 regulatory region and on preliminary data indicating their potential role in its regulation. Aim II: We hypothesize that conjunctival goblet cell differentiation is characterized by induction of expression of the MUC5AC gene and that such induction can be regulated by environmental stimuli as well as cellular effectors. We propose to: a. determine in a mouse model whether goblet cell differentiation/Muc5AC expression can be influenced by surface irritants, infections, or specific allergens; b. determine whether conjunctival goblet cell differentiation can be enhanced in vitro, based on demonstrated presence of regulatory elements in the promoter region of MUC5AC and on culture conditions known to affect gastrointestinal goblet cell differentiation. Aim III: Determine if MUC5AC has specific affinities for MUC4 and the bactericidal proteins prevalent in the tear film, lysozyme, and secretory IgA. Aim IV: Determine in a specific type of dry eye (Sjogren's syndrome), and in seasonal allergic conjunctivitis whether amounts of MUC4 and MUC5AC mRNA and protein differ from the normal population. We hypothesize that dry eye syndromes are characterized by loss of surface wetting due to reduced amounts of MUC5AC and MUC4 protein, whereas, allergic conjunctivitis is characterized by an increased amount of mucins to facilitate allergen removal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: MUCOSAL INFLAMMATION

IMMUNE

BARRIER

IN

INFECTION

AND

Principal Investigator & Institution: Mostov, Keith E.; Professor; Anatomy; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-MAR-2007 Summary: (provided by applicant): Exposed mucosal surfaces, such as the respiratory, gastrointestinal, and genitourinary surfaces, are lined primarily by a single layer of epithelial cells. This cell layer serves at least two primary functions in the mucosal immune system. First, it is a barrier to the entry of the >95% of infectious agents that

Studies

49

enter through mucosal surfaces, as well as a barrier to allergens and other noxious agents. Mucosal infectious diseases include such high priority agents as AIDS and other sexually transmitted diseases, numerous opportunistic infections and emerging and reemerging diseases, and bio-terrorist agents. Second, in response to these pathologic agents, inflammatory and immune cells are recruited and cross the epithelial barrier, following a chemotactic gradient. This Program Project presents a multidisciplinary and highly interactive approach to these problems. The Project and Core leaders combine a great deal of experience and diverse insights and techniques. Our experimental systems range from in vitro cell culture to genetically modified whole animals, though we focus on lung epithelium as an exemplary mucosal, and Pseudomonas aeruginosa as an exemplary mucosal pathogen. The integrity of the epithelial monolayer is essential to its mucosal immune function. The epithelial monolayer has sophisticated wound-healing mechanisms to maintain its integrity. Project 1 concentrates on the basic mechanisms of epithelial wound healing. Project 2 focuses on how wound healing is altered by P. aeruginosa and closely parallels Project 1. Projects 3 and 4 focus on the movement of inflammatory cells across the epithelial monolayer into the lumen. Project 3 considers the transmigration of the polymorphonuclear neutrophil, specifically the role of CD47 and the ligand for Mac-l. Project 4 focuses on the role of matrix metalloproteases (MMPs) in chemotaxis of inflammatory cells into the lumen. All four projects are supported by all three cores. Core A is administrative. Core B, Cell Isolation and Culture, provides primary lung epithelial cells for all projects. Core C provides Live Cell Multiphoton and Confocal Imaging, which will be vital to all projects. There is very extensive interaction and collaboration through out. For instance, Projects 1, 2 and 4 all utilize mice knocked-out for certain MMPs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NATIONAL COOPERATIVE INNER CITY ASTHMA STUDY Principal Investigator & Institution: Kattan, Meyer L.; Professor of Pediatrics; Pediatrics; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2000; Project Start 01-AUG-1996; Project End 31-JUL-2004 Summary: The National Cooperative Inner City Asthma Study is a multicenter, controlled, randomized clinical intervention trial carried out in children with asthma. The study is designed to determine the impact of primary care, clinic-based interventions (asthma counselors, physician education, and control) on symptom days. In New York City, 150 children, 4 to 12 years, from inner city areas, who have moderate to severe asthma with symptoms or on chronic medications during the past year, will be eligible for the investigation. Primary care clinics will be randomized into the 3 intervention groups and the children in these clinics will be followed for 3 years (3 visits/year) after enrollment into the trial. The asthma counselor intervention will be ongoing for 3 years and include modules to reduce environmental (allergens, nitrogen dioxide, environmental tobacco smoke, molds) and psychosocial risks associated with asthma, to increase adherence and to improve asthma management skills. The physician education intervention will consist of 2 formal sessions on asthma management per year for 2 years with feedback on their management practices 3 times per year. An observational study will be done to assess the relation of ambient air pollution to asthma symptoms. A substudy will evaluate the effect of reducing indoor nitrogen dioxide by replacing stoves with pilot lights with ones with auto-ignition lights. Follow-up of symptoms in control and intervention groups will be done by telephone every 2 months. The groups will be compared with respect to symptom days. In addition, comparisons will be made with respect to utilization (unscheduled visits, hospitalizations),

50

Allergens

adherence, quality of life, physician knowledge and quality of asthma care, asthmarelated behavior skills and indoor and outdoor environmental exposures. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NOVEL MICROARRAY SYSTEM FOR IN VITRO ALLERGEN TESTING Principal Investigator & Institution: Olejnik, Jerzy; Director of Research; Ambergen, Inc. 1106 Commonwealth Ave Boston, Ma 02215 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2005 Summary: (provided by applicant): Fifty million Americans suffer from allergic diseases including asthma, rhinitis, sinusitis, dermatitis and food allergy. Allergies constitute the 6th leading cause of chronic disease and involve at least $20 billion in annual health care costs. For type I allergy, which manifests itself by elevated levels of IgE in the serum, there is a growing need for in vitro immunoassays capable of rapidly quantifying allergen-specific IgEs for the over 300 most common allergens using a single drop of blood. Such a testing modality could significantly improve the efficiency of allergy diagnosis by providing the clinician with data to design a patient-specific, cost effective program of symptom management and therapy. One promising candidate is an allergen microarray system. However, current microarray technology is not sufficiently developed to meet the rigorous demands of clinical diagnostics in terms of low cost, reliability and automation. During Phase I, AmberGen in collaboration with Clinical MicroArrays (CMA), a subcontractor on this project, plans to develop and evaluate an integrated microarray system for simultaneous in vitro measurements of hundreds of allergen-specific IgEs. This integrated system will be based on innovations in several areas of microarray technology including array substrates, method for allergen immobilization, array immunoassays and fluorescent readout. Ultra-low fluorescence array substrates will be produced and evaluated which will be based on polystyrene and nitrocellulose thin films. Novel methods of allergen attachment through covalent bonding to surfaces and by directed binding using biotin-streptavidin bridges will be evaluated. A microarray reader which features high sensitivity evanescent wave detection technology will be evaluated. The integrated system including cassette processing of disposable microarrays will be low-cost and highly automated. Dr. Lynda Schneider, an expert in the field of pediatric in vitro allergy diagnostics and Director of the Allergy/Clinical immunology Program at Boston Children's Hospital and Dr. Helen Hollingsworth, an expert in adult allergies and Director of the allergy unit at Boston University Medical Center will serve as consultants. During Phase II, a complete integrated system including a scanner and array processor, along with a prototype microarray containing several hundred antigens will be developed and evaluated in a clinical setting. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: OUTDOOR ALLERGEN EXPOSURE, SENSITIVITY, AND ACUTE ASTHMA Principal Investigator & Institution: Burge, Harriet A.; Associate Professor; Environmental Health; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 05-AUG-2000; Project End 31-JUL-2005 Summary: (Adapted from the Investigator's Abstract) Asthma is a growing problem, and outdoor allergens play a role in exacerbation of many cases. A clearer

Studies

51

understanding of this role and its magnitude, and a means of controlling the effects of outdoor allergen exposures are needed. We propose Poisson time-series and conditional panel studies to test these hypotheses: 1) the incidence of acute asthma attacks, as measured by urgent care inhalation treatments and hospitalizations for asthma, has a dose-dependent relationship with exposure to specific outdoor allergens; 2) specific sensitization to outdoor allergens is a risk factor for having an acute asthma attack; and 3) exposure conditions that lead to acute asthma attacks can be forecast, creating an opportunity to reduce asthma morbidity and mortality by targeted pretreatment and/or exposure controls. We will test Hypothesis I using Poisson time-series analysis of daily outdoor allergen levels and urgent asthma treatments in a large HMO population over 4 years, controlled for air pollution, and meteorological conditions. We will test Hypothesis 2 in a subset of 1,000 of the acute asthma patients by skin testing them with standard allergen preparations and with extracts of air samples. Analyses will be controlled for age, total IgE level, indoor allergen sensitivity and exposure, time spent outdoors, and occupational and cold air exposures. Finally, we will develop models to forecast outdoor allergen exposure, and validate them using general cross-validation techniques. We have demonstrated that this study design is feasible in preliminary work: a) showing a dose-dependent relationship between both total pollen and urgent asthma treatments, b) recruiting and skin testing a small panel of Fallon patients with extracts of outdoor air samples c) generating a predictive model for ragweed pollen. This work demonstrates that we have access to useable clinical data, that we can recruit and test patients, that the study design has sufficient power to be definitive, and that there is a reasonable likelihood that the hypotheses are true. This study will lay a foundation for controlling acute asthma exacerbations caused by outdoor allergens, by identifying the specific allergens responsible, the patients at risk, and providing a means of forecasting hazardous exposure that can provide a focus for targeted prophylactic therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OXIDATIVE STRESS IN ASTHMA INITIATION Principal Investigator & Institution: Sur, Sanjiv; Associate Professor of Internal Medicine; Internal Medicine; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2004; Project Start 15-APR-2004; Project End 31-MAR-2008 Summary: (provided by applicant): Asthma is a major health problem in this country. Intrapulmonary allergen challenge in asthma induces a "late phase asthma phenotype," consisting of airway hyperresponsiveness (AHR), airway mucus production, and Th2 eosinophilic inflammation. A large body of literature has dissected out how peptides and epitopes of pollen-derived antigenic proteins interact with critical components of the adaptive immune system namely Class II MHC on antigen presenting cells, and Tcell receptor on Th2 cells, to induce late phase asthma phenotype. However, it has never been shown that pollens contain a second set of protein(s) with unique biochemical properties that vigorously augments late phase asthma phenotype. Ragweed pollens are known to induce allergic rhinitis and asthma in humans. We discovered that ragweed extract (RW) and many environmental pollen extracts contain potent pro-oxidant activity. Using RW as a prototypic pro-oxidant allergen, we demonstrated that this activity was due to a protein complex consisting of several distinct Pro-Oxidant Proteins (POP) tightly associated with Amb A1 (antigen E), the major antigenic component of RW. We coined a term" Pro-Oxidant Protein and Antigen Complex, (POPAC)" to describe this POP + antigen protein complex. Purified Arab A1, unlike whole RW or

52

Allergens

Amb A1 complexed in POPAC, did not possess pro-oxidant activity. Consistent with this difference in pro-oxidant activity, intrapulmonary challenge of sensitized mice with POPAC, but not Amb A1, potently induced allergic inflammation. We propose that RW (and many other pollen and mold allergens) contains POPAC, a protein complex of at least two physically associated components, the well-known antigenic component, and a novel POP. The overarching goal of this proposal is to determine the mechanism by which POP vigorously augments the late phase asthma phenotype induced by the antigenic component of POPAC. In this proposal, we will test the hypotheses that POPAC-induced immediate oxidative burst is independent of allergic sensitization and adaptive immunity (specific aim 1), and that pro-oxidant proteins augment allergic sensitization and antigen-induced late phase AHR, mucin production and Th2 allergic inflammation in mice (specific aim 2), pro-oxidant activity of RW augments immediate ROS production and late phase symptoms, mucus production and Th2 allergic inflammation in atopic patients (specific aim 3). These studies are designed to elucidate a novel paradigm of late phase asthma phenotype that is initiated by pro-oxidant protein complex (POPAC) present in many environmental pollen and mold allergens. Future studies of POPAC may identify novel therapeutic approaches in asthma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PEER EDUCATION IN PREGNANCY STUDY Principal Investigator & Institution: Persky, Victoria W.; Professor; Epidemiology and Biostatistics; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 18-APR-2002; Project End 31-JAN-2007 Summary: (provided by applicant): The purpose of this project is to extend the investigators' previously funded Peer Education in Pregnancy Study. The overall goal of the study is to examine the effect of peer education aimed at modification of the home environment on the development of asthma in children at risk for the disease. Secondary goals are to examine the effect of environmental, psychosocial, and nutritional risk factors on the development of asthma in the overall cohort. Specific aims of this proposal are to increase the total recruitment to 500 pregnant women and their unborn infants; increase the time of follow-up of the children to age 3-5 years; expand the exposure assessment to include dust measurements of endotoxins, pyrethroids, and organophosphates and urine measurements of pesticide metabolites; extend the psychosocial and nutritional assessments to include measurements of family function stress and diet during years 1-5; and expand immune assessments to include measurements of interleukins (IL-4, IL-13, and interferon-gamma) at one year of age. The effect of peer education on the development of asthma by age 3-5, as well as the effect of peer education on intermediary endpoints such as smoking, exposure to indoor allergens (cat, cockroach, mite, mouse, beta-glucan, and endotoxins), exposure to pesticides (pyrethroids and organophosphates), and immune function (IgE levels, skin testing for allergens, and cytokines) will be examined. Relationships of exposure to passive smoke, allergens, and pesticides, as well as measures of psychosocial function and nutrition, with the development of asthma and respiratory symptoms in the overall cohort will also be explored. Results of this study will assist in elucidating the etiologic pathway by which asthma develops early in life, as well as assist in the development of effective intervention programs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

Studies

•

53

Project Title: PERMEABILITY OF THE LUNG TO WATER SOLUBLE SOLUTES Principal Investigator & Institution: Schneeberger, Eveline E.; Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 20-DEC-1990; Project End 31-MAY-2005 Summary: (Applicant's Abstract): The long term goal of this proposal is to define the interactions between tight junction (TJ) proteins and the factors regulating their activity in the lung. Four central questions in TJ biology are addressed. 1. What is the role of occludin, claudin-1 and ZO-1 in regulating the barrier function of TJs? This is assessed using unique inducible, doubly transfected epithelial cell clones to vary the relative expression of these proteins; the effect on TJ permeability is then examined. 2. How do specific domains of the claudins determine TJ barrier function? To examine this, specific amino acid sequences are deleted from cytoplasmic and extra-cellular domains of claudin-1 or -4. The TJ permeability properties of epithelial cell clones expressing these modified proteins are evaluated. 3. How is the profound effect of cholesterol (CH) efflux on TJ function related to detergent insoluble CH/glycolipid rafts and is CH closely associated with TJ proteins? A novel radiolabeled, photoactivatable CH analog is used to determine whether CH is bound to occludin and/or the claudins. Differences in the proportions of integral TJ proteins and the lipid composition of the TJ rafts in high and low resistance strains of epithelial cells will provide new clues as to their role in TJ permeability. Increased lipid 2M messenger generation by activation of phospholipases during CH efflux suggest that they are important regulators of TJ barrier function. These phospholipases will be identified and characterized. 4. To what extent are the permeability properties of pulmonary TJs dictated by their protein composition? Immunogold labeling of occludin and six lung-associated claudins is used to map their location to specific epitheliall endothelial TJs of the lung. An LPS-induced model of acute inflammation is used to explore how TJ proteins and the associated lipid rafts, isolated from airway epithelium, are modified during migration of inflammatory cells. The proposed studies will provide new insights into TJ biology and allow development of new strategies to regulate passage of therapeutic agents across lung epithelia and/or to prevent the penetration of allergens through the TJ barrier. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: PGE2 REGULATION OF ALLERGIC INFLAMMATION IN THE LUNG Principal Investigator & Institution: Peebles, R. Stokes.; Associate Professor of Medicine; Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): One of the primary byproducts of acute allergic (IgE-mediated type I hypersensitivity) reactions is the generation of arachidonic acid from inflammatory cell membranes. Work by several investigators in in vitro systems suggests that arachidonic acid metabolites, particularly PGE2, may have immunomodulatory effects. However, conflicting results from these in vitro studies have not yielded solid conclusions on the actual roles of these mediators in the development of allergic inflammation. Using an in vivo murine model of type I hypersensitivity to ovalbumin, we have recently reported that inhibition of the cyclooxygenase pathway of arachidonic acid metabolism, and therefore PGE2 production, during the development of allergic inflammation conclusively caused a substantial increase in the allergic phenotype. More recently, we found that antibody neutralization of PGE2 in our model increased allergic inflammation. Additionally, in the same model, mice that lacked the PGE2 receptor EP1 also had significantly increased

54

Allergens

allergic inflammation. Based on our preliminary data, we hypothesize that PGE2 downregulates and inhibits lung-specific immune responses. The long-term goal of this proposal is to explore how PGE2 regulates inflammation and immune responses to allergens in the lung. In Specific Aim 1 we will define the immunomodulatory effects of PGE2 on the development of allergic disease. We will define the time (either antigen presentation or effector cell development) at which PGE2 has the greatest influence on Type 2 CD4+ T cell development using antibody neutralization of PGE2, exogenous administration of PGE2, and PGE2 synthase overexpressing mice. We will also determine if the immunomodulatory effect of PGE2 on allergic disease is through PGE2's regulation of leukotriene synthesis. In Specific Aim 2, we will determine the effect of signaling through the four different PGE2 receptors on the development of allergic inflammation in the lung. We will also determine the effect of signaling through the four EP receptors at the initial presentation of antigen on Type 2 cytokine production in vivo and test the effect of signaling through the EP receptors on the antigenindependent development of CD4+ T lymphocytes in vitro. Defining the role of PGE2 and the cellular receptors for PGE2 in the immunobiology of allergic inflammation in the lung may result in novel targets for drug development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHASE I/II TRIAL OF HOKT3(1(ALA-ALA) IN TYPE 1 DIABETES Principal Investigator & Institution: Herold, Kevan C.; Associate Professor; Naomi Berrie Diabetes Center; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 15-JUN-2000; Project End 31-MAR-2005 Summary: (Adapted from the Investigator's abstract): Type I diabetes mellitus (T1DM) is an autoimmune disease thought to be caused by a T cell mediated destruction of the insulin producing beta cells in the islets of Langerhans. Studies in animal models and limited human clinical studies demonstrate that modulation of T cell responses can alter the natural history of diabetes, but none of the currently available immune suppressive treatments induce a permanent remission of the disease. Animal studies, however, suggest that anti-CD3 monoclonal antibody (mAb) can reverse diabetes and induce long term tolerance to recurrent autoimmunity. This application is for a Phase I/II trial of a new anti-CD3 mAb, hOKT3gamma1 (Ala-Ala) for treatment of new onset (T1DM). This mAb is a humanized form of OKT3 that does not bind the FcR receptor and thus, will not cause the cytokine release syndrome or development of neutralizing antibodies that preclude use of OKT3 in otherwise healthy patients with T1DM. These and other studies in mice suggest that the reagent can selectively inhibit previously activated cells that produce Th1 cytokines thought to be involved in diabetes. The aims of this phase I/II trial are to test the safety, tolerability, and immune effects of hOKT3gamma1(Ala-Ala). The investigators have designed their application to have sufficient statistical power to test whether treatment with the drug will alter the natural history of beta-cell destruction in T1DM. They will study the effects of the drug on depletion of peripheral T cells, activation of T cells using cellular approaches, T cell proliferative responses to common antigens, and stimulation of anti-Ig responses. They will also study the effects of the drug on diabetes specific immune responses including the titer and isotype of autoantibodies and cellular responses, including cytokine production, to islet antigens such as IA-2. They will compare the effects of the mAb on these responses, thought to be of a Th/Tc1 phenotype to responses to common allergens, which are of a Th2 phenotype. The hypothesis to be tested in this Project is that non-FcR binding mAb will inhibit islet antigen reactive Th1 cells that mediate the destruction of beta cells, and

Studies

55

thereby alter the natural history of T1DM. Their studies will test a new immunologic approach to treatment that is based on the current understanding of the natural history of diabetes. As a result of these studies, future studies will be of broader scope with a focus on clinical efficacy of non-FcR binding anti-CD3 therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PILOT--INTRINSIC PROPERITES PRECURSORS IN ATOPIC DERMATITIS

OF

LANGERHANS

CELL

Principal Investigator & Institution: Gruchalla, Rebecca S.; Assistant Professor; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2006 Summary: The development of atopic dermatitis (AD), a common chronic inflammatory skin diseases, is thought to be influenced by both environmental factors (allergens) and by genetic factors that control immunological responsiveness to the relevant allergens. Because of their remarkable ability to initiate and regulate cutaneous immune responses, epidermal Langerhans cells (LC), the principal antigen presenting cells (APC) in skin, are thought to play a pivotal role in both the induction and amplification of the inflammation in AD. Moreover, recent evidence show that LC from AD skin differ, both phenotypically and functionally, from those isolated from the skin of normal individuals. These differences may exist at the level of LC precursors as well, since LClike DC precursor CD14+ cells of AD patients are phenotypically and functionally different from LC-like DC generated from counterpart precursors of healthy individuals. The goal of this pilot and feasibility (P&F) study is to characterize the intrinsic properties of LC precursors that govern their differentiation towards the abnormal phenotype characteristic of that seen in patients with AD. The proposed studies are related to, but nonetheless a distinct departure from the PI's previous research focus. The specific aims are: Aim 1. To determine whether phenotypic abnormalities exist at the level of DD14+ LC precursors in AD. Aim 2. To determine whether genetic polymorphisms reported for AD are present in CD14+ LC precursors of AD patients. Aim 3. To determine whether CD14+ precursors from AD patients vs. normal controls are differentially regulated by specific cytokines. Aim 4. To examine whether drugs used for treatment of AD modulate properties of LC CD14+ precursors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: POSITIONAL RESPONSIVENESS

CANDIDATE

GENES

FOR

AIRWAY

Principal Investigator & Institution: Ewart, Susan L.; Associate Professor; Large Animal Clinical Sciences; Michigan State University 301 Administration Bldg East Lansing, Mi 48824 Timing: Fiscal Year 2002; Project Start 05-AUG-2000; Project End 31-JUL-2005 Summary: (Adapted from the applicant's abstract): A genetic predisposition to the development of asthma along with exposure to environmental factors such as allergens are required for the development of clinical symptoms. Airway hyperresponsiveness, airway inflammation, and elevated serum IgE are integral components of the asthma phenotype. Abhr1(lod=4.2) and Abhr2(lod=3.7) are quantitative genes that control susceptibility to airway hyperresponsiveness in the progeny of inbred mouse strains(A/J and C3H/HeJ) with significantly different susceptibilities to allergeninduced airway hyperresponsiveness. These genes are located on murine chromosome 2 near the genes for GATA-3 and interleukin-1 receptor antagonist. GATA-3 is essential

56

Allergens

for Th2-driven inflammation and has been shown to be increased in the airways of asthmatics. Interleukin (IL-1) is a potent proinflammatory cytokine and has been implicated in chronic diseases, including asthma. Thus, based on compelling evidence for linkage and relevant mechanisms of action, we hypothesize that genes encoding GATA-3 and/or interleukin-1 receptor antagonist contribute to allergen-induced airway hyperresponsiveness in our murine model. The overall objective of the current study is to understand the molecular mechanisms that cause airway hyperresponsiveness. The investigators will fine map the location of the gene(s) causing allergen-induced airway hyperresponsiveness in our mouse model by refining quantitative associations between allergen-induced airway responsiveness and DNA marker genotypes using crosses between A/J and C3H/HeJ mice. They will investigate the role of positional candidate genes for antigen-induced airway hyperresponsiveness by 1) determining polymorphisms in genes encoding GATA-3 and interleukin-1 receptor antagonist; 2) determining whether these polymorphisms result in altered message or protein levels, and lastly determining whether polymorphisms are associated with allergen-induced airway hyperresponsiveness via consegregation and functional studies. The results of these studies may lead to better prevention and treatment of asthma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PREVENTION OF CHRONIC ASTHMA: AGE 7 FOLLOW UP Principal Investigator & Institution: Klinnert, Mary D.; Associate Professor; National Jewish Medical & Res Ctr and Research Center Denver, Co 80206 Timing: Fiscal Year 2002; Project Start 01-SEP-1997; Project End 30-JUN-2006 Summary: (provided by applicant): The goal of the proposed project is to follow up and evaluate at age 7 a cohort of low income urban children who have participated in the Childhood Asthma Prevention Study (CAPS) since their enrollment prior to age 2. CAPS is a Demonstration and Education randomized, controlled intervention study, now in its 5th year of funding, that has been aimed at reducing asthma prevalence, severity, and morbidity among low income, urban children. Children ages 9-24 months with documentation of multiple wheezing episodes and additional risk factors for childhood asthma were enrolled. They received a nurse home visitor intervention that targeted allergens in the home, environmental tobacco smoke exposure, and quality of maternal caregiving, particularly in relation to asthma prevention and management. Original study goals included following the children to age 4. At this time almost half of the children have reached their 4th birthday and have been evaluated for asthma. Preliminary data suggest that the intervention may have been effective in reducing asthma at age 4. However, asthma at age 4 is a mixture of asthma phenotypes that will become much more clear by the time the children reach age 7. Thus, evaluating the children for asthma at age 7 will provide valuable information regarding the effects of the intervention. Further, for 4-year-olds methods for obtaining objective assessments of pulmonary functions are still under development, whereas by age 7 children can perform spirometry adequately to derive objective measures. Besides evaluating the long-term effects of the intervention, follow-up of the cohort to age 7 will provide an opportunity for a detailed examination of psychosocial, environmental, and ethnicity factors that were shown in baseline analyses to be associated with initial outcomes. Finally, the follow-up provides a unique opportunity to investigate the role of concurrent caregiver mental health on asthma morbidity and related health care utilization among these low-income children. We plan to obtain objective evaluations of cigarette smoke exposure (cotinine) and asthma medication adherence (electronic monitoring) at age 7 in order to determine the extent to which poor medication

Studies

57

adherence and cigarette smoke exposure mediate the relationship between caregiver mental health and child asthma morbidity. In addition, we will use the early data to identify developmental precursors for poor adherence and increased asthma morbidity at age 7. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROTEOMICS OF DEP-INDUCED OXIDATIVE STRESS Principal Investigator & Institution: Nel, Andre E.; Professor of Medicine; Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 10-SEP-2002; Project End 31-JUL-2007 Summary: (provided by applicant) An urgent need exists for toxicological profiling of ambient air particulates. The investigators are studying the adjuvant effects of DEP and CAPS in allergic airway inflammation and asthma. In vivo studies in animals and humans have demonstrated that DEP enhance IgE production and allergic inflammation during challenges by common environmental allergens. This effect involves the generation of oxidative stress and can be reversed with thiol antioxidants. The prooxidative and pro-inflammatory effects of DEP can be reproduced in vitro with organic DEP extracts as well as aromatic and polar chemical groups prepared from these particles and fractionated by silica gel chromatography. The investigators hvpothesize that redox cycling polycyclic aromatic hydrocarbons and their oxidized derivatives are responsible for oxidative stress effects in the respiratory tree, and that new biomarkers can be developed around this principle with a proteomics approach. Novel proteome display techniques have recently been developed to identify oxidatively modified proteins in tissue culture cells and bronchoalveolar lavage (BAL) fluid. The principal investigator's long-term goal is to use the comprehensive particle and proteomics infrastructure at UCLA to develop new biomarkers to follow the adverse health effects of particulate matter (PM) in susceptible populations. In order to accomplish this goal, the researchers will use a proteomics approach to identify newly induced as well as oxidatively modified proteins in macrophage and epithelial cell lines during exposure to organic DEP chemicals (Specific Aim 1). These cells will be exposed to crude DEP extracts as well as polar and aromatic chemical groups fractionated from these particles by silica gel chromatography. Whole cell extracts will be resolved by 2-D electrophoresis, followed by protein image analysis and generation of a 2-D database for identifying newly expressed proteins by in-gel digestion and mass spectrometry. The contribution of oxidative stress will be tested by the inclusion of thiol antioxidants in the culture medium, as well as by the implementation of novel techniques for the display of protein carbonyls and nitrotyrosines by 2-D electrophoresis. A complementary approach will be to use proteomics to identify oxidative stress and oxidatively modified proteins in the BAL fluid from an established murine model demonstrating the adjuvant effects of aerosolized DEP towards an inhaled antigen (ovalbumin)(Specific Aim 2). The investigators will determine whether treatment of these animals with a thiol antioxidant can suppress DEP-induced oxidative stress events in the BAL fluid. They will also use a display of protein carbonyls to identity oxidatively modified proteins in the BAL fluid. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

58

•

Allergens

Project Title: POLLUTANTS

PULMONARY

EFFECTS

OF

ENVIROMENTAL

OXIDANT

Principal Investigator & Institution: Plopper, Charles G.; Professor and Chairperson; Vet Anatomy/Physiol/Cell Biol; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 956165200 Timing: Fiscal Year 2002; Project Start 30-SEP-1978; Project End 30-JUN-2005 Summary: Ozone is the principal oxidant air pollutant in most American cities. Our program has established that the pathobiologic response of the mammalian respiratory system to inhalation system to inhalation of ambient concentrations of ozone focuses on the epithelium and varies by species, position within the airway tree and duration of exposure. The focus of this renewal will be the cellular, physiologic, and molecular mechanisms by which exposure to oxidant air pollutant sin concern with allergens, contributes to the development of asthma. Our studies will be directed towards the impact of environmental exposures on children, a special population in which the incidence of asthma has been increasing in recent years. The program is organized around the premise that the cellular and acellular components in the walls of tracheobronchial airways form an interactive, trophic unit. The overall hypothesis being tested is that the episodic nature of environmental exposure to oxidant air pollutants: a) promotes the development of asthma and exacerbates the allergen response in asthmatics by altering the homeostasis of the airway epithelial mesenchymal trophic unit in adults; and b) elevates the severity of asthma in the young by fundamentally altering the postnatal development of these trophic interactions. These changes result from continual cycles of acute injury, inflammation and repair superimposed on the immune response to allergen exposure. Project 1 will address the change sin the epithelial and mesenchymal compartments of the trophic unit. Project 2 will address the impact of the immune response and inflammation on the organization of this unit Project 3 will address changes in the nervous components of this unit. All three projects will compare response in the same neonatal and adult rhesus monkeys following episodic exposure to ozone and repeated challenge with a human allergen, house dust mite, during either the injury inflammation phase of ozone exposure or the repair phase. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RAPID AND INEXPENSIVE BIOCHIP-BASED ALLERGY TESTING Principal Investigator & Institution: Strother, Todd C.; Gen Tell Biosurfaces, Inc. 510 Charmany Dr, Ste 160 Madison, Wi 53719 Timing: Fiscal Year 2004; Project Start 15-MAR-2004; Project End 30-SEP-2004 Summary: GenTel BioSurfaces (GenTel) seeks to establish the technical merit and feasibility of an allergen biochip for use as a rapid, inexpensive and easy-to-use in vitro method for identifying elevated allergen-specific IgE titers in serum. This biochip is based upon a uniform gold surface that is highly amenable to chemical modification and uses a unique microchannel technology (Array 2 Microchannels). On-chip microchannels enable many discreet interactions to be studied simultaneously and allow rapid, on-chip generation of a standard curve. Quantification is obtained in an analogous manner to an enzyme linked immunosorbent assays (ELISAs). Together, these technologies allow GenTel to develop a robust allergen biochip that can be used to rapidly quantitate allergen-specific IgE titers in serum. This biochip will find applications in the clinical and research communities including, but not limited to, allergen-specific IgE profiling of human patients, monitoring vaccine and therapeutic antibody efficacy in animal models, antigenic determination and localization of

Studies

59

antibody populations. The objectives of this proposal are to: (1) Select optimal surface chemistry for attachment of allergens as measure by the highest, specific binding of target IgE; (2) develop and determine optimal surface chemistry for blocking nonspecific adsorption of human serum components to the array surface as measured by the highest signal: noise ratio and (3) to validate the ability of the proposed allergen biochip to quantitatively determine the titer of an allergen-specific IgE using our innovative Array" Microchannels by comparing the results to those obtained by ELISA. A followup Phase II proposal will broaden the number of allergens tested and further develop our Array 2 Microfluidics technology by integrating sample purification with the biochip. This will enable direct application of whole blood to the biochip and an inexpensive chip-reading allergy test with a turnaround time of about one hour. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RAPID TEST FOR MONITORING DUST MITE AVOIDANCE IN HOMES Principal Investigator & Institution: Chapman, Martin D.; Associate Professor; Indoor Biotechnologies 1216 Harris St Charlottesville, Va 22903 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): Allergens found in the home derived from dust mites, animal dander, cockroaches and fungi are commonly associated with the development of asthma. Reducing allergen exposure is a primary goal of asthma management, yet there are no simple tests that enable allergic patients and consumers to measure allergen exposure in the home. In Phase I, the feasibility of using a lateral flow test for mite Group 2 allergen as part of home based allergen detection kit was demonstrated. The test detected mite allergen in dust samples within 10 minutes, correlated with enzyme immunoassay (ELISA) results, and was used to monitor allergen levels in homes and changes in allergen levels following an intervention procedure (steam cleaning). The aims of Phase II are to optimize tests for mite allergen and to investigate the hypothesis that using the test as a tool to educate patients about allergen exposure will encourage implementation and compliance with allergen avoidance procedures. The predictive value of tests for mite Group 1 and Group 2 allergens will be compared to select the optimal test for allergen assessment. A randomized controlled trial will study allergic patients compliance with avoidance procedures, comparing patients who use the mite test on a regular basis, with those who have educational materials but no test. Rapid tests will be developed for cat, dog and cockroach allergens, with the aim of producing a single allergen test card for multiple allergens that can be used to screen for allergen exposure in the home. PROPOSED COMMERCIAL APPLICATIONS: Effective consumer tests for allergens are not available. INDOOR Biotechnologies will market the test through distributors that sell allergen control products, indoor air quality testing services, and household cleaning products. Several companies have expressed strong interest in marketing the allergen tests. Our goals are to market 100,000 tests by the end of Phase II. Lateral flow technology will enable tests for food and latex allergens to be developed, as well as a new generation of rapid allergen diagnostic tests using genetically engineered allergens. The Phase II project will result in the development of consumer based allergen tests that will improve asthma management using environmental control procedures. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

60

•

Allergens

Project Title: REDEFINING THE MAJOR PEANUT ALLERGENS Principal Investigator & Institution: Dreskin, Stephen C.; Medicine; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-DEC-2005 Summary: (provided by applicant): Allergic reactions to peanuts occur because susceptible individuals respond to exposure to peanuts by producing a plasma protein, IgE that binds to a high affinity receptor, FcepsilonRI on mast cells and basophils. This IgE can be cross-linked by specific allergens leading to activation of mast cells and basophils and subsequent allergic reactions. Three major peanut allergens have been described in detail based on their ability to bind IgE on Western blots and to interact with IgE in RAST-inhibition assays. These are Ara h1, Ara h2, and Ara h3. The degree to which these allergens contribute functionally to the activity in crude peanut extracts has never been documented. We propose to use in vitro functional assays to better define the major peanut allergens and will test our in vitro findings in vivo using a mouse model of peanut allergy. Our preliminary data suggests that most of our patients with hypersensitivity to peanuts react to Ara h2 at a 2 log or better sensitivity than to Ara h1. As part of this proposal, these observations will be correlated with independent analysis of these sera on immunoblot. We have further assessed the reactivity of our patients to Ara hl and Ara h2 by quantitating the reactivity to purified proteins and comparing that reactivity to the reactivity with crude peanut extracts. Based on our preliminary data, neither Ara hl nor Ara h2 appear to be major functional allergens in 6 of 7 patients we have examined, whereas Ara h2 may be of great importance in one of seven patients. In a preliminary study, we have separated peanut proteins by anion exchange chromatography and find that a significant portion of the functional allergic activity chromatographs in fractions that do not contain Ara hl or Ara h2. The contents of these fractions is unknown but will be analyzed by functional assays, 2d gels, mass spectroscopy, and IgE immunoblotting. Therefore, we propose to combine functional assays with standard immunoblotting techniques and the power of proteomics to define in molecular detail the peanut allergens quantitatively responsible for mast cell activation in patients with systemic reactions to peanuts. Employment of this approach to define novel, functional major allergens has the potential to completely change our thinking as to which peanut allergens are the most important in specific patients for allergic reactions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: REGULATION OF EXOCYTOSIS IN MAST CELLS Principal Investigator & Institution: Castle, John D.; Cell Biology; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 15-APR-2000; Project End 31-MAR-2005 Summary: Mast cells are specialized for responding to immunoglobulin E and associated allergens and play a key role in initiating allergic inflammation. They respond to stimulation by secreting a variety of inflammatory mediators and cytokines that alter vascular permeability, remodel extracellular matrix, and recruit other host defense cells that amplify the inflammatory response. Many of the secretory products are stored in membrane-bounded granules within the cytoplasm, and their release occurs by compound exocytosis, a massive cascade of granule-plasma membrane and granule-granule fusions involving most if not all of the storage granules. While much progress has been made in understanding the structure and early signaling of the IgE receptor (FceR), much less is known about the regulation and mechanisms of

Studies

61

downstream events in the cascade that links stimulation to compound exocytosis. Understanding these events is of great medical interest as early occurrence in the hierarchical inflammatory response suggests an attractive site for intervention in developing therapies that control asthma, anaphylactic shock, and other acute host reactions to allergens and active peptides. Studies forming the basis of this proposal have shown that compound exocytosis in mast cells is regulated by a novel mechanism involving stimulus-dependent relocation within the cell of the protein SNAP-23 that is thought to comprise part of the fusion machinery. SNAP-23, one of the SNARE family of membrane fusion proteins, relocates in response to secretory stimulation from lamellipodia-like plasma membrane folds along the plasma membrane and intracellularly to granule surfaces. Relocation of SNAP-23 is essential for compound exocytosis and is hypothesized to involve distinct steps of mobilization, cytoskeletallyassisted relocation, and engagement with other SNARE proteins to promote membrane fusion. The overall goal of this proposal is to characterize the molecular mechanisms comprising each of these steps. Streptolysin-O permeabilized mast cells and rat basophilic leukemia (RBL-2H3) cells will be used to address how phosphorylation of SNAP-23 regulates mobilization; what proteins interact with SNAP-23 preceding and following mobilization; how Rho family GTPases and F-actin promote relocation; and how assembly of SNAP-23-containing SNARE complexes relates to engagement and secretion. In addition, a newly discovered inhibitor of compound exocytosis, a peptide derived from one of the secretory carrier membrane proteins (SCAMPs), will be used to analyze its effects on the relocation and function of SNAP-23. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RESPONSES TO RSV AND ALLERGENS AS ANTECEDENTS OF ASTHMA Principal Investigator & Institution: Halonen, Marilyn J.; Professor; None; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2002; Project Start 17-AUG-1998; Project End 31-JUL-2004 Summary: The long-term objective of this project is to elucidate the mechanisms by which allergen sensitization and viral respiratory illnesses mutually influence one another early in life so as to confer risk for asthma. The relationships of asthma to wheezing lower respiratory illnesses (wLRIs) early in life and to sensitization to certain asthma-related allergens have often been addressed but remain poorly defined. This project proposes and tests a mechanistic basis for these relationships. Three specific aims are proposed: 1) to identify the temporal patterns in and mechanisms of development of mitogen and RSV-specific T cytotoxic cell subsets (CD8+ Tc1 and Tc2) and mitogen and Alt-specific T helper cell subsets (CD4+ Th1 and Th2); 2) to determine the immune mechanisms for the absence of peripheral blood eosinopenic responses during viral respiratory infections in children at risk for asthma; and 3) to identify temporal pattern and the mechanisms of the induction of Alt-specific IgE and RSV-specific IgE in infancy in relation to the occurrence of LRIs and parental history of asthma. A unifying hypothesis is offered that children at risk for asthma may have wLRIs in the third year of life because of a persisting deficiency in cytotoxic function of the CD8+ Tc1 subset of cells, a deficiency which is suggested to originate differently in children with and without a parental history of asthma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

62

•

Allergens

Project Title: RODENT ALLERGEN IN HOMES OF LATINO CHILDREN WITH ASTHMA Principal Investigator & Institution: Berg, Jill; None; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2005 Summary: Asthma affects approximately 6 million American children (President's task force, 2000) and is the most common cause of school absences and the second leading cause of pediatric emergency room visits (Clark, 1998). Indoor environmental allergens contribute substantially to childhood asthma morbidity. Eggleston (2000) reported in his review of the National Cooperative Inner City Asthma Study, that children with sensitivity to indoor allergens, such as cockroach, had more asthma attacks and ER visits. Indoor environmental allergens such as cockroaches, dust mites, mold, pet dander, tobacco smoke and other agents can be effectively controlled and have been linked to a reduction in asthma symptoms (Kreiger et al., 2000). Recently, a study has been published that examined the effect of rodent allergen in inner city children with asthma (Phipatanakul et al., 2000). Rodent allergen had previously been implicated as an asthma trigger in occupational health settings but had not been the subject of study in indoor environments for children with asthma. The proposed research plan targets rodent allergen in Latino children with asthma residing in Los Angeles. The specific aims of the research plan are to: 1. Determine the presence of rodent allergen and examine the correlation between self-reported appearance of rodents and detectable rodent allergen levels in inner city homes in LA; 2. Examine the relationship between rodent allergen concentration, sensitization and asthma quality of life in Los Angeles inner-city Latino children with asthma; 3. Determine the effect of a standard rodent eradication protocol on levels of rodent allergen in the home and 4. Explore cultural and environmental barriers to effective rodent eradication in Latino inner city families with a child with asthma. To accomplish these aims, the applicant seeks further training in environmental allergen assessment for children with asthma. This is a natural extension of the applicant's background in nursing, asthma and behavioral science. The training portion of this application is designed to provide solid theoretical foundation, environmental allergen particle measurement skills, cultural competency skills related to influencing adherence to environmental changes and statistical knowledge to prepare the candidate for a research career in the area of environmental allergen exposure for Latino families with a child with asthma. The candidate's prior studies focused on asthma and adherence among non- Latino adults. Latinos are the most rapidly growing ethnic group in the nation and the candidate's long-term research plans target asthma intervention in this impoverished, underserved and vulnerable population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: ROLE OF EXTRACELLULAR PROTEOLYSIS IN EPITHELIAL DEFENSE Principal Investigator & Institution: Werb, Zena; Professor and Vice Chair; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-DEC-2002; Project End 30-NOV-2007 Summary: Infectious agents, allergens and other noxious agents enter through exposed mucosal surfaces, such as the respiratory, gastrointestinal and genitourinary tracts. In response to these pathological agents inflammatory and immune cells are recruited and cross the epithelial barrier in response to a chemotactic gradient. To maintain their function as a barrier to infection, an adequate number of inflammatory cells must cross

Studies

63

into the lumenal spaces. In addition, if the mucosal epithelium is compromised, the defense against infection is lost. The epithelial barrier musttherefore be restored as quickly as possible, to minimize the opportunity for entry of infectious agents. Matrix metalloproteinases (MMPs) are upregulated during lung injury, repair and inflammation. Transgenic mouse models with altered proteolytic potential present unique opportunities to elucidate important cellular and genetic pathways by which extracellular proteolysis participates in these epithelial defenses a mechanism. The overall goal of this proposal is to identify the pathways impacting epithelial defense (inflammatory cell recruitment, epithelial repair) regulated by MMPs and to identify their ma.ior tissue substrates. We will address the characteristics and functional significance of MMP interactions by combined in vivo and in vitro approaches. We propose to determine the role of MMPs in regulating chemoattractants for inflammatory cells in the bronchioalveolar spaces. We hypothesize that dysregulated airway MMP activity modifies the synthesis or release of chemoattractants and/or antagonists of chemoattractant action, into the airspaces, and thus chemoattractant gradients needed to attract the cells out of the parenchymal space into the airspaces are not formed or maintained. We will study this in vivo using micro-organisms or their products in models of infection or allergic sensitization in mice that have genetic modifications in MMP expression or activity, or treat mice with MMP inhibitors. We will evaluate cell recruitment as well as analyse the production of chemoattractants in the spaces. We then propose to determine the mechanism of action and molecular targets of MMPs that regulate inflammatory cell recruitment into the airspaces using normal and genetically modified epithelial cell in culture in collaboration with Project 3 and Cores B and C. We use both candidate and unbiased biochemical approaches. In collaboration with Projects 1 and 2 we will also investigate the role of MMPs in epithelial wound healing using MMP mutant mice, and cells and MMP inhibitors. The immediate implications of this work are in its applications to use of instilled chemoattractant agents and other molecules that modify epithelial defense and will provide proof-of-principle that these critical MMP substrates are potentially efficacious in intervention in epithelial defense mechanisms. Only a thorough understanding of the actions and effects of MMPs and their major substrates will help mitigate the defense against infection so that recruitment of adequate numbers of inflammatory cells into the spaces beyond the epithelial barrier and the ability of the epithelial to repair itself can be accelerated. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE INFLAMMATION

OF

THE

IGE-FCERI

NETWORK

IN

ALLERGIC

Principal Investigator & Institution: Kinet, Jean-Pierre M.; Director, Laboratory of Allergy & Immuno; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-MAY-2006 Summary: This proposal outlines a project designed to meet the requirements for an Asthma and Allergic Diseases Research (AADRC). Role of the IgE-FceRi network in allergic inflammation. All are united by the central theme that three major steps lead to the development of the asthmatic disease: the initial immunization phase against allergens (step 1) the amplification of the Th2 response (step 2), and the development of the effector response and asthma (step3). The hypothesis of this project is that cells expressing high affinity IgE receptor in the form of alphagamma2 contributes to the regulation of the IgE immune response (step 2) and participates in the effector functions of the IgE- FcepsilonRI network in vivo (step 3). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

64

•

Allergens

Project Title: SOCIO-CULTURAL INFLUENCES ON ALLERGIC SENSITIZATION Principal Investigator & Institution: Chew, Ginger L.; Assistant Professor; Environmental Health Sciences; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 10-JUN-2002; Project End 31-MAR-2007 Summary: (provided by applicant): The prevalence of asthma among children of Puerto Rican ethnicity residing in New York City (NYC) has already been reported as among the highest in the world. In addition, we understand that housing factors influence levels of indoor allergens, such that poor housing lends rise to cockroach and mouse allergens, and high humidity is associated with high house dust mite (HDM) allergen levels. What is NOT known is the critical period of exposure in early life, the level of allergen exposure, and the duration of the exposure that leads to sensitization to indoor allergens, and how socioeconomic status, level of acculturation, and travel between NYC and Puerto Rico among these families influences this critical exposure. Our hypothesis is that Puerto Rican children living in NYC are exposed to more indoor allergens early in life than other children in NYC because they do travel to tropical environments where different types of dust mites are more abundant than in NYC. We will assess socioeconomic status, level of acculturation, travel between NYC and Puerto Rico, and the indoor allergen levels in their home environment in NYC and in the homes in Puerto Rico that are visited by them during the first 4 years of life among a birth cohort of Puerto Rican ethnicity from families where the mother has inhalant allergy living in NYC. At two timepoints, 2 and 4 years, we will collect blood from the child and measure IgE specific for dust mite, cat, cockroach, and mouse allergens. At the 4 yr clinic visit, we will also assess whether the child has a diagnosis of probable persistent wheeze asthma or other allergic diseases. Our assembled team includes an aeroallergen scientist, asthma and social epidemiologists, a pediatric pulmonologist, and a statistician, all of which are experienced in conducting large-scale, population-based studies. If we show that travel to Puerto Rico is associated with sensitization to HDM, will this deter parents from taking their children with them to the island? We hope not, because familial and cultural relations are important. This is where the blend of social and environmental science is crucial. We must understand how the two lead to allergic sensitization and be cognizant that they both will be required for the most effective primary prevention of allergic asthma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: STRUCTURAL BIOLOGY OF CEDAR POLLEN ALLERGY Principal Investigator & Institution: Midoro-Horiuti, Terumi; Pediatrics; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-JAN-2008 Summary: (provided by applicant): Candidate: The applicant, Terumi Midoro-Horiuti, M.D., Ph.D., is an Assistant Professor in the Department of Pediatrics at the University of Texas Medical Branch (UTMB). Dr. Midoro completed her residency in pediatrics, her clinical fellowship in allergy/immunology in Japan, research fellowship in Child Health Research Center at the University of Texas Medical Branch. Dr. Midoro and her supervisors at the University of Texas Medical Branch realize additional training in structural and molecular biology will enhance Dr. Midoro's transition into independent investigator. Sponsor: Her mentor, Randall Goldblum, M.D. is a Professor in the Department of Pediatrics and Human Biological Chemistry and Genetics and a Director of Child Health Research Center. Co-mentor, Werner Braun, PhD. is a Professor in the

Studies

65

Department of Human Biological Chemistry and Genetics and a Senior Scientist of the Sealy Center for Structural Biology. Career Development Plan: The educational goal Dr. Midoro proposes here is to learn the theory and practice of structural biology through course work and an investigation of the mechanisms of allergen recognition and allergic sensitization. During the first two years Dr. Midoro will take formal courses: Structure and Function of Biomolecules, and Bioinformatics tools on the Web supported by the Department of Human Biological Chemistry and Genetics. She will devote 80% of her time to her training and her research project. The hypothesis that will be tested by the proposed studies is that conformational IgE epitopes are structurally different from epitopes recognized by other isotypes and are, at least in part, responsible for the allergenicity of certain proteins. The specific aims that will test the hypothesis are to: (1) Identify conformational IgE and IgG epitopes by probing a phage display peptide library. (2) Identify critical elements of linear and conformational epitopes by comparing structures of sensitizing allergens with those of their phylogenetic homologues. (3) Design epitope mimics (mimotopes) of Jun a 1 epitopes that prevent IgE binding and cross-linking by allergens. Child Health Research Center and Searly Center for Structural Biology at the UTMB provide an ideal environment for training Dr. Midoro by incorporating expertise from diverse fields. Completion of this project should greatly enhance Dr. Midoro's chances of an independent research carrier. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TARGETED DELIVERY OF INTERLEUKIN-10 Principal Investigator & Institution: Ferkol, Thomas W.; Associate Professor; Pediatrics; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-MAY-2001; Project End 31-MAR-2005 Summary: (Applicant's Abstract): The respiratory epithelium is the first line of defense in the lung, and is constantly exposed to numerous airborne pathogens, allergens, and other noxious agents. Several innate host defenses have evolved to protect the lung, but a critical feature of pulmonary immunity is the ability of the airway to defend itself yet regulate the inflammatory response to avoid its injury and destruction. This inflammatory response is dysregulated in cystic fibrosis (CF), and similar defects may also exist in other airway diseases like asthma. Recent investigations suggest that an intrinsic, inhibitory mechanism is defective in chronic airway diseases and could account for exaggerated or persistent airway inflammation. Various effector cells that reside in the respiratory tract could be modulated by this inhibition, but we postulate that the respiratory epithelial cell is the primary target and is central to the airway's response to bacterial and antigenic stimuli. In this proposal, we will test this hypothesis by blocking the respiratory epithelium's response to such stimuli, using a novel delivery system that transports interleukin-10 (IL-10) to the epithelial lumen by exploiting the properties of the polymeric immunoglobulin receptor (pIgR). We have constructed fusion proteins that consist of single-chain Fv antibodies directed against the extracellular portion of plgR, or secretory component (SC), linked to the antiinflammatory cytokine, human IL-10 (hIL-l0). Using this approach, we will be able to define the role(s) of the respiratory epithelial cell in the development of airway inflammation by concentrating the anti-inflammatory agent at the immediate epithelial surface. First, we will compare the penetration of free and "targeted" hIL-10 (i.e., anti-SC Fv/hIL-10 fusion protein) through epithelial monolayers in culture, and examine the immunomodulatory effects of these cytokines in model cell systems. We will then define the pharmacological and immunological properties of the targeted IL-10 in transgenic mice that express human pIgR in their airways, and establish that hIL-10 is effectively

66

Allergens

delivered to the respiratory epithelium. Finally, we will examine the effects of hIL-10 delivered specifically to the lumenal surface of the respiratory epithelium in disease models of endobronchial inflammation, and compare the anti-inflammatory effects of the fusion protein with free hIL-10. These investigations will allow us to define the mechanisms by which IL-l0 may act in the airway, and determine if such fusion proteins could potentially be used for therapeutic purposes in CF, asthma, and other airway diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TEAM TARGETING THE ENVIRONMENT AND ASTHMA MANAGEMENT Principal Investigator & Institution: Crain, Ellen F.; Pediatrics; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2000; Project Start 01-AUG-1996; Project End 31-JUL-2004 Summary: (adapted from applicant's Abstract): Hospitalizations and deaths from asthma are highest among inner-city African-American and Latino children. These children may be at greatest risk because they have disproportionately worse access to health care and to quality asthma care, poor self-management skills, and increased exposure to environmental allergens and irritants, particularly ETS and cockroach allergens. The applicants propose to implement a culturally sensitive, cost-effective sixsite intervention for inner-city poor children with asthma aged 4 to 12 years of age called Targeting the Environment and Asthma Management (TEAM). This is a three-pronged intervention which includes the following: (1) the delivery of high-quality asthma care by primary care physicians trained in quality asthma management and behavioral strategies to enhance patient satisfaction; (2) a self- management component by a bilingual Asthma Counselor, who will reinforce the physicians' teaching, review the medication plan, and teach culturally-appropriate self-management skills; and (3) an environmental component in which all TEAM families will be taught environmental control, and TEAM patients who are skin-test positive to cockroach allergens will be offered cockroach eradication services. At each site, three cohorts of 60 subjects each will undergo a baseline interview and be randomly assigned to the TEAM intervention group or the control group. Data will be collected at baseline, at 3, 6, 9, and 12 months during the intervention, and at 3, 6, 9, and 12 months following the intervention period. The intervention will be evaluated for its short- and long-term effectiveness. Primary outcomes include days of cough and wheeze, sleep and play disruption, school days missed, and disruption of caretaker plans. Health utilization outcomes include emergency room (ER) visits, unscheduled and scheduled visits, and hospitalizations. Costs of care for the intervention and control groups will also be monitored. It is hypothesized that functional morbidity and utilization will be significantly less for children in the TEAM intervention group compared with the control group. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: THE PATHOGENESIS AND GENETICS OF ENVIRONMENTAL ASTHMA Principal Investigator & Institution: Schwartz, David A.; Professor of Medicine and Genetics; Medicine; Duke University Durham, Nc 27710 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 30-JUN-2008 Summary: The overall theme of this Program Project Grant (P01) is to understand further the pathogenesis and genetics of asthma by studying environmental airway

Studies

67

disease. We chose this theme for our PPG for the following reasons: 1) the symptoms and signs of asthma constitute a broad clinical phenotype; 2) asthma is a complex genetic disease caused by many biologically unique gene-gene and gene-environment interactions; 3) environmental models of airway disease serve to narrow the biological phenotype of asthma, providing an ideal opportunity to study the pathogenesis and genetics of this complex disease; and 4) this theme builds on existing scientific expertise and ensures a highly interactive program. Since acquired and innate mechanisms of immunity can function independently or interactively to cause or exacerbate asthma, we have chosen to use allergens and/or irritants (endotoxin and ozone) in the proposed projects to narrow the exposure-response phenotype and investigate the pathogenesis and genetics of environmental airway disease. The end result is a highly integrated and focused program that has the potential to make a number of novel, related observations. The primary hypothesis unifying this research program is that investigating environmental airway disease by modeling biologically unique gene-environmentasthma phenotypes will advance our understanding of the pathogenesis and genetics of asthma. The project-specific hypotheses proposal are: Project 1: Polymorphisms of genes expressed by airway cells in asthmatics following specific subsegmental airway challenges predispose individuals to the development of asthma. Project 2: Integrating the assessment of the environmental risk factors with an enhanced understanding of specific asthma susceptibility genes will lead to a coherent understanding of the relationship between genes, environment, and the development of asthma in an African American population. Project 3: Specific gene polymorphisms/mutations contribute to differential susceptibility to Oa-induced lung injury in asthmatic and normal subjects, and specific acquired host factors regulate injury from exposure to O3. Project 4: Alteration in airway SNO metabolism is important in the pathogenesis of asthma resulting in the dysregulation of airway cell apoptosis that contributes to the acute and chronic inflammatory changes seen in asthma. In aggregate, the coupled scientific findings in this program will substantially enhance our understanding of the pathogenesis and genetics of asthma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE ROLE OF TH CELL SUBSETS AND ALLERGIC LUNG INFLAMMATI Principal Investigator & Institution: Umetsu, Dale T.; Associate Professor; Pediatrics; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 01-APR-1999; Project End 31-MAR-2003 Summary: The long term goals of this project are to determine and understand the role of CD4 Th cell subsets in the development, maintenance, reduction, and prevention of allergen-induced airway hyperreactivity. We and others have shown that Th2 cells play a major role in producing and exacerbating allergic inflammation, and it has been assumed that Th cells with the "alternative" cytokine profile (i.e., Th1 cells) inhibit and prevent allergic inflammation in nonallergic individuals. Preliminary data in our laboratory however, indicate that antigen-specific Th1 cell lines when transferred into recipient mice, do not down regulate airway hyperreactivity but instead cause severe lung disease. This suggests that cell types other than Th1 cells (e.g., those producing TGF-beta), and other cellular processes may be involved in protective immune responses to allergens that down regulate and prevent allergic inflammatory responses in normal nonallergic individuals. The goals therefore of this proposal are to directly examine the capacity of Th1 cells and other types of regulatory cells to mitigate allergic inflammation and allergen- induced airway hyperreactivity. We will directly examine: 1.

68

Allergens

the role of Th1 and ThO cells in allergic airway hyperreactivity (a model for asthma). 2. the role of TGF-beta producing cells (established by gene transfer) in the regulation of airway hyperreactivity. 3. specific mechanisms that induce tolerance and inhibit airway hyperreactivity in mice rendered unresponsive to ovalbumin (e.g., the role of antigen presentation by B cells and by alveolar macrophages, and the role of costimulation with CTLA-4). We have established several unique models for airway hyperreactivity and intranasal tolerance, have assembled a broad range of reagents, and have exciting preliminary data to perform the proposed experiments. These innovative studies will expand our understanding of the complexity and diversity of Th cells and of immune responses that protect against allergy and asthma. They will provide the basis for development of new disease-modifying strategies to treat and potentially cure patients with allergy and asthma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TRIAL OF INTERVENTIONS TO REDUCE ASTHMA MORBIDITY Principal Investigator & Institution: O'connor, George T.; Associate Professor; Pediatrics; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2000; Project Start 01-AUG-1996; Project End 31-JUL-2004 Summary: (adapted from applicant's Abstract): Comprehensive case management by a specially trained nurse and home environmental evaluation and intervention by trained personnel have been proposed as interventions which can reduce childhood asthma morbidity. Both of these, however, are of unproven benefit among urban asthmatic children of low-income families. Furthermore, the impact if these interventions, which require an initial financial investment by health care organizations, on health care costs has not been established. The applicants propose to conduct a randomized, controlled trial of the effectiveness and cost impact of (a) case management by a specially trained nurse and (b) a home environment control intervention among four- to twelve-year-old children with moderate-to-severe asthma receiving care in five inner-city neighborhood health centers and in the Pediatric Clinic of Boston City Hospital (BCH). Using a factorial design, subjects will be randomized to receive one, both, or neither intervention. The following specific questions will be addressed: (1) Does case management by a nurse with special training in asthma care, working in concert with the primary care clinician, result in decreased utilization of acute care (i.e., hospitalization, emergency department care, and unscheduled clinic visits), decreased school absenteeism, and increased quality of life? (2) Does a home environment control intervention implemented by trained personnel visiting the patient's home result in the outcomes listed for Aim 1? (3) Does the combination of both interventions provide additional benefit beyond that provided by either intervention alone? (4) To what extent do these interventions lead to sustained reductions in the concentrations of important indoor allergens in house dust? To what extent are these reductions correlated with improvement in clinical outcomes? (5) What is the impact of these two interventions, alone or in combination, on direct health care costs? Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: WISCONSIN TRAINING PROG

ALLERGY

AND

IMMUNOLOGY

RESEARCH

Principal Investigator & Institution: Busse, William W.; Professor of Medicine; Medicine; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 01-AUG-2000; Project End 31-JUL-2005

Studies

69

Summary: (adapted from the application): The proposed allergy/immunology training (Wisconsin Allergy Research Training) (WISCART) program will provide structured and interactive research training to researchers with either M.D. or Ph.D. degrees, and in doing so, will prepare the trainees for careers in academic medicine. In addition to postdoctoral training, the WISCART program will provide predoctoral trainees with an indepth summer research program in order to foster interest and gain experience in allergy/immunology research. The WISCART program is designed to provide 4-5 years of research training largely through mentored research. The faculty of the program has well-established and federally funded research programs with interdisciplinary research activities that emphasize the application of basic concepts of immunology, virology, molecular biology, and cell biology to clinically relevant questions pertaining to allergy and immunology. Projects available for trainee participation include: 1) biology of inflammatory cells: eosinophils, mast cells, T cells, and neutrophils; 2) cytokines/inflammatory mediators; 3) cell adhesion; 4) molecular biology of allergens; 5) viral immunology; 6) pulmonary physiology /pharmacology; 7) signal transduction; and 8) asthma clinical research. Training in the laboratory will be supplemented by additional courses and seminars pertaining to medical ethics, biostatistics, scientific writing and presentations, and preparation of grants for extramural funding. These activities and trainee evaluations will be coordinated with an established Clinical Investigator Preparatory Program (CIPP) at the University of Wisconsin. The objectives of the program include developing a research project, establishing a record of publication, obtaining extramural grant funding, and ultimately, preparing trainees to be independent research scientists in the area of allergy and immunology. 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 “allergens” (or synonyms) into the search box. This search gives you access to fulltext articles. The following is a sample of items found for allergens in the PubMed Central database: •

Amino acid sequence of Fel dI, the major allergen of the domestic cat: protein sequence analysis and cDNA cloning. by Morgenstern JP, Griffith IJ, Brauer AW, Rogers BL, Bond JF, Chapman MD, Kuo MC.; 1991 Nov 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=52784

•

Chaperone Coexpression Plasmids: Differential and Synergistic Roles of DnaK-DnaJGrpE and GroEL-GroES in Assisting Folding of an Allergen of Japanese Cedar

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.

70

Allergens

Pollen, Cryj2, in Escherichia coli. by Nishihara K, Kanemori M, Kitagawa M, Yanagi H, Yura T.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106217 •

Conformational and Linear B-Cell Epitopes of Asp f 2, a Major Allergen of Aspergillus fumigatus, Bind Differently to Immunoglobulin E Antibody in the Sera of Allergic Bronchopulmonary Aspergillosis Patients. by Banerjee B, Greenberger PA, Fink JN, Kurup VP.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115968

•

Endobronchial allergen challenge in asthma. Demonstration of cellular source of granulocyte macrophage colony-stimulating factor by in situ hybridization. by Broide DH, Firestein GS.; 1991 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=295519

•

Group I allergens of grass pollen as cell wall-loosening agents. by Cosgrove DJ, Bedinger P, Durachko DM.; 1997 Jun 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21089

•

Immunological Characterization of Asp f 2, a Major Allergen from Aspergillus fumigatus Associated with Allergic Bronchopulmonary Aspergillosis. by Banerjee B, Greenberger PA, Fink JN, Kurup VP.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108645

•

Mass spectrometric analysis of electrophoretically separated allergens and proteases in grass pollen diffusates. by Raftery MJ, Saldanha RG, Geczy CL, Kumar RK.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=239031

•

Mast cells are required for experimental oral allergen --induced diarrhea. by Brandt EB, Strait RT, Hershko D, Wang Q, Muntel EE, Scribner TA, Zimmermann N, Finkelman FD, Rothenberg ME.; 2003 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=281649

•

Natural Immunity to Ascaris lumbricoides Associated with Immunoglobulin E Antibody to ABA-1 Allergen and Inflammation Indicators in Children. by McSharry C, Xia Y, Holland CV, Kennedy MW.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96345

•

Peripheral T-Cell Tolerance Induced in Naive and Primed Mice by Subcutaneous Injection of Peptides from the Major Cat Allergen Fel d I. by Briner TJ, Kuo M, Keating KM, Rogers BL, Greenstein JL.; 1993 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47191

•

Recombinant peanut allergen Ara h I expression and IgE binding in patients with peanut hypersensitivity. by Burks AW, Cockrell G, Stanley JS, Helm RM, Bannon GA.; 1995 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=185807

•

Synergism between allergens and viruses and risk of hospital admission with asthma: case-control study. by Green RM, Custovic A, Sanderson G, Hunter J, Johnston SL, Woodcock A.; 2002 Mar 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=100316

Studies

•

71

Use of ultramolecular potencies of allergen to treat asthmatic people allergic to house dust mite: double blind randomised controlled clinical trial. by Lewith GT, Watkins AD, Hyland ME, Shaw S, Broomfield JA, Dolan G, Holgate ST.; 2002 Mar 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=67767

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

A case of allergy to airborne, heat-labile shrimp allergens. Author(s): Asero R, Mistrello G, Roncarolo D, Amato S. Source: The Journal of Allergy and Clinical Immunology. 2002 February; 109(2): 371-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11842314

•

A comparison of two skin test methodologies and allergens from two different manufacturers. Author(s): Rhodius R, Wickens K, Cheng S, Crane J. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2002 April; 88(4): 374-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11991555

•

A recombinant fragment of human SP-D reduces allergic responses in mice sensitized to house dust mite allergens. Author(s): Strong P, Townsend P, Mackay R, Reid KB, Clark HW. Source: Clinical and Experimental Immunology. 2003 November; 134(2): 181-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14616775

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.

72

Allergens

•

Abatement of cockroach allergens (Bla g 1 and Bla g 2) in low-income, urban housing: month 12 continuation results. Author(s): Arbes SJ Jr, Sever M, Mehta J, Gore JC, Schal C, Vaughn B, Mitchell H, Zeldin DC. Source: The Journal of Allergy and Clinical Immunology. 2004 January; 113(1): 109-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14713915

•

Age-related T cell responses to allergens in childhood. Author(s): Smart JM, Suphioglu C, Kemp AS. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2003 March; 33(3): 317-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12614445

•

Allergic sensitization to indoor and outdoor allergens and relevance to bronchial hyperresponsiveness in younger and older subjects. Author(s): Kerkhof M, Postma DS, Schouten JP, de Monchy JG. Source: Allergy. 2003 December; 58(12): 1261-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14616101

•

Allergy to asticot maggots. Identification of allergens. Author(s): Porcel Carreno S, Jimenez-Timon S, Camara Hijon C, Rodriguez Trabado A, Rodriguez Martin E, Fletes Peral C, Hernandez Arbeiza J, Cobo Lopez R. Source: Allergologia Et Immunopathologia. 2003 September-October; 31(5): 265-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14572415

•

Allergy to fungal allergens in northern Italy. Author(s): Zauli D, Grassi A, Vukatana G, Ballardini G, Bianchi FB. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2004 January; 92(1): 92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14756471

•

Ammonium thiolactate and thiolactic acid: important hairdressers' allergens? Author(s): Uter W, Geier J, Pirker C, Aberer W, Kranke B, Richter G, John SM, Becker D, Koch P, Szliska C, Fartasch M, Frosch PJ; German Contact Dermatitis Research Group (DKG). Source: Contact Dermatitis. 2002 April; 46(4): 242-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12081707

Studies

73

•

An ELISA for recombinant Lepidoglyphus destructor, Lep d 2, and the monitoring of exposure to dust mite allergens in farming households. Author(s): Parvaneh S, Johansson E, Elfman LH, van Hage-Hamsten M. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2002 January; 32(1): 80-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12002743

•

Animal allergens and their control. Author(s): Phipatanakul W. Source: Curr Allergy Asthma Rep. 2001 September; 1(5): 461-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11892073

•

Antenatal determinants of neonatal immune responses to allergens. Author(s): Devereux G, Barker RN, Seaton A. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2002 January; 32(1): 43-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12002736

•

Antineutrophil cytoplasmic antibodies, anti-Saccharomyces cerevisiae antibodies, and specific IgE to food allergens in children with inflammatory bowel diseases. Author(s): Bartunkova J, Kolarova I, Sediva A, Holzelova E. Source: Clinical Immunology (Orlando, Fla.). 2002 February; 102(2): 162-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11846458

•

Approaches based on mutated or modified recombinant grass pollen allergens--in vivo evaluation of the constructs. Author(s): Lepp U, Eberhardt F, Schramm G, Zabel P, Suck R, Meyer H, Fiebig H, Cromwell O, Becker WM. Source: Arb Paul Ehrlich Inst Bundesamt Sera Impfstoffe Frankf a M. 2003; (94): 188-91. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15119038

•

Are we closer to developing threshold limit values for allergens in the workplace? Author(s): Heederik D. Source: Current Opinion in Allergy and Clinical Immunology. 2001 April; 1(2): 185-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11964688

•

Assessment and control of fungal allergens. Author(s): Dziadzio L, Bush RK. Source: Curr Allergy Asthma Rep. 2001 September; 1(5): 455-60. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11892072

74

Allergens

•

Associations of Fc epsilon R1-beta polymorphisms with immunoglobin E antibody responses to common inhalant allergens in a rural population. Author(s): van Hage-Hamsten M, Johansson E, Kronqvist M, Loughry A, Cookson WO, Moffatt MF. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2002 June; 32(6): 838-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12047428

•

Atopic allergens of plant foods. Author(s): Breiteneder H, Ebner C. Source: Current Opinion in Allergy and Clinical Immunology. 2001 June; 1(3): 261-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11964699

•

Atopy patch test reactions to Malassezia allergens differentiate subgroups of atopic dermatitis patients. Author(s): Johansson C, Sandstrom MH, Bartosik J, Sarnhult T, Christiansen J, Zargari A, Back O, Wahlgren CF, Faergemann J, Scheynius A, Tengvall Linder M. Source: The British Journal of Dermatology. 2003 March; 148(3): 479-88. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12653739

•

Avoidance of hidden allergens in processed foods: a challenge for food chemists and manufacturers. Author(s): Vieths S. Source: Die Nahrung. 2003 April; 47(2): 73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12744281

•

Baker's asthma: diversity of allergens. Author(s): Savolainen J. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 1997 October; 27(10): 1111-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9383249

•

Basidiomycete allergens. Author(s): Horner WE, Helbling A, Lehrer SB. Source: Allergy. 1998 December; 53(12): 1114-21. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9930586

•

Beer-induced anaphylaxis: identification of allergens. Author(s): Figueredo E, Quirce S, del Amo A, Cuesta J, Arrieta I, Lahoz C, Sastre J. Source: Allergy. 1999 June; 54(6): 630-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10435480

Studies

75

•

Beta(1-->3)-glucan in house dust of German homes: housing characteristics, occupant behavior, and relations with endotoxins, allergens, and molds. Author(s): Gehring U, Douwes J, Doekes G, Koch A, Bischof W, Fahlbusch B, Richter K, Wichmann HE, Heinrich J; INGA Study Group. Indoor Factors and Genetics in Asthma. Source: Environmental Health Perspectives. 2001 February; 109(2): 139-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11266323

•

Binding affinities of allergens from pollen, mites, and house dust for specific IgG subclass antibodies. Author(s): Boluda L, de la Cuadra B, Berrens L. Source: Allergy. 1996 October; 51(10): 706-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8904998

•

Biochemical characterization and surfactant properties of horse allergens. Author(s): Goubran Botros H, Poncet P, Rabillon J, Fontaine T, Laval JM, David B. Source: European Journal of Biochemistry / Febs. 2001 May; 268(10): 3126-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11358533

•

Biochemistry of food allergens. Author(s): Stanley JS, Bannon GA. Source: Clinical Reviews in Allergy & Immunology. 1999 Fall; 17(3): 279-91. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10597368

•

Bioinformatics for characterisation of allergens, allergenicity and allergic crossreactivity. Author(s): Brusic V, Petrovsky N. Source: Trends in Immunology. 2003 May; 24(5): 225-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12738409

•

Biologic activity of Dermatophagoides siboney and Blomia tropicalis allergens in exposed and unexposed mite-allergic individuals. Effect of patient selection on the biologic standardization of mite extracts. Author(s): Casas R, Ferrandiz R, Wihl JA, Fernandez B, Dreborg S. Source: Allergy. 1999 April; 54(4): 392-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10371100

•

Biological activity of recombinant Der p 2, Der p 5 and Der p 7 allergens of the housedust mite Dermatophagoides pteronyssinus. Author(s): Lynch NR, Thomas WR, Garcia NM, Di Prisco MC, Puccio FA, L'opez RI, Hazell LA, Shen HD, Lin KL, Chua KY. Source: International Archives of Allergy and Immunology. 1997 September; 114(1): 5967. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9303332

76

Allergens

•

Biological reference preparations for allergens. Author(s): Dorpema JW. Source: Arb Paul Ehrlich Inst Bundesamt Sera Impfstoffe Frankf a M. 1997; (91): 111-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9383898

•

Birch and ragweed pollinosis north of Milan: a model to investigate the effects of exposure to "new" airborne allergens. Author(s): Asero R. Source: Allergy. 2002 November; 57(11): 1063-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12359005

•

Biting-insect allergens. Author(s): Hoffman DR. Source: Clin Allergy Immunol. 2004; 18: 355-68. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15042924

•

Blomia tropicalis: more than just another source of mite allergens. Author(s): Thomas WR, Hales BJ, Smith W. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2003 April; 33(4): 416-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12680854

•

Booster immunization of children with an acellular pertussis vaccine enhances Th2 cytokine production and serum IgE responses against pertussis toxin but not against common allergens. Author(s): Ryan EJ, Nilsson L, Kjellman N, Gothefors L, Mills KH. Source: Clinical and Experimental Immunology. 2000 August; 121(2): 193-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10931131

•

Bronchial allergen challenge in subjects with low levels of allergic sensitization to indoor allergens. Author(s): Witteman AM, Mulder M, Aalberse RC, Jansen HM, van der Zee JS. Source: Allergy. 1999 April; 54(4): 366-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10371096

•

Bronchial allergen challenge with isolated major allergens of Dermatophagoides pteronyssinus: the role of patient characteristics in the early asthmatic response. Author(s): van der Veen MJ, Lopuhaa CE, Aalberse RC, Jansen HM, van der Zee JS. Source: The Journal of Allergy and Clinical Immunology. 1998 July; 102(1): 24-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9679844

Studies

77

•

Bronchial responsiveness to adenosine-5'-monophosphate and methacholine as predictors for nasal symptoms due to newly introduced allergens. A follow-up study among laboratory animal workers and bakery apprentices. Author(s): de Meer G, Postma DS, Heederik D. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2003 June; 33(6): 789-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12801314

•

Can knowledge of the molecular structure of allergens improve immunotherapy? Author(s): Pomes A, Chapman MD. Source: Current Opinion in Allergy and Clinical Immunology. 2001 December; 1(6): 54954. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11964740

•

cDNA cloning and heterologous expression of the major allergens from peach and apple belonging to the lipid-transfer protein family. Author(s): Diaz-Perales A, Garcia-Casado G, Sanchez-Monge R, Garcia-Selles FJ, Barber D, Salcedo G. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2002 January; 32(1): 87-92. Erratum In: Clin Exp Allergy. 2002 September; 32(9): 1387. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12002744

•

Characterisation of pollen allergens. Author(s): Puc M. Source: Annals of Agricultural and Environmental Medicine : Aaem. 2003; 10(2): 143-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14677904

•

Characteristics and immunobiology of grass pollen allergens. Author(s): Andersson K, Lidholm J. Source: International Archives of Allergy and Immunology. 2003 February; 130(2): 87107. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12673063

•

Characterization of allergens of Anisakis simplex. Author(s): Arlian LG, Morgan MS, Quirce S, Maranon F, Fernandez-Caldas E. Source: Allergy. 2003 December; 58(12): 1299-303. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14616106

78

Allergens

•

Characterization of allergens secreted by Anisakis simplex parasite: clinical relevance in comparison with somatic allergens. Author(s): Baeza ML, Rodriguez A, Matheu V, Rubio M, Tornero P, de Barrio M, Herrero T, Santaolalla M, Zubeldia JM. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2004 February; 34(2): 296-302. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14987311

•

Characterization of specific IgE response in vitro against protein and drug allergens using atopic and normal donors. Author(s): Akesson A, Ingvarsson S, Karlsson F, Leyva L, Blanca M, Cuerden SA, Smith JA, Coleman JW, Borrebaeck CA. Source: Allergy. 2002 March; 57(3): 193-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11906332

•

Characterization of the major allergens purified from the venom of the paper wasp Polistes gallicus. Author(s): Pantera B, Hoffman DR, Carresi L, Cappugi G, Turillazzi S, Manao G, Severino M, Spadolini I, Orsomando G, Moneti G, Pazzagli L. Source: Biochimica Et Biophysica Acta. 2003 October 13; 1623(2-3): 72-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14572904

•

Childhood asthma and indoor allergens: the classroom may be a culprit. Author(s): Epstien BL. Source: J Sch Nurs. 2001 October; 17(5): 253-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11885341

•

Cockroach allergens: environmental distribution and relationship to disease. Author(s): Arruda LK, Ferriani VP, Vailes LD, Pomes A, Chapman MD. Source: Curr Allergy Asthma Rep. 2001 September; 1(5): 466-73. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11892074

•

Cockroach and other inhalant insect allergens. Author(s): Helm RM, Pomes A. Source: Clin Allergy Immunol. 2004; 18: 271-96. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15042920

•

Common environmental allergens causing respiratory allergy in India. Author(s): Singh AB, Kumar P. Source: Indian J Pediatr. 2002 March; 69(3): 245-50. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12003301

Studies

79

•

Common shoe allergens undetected by commercial patch-testing kits: dithiodimorpholine and isocyanates. Author(s): Belsito DV. Source: American Journal of Contact Dermatitis : Official Journal of the American Contact Dermatitis Society. 2003 June; 14(2): 95-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14749029

•

Comparative prevalence of sensitization to common animal, plant and mould allergens in subjects with asthma, or atopic dermatitis and/or allergic rhinitis living in a tropical environment. Author(s): Montealegre F, Meyer B, Chardon D, Vargas W, Zavala D, Hart B, Bayona M. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2004 January; 34(1): 51-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14720262

•

Comparison of two dust collection methods for reservoir indoor allergens and endotoxin on carpets and mattresses. Author(s): Wickens K, Lane J, Siebers R, Ingham T, Crane J. Source: Indoor Air. 2004 June; 14(3): 217-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15104790

•

Contact allergens in shoe leather among patients with foot eczema. Author(s): van Coevorden AM, Coenraads PJ, Pas HH, van der Valk PG. Source: Contact Dermatitis. 2002 March; 46(3): 145-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12000322

•

Controlling indoor allergens. Author(s): Custovic A, Murray CS, Gore RB, Woodcock A. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2002 May; 88(5): 432-41; Quiz 442-3, 529. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12027062

•

Current mite, cat, and dog allergen exposure, pet ownership, and sensitization to inhalant allergens in adults. Author(s): Custovic A, Simpson BM, Simpson A, Hallam CL, Marolia H, Walsh D, Campbell J, Woodcock A; National Asthma Campaign Manchester Asthma and Allergy Study Group. Source: The Journal of Allergy and Clinical Immunology. 2003 February; 111(2): 402-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12589363

80

Allergens

•

Current understanding of cross-reactivity of food allergens and pollen. Author(s): Vieths S, Scheurer S, Ballmer-Weber B. Source: Annals of the New York Academy of Sciences. 2002 May; 964: 47-68. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12023194

•

Current understanding of food allergens. Author(s): Lehrer SB, Ayuso R, Reese G. Source: Annals of the New York Academy of Sciences. 2002 May; 964: 69-85. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12023195

•

Date palm and sandstorm-borne allergens. Author(s): Kwaasi AA. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2003 April; 33(4): 419-26. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12680855

•

Detection and clinical characterization of patients with oral allergy syndrome caused by stable allergens in Rosaceae and nuts. Author(s): Asero R. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 1999 November; 83(5): 377-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10582717

•

Detection of allergens in plantain (Plantago lanceolata) pollen. Author(s): Asero R, Mistrello G, Roncarolo D, Casarini M. Source: Allergy. 2000 November; 55(11): 1059-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11097317

•

Detection of cross-reactivity for atopic immunoglobulin E against multiple allergens. Author(s): Chiou YH, Yuo CY, Wang LY, Huang SP. Source: Clinical and Diagnostic Laboratory Immunology. 2003 March; 10(2): 229-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12626447

•

Detection of IgA antibodies to cat, beta-lactoglobulin, and ovalbumin allergens in human milk. Author(s): Casas R, Bottcher MF, Duchen K, Bjorksten B. Source: The Journal of Allergy and Clinical Immunology. 2000 June; 105(6 Pt 1): 1236-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10856160

Studies

81

•

Detection of peanut allergens in breast milk of lactating women. Author(s): Vadas P, Wai Y, Burks W, Perelman B. Source: Jama : the Journal of the American Medical Association. 2001 April 4; 285(13): 1746-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11277829

•

Detection of specific IgE antibodies in the sera of patients allergic to birch pollen using recombinant allergens Bet v 1, Bet v 2, Bet v 4: evaluation of different IgE reactivity profiles. Author(s): Rossi RE, Monasterolo G, Monasterolo S. Source: Allergy. 2003 September; 58(9): 929-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12911423

•

Detection of trace amounts of hidden allergens: hazelnut and almond proteins in chocolate. Author(s): Scheibe B, Weiss W, Rueff F, Przybilla B, Gorg A. Source: J Chromatogr B Biomed Sci Appl. 2001 May 25; 756(1-2): 229-37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11419715

•

Detection of workers sensitised to high molecular weight allergens: a diagnostic study in laboratory animal workers. Author(s): Meijer E, Grobbee DE, Heederik D. Source: Occupational and Environmental Medicine. 2002 March; 59(3): 189-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11886950

•

Determinants of clinical allergic disease. The relevance of indoor allergens to the increase in asthma. Author(s): Platts-Mills TA, Blumenthal K, Perzanowski M, Woodfolk JA. Source: American Journal of Respiratory and Critical Care Medicine. 2000 September; 162(3 Pt 2): S128-33. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10988167

•

Different IgE reactivity profiles in birch pollen-sensitive patients from six European populations revealed by recombinant allergens: an imprint of local sensitization. Author(s): Moverare R, Westritschnig K, Svensson M, Hayek B, Bende M, Pauli G, Sorva R, Haahtela T, Valenta R, Elfman L. Source: International Archives of Allergy and Immunology. 2002 August; 128(4): 325-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12218371

•

Digestibility of allergens extracted from natural rubber latex and vegetable foods. Author(s): Yagami T, Haishima Y, Nakamura A, Osuna H, Ikezawa Z. Source: The Journal of Allergy and Clinical Immunology. 2000 October; 106(4): 752-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11031347

82

Allergens

•

Dissociation of allergen-specific IgE and IgA responses in sera and tears of pollenallergic patients: a study performed with purified recombinant pollen allergens. Author(s): Aghayan-Ugurluoglu R, Ball T, Vrtala S, Schweiger C, Kraft D, Valenta R. Source: The Journal of Allergy and Clinical Immunology. 2000 April; 105(4): 803-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10756233

•

Distribution of dust-mite allergens (Lep d 2, Der p 1, Der f 1, Der 2) in pig-farming environments and sensitization of the respective farmers. Author(s): Radon K, Schottky A, Garz S, Koops F, Szadkowski D, Radon K, Nowak D, Luczynska C. Source: Allergy. 2000 March; 55(3): 219-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10753011

•

Distribution variations of multi allergens at asthmatic children's homes. Author(s): Chen HL, Su HJ, Lin LL. Source: The Science of the Total Environment. 2002 April 22; 289(1-3): 249-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12049401

•

Do allergens play a role in early childhood asthma? Author(s): Kemp AS. Source: The Medical Journal of Australia. 2002 September 16; 177 Suppl: S52-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12225259

•

Dosage considerations in patch testing with liquid allergens. Author(s): Shaw DW, Zhai H, Maibach HI, Niklasson B. Source: Contact Dermatitis. 2002 August; 47(2): 86-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12423405

•

Dose-dependent and preterm- accentuated diaplacental transport of nutritive allergens in vitro. Author(s): Edelbauer M, Loibichler C, Witt A, Gerstmayr M, Putschogl B, Urbanek R, Szepfalusi Z. Source: International Archives of Allergy and Immunology. 2003 January; 130(1): 25-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12576732

•

Drug allergens, haptens, and anaphylatoxins. Author(s): Hernandez-Trujillo VP, Lieberman PL, Chowdhury BA. Source: Clin Allergy Immunol. 2004; 18: 387-419. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15042926

Studies

83

•

Dust mites: update on their allergens and control. Author(s): Arlian LG. Source: Curr Allergy Asthma Rep. 2001 November; 1(6): 581-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11892088

•

Early life exposure to dietary and inhalant allergens. Author(s): Vance GH, Holloway JA. Source: Pediatric Allergy and Immunology : Official Publication of the European Society of Pediatric Allergy and Immunology. 2002; 13 Suppl 15: 14-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12688618

•

Effect and correlation of serum total IgE, eosinophil granule cationic proteins and sensitized allergens in atopic dermatitis patients with or without rhinitis. Author(s): Wu CS, Yu CL, Chang CH, Kuo WR, Lin HJ, Yu HS. Source: Kaohsiung J Med Sci. 2002 May; 18(5): 229-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12197429

•

Effect of airborne allergens on emergency visits by children for conjunctivitis and rhinitis. Author(s): Cakmak S, Dales RE, Burnett RT, Judek S, Coates F, Brook JR. Source: Lancet. 2002 March 16; 359(9310): 947-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11918918

•

Effect of bedding control on amount of house dust mite allergens, asthma symptoms, and peak expiratory flow rate. Author(s): Lee IS. Source: Yonsei Medical Journal. 2003 April 30; 44(2): 313-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12728474

•

Effect of montelukast on exhaled NO in asthmatic children exposed to relevant allergens. Author(s): Piacentini GL, Peroni DG, Del Giudice MM, Bodini A, Costella S, Vicentini L, Boner AL. Source: Pediatric Allergy and Immunology : Official Publication of the European Society of Pediatric Allergy and Immunology. 2002 April; 13(2): 137-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12000487

•

Egg white proteins as inhalant allergens associated with baker's asthma. Author(s): Escudero C, Quirce S, Fernandez-Nieto M, Miguel J, Cuesta J, Sastre J. Source: Allergy. 2003 July; 58(7): 616-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12823120

84

Allergens

•

Environmental allergens and asthma in urban elementary schools. Author(s): Amr S, Bollinger ME, Myers M, Hamilton RG, Weiss SR, Rossman M, Osborne L, Timmins S, Kimes DS, Levine ER, Blaisdell CJ. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2003 January; 90(1): 34-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12546335

•

Environmental allergens and irritants in schools: a focus on asthma. Author(s): Tortolero SR, Bartholomew LK, Tyrrell S, Abramson SL, Sockrider MM, Markham CM, Whitehead LW, Parcel GS. Source: The Journal of School Health. 2002 January; 72(1): 33-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11865797

•

Environmental allergens in Kuwait. Author(s): al Mousawi M, Behbehani N, Arifhodzic N, Lovel H, Woodcock A, Custovic A. Source: Allergy. 2001 December; 56(12): 1237-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11736766

•

Eotaxin represents the principal eosinophil chemoattractant in a novel murine asthma model induced by house dust containing cockroach allergens. Author(s): Kim J, Merry AC, Nemzek JA, Bolgos GL, Siddiqui J, Remick DG. Source: Journal of Immunology (Baltimore, Md. : 1950). 2001 September 1; 167(5): 280815. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11509626

•

Epidermal Langerhans cell migration and sensitisation to chemical allergens. Author(s): Cumberbatch M, Dearman RJ, Griffiths CE, Kimber I. Source: Apmis : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica. 2003 July-August; 111(7-8): 797-804. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12974781

•

Estimating the incidence of occupational asthma and rhinitis from laboratory animal allergens in the UK, 1999-2000. Author(s): Draper A, Newman Taylor A, Cullinan P. Source: Occupational and Environmental Medicine. 2003 August; 60(8): 604-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12883023

Studies

85

•

Evaluation of a rule base for identifying contact allergens by using a regulatory database: Comparison of data on chemicals notified in the European Union with "structural alerts" used in the DEREK expert system. Author(s): Zinke S, Gerner I, Schlede E. Source: Alternatives to Laboratory Animals : Atla. 2002 May-June; 30(3): 285-98. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12106006

•

Evaluation of contact sensitization in vulvar lichen simplex chronicus. A proposal for a battery of selected allergens. Author(s): Virgili A, Bacilieri S, Corazza M. Source: J Reprod Med. 2003 January; 48(1): 33-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12611092

•

Evidence for the genetic control of immunoglobulin E reactivity to the allergens of Alternaria alternata. Author(s): Karihaloo C, Tovey ER, Mitakakis TZ, Duffy DL, Britton WJ. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2002 September; 32(9): 1316-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12220470

•

Exposure and sensitization to indoor allergens: association with lung function, bronchial reactivity, and exhaled nitric oxide measures in asthma. Author(s): Langley SJ, Goldthorpe S, Craven M, Morris J, Woodcock A, Custovic A. Source: The Journal of Allergy and Clinical Immunology. 2003 August; 112(2): 362-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12897743

•

Exposure to airborne allergens: a review of sampling methods. Author(s): Renstrom A. Source: Journal of Environmental Monitoring : Jem. 2002 October; 4(5): 619-22. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12400904

•

Exposure to indoor allergens in homes of patients with asthma and/or rhinitis in southeast Brazil: effect of mattress and pillow covers on mite allergen levels. Author(s): Tobias KR, Ferriani VP, Chapman MD, Arruda LK. Source: International Archives of Allergy and Immunology. 2004 April; 133(4): 365-70. Epub 2004 March 17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15031610

86

Allergens

•

Exposure to inhalable dust, wheat flour and alpha-amylase allergens in industrial and traditional bakeries. Author(s): Bulat P, Myny K, Braeckman L, van Sprundel M, Kusters E, Doekes G, Possel K, Droste J, Vanhoorne M. Source: The Annals of Occupational Hygiene. 2004 January; 48(1): 57-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14718346

•

Expression and cloning of recombinant indoor allergens. Author(s): Chapman MD. Source: Arb Paul Ehrlich Inst Bundesamt Sera Impfstoffe Frankf a M. 1999; (93): 233-8; Discussion 238-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11487880

•

Fagales pollen sensitization in a birch-free area: a respiratory cohort survey using Fagales pollen extracts and birch recombinant allergens (rBet v 1, rBet v 2, rBet v 4). Author(s): Mari A, Wallner M, Ferreira F. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2003 October; 33(10): 1419-28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14519150

•

FDA targets snack foods industry over allergens. Author(s): Josefson D. Source: The Western Journal of Medicine. 2001 June; 174(6): 380. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11380996

•

First National Survey of Lead and Allergens in Housing: survey design and methods for the allergen and endotoxin components. Author(s): Vojta PJ, Friedman W, Marker DA, Clickner R, Rogers JW, Viet SM, Muilenberg ML, Thorne PS, Arbes SJ Jr, Zeldin DC. Source: Environmental Health Perspectives. 2002 May; 110(5): 527-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12003758

•

First report on sensitization to allergens of a house dust mite, Suidasia pontifica (Acari: Saproglyphidae). Author(s): Mariana A, Ho TM, Gendeh BS, Iskandar H, Zainuldin-Taib M. Source: Southeast Asian J Trop Med Public Health. 2000 December; 31(4): 722-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11414419

•

Food allergens and blood transfusions: a cause for concern? Author(s): Erick M. Source: Archives of Internal Medicine. 2003 August 11-25; 163(15): 1861. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12912726

Studies

87

•

Food allergens and the mucosal immune system. Author(s): Kaminogawa S. Source: Biofactors (Oxford, England). 2000; 12(1-4): 29-32. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11216499

•

Food allergens as the possible cause of asthma and anaphylaxis. Author(s): Nakagawa T. Source: Intern Med. 1998 January; 37(1): 5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9510391

•

Food allergens. Author(s): Burks W. Source: Clin Allergy Immunol. 2004; 18: 319-37. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15042922

•

Food allergens. Author(s): Burks W, Helm R, Stanley S, Bannon GA. Source: Current Opinion in Allergy and Clinical Immunology. 2001 June; 1(3): 243-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11964696

•

Food allergies in Spain: causal allergens and diagnostic strategies. Author(s): Martin Esteban M, Pascual CY. Source: Pediatr Pulmonol Suppl. 1999; 18: 154-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10093129

•

Food hypersensitivity in children: clinical aspects and distribution of allergens. Author(s): Rance F, Kanny G, Dutau G, Moneret-Vautrin DA. Source: Pediatric Allergy and Immunology : Official Publication of the European Society of Pediatric Allergy and Immunology. 1999 February; 10(1): 33-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10410915

•

Foot dermatitis in children: causative allergens and follow-up. Author(s): Cockayne SE, Shah M, Messenger AG, Gawkrodger DJ. Source: Contact Dermatitis. 1998 April; 38(4): 203-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9565291

88

Allergens

•

Formulation of therapeutic allergen mixtures problems associated with the number, proportion, and enzymatic activities of allergens. Author(s): Esch RE. Source: Arb Paul Ehrlich Inst Bundesamt Sera Impfstoffe Frankf a M. 1999; (93): 57-61; Discussion 73-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11487896

•

Frequency and specific sensitization to inhalant allergens within nuclear families of children with asthma and/or rhinitis. Author(s): Silvestri M, Oddera S, Crimi P, Rossi GA. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 1997 December; 79(6): 512-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9433366

•

Frequency of delayed-type hypersensitivity to contact allergens in psoriatic patients. Author(s): Stinco G, Frattasio A, De Francesco V, Bragadin G, Patrone P. Source: Contact Dermatitis. 1999 June; 40(6): 323-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10385335

•

Fungal allergens. Author(s): Vijay HM, Kurup VP. Source: Clin Allergy Immunol. 2004; 18: 223-49. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15042918

•

Fungal allergens. Author(s): Kurup VP. Source: Curr Allergy Asthma Rep. 2003 September; 3(5): 416-23. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12906780

•

Further characterization of IgE-binding antigens in kiwi, with particular emphasis on glycoprotein allergens. Author(s): Fahlbusch B, Rudeschko O, Schumann C, Steurich F, Henzgen M, Schlenvoigt G, Jager L. Source: J Investig Allergol Clin Immunol. 1998 November-December; 8(6): 325-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10028478

•

Fusarium culmorum causes strong degradation of pollen allergens in extract mixtures. Author(s): Hoff M, Krail M, Kastner M, Haustein D, Vieths S. Source: The Journal of Allergy and Clinical Immunology. 2002 January; 109(1): 96-101. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11799372

Studies

89

•

Gastrointestinal stability of baker's yeast allergens: an in vitro study. Author(s): Kortekangas-Savolainen O, Savolainen J, Einarsson R. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 1993 July; 23(7): 587-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8221259

•

Generation and characterization of cDNA clones from Sarcoptes scabiei var. hominis for an expressed sequence tag library: identification of homologues of house dust mite allergens. Author(s): Fischer K, Holt DC, Harumal P, Currie BJ, Walton SF, Kemp DJ. Source: The American Journal of Tropical Medicine and Hygiene. 2003 January; 68(1): 61-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12556150

•

Genes, factor X, and allergens: what causes allergic diseases? Author(s): Wjst M, Dold S. Source: Allergy. 1999 July; 54(7): 757-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10442534

•

Genetic engineering of allergens: future therapeutic products. Author(s): Ferreira F, Wallner M, Breiteneder H, Hartl A, Thalhamer J, Ebner C. Source: International Archives of Allergy and Immunology. 2002 July; 128(3): 171-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12119498

•

Genetic engineering of pollen allergens for hayfever immunotherapy. Author(s): Bhalla PL. Source: Expert Review of Vaccines. 2003 February; 2(1): 75-84. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12901599

•

Genetic influences of chromosomes 5q31-q33 and 11q13 on specific IgE responsiveness to common inhaled allergens among African American families. Collaborative Study on the Genetics of Asthma (CSGA). Author(s): Hizawa N, Freidhoff LR, Ehrlich E, Chiu YF, Duffy DL, Schou C, Dunston GM, Beaty TH, Marsh DG, Barnes KC, Huang SK. Source: The Journal of Allergy and Clinical Immunology. 1998 September; 102(3): 44953. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9768587

90

Allergens

•

Genetic variation of Der p 2 allergens: effects on T cell responses and immunoglobulin E binding. Author(s): Hales BJ, Hazell LA, Smith W, Thomas WR. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2002 October; 32(10): 1461-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12372126

•

Genetically engineered plant allergens with reduced anaphylactic activity. Author(s): Singh MB, de Weerd N, Bhalla PL. Source: International Archives of Allergy and Immunology. 1999 June; 119(2): 75-85. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10394098

•

Glucosides as unexpected allergens in cosmetics. Author(s): Goossens A, Decraene T, Platteaux N, Nardelli A, Rasschaert V. Source: Contact Dermatitis. 2003 March; 48(3): 164-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12755735

•

Glycidyl methacrylate and ethoxyethyl acrylate: new allergens in emulsions used to impregnate paper and textile materials. Author(s): Matura M, Poesen N, de Moor A, Kerre S, Dooms-Goossens A. Source: Contact Dermatitis. 1995 August; 33(2): 123-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8549129

•

Grass group I allergens (beta-expansins) are novel, papain-related proteinases. Author(s): Grobe K, Becker WM, Schlaak M, Petersen A. Source: European Journal of Biochemistry / Febs. 1999 July; 263(1): 33-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10429184

•

Grass pollen allergens. Author(s): Esch RE. Source: Clin Allergy Immunol. 2004; 18: 185-205. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15042916

•

Grass pollen allergens: new developments. Author(s): Wissenbach M, Holm J, Van Neerven RJ, Ipsen H. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 1998 July; 28(7): 784-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9720810

Studies

91

•

Group 13 grass allergens: structural variability between different grass species and analysis of proteolytic stability. Author(s): Petersen A, Suck R, Hagen S, Cromwell O, Fiebig H, Becker WM. Source: The Journal of Allergy and Clinical Immunology. 2001 May; 107(5): 856-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11344353

•

Group 5 allergens of timothy grass (Phl p 5) bear cross-reacting T cell epitopes with group 1 allergens of rye grass (Lol p 1). Author(s): Muller WD, Karamfilov T, Bufe A, Fahlbush B, Wolf I, Jager L. Source: International Archives of Allergy and Immunology. 1996 April; 109(4): 352-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8634519

•

Group V allergens in grass pollens: IV. Similarities in amino acid compositions and NH2-terminal sequences of the group V allergens from Lolium perenne, Poa pratensis and Dactylis glomerata. Author(s): Klysner S, Welinder KG, Lowenstein H, Matthiesen F. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 1992 April; 22(4): 491-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1611548

•

Grouping strategies for exposure to inhalable dust, wheat allergens and alphaamylase allergens in bakeries. Author(s): Houba R, Heederik D, Kromhout H. Source: The Annals of Occupational Hygiene. 1997 June; 41(3): 287-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9204756

•

Guidelines for the clinical evaluation of occupational asthma due to high molecular weight (HMW) allergens. Report of the Subcommittee on the Clinical Evaluation of Occupational Asthma due to HMW Allergens. Author(s): Novey HS, Bernstein IL, Mihalas LS, Terr AI, Yunginger JW. Source: The Journal of Allergy and Clinical Immunology. 1989 November; 84(5 Pt 2): 829-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2809032

•

Guidelines for the preparation and characterization of high molecular weight allergens used for the diagnosis of occupational lung disease. Report of the Subcommittee on Preparation and Characterization of High Molecular Weight Allergens. Author(s): Bush RK, Kagen SL. Source: The Journal of Allergy and Clinical Immunology. 1989 November; 84(5 Pt 2): 814-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2809029

92

Allergens

•

Guidelines for the standardization of bronchial provocation tests with allergens. An update by an international committee. Author(s): Melillo G, Aas K, Cartier A, Davies RJ, Debelic M, Dreborg S, Kerrebijn KF, Lassen A, Pinto Mendes J, Rizzo A, et al. Source: Allergy. 1991 July; 46(5): 321-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1928655

•

Heterogeneity of atopic dermatitis defined by the immune response to inhalant and food allergens. Author(s): Fabrizi G, Romano A, Vultaggio P, Bellegrandi S, Paganelli R, Venuti A. Source: European Journal of Dermatology : Ejd. 1999 July-August; 9(5): 380-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10417442

•

Heterogeneity of banana allergy: characterization of allergens in banana-allergic patients. Author(s): Grob M, Reindl J, Vieths S, Wuthrich B, Ballmer-Weber BK. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2002 November; 89(5): 513-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12452211

•

Hidden food allergens. Author(s): Hefle SL. Source: Current Opinion in Allergy and Clinical Immunology. 2001 June; 1(3): 269-71. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11964700

•

Hidden peanut allergens detected in various foods: findings and legal measures. Author(s): Schappi GF, Konrad V, Imhof D, Etter R, Wuthrich B. Source: Allergy. 2001 December; 56(12): 1216-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11736754

•

High-molecular-weight allergens of the house dust mite: an apolipophorin-like cDNA has sequence identity with the major M-177 allergen and the IgE-binding peptide fragments Mag1 and Mag3. Author(s): Epton MJ, Dilworth RJ, Smith W, Hart BJ, Thomas WR. Source: International Archives of Allergy and Immunology. 1999 November; 120(3): 18591. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10592463

Studies

93

•

HLA associations with occupational sensitization to rat lipocalin allergens: a model for other animal allergies? Author(s): Jeal H, Draper A, Jones M, Harris J, Welsh K, Taylor AN, Cullinan P. Source: The Journal of Allergy and Clinical Immunology. 2003 April; 111(4): 795-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12704360

•

HLA DPB1*0201 allele is negatively associated with immunoglobulin E responsiveness specific for house dust mite allergens in Taiwan. Author(s): Hu C, Hsu PN, Lin RH, Hsieh KH, Chua KY. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2000 April; 30(4): 538-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10718851

•

HLA-DQ/human CD4-restricted immune response to cockroach allergens in transgenic mice. Author(s): Papouchado BG, Chapoval SP, Marietta EV, Weiler CR, David CS. Source: Tissue Antigens. 2000 April; 55(4): 303-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10852381

•

HLA-DRB1*01 alleles are associated with sensitization to cockroach allergens. Author(s): Donfack J, Tsalenko A, Hoki DM, Parry R, Solway J, Lester LA, Ober C. Source: The Journal of Allergy and Clinical Immunology. 2000 May; 105(5): 960-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10808177

•

House dust mite allergen in US beds: results from the First National Survey of Lead and Allergens in Housing. Author(s): Arbes SJ Jr, Cohn RD, Yin M, Muilenberg ML, Burge HA, Friedman W, Zeldin DC. Source: The Journal of Allergy and Clinical Immunology. 2003 February; 111(2): 408-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12589364

•

House dust mite allergens in Turkish homes. Author(s): Gulbahar O, Mete N, Kokuludag A, Sin A, Sebik F. Source: Allergy. 2004 February; 59(2): 231. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14763941

•

House dust mite allergens induce proinflammatory cytokines from respiratory epithelial cells: the cysteine protease allergen, Der p 1, activates protease-activated receptor (PAR)-2 and inactivates PAR-1. Author(s): Asokananthan N, Graham PT, Stewart DJ, Bakker AJ, Eidne KA, Thompson PJ, Stewart GA. Source: Journal of Immunology (Baltimore, Md. : 1950). 2002 October 15; 169(8): 4572-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12370395

94

Allergens

•

House dust mites and their allergens at selected locations in the homes of house dust mite-allergic patients. Author(s): Sidenius KE, Hallas TE, Brygge T, Poulsen LK, Mosbech H. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2002 September; 32(9): 1299-304. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12220467

•

House dust mites and their allergens in Danish mattresses -- results from a population based study. Author(s): Sidenius KE, Hallas TE, Poulsen LK, Mosbech H. Source: Annals of Agricultural and Environmental Medicine : Aaem. 2002; 9(1): 33-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12088395

•

House-dust mite allergens in Italy and Spain. Author(s): Moscato G, Perfetti L. Source: Allergy. 2003 January; 58(1): 83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12580813

•

How good are carbohydrates as allergens? Author(s): Thomas WR, Smith W. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2002 May; 32(5): 658-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11994086

•

Human monoclonal antibody-based quantification of group 2 grass pollen allergens. Author(s): Marth K, Focke M, Flicker S, Valenta R. Source: The Journal of Allergy and Clinical Immunology. 2004 March; 113(3): 470-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15007349

•

Hymenoptera allergens. Author(s): King TP, Guralnick M. Source: Clin Allergy Immunol. 2004; 18: 339-53. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15042923

•

Hypoallergenic derivatives of major grass pollen allergens for allergy vaccination. Author(s): Singh MB, Bhalla PL. Source: Immunology and Cell Biology. 2003 February; 81(1): 86-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12534952

Studies

95

•

I are we closer to developing threshold limit values for allergens in the workplace? Author(s): Baur X. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2003 May; 90(5 Suppl 2): 11-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12772945

•

Identification and characterization of the allergens in the tomato fruit by immunoblotting. Author(s): Kondo Y, Urisu A, Tokuda R. Source: International Archives of Allergy and Immunology. 2001 December; 126(4): 2949. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11815736

•

Identification of cross-reactive and genuine Parietaria judaica pollen allergens. Author(s): Stumvoll S, Westritschnig K, Lidholm J, Spitzauer S, Colombo P, Duro G, Kraft D, Geraci D, Valenta R. Source: The Journal of Allergy and Clinical Immunology. 2003 May; 111(5): 974-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12743560

•

Identification of grape and wine allergens as an endochitinase 4, a lipid-transfer protein, and a thaumatin. Author(s): Pastorello EA, Farioli L, Pravettoni V, Ortolani C, Fortunato D, Giuffrida MG, Perono Garoffo L, Calamari AM, Brenna O, Conti A. Source: The Journal of Allergy and Clinical Immunology. 2003 February; 111(2): 350-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12589356

•

Identification of hazelnut major allergens in sensitive patients with positive doubleblind, placebo-controlled food challenge results. Author(s): Pastorello EA, Vieths S, Pravettoni V, Farioli L, Trambaioli C, Fortunato D, Luttkopf D, Calamari M, Ansaloni R, Scibilia J, Ballmer-Weber BK, Poulsen LK, Wutrich B, Hansen KS, Robino AM, Ortolani C, Conti A. Source: The Journal of Allergy and Clinical Immunology. 2002 March; 109(3): 563-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11898007

•

Identification of the soybean hull allergens involved in sensitization to soybean dust in a rural population from Argentina and N-terminal sequence of a major 50 KD allergen. Author(s): Codina R, Ardusso L, Lockey RF, Crisci CD, Jaen C, Bertoya NH. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2002 July; 32(7): 1059-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12100054

96

Allergens

•

IgE antibody to Aspergillus fumigatus recombinant allergens in cystic fibrosis patients with allergic bronchopulmonary aspergillosis. Author(s): Knutsen AP, Hutcheson PS, Slavin RG, Kurup VP. Source: Allergy. 2004 February; 59(2): 198-203. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14763934

•

IgE-mediated allergy to fungal allergens in Finland with special reference to Alternaria alternata and Cladosporium herbarum. Author(s): Reijula K, Leino M, Mussalo-Rauhamaa H, Nikulin M, Alenius H, Mikkola J, Elg P, Kari O, Makinen-Kiljunen S, Haahtela T. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2003 September; 91(3): 280-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14533661

•

IgE-mediated anaphylaxis to Thiomucase, a mucopolyssacharidase: allergens and cross-reactivity. Author(s): Caballero T, Alonso A, De Miguel S, Martin-Esteban M, Varga B, Pascual CY, Lopez-Serrano MC. Source: Allergy. 2002 March; 57(3): 254-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11906341

•

IL-10 and TGF-beta cooperate in the regulatory T cell response to mucosal allergens in normal immunity and specific immunotherapy. Author(s): Jutel M, Akdis M, Budak F, Aebischer-Casaulta C, Wrzyszcz M, Blaser K, Akdis CA. Source: European Journal of Immunology. 2003 May; 33(5): 1205-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12731045

•

Immediate skin reactivity to histamine and to allergens in cohorts of 9-year-old schoolchildren studied 16 years apart. Author(s): Ronchetti R, Villa MP, Pagani J, Martella S, Guglielmi F, Paggi B, Bohmerova Z, Falasca C, Barreto M. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2003 September; 33(9): 1232-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12956744

•

Immune reactivity of recombinant group 2 allergens of house dust mite, Dermatophagoides pteronyssinus, and Dermatophagoides farinae. Author(s): Jin HS, Yong TS, Park JW, Hong CS, Oh SH. Source: J Investig Allergol Clin Immunol. 2003; 13(1): 36-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12861849

Studies

97

•

Immune responses to allergens early in life: when and why do allergies arise? Author(s): Hamelmann E, Wahn U. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2002 December; 32(12): 1679-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12653155

•

Individual allergens as risk factors for asthma and bronchial hyperresponsiveness in Chinese children. Author(s): Wong GW, Li ST, Hui DS, Fok TF, Zhong NS, Chen YZ, Lai CK. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2002 February; 19(2): 288-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11871366

•

Influence of sensitization to inhalative allergens on adenotonsillar disease. Author(s): Hofmann T, Lackner A, Berghold A, Lang-Loidolt D. Source: Otolaryngology and Head and Neck Surgery. 2003 July; 129(1): 11-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12869910

•

Inhalant allergens as risk factors for the development and severity of mild-tomoderate asthma in Hong Kong Chinese children. Author(s): Leung TF, Lam CW, Chan IH, Li AM, Ha G, Tang NL, Fok TF. Source: The Journal of Asthma : Official Journal of the Association for the Care of Asthma. 2002 June; 39(4): 323-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12095182

•

Inhalation challenge with bovine dander allergens: who needs it? Author(s): Koskela H, Taivainen A, Tukiainen H, Chan HK. Source: Chest. 2003 July; 124(1): 383-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12853550

•

Injection immunotherapy with different airborne allergens did not prevent de novo sensitization to ragweed and birch pollen north of Milan. Author(s): Asero R. Source: International Archives of Allergy and Immunology. 2004 January; 133(1): 49-54. Epub 2003 November 28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14646378

•

Intracutaneous tests with recombinant allergens in cystic fibrosis patients with allergic bronchopulmonary aspergillosis and Aspergillus allergy. Author(s): Nikolaizik WH, Weichel M, Blaser K, Crameri R. Source: American Journal of Respiratory and Critical Care Medicine. 2002 April 1; 165(7): 916-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11934714

98

Allergens

•

Key pollen allergens in North America. Author(s): White JF, Bernstein DI. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2003 November; 91(5): 425-35; Quiz 435-6, 492. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14692424

•

Laboratory animal allergens. Author(s): Wood RA. Source: Ilar J. 2001; 42(1): 12-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11123185

•

Lack of human IgE cross-reactivity between mite allergens Blo t 1 and Der p 1. Author(s): Cheong N, Soon SC, Ramos JD, Kuo IC, Kolatkar PR, Lee BW, Chua KY, Kolortkar PR. Source: Allergy. 2003 September; 58(9): 912-20. Erratum In: Allergy. 2003 October; 58(10): 1070. Kolortkar Pr [corrected to Kolatkar Pr]. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12911421

•

Langerhans-like dendritic cells generated from cord blood progenitors internalize pollen allergens by macropinocytosis, and part of the molecules are processed and can activate autologous naive T lymphocytes. Author(s): Noirey N, Rougier N, Andre C, Schmitt D, Vincent C. Source: The Journal of Allergy and Clinical Immunology. 2000 June; 105(6 Pt 1): 1194201. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10856155

•

Large scale production and quality criteria of recombinant allergens. Author(s): Valenta R, Twardosz A, Vrtala S, Kraft D. Source: Arb Paul Ehrlich Inst Bundesamt Sera Impfstoffe Frankf a M. 1999; (93): 211-24; Discussion 224-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11487878

•

Latex allergens. Author(s): Slater JE. Source: Clin Allergy Immunol. 2004; 18: 369-86. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15042925

•

Lipid transfer proteins and 2S albumins as allergens. Author(s): Pastorello EA, Pompei C, Pravettoni V, Brenna O, Farioli L, Trambaioli C, Conti A. Source: Allergy. 2001; 56 Suppl 67: 45-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11298008

Studies

99

•

Lipocalin allergens. Author(s): Virtanen T. Source: Allergy. 2001; 56 Suppl 67: 48-51. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11298009

•

Lipocalins as allergens. Author(s): Mantyjarvi R, Rautiainen J, Virtanen T. Source: Biochimica Et Biophysica Acta. 2000 October 18; 1482(1-2): 308-17. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11058771

•

Low domestic exposure to house dust mite allergens (Der p 1) is associated with a reduced non-specific bronchial hyper-responsiveness in mite-sensitized asthmatic subjects under optimal drug treatment. Author(s): Maestrelli P, Zanolla L, Puccinelli P, Pozzan M, Fabbri LM; Regione Veneto Study Group. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2001 May; 31(5): 715-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11422130

•

Low-flow, long-term air sampling under normal domestic activity to measure house dust mite and cockroach allergens. Author(s): Park JW, Kim CW, Kang DB, Lee IY, Choi SY, Yong TS, Shin DC, Kim KE, Hong CS. Source: J Investig Allergol Clin Immunol. 2002; 12(4): 293-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12926189

•

Low-molecular-weight contact allergens in p-tert-butylphenol-formaldehyde resin. Author(s): Zimerson E, Bruze M. Source: American Journal of Contact Dermatitis : Official Journal of the American Contact Dermatitis Society. 2002 December; 13(4): 190-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12478534

•

Lung surfactant, asthma, and allergens: a story in evolution. Author(s): Baritussio A. Source: American Journal of Respiratory and Critical Care Medicine. 2004 March 1; 169(5): 550-1. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14982818

100

Allergens

•

Lymphoproliferative responses in cord blood and at one year: no evidence for the effect of in utero exposure to dust mite allergens. Author(s): Smillie FI, Elderfield AJ, Patel F, Cain G, Tavenier G, Brutsche M, Craven M, Custovic A, Woodcock A. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2001 August; 31(8): 1194-204. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11529888

•

Mammalian allergens. Author(s): Virtanen T, Jarvi RM. Source: Clin Allergy Immunol. 2004; 18: 297-317. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15042921

•

Maternal history, sensitization to allergens, and current wheezing, rhinitis, and eczema among children in Costa Rica. Author(s): Soto-Quiros ME, Silverman EK, Hanson LA, Weiss ST, Celedon JC. Source: Pediatric Pulmonology. 2002 April; 33(4): 237-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11921451

•

Maternally delivered nutritive allergens in cord blood and in placental tissue of term and preterm neonates. Author(s): Edelbauer M, Loibichler C, Nentwich I, Gerstmayr M, Urbanek R, Szepfalusi Z. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2004 February; 34(2): 189-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14987296

•

Measurement of airborne latex allergens. Author(s): Baur X. Source: Methods (San Diego, Calif.). 2002 May; 27(1): 59-62. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12079418

•

Mechanisms of immunotherapy with allergoids: lessons for the development of recombinant allergens with reduced IgE-binding activity. Author(s): Cromwell O, Kahlert H, Schramm G, Suck R, Nandy A, Weber B, Fiebig H. Source: Arb Paul Ehrlich Inst Bundesamt Sera Impfstoffe Frankf a M. 2003; (94): 156-61; Discussion 161-2. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15119034

•

Mite allergens. Author(s): Fernandez-Caldas E, Puerta L, Caraballo L, Lockey RF. Source: Clin Allergy Immunol. 2004; 18: 251-70. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15042919

Studies

101

•

Modifying allergens and using adjuvants for specific immunotherapy. Author(s): Larche M, Ferreira F, Mohapatra SS. Source: Clin Allergy Immunol. 2004; 18: 641-61. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15042940

•

Molecular cloning and immunological characterisation of potential allergens from the mould Fusarium culmorum. Author(s): Hoff M, Ballmer-Weber BK, Niggemann B, Cistero-Bahima A, San MiguelMoncin M, Conti A, Haustein D, Vieths S. Source: Molecular Immunology. 2003 May; 39(15): 965-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12695122

•

Molecular cloning of Aspergillus fumigatus allergens and their role in allergic bronchopulmonary aspergillosis. Author(s): Crameri R. Source: Chem Immunol. 2002; 81: 73-93. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12102006

•

Molecular, structural, and immunologic relationships between different families of recombinant calcium-binding pollen allergens. Author(s): Tinghino R, Twardosz A, Barletta B, Puggioni EM, Iacovacci P, Butteroni C, Afferni C, Mari A, Hayek B, Di Felice G, Focke M, Westritschnig K, Valenta R, Pini C. Source: The Journal of Allergy and Clinical Immunology. 2002 February; 109(2): 314-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11842303

•

National rates and regional differences in sensitization to allergens of the standard series. Population-adjusted frequencies of sensitization (PAFS) in 40,000 patients from a multicenter study (IVDK). Author(s): Schnuch A, Geier J, Uter W, Frosch PJ, Lehmacher W, Aberer W, Agathos M, Arnold R, Fuchs T, Laubstein B, Lischka G, Pietrzyk PM, Rakoski J, Richter G, Rueff F. Source: Contact Dermatitis. 1997 November; 37(5): 200-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9412746

•

Natural course of sensitization to food and inhalant allergens during the first 6 years of life. Author(s): Kulig M, Bergmann R, Klettke U, Wahn V, Tacke U, Wahn U. Source: The Journal of Allergy and Clinical Immunology. 1999 June; 103(6): 1173-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10359902

102

Allergens

•

Natural rubber pharmaceutical vial closures release latex allergens that produce skin reactions. Author(s): Primeau MN, Adkinson NF Jr, Hamilton RG. Source: The Journal of Allergy and Clinical Immunology. 2001 June; 107(6): 958-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11398071

•

New allergens in fruits and vegetables. Author(s): Pastorello EA, Incorvaia C, Pravettoni V, Farioli L, Conti A, Vigano G, Rivolta F, Ispano M, Rotondo F, Ortolani C. Source: Allergy. 1998; 53(46 Suppl): 48-51. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9825998

•

New mattresses: how fast do they become a significant source of exposure to house dust mite allergens? Author(s): Custovic A, Green R, Smith A, Chapman MD, Woodcock A. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 1996 November; 26(11): 1243-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8955572

•

Nonallergenic peptides from surface-exposed areas or B-cell epitopes of allergens for specific immunotherapy. Author(s): Focke M, Mahler V, Ball T, Kraft D, Valenta R. Source: International Archives of Allergy and Immunology. 2001 January-March; 124(13): 398-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11307027

•

Nonspecific binding of IgE to allergens. Author(s): Jensen-Jarolim E, Vogel M, Zavazal V, Stadler BM. Source: Allergy. 1997 August; 52(8): 844-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9284984

•

North American Contact Dermatitis Group patch test results for the detection of delayed-type hypersensitivity to topical allergens. Author(s): Marks JG, Belsito DV, DeLeo VA, Fowler JF Jr, Fransway AF, Maibach HI, Mathias CG, Nethercott JR, Rietschel RL, Sherertz EF, Storrs FJ, Taylor JS. Source: Journal of the American Academy of Dermatology. 1998 June; 38(6 Pt 1): 911-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9631997

•

Novel predictive assay for contact allergens using human skin explant cultures. Author(s): Pistoor FH, Rambukkana A, Kroezen M, Lepoittevin JP, Bos JD, Kapsenberg ML, Das PK. Source: American Journal of Pathology. 1996 July; 149(1): 337-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8686758

Studies

103

•

N-terminal sequences of high molecular weight allergens from celery tuber. Author(s): Ganglberger E, Radauer C, Grimm R, Hoffmann-Sommergruber K, Breiteneder H, Scheiner O, Jensen-Jarolim E. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2000 April; 30(4): 566-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10718855

•

Occupational allergens. Author(s): Lachowsky F, Lopez M. Source: Curr Allergy Asthma Rep. 2001 November; 1(6): 587-93. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11892089

•

Occurrence of dog, cat, and mite allergens in public transport vehicles. Author(s): Partti-Pellinen K, Marttila O, Makinen-Kiljunen S, Haahtela T. Source: Allergy. 2000 January; 55(1): 65-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10696858

•

Ole e 4 and Ole e 5, important allergens of Olea europaea. Author(s): Carnes J, Fernandez-Caldas E. Source: Allergy. 2002; 57 Suppl 71: 24-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12173265

•

On allergens and asthma (again): does exposure to allergens in homes exacerbate asthma? Author(s): Custovic A, Woodcock A. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2001 May; 31(5): 670-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11422124

•

On early sensitization to allergens and development of respiratory symptoms. Author(s): Sherrill D, Stein R, Kurzius-Spencer M, Martinez F. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 1999 July; 29(7): 905-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10383590

•

On the physiology of airway absorption of allergens. Author(s): Greiff L, Persson CG. Source: Allergy. 1999; 54 Suppl 57: 31-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10565478

104

Allergens

•

Optimization of electrophoresis for the identification of low molecular mass allergens in hazelnuts. Author(s): Schocker F, Becker WM. Source: J Chromatogr B Biomed Sci Appl. 2001 May 25; 756(1-2): 105-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11419700

•

Optimized allergen extracts and recombinant allergens in diagnostic applications. Author(s): Vieths S, Scheurer S, Reindl J, Luttkopf D, Wangorsch A, Kastner M, Haase T, Haustein D. Source: Allergy. 2001; 56 Suppl 67: 78-82. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11298016

•

Outdoor allergens. Author(s): Burge HA, Rogers CA. Source: Environmental Health Perspectives. 2000 August; 108 Suppl 4: 653-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10931783

•

Par j 1 and Par j 2, the major allergens from Parietaria judaica pollen, have similar immunoglobulin E epitopes. Author(s): Asturias JA, Gomez-Bayon N, Eseverri JL, Martinez A. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2003 April; 33(4): 518-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12680870

•

Patch testing with the irritant sodium lauryl sulfate (SLS) is useful in interpreting weak reactions to contact allergens as allergic or irritant. Author(s): Geier J, Uter W, Pirker C, Frosch PJ. Source: Contact Dermatitis. 2003 February; 48(2): 99-107. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12694214

•

Pattern of sensitization to common environmental allergens amongst atopic Singapore children in the first 3 years of life. Author(s): Khoo J, Shek L, Khor ES, Wang DY, Lee BW. Source: Asian Pac J Allergy Immunol. 2001 December; 19(4): 225-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12009071

•

Phenotypic alterations and IL-1beta production in CD34(+) progenitor- and monocyte-derived dendritic cells after exposure to allergens: a comparative analysis. Author(s): De Smedt AC, Van Den Heuvel RL, Van Tendeloo VF, Berneman ZN, Schoeters GE, Weber E, Tuschl H. Source: Archives of Dermatological Research. 2002 May; 294(3): 109-16. Epub 2002 April 09. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12029496

Studies

105

•

Pigeon allergens in indoor environments: a preliminary study. Author(s): Curtis L, Lee BS, Cai D, Morozova I, Fan JL, Scheff P, Persky V, Einoder C, Diblee S. Source: Allergy. 2002 July; 57(7): 627-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12100304

•

Positive patch tests with a dermatophagoides mix relate to an increased responsiveness to standard patch test allergens. Author(s): Brasch J, Uter W, Dibo M, Stockfleth E, Swensson O, Christophers E. Source: Contact Dermatitis. 2002 May; 46(5): 253-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12084076

•

Principles and methodology for identification of fragrance allergens in consumer products. Author(s): Gimenez-Arnau A, Gimenez-Arnau E, Serra-Baldrich E, Lepoittevin JP, Camarasa JG. Source: Contact Dermatitis. 2002 December; 47(6): 345-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12581281

•

Production of lymphocyte-derived cytokines by whole umbilical cord blood cultures stimulated with mitogens and allergens. Author(s): Miles EA, Bakewell L, Calder PC. Source: Cytokine. 2003 January 21; 21(2): 74-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12670446

•

Progress in the development of new methods of immunotherapy: potential application of immunostimulatory DNA-conjugated to allergens for treatment of allergic respiratory conditions. Author(s): Creticos PS, Lichtenstein LM. Source: Arb Paul Ehrlich Inst Bundesamt Sera Impfstoffe Frankf a M. 2003; (94): 304-12; Discussion 312-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15119051

•

Protective effects of a recombinant fragment of human surfactant protein D in a murine model of pulmonary hypersensitivity induced by dust mite allergens. Author(s): Singh M, Madan T, Waters P, Parida SK, Sarma PU, Kishore U. Source: Immunology Letters. 2003 May 1; 86(3): 299-307. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12706535

•

Quantification of birch and grass pollen allergens in indoor air. Author(s): Holmquist L, Vesterberg O. Source: Indoor Air. 1999 June; 9(2): 85-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10390933

106

Allergens

•

Quantification of group 5 grass pollen allergens in house dust. Author(s): Fahlbusch B, Hornung D, Heinrich J, Dahse HM, Jager L. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2000 November; 30(11): 1645-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11069575

•

Quantification of house dust mite allergens in ambient air. Author(s): Paufler P, Gebel T, Dunkelberg H. Source: Rev Environ Health. 2001 January-March; 16(1): 65-80. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11354542

•

Quantification of major insect and animal allergens by protease assay. Author(s): Berrens L. Source: Arb Paul Ehrlich Inst Bundesamt Sera Impfstoffe Frankf a M. 1992; (85): 161-9; Discussion 169-70. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1540288

•

Quantification of major peanut allergens Ara h 1 and Ara h 2 in the peanut varieties Runner, Spanish, Virginia, and Valencia, bred in different parts of the world. Author(s): Koppelman SJ, Vlooswijk RA, Knippels LM, Hessing M, Knol EF, van Reijsen FC, Bruijnzeel-Koomen CA. Source: Allergy. 2001 February; 56(2): 132-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11167373

•

Quantitation of latex allergens. Author(s): Palosuo T, Alenius H, Turjanmaa K. Source: Methods (San Diego, Calif.). 2002 May; 27(1): 52-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12079417

•

Quantitation of major allergens in dust samples from urban populations collected in different seasons in two climatic areas of the Basque region (Spain). Author(s): Echechipia S, Ventas P, Audicana M, Urrutia I, Gastaminza G, Polo F, Fernandez de Corres L. Source: Allergy. 1995 June; 50(6): 478-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7573840

•

Quantitative assessment of exposure to dog (Can f 1) and cat (Fel d 1) allergens: relation to sensitization and asthma among children living in Los Alamos, New Mexico. Author(s): Ingram JM, Sporik R, Rose G, Honsinger R, Chapman MD, Platts-Mills TA. Source: The Journal of Allergy and Clinical Immunology. 1995 October; 96(4): 449-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7560654

Studies

107

•

Quantitative assessment of immediate cutaneous hypersensitivity in a mouse model exhibiting an IgE response to Timothy grass allergens. Author(s): Seitzer U, Bussler H, Kullmann B, Petersen A, Becker WM, Ahmed J. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2003 December; 9(12): Br407-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14646968

•

Quantitative IgE inhibition experiments with purified recombinant allergens indicate pollen-derived allergens as the sensitizing agents responsible for many forms of plant food allergy. Author(s): Kazemi-Shirazi L, Pauli G, Purohit A, Spitzauer S, Froschl R, HoffmannSommergruber K, Breiteneder H, Scheiner O, Kraft D, Valenta R. Source: The Journal of Allergy and Clinical Immunology. 2000 January; 105(1 Pt 1): 11625. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10629461

•

Recombinant allergens for immunotherapy. Author(s): Chapman MD, Smith AM, Vailes LD, Pomes A. Source: Allergy and Asthma Proceedings : the Official Journal of Regional and State Allergy Societies. 2002 January-February; 23(1): 5-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11894735

•

Recombinant allergens/allergen standardization. Author(s): Lowenstein H, Larsen JN. Source: Curr Allergy Asthma Rep. 2001 September; 1(5): 474-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11892075

•

Recombinant birch allergens (Bet v 1 and Bet v 2) and the oral allergy syndrome in patients allergic to birch pollen. Author(s): De Amici M, Mosca M, Vignini M, Quaglini S, Moratti R. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2003 November; 91(5): 490-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14692434

•

Recombinant food allergens in the diagnosis of pollen-related food allergy. Author(s): Ballmer-Weber BK, Wangorsch A, Scheurer S. Source: Arb Paul Ehrlich Inst Bundesamt Sera Impfstoffe Frankf a M. 2003; (94): 192-6; Discussion 197. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15119039

108

Allergens

•

Recombinant Hymenoptera venom allergens. Author(s): Muller UR. Source: Allergy. 2002 July; 57(7): 570-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12100296

•

Recombinant marker allergens: diagnostic gatekeepers for the treatment of allergy. Author(s): Kazemi-Shirazi L, Niederberger V, Linhart B, Lidholm J, Kraft D, Valenta R. Source: International Archives of Allergy and Immunology. 2002 April; 127(4): 259-68. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12021544

•

Recombinant mite allergens: validation strategies and clinical trials. Author(s): Chapman MD. Source: Arb Paul Ehrlich Inst Bundesamt Sera Impfstoffe Frankf a M. 2003; (94): 205-10; Discussion 210-2. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15119041

•

Reduction of exposure to laboratory animal allergens in a research laboratory. Author(s): Thulin H, Bjorkdahl M, Karlsson AS, Renstrom A. Source: The Annals of Occupational Hygiene. 2002 January; 46(1): 61-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12005134

•

Regulation of the adaptive immune response to inhaled allergens. Author(s): Roberts K, Jaffar Z. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2002 March; 32(3): 343-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11940060

•

Response of furniture factory workers to work-related airborne allergens. Author(s): Skorska C, Krysinska-Traczyk E, Milanowski J, Cholewa G, Sitkowska J, Gora A, Dutkiewicz J. Source: Annals of Agricultural and Environmental Medicine : Aaem. 2002; 9(1): 91-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12088404

•

Seafood allergy and allergens: a review. Author(s): Lehrer SB, Ayuso R, Reese G. Source: Marine Biotechnology (New York, N.Y.). 2003 July-August; 5(4): 339-48. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14719162

Studies

109

•

Sensitisation to occupational allergens in bakers' asthma and rhinitis: a case-referent study. Author(s): Brisman J, Lillienberg L, Belin L, Ahman M, Jarvholm B. Source: International Archives of Occupational and Environmental Health. 2003 March; 76(2): 167-70. Epub 2002 November 01. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12733091

•

Sensitization to food or inhalant allergens in pediatric patients. Clinical usefulness of first-level panel tests for specific IgE. Author(s): Altrinetti V, Salmaso C, Montagna P, Castellano E, Cosentino C, Pesce G, Bagnasco M. Source: J Investig Allergol Clin Immunol. 2003; 13(4): 286-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14989121

•

Serum IgE reactivity to Malassezia furfur extract and recombinant M. furfur allergens in patients with atopic dermatitis. Author(s): Zargari A, Eshaghi H, Back O, Johansson S, Scheynius A. Source: Acta Dermato-Venereologica. 2001 November-December; 81(6): 418-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11859945

•

Something old, something new: indoor endotoxin, allergens and asthma. Author(s): Liu AH. Source: Paediatric Respiratory Reviews. 2004; 5 Suppl A: S65-71. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14980246

•

Soybean allergy in patients allergic to birch pollen: clinical investigation and molecular characterization of allergens. Author(s): Mittag D, Vieths S, Vogel L, Becker WM, Rihs HP, Helbling A, Wuthrich B, Ballmer-Weber BK. Source: The Journal of Allergy and Clinical Immunology. 2004 January; 113(1): 148-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14713921

•

Specific sensitization to common allergens and pulmonary function in the European Community Respiratory Health Survey. Author(s): Jaen A, Sunyer J, Basagana X, Chinn S, Zock JP, Anto JM, Burney P; European Community Respiratory Health Survey. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2002 December; 32(12): 1713-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12653161

110

Allergens

•

Suitability of the European standard series of patch test allergens in Pakistani patients. Author(s): Hussain I, Rani Z, Rashid T, Haroon TS. Source: Contact Dermatitis. 2002 January; 46(1): 50-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11918589

•

Surfactants enhance the tight-junction permeability of food allergens in human intestinal epithelial Caco-2 cells. Author(s): Mine Y, Zhang JW. Source: International Archives of Allergy and Immunology. 2003 February; 130(2): 13542. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12673067

•

Synergism between allergens and viruses and risk of hospital admission with asthma: case-control study. Author(s): Green RM, Custovic A, Sanderson G, Hunter J, Johnston SL, Woodcock A. Source: Bmj (Clinical Research Ed.). 2002 March 30; 324(7340): 763. Erratum In: Bmj 2002 May 11; 324(7346): 1131. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11923159

•

The allergen profile of ash (Fraxinus excelsior) pollen: cross-reactivity with allergens from various plant species. Author(s): Niederberger V, Purohit A, Oster JP, Spitzauer S, Valenta R, Pauli G. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2002 June; 32(6): 933-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12047442

•

The allergens of Cladosporium herbarum and Alternaria alternata. Author(s): Breitenbach M, Simon-Nobbe B. Source: Chem Immunol. 2002; 81: 48-72. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12102004

•

The allergens of Parietaria. Author(s): Colombo P, Bonura A, Costa M, Izzo V, Passantino R, Locorotondo G, Amoroso S, Geraci D. Source: International Archives of Allergy and Immunology. 2003 March; 130(3): 173-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12660421

Studies

111

•

The British standard series of contact dermatitis allergens: validation in clinical practice and value for clinical governance. Author(s): Britton JE, Wilkinson SM, English JS, Gawkrodger DJ, Ormerod AD, Sansom JE, Shaw S, Statham B. Source: The British Journal of Dermatology. 2003 February; 148(2): 259-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12588377

•

The CREATE project: a new beginning of allergen standardization based on mass units of major allergens. Author(s): van Ree R. Source: Arb Paul Ehrlich Inst Bundesamt Sera Impfstoffe Frankf a M. 2003; (94): 70-3; Discussion 74-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15119023

•

The interaction between particulate air pollution and allergens in enhancing allergic and airway responses. Author(s): Polosa R. Source: Curr Allergy Asthma Rep. 2001 March; 1(2): 102-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11899291

•

The role of allergens in the induction of asthma. Author(s): Platts-Mills TA. Source: Curr Allergy Asthma Rep. 2002 March; 2(2): 175-80. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11892098

•

The role of patch testing for chemical and protein allergens in atopic dermatitis. Author(s): Nedorost ST, Cooper KD. Source: Curr Allergy Asthma Rep. 2001 July; 1(4): 323-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11892054

•

The seasonal variation in allergic rhinitis and its correlation with outdoor allergens in Kuwait. Author(s): Behbehani N, Arifhodzic N, Al-Mousawi M, Marafie S, Ashkanani L, Moussa M, Al-Duwaisan A. Source: International Archives of Allergy and Immunology. 2004 February; 133(2): 164-7. Epub 2004 February 05. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14764943

•

Tree pollen allergens. Author(s): Mothes N, Westritschnig K, Valenta R. Source: Clin Allergy Immunol. 2004; 18: 165-84. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15042915

112

Allergens

•

Ubiquitous structures responsible for IgE cross-reactivity between tomato fruit and grass pollen allergens. Author(s): Petersen A, Vieths S, Aulepp H, Schlaak M, Becker WM. Source: The Journal of Allergy and Clinical Immunology. 1996 October; 98(4): 805-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8876557

•

Uncommon allergens. Author(s): Munoz-Lopez F. Source: Allergologia Et Immunopathologia. 2001 September-October; 29(5): 181-4. English, Spanish. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11720649

•

Uneasy breather: the implications of dust mite allergens. Author(s): Sharma S, Lackie PM, Holgate ST. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2003 February; 33(2): 163-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12580906

•

Unique role of allergens and the epithelium in asthma. Author(s): Thompson PJ. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 1998 November; 28 Suppl 5: 110-6; Discussion 117-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9988456

•

Unusual responses to contact allergens. Author(s): Slavin RG. Source: Allergy and Asthma Proceedings : the Official Journal of Regional and State Allergy Societies. 1999 July-August; 20(4): 229-30. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10476321

•

Use of differential display-polymerase chain reaction to identify genes selectively modulated by chemical allergens in reconstituted human epidermis. Author(s): Corsini E, Sheasgreen J, Marinovich M, Galli CL. Source: Toxicology in Vitro : an International Journal Published in Association with Bibra. 2002 August; 16(4): 427-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12110282

•

Use of liposomes for standardized therapeutic allergens. Author(s): Tran XT, Millet-Genin I. Source: Arb Paul Ehrlich Inst Bundesamt Sera Impfstoffe Frankf a M. 1994; (87): 203-9; Discussion 209-10. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7873060

Studies

113

•

Use of modified BL21(DE3) Escherichia coli cells for high-level expression of recombinant peanut allergens affected by poor codon usage. Author(s): Kleber-Janke T, Becker WM. Source: Protein Expression and Purification. 2000 August; 19(3): 419-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10910733

•

Use of recombinant group 5 allergens to investigate IgE-mediated sensitization to Blomia tropicalis and Dermatophagoides pteronyssinus. Author(s): Arruda LK, Vailes LD, Fernandez-Caldas E, Naspitz CK, Montealegre F, Chapman MD. Source: Advances in Experimental Medicine and Biology. 1996; 409: 173-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9095238

•

Use of specific IgE in assessing the relevance of fungal and dust mite allergens to atopic dermatitis: a comparison with asthmatic and nonasthmatic control subjects. Author(s): Scalabrin DM, Bavbek S, Perzanowski MS, Wilson BB, Platts-Mills TA, Wheatley LM. Source: The Journal of Allergy and Clinical Immunology. 1999 December; 104(6): 1273-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10589012

•

Vacuum cleaning does not sufficiently reduce mite allergens from beddings. Author(s): Vichyanond P, Visitsuntorn N, Ruengruk S, Malainual N. Source: J Med Assoc Thai. 2002 August; 85 Suppl 2: S586-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12403236

•

Value of immunoglobulin E density in predicting nasal and bronchial response to inhaled allergens in rhinitic and asthmatic subjects with multiple sensitizations. Author(s): Crimi E, Voltolini S, Minale P, Falagiani P. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 1999 December; 29(12): 1663-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10594543

•

Variability of crossreactivity of IgE antibodies to group I and V allergens in eight grass pollen species. Author(s): Van Ree R, Driessen MN, Van Leeuwen WA, Stapel SO, Aalberse RC. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 1992 June; 22(6): 611-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1382820

114

Allergens

•

Variable effects of chemical allergens on serum IgE concentration in mice. Preliminary evaluation of a novel approach to the identification of respiratory sensitizers. Author(s): Dearman RJ, Basketter DA, Kimber I. Source: Journal of Applied Toxicology : Jat. 1992 October; 12(5): 317-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1447476

•

Variation in skin reactivity inhalant allergens estimated by the end-point technique. Author(s): Bordignon V, Parmiani S. Source: J Investig Allergol Clin Immunol. 2001; 11(3): 161-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11831447

•

Vitiligo and topical allergens. Author(s): Orecchia G, Perfetti L. Source: Dermatologica. 1989; 179(3): 137-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2591620

•

Weed pollen allergens. Author(s): Mohapatra SS, Lockey RF, Polo F. Source: Clin Allergy Immunol. 2004; 18: 207-22. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15042917

•

Western blot analysis of water-soluble wheat flour (Triticum vulgaris) allergens. Author(s): Pfeil T, Schwabl U, Ulmer WT, Konig W. Source: Int Arch Allergy Appl Immunol. 1990; 91(3): 224-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1693911

•

What are allergens? Author(s): Cromwell O. Source: Allergy. 1999; 54 Suppl 56: 7-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10532288

•

What are the important allergens in grass pollen that are linked to human allergic disease? Author(s): Suphioglu C. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2000 October; 30(10): 1335-41. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10998006

Studies

115

•

Where are we in risk assessment of food allergens? The regulatory view. Author(s): Madsen C. Source: Allergy. 2001; 56 Suppl 67: 91-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11298019

•

Why are nasal and bronchial symptoms mostly perennial in patients with monosensitization to Olea europaea pollen allergens? Author(s): Liccardi G, Kordash TR, Russo M, Noschese P, Califano C, D'Amato M, D'Amato G. Source: J Investig Allergol Clin Immunol. 1996 November-December; 6(6): 371-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9015781

•

Why are some proteins allergens? Author(s): Huby RD, Dearman RJ, Kimber I. Source: Toxicological Sciences : an Official Journal of the Society of Toxicology. 2000 June; 55(2): 235-46. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10828254

•

Wipe test for the detection of indoor allergens. Author(s): Polzius R, Wuske T, Mahn J. Source: Allergy. 2002 February; 57(2): 143-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11929417

•

Working out the asthma allergens. Author(s): Hartley J. Source: Nurs Times. 1999 July 21-27; 95(29): 53-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10568978

•

Workshop overview. Identification of respiratory allergens. Author(s): Kimber I, Bernstein IL, Karol MH, Robinson MK, Sarlo K, Selgrade MK. Source: Fundamental and Applied Toxicology : Official Journal of the Society of Toxicology. 1996 September; 33(1): 1-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8812200

117

CHAPTER 2. NUTRITION AND ALLERGENS Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and allergens.

Finding Nutrition Studies on Allergens 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 “allergens” (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.

118

Allergens

The following is a typical result when searching for recently indexed consumer information on allergens: •

Biochemical features of grain legume allergens in humans and animals. Author(s): INRA, Laboratoire du Jeune Ruminant, Rennes, France. Source: Lalles, J P Peltre, G Nutr-Revolume 1996 April; 54(4 Pt 1): 101-7 0029-6643

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

Expression of Bet v 1, the major birch pollen allergen during anther development: an in situ hybridization study. Source: Swoboda, I. Dang, T.C.H. Heberle Bors, E. Vicente, O. Protoplasma. Wien : Springer-Verlag. 1995. volume 187 (1/4) page 103-110. 0033-183X

•

Four recombinant isoforms of Cor a I, the major allergen of hazel pollen, show different IgE-binding properties. Source: Breiteneder, H. Ferreira, F. Hoffmann Sommergruber, K. Ebner, C. Breitenbach, M. Rumpold, H. Kraft, D. Scheiner, O. Eur-J-Biochem. New York, NY : Springer-Verlag New York Inc. March 1993. volume 212 (2) page 355-362. 0014-2956

•

Industry labelling guidelines for allergens and food safety advice. Source: Sadler, M. Gatenby, S. Nutr-food-sci. Bradford, West Yorkshire, England : MCB University Press. Mar/June 2001. volume 31 (2/3) page 79-83. 0034-6659

•

Isolation and characterization of allergens from the seeds of Vigna sinensis. Author(s): Department of Biochemistry, Andhra University, Visakhapatnam, India. Source: Rao, T R Rao, D N Kotilingam, K Athota, R R Asian-Pac-J-Allergy-Immunol. 2000 March; 18(1): 9-14 0125-877X

•

Modulation of IgE-binding properties of tree pollen allergens by site-directed mutagenesis. Source: Ferreira, F. Rohlfs, A. Hoffmann Sommergruber, K. Schenk, S. Ebner, C. Briza, P. Jilek, A. Kraft, D. Breitenbach, M. Scheiner, O. New horizons in allergy immunotherapy /. New York : Plenum Press, c1996. page 127-135. ISBN: 030645498X

•

Phenylcoumaran benzylic ether and isoflavonoid reductases are a new class of crossreactive allergens in birch pollen, fruits and vegetables. Author(s): Swiss Institute of Allergy and Asthma Research, Davos Platz, Switzerland. Source: Karamloo, F Wangorsch, A Kasahara, H Davin, L B Haustein, D Lewis, N G Vieths, S Eur-J-Biochem. 2001 October; 268(20): 5310-20 0014-2956

•

Seasonal changes of humoral and cellular immune responses to Japanese cedar (Cryptomeria japonica) pollen allergens in Japanese monkeys (Macaca fuscata) with pollinosis. Author(s): Department of Immunology, Nippon Veterinary and Animal Science University, Tokyo, Japan. [email protected] Source: Sakaguchi, M Yamada, T Hirahara, K Shiraishi, A Saito, S Miyazawa, H Taniguchi, Y Inouye, S Nigi, H J-Med-Primatol. 2001 April; 30(2): 112-20 0047-2565

•

Sensitization to common food allergens is a risk factor for asthma in young Chinese children in Hong Kong. Author(s): Department of Pediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR. [email protected] Source: Leung, T F Lam, C W Chan, I H Li, A M Tang, N L J-Asthma. 2002 September; 39(6): 523-9 0277-0903

Nutrition

119

•

Structure of food allergens in relation to allergenicity. Author(s): CLB and Laboratory for Experimental and Clinical Immunology, Academic Medical Centre, University of Amsterdam, The Netherlands. Source: Aalberse, R C Stapel, S O Pediatr-Allergy-Immunol. 2001; 12 Suppl 14: 10-4 09056157

•

The crystal structure of a major dust mite allergen Der p 2, and its biological implications. Author(s): Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22908, USA. [email protected] Source: Derewenda, U Li, J Derewenda, Z Dauter, Z Mueller, G A Rule, G S Benjamin, D C J-Mol-Biol. 2002 April 19; 318(1): 189-97 0022-2836

•

The evaluation of allergens and allergic diseases in children. Author(s): Department of Pediatrics, Taipei Veterans General Hospital and National Yang-Ming University, Taiwan, ROC. Source: Lee, C S Tang, R B Chung, R L J-Microbiol-Immunol-Infect. 2000 December; 33(4): 227-32

•

The role of allergens and pseudoallergens in urticaria. Author(s): Department of Dermatology and Allergy, Charite, Humboldt University, Berlin, Germany. [email protected] Source: Zuberbier, T J-Investig-Dermatol-Symp-Proc. 2001 November; 6(2): 132-4 10870024

•

The use of image analysis to study the allergens in foods. Source: Morgan, N.L. Albert, C.J. Spears, K. Tech-Ser-Soc-Appl-Bacteriol. Oxford : Blackwell Scientific Publications. 1987. (24) page 153-161. ill. 0300-9610

•

Time course study on the development of allergen-induced airway remodeling in mice: the effect of allergen avoidance on established airway remodeling. Author(s): Department of Pharmacology, Gifu Pharmaceutical University, Japan. Source: Tanaka, H Masuda, T Tokuoka, S Takahashi, Y Komai, M Nagao, K Nagai, H Inflamm-Res. 2002 June; 51(6): 307-16 1023-3830

•

Tomato (Lycopersicon esculentum) allergens in pollen-allergic patients. Source: Foetisch, K. Son, D.Y. Altmann, F. Aulepp, H. Conti, A. Haustein, D. Vieths, S. Eur-food-res-technol. Berlin : Springer, c1999-. October 2001. volume 213 (4/5) page 259266. 1438-2377

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

•

The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

•

The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

120

Allergens

•

The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

•

The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

•

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

•

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

•

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

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

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

The following is a specific Web list relating to allergens; 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 B6 Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin C Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin C Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,904,00.html

Nutrition

•

Minerals Zinc Source: Healthnotes, Inc.; www.healthnotes.com

•

Food and Diet Barley Source: Healthnotes, Inc.; www.healthnotes.com Chocolate Source: Healthnotes, Inc.; www.healthnotes.com Coffee Source: Healthnotes, Inc.; www.healthnotes.com Corn-Free Diet Source: Healthnotes, Inc.; www.healthnotes.com Dairy-Free Diet Source: Healthnotes, Inc.; www.healthnotes.com Egg-Free Diet Source: Healthnotes, Inc.; www.healthnotes.com Gluten-Free Diet Source: Healthnotes, Inc.; www.healthnotes.com Grapefruit Source: Healthnotes, Inc.; www.healthnotes.com Kumquat Source: Healthnotes, Inc.; www.healthnotes.com Lamb and Mutton Source: Healthnotes, Inc.; www.healthnotes.com Lemons Source: Healthnotes, Inc.; www.healthnotes.com Limes Source: Healthnotes, Inc.; www.healthnotes.com Low-Allergen Diet Source: Healthnotes, Inc.; www.healthnotes.com Oranges Source: Healthnotes, Inc.; www.healthnotes.com Rabbit Source: Healthnotes, Inc.; www.healthnotes.com

121

122

Allergens

Rye Source: Healthnotes, Inc.; www.healthnotes.com Soy-Free Diet Source: Healthnotes, Inc.; www.healthnotes.com Special Diets Index Source: Healthnotes, Inc.; www.healthnotes.com Tangerines Source: Healthnotes, Inc.; www.healthnotes.com Turkey Source: Healthnotes, Inc.; www.healthnotes.com Ugli Tangelo Fruit Source: Healthnotes, Inc.; www.healthnotes.com Weight Management Index Source: Healthnotes, Inc.; www.healthnotes.com Wheat Source: Healthnotes, Inc.; www.healthnotes.com

123

CHAPTER 3. ALTERNATIVE MEDICINE AND ALLERGENS Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to allergens. At the conclusion of this chapter, we will provide additional sources.

National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to allergens and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “allergens” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to allergens: •

A novel inhalation allergen present in the working environment of beekeepers. Author(s): Rudeschko O, Machnik A, Dorfelt H, Kaatz HH, Schlott B, Kinne RW. Source: Allergy. 2004 March; 59(3): 332-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14982517

•

A simple washing procedure with eucalyptus oil for controlling house dust mites and their allergens in clothing and bedding. Author(s): Tovey ER, McDonald LG. Source: The Journal of Allergy and Clinical Immunology. 1997 October; 100(4): 464-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9338538

•

Allergen avoidance in the primary prevention of asthma. Author(s): Simpson A, Custovic A.

124

Allergens

Source: Current Opinion in Allergy and Clinical Immunology. 2004 February; 4(1): 4551. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15090919 •

Allergen-immunostimulatory oligodeoxynucleotide conjugate: a novel allergoid for immunotherapy. Author(s): Spiegelberg HL, Horner AA, Takabayashi K, Raz E. Source: Current Opinion in Allergy and Clinical Immunology. 2002 December; 2(6): 54751. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14752340

•

Allergens in pepper and paprika. Immunologic investigation of the celery-birchmugwort-spice syndrome. Author(s): Leitner A, Jensen-Jarolim E, Grimm R, Wuthrich B, Ebner H, Scheiner O, Kraft D, Ebner C. Source: Allergy. 1998 January; 53(1): 36-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9491227

•

Allergens, dysbiosis and immune dysregulation: case studies on inflammatory bowel disease. Author(s): Lukaczer D, Lerman RH. Source: Alternative Therapies in Health and Medicine. 2003 May-June; 9(3): 136, 130-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12776484

•

Allergic contact dermatitis caused by Lithraea molleoides and Lithraea brasiliensis: identification and characterization of the responsible allergens. Author(s): Ale SI, Ferreira F, Gonzalez G, Epstein W. Source: American Journal of Contact Dermatitis : Official Journal of the American Contact Dermatitis Society. 1997 September; 8(3): 144-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9249282

•

Allergic contact dermatitis elicitation thresholds of potent allergens in humans. Author(s): Jerschow E, Hostynek JJ, Maibach HI. Source: Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association. 2001 November; 39(11): 1095-108. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11527569

•

Allergic contact dermatitis from common ivy confirmed with stored allergens. Author(s): Sanchez-Perez J, Cordoba S, Hausen BM, De Vega MJ, Aragues M, GarciaDiez A.

Alternative Medicine 125

Source: Contact Dermatitis. 1998 November; 39(5): 259-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9840266 •

Allergy to date fruits: characterization of antigens and allergens of fruits of the date palm (Phoenix dactylifera L.). Author(s): Kwaasi AA, Harfi HA, Parhar RS, Al-Sedairy ST, Collison KS, Panzani RC, Al-Mohanna FA. Source: Allergy. 1999 December; 54(12): 1270-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10688430

•

Are contact allergens stable in patch test preparations? Investigation of the degradation of d-limonene hydroperoxides in petrolatum. Author(s): Nilsson U, Magnusson K, Karlberg O, Karlberg AT. Source: Contact Dermatitis. 1999 March; 40(3): 127-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10073439

•

Bell peppers (Capsicum annuum) express allergens (profilin, pathogenesis-related protein P23 and Bet v 1) depending on the horticultural strain. Author(s): Jensen-Jarolim E, Santner B, Leitner A, Grimm R, Scheiner O, Ebner C, Breiteneder H. Source: International Archives of Allergy and Immunology. 1998 June; 116(2): 103-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9652302

•

Biochemical features of grain legume allergens in humans and animals. Author(s): Lalles JP, Peltre G. Source: Nutrition Reviews. 1996 April; 54(4 Pt 1): 101-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8710238

•

Biologic allergen assay for in vivo test allergens with an in vitro model of the murine type I reaction. Author(s): Hoffmann A, Vieths S, Haustein D. Source: The Journal of Allergy and Clinical Immunology. 1997 February; 99(2): 227-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9042050

•

Characterization of allergens in plant-derived spices: Apiaceae spices, pepper (Piperaceae), and paprika (bell peppers, Solanaceae). Author(s): Ebner C, Jensen-Jarolim E, Leitner A, Breiteneder H. Source: Allergy. 1998; 53(46 Suppl): 52-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9825999

•

Class I chitinases, the panallergens responsible for the latex-fruit syndrome, are induced by ethylene treatment and inactivated by heating.

126

Allergens

Author(s): Sanchez-Monge R, Blanco C, Perales AD, Collada C, Carrillo T, Aragoncillo C, Salcedo G. Source: The Journal of Allergy and Clinical Immunology. 2000 July; 106(1 Pt 1): 190-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10887324 •

Cloning and molecular and immunological characterisation of two new food allergens, Cap a 2 and Lyc e 1, profilins from bell pepper (Capsicum annuum) and Tomato (Lycopersicon esculentum). Author(s): Willerroider M, Fuchs H, Ballmer-Weber BK, Focke M, Susani M, Thalhamer J, Ferreira F, Wuthrich B, Scheiner O, Breiteneder H, Hoffmann-Sommergruber K. Source: International Archives of Allergy and Immunology. 2003 August; 131(4): 245-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12915767

•

Cross-reactivity of IgE antibodies to allergens. Author(s): Aalberse RC, Akkerdaas J, van Ree R. Source: Allergy. 2001 June; 56(6): 478-90. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11421891

•

Delayed-type hypersensitivity to contact allergens in psoriasis. A clinical evaluation. Author(s): Heule F, Tahapary GJ, Bello CR, van Joost T. Source: Contact Dermatitis. 1998 February; 38(2): 78-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9506219

•

Endogenous function and biological significance of aeroallergens: an update. Author(s): Stewart GA, McWilliam AS. Source: Current Opinion in Allergy and Clinical Immunology. 2001 February; 1(1): 95103. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11964676

•

Fragrance and contact allergens in vitro modulate the HLA-DR and E-cadherin expression on human epidermal Langerhans cells. Author(s): Verrier AC, Schmitt D, Staquet MJ. Source: International Archives of Allergy and Immunology. 1999 September; 120(1): 5662. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10529589

•

Human skin absorption and metabolism of the contact allergens, cinnamic aldehyde, and cinnamic alcohol. Author(s): Smith CK, Moore CA, Elahi EN, Smart AT, Hotchkiss SA. Source: Toxicology and Applied Pharmacology. 2000 November 1; 168(3): 189-99. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11042091

Alternative Medicine 127

•

Identification and immunologic characterization of an allergen, alliin lyase, from garlic (Allium sativum). Author(s): Kao SH, Hsu CH, Su SN, Hor WT, Chang T WH, Chow LP. Source: The Journal of Allergy and Clinical Immunology. 2004 January; 113(1): 161-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14713923

•

Identification by immunoblot of venom glycoproteins displaying immunoglobulin Ebinding N-glycans as cross-reactive allergens in honeybee and yellow jacket venom. Author(s): Hemmer W, Focke M, Kolarich D, Dalik I, Gotz M, Jarisch R. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2004 March; 34(3): 460-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15005742

•

Identification of serine protease as a major allergen of Curvularia lunata. Author(s): Gupta R, Sharma V, Sridhara S, Singh BP, Arora N. Source: Allergy. 2004 April; 59(4): 421-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15005766

•

Identification of soyabean allergens and immune mechanisms of dietary sensitivities in preruminant calves. Author(s): Lalles JP, Dreau D, Salmon H, Toullec R. Source: Research in Veterinary Science. 1996 March; 60(2): 111-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8685530

•

Identification of unique peanut and soy allergens in sera adsorbed with crossreacting antibodies. Author(s): Eigenmann PA, Burks AW, Bannon GA, Sampson HA. Source: The Journal of Allergy and Clinical Immunology. 1996 November; 98(5 Pt 1): 969-78. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8939161

•

Interaction of human lung surfactant proteins A and D with mite (Dermatophagoides pteronyssinus) allergens. Author(s): Wang JY, Kishore U, Lim BL, Strong P, Reid KB. Source: Clinical and Experimental Immunology. 1996 November; 106(2): 367-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8918587

•

Isolated colophony allergens as screening substances for contact allergy. Author(s): Karlberg AT, Gafvert E. Source: Contact Dermatitis. 1996 October; 35(4): 201-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8957638

128

Allergens

•

Isolation and characterization of relevant allergens from boiled lentils. Author(s): Sanchez-Monge R, Pascual CY, Diaz-Perales A, Fernandez-Crespo J, MartinEsteban M, Salcedo G. Source: The Journal of Allergy and Clinical Immunology. 2000 November; 106(5): 95561. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11080720

•

Kiwi allergens and their cross-reactivity with birch, rye, timothy, and mugwort pollen. Author(s): Rudeschko O, Fahlbusch B, Steurich F, Schlenvoigt G, Jager L. Source: J Investig Allergol Clin Immunol. 1998 March-April; 8(2): 78-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9615299

•

Multiple contact allergens in a violinist. Author(s): Alvarez MS, Brancaccio RR. Source: Contact Dermatitis. 2003 July; 49(1): 43-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14641123

•

Nitric oxide production by alveolar macrophages in response to house dust mite fecal pellets and the mite allergens, Der p 1 and Der p 2. Author(s): Peake HL, Currie AJ, Stewart GA, McWilliam AS. Source: The Journal of Allergy and Clinical Immunology. 2003 September; 112(3): 531-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13679812

•

Occupational asthma caused by exposure to asparagus: detection of allergens by immunoblotting. Author(s): Lopez-Rubio A, Rodriguez J, Crespo JF, Vives R, Daroca P, Reano M. Source: Allergy. 1998 December; 53(12): 1216-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9930601

•

Occupational rhinitis and asthma by Lathyrus sativus flour: characterization of allergens. Author(s): Porcel S, Leon F, Valero AM, Calderin PM, Cuevas M, Cuesta EA. Source: The Journal of Allergy and Clinical Immunology. 2001 April; 107(4): 743-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11295670

•

Patch testing with allergens from modified rosin (colophony) discloses additional cases of contact allergy. Author(s): Gafvert E, Bordalo O, Karlberg AT. Source: Contact Dermatitis. 1996 November; 35(5): 290-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9007375

Alternative Medicine 129

•

Pectin and cashew nut allergy: cross-reacting allergens? Author(s): Rasanen L, Makinen-Kiljunen S, Harvima RJ. Source: Allergy. 1998 June; 53(6): 626-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9689352

•

Pistachio nut hypersensitivity: identification of pistachio nut allergens. Author(s): Parra FM, Cuevas M, Lezaun A, Alonso MD, Beristain AM, Losada E. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 1993 December; 23(12): 996-1001. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10779292

•

Pollen mixtures used as health food may be a harmful source of allergens. Author(s): Angiola Crivellaro M, Senna G, Riva G, Cislaghi C, Falagiani P, Walter Canonica G, Passalacqua G. Source: J Investig Allergol Clin Immunol. 2000 September-October; 10(5): 310-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11108445

•

Prevalence of sensitization to food allergens in adult Swedes. Author(s): Bjornsson E, Janson C, Plaschke P, Norrman E, Sjoberg O. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 1996 October; 77(4): 327-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8885811

•

Quantification of allergenic urushiols in extracts of Ginkgo biloba leaves, in simple one-step extracts and refined manufactured material (EGb 761). Author(s): Schotz K. Source: Phytochemical Analysis : Pca. 2004 January-February; 15(1): 1-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14979519

•

Recalls of foods containing undeclared allergens reported to the US Food and Drug Administration, fiscal year 1999. Author(s): Vierk K, Falci K, Wolyniak C, Klontz KC. Source: The Journal of Allergy and Clinical Immunology. 2002 June; 109(6): 1022-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12063535

•

Recombinant allergens for skin testing. Author(s): Schmid-Grendelmeier P, Crameri R. Source: International Archives of Allergy and Immunology. 2001 June; 125(2): 96-111. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11435726

130

Allergens

•

Sensitization to grass, ragweed, mugwort pollen allergens in Japanese monkeys (Macaca fuscata): preliminary report. Author(s): Sakaguchi M, Kobayashi C, Inouye S, Konaka A, Yamada T, Nigi H. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 1999 December; 29(12): 1692-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10594546

•

Sensitization to soybean hull allergens in subjects exposed to different levels of soybean dust inhalation in Argentina. Author(s): Codina R, Ardusso L, Lockey RF, Crisci C, Bertoya N. Source: The Journal of Allergy and Clinical Immunology. 2000 March; 105(3): 570-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10719309

•

Serological characterization of allergens in poppy seeds. Author(s): Jensen-Jarolim E, Gerstmayer G, Kraft D, Scheiner O, Ebner H, Ebner C. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 1999 August; 29(8): 1075-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10457111

•

Structural biology of allergens. Author(s): Aalberse RC. Source: The Journal of Allergy and Clinical Immunology. 2000 August; 106(2): 228-38. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10932064

•

Systemic allergic reaction to coconut (Cocos nucifera) in 2 subjects with hypersensitivity to tree nut and demonstration of cross-reactivity to legumin-like seed storage proteins: new coconut and walnut food allergens. Author(s): Teuber SS, Peterson WR. Source: The Journal of Allergy and Clinical Immunology. 1999 June; 103(6): 1180-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10359903

•

The allergens of Dendropanax trifidus Makino and Fatsia japonica Decne. et Planch. and evaluation of cross-reactions with other plants of the Araliaceae family. Author(s): Oka K, Saito F, Yasuhara T, Sugimoto A. Source: Contact Dermatitis. 1999 April; 40(4): 209-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10208509

•

The utility of patch tests using larger screening series of allergens. Author(s): Larkin A, Rietschel RL.

Alternative Medicine 131

Source: American Journal of Contact Dermatitis : Official Journal of the American Contact Dermatitis Society. 1998 September; 9(3): 142-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9744905

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

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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

General Overview Acne Source: Integrative Medicine Communications; www.drkoop.com Allergic Rhinitis Source: Integrative Medicine Communications; www.drkoop.com Allergies Alternative names: Hay Fever Source: Prima Communications, Inc.www.personalhealthzone.com Allergies and Sensitivities Source: Healthnotes, Inc.; www.healthnotes.com

132

Allergens

Anaphylaxis Source: Integrative Medicine Communications; www.drkoop.com Angioedema Source: Integrative Medicine Communications; www.drkoop.com Anxiety Source: Integrative Medicine Communications; www.drkoop.com Asthma Source: Healthnotes, Inc.; www.healthnotes.com Asthma Source: Integrative Medicine Communications; www.drkoop.com Attention Deficit-Hyperactivity Disorder Source: Healthnotes, Inc.; www.healthnotes.com Autism Source: Healthnotes, Inc.; www.healthnotes.com Bronchitis Source: Healthnotes, Inc.; www.healthnotes.com Bronchitis Source: Integrative Medicine Communications; www.drkoop.com Candida/Yeast Hypersensitivity Syndrome Source: Prima Communications, Inc.www.personalhealthzone.com Canker Sores Source: Healthnotes, Inc.; www.healthnotes.com Celiac Disease Source: Healthnotes, Inc.; www.healthnotes.com Chronic Obstructive Pulmonary Disease Source: Healthnotes, Inc.; www.healthnotes.com Colic Source: Healthnotes, Inc.; www.healthnotes.com Conjunctivitis and Blepharitis Source: Healthnotes, Inc.; www.healthnotes.com Cough Source: Integrative Medicine Communications; www.drkoop.com Crohn's Disease Source: Healthnotes, Inc.; www.healthnotes.com

Alternative Medicine 133

Crohn's Disease Source: Integrative Medicine Communications; www.drkoop.com Dermatitis Source: Integrative Medicine Communications; www.drkoop.com Ear Infection Source: Integrative Medicine Communications; www.drkoop.com Eczema Source: Healthnotes, Inc.; www.healthnotes.com Eczema Source: Integrative Medicine Communications; www.drkoop.com Edema Source: Integrative Medicine Communications; www.drkoop.com Endometriosis Source: Integrative Medicine Communications; www.drkoop.com Epilepsy Source: Healthnotes, Inc.; www.healthnotes.com Fibromyalgia Source: Integrative Medicine Communications; www.drkoop.com Food Allergy Source: Integrative Medicine Communications; www.drkoop.com Gallbladder Disease Source: Integrative Medicine Communications; www.drkoop.com Gallstones Source: Healthnotes, Inc.; www.healthnotes.com Gastritis Source: Integrative Medicine Communications; www.drkoop.com Glaucoma Source: Integrative Medicine Communications; www.drkoop.com Hay Fever Source: Healthnotes, Inc.; www.healthnotes.com Hay Fever Source: Integrative Medicine Communications; www.drkoop.com Hives Source: Healthnotes, Inc.; www.healthnotes.com

134

Allergens

Hypertension Source: Healthnotes, Inc.; www.healthnotes.com Irritable Bowel Syndrome Source: Integrative Medicine Communications; www.drkoop.com Lupus Source: Integrative Medicine Communications; www.drkoop.com Ménière's Disease Source: Healthnotes, Inc.; www.healthnotes.com Migraine Headache Source: Integrative Medicine Communications; www.drkoop.com Migraine Headaches Source: Prima Communications, Inc.www.personalhealthzone.com Multiple Sclerosis Source: Integrative Medicine Communications; www.drkoop.com Muscular Dystrophy Source: Integrative Medicine Communications; www.drkoop.com Otitis Media Source: Integrative Medicine Communications; www.drkoop.com Peptic Ulcer Source: Healthnotes, Inc.; www.healthnotes.com Peptic Ulcer Source: Integrative Medicine Communications; www.drkoop.com Psoriasis Source: Healthnotes, Inc.; www.healthnotes.com Rheumatoid Arthritis Source: Integrative Medicine Communications; www.drkoop.com Rheumatoid Arthritis Source: Prima Communications, Inc.www.personalhealthzone.com Sarcoidosis Source: Integrative Medicine Communications; www.drkoop.com Seborrheic Dermatitis Source: Healthnotes, Inc.; www.healthnotes.com Shock Source: Integrative Medicine Communications; www.drkoop.com

Alternative Medicine 135

Sinus Congestion Source: Healthnotes, Inc.; www.healthnotes.com Sinus Infection Source: Integrative Medicine Communications; www.drkoop.com Sinusitis Source: Healthnotes, Inc.; www.healthnotes.com Sinusitis Source: Integrative Medicine Communications; www.drkoop.com Spastic Colon Source: Integrative Medicine Communications; www.drkoop.com Stomach Inflammation Source: Integrative Medicine Communications; www.drkoop.com Systemic Lupus Erythematosus Source: Healthnotes, Inc.; www.healthnotes.com Systemic Lupus Erythematosus Source: Integrative Medicine Communications; www.drkoop.com Ulcerative Colitis Source: Healthnotes, Inc.; www.healthnotes.com Urethral Inflammation Source: Integrative Medicine Communications; www.drkoop.com Urethritis Source: Integrative Medicine Communications; www.drkoop.com Vaginal Inflammation Source: Integrative Medicine Communications; www.drkoop.com Vaginitis Source: Integrative Medicine Communications; www.drkoop.com Vertigo Source: Healthnotes, Inc.; www.healthnotes.com Water Retention Source: Integrative Medicine Communications; www.drkoop.com Yeast Infection Source: Healthnotes, Inc.; www.healthnotes.com •

Alternative Therapy Ionized Air (negative Ions) Source: Healthnotes, Inc.; www.healthnotes.com

136

Allergens

Lepore Technique of M.r.t. Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/l.html Magnet Therapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,715,00.html Naturopathy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,722,00.html Nutrition Source: Integrative Medicine Communications; www.drkoop.com Nutrition Kinesiology Alternative names: NK Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/n.html •

Herbs and Supplements Achillea Alternative names: Yarrow; Achillea millefolium L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Arnica Alternative names: Arnica montana L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Australian Fevertree Source: Integrative Medicine Communications; www.drkoop.com Bee Products Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,756,00.html Betula Alternative names: Birch; Betula sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Chamomile Alternative names: Matricaria recutita Source: Healthnotes, Inc.; www.healthnotes.com

Alternative Medicine 137

Chamomile Source: Prima Communications, Inc.www.personalhealthzone.com Cinnamomum Alternative names: Cinnamon; Cinnamomum zeylanicum Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Eucalyptus Alternative names: Eucalyptus globulus, Eucalyptus fructicetorum, polybractea, smithii, Australian Fevertree Source: Integrative Medicine Communications; www.drkoop.com Eucalyptus globulus Source: Integrative Medicine Communications; www.drkoop.com Foeniculum Alternative names: Fennel; Foeniculum vulgare Mill Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Ginkgo Alternative names: Ginkgo biloba Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Ginkgo Biloba Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,788,00.html Goldenrod Source: Prima Communications, Inc.www.personalhealthzone.com Juniperus Alternative names: Juniper; Juniperus sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Kochia Alternative names: Summer Cypress, Fireweed; Kochia scoparia (L.) Schrad Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Luffa Alternative names: Luffa sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Matricaria Alternative names: Chamomile; Matricaria chamomilla Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Melaleuca Alternative names: Tea Tree Oil; Melaleuca alternifolia Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org

138

Allergens

Nettle Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10048,00.html Panax Alternative names: Ginseng; Panax ginseng Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Picrorhiza Alternative names: Picrorhiza kurroa Source: Healthnotes, Inc.; www.healthnotes.com Plantago Major Alternative names: Plantain; Plantago major/lanceolata Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Plantago Psyllium Alternative names: Psyllium, Ispaghula; Plantago psyllium/ovata Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Tanacetum Alternative names: Feverfew; Tanacetum parthenium (L.) Schultz-Bip. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Thuja Plicata Alternative names: Western Red Cedar Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org

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

139

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

Dissertations on Allergens 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 allergens. 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: •

Home environments and allergen avoidance practices in a hot, humid climate by Kutintara, Benjamas; PhD from Virginia Polytechnic Institute and State University, 2002, 106 pages http://wwwlib.umi.com/dissertations/fullcit/3047983

•

The distribution of the neural components within the airway epithelium in healthy animals and animals exposed to allergens and/or ozone by Larson, Shawnessy Dawn; PhD from University of California, Davis, 2003, 115 pages http://wwwlib.umi.com/dissertations/fullcit/3108000

140

Allergens

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.

141

CHAPTER 5. PATENTS ON ALLERGENS 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 “allergens” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on allergens, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Allergens By performing a patent search focusing on allergens, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We

8Adapted from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

142

Allergens

will tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on allergens: •

Allergy test strip Inventor(s): McLernon, III; William J. (22-57 78th St., Astoria Heights, NY 11370) Assignee(s): none reported Patent Number: 6,319,467 Date filed: April 19, 1994 Abstract: A single allergy test strip is used in determining if a person has allergic reactions to allergens. A perforated layer of non-allergenic material has an adhesive layer on a back side thereof. The perforated layer has a top side with at least one perforation extending from the top side through the material and through the back side adhesive layer. A multilayer pad of allergy test strips contains several test strips each having an adhesive perimeter around the back edges thereof. Excerpt(s): The present invention relates to an allergy test strip for use in determining if a person has allergic reactions to allergens. It is known to test individuals for allergic reactions to various substances that produce these reactions and which are known as allergens. In the past, the testing protocols included applying to a selected area of the person's skin, one or more allergens and to determine what reaction, if any, did occur. Examples of these allergens include dust, mold spores, pollens (i.e., trees and grasses), foods, and insect bites. Occasionally the medical person conducting the testing loses track of the location for some of the various allergens previously applied to the skin of the person being tested. This places into jeopardy the accuracy of the tests being conducted. Web site: http://www.delphion.com/details?pn=US06319467__

•

Antiallergenic covering for receiving objects contaminated with allergens and/or fine dust absorbed into the lung Inventor(s): Baumgartel; Falko (Steinfurt, DE), Vopel; Ulrich (Flammersfeld, DE) Assignee(s): Lohmann GmbH & Co. KG (Neuwied, DE) Patent Number: 6,363,553 Date filed: September 1, 2000 Abstract: The allergen-inhibiting encasing for receiving objects contaminated with respirable fine and extremely fine dust, house dust, moulds and allergens, e.g. excretions of house dust mites, together with air, especially bedding and/or upholstery of all kinds, comprising at least a web of woven fabric or a nonwoven and a mechanical closure, such as a zip fastener, in a configuration blocking the passage of allergens and extremely fine particles. The encasing is characterized in that the web includes a fabric which is coated with polyurethane-acrylate copolymer foam and is equipped with increased density, by calendering, up to a degree of filtration of almost 100% for particles smaller than 1.mu.m. Also, the zip fastener is sealed on the inner face of the encasing by overlapping with a sealing strip comprising at least three plies of fabric. Excerpt(s): The invention relates to an allergen-inhibiting encasing for receiving objects contaminated with respirable fine dust and extremely fine dust, house dust, moulds and

Patents 143

allergens, e.g. excretions of house dust mites, together with air, especially bedding and/or upholstery of all kinds. The encasing has at least one web of woven fabric or nonwoven and a mechanical closure such as a zip fastener, in a configuration blocking the passage of allergens and extremely fine dust. With allergen-inhibiting encasings intended to receive the aforementioned objects, the encasings must on the one hand be air-permeable to a limited extent and on the other hand are to prevent contamination of the surrounding air with respirable fine or extremely fine dust and allergens. It is, inter alia, necessary to clean the encasing in regular intervals. For this reason, such encasings must be provided with a suitable closure system which is easy to handle, suitable for repeated use and likewise allergen-inhibiting. It must be capable of diminishing the excess pressure, which occasionally occurs within the encasing upon volume reduction such as that caused by pushing or kneading movements. Preferably, the diminishing of the excess pressure should be gradual enough for the sudden change of pressure both in the region of the textile web as well as of the closure systems to be uniformly low, so that no respirable fine dust and allergens may be emitted thereby. It is known to provide an almost air-impermeable encasing for bedding and upholstery with a zip fastener which can, in addition, be sealed by means of a pressure-sensitive adhesive tape suitable for multiple repeated closing. To this end, the constitution of the web material must have comparatively satisfactory air permeability with simultaneous particle impermeability to respiratory fine dust in the range of <10.mu.m (U.S. Pat. No. 5,321,861). Web site: http://www.delphion.com/details?pn=US06363553__ •

Attractant miticide and capturing device Inventor(s): Watanabe; Hideo (13-51 Minamino-Machi, Kitahirano, Himezi-shi, Hyogo, JP) Assignee(s): none reported Patent Number: 6,415,545 Date filed: August 31, 2000 Abstract: An attractant miticide and a capturing device containing the miticide to capture and exterminate mites that are implicated as a source of allergens in the home, without polluting the inhabited environment. The miticide is a mixture of a non-toxic feeding attractant, a non-toxic aromatic attractant and a non-toxic miticidal substance, which contains non-toxic feeding attractants such as beer yeast, chocolate, cheese, food scraps, rice malt, and the like. The food aroma additive-type ester-based aromatic attractant can be geranyl and the miticidal substance can be silica gel that absorbs moisture and generates heat to kill mites that have been attracted to eat the bait. Excerpt(s): The present invention relates to an attractant miticide and a capturing device for the elimination of parasites in the field of sanitation. In particular, the invention relates to a safe attractant miticide and a mite capturing device containing no harmful petroleum-based chemical substances. With the proliferation of mites in indoor carpets, straw mats, mattresses, beds, rugs, automobile fabrics, etc. in modern home environments, such mites are increasingly being implicated as the cause of atopic dermatitis, bronchial asthma and similar conditions. As living styles become more Westernized, to include sashes and the like, environments are being provided that are more ideal for mites to live in and the proliferation of mites is promoted, such that it is becoming a major issue to deal with these health-threatening mites.

144

Allergens

Web site: http://www.delphion.com/details?pn=US06415545__ •

Benzimidazole derivatives as modulators of IgE Inventor(s): Campbell; Michael G. (Durham, NC), Major; Michael W. (Glendale, WI), Richards; Mark L. (La Jolla, CA), Sircar; Jagadish C. (San Diego, CA) Assignee(s): Avanir Pharmaceuticals (San Diego, CA) Patent Number: 6,303,645 Date filed: October 21, 1999 Abstract: This invention relates to a family of diacyl benzimidazole analogs, which are inhibitors of the IgE response to allergens. These compounds are useful in the treatment of allergy and/or asthma or any diseases where IgE is pathogenic. Excerpt(s): This invention relates to small molecule inhibitors of the IgE response to allergens that are useful in the treatment of allergy and/or asthma or any diseases where IgE is pathogenic. An estimated 10 million persons in the United States have asthma, about 5% of the population. The estimated cost of asthma in the United States exceeds $6 billion. About 25% of patients with asthma who seek emergency care require hospitalization, and the largest single direct medical expenditure for asthma has been inpatient hospital services (emergency care), at a cost of greater than $1.6 billion. The cost for prescription medications, which increased 54% between 1985 and 1990, was close behind at $1.1 billion (Kelly, Pharmacotherapy 12:13S-21S (1997)). According to the National Ambulatory Medical Care Survey, asthma accounts for 1% of all ambulatory care visits, and the disease continues to be a significant cause of missed school days in children. Despite improved understanding of the disease process and better drugs, asthma morbidity and mortality continue to rise in this country and worldwide (U.S. Department of Health and Human Services; 1991, publication no. 91-3042). Thus, asthma constitutes a significant public health problem. Web site: http://www.delphion.com/details?pn=US06303645__

•

Clean air tent system Inventor(s): Kotliar; Igor K. (P.O. Box 2021, New York, NY 10159-2021) Assignee(s): none reported Patent Number: 6,508,850 Date filed: November 16, 2000 Abstract: A system for providing clean air environments for sleeping, resting, working or exercising in order to provide relieve and therapeutic benefits to people with bronchial asthma and respiratory allergies, such system comprising of a tent or stationary enclosure, an air-pumping device and a HEPA filter that removes dust, bacteria and allergens from air entering tent or enclosure; the air-pumping device can be installed in two different configurations: in air-supply or air-removal mode, in both providing necessary ventilation and supply of clean air for breathing. Excerpt(s): This invention relates to enclosed clean air environments created for resting in for the purposes of improving health conditions of people with bronchial asthma and respiratory allergies. Every year more and more people throughout the world become affected by polluted atmosphere and growing number of allergens, especially in urban

Patents 145

areas where bronchial asthma and respiratory allergies spread at growing speed. All people with such illnesses would greatly benefit from a possibility to sleep, rest, work or exercise in environments, substantially free of dust mites, bacteria and allergens. The invention presented here provides a convenient, low cost solution to create such clean air environment for sleeping. This invention makes it possible to make a portable sleeping enclosure that may be easily installed at home or in any hotel room. Web site: http://www.delphion.com/details?pn=US06508850__ •

Cloning and sequencing of allergens of dermatophagoides (house dust mite) Inventor(s): Simpson; Richard J. (Richmond, AU), Stewart; Geoffrey A. (Leeming, AU), Thomas; Wayne Robert (Nedlands, AU), Turner; Keven J. (Claremont, AU) Assignee(s): ImmuLogic Pharmaceutical Corporation (Waltham, MA) Patent Number: 6,147,201 Date filed: June 7, 1995 Abstract: Isolated DNA encoding allergens of Dermatophagoides (house dust mites) particularly of the species Dermatophagoides farinae and Dermatophagoides pteronyssinus, which are protein allergens or peptides which include at least one epitope of the protein allergen. In particular, DNA encoding two major D. farinae allergens, Der f I and Der f II and DNA encoding a D. pteronyssinus allergen, Der p I. In addition, the proteins or peptides encoded by the isolated DNA, their use as diagnostic and therapeutic reagents and methods of diagnosing and treating sensitivity to house dust mite allergens. Excerpt(s): Work described herein was funded by grants from the Princess Margaret Children's Medical Research Foundation, the Australian Health and Medical Research Council and the Asthma Foundation of Australia. Recent reports have documented the importance of responses to the Group I and Group II allergens in house dust mite allergy. For example, it has been documented that over 60% of patients have at least 50% of their anti-mite antibodies directed towards these proteins (Lind, P. et al., Allergy, 39:259-274 (1984); van der Zee, J. S. et al., J. Allergy Clin. Immunol., 81:884-896 (1988)). It is possible that children show a greater degree of reactivity (Thompson, P. J. et al., Immunology, 64:311-314 (1988)). Allergy to mites of the genus Dermatophagoides (D.) is associated with conditions such as asthma, rhinitis and ectopic dermatitis. Two species, D. pteronyssinus and D. farinae, predominate and, as a result, considerable effort has been expended in trying to identify the allergens produced by these two species. D. pteronyssinus mites are the most common Dermatophagoides species in house dust in Western Europe and Australia. The species D. farinae predominates in other countries, such as, North America and Japan (Wharton, G. W., J. Medical Entom, 12:577-621 (1976)). It has long been recognized that allergy to mites of this genus is associated with diseases such as asthma, rhinitis and atopic dermatitis. It is still not clear what allergens produced by these mites are responsible for the allergic response and associated conditions. The present invention relates to isolated DNA which encodes a protein allergen of Dermatophagoides (D.) house dust mite) or a peptide which includes at least one epitope of a protein allergen of a house dust mite of the genus Dermatophagoides. It particularly relates to DNA encoding major allergens of the species D. farinae, designated Der f I and Der f II, or portions of these major allergens (i.e., peptides which include at least one epitope of Der f I or of Der f II). It also particularly relates to DNA encoding major allergens of D. pteronyssinus, designated Der p I and Der p II, or

146

Allergens

portions of these major allergens (i.e., peptides which include at least one epitope of Der p I or of Der p II. Web site: http://www.delphion.com/details?pn=US06147201__ •

House dust mite allergen, Der f VII, and uses therefor Inventor(s): Chua; Kaw-Yan (Taipei, TW), Thomas; Wayne Robert (Nedlands, AU) Assignee(s): ImmuLogic Pharmaceutical Corporation (Waltham, MA) Patent Number: 6,413,738 Date filed: June 10, 1996 Abstract: Isolated nucleic acids encoding allergens of the species Dermatophagoides pteronyssinus and Dermatophagoides farinae, Der p VII and Der f VII, respectively, are disclosed. A cDNA encoding a peptide having a Der p VII activity and a predicted molecular weight of about 22, 177 daltons is described. A cDNA encoding a peptide having Der f VII activity is also described. The nucleic acids of the invention can be used as probes to detect the presence of Der p VII or Der f VII nucleic acid in a sample or for the recombinant production of peptides having a Der p VII or Der f VII activity. Peptides having a Der p VII or Der f VII activity can be used in compositions suitable for pharmaceutical administration or methods of diagnosing sensitivity to house dust mite allergens. Excerpt(s): Approximately 10% of the population become hypersensitized (allergic) upon exposure to antigens from a variety of environmental sources. Those antigens that induce immediate and/or delayed types of hypersensitivity are known as allergens (King, T. P., (1976) Adv. Immunol., 23:77-105). These include products of grasses, trees, weeds, animal dander, insects, food, drugs, and chemicals. Genetic predisposition of an individual is believed to play a role in the development of immediate allergic responses (Young, R. P. et al., (1990) Clin. Sci., 79:19) such as atopy and anaphylaxis whose symptoms include hay fever, asthma, and hives. The antibodies involved in atopic allergy belong primarily to the IgE class of immunoglobins. IgE binds to basophils, mast cells and dendritic cells via a specific, high-affinity receptor Fc.epsilon.RI (Kinet, J. P., (1990) Curr. Opin. Immunol., 2:499-505). Upon combination of an allergen acting as a ligand with its cognate receptor IgE, FceRI bound to the IgE may be cross-linked on the cell surface, resulting in physiological manifestations of the IgE--allergen interaction. These physiological effects include the release of, among other substances, histamine, serotonin, heparin, chemotactic factor(s) for eosinophilic leukocytes and/or leukotrienes C4, D4, and E4, which cause prolonged constriction of bronchial smooth muscle cells (Hood, L. E. et al., Immunology (2nd ed.), The Benjamin/Cumming Publishing Co., Inc. (1984)). Hence, the ultimate consequence of the interaction of an allergen with IgE is allergic symptoms triggered by the release of the aforementioned mediators. Such symptoms may be systemic or local in nature, depending on the route of entry of the antigen and the pattern of deposition of IgE on mast cells or basophils. Local manifestations generally occur on epithelial surfaces at the site of entry of the allergen. Systemic effects can induce anaphylaxis (anaphylactic shock) which results from IgEbasophil response to circulating (intravascular) antigen. Studies with purified allergens have shown that about 80% of patients allergic to the mite Dermatophagoides pteronyssinus produce IgE reactive to Der p I and Der p II (Chapman M. D. et al., J. Immunol. (1980) 125:587-92; Lind P., J. Allergy Clin. Immunol. (1985) 76:753-61; Van derZee J. S. et al., J. Allergy Clin. Immunol. (1988) 81:884-95). For about half of the patients, these specificities constitute 50% of the IgE antimite antibody. The allergen Der

Patents 147

p III, recently identified as trypsin, (Stewart G. A. et al., Immunology (1992) 75:29-35) reacts with a similar or higher frequency (Stewart G. A. et al., supra; Ford S. A. et al., Clin. Exp. Allergy (1989) 20:27-31). However, in the only quantitative study performed to date, the investigators reported the level of IgE binding to be considerably less than Der p I. Electrophoretic techniques (Ford S. A. et al, supra; Bengtsson A. et al., Int. Arch. Allergy Appl. Immunol. (1986) 80:383-90; Lind P. et al., Scand. J. Immunol. (1983) 17:26373; Tovey E. R. et al, J. Allergy Clin. Immunol. (1987) 79:93-102) have shown that most sera recognize other allergens. For example, in the study of Ford et al (supra) Western blotting showed 8 sera reacting with 1-2 bands, 6 with 3-6 and 3 with a greater number including one with at least 13. In another study, Baldo et al. (Adv. Bioscience (1989) 4:1331) report the finding of components at Mr 30, 26, 25K reacting with 50% of sera. To determine the importance of particular specificities in the allergic reactions, purified allergens would be required for quantitative IgE binding tests and to examine the frequency and lymphokine profile for T cell reactivity. Web site: http://www.delphion.com/details?pn=US06413738__ •

Identification of human allergens and T-lymphocyte antigens in vitro Inventor(s): Kalish; Richard S. (East Setauket, NY) Assignee(s): The Research Foundation of State University of New York (Albany, NY) Patent Number: 6,713,250 Date filed: August 8, 1997 Abstract: The invention provides a method for screening a test compound for the ability of the test compound to induce a response from human naive T-cells. The method comprises admixing human naive T cells, macrophages/monocytes, immortalized B cells lacking class I and class II major histocompatibility antigens, and a test compound; and determining whether the test compound induces a response from the human naive T cells. The invention further provides a method for primary in vitro sensitization of human naive T-cells. The method comprises admixing human naive T cells, macrophages/monocytes, immortalized B cells lacking class I and class II major histocompatibility antigens, and an antigen. Excerpt(s): The subject invention is directed generally to immunology, and more particularly to a method for screening a test compound for the ability of the test compound to induce a response from human naive T-cells, and to a method for primary in vitro sensitization of human naive T-cells. Throughout this application various publications are referenced, many in parenthesis. Full citations for each of these publications are provided at the end of the Detailed Description. The disclosures of each of these publications in their entireties are hereby incorporated by reference in this application. There is a great need for in vitro methods for testing allergenicity of compounds. This need is driven by socioeconomic factors related to concerns over animal testing. In particular, a method is needed to screen for potential allergens in products intended for topical application, such as cosmetics, and toiletry products. Currently, testing of potential allergens is largely performed on human subjects at great expense (1). Unfortunately, even the most extensive clinical trials employing over 100 subjects are unlikely to detect severe allergic reactions that may occur in 1/1,000 persons. Yet these rare severe reactions may present a significant risk to the population, as well as a large legal liability to the manufacturer. Web site: http://www.delphion.com/details?pn=US06713250__

148

•

Allergens

Immunoassay for peanut allergen Inventor(s): Burks, Jr.; A. Wesley (Little Rock, AR), Helm; Ricki M. (Little Rock, AR) Assignee(s): University of Arkansas (Little Rock, AR) Patent Number: 6,441,142 Date filed: June 18, 1999 Abstract: Peanuts are a common cause of food hypersensitivity reactions. The sera of 10 patients who had atopic dermatitis and a positive double-blind placebo-controlled food challenge to peanut were used to investigate the major allergens of peanut. Crude Florunner extracts were fractionated by anion-exchange chromatography using a step gradient (limit buffer, 0.05M BisTris/1.5M NaCl). One hundred microliters of each 2.0 ml fraction was dot-blotted onto nitrocellulose paper and IgE-binding activity assessed using the serum pool to select allergen-containing fractions. A protein peak (OD 280) which eluted at 10% NaCl and demonstrated intense IgE-binding was further analyzed by two-dimensional SDS-PAGE/immunoblot analysis. The majority of this fraction is a protein which has a molecular weight of 17 kD and a pI of 5.2. Sequencing data from the N-terminus revealed the following initial 9 amino acids: (*)-Q-Q-(*)-E-L-Q-D-L. Based on IgE-binding activity and no known amino acid sequence identity to other allergens, this allergen is designated Ara h II. Excerpt(s): The present invention is directed to methods and apparatus for detecting and quantifying allergens in foodstuffs, and, more particularly, concerns peanut allergens, antigens, monoclonal antibodies having specificity for peanut allergens, hybridoma cell lines which produce the monoclonal antibodies and immunoassay methods and apparatus including the monoclonal antibodies for detecting and quantifying peanut allergens in food-processing equipment and materials as well as natural, processed, and finished foods. The ingestion of peanuts is a common cause of food hypersensitivity reactions. Symptoms can vary from mild abdominal discomfort to severe anaphylaxis. In a recent report by Yunginger et al., "Fatal Food-Induced Anaphylaxis", Journal of the American Medical Association 1988; 260:1450-2, four of seven patients who experienced fatal anaphylaxis died after peanut ingestion. All four of these patients unknowingly had eaten peanut in food prepared and consumed away from home. In the most recent studies involving children and food challenges, peanut is among the three leading foods that cause food hypersensitivity reactions. The increasing use of peanut products in our food supply has served to aggravate the problem of peanut allergy. Peanuts, generally in the form of peanut butter, are introduced into the American diet at a very young age. Some children react on challenge to peanut on their first known exposure, indicating that they had been sensitized in utero, by breast feeding, or by an unknown exposure. Unlike other food sensitivities in children, long-term follow-up studies of up to fourteen years indicate that peanut hypersensitivity is rarely outgrown. Web site: http://www.delphion.com/details?pn=US06441142__

•

Immunochemical determination of substances contained on textile fibers or polymers Inventor(s): Brosius; Rupert (Munchen, DE), Hock; Bertold (Freising, DE), Langhals; Heinz (Ottobrunn, DE) Assignee(s): Diagnostic SYstems Biotechnologie GmbH (Munich, DE) Patent Number: 6,335,171 Date filed: June 10, 1999

Patents 149

Abstract: A method for the detection of substances contained on textile fibers or other natural or synthetic polymers is disclosed. The contained substances are identified with immunochemical methods, where the immunochemical reaction can occur on the fiber or polymer. The method is especially suitable for the determination of substances that can act as allergens. Excerpt(s): The invention is concerned with a method for the detection of substances contained on textile fibers or other natural or synthetic polymers. Textiles or foods, e.g., luxury foods, have numerous substances contained in them which could act as allergens for consumers, depending on immunological disposition. These allergens trigger allergic reactions which are manifested with an extensive symptomatology, mostly by strong release of histamine. Erythema, irritation of mucosa, asthmatic reactions, or even drop in blood pressure with shock-like states may result in allergic persons. Therefore, it is of great importance for allergic persons to identify substances that represent a risk potential according to the particular individual allergic profile in textiles and foods, e.g., luxury foods, etc., with a rapid process that is easy to perform. U.S. Pat. No. 5,324,642 describes a method for the analysis of an analyte in a keratin structure (e.g., hair, nails), in which an enzyme and a compound with low redox potential are allowed to act on a sample of the keratin structure, in order to degrade the structure and to dissolve the analyte in this digesting solution. The detection of the analyte is preferably done by immunoassay techniques on a protein basis (that is, with antibodies). Web site: http://www.delphion.com/details?pn=US06335171__ •

Inactivation of granulocytes in the treatment of established allergic responses Inventor(s): Bitoh; Soji (5-2-29, Matsushiro, Tsukuba city, Ibaraki 305, JP), Sehon; Alec (695 Academy Road, Winnipeg, Manitoba, CA) Assignee(s): none reported Patent Number: 6,383,489 Date filed: May 2, 1996 Abstract: This invention is based on the discovery that an essentially nonallergenic covalent conjugate of a model allergen, ovalbumin (OA), and monomethoxypolyethylenc glycol (mPEG) is capable of inactivating in vivo and ex vivo granulocytes sensitized with anti-OA IgE antibodies (Abs). As a result of the inactivation of the granulocytes, subsequent challenge with OA was not followed by degranulation and the consequent release of the mediators of anaphylaxis (vasoactive compounds) from the granules of these cells. These results, therefore, provide a basis for the treatment of symptoms of an already established immune response against an allergen or allergens. Excerpt(s): The present invention relates to materials and methods relating to cell control and cell suppression. One of the greatest challenges is to devise strategies for the selective control of the activities of particular cells. For example, a strategy for the inactivation of harmful cell responses such as undesirable immune responses, as in the case of IgE-mediated allergies, auto-immune disease, rejection of transplants. Allergies are caused by a wide variety of substances eg pollens, foods, dust, chemicals collectively referred to hereafter as environmental allergens. Generally speaking allergens are antigens and the terms allergen and antigen may be used interchangeably in the context of this application, but the term allergen is particularly used to denote a type of antigen which induces the production of antibodies of isotype IgE (which mediate Type I

150

Allergens

allergies) in addition to antibodies of other isotypes as generated in response to common antigens. Web site: http://www.delphion.com/details?pn=US06383489__ •

Ionization filter for purifying air Inventor(s): Holter; Heinz (Beisenstrasse 39-41, Gladbeck, DE) Assignee(s): none reported Patent Number: 6,375,721 Date filed: December 3, 1999 Abstract: The invention relates to an ionization filter for purifying air that is enriched with dust particles and other inorganic and organic pollutants. The filter has at least one electrically charged emission electrode for producing electrically conductive particles, and at least one passive electrode for collecting the pollutant particles that are in movement in the electric field between the emission electrode and the passive electrode. In accordance with the invention, an extra layer having denaturing properties is placed in the flow path of the pollutant particles that are to be precipitated. This layer is preferably composed of strongly acidic and strongly alkaline layers, or vice versa, with a neutral intermediate layer between layers of different pH values in each case. Microorganisms, such as bacteria, fungi, spores and/or allergens which move in the electric field of the ionization filter are simultaneously destroyed by this denaturing property. Excerpt(s): This application is the national stage of International Application No. PCT/DE98/01599, filed Jun. 12, 1998. The invention concerns an ionization filter for purifying air that is enriched with dust particles and other organic and inorganic pollutants, with at least one electrically charged emission electrode that is used to produce electrically conductive parts, and at least one passive electrode that is used to collect the pollutant particles which circulate between the emission electrode and the passive electrode. In situations of high dust precipitation, such ionization filters, which so far are being utilized especially for the precipitation of dust from the smoke gas of fossil-fired plants, distinguish themselves by their low flow resistance towards smoke gas, which passes the electrodes and is purified. Beyond that, such electrostatic filters undergo very little wear and tear, and therefore need repairs only to a limited extent due their simple design, excluding movable parts. Web site: http://www.delphion.com/details?pn=US06375721__

•

Method and apparatus for reducing air borne allergens in evaporative air coolers Inventor(s): Schmoldt; Hans Karl (124 N. 22nd Ct., Grand Junction, CO 81501) Assignee(s): none reported Patent Number: 6,609,386 Date filed: June 4, 2002 Abstract: The invention relates to a method and apparatus for reducing air borne allergens in evaporative air coolers. In another aspect the invention relates to a method for reducing the cost of operating evaporative air coolers.

Patents 151

Excerpt(s): Evaporative air coolers have been produced and used for more than 50 years. They are devices that use the heat of vaporization of water to cool the air. Such devices have been used around the world and are relatively inexpensive to build and operate compared to refrigeration air conditioning systems. However, it is well established that while refrigeration air conditioning systems are the preferred method to cool homes and businesses, they are expensive to purchase, install and operate. Further, in refrigeration air conditioning systems the air can be filtered using sophisticated filters, such as electrostatic filters, to remove dust, pollen and germs, etc. Also, these systems dehumidify the air, so they are useful in all climates. On the other hand, evaporative air coolers add water vapor or moisture to the air in order to cool it. They are most useful in desert or dry climates where the additional water vapor added to the air to cool it does not raise the relative humidity in the area being cooled to an uncomfortable level. Also, they are used where the cost to purchase, install and operate an air conditioning system is an important consideration. Filter systems mentioned above are not generally used in evaporative air coolers due at least in part to the added expense for purchase and installation of such filters. For many years, evaporative air coolers have been constructed from metal and as a result over time they will rust and have to be replaced. In more recent times, a device was placed in the water bath compartment of the evaporative air cooler to act as a sacrificial anode. These devices were usually a small zinc plate or a magnesium rod with a wire attached to the zinc plate or the magnesium rod. The end of the wire not attached to the zinc plate or the magnesium was then attached to the metal housing of the evaporative air cooler with a sheet metal screw. In the last several years, the housings of evaporative air coolers have been constructed from non-metallic materials and thus are immune to the past problems of the housing rusting out. Since the housing is not subject to rusting and the non-metallic housing eliminates the electrolytic action necessary for the zinc plate or the magnesium rod to function as a sacrificial anode, sacrificial anodes have not been used in evaporative air coolers having a non-metallic water bath compartment. Web site: http://www.delphion.com/details?pn=US06609386__ •

Method for denaturing allergens Inventor(s): Inui; Keiichiro (Matsubara, JP), Mikame; Mariko (Tsu, JP) Assignee(s): Shinto Fine Co., Ltd. (Osaka, JP), Sumitomo Chemical Co., Ltd. (Osaka, JP) Patent Number: 6,706,272 Date filed: March 6, 2001 Abstract: A method for denaturing allergens with an effective amount of a rare earth metal salt. Excerpt(s): This invention relates to a method for denaturing allergens in the environment. A lot of people suffered from allergic diseases like asthma, atopic dermatitis and so on for long years. Mainly house dust mites that live in the house, hair of pets and various kinds of pollens can be the substances that cause these allergic diseases. Recently, treatments that use medicines are applied to allergic patients. On the other hands, removing allergens those cause allergic disease from the environment where allergic patients live is also a useful method that protects from the exposure of allergens. It is reported in Japan, Europe and the United States of America that removing allergens can improve condition of patients. Cleaning using a vacuum cleaner or an air conditioner and the use of high-density cover on the bedclothes are applied for removing allergens. However, a vacuum cleaner cannot remove all of the allergens that

152

Allergens

exist in the house, and an air conditioner can remove allergens that exist only in the atmosphere. Further, high-density cover merely protects allergens inside of bedclothes and is not useful for the allergens that come from the environment. Therefore, these methods are not fully satisfied. Web site: http://www.delphion.com/details?pn=US06706272__ •

Method for the visual detection of specific antibodies in human serum by the use of lateral flow assays Inventor(s): Ford; Glen M (Gaithersburg, MD), Hubscher; Thomas T. (Gaithersburg, MD), Ruppenthal; Teri M (Hedgesville, WV) Assignee(s): Dexall Biomedical Labs, Inc. (Gaithersburg, MD) Patent Number: 6,528,325 Date filed: October 13, 2000 Abstract: This invention discloses a method and composition for detecting the presence of class specific antibodies reactive with analytes such as bacteria, allergens, autoimmune antigens, viral proteins, and carbohydrates by lateral flow techniques. In one embodiment of the invention, a test sample obtained from bodily fluids reacts with a gold labeled antigen. The resulting complex travels across the membrane, and along the lateral flow strip. Red colored lines formed in specific locations along the test strip indicate the presence of class specific antibodies in the test specimen. In another embodiment of the invention, the lateral flow assay serves as an immunochromatographic screening test for the detection of allergen-specific IgE antibodies in human serum. Test sample reacts with gold labeled anti-IgE antibody. The resulting complex travels across the membrane where immobilized allergens capture the allergen specific IgE complex. Colored lines are formed in the test areas to indicate the presence of allergen-specific IgE antibodies. Excerpt(s): The present invention discloses a method and composition for detecting the presence of antibodies in human or animal bodily fluids (blood, serum, plasma, urine, colostrum, milk, tears, or saliva) to analytes such as bacteria, Chlamydiae, Rickettsiae, protozoa, allergens, autoimmune antigens, viral proteins, and carbohydrates by lateral flow techniques. c) Bibulous material (the lateral flow strip) having immobilized specific binding members (analytes) capable of reacting with antigens or antibodies. f) A strip of bibulous material in contact with the sample well material and the lateral flow strip and containing a dried colored solid phase reagent, the solid phase coated with proteins or haptens. Web site: http://www.delphion.com/details?pn=US06528325__

•

Method of forming a textile article Inventor(s): Law; John Richard Dudley (Alderley Edge, GB) Assignee(s): Richard Hudson and Sons Limited (Burnley, GB) Patent Number: 6,256,816 Date filed: February 26, 1998 Abstract: A method of forming a textile article and the resultant article has contained filling preventing penetration by allergens. A continuous rectilinear strip of air

Patents 153

permeable material has parallel side edges and terminates at an edge transverse to the parallel side edges at substantial right angles to the parallel side edges. This continuous rectilinear strip of air permeable material is non-permeable to allergens. The continuous rectilinear strip of air permeable material is folded back upon itself at a fold such that at least the parallel side edges overlie one another and the edge transverse to the parallel side edges spans the continuous rectilinear strip of air permeable material between the parallel side edges. The continuous rectilinear strip underlying the edge transverse to the parallel side edges of air permeable material is cut to form the textile article having a fold and three pairs of overlying edges. Welding occurs along at least two of the three pairs of overlying edges one to another along welds to form the textile article closed on one side at the fold, closed on two sides at the welds, and having an opening between two overlying sides. Filling material is introduced into the textile article at the opening followed by welding of the opening closed. A textile article is formed with three welded sides and a fold for allergen free containment of the filling material therein. Excerpt(s): This invention relates to a method of forming a textile article and more particularly to a method of forming a textile article comprising a cover which encloses a filling material. The invention also relates to a textile article made according to the method. Conventionally when forming textile articles, especially those which have filling material with an external cover, it is usual for the material from which the article is to be made to be cut to size, folded or otherwise arranged whereby adjacent edges can be secured together by stitching to form a complete enclosure. Conventionally, if filling material is to be included in the enclosure, this is either introduced into the article prior to the securing of at least one of the edges or alternatively a zip fastener or other releasable fastener can be introduced into one edge of the article to allow the filling to be inserted after the edges have been secured together. Whilst such methods are acceptable for the production of textile articles, the introduction of stitching or other means of securing the edges together can produce an article in which the edges are not adequately sealed insofar as the stitching or other means of securing may not be capable or preventing the passage of matter, for example allergens, through the edges into The body of the article. A particular problem of this kind exists if the passage of dust mite material through the edges is permitted as such material can give rise to allergic symptoms in some people. Web site: http://www.delphion.com/details?pn=US06256816__ •

Methods for controlling dust mites and the allergens produced by dust mites Inventor(s): Bogart; Robert (River Vale, NJ), Suh; Janette (New Milford, NJ), Vaccaro; Laura (Montclair, NJ) Assignee(s): Reckitt Benckiser Inc. (Wayne, NJ) Patent Number: 6,428,801 Date filed: May 31, 2000 Abstract: Alcohol based aerosol spray compositions which contain 1-20% of an alcoholsoluble polymer which, on evaporation, leaves on a sprayed surface a film which acts as a barrier to dust, dust mites and their faecal excretions. These compositions optionally can include an acaricidal ingredient, such as benzyl benzoate, and one or more antimicrobial ingredients such as a quaternary ammonium salt. Excerpt(s): This invention relates to alcohol-based disinfectant compositions containing one or more additional ingredients which form a barrier against dust particles and

154

Allergens

particularly dust mites and their allergens. More specifically, the invention relates to aerosol spray disinfectants suitable for indoor use which, in addition to having the usual antimicrobial properties, are also effective in preventing people from coming in contact with allergens found in dust, notably dust mite allergens. The invention also provides methods for effectively controlling dust mites and their allergens and for significantly reducing their attendant adverse reactions. Common house dust is an important cause of asthma, rhinitis, atopic dermatitis, eczema and other allergic conditions in sensitive individuals. Household dust generally comprises a variety of particulate matter including pollen, dust mites, dust mite allergens, dirt, skin cells, animal dander, insect parts, pillow feathers, food particles and mould spores. The particular constituents of dust will depend on location within the house, whether pets are present and other obvious factors. One of the principal sources of allergies is dust mites, which inhabit rugs, carpets, and other fabric surfaces, particularly sofas, mattresses, pillows, upholstered chairs and the like. The mite Dermatophygoides pteronyssinus has been identified as a major source of house dust allergen. This mite and the related mites D. farinae, D. microceras and Euroglyphus maynei are the predominant house dust mites in temperate climates in North America, Europe, Australia and other areas. Dust mites are not insects, but are eight-legged arachnids, relatives to ticks and spiders. They live in close association with humans (or other mammals), their main food source being the shed scales from skin. Adult mites are approximately 300 microns (3/10 mm) in size, having developed over approximately 25 days through egg, larval and nymph stages. Adults live for 2 to 31/2 months, during which time each female can produce about 2040 eggs. Dust mites are photophobic, living deep in pillows, mattresses, carpets, upholstered furniture and other soft materials. Web site: http://www.delphion.com/details?pn=US06428801__ •

Methods to block IGE binding to cell surface receptors of mast cells Inventor(s): Caplan; Michael (Woodbridge, CT), Sosin; Howard (Fairfield, CT) Assignee(s): Panacea Pharmaceuticals, LLC (Fairfield, CT) Patent Number: 6,299,875 Date filed: June 4, 1998 Abstract: Compositions are administered to block IgE binding to receptors and ultimately displace native IgE from mast cells and related cell types, to prevent the activation of these cells during an allergic response. The compositions consist of a pharmaceutically acceptable carrier for systemic or local administration and an amount of compound binding specifically to the Fc.epsilon.RI IgE binding sites, and more preferably, Fc.epsilon.RI and Fc.epsilon.RII IgE binding sites, to prevent activation and degranulation of mast cells in response to exposure to allergens. The compounds can consist of IgE molecules and fragments and modifications thereof, such as IgE fragments, humanized or single chain IgE antibodies or fragments thereof, IgE with a modified Fab, non-crosslinkable IgE, or peptidomimetics which bind to the same site on the receptor as the IgE, jointly referred to herein as "IgE fragments" unless otherwise stated. Excerpt(s): The symptoms of allergy in humans and animals are primarily attributable to the release of histamine and a large variety of other bioactive compounds from mast cells and related cell types. The mast cell contains numerous secretary granules in which these substances are stored at extremely high concentrations. Activation of the mast cell results in the fusion of these granules with the cell surface membrane, leading to the

Patents 155

exocytosis of the granule contents and the concomitant induction of allergic symptoms. The plasma membrane of these cells are endowed with receptors for the Fc portion of the IgE (Fc.epsilon.RI). This receptor binds circulating IgE with very high affinity and retains it at the mast cell surface for extended periods of time. Activation is accomplished through the binding of an allergen simultaneously to more than one polyvalent molecule of Fc.epsilon.RI-bound IgE. This "cross linking" of at least two surface-bound IgE molecules brings Fc.epsilon.RI proteins into close association with one another in the plane of the mast cell plasma membrane. Kinases associated with these receptors become activated as a result of this proximity, initiating the second messenger cascade which results in cell degranulation. At least one other class of receptors can bind to the Fc portion of IgE. The low affinity receptor for IgE, Fc.epsilon.RII (also known as CD23) is expressed on mast cells and related cell types, B cells, and subsets of antigen presenting cells. It has been suggested that occupancy of Fc.epsilon.RII negatively regulates IgE synthesis. It is an object of the present invention to provide a means and method of preventing activation and degranulation of mast cells and related cell types in response to exposure to allergens. Web site: http://www.delphion.com/details?pn=US06299875__ •

Nutritional composition which contain non-digestible polysaccharides and use thereof to reduce transport through tight junctions Inventor(s): Bijlsma; Pieter Brandt (Amsterdam, NL), Groot; Jacques Alphons (Heiloo, NL), Kiliaan; Amanda Johanne (Wageningen, NL), Timmermans; Johannes Wilhelmus (Ede, NL), Van Der Meulen; Jan (Dronten, NL), Van Laere; Katrien Maria Jozefa (Heteren, NL) Assignee(s): N. V. Nutricia (Zoetermeer, NL) Patent Number: 6,730,661 Date filed: July 16, 2002 Abstract: The present invention relates to the use of one or more non-digestible polysaccharides selected from the group consisting of dextrans having a molecular weight of 8 kD to 40,000 kD, hydrolysed (gluco)mannans having a molecular weight of 0.5 kD to 1,000 kD and hydrolysed (galacto) mannans having a molecular weigth of 0.5 kD to 1,000 kD for the preparation of a nutritional composition to reduce the uptake of high molecular weight substances, allergens and microorganisms through the intestinal wall, more particularly to reduce transport of high molecular weight substances, allergens and microorganisms through the tight junctions in the intestines, the rise in the viscosity of the nutritional composition caused by the polysaccharides being less than 20 mPa.s. The nutritional compositions can be used to prevent or to treat allergy, allergic reactions, sepsis and inflammatory processes, such as can arise under emotional and physical stress, ischaemia, reperfusion damage during and after operations, after radiation treatment and/or chemotherapy of cancer patients and in the case of inflammatory diseases of the intestine, diarrhoea and allergies. Excerpt(s): The present invention relates to nutritional compositions which contain a specific class of non-digestible dextrans, hydrolysed (galacto)mannans and/or hydrolysed (gluco)mannans. These compositions reduce the uptake of high molecular weight substances, allergens and microorganisms through the intestinal wall. In particular, the present invention relates to reduction of the free transport of such substances through the tight junctions (TJ) of the intestines, without the transport of low molecular weight substances, such as nutrients, via the intestinal epithelium being

156

Allergens

impeded. The compositions can be used to prevent the increased permeability of the intestinal wall, resulting from various causes, and the penetration of toxins, antigens and pathogenic microorganisms present in the lumen which is caused as a result. The structure and function of tight junctions is described, inter alia, in Ann. Rev. Physiol. 60, 121-160 (1998) and in Ballard T. S. et al., Annu.Rev.Nutr., 1995, 15:35-55. Tight junctions do not form a rigid barrier but play an important role in the diffusion through the intestinal epithelium from lumen to bloodstream and vice versa. The permeability of the tight junctions is highly regulated and can be disturbed by illness and certain toxins in the lumen. Regulation takes place from the nervous system, the hormonal system and the immune system. When the tight junctions open, substances which have a high molecular weight, allergens and even microorganisms will pass through the tight junctions. The translocation of substances having a high molecular weight can under certain circumstances give rise to sensitisation of the immune system and result in allergic reactions on subsequent exposure. Translocation of pathogenic microorganisms imposes greater strain on the immune system and can make persons and animals ill, inter alia in periods of lowered resistance. The same applies, for example, in the case of bacterial toxins which have been able to pass through the epithelial layer and have been able to reach the bloodstream. Web site: http://www.delphion.com/details?pn=US06730661__ •

Nutritional compositions which contain slightly negatively charged, non-digestible polysaccharides and use thereof for reducing transport through tight junctions Inventor(s): Bijlsma; Pieter Brandt (Amsterdam, NL), Groot; Jacques Alphons (Heiloo, NL), Kiliaan; Amanda Johanna (Wageningen, NL), Timmermans; Johannes Wilhelmus (Ede, NL), Van Der Meulen; Jan (Dronten, NL) Assignee(s): N.V. Nutricia (Zoetermeer, NL) Patent Number: 6,686,341 Date filed: January 2, 2002 Abstract: A nutritional composition which contains slightly negatively charged nondigestible polysaccharides having a molecular weight of 8 kD to 40,000 kD, characterized in that the rise in the viscosity of the composition caused by the polysaccharides is less than 20 mpa.multidot.s. This nutritional composition is used to reduce the uptake of high molecular weight substances, allergens and microorganisms through the intestinal wall, more particularly to reduce transport of high molecular weight substances, allergens and microorganisms through the intestinal wall, ore particularly to reduce transport of high molecular weight substances, allergens and microorganisms through the tight junctions in the intestines. The nutritional compositions can be used to prevent or to treat allergies, allergic reactions, sepsis and inflammatory processes, such as those which can arise under emotional and physical stress, ischaemia, reperfusion damage during and after operations, following radiation treatment and/or chemotherapy of cancer patients and in the case of inflammatory intestinal diseases, diarrhoea and allergies. Excerpt(s): The present invention relates to nutritional compositions which contain certain classes of non-digestible polysaccharides. These compositions reduce the uptake of high molecular weight substances, allergens and microorganisms through the intestinal wall. In particular the present invention relates to reduction of the free transport of such substances through the tight junctions (TJs) of the intestines, without the transport of low molecular weight substances, such as nutrients, via the intestinal

Patents 157

epithelium being impeded. The compositions can be used to prevent the increased permeability of the intestinal wall, due to various causes, and the penetration, resulting therefrom, of toxins, antigens and pathogenic microorganisms present in the lumen. The structure and fraction of tight junctions is described, inter alia, in Ann. Rev. Physiol. 60, 121-160 (1998) and in Ballard T. S. et al., Annu.Rev.Nutr., 1995, 15:35-55. Tight junctions do not form a rigid barrier but play an important role in diffusion through the intestinal epithelium from lumen to bloodstream and vice versa. Web site: http://www.delphion.com/details?pn=US06686341__ •

Oral delivery of nucleic acid vaccines by particulate complexes Inventor(s): Huang; Shau-Ku (Towson, MD), Leong; Kam W. (Ellicot City, MD), Roy; Krishnendu (Baltimore, MD), Sampson; Hugh (Larchmont, NY) Assignee(s): The Johns Hopkins University (Baltimore, MD) Patent Number: 6,475,995 Date filed: January 15, 1999 Abstract: Nanoparticle coacervates of nucleic acids and polycations serve as effective vaccines when administered orally. They can induce immunity to a variety of disease causing agents and raise a protective response to allergens. Excerpt(s): This invention is related to the field of immunology and allergic diseases. In particular it relates to the area of food allergies. IgE is critical in the pathogenesis of various allergic diseases, including type I immediate hypersensitivity (1), and the bestcharacterized food-allergic responses involve IgE-mediated responses (2). A failure to develop, or a breakdown in, oral tolerance results in the production of food-specific IgE Abs. IgE Abs and allergens activate mast cells and basophils through the high affinity IgE receptor (Fce RI), and systemic anaphylactic reaction are provoked by histamine and other mediators released from activated mast cells and basophils (3). Numerous clinical and experimental animal studies have indicated the pivotal role of T cells and cytokines in the development of IgE-associated allergic diseases (4-5). In particular, a subset (Th2) of T cells, which has been distinguished functionally by its pattern of cytokine secretion, is thought to play a key role. Th2 cells are thought to promote allergic responses through their secretion of the cytokines,IL-4 and IL5, which promote IgE production and mast cell development, and eosinophilia, respectively. Cytokines released by the opposing pathway (Th1), such as IFN-.gamma., inhibit the development and expansion of Th2 cells and cytokine production. These studies demonstrate the importance of cytokines in the regulation of Th2 responses, and suggest potential therapeutic approaches to modify the development of IgE- and Th2-associated phenotypes. Food allergy (including allergic reactions to nuts, egg, milk, and seafood) is a major health problem because of the potential severity of allergic reactions, the nature of the allergic hypersensitivity, and the ubiquitous use of food products. Recent surveys in the US determined that food allergies are the most common single cause of anaphylaxis treated in hospital emergency departments (6, 7). In both reports, food-induced anaphylaxis accounted for about one-third of anaphylactic cases, with peanuts and tree nuts accounting for the majority of reactions to foods. It is believed that about 100 fatal cases of food-induced anaphylaxis occur in the US each year (8), that peanuts are one of the leading causes of food-allergic reactions (9, 10), and that peanuts and tree nuts together represent the leading cause of fatal and near-fatal food-induced anaphylaxis (6, 8, 11-12). Web site: http://www.delphion.com/details?pn=US06475995__

158

•

Allergens

Polymerized liposomes targeted to M cells and useful for oral or mucosal drug delivery Inventor(s): Chen; Hongming (Lansdale, PA), Langer; Robert S. (Newton, MA) Assignee(s): Massachusetts Institute of Technology (Cambridge, MA) Patent Number: 6,387,397 Date filed: June 2, 1999 Abstract: The present invention relates to targeted polymerized liposomes for oral and/or mucosal delivery of vaccines, allergens and therapeutics. In particular, the present invention relates to polymerized liposomes which have been modified on their surface to contain a molecule or ligand which targets the polymerized liposome to a specific site or cell type. More particularly, the invention relates to the use of polymerized liposomes modified to contain a carbohydrate or lectin on their surface. Excerpt(s): Drug delivery takes a variety of forms, depending on the agent to be delivered and the administration route. The most convenient way to administer drugs into the body is by oral administration. However, many drugs, in particular proteins and peptides, are poorly absorbed and unstable during passage through gastrointestinal (G-I) tract. The administration of these drugs is generally performed through parenteral injection. Although oral vaccination is more convenient, vaccines are generally given through injection. This is particularly true with killed or peptidic vaccines, because of their low absorbability and instability in the G-I tract. A problem with systemic immunization is that it may not effectively induce mucosal immune responses, particularly production of IgA, that are important as the first defense barrier to invaded microorganisms. For this reason, it would be beneficial to provide oral vaccination, if the problems of low absorbability and instability could be overcome. Web site: http://www.delphion.com/details?pn=US06387397__

•

Process for reducing protein allergens in latex products Inventor(s): Weinert; George W. (09 Cedar Point Dr., Pocasset, MA 02559) Assignee(s): none reported Patent Number: 6,740,719 Date filed: March 29, 2002 Abstract: Described is a process for reducing the antigenicity of sap and products made from the sap of the Hevea brasilisensis plant and other rubber plants. The process involves contacting sap or a latex rubber product with a mono or dialdehyde, a semialdehyde or any chemical containing an aldehyde group, to cross-link antigenic proteins within the sap or the latex product. The cross-linked proteins no longer have the capability to cause an allergic reaction to persons coming into contact with the latex products made by the process of the invention. The cross-linking reaction between the proteins in the latex sap and the aldehyde can take place in the solution used to the final product, or after the final latex product has been formed, or during various intermediate steps of the processes for forming the latex products. Excerpt(s): This invention relates to a process for reducing protein allergy caused by latex products, such as latex gloves and latex-containing devices used by the medical

Patents 159

profession, which are made from the latex sap of the Hevea brasilisensis tree. It is well known that latex products, such as latex gloves, condoms, catheters and automobile tires made from the sap of the Hevea brasilisensis tree cause allergic reactions to some individuals who come into contact with such products. The allergic reaction is caused by the water-soluble proteins present in the sap of the tree and in the product made therewith. In the late 1980s the United States Occupational Safety and Health Administration (OSHA) published Bloodborne Pathogen Standards requiring increased use of gloves to protect health care workers from exposure to the AIDS and hepatitis B viruses. Latex glove production substantially increased prior to and following the publication of such Standards. In 1991, the United States Food and Drug Administration (FDA) issued a latex alert regarding allergic reactions of patients and medical personnel who had come in contact with latex products. Among the latex products identified as potentially hazardous by the FDA were surgeon's gloves, latex exam gloves, latex condoms, barium enema retention rings and Foley catheters. The latex alert was issued after the number of annual cases regarding allergic reactions resulting from latex products increased from a few to 1,600. Of the three types of latex related diseases-dermatitis, cell mediated allergy and systemic allergy--which manifest themselves through different symptoms, cell mediated allergic response is a true allergic response, with reaction restricted to the area of contact between the glove and the skin when the glove is made from the sap of the Hevea brasilisensis tree. The reaction may include swelling and blistering and, after washing of the hands upon removal of the gloves, it takes from about 24 to 48 hours for the person's skin to return to normal. This allergy is caused by several water soluble proteins in latex sap. Web site: http://www.delphion.com/details?pn=US06740719__ •

Protein allergens of the species Cynodon dactylon Inventor(s): Knox; Robert Bruce (North Balwyn, AU), Singh; Mohan Bir (Templestowe, AU), Smith; Penelope (North Fitzroy, AU) Assignee(s): ImmuLogic Pharamaceutical Corp. (Waltham, MA) Patent Number: 6,214,358 Date filed: May 15, 1995 Abstract: The present invention provides nucleic acid sequences coding Cyn d I, or at least one fragment thereof or the functional equivalent of such nucleic acid sequences. The present invention also provides expression vectors comprising such nucleic acid sequences and host cells transformed therewith. The present invention further provides isolated Bermuda grass pollen protein allergen Cyn d I or fragments thereof. Isolated Bermuda grass pollen protein allergens or antigenic or allergenic fragments thereof are useful for diagnosing and treating sensitivity in an individual to Bermuda grass pollen allergens. Excerpt(s): Bermuda grass (Cynodon dactylon) is an important source of pollen allergens in many areas of the world, especially in tropical and sub-tropical climates. These allergens have been studied by a number of means including IgE immunoblotting (Ford D., and Baldo, B. A. J. Allergy Clin. Immunol. 79: 711-720 (1987); Shen H. D., et al., Clin. Allergy 18: 401-409 (1988), column chromatography (Orren, A., and Dowdle, S. Afr. Med. J. 51: 586 (1977); Matthiesen et al., J. Allergy Clin. Immunol. 81: 266 (Ab) (1988)), and immunoelectrophoresis (Matthiesen et al., supra, 1988). The major allergen of Bermuda grass pollen allergen has been identified as a protein with a molecular weight (MW) in the range of 30-34 kD, binding IgE from sera of more than 76% of

160

Allergens

individuals allergic to Bermuda grass (Ford and Baldo, (1987) Supra; Shen et al, (1988) Supra, and has been designated Cyn d I (Kahn and Marsh, (1986) Mol. Immunol., 23:1281-1288; Marsh et al., (1988) Ann. Allergy, 60:499-504, Matthiesen et al, 1988, Supra). Cyn d I is a member of the Group I family of allergens (Kahn and Marsh, (1986) Supra, found in many taxonomically related grasses including ryegrass (Lol p I), Kentucky bluegrass (Poa p I) and Timothy grass (Phl p I) (Standring et al, 1987 Int. Archs Allergy Appl. Immun., 83, 96-103; Esch and Klapper, (1987) J. Allergy Clin. Immunol., 79:489-495; Matthiesen and Lowenstein (1991) Clin. Exp. Allergy, 21, 309-320. However, the allergens of Bermuda grass show limited antibody cross-reactivity with those of other grasses (March et al., Supra, Berstein et al. (1976) J. Allergy Clin. Immunol., 57:141-152. A number of studies have shown that Cyn d I differs from the Group I homologues of closely related grasses (Matthiesen and Lowenstein, (1991) Supra. The sequence of the first 27 amino acids at the N-terminus of Cyn d I has been determined. (Matthiesen et al, 1988, Supra; Matthiesen et al, (1990) Epitopes of Atopic Allergens, Brussels, UCB Institute of Allergy, 9-13; Singh et al, Monographs in Allergy, (1990), 28:101-120; Matthiesen and Lowenstein, (1991), supra). The presence of Bermuda grass pollen allergens in the environment causes hayfever and seasonal asthma in many individuals and continues to have significant socioeconomic impact on Western communities. While the available spectrum of drugs, including anti-histamines and steroids, have resulted in improvement in the treatment of allergic disease, they do have unfortunate side-effects associated with long term usage. Because of these problems, renewed interest has been shown in the immunotherapy of allergic disease. Immunotherapy involves the injection of potent allergen extracts to desensitize patients against allergic reactions (Bousquet, J. and Michel, F. B., (1989) Allergy and Clin Immol. News 1: 7-10. Unfortunately, the pollen preparations used as allergens are polyvalent and of poor quality. Consequently, crude extracts are frequently used at high concentrations and may trigger potentially lethal systemic reactions, including anaphylaxis. The product expressed from the cloned gene, fragments thereof, or synthetic peptides based on the sequence of the allergens provide a safer medium for therapy since they can be quality controlled, characterized and standardized, and they optimally do not bind IgE. Web site: http://www.delphion.com/details?pn=US06214358__ •

Ryegrass pollen allergen Inventor(s): Avjioglu; Asil (Doncaster, AU), Hough; Terryn (Mordialloc, AU), Knox; Robert Bruce (North Balwyn, AU), Singh; Mohan Bir (Templestowe, AU), Smith; Penelope (North Fitzroy, AU), Theerakulpisut; Piyada (Khon Kaen, TH) Assignee(s): University of Melbourne (Victoria, AU) Patent Number: 6,180,368 Date filed: March 31, 1995 Abstract: The present invention provides a nucleic acid sequences coding for the ryegrass pollen allergens Lol pIa and Lol pIb, purified Lol pIa and Lol pIb protein and fragments thereof, methods of producing recombinant Lol pIa and Lol pIb or at least one fragment thereof or derivative or homologue thereof, and methods of using the nucleic acid sequences, proteins and peptides of the invention. Excerpt(s): The present invention relates to the major allergenic protein Lol pIb from pollen of ryegrass, Lolium perenne L. and to derivatives and homologues thereof and to allergenic proteins immunologically related thereto. The present invention is also

Patents 161

directed to recombinant Lol pIa and Lol pIb and their drivatives and to expression vectors capable of directing synthesis of same. Even more particularly, the present invention is directed to cDNA separately encoding Lol pIa and Lol pIb and to expression vectors comprising same. Allergens constitute the most abundant proteins of grass pollen, which is the major cause of allergic disease in temperate climates (Marsh (1975) Allergens and the genetics of allergy; in M. Sela (ed), The Antigens, Vol. 3, pp 271-359, Academic Press Inc., London, New York)., Hill et al. (1979) Medical Journal of Australia 1, 426-429). The first descriptions of the allergenic proteins in ryegrass showed that they are immunochemically distinct, and are known as groups I, II, III and IV (Johnson and March (1965) Nature, 206, 935-937; and Johnson and Marsh (1966) Immunochemistry 3, 91-100). Using the International Union of Immunological Societies' (IUIS) nomenclature, these allergens are designated Lol pI, Lol pII, Lol pIII and Lol pIV. These four proteins have been identified in pollen ryegrass, Lolium perenne L., which act as antigens in triggering immediate (Type 1) hypersensitivity in susceptible humans. Web site: http://www.delphion.com/details?pn=US06180368__ •

Stabilization of hypoallergenic, hyperdigestible previously reduced proteins Inventor(s): Buchanan; Bob B. (Berkeley, CA), del Val; Gregorio (San Diego, CA), Frick; Oscar L. (San Francisco, CA), Morigasaki; Susumu (Berkeley, CA) Assignee(s): The Regents of the University of California (Berkeley, CA) Patent Number: 6,677,433 Date filed: February 7, 2001 Abstract: Disulfide proteins showed mitigated allergenicity and increased digestibility by pepsin following reduction by thioredoxin. The sulfhydryl groups newly formed on reduction by thioredoxin (at 4.degree. C.) or dithiothreitol (DTT) (at 55.degree. C.) were blocked with a physiological disulfide, such as cystamine or oxidized glutathione (GSSG) to obtain stable forms of the disarmed allergen. When derivatized with cystamine, BLG was separated from its oxidized and reduced forms on non-reducing SDS-PAGE and appeared to lack sulfhydryl groups. Although less effective GSSG, gave similar results. Allergenicity of the two derivatives was compared with that of the oxidized, reduced and reoxidized forms of BLG by skin testing dogs from a colony sensitized to cow's milk. Both the cystamine and GSSG derivatized BLG showed decreased allergenicity and increased sensitivity to pepsin as compared to controls. The reoxidized form resembled the derivatives in having lower allergenicity. The thioredoxin- and DTT-reduced forms showed hypoallergenic, hyperdigestible properties, most effectively when the reduced proteins were heated at 55.degree. C. Whole milk subjected to these procedures showed results similar to those obtained with pure BLG. Other proteins are similarly stabilized. Stable forms of such disarmed, hypoallergenic and hyperdigestible disulfide protein allergens or just hypoallergenic or just hyperdigestible protein allergens are useful in foods as well as clinical preparations. Excerpt(s): The present invention relates to the use of thiol redox proteins to reduce seed proteins such as cereal proteins, and to reduce enzyme inhibitor proteins, venom toxin proteins, pollen proteins and the intramolecular disulfide bonds of certain other proteins. More particularly, the invention involves use of thioredoxin and glutaredoxin to reduce gliadins, glutenins, albumins and globulins to improve the characteristics of dough and baked goods and create new doughs and to reduce cystine containing proteins such as amylase and trypsin inhibitors so as to improve the quality of feed and cereal products. Additionally, the invention involves the isolation of a novel protein that

162

Allergens

inhibits pullulanase and the reduction of that novel protein by thiol redox proteins. The invention further involves the reduction by thioredoxin of 2S albumin proteins characteristic of oil-storing seeds. Also, the invention involves inactivating snake neurotoxins and certain insect and scorpion venom toxins in vitro and treating the corresponding toxicities in individuals. The invention also involves using thioredoxin and dithiothreitol to decrease the allergenicity of food and pollen allergens and to increase the proteolysis of food and pollen proteins and the digestibility of food and pollens. The invention also relates to pollen proteins which are reduced by lipoic acid or by reduced thiol-redox proteins or by thioredoxin in combination with lipoic acid for use in immunotherapy. The invention further involves use of thiol-redox proteins and lipoic acid to treat and prevent allergies and allergic symptoms. Also the invention relates to the stabilization by physiological disulfides such as cystamine and oxidized glutathione of previously reduced proteins for purposes of mitigating allergenicity and increasing pepsin digestibility of the proteins. Thioredoxin h is also known to reductively activate cytosolic enzyme of carbohydrate metabolism, pyrophosphate fructose-6-P, 1-phosphotransferase or PFP (Kiss, F. et al. (1991), Arch. Biochem. Biophys. 287:337-340). Cereal seeds such as wheat, rye, barley, corn, millet, sorghum and rice contain four major seed protein groups. These four groups are the albumins, globulins, gliadins and the glutenins or corresponding proteins. The thionins belong to the albumin group or faction. Presently, wheat and rye are the only two cereals from which gluten or dough has been formed. Gluten is a tenacious elastic and rubbery protein complex that gives cohesiveness to dough. Gluten is composed mostly of the gliadin and glutenin proteins. It is formed when rye or wheat dough is washed with water. It is the gluten that gives bread dough its elastic type quality. Flour from other major crop cereals barley, corn, sorghum, oat, millet and rice and also from the plant, soybean do not yield a gluten-like network under the conditions used for wheat and rye. Web site: http://www.delphion.com/details?pn=US06677433__ •

T cell epitopes of the major allergens from dermatophagoides (house dust mite) Inventor(s): Chen; Xian (North Chelmsford, MA), Evans; Sean (Acton, MA), Franzen; Henry M. (Watertown, MA), Garman; Richard D. (Arlington, MA), Greenstein; Julia L. (West Newton, MA), Kuo; Mei-chang (Winchester, MA), Rogers; Bruce L. (Belmont, MA), Shaked; Ze'ev (Berkeley, CA) Assignee(s): ImmuLogic Pharmaceutical Corporation (Waltham, MA) Patent Number: 6,268,491 Date filed: June 7, 1995 Abstract: The present invention provides isolated peptides of the major protein allergens of the genus Dermatophagoides. Peptides within the scope of the invention comprises at least one T cell epitope, or preferably at least two T cell epitopes of a protein allergen selected from the allergens Der p I, Der p II, Der f I, or Der f II. The invention also pertains to modified peptides having similar or enhanced therapeutic properties as the corresponding, naturally-occurring allergen or portion thereof, but having reduced side effects. The invention further provides nucleic acid sequences coding for peptides of the invention. Methods of treatment or of diagnosis of sensitivity to house dust mites in an individual and therapeutic compositions comprising one or more peptides of the invention are also provided. Excerpt(s): Recent reports have documented the importance of responses to the Group I (e.g., Der p I and Der f I) and Group II (e.g., Der p II and Der f II) protein allergens in

Patents 163

house dust mite allergy. For example, it has been documented that over 60% of patients have at least 50% of their anti-mite antibodies directed towards these proteins (e.g., Lind, P. et al., Allergy, 39:259-274 (1984); van der Zee, J. S. et al., Journal Allergy and Clinical Immunology, 81:884-896 (1988)). It is possible that children show a greater degree of reactivity to the Group I and Group II allergens (Thompson, P. J., et al., Immunology, 64:301-314 (1988)). Allergy to mites of the genus Dermatophagoides (D.) is associated with conditions such as asthma, rhinitis and ectopic dermatitis. Two species, D. pteronyssinus and D. farinae, predominate and, as a result, considerable effort has been expended in trying to identify the allergens produced by these two species. A concerted effort has been made to characterize by gene cloning the major allergens from both D. pteronyssinus and D. farinae. Consequently, several publications have reported the complete nucleotide sequences of several allergens including Der p I (Thomas, W. R., et al., International Archives of Allergy and Applied Immunology, 85:127-129 (1988); and Chua, K. Y., et al., Journal of Experimental Medicine, 167:175-182 (1988)), Der p II (Chua, K. Y., et al., International Archives of Allergy and Applied Immunology, 91:118123 (1990)), Der f I (Dilworth, R. J., et al., Clinical and Experimental Allergy, 21:25-32 (1891)), Der f II (Yuuki, T., et al., Japan Journal Allergol., 39:557-461 (1990); and Trudinger, M., et al., Clinical and Experimental Allergy, 21:33-37 (1991)) and a low molecular weight allergen (Ovey, E. R., et al., Journal of Experimental Medicine, 170:1457-1462 (1989)). The published nucleotide sequences of cDNAs encoding Der p I and Der f I demonstrate that these two proteins are highly homologous at the amino acid level (81% identity) and that the mature protein products are comprised of 222 and 223 residues, respectively (Chua, K. Y., et al., Journal of Experimental Medicine, 167:175182 (1988); and Dilworth, R. J., et al., supra)). The protein allergens Der p II and Der f II are both comprised of 129 residues, and are also highly homologous (88% identity) in amino acid sequence (Trudinger, M., et al. supra; Yuuki, T., et al. supra); Chua, K. Y., et al, International Archives of Allergy and Applied Immunology, 91:118-123 (1990)). Web site: http://www.delphion.com/details?pn=US06268491__ •

Tolerogenic fragments of natural allergens Inventor(s): Berrens; Lubertus (Utrecht, NL), Gallego Camara; Maria Teresa (Tres Cantos, ES), Gonzales Romano; Maria Leticia (Tres Cantos, ES) Assignee(s): C.B.F. Leti, S.A. (Tres Cantos, ES) Patent Number: 6,350,590 Date filed: June 23, 2000 Abstract: The present invention relates to a process for the controlled enzymatic cleavage of purified and depigmented active allergenic proteins from indoor and outdoor source materials, which process produces fragments of allergens that retain the the natural T-lymphocyte stimulating epitopes, but are depleted of IgE-binding B-cell epitopes and complement-activating agents. The invention also relates to the new pharmaceutical products. These allergen fragments do not exhibit the disadvantages of conventional allergenic extracts for immunotherapy and can be safely used to induce a state of specific T-cell anergy and immunological tolerance in allergic human beings. Excerpt(s): The present invention relates to a process for the controlled enzymatic cleavage of purified and depigmented active allergenic proteins from indoor and outdoor source materials, which process produces fragments of allergens that retain the natural T-lymphocyte stimulating epitopes, but are depleted of IgE-binding B-cell epitopes and complement-activating agents. The invention also relates to the new

164

Allergens

pharmaceutical products. These allergen fragments do not exhibit the disadvantages of conventional allergenic extracts for immunotherapy and can be safely used to induce a state of specific T-cell anergy and immunological tolerance in allergic human beings. Aqueous extracts of various environmental substrates, like house dust, the shed epithelial debris of animal skins, the pollen grains of grasses, weeds, trees, and several other materials are widely used for the in vivo and in vitro diagnosis of allergic diseases like bronchial asthma, vasomotor rhinitis and pollinosis in predisposed human, socalled "atopic" patients. Since the first clinical reports by Noon and Freeman in 1911, such extracts have also been applied for the treatment of atopic allergic diseases in a regimen of subcutaneous injections for the "desensitization", "hyposensitization", or "immunotherapy" of these ailments. Based on the observation that the causative and predominant allergenic components in the extracts comprise protein backbone structures in the molecular weight range of 10-70 kDa, it has become common practice in the manufacturing process of allergenic extracts to dialyse or ultrafilter the aqueous extracts through membranes of 10 kDa nominal cut-off in order to remove less relevant components with a molecular size lower than 10 kDa, thereby retaining the multivalent antigenic proteins in the range of 10-100 kDa in order to improve the quality of the allergenic extracts for clinical application. In some cases, a lower cut-off limit is chosen of 3 kDa or 5 kDa. According to current theory the exposure to environmental allergens in man causes the formation of allergen-specific antibodies of the IgG- and IgE-isotypes. Within an immunological context, allergens may therefore be regarded as ordinary IgGantibody inducing foreign antigens endowed with the ancillary property--either due to special molecular characteristics or to the simultaneous presence in allergenic extracts of appropriate modulators--to additionally promote the biosynthesis of antibodies of the IgE class. At one time, such antigens were therefore more appropriately called "atopic allergens" [1]. Genetically predisposed, socalled "atopic" human beings are particularly prone in this respect to respond with elevated levels of allergen-specific IgE antibodies. After the initial induction or "sensitization" phase, renewed contact with the allergen is considered to lead to the local formation of allergen--(IgE) antibody complexes being responsible for the ultimate disease symptoms. More particularly, it is the interaction of allergens with their specific IgE-class sessile antibodies bound to IgE-(e) receptors on cell membranes (i.e. of mast cells or basophilic leucocytes) which is thought to trigger the sequence of biochemical events eventually leading to the release of mediator substances responsible for the clinically manifest symptoms of allergy. In order to reduce the risk of anaphylactic side-reactions during immunotherapy a large number of approaches has been described. Recently, PCT/EP96/01733 was published (Nov. 7, 1996) disclosing a novel pharmaceutical composition for use in desensitisation therapy of allergy sufferers. This composition comprises tyrosine and a polymerised allergen. Other approaches were presented already in the early eighties but were found inadequate. GB-A-1,492,973 describes a coprecipitate of tyrosine and an allergen that has been modified by an agent causing intramolecular crosslinking. EP-A-0.367.306 describes a process of preparing polymerised allergens also providing crosslinking and purportedly resulting in reduced allergenicity. In yet another old publication EP-B0.038.154 which was published already in 1981 the treatment of an allergen with polysarcosine to reduce its allergenicity is described. In particular polysarcosine with a molecular weight of 2.000-12.000 is useful according to the publication. This document also refers to UK patent 1.282.163 describing an improved form of therapy wherein the allergenicity of an allergen is reduced by treatment with glutaraldehyde, which is suggested as retaining the ability to elicit blocking antibodies but exhibiting reduced allergenicity, thus rendering it more suitable for desensitisation therapy. An alternative approach was provided in UK patent no 1.578.348 wherein it is stated that allergenpolyethylene glycol conjugates are capable of eliciting the desired therapeutic effect of

Patents 165

suppressing allergen specific IgE production. These materials are stated as being non allergenic and non immunogenic. For the intended immunotherapy of allergic diseases by means of tolerogenic allergen fragments, the products of choice should be closely similar to the natural T-cell epitopes generated within socalled "antigen-presenting cells" (APCs) by acid hydrolases and other enzymes under physiological conditions. This particular approach has been taken in the prior art in U.S. Pat. No. 4,469,667 and European Patent EP 0113712 B1 (see also ref. 6 and 7). Such natural elements include possible peptide-bound haptenic chemical structures and may be imitated in the laboratory by subjecting the allergenic extract components to proteolytic cleavage under controlled conditions. One of the many routes of research in this field suggests that the treatment of allergy in man should be performed using allergen derivatives which do not induce specific IgE antibodies, i.e. allergen derivatives depleted of their socalled IgE-binding "B-cell epitopes". Web site: http://www.delphion.com/details?pn=US06350590__ •

Treatment of airborne allergens Inventor(s): Fox; Rodney Thomas (Cottingham, GB), Harper; Duncan Roger (Hull, GB), Harrison; Neale (Staffordshire, GB), Hughes; John Farrell (Southampton, GB), Whitmore; Lindsey Faye (Winchester, GB) Assignee(s): Reckitt Benckiser Limited (Slough, GB) Patent Number: 6,482,357 Date filed: June 8, 2001 Abstract: An improved method of denaturing or deactivating an airborne allergen comprising directing at the airborne source of the allergen liquid droplets from a spray device containing a liquid composition which includes an allergen denaturant or allergen deactivant, the improved method comprising imparting a unipolar charge to the said liquid droplets by double layer charging during the spraying of the liquid droplets by the spray device, the unipolar charge being at a level such that the said droplets have a charge to mass ratio of at leaset.+-.1.times.10.sup.-4 C/kg. Excerpt(s): The present invention relates to the treatment of airborne allergens. Various allergens are known which are transported through the air to trigger a human reaction. For example, it has been known for a long time that house dust can trigger allergenic reactions in humans, such as asthma and rhinitis. It was reported, as early as 1928 that it was the dust mites in the dust that were the primary source of the allergenic response, but it was only in the 1960's that researchers appreciated its significance. It is believed that the faeces of the house dust mite, Dermatophogoides farinae (known as Der-f) and Dermatophagoides pteronyssinus (known as Der-p) trigger the immune response of the body, thereby giving rise to well known allergenic symptoms. Web site: http://www.delphion.com/details?pn=US06482357__

166

Allergens

Patent Applications on Allergens 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 allergens: •

ALLERGEN BARRIER FABRICS Inventor(s): CARR, GREGORY DEWAYNE; (MOORE, SC), WOLYNES, EARLE; (SPARTANBURG, SC) Correspondence: Milliken & Company; 920 Milliken RD; PO Box 1926; Spartanburg; SC; 29304; US Patent Application Number: 20030129904 Date filed: November 13, 1999 Abstract: Fabrics having enhanced allergen barrier capabilities are described. The fabrics are woven and calendered, and desirably face finished to provide lightweight, thin fabrics having good aesthetic properties. The fabrics also have good moisture vapor transport characteristics and superior allergen barrier capabilities, and in particular, superior barrier capabilities for cat dander allergen (representing smaller allergen particle size), as well as dust mite allergen. Protective coverings made from the fabrics and methods for their production are also described. Excerpt(s): This invention generally relates to protective fabrics and covers. More specifically, the invention relates to protective fabrics which have enhanced allergen barrier capabilities, rendering them particularly useful as a barrier to allergens and the like. Many people suffer from allergies caused by airborne fine particulate matter such as pollen, dust, house dust mites and their fecal matter, animal and human dander, molds, inorganic dust, and the like. In fact, it has been found that the condition of many asthma sufferers can be exacerbated by, and in some cases even caused as a result of, exposure to common house dust and the dust mites that live in the dust. In addition, the problems associated with human allergies to animal dander are widely known; as a result, many individuals are unable to have dander-producing house pets. The house dust mite (Dermatophagoides pteronyssimus), which is a member of the spider family, measures about 0.3 mm across and to the naked eye, is indistinguishable from a speck of dust. It accounts for a large percentage of the mite population in samples taken from homes. Because the house dust mites require a moist environment and feed on such things as human skin, they are typically concentrated in high numbers in and around beds and bedding items. 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.

Patents 167

•

Allergen neutralization compositions Inventor(s): Hasan, Abul Khaer Mohamad Quamrul; (Kobe, JP), Kobayashi, Ryoko; (Kobe, JP), Mao, Mark Hsiang-Kuen; (Kobe, JP) Correspondence: The Procter & Gamble Company; Intellectual Property Division; Winton Hill Technical Center - Box 161; 6110 Center Hill Avenue; Cincinnati; OH; 45224; US Patent Application Number: 20030203035 Date filed: March 26, 2003 Abstract: Allergen neutralization compositions that retain at least about 30% of dust particles as measured by the Dust Control Test, and the compositions have an average MIU value of less than 3.4 as measured by the Friction Coefficient Analysis method. The compositions preferably contain a film forming polymer to control dust while maintaining a smooth feeling on the surface being treated. These allergen neutralization compositions are for use on inanimate objects, and are sprayable. Preferably these allergen neutralization compositions contain allergen denaturing compounds such as an effective amount of an allergy neutralizing metal ion, polyphenol compounds, hydrogen peroxide, salicylic acid, citric acid, lactic acid, glycolic acid, and mixtures of these. By controlling dust particles that contain allergenic proteins, these allergen neutralization compositions provide excellent efficacy against various allergens, and specifically, the allergens associated with house dust mites and other common allergens such as cat dander, pollen and the like. Excerpt(s): This is a continuation of International Application PCT/US00/27018, with an international filing date of Sep. 29, 2000, published in English. The present invention relates to aqueous allergen neutralizing compositions that control allergen containing dust particles while not leaving behind a sticky film on household surfaces. These compositions do not stain fabric materials and are effective for suppressing allergen compounds. The present compositions are particularly effective against the allergens associated with house dust mites and other common allergens such as cat dander, pollen and the like. Sensitivity to allergens is a problem for an increasing number of consumers. This issue has been complicated by a surprising increase in asthma over the past few years. Asthma sufferers are especially sensitive to airborne allergens. Allergy rates are also on the rise. This gives rise to increased awareness of the causes of allergy symptoms and how to decrease the associated discomfort. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Allergy lamp Inventor(s): Branham, John David; (Winnsboro, SC) Correspondence: John David Branham; 201 Sand Creek Drive; Winnsboro; SC; 29180; US Patent Application Number: 20040005251 Date filed: June 14, 2003 Abstract: This is an apparatus that disinfects room air by destroying common allergens such as mold spore, dust mites, microbes, and VOCs, as well as dangerous substances, both organic and inorganic. Using photocatalytic oxidation, it places a continuing supply of the oxygen radical hydroxyl into a local environment. This helps prevent the spread of infectious diseases by destroying infectious microbes, contained in the droplet

168

Allergens

nuclei of human and animal respiration, as they float in the air. This apparatus also removes carbon monoxide, radon and other contaminants from the air by turning them into such harmless substances as carbon dioxide and water. It uses little energy, needs no filters, and operates silently. Excerpt(s): This application claims the benefits of U.S. Provisional Application No. 60/390,222 filed Jun. 2, 2002, which is hereby incorporated by reference for all that is disclosed therein. Tens of millions of Americans suffer from respiratory allergies. The respiratory symptoms of asthma, which affects approximately 15 million Americans, are often provoked by airborne allergens (substances that cause an allergic reaction). Overall, allergic diseases are among the major causes of illness and disability in the United States. Common causes of allergic reactions are mold spores, mildew, bacteria, viruses, pet dander, volatile organic compounds (VOCs), and dust mites. Inorganic compounds also pose a problem. Airborne toxins injure many Americans each year. Carbon monoxide kills over 500 people each year and hospitalizes another 10,000. Carpets and furniture give off formaldehyde and other noxious substances. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Allergy test chamber Inventor(s): Horak, Friedrich; (Innemanzing, AT) Correspondence: Drinker Biddle & Reath; One Logan Square; 18th And Cherry Streets; Philadelphia; PA; 19103-6996; US Patent Application Number: 20040054262 Date filed: January 30, 2003 Abstract: The invention relates to an allergy test chamber comprising at least one inlet for supplying allergen-free air, especially fresh air, into the chamber. Said chamber is characterised in that the at least one inlet (23) for allergen-free air is provided with an air flow distribution device (26, 27), and in that the allergy test chamber (20) also comprises at least one inlet (25) for allergen test particles, such as plant pollen or mite faeces, and at least one outlet (24) for removing air loaded with allergen test particles from the chamber by means of suction. Said outlet (24) is arranged at a distance from the inlets (23, 25) for allergen-free air and allergen test particles. Said air movement principle i.e. introducing air into the chamber, mixing it with a defined quantity of allergens, and removing by suction the allergen-loaded air to another area of the chamber, enables uniformity of the distribution of the allergen particles in the test chamber to be significantly improved, compared with known allergy test chambers wherein allergenloaded air is circulated in the test chamber. Excerpt(s): The present invention relates to an allergy test chamber having at least one inlet for supplying allergen-free air, especially fresh air, into the chamber. Another problem is the consistent registration over a period of several days, as it can almost only be achieved by a subjective evaluation of symptoms. The reliability of documentation in diaries kept by patients declines with every day of the study. In order to obtain statistical material that can be used in studies for doses finding, effectiveness or duration of effect, a large number of patients and long periods of observation are necessary. However, a low amount of pollen and many other environmental factors may lead to unexpectedly insignificant results in field studies. Therefore it is necessary to find a solution for clinical experiments with patients suffering from allergies to pollen and house-dust mites which come close to field studies without having their disadvantages.

Patents 169

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

Alleviation of the allergenic potential of airborne and contact allergens by thioredoxin Inventor(s): Buchanan, Bob B.; (Berkeley, CA), Frick, Oscar L.; (San Francisco, CA), Lozano, Rosa M.; (Madrid, ES), Val, Gregorio del; (Wokingham, GB), Wong, Joshua H.; (South San Francisco, CA), Yee, Boihon C.; (Walnut Creek, CA) Correspondence: Michael R. Ward; Morrison & Foerster Llp; 425 Market Street; San Francisco; CA; 94105-2842; US Patent Application Number: 20040071738 Date filed: April 23, 2003 Abstract: Thioredoxin, a small dithiol protein, is a specific reductant for allergenic proteins and particularly allergenic proteins present in pollen and animal and plant sources. All targeted proteins contain disulfide (S--S) bonds that are reduced to the sulfhydryl (SH) level by thioredoxin. The proteins are allergenically active and less digestible in the oxidized (S--S) state. When reduced (SH state), they lose their allergenicity and/or become more digestible. Thioredoxin achieved this reduction when activated (reduced) either by NADPH via NADP-thioredoxin reductase (physiological conditions) or by lipoic acid chemical reductant. Skin tests carried out with sensitized dogs showed that treatment of the pollens with reduced thioredoxin prior to injection eliminated or decreased the allergenicity of the pollen. Studies showed increased digestion of the pollen proteins by pepsin following reduction by thioredoxin. Pollen proteins that have been reduced by thioredoxin are effective and safe immunotherapeutic agents for decreasing or eliminating an animal's allergic reaction that would otherwise occur upon exposure to the non-reduced pollen protein. Excerpt(s): This application is a continuation-in-part of application Ser. No. 08/953,703 filed Oct. 17, 1997, which is a continuation-in-part of application Ser. No. 08/326,976 filed Oct. 21, 1994, now U.S. Pat. No. 5,792,506 issued Aug. 11, 1998, which is a continuation-in-part of application Ser. No. 08/211,673, filed Apr. 12, 1994, which is a continuation-in-part of application Ser. No. 07/935,002, filed Aug. 25, 1992 (now abandoned), which is a continuation-in-part application of Ser. No. 07/776,109, filed Oct. 12, 1991 (now abandoned). The present invention relates to the use of thiol redox proteins to reduce seed proteins such as cereal proteins, and to reduce enzyme inhibitor proteins, venom toxin proteins, pollen proteins and the intramolecular disulfide bonds of certain other proteins. More particularly, the invention involves use of thioredoxin and glutaredoxin to reduce gliadins, glutenins, albumins and globulins to improve the characteristics of dough and baked goods and create new doughs and to reduce cystine containing proteins such as amylase and trypsin inhibitors so as to improve the quality of feed and cereal products. Additionally, the invention involves the isolation of a novel protein that inhibits pullulanase and the reduction of that novel protein by thiol redox proteins. The invention further involves the reduction by thioredoxin of 2S albumin proteins characteristic of oil-storing seeds. Also, the invention involves inactivating snake neurotoxins and certain insect and scorpion venom toxins in vitro and treating the corresponding toxicities in individuals. The invention also involves using thioredoxin to decrease the allergenicity of food and pollen allergens and to increase the proteolysis of food and pollen proteins and the digestibility of food and pollens. The invention also relates to pollen proteins which are reduced by lipoic acid or by reduced thiol-redox proteins or by thioredoxin in combination with lipoic acid for use in immunotherapy.

170

Allergens

The invention further involves use of thiolredox proteins and lipoic acid to treat and prevent allergies and allergic symptoms. This invention was made with government support under Grant Contract Nos. DCB 8825980 and DMB 88-15980 awarded by the National Science Foundation. The United States Government has certain rights in this invention. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Anti-allergic pharmaceutical composition containing at least one allergen and at least one antihistamine compound Inventor(s): Loria, Emile; (Toulouse, FR), Terrasse, Gaetan; (Saint-Valier, FR), Trehin, Yves; (Toulouse, FR) Correspondence: Gregory P. LA Pointe; Bachman & Lapointe, P.C.; Suite 1201; 900 Chapel Street; New Haven; CT; 06510-2802; US Patent Application Number: 20030104013 Date filed: May 29, 2001 Abstract: The present invention relates to an anti-allergic pharmaceutical composition containing at least two active agents chosen among: (i) one allergen, (ii) one antihistamine compound, (iii) one inhibitor of histamine synthesis, said active agents being associated in said composition with a pharmaceutically acceptable vehicle. Excerpt(s): The present invention relates to new pharmaceutical compositions for the prevention and treatment of allergies. Allergies are a scourge which affects 25% of the world's population. This number is on the increase in connection with growing environmental toxicity (dust, food, motor vehicles). In addition, a person's risk of suffering from allergy is increased if there is a previous family history of allergy. the terminal phase of the reaction is the release of histamine and serotonin having a recruiting effect on the Th2 clones. toxic and inflammatory self-maintaining reaction, even without any antigen stimulation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Benzimidazole compounds for regulating IgE Inventor(s): Campbell, Michael G.; (Durham, NC), Major, Michael W.; (Mequon, WI), Richards, Mark L.; (San Diego, CA), Sircar, Jagadish C.; (San Diego, CA) Correspondence: Knobbe Martens Olson & Bear Llp; 2040 Main Street; Fourteenth Floor; Irvine; CA; 92614; US Patent Application Number: 20030100582 Date filed: March 20, 2002 Abstract: This invention relates to a family of phenylbenzimidazole analogs, which are inhibitors of the IgE response to allergens. These compounds are useful in the treatment of allergy and/or asthma or any diseases where IgE is pathogenic. Excerpt(s): This application is a continuation-in-part application of pending U.S. application Ser. No. 09/422,304, filed on Oct. 21, 1999, which claims priority to U.S. application Ser. No. 09/316,870, filed on May 21, 1999, now U.S. Pat. No. 6,271,390, which claims priority under 35 U.S.C.sctn.119(e) to U.S. Provisional Application No.

Patents 171

60/086,494, filed on May 21, 1998, all herein incorporated by reference. This invention relates to small molecule inhibitors of the IgE response to allergens that are useful in the treatment of allergy and/or asthma or any diseases where IgE is pathogenic. An estimated 10 million persons in the United States have asthma, about 5% of the population. The estimated cost of asthma in the United States exceeds $6 billion. About 25% of patients with asthma who seek emergency care require hospitalization, and the largest single direct medical expenditure for asthma has been inpatient hospital services (emergency care), at a cost of greater than $1.6 billion. The cost for prescription medications, which increased 54% between 1985 and 1990, was close behind at $ 1.1 billion (Kelly, Pharmacotherapy 12:13 S-2 IS (1997)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Cleaners for the control and removal of allergens Inventor(s): Kistler, Annastacia; (Appleton, WI), Koenig, David William; (Manasha, WI), Schmidt, Richard John; (Roswell, GA), Williamson, Bruce Scott; (Alpharetta, GA) Correspondence: Senniger Powers Leavitt And Roedel; One Metropolitan Square; 16th Floor; ST Louis; MO; 63102; US Patent Application Number: 20040007251 Date filed: July 10, 2002 Abstract: Wet and dry wipes comprising additives for removing allergens from surfaces are disclosed. The wipe substrate comprises an additive capable and binding the allergen onto the substrate such that the allergen can be removed from the surface. Various allergens including animal and pet dander can be removed from numerous surfaces utilizing the wipes of the present invention. In some embodiments of the invention, the allergenicity of the allergen is also reduced. Suitable additives for immobilization onto the wipe substrate include lectins, proteases, and enzyme inhibitors. Excerpt(s): The present invention relates to cleaners for removing allergens from various surfaces including human and animal skin and hair. More specifically, the present invention relates to cleaners comprising a wipe, such as a wet or dry wipe, comprising an additive comprising a lectin, a protease, and/or an enzyme inhibitor capable of binding an allergen, such as animal dander, to the cleaner and removing it from a surface. Additionally, the additive may be capable of reducing the allergenicity of the allergen upon contacting the allergen. Allergens are substances that trigger allergic reactions in a host organism such as a human, and are typically small, acidic glycoproteins. Many allergens are members of a superfamily of extracellular proteins commonly referred to as lipocalins. Allergens such as animal dander and other animal secretions, such as saliva and urine, are commonplace in many households and businesses where animals and/or pets are present. Other allergens commonly found in the home include plant pollens, fungi allergens, cockroach allergens, and dust mite feces. These allergens are typically introduced into a host through direct inhalation of dust particles carrying the allergen into the nose and lungs, and can result in serious allergic reactions in the host such as perennial asthma, rhinitis, and conjunctivitis. Animal dander, such as cat or dog dander for example, is one of the most common allergens. Animal dander is not only the hair or fur of the animal, but includes minute skin scales that fall from the hair, feathers, and skin of all warm-blooded animals. Animal dander carries antigens that can cause allergic reactions in sensitive people. Typically, older animals produce more skin-scale type dander than young ones because

172

Allergens

their skin is drier. Animal dander is extremely light weight and tiny in size, and can stay airborne for extended periods of time increasing the risk of penetration into the lower airways of exposed hosts. One specific cat allergen, Felis domesticus allergen I, has been shown to cause significant allergic reactions in some individuals. This allergen is a glycoprotein found in the sebaceous glands of the cat's hair roots and in their sublingual salivary glands and in the urine of male cats. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Cleaning system for animal litter and bedding Inventor(s): Opfel, William; (Mesa, AZ) Correspondence: Kenneth C. Booth; Schmeiser, Olsen & Watts Llp; 18 East University Drive, #101; Mesa; AZ; 85201; US Patent Application Number: 20030192816 Date filed: April 9, 2003 Abstract: A cleaning system is disclosed for cleaning contaminants from animal litter. In a first embodiment of the invention, a vacuum and a blower are coupled together and configured so that the blower blows a first fluid stream into animal litter simultaneous with the vacuum drawing a second fluid stream from the animal litter. Relatively light contaminants are drawn into the vacuum while the relatively heavy animal litter is left behind. In a second embodiment of the invention, a cyclonic separator is used to draw the animal litter and the intermixed contaminants into the cyclonic separator simultaneously, and separate the animal litter from the contaminants. The animal litter is returned to the area from which it was removed. In a third embodiment of the invention, mechanical agitation is coupled with air separation to further enhance separation of contaminants from the animal litter. The embodiments of the invention have particular use in cleaning horse stalls to separate the horse bedding from the allergens which collect in the horse bedding over time and present health risks to the horse, and return the horse bedding for continued use. Embodiments of the invention prolong the usefulness of the horse bedding, promote a healthy environment for the horse, and reduce the overall maintenance and health care costs for the horse. Excerpt(s): This application is a continuation-in-part application of U.S. Utility patent application to William Opfel, Ser. No. 10/120,858, titled "ANIMAL LITTER AND METHODS OF FABRICATING SAME," filed on Apr. 10, 2002, and is a continuation-inpart application of U.S. Utility patent application Ser. No. 10/188,611, filed on Jul. 2, 2002, entitled "CLEANING SYSTEM FOR ANIMAL LITTER AND BEDDING" which claims priority to U.S. Provisional Patent Application Serial No. 60/371,783, filed on Apr. 10, 2002, entitled "CLEANING SYSTEM FOR ANIMAL LITTER". This application also claims priority to U.S. Provisional Patent Application Serial No. 60/431,106, filed on Dec. 4, 2002, entitled "CLEANING SYSTEM FOR ANIMAL LITTER AND BEDDING". This invention generally relates to a method and apparatus for cleaning animal litter for reuse, and more particularly to cleaning allergens, germs and other light-weight contaminants from animal litter and bedding. Animal bedding, also called animal litter in the small animal industry (collectively referred to herein as "bedding"), is a common hiding place for many allergens such as animal hair and fur, dander, dust mites, dust, dirt, protein from decomposing animal feces, and the like, and for germs such as bacteria, viruses and fungi, and the like. Allergens and germs can be a problem not only for the animal using the bedding, but for the care givers of the animal. Both the animal and the care giver may develop respiratory ailments and diseases, hair loss, rashes and

Patents 173

the like from common allergens and germs present in the animal bedding. Horse stalls are typically overwhelmed with as much as 15-30 gallons of urine and 10-50 pounds of manure per day, per animal. While much of the obvious animal waste can be removed directly from the horse bedding, portions of the animal waste, and the smaller allergens and germs can not. The present solution to the problem of allergens, germs and other contaminants is to remove the contaminated bedding and replace it with new bedding frequently. While this approach is effective, it can also be monetarily as well as environmentally expensive to dispose of the contaminated bedding materials, and to use new bedding in the stall frequently. Typically, bedding materials are replaced daily, weekly or monthly to remove the contaminants. There is presently no known system available for easily separating the contaminants from the bedding to enable the bedding to be reused without the contaminants. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Cloning and sequencing of the allergen Dac g5 of Dactylis glomerata pollen, its preparation and its use Inventor(s): Bonneau, Caroline; (Rouen, FR), Faye, Loic; (Saint-Jacques-sur-Darnetal, FR), Gomord, Veronique; (Rouen, FR), Van Oort, Erica; ( Vleuten, NL), Van Ree, Ronald; ( Amsterdam, NL) Correspondence: Schnader Harrison Segal & Lewis, Llp; 1600 Market Street; Suite 3600; Philadelphia; PA; 19103 Patent Application Number: 20030147880 Date filed: November 25, 2002 Abstract: A purified nucleic acid molecule comprising a nucleotide sequence coding for allergen Dac g5 havinge amino acid sequence SEQ ID NO. 2, a derivative or a fragment thereof. Excerpt(s): This is a continuation of International Application No. PCT/FR01/01666, with an international filing date of May 29, 2001, which is based on French Patent Application No. 00/06857, filed May 29, 2000. This invention relates to the cloning and sequencing of Dactylis glomerata pollen allergens, more particularly, the allergen Dac g5. The invention also relates to the production of the recombinant allergen for incorporation in preparations useful for the diagnosis or treatment of allergies. Allergens are the most abundant proteins of pollen and constitute the major cause of allergies in temperate regions. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Codon optimised recombinant dermaphagoides allergens Inventor(s): Bollen, Alex; (Gosselies, BE), Jacobs, Paul; (Brussels, BE), Jacquet, Alain; (Gosselies, BE), Massaer, Marc Georges Francis; (Brussels, BE) Correspondence: Smithkline Beecham Corporation; Corporate Intellectual Property-Us, Uw2220; P. O. Box 1539; King OF Prussia; PA; 19406-0939; US Patent Application Number: 20030138441 Date filed: December 9, 2002

174

Allergens

Abstract: The present invention relates to codon optimised polynucleotides which are efficiently expressed in mammalian cells and encode insect proteins from Dermaphagoids dust mite. In particular, the optimised codon polynucleotides encode a protein from Dermaphagoides pteronyssinus, such as DerP1 or proDerP1. The present invention also provides methods of preparing pharmaceutical compositions comprising the expression of the codon optimised polynucleotides, and vectors and transformed host cells comprising them. Excerpt(s): The present invention relates to codon optimised polynucleotides which are efficiently expressed in mammalian cells and encode insect proteins from Dermaphagoides dust mite. In particular, the optimised codon polynucleotides encode a protein from Dermaphagoides pteronyssinus, such as DerP1 or proDerP1. The present invention also provides methods of preparing pharmaceutical compositions comprising the expression of the codon optimised polynucleotides, and vectors and transformed host cells comprising them. The allergens from the house dust mite Dermatophagoides have long been recognised to be associated with allergic hypersensitivity reactions such as asthma [1]. Amongst these molecules, Der p 1 is an immunodominant allergen which elicits the strongest IgE-mediated immune response [2,3]. The cysteine proteinase activity of Der p 1 was shown to amplify its potent allergenicity [4,5]. The Der p 1 encoding cDNA sequence reveals that, like many mammalian and plant proteinases, Der p 1 is synthetised as an inactive preproenzyme of 320 amino acid residues which is subsequently processed into a 222-amino acid mature form [6,7]. The maturation of ProDer p 1 is not known to date but it is thought that the allergen is processed by the cleavage of the 80-residues proregion. Mature Der p 1 was successfully purified from the whole house dust mite culture but with weak overall yield [8]. Recombinant production of allergens represents an efficient way to obtain defined materials with high yields for a variety of experimental procedures such as immunological studies, diagnosis, treatment of IgE-mediated allergic disorders by immunotherapy and understanding structure-function relationships [9]. Previous attempts of Der p 1 expression in bacteria and yeast indicated that the allergen was poorly expressed and mainly under an insoluble form [10-12]. Moreover, recombinant Der p 1 produced in bacteria was shown to have weak IgE binding activity. The recombinant protein expressed in yeast was recognized by specific IgE at, however, a lower level than the natural protein. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Detection of allergen-associated materials Inventor(s): Bolbot, John Anthony; (Bedfordshire, GB), Setford, Steven John; (Bedfordshire, GB), White, Stephen Frederick; (Bedfordshire, GB) Correspondence: Sughrue Mion, Pllc; 2100 Pennsylvania Avenue, N.W.; Suite 800; Washington; DC; 20037; US Patent Application Number: 20040058454 Date filed: October 20, 2003 Abstract: Measurement of the redox properties of household dust is used to detect the presence of allergen-associated materials. Measurement may be electrochemical, preferably amperometric. A disposable electrode assembly may be made by screen printing with conductive (e.g. carbon and Ag/AgCl) inks. An absorbent pad overlying the electrodes can be used to wipe a surface to collect a sample. It may contain

Patents 175

electrolyte and buffer components, so that adding water carries sample in an electrolyte/buffer solution to the electrodes. Excerpt(s): The present invention relates to methods and apparatus for the detection of allergen-associated materials, particularly in an indoor environment. It is especially concerned to facilitate rapid, economical and simple detection which is suitable for domestic use. The incidence of allergic reactions to materials commonly encountered within the home environment is ever increasing. Common allergens include cat dander, dust mite faeces, cockroach detritus and the mould Aspergillus niger. A primary reason for this increase in allergies has been attributed to changes in lifestyle as a result of improved living standards. Many homes in the developed world are carpeted and contain many soft furnishings as well as being centrally heated and double-glazed. All of these factors summate to produce a warm and moist environment for propagation of allergens whilst at the same time preventing their `natural` removal. Given the dramatic increase in the number of people suffering from allergies, there is a need for tools to help sufferers manage their lifestyle appropriately. Simple diagnostic tests could be used at home to help to assess the levels of allergens or allergen-containing materials present. This would allow the sufferer to perform routine environmental control procedures as required. Soft furnishings, such as mattresses, duvets, pillows, armchairs and other items such as carpets and curtains are well-known to act as repositories of allergencontaining materials. By routinely assessing their allergen levels, appropriate cleaning or replacement regimes may be implemented and maintained. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Furniture cover sheet Inventor(s): Schmid, William; (Plymouth, MN) Correspondence: Merchant & Gould PC; P.O. Box 2903; Minneapolis; MN; 55402-0903; US Patent Application Number: 20030145380 Date filed: February 6, 2003 Abstract: A sheet of pliable, washable material is configured to cover at least a portion of a piece of furniture, such as a mattress. A manifold and a plurality of air flow tubes are formed in the sheet, with the air flow tubes in communication with the manifold. The air flow tubes include top surfaces that are constructed to release air at a controlled rate therethrough. The sheet helps reduce exposure to allergens and other harmful particles, including the house dust mite. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/354,653, filed Feb. 6, 2002. This invention relates to furniture covers. More particularly, this invention relates to a furniture cover sheet that is designed with air channels to which can be delivered a variety of air flows that are beneficial, such as improving air quality adjacent the cover and reducing exposure to allergens, to an individual's personal breathing environment. The furniture cover sheet can be used on numerous furniture items, including bed mattresses, chairs, sofas, and other furniture items upon which individuals lay or sit. Asthma in the U.S. and around the world has increased at an alarming rate over the last 20 years and currently affects more than 15 million Americans. There is some speculation as to the cause of this increase, whether due to more time spent indoors in "tighter" homes with less fresh air or because of improvements in early diagnosis of disease. A recent study concluded that the risk due

176

Allergens

to residential allergen and pollutant exposure accounted for 39% of doctor-diagnosed asthma in U.S. children less than 6 years old. 5,000,000 U.S. children (1 in 13) now suffer from asthma, accounting for 17% of all pediatric emergency room visits. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Homogeneous immunoassays for multiple allergens Inventor(s): Brown, Christopher R.; (San Mateo, CA), Murai, James T.; (San Bruno, CA) Correspondence: Townsend And Townsend And Crew, Llp; Two Embarcadero Center; Eighth Floor; San Francisco; CA; 94111-3834; US Patent Application Number: 20030109067 Date filed: December 6, 2001 Abstract: A homogeneous immunoassay method and system for quantitative determination of total immunoglobulin E and specific antibody levels to a plurality of allergens, in which a relatively small sampling of blood is required. The method utilizes relatively small microparticles in suspension with 1-5.mu.L of undiluted sample. The immunoassay procedure is an immunometric sandwich procedure preferably utilizing biotin-streptavidin signal amplification techniques and R-phycoerytherin fluorescent labels. Excerpt(s): This invention relates to a homogenous immunoassay method for determining specific antibody levels to a multiplicity of allergens from a blood sample, or for determining total immunoglobulins E levels in such a sample, for the purpose of diagnosing allergy. Confirmatory diagnostic testing may be conducted by in-vivo skin testing, in-vivo provocation testing, or in-vitro testing for the presence of circulating allergen-specific antibodies from blood samples. Direct provocation, by direct inhalation or ingestion of possible offending allergens, while relevant, is unpleasant, possibly dangerous and cannot be performed for multiple allergens at one sitting. Skin testing (also referred to as skin prick testing or scratch testing) is an in vivo procedure that involves applying an allergen sample, or more generally a multiplicity of allergens, directly to a patient's forearm or back via a small needle scratch and measuring the size of the inflammatory reaction (wheal) at the applied site on the skin. Skin prick testing is widely used, is reliable under optimal testing conditions, can be painful, is subject to large differences in technique and interpretations, and cannot be used on patients taking certain drugs or patients with skin problems. Furthermore, both provocation and skin prick in-vivo diagnostic methods have the potential for sensitizing patients to new allergens and, in extreme cases, eliciting a life-threatening anaphylactic reaction upon direct exposure to the offending allergen(s). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 177

•

Immunochemical methods Inventor(s): Alenius, Harri; (Helsinki, FI), Kalkkinen, Nisse; (Espoo, FI), Karkkainen, Tytti; (Espoo, FI), Krohn, Kai; (Salmentaka, FI), Kulomaa, Markku; (Siivikkala, FI), Ovod, Vladimir; (Tampere, FI), Palosuo, Timo; (Espoo, FI), Reunala, Timo; (Kangasala, FI), Sillanaukee, Pekka; (Tampere, FI), Turjanmaa, Kristiina; (Helsinki, FI) Correspondence: Nixon & Vanderhye, PC; 1100 N Glebe Road; 8th Floor; Arlington; VA; 22201-4714; US Patent Application Number: 20040106146 Date filed: November 25, 2002 Excerpt(s): The present invention relates to immunochemical analysis methods, which are useful in the detection of natural rubber latex allergens or specific antibodies against them. Specifically, the present invention relates to immunochemical analysis methods, which are useful in the detection the possible residual content of allergenic proteins or peptides derived from natural rubber latex in a finished product made of or containing natural rubber latex. Additionally, the present invention relates to immunochemical analysis methods which are useful in the diagnosis of latex allergy, specifically in the in vitro detection and analysis of specific immunoglobulin E (IgE) and/or G.sub.4 (IgG.sub.4) antibodies against latex allegens in a patient suspected of suffering from latex allergy and in in vivo diagnosis of latex allergy. The present invention further relates to preparations and specific immunochemical test kits useful in such methods. Products containing natural rubber latex (NRL) from the rubber tree Hevea brasiliensis are widely used due to the economical price and advantageous processing properties of natural rubber. However, adverse reactions against a number of allergenic proteins contained in the NRL are well known and documented, and in the past years allergy to NRL has become a major occupational problem especially among health care and dental professionals. NRL-containing surgical and protection gloves and various medical devices (like catheters, tubes, masks, etc.) contribute to the major portion of these adverse reactions, and even the glove powder may contain NRL proteins, absorbed from the NRL onto the powder particles, and thus cause both sensitisation and adverse reactions. In healthcare, the NRL-based medical devices exhibit a potential source of sensitisation not only to the personnel but also to the patients undergoing an examination or a surgery. In addition, workers in other professions where protection gloves are used, such as kitchen workers or greenhouse workers, or workers in rubber industry, may become sensitised to allergenic NRL proteins, and they also may be subjected to airborne NRL proteins. Finally, even the general population becomes in a daily contact with diverse NRL-containing products, such as household gloves, condoms and balloons, manufactured by the dipping procedure, and also with tubes, tires, erasers and like. Although natural rubber latex gloves have been used in medicine and industry for over 100 years, latex allergy as a disease entity has come to the attention of the medical and scientific community not until about 10-15 years ago. Currently, latex allergy is recognised as a serious world wide health problem: a significant proportion of health care workers (3-15%) and approximately 1% of the whole population have become sensitised to natural rubber latex [Turjanmaa, K. et al., Allergy 51 (1996) 593-602; Liss, G. M. and Sussman, G. L., Am. J. Ind. Med. 35 (1999) 196200; Poley Jr, G. E. and Slater, J. E., J. Allergy Clin. Immunol. 105 (2000) 1054-1062]. Importantly, due to an increasing need for protection against HIV, hepatitis B, and other infectious agents, the frequency to exposure and, subsequently, the number of sensitisations are going up. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

178

•

Allergens

Local nasal immunotherapy for allergen-induced airway inflammation Inventor(s): Tsai, Jaw-Ji; (Taipei, TW) Correspondence: Birch Stewart Kolasch & Birch; PO Box 747; Falls Church; VA; 220400747; US Patent Application Number: 20040071718 Date filed: September 18, 2002 Abstract: Methods and pharmaceutical compositions for treating allergen-induced airway inflammation. The method includes administering a therapeutically effective amount of a pharmaceutical composition comprising a Dermatophoides pteronyssinus group 2 (Dp2) epitope peptide and a pharmaceutically acceptable carrier to an individual having allergen-induced airway inflammation, in a manner consistent with local nasal immunotherapy. Excerpt(s): The present invention relates to pharmaceutical compositions and methods for the treatment of allergen-induced airway inflammation. More particularly, the present invention relates to pharmaceutical compositions and methods for local nasal immunotherapy of allergen-induced airway inflammation. Epidemiological studies suggest that between 10 and 20% of the world population exhibits some form of IgE mediated hypersensitivity, which is manifested as asthma, atopic dermatitis, or allergic rhinitis (Platts-Mills TA, et al. J Allergy Clin Immunol 1997; 100: S2-24). A number of studies have shown that sensitivity to house dust mite allergens is the most important risk factor for asthma (Platts-Mills TA, et al. J Allergy Clin Immunol 1997; 100: S2-24; Sporik R, et al. Clin Exp Allergy 1992; 22: 897-906). More than 10 mite allergens have been defined, and the 14-kDa Group 2 allergens (Dp2 and Df2) are considered major allergens because of the fact that 80-90% of patients have specific IgE antibodies to these allergens (Heymann, P W, et al. J Allergy Clin Immunol 1989; 83: 1055-67). Therapy for allergic disease includes allergen avoidance, pharmacotherapy, and allergen-specific immunotherapy (Smith A M, and Chapman M D. In immunotherapy in Asthma, Bousquet, J. and Yssel, H., eds, Marcel Dekker, Inc., New York.1999). For the control of intractable atopic disease against unavoidable allergens, hyposensitizing therapy, or allergen immunotherapy, has been the major realistic means of control (Noon L. Lancet 1911; 1:1572; Rolland J, and R.O'Hehir. Curr. Opin. Immunol 1998; 10:640-5; Barnes P J. Nature1999; 402 :S31-8). However, the therapy has suffered from a number of problems (Grant J A. New Engl J Med 1979; 300:565-565; Reid M J, et al. J Allergy Clin Immunol 1993; 92:6-15; Korematsu S, et al. J Immunol. 2000; 165:2895-902). Although complications deriving from the impurity of allergens have been overcome by the production of purified recombinant allergens, provocation of possibly life-threatening anaphylactic reactions remains a serious adverse effect. There is still a need for therapies of allergen-induced airway inflammation with improved efficacy, patient compliance and associated risk reduction. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 179

•

Local nasal immunotherapy with allergen strip for allergic rhinitis Inventor(s): Tsai, Jaw-Ji; (Taipei, TW) Correspondence: Birch Stewart Kolasch & Birch; PO Box 747; Falls Church; VA; 220400747; US Patent Application Number: 20040052808 Date filed: December 23, 2002 Abstract: A method and strip for treating allergen-induced airway inflammation. The method includes applying a nasal or skin strip containing a mixture of an allergen and a pharmaceutically acceptable carrier to an individual having allergen-induced airway inflammation in a manner consistent with local nasal immunotherapy. Excerpt(s): This application is a CIP of patent application Ser. No. 10/245,514. The present invention relates to local nasal immunotherapy for allergen-induced airway inflammation. More particularly, the present invention relates to an allergen strip for local nasal immunotherapy of allergic rhinitis. Allergic Rhinitis (AR) is one of the most common allergic diseases in humans. In developed countries, more than 10% of the population suffer from AR and the disease creates burdens such as medical expenses and loss of productivity (Malone D C, et al. J Allergy Clin Immunol. (1997) 99:22-7). Allergen specific immunotherapy was introduced to treat AR by Noon in 1911 (Noon L. Lancet (1911) i:1572-3). There is good evidence that immunotherapy using inhalant allergens to treat seasonal or perennial AR and asthma is clinically effective (Bousquent J, et al. Allergy (1998) 53, suppl 54). Despite the effectiveness of subcutaneous immunotherapy, poor compliance and systemic side-effects may limit its applicability (Cohn J R, et al. J Allergy Clin Immunol. (1993) 91:734-7; Committee on the Safety of Medicine. CSM update. Desensitizing vaccines. BMJ (1986) 293:948; Greenberg M A, et al. J Allergy Clin Immunol. (1986) 77:865-70; Lockey R F, et al. J Allergy Clin Immunol (1987) 79:660-77). The reports of severe reactions questioned the safety of subcutaneous immunotherapy and raised an interest in local nasal immunotherapy (LNIT). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Mattress cover with expandable sidewalls Inventor(s): Chase, Samuel; (Succasuna, NJ) Correspondence: Wolff & Samson PC; One Boland Drive; West Orange; NJ; 07052; US Patent Application Number: 20040088790 Date filed: June 20, 2003 Abstract: A generally impermeable mattress cover having expandable sidewalls is provided to enclose a mattress to provide protection against allergens, dust mites, fluids, and other spills and spoils. The cover comprises generally impermeable top and bottom walls, and sidewalls connected at edges between the top and bottom walls. The sidewalls are formed of a double wall construction comprising a generally impermeable inner wall of a fixed height joined at edges to an elastic outer wall. The outer wall stretches and the inner wall extends to accommodate mattresses of different thicknesses. The outer wall can be relaxed and the inner wall retained neatly against the mattress and by the outer wall. An aperture can be provided in the bottom wall for allowing insertion and removal of a mattress and a fastener can be used to close the aperture.

180

Allergens

Excerpt(s): The present invention relates generally to covers for mattresses, and more specifically, to a generally impermeable mattress cover with expandable sidewalls to fit mattresses of different thicknesses. Allergens and other irritants such as spores and dust mites can freely exist in mattresses, and can be the cause of allergic reactions to certain individuals. As such, it is often desirable to cover a mattress to protect same from allergens, dust mites, fluids, and other spoils. It is also desirable to protect mattresses from spills and other fluids, such as urine and blood. In locations where mattresses are frequently used, such covers are beneficial in preserving the life of the mattress and providing added comfort for users. Even at home, one can use such a cover to protect a mattress and extend its life. Indeed, by using a mattress cover to keep a mattress free of stains, one can assure that they comply with the warranty provided by the mattress manufacturers which are voided when mattresses are stained. It is known in the art to provide covers for mattresses to protect same from the aforementioned fluids and allergens existing in the mattress. However, there do not exist any covers with expandable sidewalls that completely cover a mattress and allow the cover to be used on mattresses of different thicknesses. Rather, such covers must be made in numerous sizes or must be custom-manufactured to fit beds and/or mattresses of different thicknesses. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method and test kit for detecting cockroach allergens and determining total allergen level Inventor(s): Chang, Frank N.; (Dresher, PA), Duong, Phu T.; (Malvern, PA) Correspondence: Ratnerprestia; P O Box 980; Valley Forge; PA; 19482-0980; US Patent Application Number: 20030180826 Date filed: March 19, 2003 Abstract: The present invention is directed to a method and a test kit for detecting cockroach allergens and/or determining the total allergen level. A sample from an environment in which cockroaches are present or are suspected to be present is provided. The sample and a substrate composition comprising a chitinase substrate are then contacted. The presence of cockroach allergens can be determined by observing or detecting the magnitude of a measurable change of a property of the substrate composition following the contact between the sample and the substrate composition wherein the magnitude of the measurable change of a property of the substrate composition is proportional to the total allergen level. The total allergen level can be determined by measuring the magnitude of the measurable change of a property of the substrate composition, or by comparing the magnitude with a reference standard. Excerpt(s): This application claims the benefit of the priority date of Provisional U.S. Patent Application Serial No. 60/367,063, filed Mar. 22, 2002 for the subject matter disclosed therein. The present invention relates to allergens. More specifically, it relates to a method and a test kit for detecting cockroach allergens and/or determining the total allergen level. About 17.3 million Americans suffer from asthma, which is a chronic inflammatory disorder of the airways. In susceptible individuals, this inflammation causes recurrent episodes of coughing, wheezing, chest tightness and difficult breathing. Inflammation makes the airways sensitive to indoor allergens such as those derived from cockroaches, dust mites and animal dander. Asthma is also the most common chronic childhood illness, particularly in inner-city homes, and is the leading cause of children's emergency room use, hospital admission and school absence.

Patents 181

Chronic asthma in children is highly associated with chronic respiratory disease in adulthood and has a huge health, economical and societal impact. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method for allergen characterization Inventor(s): Beardslee, Thomas A.; (Lincoln, NE), Markwell, John P.; (Lincoln, NE), Sarath, Guatam; (Lincoln, NE), Zeece, Michael G.; (Lincoln, NE) Correspondence: Senniger Powers Leavitt And Roedel; One Metropolitan Square; 16th Floor; ST Louis; MO; 63102; US Patent Application Number: 20030166518 Date filed: January 12, 2001 Abstract: Disclosed are methods for the characterization of allergens using recombinant fusion protein in an enzyme-linked immunosorbent (ELISA) assay. Also disclosed are methods for determining allergen sensitivity and methods for immunotherapy using the ELISA of the present invention. Excerpt(s): This application claims the benefit of provisional application No. 60/175,948, filed Jan. 13, 2000, which is hereby incorporated by reference in its entirety for all purposes. Type I allergy is a genetically determined hypersensitivity disease that affects approximately 20% of the population. Type I allergy is characterized by the production of immunoglobulin E (IgE) antibodies against what are normally harmless antigens (allergens). Immunoglobulin E is the least abundant class of immunoglobulins present in blood and other body fluids such as tears, nasal and bronchial secretions. Acute symptoms of Type I allergy include allergic rhinitis, conjunctivitis, asthma, dermatitis, and anaphylactic shock. These symptoms are due to the release of biological mediators such as histamine and leukotrienes from effector cells (mast cells and basophils). Release of biological mediators is due, in turn, to allergen induced crosslinking of Fc.sub.epsilon.RI-bound IgE antibodies bound to effector cells. Diagnosis of Type I allergy can be accomplished by detection of allergen specific IgE in serum (Wide et al., Lancet, 2:1105-1107, 1967; Eriksson and Ahlstedt, Int. Arch. Allergy Appl. Immunol. 54:88-95, 1977). These tests, however, have not been found to correlate highly with clinical symptoms and usually must be confirmed by provocation testing. The low correlation with clinical allergies may be due to impurities in the allergens used in such tests resulting in false positives, or the masking of IgE binding sites when the allergen is bound to a solid surface such as occurs in ELISA assays or immunoblotting. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Method for purifying recombinant proteins expressed as insoluble aggregates Inventor(s): Cromwell, Oliver; (Wentorf, DE), Fiebig, Helmug; (Schwarzenbek, DE), Suck, Roland; (Hamburg, DE) Correspondence: Millen, White, Zelano & Branigan, P.C.; 2200 Clarendon BLVD.; Suite 1400; Arlington; VA; 22201; US Patent Application Number: 20030170815 Date filed: March 7, 2003

182

Allergens

Abstract: The invention relates to a method for solubilising and purifying recombinant proteins which are expressed in bacterial host cells and are deposited as insoluble aggregates (inclusion bodies). The purification is based on conversion of the inclusion bodies into soluble forms using organic denaturing reagents and using chromatographic methods. Inorganic, alkaline, salt-containing eluents are selected here which, after purification is complete, enable the recombinant proteins, after neutralisation, to be made available in a form which can be employed directly for medical use and is physiologically acceptable. The method is particularly suitable for purifying allergens and allergen fragments. Excerpt(s): The invention relates to a method for solubilising and purifying recombinant proteins which are expressed in bacterial host cells and are deposited as insoluble aggregates (inclusion bodies). The purification is based on conversion of the said nclusion bodies into soluble forms using organic denaturing reagents and using chromatographic methods. Inorganic, alkaline, salt-containing eluents are selected here which, after purification is complete, enable the recombinant proteins, after neutralisation, to be made available in a form which can be employed directly for medical use and is physiologically acceptable. The method is particularly suitable for purifying allergens and allergen fragments. The method according to the invention is carried out under conditions which are necessary for pharmaceuticals (GMP). The pharmaceutical active ingredients can be used directly, after solubilisation, as parenteral preparations. The preferred recombinant allergens or allergen variants prepared by the method according to the invention can be used both for improved therapy and also for diagnosis of allergic diseases. It is a general problem in the preparation of recombinant proteins by bacterial or procaryontic host cells, such as, for example, E. coli, that the expressed proteins do not have the correct or native folding that they generally require in order to exhibit full biological activity. The incorrect folding frequently results in the a series of proteins being only in a form which is insoluble in the expression medium or are deposited in the form of aggregates, which have come to be known in the scientific literature as so-called "inclusion bodies". The formation of the said "inclusion bodies" has an adverse effect on the purification and requisite soluble availability of the expressed recombinant protein (Marston et al., 1986, Biochem J. 240: 1-12). In order to be able to purify the recombinant proteins deposited in bacteria, denaturing substances, such as, for example, urea or guanidinium hydrochloride, are frequently added to chromatographic eluents. However, these additives cannot be combined with every separation principle, such as, for example, hydrophobic interaction chromatography. Moreover, the products may be modified in a disadvantageous manner by chemical reactions, such as, for example, by cyanate, which can form in urea solutions. Removal of the denaturing agent and thus possible renaturing is usually carried out by dialysis, diafiltration or gel filtration. These processes are not only protracted, but also frequently result in re-precipitation of the products. Analytical detection of complete removal of the above-mentioned denaturing agents in the final product is difficult. The problem described above is particularly important in the preparation and purification of recombinant allergens and allergen variants. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 183

•

Method of deactivating dust mite allergens Inventor(s): Hughes, John Farrell; (Hampshire, GB), Jerrim, Karen Louise; (Salisbury, GB), McKechnie, Malcolm Tom; (East Yorkshire, GB) Correspondence: Akin Gump Strauss Hauer & Feld L.L.P.; One Commerce Square; 2005 Market Street, Suite 2200; Philadelphia; PA; 19103-7013; US Patent Application Number: 20030086991 Date filed: October 7, 2002 Abstract: A method is provided for deactivating a Der-p and/or Der-f allergen which comprises volatilizing into a space to be treated a deactivating amount of a volatile oil selected from cajeput oil (tea tree oil) or an oil comprising one or more terpene hydrocarbons. Excerpt(s): This application is a Continuation of International Application No. PCT/GB01/01572, filed Apr. 9, 2001, which was published in the English language on Oct. 18, 2001, under International Publication No. WO 01/76371 A1 and the disclosure of which is incorporated herein by reference. The present invention relates to a method of deactivating dust mite allergens. Various allergens are known which are transported through the air to trigger a human reaction. For example, it has been known for a long time that house dust can trigger allergenic reactions in humans, such as asthma and rhinitis. It was reported as early as 1928 that it was the dust mites in the dust that were the primary source of the allergenic response, but it was only in the 1960's that researchers appreciated their significance. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Methods and composition for delivering nucleic acids and/or proteins to the respiratory system Inventor(s): Chen, Wei; (San Diego, CA), Fu, Xiaoli; (Carlsbad, CA), Nouraini, Sherry; (Vista, CA), Zhang, Zhiqing; (Carlsbad, CA) Correspondence: Oppenheimer Wolff & Donnelly Llp; 840 Newport Center Drive; Suite 700; Newport Beach; CA; 92660; US Patent Application Number: 20040009937 Date filed: January 27, 2003 Abstract: Methods and compostions related to the fields of bacteriology, immunology and gene therapy are provided. In general modified microflora for the delivery of vaccines, allergens and therapeutics to the mucosal surfaces of the respiratory tract are provided. In particular, the compositions and methods are directed at inducing an Mcell mediated immune response to pathogenic diseases. Specifically, methods of vaccine preparation, delivery and mucosal immunization using a Lactic Acid Bacteria (LAB), yeast and LAB that have been modified through fusion with E. coli to either present on its cell surface, or secrete, antigenic epitopes derived from pathogenic microorganisms and/or to secrete a therapeutic protein sequence are disclosed. Excerpt(s): This application claims priority to provisional application serial Nos. 60/401,465 filed Aug. 5, 2002, 60/353,885 filed Jan. 31, 2002, 60/353,923 filed Jan. 31, 2002, and 60/353,964 filed Jan. 31, 2002 and is a continuation-in-part of co-pending U.S. patent application Ser. No. 10/280,769 filed Oct. 25, 2002 the contents of which are incorporated herein by reference in their entirety. The present invention relates to the

184

Allergens

fields of bacteriology, immunology and gene therapy. In general, this invention relates to the use of modified microflora for the delivery of vaccines, allergens and therapeutics to the mucosal surfaces of the respiratory tract. In particular, this invention provides novel compositions and methods for inducing an M-cell mediated immune response to pathogenic diseases. Specifically, this invention relates to a method of vaccine preparation, delivery and mucosal immunization using a Lactic Acid Bacteria (LAB), yeast and LAB that have been modified through fusion with E. coli to either present on its cell surface, or secrete, antigenic epitopes derived from pathogenic microorganisms and/or to secrete a therapeutic protein sequence. Various publications or patents are referred to in parentheses throughout this application to describe the state of the art to which the invention pertains. Each of these publications or patents is incorporated by reference herein. Complete citations of scientific publications are set forth in the text or at the end of the specification. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods and reagents for decreasing clinical reaction to allergy Inventor(s): Bannon, Gary A.; (Wentzville, MO), Burks, A. Wesley JR.; (Little Rock, AR), Caplan, Michael J.; (Woodbridge, CT), Cockrell, Gael; (Cabot, AR), Compadre, Cesar M.; (Little Rock, AR), Connaughton, Cathie; (Conway, AR), Helm, Ricki M.; (Little Rock, AR), King, Nina E.; (Mason, OH), Kopper, Randall A.; (Conway, AR), Maleki, Soheila J.; (New Orleans, LA), Rabjohn, Patrick A.; (Little Rock, AR), Sampson, Hugh; (Larchmont, NY), Shin, David S.; (San Diego, CA), Sosin, Howard B.; (Fairfield, CT), Stanley, J. Steven; (North Little Rock, AR) Correspondence: Choate, Hall & Stewart; Exchange Place; 53 State Street; Boston; MA; 02109; US Patent Application Number: 20030202980 Date filed: March 18, 2002 Abstract: It has been determined that allergens, which are characterized by both humoral (IgE) and cellular (T-cell) binding sites, can be modified to be less allergenic by modifying the IgE binding sites. The IgE binding sites can be converted to non-IgE binding sites by altering as little as a single amino acid within the protein, preferably a hydrophobic residue towards the center of the IgE epitope, to eliminate IgE binding. Additionally or alternatively a modified allergen with reduced IgE binding may be prepared by disrupting one or more of the disulfide bonds that are present in the natural allergen. The disulfide bonds may be disrupted chemically, e.g., by reduction and alkylation or by mutating one or more cysteine residues present in the primary amino acid sequence of the natural allergen. In certain embodiments, modified allergens are prepared by both altering one or more linear IgE eitopes and disrupting one or more disulfide bonds of the natural allergen. In certain embodiments, the methods of the present invention allow allergens to be modified while retaining the ability of the protein to activate T-cells, and, in some embodiments by not significantly altering or decreasing IgG binding capacity. The Examples provided herein use peanut allergens to illustrate applications of the invention. Excerpt(s): The present application is a continuation-in-part of U.S. Ser. No. 09/494,096 filed Jan. 28, 2000 which is in turn a continuation-in-part of U.S. Ser. No. 09/267,719 filed Mar. 11, 1999; U.S. Ser. No. 09/248,674 filed Feb. 11, 1999; U.S. Ser. No. 09/248,673 filed Feb. 11, 1999; U.S. Ser. No. 09/241,101 filed Jan. 29, 1999; U.S. Ser. No. 09/240,557 filed Jan. 29, 1999; U.S. Ser. No. 09/141,220 filed Aug. 27, 1998; U.S. Ser. No. 09/106,872 filed

Patents 185

Jun. 29, 1998; and U.S. Ser. No. 09/191,593 filed Nov. 13, 1998 which is in turn a continuation of U.S. Ser. No. 08/717,933 filed Sep. 26, 1996. These applications claim priority to provisional applications U.S. Ser. No. 60/122,450 filed Mar. 2, 1999; U.S. Ser. No.60/122,452 filed Mar. 2, 1999; U.S. Ser. No.60/122,560 filed Mar. 2, 1999; U.S. Ser. No. 60 /122,5 65 filed Mar. 2 , 1999; U.S. Ser. No. 60 /122,56 6 filed Mar. 2, 1999; U.S. Ser. No. 60/074,633 filed Feb. 13, 1998; U.S. Ser. No. 60/074,624 filed Feb. 13, 1998; U.S. Ser. No. 60/074,590 filed Feb. 13, 1998; U.S. Ser. No. 60/073,283 filed Jan. 31, 1998; and U.S. Ser. No. 60/009,455 filed Dec. 29, 1995. This application also claims priority to co-pending provisional application, U.S. Ser. No. 60/276,822, filed Mar. 16, 2001. These and every other U.S. patent application cited herein are incorporated in their entirety by reference. Allergic disease is a common health problem affecting humans and companion animals (mainly dogs and cats) alike. Allergies exist to pollens, mites, animal danders or excretions, fungi, insects, foods, latex, drugs, and other substances present in the environment. It is estimated that up to 8% of young children and 2% of adults have allergic reactions just to foods alone. Some allergic reactions (especially those to insects, foods, latex, and drugs) can be so severe as to be life threatening. Allergic reactions result when an individual's immune system overreacts, or reacts inappropriately, to an encountered allergen. Typically, there is no allergic reaction the first time an individual is exposed to a particular allergen. However, it is the initial response to an allergen that primes the system for subsequent allergic reactions. In particular, the allergen is taken up by antigen presenting cells (APCs; e.g., macrophages and dendritic cells) that degrade the allergen and then display allergen fragments to T-cells. T-cells, in particular CD4+ "helper" T-cells, respond by secreting a collection of cytokines that have effects on other immune system cells. The profile of cytokines secreted by responding CD4+ T-cells determines whether subsequent exposures to the allergen will induce allergic reactions. Two classes of CD4+ T-cells (Th1 and Th2; T-lymphocyte helper type) influence the type of immune response that is mounted against an allergen. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Modified mite allergen and pharmaceutical uses thereof Inventor(s): Ching-Hsiang, Hsu; (Tainan County, CN), Wei-Chih, Su; (Tainan County, CN) Correspondence: Banner & Witcoff; 1001 G Street N W; Suite 1100; Washington; DC; 20001; US Patent Application Number: 20040091499 Date filed: September 4, 2003 Abstract: The present invention provides a modified Dermatophagoides pteronyssinus allergen Der p 5 protein which has ability to inhibit IgE binding when exposed against to the antigen. A method for treating allergy comprising administrating a therapeutically effective dose of the modified D. pteronyssinus allergen Der p 5 protein to a subject suffering from allergy Der p 5 is also provided. Excerpt(s): The invention mainly relates to a modified allergen obtained by altering Der p 5 allergen of house dust mite and the pharmaceutical uses thereof. Allergy refers to an acquired potential to develop immunologically mediated adverse reaction to normally innocuous substances. Allergic reaction provokes symptoms such as itching, coughing, wheezing, sneezing, watery eyes, inflammation and fatigue. Many allergic diseases are due to several kinds of symptoms which are developed by sensitization to the antigen causing the diseases. In an allergic disease, an IgE antibody specific for an allergen (e.g.

186

Allergens

pollens and mite dust) in blood serum and tissue is produced, and when the antibody is exposed again to the antigen, the antibody reacts with the antigen in each tissue. It is normally believed that an allergic reaction includes an early specific immune response and a late inflammatory reaction. It is reported that an allergen mediates the early phase of allergy by stimulating high affinity immunoglobulin (IgE) receptors. Mast cells and basophils, when stimulated by allergens, will release histamine and cytokines. The cytokines released from mast cells and basophils then mediate the late phase of allergy by recruiting inflammatory cells. It is reported that allergic diseases, such as bronchial asthma, childhood asthma, atopic dermatitis and the like, are mainly caused by allergens from mites living in house dust. Several kinds of proteins of mite allergens, such as Der p 1 and Der p 2, have been identified. Der p 5 is a 14-k Da group 5 mite allergen which contains a 19-residue leader protein and a 113-residue mature protein was cloned and sequenced (Lin et al., Allergens, IgE, mediators, inflammatory mechanisms. J Allergy Clin Immunol 1994; 6:989-996). Although only 60% of miteallergic children reacted to Der p 5, the IgE reactivity appeared to be stronger than that of Der p 1 and Der p 2 in Taiwan. Furthermore, among the various allergic diseases, the group of children with asthma have significant more reactivity than the group with rhinitis alone. Der p 5 is regarded as a clinically significant allergen in mite allergy. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Nasal filter and sampler Inventor(s): Tovey, Euan; (New South Wales, AU) Correspondence: Nixon & Vanderhye; 8th Floor; 1100 North Glebe Road; Arlington; VA; 22201-4714; US Patent Application Number: 20030106555 Date filed: October 4, 2002 Abstract: Device (10) may be inserted in a nostril to filter and/or sample air inhaled or exhaled. Air inhaled through device (10) enters aperture (21) and exits through aperture (25). While passing through device (10) the airstream is deflected around deflector (16) and caused to encounter collector (19) extending inwardly from sidewall (18). A liquid or adhesive on collector (19) entraps particles, e.g. allergens, in the airstream, and can be subsequently removed for analysis. Alternatively collector (19) can be replaced by a reservoir for delivery of a pharmaceutical to a subject by inhalation. Excerpt(s): The present invention relates to a filter or sampler adapted to recover all or some fine particulate matter from air inhaled or exhaled by a human or other mammalian animal. The inhalation of various aeroallergens may cause asthma, rhinitis and other conditions in many people and animals. In order to understand the nature of the condition and possible treatments it is desirable to collect these aeroallergens from the inhaled air stream. In addition, such collection can be used as a prophylactic measure to prevent aeroallergens from entering the airways of a subject. While there is strong epidemiological evidence associating exposure to aeroallergens to both sensitisation and symptoms at a communal level, and to a lesser extent at an individual level, the methods for estimating personal exposure to aeroallergens are poorly developed. The most common method is to measure allergen concentration in settled dust (collected by a vacuum cleaner) which functions as a source of aeroallergens. The method has, however, serious confounders such as the concentration of allergen and quantity of dust/unit area varying more than 10 fold at different sites within a room.

Patents 187

There is, however no consistent data to directly show that such samples relate to individual personal exposure. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Non-anaphylactic forms of grass pollen Phl p 6 allergen and their use Inventor(s): Gronlund, Hans; (Lidingo, SE), Grote, Monika; (Munster, DE), Kraft, Dietrich; (Vienna, AT), Pastore, Annalisa; (London, GB), Sperr, Wolfgang R.; (Vienna, AT), Stumvoll, Sabine; (St. Peter, AT), Valent, Peter; (Vienna, AT), Valenta, Rudolf; (Theresienfeld, AT), Vangelista, Luca; (Padova, IT), Vrtala, Susanne; (Vienna, AT) Correspondence: Birch Stewart Kolasch & Birch; PO Box 747; Falls Church; VA; 220400747; US Patent Application Number: 20030143239 Date filed: November 27, 2002 Abstract: The invention relates to a hypoallergenic immunogenic molecule derived from the Phl p 6 allergen, wherein the Phl p 6 molecule has an N-terminal and/or C-terminal deletion which makes the molecule at least substantially lack IgE binding capacity. The invention also relates to a hypoallergenic immunogenic combination of molecules derived from the Phl p 6 allergen, comprising (i) a Phl p 6 molecule having an Nterminal deletion which makes the molecule at least substantially lack IgE binding capacity, and (ii) a Phl p 6 molecule having a C-terminal deletion which makes the molecule at least substantially lack IgE binding capacity, which two molecules together encompass the complete sequence of Phl p 6. The invention further relates to the use of the hypoallergenic immunogenic molecule or molecule mixture in hyposensitization and diagnosis. Excerpt(s): The present invention relates to non-anaphylactic, i.e. hypoallergenic, forms of the major timothy grass pollen allergen Phl p 6 and the use of the forms for hyposensitization and for diagnosis. The invention also relates to a method for hyposensitization of a mammalian individual, typically a human individual, suffering from type I allergy against the Phl p 6 allergen. Type I allergy is a genetically determined hypersensitivity disease that affects more than 20% of the population in industrialized countries (1). As a consequence of this immuno-disorder, allergic patients produce IgE antibodies against per se innocuous, mostly air-born proteins from pollen, mites, moulds and animal hair/dander. The symptoms of Type I allergy (allergic rhinitis, conjunctivitis, allergic asthma and anaphylactic shock) result from allergeninduced crosslinking of effector cell (mast cell, basophil)-bound IgE antibodies and subsequent release of inflammatory mediators (2). Since approximately 40% of allergic individuals suffer symptoms following contact with grass pollen, research has concentrated on the characterization of relevant grass pollen allergens by protein and immunochemical methods (3). While groups of major allergens have been identified as cross-reactive moieties that occur in most grass species (4), nothing was known concerning their nature and biological functions. The recent application of molecular biological techniques to allergen characterization has revealed the primary structures of allergens and facilitated the production of recombinant allergens for diagnostic and therapeutic purposes (5). Components of the plant cytoskeleton (e.g., profilin) (6) as well as calcium-binding pollen proteins (7) have been identified as relevant allergens. The fact that allergic patients exhibit immediate type reactions upon contact with various unrelated allergen sources thus can be explained by cross-reactivity of their IgE antibodies with ubiquitous allergens. Evidence that group 1 grass pollen allergens

188

Allergens

belong to a family of cell wall-loosening proteins (expansins) (8) and grass group 5 allergens may possess RNAse activity (9) has restimulated ideas that the biological function of a given protein may be related to its allergenicity. The recent findings that major grass pollen allergens can either become attached to small sized particles (e.g., group 1 allergens to diesel exhaust (10)) or may become airborn as small pollen subcompartments (e.g., group 5 allergens in amyloplasts (11)) would provide a possible mechanism of how certain allergens may be able to reach the deep airways of patients and to elicit allergic asthma. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Novel allergen Inventor(s): Dewitt, Asa Marknell; (Almunge, SE), Lehtonen, Pirjo; (Uppsala, SE), Lidholm, Jonas; (Knivsta, SE), Niederberger, Verena; (Vienna, AT), Sperr, Wolfgang R.; (Vienna, AT), Spitzauer, Susanne; (Vienna, AT), Valent, Peter; (Vienna, AT), Valenta, Rudolf; (Vienna, AT) Correspondence: Browdy And Neimark, P.L.L.C.; 624 Ninth Street, NW; Suite 300; Washington; DC; 20001-5303; US Patent Application Number: 20040014155 Date filed: March 27, 2003 Abstract: The present invention relates to a novel allergen from timothy grass (Phleum pratense) pollen, Phl p 11 as disclosed in SEQ ID NO 1, and use thereof as a reagent and in a diagnostic kit as well as for immunotherapy. Excerpt(s): The present invention relates to a novel allergen from timothy grass (Phleum pratense) pollen, Phl p11, and use thereof as a reagent and in a diagnostic kit as well as for immunotherapy. A hallmark of atopic allergy is the formation of IgE antibodies to proteins present in the sensitizing biological material. Upon contact with the allergen source, these proteins will act to crosslink IgE antibodies present on the surface of mast cells, thereby eliciting the release of inflammation mediators such as histamine. As a result, an allergic reaction occurs (1). In the industrialized world, up to 10% of the human population shows allergic sensitization to grass pollen, making this one of the most important airborne allergen sources (2). Considerable efforts have been made towards the characterization of pollen allergens from a variety of grass species using biochemical and immunological methods. A number of IgE binding proteins have thus been identified which exhibit conserved structure and serological cross-reactivity between species. Based on these criteria, such immunologically related grass pollen allergens have been assigned to groups designated by numbers. These include group 1, group 2/3, group 4, and group 5 allergens, which are represented in pollen of most grass species (3). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 189

•

Novel composition and method for altering allergenic protein in the environment Inventor(s): Smith, C. Steven; (Louisville, KY) Correspondence: King & Schickli, Pllc; 247 North Broadway; Lexington; KY; 40507; US Patent Application Number: 20030118670 Date filed: July 11, 2002 Abstract: Provided are compositions and methods for prevention or mitigation of allergic reactions in humans and animals. Novel compositions comprised of, e.g., an acidic salt solution of aluminum, calcium or magnesium, are provided for topical or contact application to physically and/or chemically alter an allergenic protein present in the environment and thereby lower the allergenicity of the protein. The compositions of the invention, e.g., comprised of aluminum sulfate, can be used to deactivate many types of proteinaceous allergens such as dust mite and cockroach body dust, animal dander, dried saliva, mold spore antigens, airborne pollen protein and the like. Compositions can be applied on an as needed basis to a wide variety of surfaces, e.g., floor coverings, walls bedding, window coverings, vehicle (e.g., automobile) interiors, furniture, pet bedding, plants (e.g., household plants) and the like. The compositions provided may also be utilized to mitigate allergens present on clothing, e.g., for use in commercial dry cleaning or in household laundry applications. Excerpt(s): This application claims the benefit of priority in U.S. Provisional Application Serial No.: 60/304,722; filed on Jul. 11, 2001. The present invention generally relates to the prevention or material mitigation of allergic reactions in humans (and other susceptible animals). In particular, the present invention relates to a novel composition, e.g., comprised of salts of aluminum, calcium and/or magnesium in a water or buffer solution and to the methods of use thereof to alter selected proteins that constitute allergens (or antigens) and thereby to lower their ability to cause allergic reactions in susceptible humans (and/or in other susceptible animals, e.g., in household pets or other companion and/or production animals). One critical function of the human (and animal) immune system is to assess whether a physical particle entering the body is a friend or foe. Occasionally for some people (and animals) and frequently or continuously for others, the immune system wrongly identifies an otherwise harmless particle as foe--acting as if the particle were a dangerous, infectious microorganism. The overtly harmless particle may be, e.g., a molecule of pollen, or dog dander, or cat saliva or any of a host of other proteins we know to be allergens, i.e., antigens that trigger an adverse immune system response in susceptible humans (and susceptible animals). Chromosomal characteristics seem to determine which members of any given population will "have allergies"; estimates of the United States population are that at least 20% and as many as 30% are atopic, i.e., they produce abnormal IgE and/or abnormal amounts of IgE, and thus develop hypersensitivity to allergens. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Novel mutant allergens Inventor(s): Holm, Jens; (Fredensborg, DK), Ipsen, Hans Henrik; (Hillerod, DK), Larsen, Jorgen Nedergaard; (Graested, DK), Spangfort, Michael Dho; (Helsingborg, SE) Correspondence: Darby & Darby P.C.; 805 Third Avenue; New York; NY; 10022; US Patent Application Number: 20030175312 Date filed: November 15, 2001

190

Allergens

Abstract: Novel recombinant allergens with multiple mutations and reduced IgE binding affinity are disclosed. The allergens are non-naturally occurring mutants of naturally-occurring allergens. The overall.alpha.-carbon backbone tertiary structure is essentially preserved. Also disclosed is a method for preparing such recombinant allergens as well as uses thereof. Excerpt(s): The present invention relates to novel recombinant allergens, which are mutants of naturally occurring allergens. Also, the invention relates to a composition comprising a mixture of the novel recombinant mutant allergens. Further, the invention relates to a method of preparing such recombinant mutant allergens as well as to pharmaceutical compositions, including vaccines, comprising the recombinant mutant allergens. In further embodiments, the present invention relates to methods of generating immune responses in a subject, vaccination or treatment of a subject as well as processes for preparing the compositions of the invention. Genetically predisposed individuals become sensitised (allergic) to antigens originating from a variety of environmental sources, to the allergens of which the individuals are exposed. The allergic reaction occurs when a previously sensitised individual is re-exposed to the same or a homologous allergen. Allergic responses range from hay fever, rhinoconductivitis, rhinitis and asthma to systemic anaphylaxis and death in response to e.g. bee or hornet sting or insect bite. The reaction is immediate and can be caused by a variety of atopic allergens such as compounds originating from grasses, trees, weeds, insects, food, drugs, chemicals and perfumes. However, the responses do not occur when an individual is exposed to an allergen for the first time. The initial adaptive response takes time and does usually not cause any symptoms. But when antibodies and T cells capable of reacting with the allergen have been produced, any subsequent exposure may provoke symptoms. Thus, allergic responses demonstrate that the immune response itself can cause significant pathological states, which may be life threatening. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Plant cell wall loosening activity of group 2/3 allergens of grass pollen Inventor(s): Cosgrove, Daniel J.; (Pennsylvania Furnace, PA), Li, Lian-Chao; (State College, PA) Correspondence: Mckee, Voorhees & Sease, P.L.C.; Attn: Pennsylvania State University; 801 Grand Avenue, Suite 3200; Des Moines; IA; 50309-2721; US Patent Application Number: 20040110190 Date filed: July 28, 2003 Abstract: The present invention provides nucleic acids and polypeptide sequences for a novel class of expansin-related proteins, designated group 2/3 allergen, which comprise the group 2 and group 3 allergens from grass, a purified group 3 allergen Lol p 3, and method of using the nucleic acids sequences and proteins of the invention. Group 2/3 allergens of the invention are significant wall-loosening agents. They are capable of altering cell wall properties, which may effect growth, flexibility, and mechanical strength in tissues in which they are expressed. Excerpt(s): This application claims priority under 35 U.S.C.sctn. 120 to provisional application Serial No. 60/399,688 filed Jul. 29, 2002, which is herein incorporated by reference in its entirety. Group 2 and group 3 allergens (designated group 2/3 allergens) were first recognized as significant allergenic components of grass pollen in

Patents 191

the early 1960's and caused allergenic reaction in about 45.about.70% of grass allergic patients. After about a quarter of a century, the complete primary structure of group 2/3 allergen from ryegrass pollen was analyzed by automated Edman degradation. This was soon followed by cDNA cloning from cocksfoot/orchard grass (Dactylis glomerata), timothy grass (Phleum pretense), and perennial ryegrass (Lolium perenne). Up until now, they have been studied exclusively by immunologists concerned with how these proteins elicit hay fever and related allergic responses in humans, but the endogenous activity and role of these proteins have not yet been studied. For many years wall "loosening enzymes" have been implicated in the control of plant cell enlargement (growth), largely on the basis of rapid biophysical and biochemical changes in the wall during auxin-induced growth (reviewed by Cleland and Rayle, Bot. Mag. Tokyo, 1:125-139, 1978; Taiz, Annu. Rev. Plant Physiol., 35:585-657, 1984). Plant walls contain numerous hydrolytic enzymes, which have been viewed as catalysts capable of weakening the wall to permit turgor-driven expansion (reviewed by Fry, Physiol. Plantarum, 75:532-536, 1989). In support of this hypothesis, Huber and Nevins (Physiol. Plant., 53:533-539, 1981) and Inoue and Nevins (Plant Physiol., 96:426-431, 1991) found that antibodies raised against wall proteins could inhibit both auxin-induced growth and wall autolysis of corn coleoptiles. In addition, isolated walls from many species extend irreversibly when placed under tension in acid conditions in a manner consistent with an enzyme-mediated process (Cosgrove D. J. Planta, 177:121-130, 1989). Despite these results and other evidence in favor of "wall-loosening" enzymes, a crucial prediction of this hypothesis has never been demonstrated, namely, that exogenously added enzymes or enzyme mixtures can induce extension of isolated walls. To the contrary, Ruesink (Planta, 89:95-107, 1969) reported that exogenous wall hydrolytic enzymes could mechanically weaken the wall without stimulating expansion. Similarly, autolysis of walls during fruit ripening does not lead to cell expansion. Thus, a major piece of evidence in favor of wall-loosening enzymes as agents of growth control has been lacking. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Recombinant allergen, fragments thereof, corresponding recombinant DNA molecules, vectors and hosts containing the DNA molecules, diagnostic and therapeutic uses of said allergens and fragments Inventor(s): Ball, Tanja; (Wien, AT), Kraft, Dietrich; (Wien, AT), Laffer, Sylvia; (Wien, AT), Sperr, Wolfgang; (Wien, AT), Susani, Markus; (Salzburg, AT), Valent, Peter; (Wien, AT), Valenta, Rudolf; (Theresienfeld, AT), Vrtala, Susanne; (Wien, AT) Correspondence: Birch Stewart Kolasch & Birch; PO Box 747; Falls Church; VA; 220400747; US Patent Application Number: 20030171567 Date filed: June 5, 2002 Abstract: A recombinant DNA molecule comprising a nucleotide sequence (I) which codes for a polypeptide displaying the antigenicity of one, two or more of the Phl p I epitope clones (28, 34, 41, 42, 43, 50, 52, 64, 80, 85, 86, 95, 97, 98, 103, 108, 109, 113, 114) with the amino acid sequences defined in FIG. 2 and preferably being derived from grasses or monocotyledonic plants, or a nucleotide sequence (II) which hybridizes with such a nucleotide sequence (I) under conditions of high stringency. Polypeptides displaying the antigenicity of one, two or more of the Phl p I epitope clones (28, 34, 41, 42, 43, 50, 52, 64, 80, 85, 86. 95, 97, 98, 103, 108, 109, 113, 114) with the amino acid

192

Allergens

sequences defined in FIG. 2. Recombinant expression vectors containing the recombinant molecule and host cells transformed with the vector. Diagnostic methods based on utilizing the polypeptides in immunoassays for humoral antibodies and cellular reactions. Excerpt(s): The present invention relates to the title aspects of the major grass pollen allergen Phl p I and IgE-binding epitopes present in this allergen and corresponding haptens. The invention also relates to fragments, including IgE-binding haptens, from other grass and monocotyledonic plant allergens containing the IgE binding epitopes of Phl p I. The invention is primarily concerned with epitopes that normally are found in one or more group I allergens. Up to 20% of the population in industrialized countries suffer from Type I allergic symptoms (rhinitis, conjunctivitis, asthma bronchiale) (Myamoto et al., 1992). The crosslinking of IgE which is bound to mast cells and basophils via the high affinity receptor Fc.epsilon.RI is the key event leading to release of biological mediators such as histamine (Segal et al., 1977). The crosslinking event by allergens represents, therefore, a potential target for therapy of Type I allergy. Such therapeutical approaches could either use portions of the IgE-molecule or other ligands, to interfere with the binding of IgE to the high affinity Fc.epsilon.-receptor, or reagents to block the subsequent signal transduction cascade thus preventing the degranulation of mast cells and basophils (Dreskin et al., 1988). An additional possibility for specific therapy would be to use haptens derived from complete allergens which by binding to IgE monovalently could block the crosslinking of IgE (Valenta et al., 1993a). IgE-haptens could also be used to modulate the immune response or to induce tolerance by immunotherapy with a minimum of anaphylactic side effects. Haptens can be obtained from complete allergens by proteolytic digestion. However, this often results in a mixture of fragments and enzymes that are difficult to characterize. Synthesis of peptides based on the amino acid sequence of the allergens, is an alternative approach. Recently a number of cDNAs coding for important allergens (Scheiner et al., 1992) were isolated which can be used to determine IgE-epitopes by molecular biological techniques. Grass pollen allergy is spread world wide and according to the prevalence of grass pollen allergy it can be expected that 75% of all allergic patients suffer from grass pollen allergy (Freidhoff et al., 1986). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Recombinant allergens Inventor(s): Ipsen, Hans Henrik; (Hillerod, DK), Larsen, Jorgen Nedergaard; (Graested, DK), Spangfort, Michael Dho; (Helsingborg, SE) Correspondence: Darby & Darby P.C.; P. O. Box 5257; New York; NY; 10150-5257; US Patent Application Number: 20040091500 Date filed: November 20, 2003 Abstract: Novel recombinant allergens are disclosed. The allergens are non-naturally occurring mutants derived from naturally-occurring allergens. The overall.alpha.carbon backbone tertiary structure of the allergens is essentially preserved. Also disclosed are methods for preparing the recombinant allergens as well as the use of the recombinant allergens for the treatment of allergic reactions. Excerpt(s): The present application is a continuation and claims the benefit of priority under 35 U.S.C.sctn. 120 of Ser. No. 09/270,910, filed Mar. 16, 1999, and claims priority under 35 U.S.C.sctn. 119(e) of provisional application No. 60/078,371, filed Mar. 18,

Patents 193

1998. Each of the foregoing applications is hereby incorporated by reference in its entirety. The present invention relates to novel recombinant allergens, which are nonnaturally occurring mutants derived from naturally occurring allergens. Further, the invention relates to a method of preparing such recombinant allergens as well as to pharmaceutical compositions, including vaccines, comprising the recombinant allergens. In further embodiments, the present invention relates to methods of generating immune responses in a subject, vaccination or treatment of a subject as well as processes for preparing the compositions of the invention. Genetically predisposed individuals become sensitised (allergic) to antigens originating from a variety of environmental sources, to the allergens of which the individuals are exposed. The allergic reaction occurs when a previously sensitised individual is re-exposed to the same or a homologous allergen. Allergic responses range from hay fever, rhinoconductivitis, rhinitis and asthma to systemic anaphylaxis and death in response to e.g. bee or hornet sting or insect bite. The reaction is immediate and can be caused by a variety of atopic allergens such as compounds originating from grasses, trees, weeds, insects, food, drugs, chemicals and perfumes. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Recombinant DNA encoding the major allergen of plantago lanceolata pollen, Pla I 1, and applications thereof Inventor(s): Corrales, Florentino Polo; (Madrid, ES), Duran, Gabriel Salcedo; (Madrid, ES), Freile, Belen Calobozo; (Madrid, ES), Hernandez, Domingo Barber; (Madrid, ES), Perales, Araceli Diaz; (Madrid, ES) Correspondence: Darby & Darby P.C.; P. O. Box 5257; New York; NY; 10150-5257; US Patent Application Number: 20040071717 Date filed: September 3, 2002 Abstract: A nucleic acid molecule encoding a peptide or protein comprising at least one epitope of the major allergen of Plantago lanceolata, Pla I 1, wherein the nucleic acid molecule a) has the sequence of SEQ ID NOS.: 5-7, b) is a fragment of the sequence SEQ ID NOS.: 5-7, c) has a sequence encoding the amino acid sequence of SEQ ID NO.: 8 or a fragment thereof, d) has a sequence hybridising to SEQ ID NOS.: 5-7 under stringent conditions, e) has a sequence derivable by degeneration of SEQ ID NOS.: 5-7, or f) a complementary strand of any of the sequences a)-e). Excerpt(s): This application claims the priority of U.S. Provisional Application No. 60/294,672, filed on May 30, 2001 which is hereby incorporated hereby by reference in its entirety. The present invention relates to a nucleic acid molecule comprising at least one epitope of the major allergen of Plantago lanceolata, Pla I 1. Type I allergies affect millions of people worldwide, and its incidence has increased over the last few years in developed countries, leading to rising human and economic costs (1). Pollen allergens are proteins or glycoproteins capable of eliciting IgE-mediated allergic diseases, such as hay fever and 2 o asthma, in approximately 17% of the population who are genetically predisposed to develop allergies. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

194

•

Allergens

Recombitope peptides Inventor(s): Bond, Julian F.; (Weymouth, MA), Garman, Richard D.; (Arlington, MA), Greenstein, Julia L.; (West Newton, MA), Kuo, Mei-Chang; (Palo Alto, CA), Morgenstern, Jay P.; (Boston, MA), Morville, Malcolm; (Shrewsbury, MA), Rogers, Bruce L.; (Belmont, MA) Correspondence: Lahive & Cockfield, LLP.; 28 State Street; Boston; MA; 02109; US Patent Application Number: 20040057959 Date filed: June 16, 2003 Abstract: The present invention provides peptides having T cell stimulating activity termed recombitope peptides. Recombitope peptides of the invention preferably comprise at least two T cell epitopes derived from the same or from different protein antigens, and more preferably comprise at least two regions, each region preferably having human T cell stimulating activity and each region comprising at least one T cell epitope derived from a protein antigen. Recombitope peptides of the invention can be derived from protein allergens, autoantigens, or other protein antigens. The invention also provides methods of diagnosing sensitivity to a protein allergen or other protein antigen in an individual, methods to treat such sensitivity and therapeutic compositions comprising one or more recombitope peptides. The invention further provides methods for designing recombitope peptides of the invention where the protein antigen to which the individual is sensitive has unknown or ill-defined T cell epitopes. Excerpt(s): This application is a continuation-in-part of U.S. Ser. No. 662,276 entitled "A Human T Cell Reactive Cat Protein Isolated from House Dust and Uses Therefor," filed Feb. 28, 1991, which is a continuation-in-part of U.S. Ser. No. 431,565 entitled "A Human T Cell Reactive Cat Protein Isolated from House Dust and Uses Therefor," filed Nov. 3, 1989, the teachings of which are incorporated herein by reference. T lymphocytes can mediate and regulate both the specific and non-specific effector mechanisms of immune responses. CD4+T lymphocytes provide help for antibody production and secrete cytokines which modulate the growth of other T cells and the growth and differentiation of other immune cells such as monocytes and granulocytes. Functional and biochemical studies have demonstrated that the generation of cellular immune responses depends upon antigen receptors on T cells that recognize peptide fragments of foreign proteins associated with products of the major histocompatibility complex (MHC) that are expressed on antigen-presenting accessory cells. Recent advances in technology have made it possible to culture efficiently antigen-specific human and mouse T cell lines and clones in vitro. In addition, it is now possible to produce large amounts of protein antigens or their fragments using recombinant DNA technology or solid phase peptide synthesis. Thus, in the last few years, several research groups have begun to determine the linear amino acid sequences of antigenic proteins that are recognized by T cells in association with MHC (T cell epitopes). Peptides derived from a variety of protein antigens, including bacterial and viral pathogens, autoantigens, allergens and other experimental antigens such as hen egg lysozyme (HEL), ovalbumin (OVA) and lambda repressor (cl) have been examined for the ability to stimulate antigen-specific T cells. A wide size spectrum of peptides has been reported to serve as T cell epitopes. For example, OVA amino acid residues 324-339 (Shimonkevitz, R. et al., J. Immunol., 133:2167 (1984)), HEL amino acid residues 74-96 (Shastri, N. et al., J. Exp. Med. 164:882896 (1986); and lambda repressor (cl) amino acid residues 12-26 (Lai, M.-Z et al., J. Immunol., 139:3973-3980 (1987)) have been demonstrated to trigger efficiently whole protein-primed T cells. A peptide derived from Hepatitis B surface antigen (HBsAg amino acid residues 19-33) has recently been shown to stimulate T cell responses in a

Patents 195

majority of human subjects who had been immunized with a recombinant hepatitis B vaccine (Schad, V. C. et al., Seminars in Immunol., 3:217-224 (1991)). A major mycobacterial antigen 65-kD protein has also been epitope-mapped (Lamb, J. R. et al., EMBO J., 6(5):1245-1249 (1987)). T cell epitopes have been identified in the peptides comprised of amino acid residues 112-132 and 437-459 of the 65-kD protein. Myelin basic protein (MBP), an autoantigen which induces experimental autoimmune encephalomyelitis (EAE) and the presumed autoantigen in multiple sclerosis (MS) has also been epitope-mapped in both human (Ota, K. et al., Nature, 346:183-187 (1990)) and rodent (Zamvil et al., Nature 324:258-260(1986)) systems. Ota et al. have identified a major T cell epitope recognized by MS patients, MBP amino acid residues 84-102. Minor epitopes (MBP amino acid residues 143-168, 61-82, 124-42 and 31-50) recognized by T cells from MS patients were also described. Zamvil et al. have shown that MBP amino acid residues 1-11 contain the major T cell epitope(s) causing EAE, in susceptible rodent strains. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

System and process for removing or treating harmful biological and organic substances within an enclosure Inventor(s): Hedman, David E.; (Ojai, CA) Correspondence: Kelly Bauersfeld Lowry & Kelley, Llp; 6320 Canoga Avenue; Suite 1650; Woodland Hills; CA; 91367; US Patent Application Number: 20040028554 Date filed: February 20, 2003 Abstract: A system and process is provided for removing or treating harmful biologic and organic substances within an enclosure, such as a container, building or vehicle. Air within the enclosure is heated to a predetermined temperature to kill organisms and cause harmful substances in the structure to migrate into the ambient air. Boric acid in combination with the heat may be used to kill mold and similar undesirable organisms. Temperature and pressure levels are monitored. The heated air carrying the harmful substances is passed through a filter to remove the harmful substances, and the heated air is re-circulated to enhance efficiency. The system effectively kills insects, molds, viruses and bacteria and reduces the levels of allergens and volatile organic compounds in the structure. Excerpt(s): This is a continuation-in-part of U.S. patent application Ser. No. 10/313,901, filed Dec. 5, 2002. Priority is further claimed from U.S. Provisional Application Serial Nos. 60/358,222, and 60/358,223, both filed Feb. 20, 2002. The present invention relates to methods of sanitizing buildings, passenger occupiable vehicles, and other enclosed or enclosable spaces. More particularly, the present invention relates to a system and method for killing and removing insects, dust mites and their allergens, bacteria, viruses, fungi, molds, and volatile organic compounds from such enclosures. A large number of methods have been developed for killing insects, such as termites, in buildings. The most widely used method is tenting the building, then filling the building with a toxic gas for a period of time sufficient to kill termites or other selected insects. This method is effective for killing termites and other insects. However, this method generally requires 12 hours to be effective, requiring building occupants to move out and businesses to be closed for approximately a three day period to insure proper venting of toxic material and/or gas. Tenting the building with heavy tarpaulins requires workers to walk and arrange the tarpaulins on the roof, often damaging the

196

Allergens

roof system. Food and medications must be placed in sealed containers or removed. Generally the entire building must be treated, even if the infestation is localized. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Use of a textile material having a three-dimensional structure as protection against pollen for windows and doors Inventor(s): Schroder, Andreas; (Hamburg, DE) Correspondence: Norris Mclaughlin & Marcus; 30th Floor; 220 East 42nd Street; New York; NY; 10017; US Patent Application Number: 20040079230 Date filed: September 23, 2003 Abstract: The use of spacer textiles for attachment in front of windows or doors to guard against dusty allergens such as pollen or house dust. Excerpt(s): This invention relates to a loop-formingly knitted or woven spacer fabric which is used as a guard against the penetration of dusty, airborne allergens such as pollen and fungal spores into living and working areas by attachment in front of windows and doors over the whole area thereof. The incidence of pollinosis (hay fever), ie the allergic reaction of the mucous membranes of the eye and of the upper and lower respiratory tracts with flower pollen and other airborne allergens, in the population has been monitored in Germany for a number of years. It was found that about 11-15% of the population is affected. The allergic reaction of a pollen allergy usually manifests itself in reddening and lacrimation of the eyes (conjunctivitis), sneezing episodes (rhinitis) and a dry cough (bronchial asthma) as early reactions. Known late reactions to pollen allergy include for example neurodermatitis or eczema. As well as the personal symptoms of sufferers, there are more far-reaching consequences such as loss of earnings or work incapacity during the pollen season or increased medical treatment costs, so that there is an immense need for a gridlike pollen guard within the meaning of the invention for attachment in front of the windows and doors of living and working areas. Further information about pollinosis is available in Ratgeber Pollenallergie, Ute Kunkele, Munich 1992. The most important properties a pollen guard for windows and doors must offer the user are: sufficient ability to air the amenities, sufficient transparency for letting light in and for looking out, and an alleviating effect with regard to pollen allergy. The most important parameters for describing a pollen guard are accordingly: air perviousness, optical transparency and filtering effect with regard to pollen. 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 allergens, 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 “allergens” (or synonyms) into the

Patents 197

“Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on allergens. You can also use this procedure to view pending patent applications concerning allergens. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

199

CHAPTER 6. BOOKS ON ALLERGENS Overview This chapter provides bibliographic book references relating to allergens. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on allergens 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 “allergens” (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 allergens: •

Under My Skin: A Kid's Guide to Atopic Dermatitis Source: Deerfield, IL: Fujisawa Healthcare, Inc. 2000. 48 p. Contact: Available from Fujisawa Healthcare, Inc. Three Parkway North Center, Deerfield, IL. 60015-2548. (800) 727-7003. Website: www.fujisawa.com. Summary: This book presents information about atopic dermatitis (AD), or eczema, to children. The book is divided into four sections discussing the physical and emotional aspects of AD, healing, and common triggers of AD. Topics within these sections include causes of itching; identifying irritants; the role of stress, allergens, and weather in flare-ups; infections; understanding feelings; struggling with scratching; having a healthy attitude; working with a doctor; flare care; and side effects of medications. Tips for controlling and coping with AD from children with the condition are included. A place for the child to write down questions for their doctor and a sample daily routine are appended. Numerous illustrations.

200

•

Allergens

Food Allergy Field Guide: A Lifestyle Manual for Families Source: Centennial, CO: Savory Palate, Inc. 2000. 288 p. Contact: Available from Savory Palate, Inc. 8174 South Holly, No. 404, Centennial, CO 80122-4004. (800) 741-5418 or (303) 741-5408. Fax (303) 741-0339. E-mail: [email protected]. Website: www.savorypalate.com. PRICE: $19.95 plus shipping and handling. ISBN: 1889374075. Summary: This upbeat food guide is designed to help children, parents, and other caregivers manage food sensitivities to wheat, gluten, dairy, eggs, corn, peanuts, soy, and other common food allergens. The author includes the latest research and discoveries on food sensitivities; advice on reading labels, grocery shopping, eating at restaurants; tips on emotional, social, and psychological considerations; pointers to help the child enjoy parties, field trips, and other outings; and how to detect hidden food allergies. The book includes 100 kid-tested recipes and cooking advice. The recipes are listed by category and labeled as gluten free, dairy free, egg free, nut free, or soy free. Nutrient values are provided for each recipe. The book concludes with a bibliography, fact sheets on common food allergens, nutrition facts, a list of resources and associations, a list of vendors, and a subject index.

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 “allergens” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “allergens” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “allergens” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

Allergens & Allergen Immunotherapy by Richard F. Lockey, et al; ISBN: 0824701887; http://www.amazon.com/exec/obidos/ASIN/0824701887/icongroupinterna

•

Allergens and Allergen Immunotherapy by Richard F. Lockey, et al; ISBN: 0824756509; http://www.amazon.com/exec/obidos/ASIN/0824756509/icongroupinterna

•

Allergy & Asthma Relief: Featuring The Breathe Easy Plan : Seven Steps to Allergen Resistance by William E., MD. Berger, Debra L. Gordon; ISBN: 0762106042; http://www.amazon.com/exec/obidos/ASIN/0762106042/icongroupinterna

•

Declared and Hidden Allergens in Foods: Practical Guide for Parents, Carers and Sufferers of Food Allergies by Lola Greene; ISBN: 097294110X; http://www.amazon.com/exec/obidos/ASIN/097294110X/icongroupinterna

•

Pollen Biotechnology: Gene Expression and Allergen Characterization by Shyam S. Mohapatra, R. Bruce Knox; ISBN: 0412035219; http://www.amazon.com/exec/obidos/ASIN/0412035219/icongroupinterna

•

Potency Evaluation of Contact Allergens - Dose -response Studies Using the Guinea Pig Maximization Test (TemaNord: 1996:570) by A. Boman; ISBN: 9291209074; http://www.amazon.com/exec/obidos/ASIN/9291209074/icongroupinterna

Books

201

•

Recent Trends in Allergen & Complement Research by Alain L. De Weck (Editor), et al; ISBN: 380552580X; http://www.amazon.com/exec/obidos/ASIN/380552580X/icongroupinterna

•

Something in the air airborne allergens (SuDoc HE 20.3252:2002004438) by U.S. Dept of Health and Human Services; ISBN: B0001146BC; http://www.amazon.com/exec/obidos/ASIN/B0001146BC/icongroupinterna

•

The Low Allergen Garden: How People with Asthma and Allergies Can Enjoy Their Gardens by Mark Ragg Dr; ISBN: 0733602657; http://www.amazon.com/exec/obidos/ASIN/0733602657/icongroupinterna

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

Mechanisms of Food Allergy Source: in McCormick, D.B., Bier, D.M., and Goodridge, A.G., eds. Annual Review of Nutrition. Palo Alto, CA: Annual Reviews Inc. 1996. Volume 16: 161-177. Contact: Available from Annual Reviews Inc. 4139 El Camino Way, P.O. Box 10139, Palo Alto, CA 94303-0139. (800) 523-8635. Fax (415) 424-0910. PRICE: $53.00. ISBN: 0824328167. ISSN: 01999885. Individual article reprints available from Annual Reviews Preprints and Reprints. (800) 347-8007 or (415) 259-5017. E-mail: [email protected]. Base price $13.50 per article. Summary: This article reviews recent work in the mechanisms of food allergy. With relatively uniform definitions of the clinical presentations of food allergy now available, the scientific literature is easier to understand. The authors note that the prevalence of food allergy is up to 8 percent in children and 2 percent in adults. Additionally, recent studies have shown the role of specific allergens and mediators in the immunopathogenesis of food allergy. Much of the information available still relates to immunoglobulin E-mediated food reactions, although other immunologic mechanisms are being studied extensively. The diagnosis and treatment of food allergy is now also much more standardized. Long-term studies have revealed the natural history of many of these reactions. 83 references. (AA-M).

•

Contact Dermatitis Source: in American Academy of Allergy, Asthma, and Immunology, Inc. Allergy Report: Conditions that May Have an Allergic Component. Volume 3. Milwaukee, WI: American Academy of Allergy, Asthma, and Immunology, Inc. 2000. p. 33-50. Contact: Available from American Academy of Allergy, Asthma, and Immunology, Inc. 611 East Wells Street, Milwaukee, WI 53202. (414) 272-6071. Fax: (414) 272-6070.

202

Allergens

Summary: This book chapter provides information on the causes, diagnosis, symptoms, and treatment of contact dermatitis (CD). CD refers to a wide range of reactions that result from direct contact with allergens or irritants. It is the most common occupational disease and the most common skin disease in adults. The chapter lists common causes of irritant CD and allergic CD and describes their mechanisms. Diagnosis is usually based on medical history, distribution of the eruption, and patch testing. Non-pharmacologic treatment of CD consists of minimizing the offending agent, treating the active dermatitis, and preventing recurrence from re-exposure to the offending agent. Pharmacologic management includes oral and topical corticosteroids. Oral antihistamines can relieve the itching of CD. Special considerations for managing CD, information for specialist referral, and potency rankings for topical corticosteroids are included. 13 references. •

Food-Related Illnesses and Allergies Source: in Townsend, C.E. and Roth, R.A. Nutrition and Diet Therapy. 7th ed. Albany, NY: Delmar Publishers. 1999. 171-187 p. Contact: Available from Delmar Publishers. 3 Columbia Circle, Albany, NY 12212. (800) 865-5840. E-mail: [email protected]. PRICE: $44.95 plus shipping and handling. ISBN: 0766802965. Summary: This chapter on food related illnesses and allergies is from an undergraduate textbook on nutrition and diet therapy. The chapter identifies the diseases caused by contaminated food, along with their signs and the means by which they are spread; lists the signs of food contamination; reviews precautions for protecting food from contamination; and covers allergies and elimination diets and their uses. Foodborne illnesses covered include Campylobacter jejuni, Clostridium botulinum, Clostridium perfringens, Cyclospora, Escherichia coli (O157:H7), Listeria monocytogenes, Salmonella, Shigella, and Staphylococcus aureas. The authors stress that infection or poisoning traced to food is usually caused by human ignorance or carelessness. Food should not be prepared by anyone who has or carries a contagious disease. All fresh fruits and vegetables should be washed before being eaten. Meats, poultry, fish, eggs, and dairy products should be refrigerated. Food should be covered to prevent contamination by dust, insects, or animals. Food allergies can cause many different and unpleasant symptoms, and elimination diets are used to determine their causes. Some of the most common food allergens are milk, chocolate, eggs, tomatoes, fish, citrus fruit, legumes, strawberries, and wheat. The chapter includes lists of key terms to learn, recommended discussion topics, and suggested supplemental activities, and a section of review questions so readers can test their comprehension of the material. Two illustrative case studies are appended. 1 figure. 4 tables.

•

How Vocal Abilities Can Be Limited by Non-Infectious Diseases and Disorders of the Respiratory and Digestive Systems Source: in Thurman, L. and Welch, G., eds. Bodymind and Voice: Foundations of Voice Education, Volumes 1-3. 2nd ed. Collegeville, MN: VoiceCare Network. 2000. p. 546-555. Contact: Available from National Center for Voice and Speech (NCVS). Book Sales, 334 Speech and Hearing Center, University of Iowa, Iowa City, IA 52242. Website: www.ncvs.org. PRICE: $75.00 plus shipping and handling. ISBN: 0874141230. Summary: This chapter on noninfectious diseases and disorders of the respiratory and digestive systems is from a multi-volume text that brings a biopsychosocial approach to the study of the voice. The authors use the phrase 'bodyminds' to describe the

Books

203

interrelationship of perception, memory, learning, behavior, and health, as they combine to affect all environmental interactions, adaptations, and learning. The books are written for teachers, voice professionals, people who use their voices on an avocational basis, and interested members of the general public. This chapter describes the effects of smoking and other pollutants, sinusitis and rhinitis, laryngitis, bronchitis and other pulmonary (lung) diseases, the effects of outdoor and indoor air pollution, normal and disordered nasal (nose) conditions, asthma, obstructive sleep apnea, emphysema, and gastroesophageal reflux disease (GERD, the return of stomach acid to the esophagus and larynx). GERD can result in hoarseness, lowering of the average speaking pitch range, increased effort when singing, and a 'tired voice.' Asthma can affect voice primarily by decreasing the ability of the respiratory system to inhale and then pressurize the lung air to create sufficient breathflow between the vocal folds. Asthma symptoms can be triggered by inhalation of allergens or pollutant particles of irritant chemicals, infection, cold air, vigorous exercise, acute neuropsychobiological distress, or even vigorous singing. 68 references. •

Nutritional Management of Nephrotic Syndrome Source: in Kopple, J.D. and Massry, S.G. Nutritional Management of Renal Disease. Baltimore, MD: Williams and Wilkins. 1997. p. 533-561. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (800) 638-0672 or (410) 528-4223. Fax (800) 447-8438 or (410) 528-8550. PRICE: $99.00. ISBN: 068304740X. Summary: This chapter on the nutritional management of patients with nephrotic syndrome is from a medical textbook on nutrition and metabolism of individuals with renal disease or renal failure. Nephrotic syndrome is a consequence of the urinary loss of albumin and other plasma proteins of similar size and is characterized by hypoalbuminemia, hyperlipidemia, and edema formation. The major reasons for changing a patient's diet are to blunt manifestations of the syndrome, such as edema; to replace nutrients lost in the urine; or to reduce risks (either of progression of renal disease, as might be caused by a high protein diet, or of atherosclerosis, which might be a consequence of altered lipid metabolism). Topics include the role of dietary protein and a protein restricted diet; albumin homeostasis in nephrotic syndrome; the effects of nephrotic syndrome on solid tissue proteins; dietary proteins as potential allergens responsible for renal disease (in which case, diet therapy may prove curative); the effect of altered glomerular permselectivity on lipid metabolism; the cardiovascular effects of hyperlipidemia in nephrotic syndrome; the effects of lipids on renal disease; the role of polyunsaturated fatty acids; derangements in divalent cation metabolism in nephrotic syndrome; and derangements in salt and water metabolism (volume homeostasis). The author concludes that the safest recommendation is to prescribe a diet containing 0.8 to 1 gram per kilogram per day of protein, 35 kilocalories per kilogram, low in fat, high in complex carbohydrate, but restricted in sodium chloride. Vegetarian diets may be especially useful as it is best to avoid cholesterol and saturated fats. 5 figures. 2 tables. 166 references. (AA-M).

•

Chapter 124: Atopic Dermatitis (Atopic Eczema) Source: in Freedberg, I.M., et al., eds. Fitzpatrick's Dermatology in General Medicine. 5th ed., Vol. 1. New York, NY: McGraw-Hill. 1999. p. 1464-1480. Contact: Available from McGraw-Hill Customer Services. P.O. Box 548, Blacklick, OH 43004-0548. (800) 262-4729 or (877) 833-5524. Fax (614) 759-3749 or (614) 759-3641. E-mail:

204

Allergens

[email protected]. PRICE: $395.00 plus shipping and handling. ISBN: 0070219435. Summary: This chapter provides health professionals with information on the historical aspects, epidemiology, genetics, clinical manifestations, differential diagnosis, immunopathogenesis, management, and prognosis of atopic dermatitis (AD). AD is a chronically relapsing skin disease that occurs most often during early infancy and childhood. The increased prevalence of AD is thought to involve factors such as increased exposure to pollutants, indoor allergens, and a decline in breastfeeding. Although the precise means by which AD is familially transmitted remains uncertain, some studies suggest an autosomal dominant inheritance pattern. The diagnosis of AD is based on a constellation of clinical features, including intensive pruritus, cutaneous reactivity, eye problems, and cutaneous infections. The differential diagnosis of AD involves distinguishing AD from other inflammatory skin diseases, immunodeficiencies, skin malignancies, genetic disorders, metabolic disorders, and infectious diseases and infestations. Although serum immunoglobulin (Ig) E levels are elevated in many patients who have AD, a direct relationship of IgE to implicated allergens and the clinical exacerbation of AD has been difficult to establish. Various studies have investigated the role of foods, aeroallergens, and microbial products in AD. Other studies have examined the immunopathogenesis of AD by investigating peripheral blood cells, T helper cells, cytokine expression, and similarities in the allergic inflammation of asthma and AD. Data suggest that antigen or superantigen exposure, allergen-induced IgE synthesis and T helper 2 cell-like expansion, mast cell degranulation, and keratinocyte injury may contribute to chronic AD skin inflammation and possibly to nonspecific cutaneous hyperresponsiveness. Management of AD involves individualizing a treatment plan to address each patient's skin disease reaction pattern. Options include cutaneous hydration; topical glucocorticoid treatment; identification and elimination of triggering factors such as allergens, emotional stress, and infectious agents; and use of antihistamines and tar preparations. Methods of treating poorly controlled AD include wet dressings and occlusion, systemic glucocorticoids, ultraviolet light, and hospitalization. Unproven or evolving treatments include allergen immunotherapy, interferons, cyclosporine and FK-506, extracorporeal photopheresis, and phosphodiesterase inhibitors. Factors that correlate with a poor prognosis include widespread AD in childhood, associated allergic rhinitis and asthma, family history of AD in parents or siblings, early age at onset of AD, and female sex. 10 figures, 3 tables, and 178 references. •

Allergic and Toxic Contact Stomatitis Source: in Bork, K., et al. Diseases of the Oral Mucosa and the Lips. Orlando, FL: W.B. Saunders Company. 1993. p. 181-189. Contact: Available from W.B. Saunders Company. Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887-4430. (800) 545-2522 (individuals) or (800) 782-4479 (schools); Fax (800) 874-6418 or (407) 352-3445; http://www.wbsaunders.com. PRICE: $99.00 plus shipping and handling. ISBN: 0721640397. Summary: This chapter, from a textbook on diseases of the oral mucosa and the lips, discusses allergic and toxic contact stomatitis. The authors note that allergic contact reactions are in general extremely rare in the oral mucosa and far less common than on the skin. Topics include allergic contact stomatitis, dental materials (metal prostheses, plastic prostheses, cements, glazes and veneers, amalgam, and adhesives), other allergens in the mouth, irritant contact stomatitis, leukoedema, nicotinic stomatitis (from the action of heat and nicotine on the hard palate), and exogenous tooth

Books

205

pigmentation, from coffee, tea, smoking, or medications. For each topic, the authors describe the clinical features and present brief therapeutic recommendations. Full-color photographs illustrate the chapter; references are provided for some sections. 9 figures. 2 tables. 54 references. (AA-M).

207

CHAPTER 7. PERIODICALS AND NEWS ON ALLERGENS Overview In this chapter, we suggest a number of news sources and present various periodicals that cover allergens.

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

Treatment prevents asthma deterioration despite continued allergen exposure Source: Reuters Medical News Date: January 19, 2004

•

Rat allergen exposure tied to increased asthma morbidity in inner-city children Source: Reuters Medical News Date: August 27, 2003

208

Allergens

•

Deep breaths no help against subsequent allergen challenge Source: Reuters Medical News Date: June 23, 2003

•

Dust mite allergen exposure not tied to pediatric asthma onset Source: Reuters Medical News Date: February 26, 2003

•

Endotoxin exposure may influence allergen tolerance Source: Reuters Medical News Date: September 18, 2002

•

Indoor allergens may worsen asthma in women Source: Reuters Medical News Date: May 03, 2002

•

Montelukast may thwart adverse effects of allergen immunotherapy Source: Reuters Industry Breifing Date: March 06, 2002

•

Vacuuming in homes with cats increases personal cat allergen exposure Source: Reuters Medical News Date: March 04, 2002

•

Avoidance measures curb dust mite allergen exposure in infants Source: Reuters Medical News Date: January 30, 2002

•

Ordinary laundering removes cat and mite allergens from bed linens Source: Reuters Medical News Date: October 16, 2001

•

Zafirlukast cuts cat allergen responses in sensitive asthmatics Source: Reuters Industry Breifing Date: October 11, 2001

•

Dust mite allergen prevalent in US day care centers Source: Reuters Medical News Date: September 28, 2001

•

Fungi and cat allergen levels influence asthma and allergy manifestations Source: Reuters Medical News Date: August 21, 2001

•

In asthma model, method of allergen sensitization determines effect of anti-IgE Source: Reuters Medical News Date: July 04, 2001

•

Dust mite, cockroach allergens quantified in US households for first time Source: Reuters Medical News Date: May 23, 2001 The NIH

Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date

Periodicals and News

209

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 “allergens” (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 “allergens” (or synonyms). If you know the name of a company that is relevant to allergens, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “allergens” (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 “allergens” (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 allergens:

210

•

Allergens

Is Your Gluten-Free Food Really Gluten free? Source: Gluten-Free Living. 6(3): 1, 21, 23. Summer 2001. Contact: Available from Gluten-Free Living. P.O. Box 105, Hastings-on-Hudson, NY 10706. E-mail: [email protected]. Summary: This article is from a newsletter for people following a gluten free diet. In this article, the author describes the newer methods of testing for gluten in foods, especially in those foods that are labeled as 'gluten free.' An increasing number of companies are now trying to make sure that their labeling is accurate. This increase is being driven by consumer awareness, corporate conscience, liability concerns, and government regulation. Currently, the smallest amount of gluten that has been shown to cause damage in a gluten sensitive person in 1000 parts per million (ppm) per day; European guidelines are 200 ppm and this amount seems to have become the safety standard. The author discusses attempts by the manufacturers to not only get their products tested, but also to have experts trouble shoot any problems during the manufacturing process and to train their employees and food allergens and production line cleaning methods. Their remains a concern in the gluten free food industry that an increase in testing could result in a decrease in the number and variety of products available. Testing is expensive and levels of detection are getting more minute (the smaller the amount accepted as 'gluten free,' the more difficult it is to maintain the gluten free label). The author concludes that the testing phenomenon is a natural outgrowth of the explosion of new products aimed at those who follow a gluten free diet. Consumers, researchers, processors, and government agencies are all just beginning to face the question of how to make sure gluten free foods are what they claim to be. One sidebar describes how the testing process works.

•

IBD in Infants, Children, and Adolescents: Unique Aspects of Diagnosis and Treatment Source: Intestinal Fortitude. 9(3): 1-3. 1999. Contact: Available from Intestinal Disease Foundation. 1323 Forbes Avenue, Suite 200, Pittsburgh, PA 15219. (412) 261-5888. Fax (412) 471-2722. Summary: This newsletter article outlines some of the unique features and considerations in the diagnosis of inflammatory bowel disease (IBD) in infants, children, and adolescents. Although IBD (ulcerative colitis and Crohn's disease) has been diagnosed in early infancy, the majority of cases occur between the ages of 10 and 21. One third of the total cases of IBD occur in the pediatric age group. The author stresses that when a child under 10 presents with signs and symptoms of IBD, the physician has to be careful with the diagnosis because a number of other conditions can mimic it. In infants who have persistent diarrhea and rectal bleeding with colitis, the picture may strongly resemble ulcerative colitis, when in fact the symptoms may have been caused by food allergy. Elimination of suspected food allergens, such as milk or soy protein, will improve the clinical picture, and many times these infants will grow out of the tendency for allergies by the age of 2. School age children may have Henoch Schonlein purpura, a condition characterized by inflammation of the small blood vessels that can affect any part of the body. The gastrointestinal symptoms can include abdominal pain, diarrhea, and rectal bleeding, while x rays and colonoscopies may show changes that mimic Crohn's disease. A unique feature of adolescence is the struggle between parental dependency and self reliance, which may contribute to a mistaken or delayed diagnosis. The impact of chronic inflammation on growth can be another unique aspect of IBD in children and adolescents. In addition, the impact of chronic illness (including the effects

Periodicals and News

211

of chronic use of prednisone) on the emotional makeup of children is an important factor which must be addressed by the gastroenterologist. Physicians must also be diligent in monitoring these children for other side effects of prednisone, such as osteopenia (decreased bone density) and avascular necrosis (death of areas of bone due to insufficient blood supply). •

Allergist's View of Atopic Dermatitis Source: The Advocate. 12(4): 1-2,7. 4th Quarter 2000. Contact: Available from National Eczema Association for Science and Education (NEASE). 1220 SW Morrison, Suite 433, Portland, OR 97205. (800) 818-7546 or (503) 2284430. Fax (503) 224-3363. E-mail: [email protected]. Website: www.eczema-assn.com. Summary: This newsletter article provides health professionals with information on atopic dermatitis (AD). This common chronic skin disease, which causes an extremely itchy, red rash, affects 1 in 7 young children. AD and allergy are closely related. Many children first develop AD and then develop asthma and allergic rhinitis. Children with AD frequently develop allergic respiratory disease. About 1 out of 3 children with moderate to severe AD has food allergy. Although some allergic reactions to food, such as hives, wheezing, and vomiting, are obvious, food allergies are usually not easy to detect in most children with AD. Standard allergy tests are only partially helpful. The ultimate confirmation of food allergy is possible only through an oral food challenge. A positive reaction to an oral food challenge usually causes an itchy, raised red rash. More severe reactions, including hives, lip or throat swelling, cough, wheezing, vomiting, or abdominal pain, may also occur. Although eliminating an allergy causing food from a child's diet is preferable, it can be difficult to completely eliminate major foods such as egg, milk, wheat, or soy. The most frequent cause of dietary elimination failures is unknowing exposure to small amounts of the offending ingredient in processed foods. The prognosis for outgrowing food allergies is very good for most children. Environmental allergens such as pollens, animal dander, and dust mites should be suspected in children with asthma or chronic stuffy, itchy, runny nose or eyes. A skin prick test can be used to evaluate allergy to environmental allergens. The identification and removal of specific allergens can improve AD in these patients. Intensive moisturization is also important in the treatment of AD.

•

Skin Disease: Eczema Source: Harvard Health Letter. 26(6): 7. April 2001. Contact: Available from Harvard Health Letter. P.O. Box 380, Department BI, Boston, MA 02117. (800) 829-9045 or (617) 432-1485. E-mail: [email protected]. Summary: This newsletter article provides people who have eczema with information on its causes, symptoms, and treatment. The terms eczema and dermatitis are used interchangeably to describe almost any itchy rash. People who go to the doctor for eczema or dermatitis usually do so because they have atopic dermatitis. This chronic, hereditary condition that mainly affects children presents as a red, scaly rash. The prevalence of atopic dermatitis in the United States is 12 percent to 15 percent. People who have atopic dermatitis often have family members who suffer from asthma or other allergy based atopic disorders. Specific foods and stress can trigger an attack. Self treatment involves using a combination of moisturizers to alleviate dryness and nonprescription steroid creams to reduce itching, avoiding irritants and common allergens, bathing in warm water, and limiting the use of soap. Topical steroids are the mainstay of treatment for difficult cases. Alternatives to steroid treatments are

212

Allergens

cyclosporine and tacrolimus. Cyclosporine can cause kidney damage and is not as effective as topical cream or ointment. Tacrolimus is more potent than cyclosporine, works when applied topically, and does not have severe adverse effects. 1 figure.

Academic Periodicals covering Allergens Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to allergens. In addition to these sources, you can search for articles covering allergens 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.”

213

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 allergens. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with allergens. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The

214

Allergens

following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to allergens: Cromolyn •

Inhalation - U.S. Brands: Intal http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202166.html

Infant Formulas •

Systemic - U.S. Brands: Alimentum; Alsoy; Carnation Follow-Up Formula; Carnation Good Start; Enfamil; Enfamil Human Milk Fortifier; Enfamil Premature Formula; Enfamil Premature Formula with Iron; Enfamil with Iron; Gerber Baby Formula with Iron; Gerber Soy Formula; Isomil; Isomil SF; Lactofree; Nursoy; Nutramigen; Preemie SMA 20; Preemie SMA 24; Pregestimil; ProSobee; RCF; Similac 13; Similac 20; Similac 24; Similac 27; Similac Natural Care Human Milk Fortifier; Similac PM 60/40; Similac Special Care 20; Similac Special Care 24; Similac Special Care with Iron 24; Similac with Iron 20; Similac with Iron 24; SMA 13; SMA 20; SMA 24; SMA 27; SMA Lo-Iron 13; SMA Lo-Iron 20; SMA Lo-Iron 24; Soyalac http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202678.html

Nedocromil •

Inhalation - U.S. Brands: Tilade http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202681.html

Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html.

Researching Medications

215

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.

217

APPENDICES

219

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

•

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

•

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

•

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

10

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

220

Allergens

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

•

National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

•

National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

•

Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

•

National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

•

National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

•

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

•

Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

Physician Resources

221

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/

•

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

•

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

•

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/

•

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

•

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

•

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

•

MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

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.

222

Allergens

•

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

•

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

The 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 “allergens” (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 30265 192 185 5 109 30756

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 “allergens” (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.

Physician Resources

223

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/.

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.

225

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 allergens can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to allergens. 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 allergens. 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 “allergens”:

226

Allergens

Asthma http://www.nlm.nih.gov/medlineplus/asthma.html Asthma in Children http://www.nlm.nih.gov/medlineplus/asthmainchildren.html Dermatitis http://www.nlm.nih.gov/medlineplus/dermatitis.html Food Allergy http://www.nlm.nih.gov/medlineplus/foodallergy.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 allergens. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •

Understanding Food Allergy Source: Washington, DC: International Food Information Council Foundation. 1998. [4 p.]. Contact: Available from International Food Information Council Foundation. 1100 Connecticut Avenue, NW, Suite 430, Washington, DC 20036. (202) 296-6540. PRICE: Single copy free. Summary: Food allergy is a reaction of the body's immune system to something in a food, usually a protein. This brochure is intended for consumer and patient education and addresses the basics of food allergy, food intolerance, and other food sensitivities. Written in a question and answer format, the brochure discusses the foods that tend to cause food allergy, the symptoms, anaphylaxis, other reactions or sensitivities to foods (not allergies), diagnosis, sensitivity to food additives, and ways to avoid lifethreatening food allergy situations. The eight most common food allergens are milk, eggs, peanuts, tree nuts, soy, wheat, fish, and shellfish. Common symptoms of food allergy include skin irritations, gastrointestinal symptoms (nausea, vomiting, diarrhea), and respiratory symptoms such as sneezing, runny nose, and shortness of breath. Food intolerance is an adverse reaction to a food substance or additive that involves digestion or metabolism but does not involve the immune system (e.g., lactose intolerance). Food idiosyncrasy is an abnormal response to a food or food substance that also does not involve the immune system. Sulfite sensitivity or sulfite-induced asthma is an example of a food idiosyncrasy that affects a small number of people. Diagnosis is based on a

Patient Resources

227

thorough medical history, the analysis of a food diary, and several tests, including skinprick tests, RAST tests (blood test), and food challenges. •

Food Allergy and Atopic Dermatitis Source: Fairfax, VA: Food Allergy and Anaphylaxis Network. 2000. 12 p. Contact: Available from Food Allergy and Anaphylaxis Network (FAAN). 10400 Eaton Place, Suite 107, Fairfax, VA 22030-2208. (800) 929-4040. Fax (703) 691-2713. E-mail: [email protected]. Website: www.foodallergy.org. PRICE: $3.00 plus shipping and handling. Summary: It is estimated that up to 10 percent of young children have eczema or atopic dermatitis and one in three children with significant atopic dermatitis have food allergies. This booklet discusses food allergies and atopic dermatitis, defined as a nonscarring allergic skin disease caused by a number of factors; food is one factor. This disease is not contagious. With proper management, it can be controlled, and children can grow to be self confident and enjoy the friendship of others. This booklet offers tips and other sources of information to help parents of the child with food allergy and atopic dermatitis. The booklet covers symptoms, causes, drug therapy, complications, prevention strategies, what happens as the child gets older, and tips for keeping atopic dermatitis under control in the areas of general management, school, baths, laundry, and food allergy. Atopic dermatitis is caused by inflammation of the skin and the skin's inability to retain adequate moisture. Certain substances or factors can cause atopic dermatitis to flare, including irritants such as wool, skin infections, dry skin, low humidity, heat, sweating, or emotional stress; and allergens, such as dust mites, pollens and molds, or foods. Atopic dermatitis cannot be cured, but can be controlled with consistent treatment and avoidance of substances or factors that cause it to flare. Prescription antihistamines can be used to help treat the itching that accompanies this disease, and steroid ointments can help stop the inflammation in the skin. To keep atopic dermatitis under control it is important to avoid or reduce exposure to irritants and allergens, and to moisturize the skin. The booklet stresses that raising a child with atopic dermatitis and food allergies requires extra time, planning, and the help of a doctor that the parent feels comfortable talking with. The booklet concludes with a list of additional sources of information, including the Food Allergy Network, and organizations through which readers can locate a board certified allergist, find allergy free food products, and get information about other allergy products.

•

About Ear Infections and Other Ear Problems Source: South Deerfield, MA: Channing L. Bete Company, Inc. 1995. 16 p. Contact: Available from Channing L. Bete Company, Inc. 200 State Road, South Deerfield, MA 01373-0200. (800) 628-7733; Fax (800) 499-6464; http://www.channing.bete.com. PRICE: $1.25 each for 1-24 copies; bulk rates available. Item Number 39255A-12-95. Summary: This booklet familiarizes parents with ear infections and other ear problems common in children. The booklet emphasizes that most children will experience an ear infection (acute otitis media, or middle ear infection) and the pain and discomfort that accompanies these infections. The booklet encourages parents to educate themselves about ear infections, to recognize and avoid risk factors, and to make informed choices about treatment options. Other topics include the anatomy of the ear; the causes, symptoms, diagnosis and treatment of acute otitis media (ear infection), and otitis media with effusion (OME); what to do if hearing loss is suspected; the placement of tubes in

228

Allergens

the eardrums; treatment for the pain and discomfort of ear infections; complications; and risk factors including secondhand smoke, spending time with other children who may be ill, feeding practices (breastfeeding versus bottlefeeding), and contact with allergens. The booklet concludes with answers to common questions in the areas of swimmer's ear, the impact of a child's age on the incidence of ear infections, and how ear tubes are usually placed. The booklet includes many cartoon-like line drawings illustrating children and adults in a variety of everyday settings. •

Handout on Health: Atopic Dermatitis Source: Bethesda, MD: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Information Clearinghouse. 1999. 40 p. Contact: Available from National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Information Clearinghouse. 1 AMS Circle, Bethesda, MD 20892-3675. (877) 226-4267 or (301) 495-4484. Fax (301) 718-6366. TTY (301) 565-2966. E-mail: [email protected]. Website: www.niams.nih.gov. PRICE: 1 to 25 copies free. Order Number: AR-68 HH (booklet), or AR-68L HH (large print). Summary: This booklet provides people who have atopic dermatitis and their families and caregivers with information on the symptoms, diagnosis, and treatment of this chronic skin disease, which makes the skin extremely itchy and inflamed. Atopic dermatitis most often affects infants and young children, but it can continue into adulthood. It affects males and females equally, and its onset decreases substantially with age. Atopic dermatitis is the most common of the many types of eczema. Although the cause is unknown, the disease seems to result from a combination of genetic and environmental factors. Symptoms vary from person to person, but the most common symptoms are dry, itchy skin; cracks behind the ears; and rashes on the cheeks, arms, and legs. Other common features of atopic dermatitis include lichenification, papules, ichthyosis, keratosis pilaris, hyperlinear palms, urticaria, cheilitis, atopic pleat, and hyperpigmented eyelids. The features of atopic dermatitis depend on whether an infant, a child, or an adult is affected. Diagnosis involves obtaining a thorough medical history and observing symptoms. Skin scratch/prick tests and blood tests for airborne allergens may occasionally help the doctor rule out or confirm a specific allergen that might be important in diagnosis. Many factors can make atopic dermatitis symptoms worse. These factors can be classified as irritants or allergens. Irritants are substances that directly affect the skin, whereas allergens are substances from foods, plants, or animals that inflame the skin. Other factors, including emotional issues, temperature and climate, and skin infections, also have a role in atopic dermatitis. Treatment involves proper skin care, lifestyle changes, and medications and phototherapy. People who have atopic dermatitis can maintain a high quality of life despite their symptoms. Research supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and other components of the National Institutes of Health focuses on genetics, biochemical abnormalities, faulty regulation of immunoglobulin E, immune system imbalance, and treatment. The booklet also lists additional resources.

•

All About Atopic Dermatitis Source: San Rafael, CA: National Eczema Association for Science and Education. 2003. 8 p. Contact: Available from National Eczema Association for Science and Education. 4460 Redwood Hwy, Suite 16D, San Rafael, CA 94903-1953. (415) 499-3474. Fax: (415) 4725345. Website: www.nationaleczema.org. E-mail: [email protected].

Patient Resources

229

Summary: This brochure discusses atopic dermatitis (AD), a common, noncontagious, genetic disease that is characterized by itchy, inflamed skin. AD usually begins in individuals when they are infants and appears as dry, itchy, scaly skin. Cracks behind the ears as well as rashes on the cheeks, arms, and legs may be present. Children with AD may develop asthma or hay fever. Often AD improves and worsens (flares). Flares may be triggered by exposure to irritants or by allergens. Food allergies and stress may also cause flares. Extreme or sudden changes in temperature may result in prickly heattype symptoms. Exercise may cause sweating that leads to itching. Treatment for flares includes cortisone, ultraviolet light or sunlamps, tar baths, antihistamines, antibiotics, and topical immunomodulators. Guidelines for bathing as well as suggestions for treatment and control of AD are listed. 3 photographs. •

Allergic Contact Rashes Source: American Academy of Dermatology. 2000. 8 p. Contact: American Academy of Dermatology. 930 N. Beacham Road, P.O. Box 4014, Schaumberg, IL 60168-4014. (888) 462-DERM. Website: www.aad.org. Price: single copy free; bulk prices available. Summary: This brochure for patients provides an overview of allergic contact rashes. Allergic contact rashes, or allergic contact dermatitis, are caused by allergens that come into contact with the skin resulting in itching and blisters. Common causes of this condition are contact with items containing nickel, rubber, or chromates. In addition, hair dyes, neomycin, skin care products, and plants in the poison ivy family can cause rashes. Most contact dermatitis can be diagnosed by the location of the rash. If the cause cannot be determined by patient history or physical examination, a patch test may be performed. This patch test involves applying small amounts of the potential allergen to the skin of the patient for two days. A red spot confirms the allergy. After the allergy is confirmed, the patient should avoid the allergen and substitute for it products that do not cause reactions. 5 photographs.

•

Atopic Dermatitis in Children Source: San Rafael, CA: National Eczema Association for Science and Education. 2003. 8 p. Contact: Available from National Eczema Association for Science and Education. 4460 Redwood Highway, Suite 16-Box D, San Rafael, CA 94903-1953. (415) 499-3474. Fax: (415) 472-5345. Website: www.nationaleczema.org. Email: [email protected]. PRICE: Single copy free. Summary: This brochure provides information to parents of children with atopic dermatitis (AD). AD, or eczema, is caused by too many reactive inflammatory cells in the skin and is triggered by dry skin, irritants, stress, heat and sweating, infections, and allergens. Diagnosis of AD is based on age of onset, presence of itching, location and appearance of the rash, and heredity. AD is often associated with asthma and hay fever. It is difficult to predict if a child will outgrow AD. Strategies for negating trigger factors including keeping the skin cool, avoiding stress, systematically eliminating foods if a food allergy is suspected, and learning to recognize signs of infection so they can be treated early. Medicines used to treat AD include moisturizers, corticosteroids, antibiotics, antihistamines, topical immunomodulators, and tar preparations.

230

•

Allergens

FAN Flashbacks: Diagnosis and Treatment Source: Fairfax, VA: Food Allergy and Anaphylaxis Network (FAAN). 1996. 23 p. Contact: Available from Food Allergy and Anaphylaxis Network (FAAN). 10400 Eaton Place, Suite 107, Fairfax, VA 22030. (800) 929-4040 or (703) 691-3179. Fax (703) 691-2713. E-mail: [email protected]. Web site: http://www.foodallergy.org/. Price: $2.00 each. Summary: This brochure reprints relevant information on specific topics from previous issues of Food Allergy News, the newsletter of the Food Allergy and Anaphylaxis Network. This brochure focuses on the diagnosis and treatment of food allergies. The brochure provides information about resource organizations that have information about asthma. Articles are reprinted on food allergy in young children; information to help the health care provider diagnose a child's food allergies; how food allergic reactions occur; coping with a restricted diet in the family setting; the interrelationship of food allergies and asthma; avoiding nontraditional or potentially harmful treatments for food allergy; the use of avoidance diets during pregnancy, in the nursing mother, and in infant feedings; the role of the dietitian in helping child and parent cope with food allergies; unusual causes of food reactions, including spices (oregano, coriander, cumin, and fennel have been identified as possible allergens), tree nuts, peanut dust, and milk in unexpected food items; the diagnostic tests done to identify and confirm specific allergies; food-induced enterocolitis syndrome; the use of epinephrine, antihistamine, and other medications during an allergic reaction; and food dependent exercise-induced anaphylaxis. The brochure also reprints questions and answers to diet dilemmas posed by readers: topics include ensuring adequate nutrition for toddlers with multiple food allergies; and the difference between an allergic reaction and irritant dermatitis. The brochure includes the address, telephone numbers, and email addresses for the Food Allergy and Anaphylaxis Network, a national nonprofit organization established to help families living with food allergies and to increase public awareness about food allergies and anaphylaxis. (AA-M).

•

FAQs About Eczema, The Source: Newport News, VA: Inflammatory Skin Disease Institute (ISDI). 2002. 8 p. Contact: Available from Inflammatory Skin Disease Institute. P.O. Box 1074, Newport News, VA 23601. (757) 223-0795. Fax (757) 595-1842. E-mail: [email protected]. Website: www.isdionline.org. PRICE: Contact organization for pricing information. Summary: This brochure uses a question and answer format to provide people who have eczema with information on the causes, diagnosis, and treatment of this common noncontagious skin disorder. Eczema, also known as atopic dermatitis, causes the skin to become dry, itchy, and inflamed. Eczema is most common in infants and young children, but it can occur in older people. Sites commonly affected include the face, scalp, neck, forearms, and legs. Although the exact cause of eczema is unknown, scientists believe it is a genetic disorder involving the immune system and influenced by environmental factors. Although symptoms usually improve as childhood progresses, some people will experience eczema flare ups throughout their lives. Factors that can trigger an eczema flare up include dry skin, irritants, allergens, stress, heat and sweating, and infections. Eating foods such as milk, eggs, peanuts, soy, wheat, and seafood can also cause a flare up of eczema. Keeping the skin moist is important in protecting the skin from invasive agents which may trigger a flare up. Diagnosis is based on the medical history and a physical examination. An eczema flare up can be treated with topical steroid creams and ointments, oral steroids, antihistamines, wet and cool compresses, antibiotics, and tar preparations. There is no cure for eczema, but it can

Patient Resources

231

be controlled with proper preventive measures and treatment of flare ups. People who have eczema are prone to developing dry sensitive skin, and they are at risk of developing widespread infections. •

Allergic Contact Dermatitis Source: Kirksville, MO: American Osteopathic College of Dermatology (AOCD). 2001. 3 p. Contact: Available online from American Osteopathic College of Dermatology. 1501 East Illinois Street, P.O. Box 7525, Kirksville, MO 63501. (800) 449-2623 or (660) 665-2184. Fax (660) 627-2623. E-mail: [email protected]. Website: www.aocd.org/skin/dermatologic_diseases/ index.html. Summary: This fact sheet provides people who have allergic contact dermatitis with information on the substances that cause this skin condition. Skin manifestations include redness, swelling, and formation of water blisters. Common allergens include nickel found in earrings and clothing accessories; rubber products such as gloves; paraphenylenedeamine found in permanent hair dyes; chromates found in cement, leather, some matches, paints, and antirust compounds; and poison ivy, poison oak, and poison sumac. A dermatologist can work with a patient to identify the allergen. In addition, a dermatologist can perform a patch test to diagnose contact allergies. People with allergic contact dermatitis should avoid the allergen that causes the reaction and materials that cross react with it, as well as substitute products made of materials that do not cause reactions. 2 figures.

•

Eczema--A Skin Problem Source: American Family Physician. 60(4): 1209-1210. September 15, 1999. Contact: American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237 or (913) 906-6000. E-mail: [email protected]. Website: www.aafp.org. Summary: This journal article uses a question and answer format to provide people who have eczema with information on this skin disease. Eczema causes dry skin that can itch, become red, and crack. Although the exact cause of eczema is unknown, it may be caused or exacerbated by soaps, laundry detergents, and perfumes; allergens; low humidity; heat, high humidity, and sweating; some foods; and emotional stress. Avoiding the agents that make eczema worse is one way to treat the disease. Skin care involves taking warm instead of hot showers, washing with mild soap, patting the skin dry, using a moisturizer, drinking a lot of water, running clothing through two rinse cycles, wearing gloves when working with products that might irritate the skin, washing sheets in hot water, soaking in an oatmeal bath, and wearing loose clothes. The article also explains what a person should do if food or emotional stress causes eczema, how medications can help eczema, and how to cope with itching. 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 allergens. 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

232

Allergens

and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

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

•

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

•

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

•

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

•

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

•

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

•

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

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to allergens. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with allergens. 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 allergens. 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/.

Patient Resources

233

Simply type in “allergens” (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 “allergens”. 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 “allergens” (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 “allergens” (or a synonym) into the search box, and click “Submit Query.”

235

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.21

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

21

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

236

Allergens

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)22: •

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

•

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

•

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

•

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

•

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

•

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

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

22

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

Finding Medical Libraries

237

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

238

Allergens

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

Finding Medical Libraries

239

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

•

Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

•

Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

•

Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

•

Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

•

Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

•

Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

•

Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

240

Allergens

•

South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

•

Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

•

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

•

Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

241

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 allergens: •

Basic Guidelines for Allergens Allergen Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000109.htm Allergen Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002229.htm

•

Background Topics for Allergens Allergic reaction Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000005.htm Antibody Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002223.htm Antigen Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002224.htm

242

Allergens

Perfumes Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002715.htm

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

•

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

243

ALLERGENS DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Cramps: Abdominal pain due to spasmodic contractions of the bowel. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Ablate: In surgery, is to remove. [NIH] Absenteeism: Chronic absence from work or other duty. [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] Acculturation: Process of cultural change in which one group or members of a group assimilates various cultural patterns from another. [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] Acoustic: Having to do with sound or hearing. [NIH] Acrylonitrile: A highly poisonous compound used widely in the manufacture of plastics, adhesives and synthetic rubber. [NIH] Actin: Essential component of the cell skeleton. [NIH] Acylation: The addition of an organic acid radical into a molecule. [NIH] Adenine: A purine base and a fundamental unit of adenine nucleotides. [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] Adhesives: Substances that cause the adherence of two surfaces. They include glues (properly collagen-derived adhesives), mucilages, sticky pastes, gums, resins, or latex. [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] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adoptive Transfer: Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (immunotherapy, adoptive). [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH]

244

Allergens

Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adsorption: The condensation of gases, liquids, or dissolved substances on the surfaces of solids. It includes adsorptive phenomena of bacteria and viruses as well as of tissues treated with exogenous drugs and chemicals. [NIH] Adsorptive: It captures volatile compounds by binding them to agents such as activated carbon or adsorptive resins. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]

Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agarose: A polysaccharide complex, free of nitrogen and prepared from agar-agar which is produced by certain seaweeds (red algae). It dissolves in warm water to form a viscid solution. [NIH] Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Air Pollutants: Substances which pollute the air. [NIH] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Airway Obstruction: Any hindrance to the passage of air into and out of the lungs. [NIH] Airway Resistance: Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU]

Dictionary 245

Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alkylation: The covalent bonding of an alkyl group to an organic compound. It can occur by a simple addition reaction or by substitution of another functional group. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allergic Rhinitis: Inflammation of the nasal mucous membrane associated with hay fever; fits may be provoked by substances in the working environment. [NIH] Allergy and Immunology: A medical specialty concerned with the hypersensitivity of the individual to foreign substances and protection from the resultant infection or disorder. [NIH]

Allo: A female hormone. [NIH] Allogeneic: Taken from different individuals of the same species. [NIH] Allograft: An organ or tissue transplant between two humans. [NIH] Alopecia: Absence of hair from areas where it is normally present. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alpha-Amylase: An enzyme that catalyzes the endohydrolysis of 1,4-alpha-glycosidic linkages in starch, glycogen, and related polysaccharides and oligosaccharides containing 3 or more 1,4-alpha-linked D-glucose units. EC 3.2.1.1. [NIH] Alpha-helix: One of the secondary element of protein. [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] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Ambulatory Care: Health care services provided to patients on an ambulatory basis, rather than by admission to a hospital or other health care facility. The services may be a part of a hospital, augmenting its inpatient services, or may be provided at a free-standing facility. [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

246

Allergens

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] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Amylase: An enzyme that helps the body digest starches. [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]

Anaphylactic: Pertaining to anaphylaxis. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anaphylaxis: An acute hypersensitivity reaction due to exposure to a previously encountered antigen. The reaction may include rapidly progressing urticaria, respiratory distress, vascular collapse, systemic shock, and death. [NIH] Anaplasia: Loss of structural differentiation and useful function of neoplastic cells. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH]

Dictionary 247

Anergy: Absence of immune response to particular substances. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Angina: Chest pain that originates in the heart. [NIH] Anginal: Pertaining to or characteristic of angina. [EU] Angioedema: A vascular reaction involving the deep dermis or subcutaneous or submucal tissues, representing localized edema caused by dilatation and increased permeability of the capillaries, and characterized by development of giant wheals. [EU] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]

Anode: Electrode held at a positive potential with respect to a cathode. [NIH] Antiallergic: Counteracting allergy or allergic conditions. [EU] 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] Anticholinergic: An agent that blocks the parasympathetic nerves. Called also parasympatholytic. [EU] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antidepressant: A drug used to treat depression. [NIH] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]

Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue

248

Allergens

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] Antigens, Viral: Substances elaborated by viruses that have antigenic activity. [NIH] Antihistamine: A drug that counteracts the action of histamine. The antihistamines are of two types. The conventional ones, as those used in allergies, block the H1 histamine receptors, whereas the others block the H2 receptors. Called also antihistaminic. [EU] Anti-infective: An agent that so acts. [EU] Anti-Infective Agents: Substances that prevent infectious agents or organisms from spreading or kill infectious agents in order to prevent the spread of infection. [NIH] Anti-inflammatory: Having to do with reducing inflammation. [NIH] 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] 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] Antipruritic: Relieving or preventing itching. [EU] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] Antiserum: The blood serum obtained from an animal after it has been immunized with a particular antigen. It will contain antibodies which are specific for that antigen as well as antibodies specific for any other antigen with which the animal has previously been immunized. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Apnea: A transient absence of spontaneous respiration. [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] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Approximate: Approximal [EU] Aqueous: Having to do with water. [NIH]

Dictionary 249

Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] 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] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Articular: Of or pertaining to a joint. [EU] Asbestos: Fibrous incombustible mineral composed of magnesium and calcium silicates with or without other elements. It is relatively inert chemically and used in thermal insulation and fireproofing. Inhalation of dust causes asbestosis and later lung and gastrointestinal neoplasms. [NIH] Asbestosis: A lung disorder caused by constant inhalation of asbestos particles. [NIH] Aspartame: Flavoring agent sweeter than sugar, metabolized as phenylalanine and aspartic acid. [NIH] Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter. [NIH] Aspergillosis: Infections with fungi of the genus Aspergillus. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astringents: Agents, usually topical, that cause the contraction of tissues for the control of bleeding or secretions. [NIH] Atopic: Pertaining to an atopen or to atopy; allergic. [EU] Atopic allergy: A person with a type I allergic reaction, specifically with strong familiar tendencies, caused by allergens such as pollens, foods, etc. [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] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autolysis: The spontaneous disintegration of tissues or cells by the action of their own autogenous enzymes. [NIH]

250

Allergens

Autopsy: Postmortem examination of the body. [NIH] Auxin: A natural organic compound formed in actively growing parts of plants, particularly in the growing points of shoots, which in minute concentrations regulates cell expansion and other developmental processes. [NIH] Avidity: The strength of the interaction of an antiserum with a multivalent antigen. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial toxin: A toxic substance, made by bacteria, that can be modified to kill specific tumor cells without harming normal cells. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Barium: An element of the alkaline earth group of metals. It has an atomic symbol Ba, atomic number 56, and atomic weight 138. All of its acid-soluble salts are poisonous. [NIH] Barium enema: A procedure in which a liquid with barium in it is put into the rectum and colon by way of the anus. Barium is a silver-white metallic compound that helps to show the image of the lower gastrointestinal tract on an x-ray. [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] Baths: The immersion or washing of the body or any of its parts in water or other medium for cleansing or medical treatment. It includes bathing for personal hygiene as well as for medical purposes with the addition of therapeutic agents, such as alkalines, antiseptics, oil, etc. [NIH] Beer: An alcoholic beverage usually made from malted cereal grain (as barley), flavored with hops, and brewed by slow fermentation. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] 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

Dictionary 251

cells to grow. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotin: Hexahydro-2-oxo-1H-thieno(3,4-d)imidazole-4-pentanoic acid. Growth factor present in minute amounts in every living cell. It occurs mainly bound to proteins or polypeptides and is abundant in liver, kidney, pancreas, yeast, and milk.The biotin content of cancerous tissue is higher than that of normal tissue. [NIH] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Bladder: The organ that stores urine. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood transfusion: The administration of blood or blood products into a blood vessel. [NIH] Blood 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

252

Allergens

detected by radiolabeled antibody probes. [NIH] Body Burden: The total amount of a chemical, metal or radioactive substance present at any time after absorption in the body of man or animal. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [NIH] Body Regions: Anatomical areas of the body. [NIH] Bone Density: The amount of mineral per square centimeter of bone. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by photon absorptiometry or x-ray computed tomography. [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] 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 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] Breast Feeding: The nursing of an infant at the mother's breast. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchial Provocation Tests: Tests involving inhalation of allergens (nebulized or in dust form), nebulized pharmacologically active solutions (e.g., histamine, methacholine), or control solutions, followed by assessment of respiratory function. These tests are used in the diagnosis of asthma. [NIH] Bronchiseptica: A small, gram-negative, motile bacillus. A normal inhabitant of the respiratory tract in man, dogs, and pigs, but is also associated with canine infectious tracheobronchitis and atrophic rhinitis in pigs. [NIH] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bronchoalveolar Lavage: Washing out of the lungs with saline or mucolytic agents for diagnostic or therapeutic purposes. It is very useful in the diagnosis of diffuse pulmonary infiltrates in immunosuppressed patients. [NIH] Bronchoalveolar Lavage Fluid: Fluid obtained by washout of the alveolar compartment of the lung. It is used to assess biochemical and inflammatory changes in and effects of therapy on the interstitial lung tissue. [NIH] Bronchopulmonary: Pertaining to the lungs and their air passages; both bronchial and pulmonary. [EU] Bronchoscopy: Endoscopic examination, therapy or surgery of the bronchi. [NIH]

Dictionary 253

Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Burning Mouth Syndrome: A group of painful oral symptoms associated with a burning or similar sensation. There is usually a significant organic component with a degree of functional overlay; it is not limited to the psychophysiologic group of disorders. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium Signaling: Signal transduction mechanisms whereby calcium mobilization (from outside the cell or from intracellular storage pools) to the cytoplasm is triggered by external stimuli. Calcium signals are often seen to propagate as waves, oscillations, spikes or puffs. The calcium acts as an intracellular messenger by activating calcium-responsive proteins. [NIH]

Callus: A callosity or hard, thick skin; the bone-like reparative substance that is formed round the edges and fragments of broken bone. [NIH] Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [NIH] 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] Carcinogenic: Producing carcinoma. [EU] Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH] Cardiac: Having to do with the heart. [NIH] Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheters: A small, flexible tube that may be inserted into various parts of the body to inject

254

Allergens

or remove liquids. [NIH] Cathode: An electrode, usually an incandescent filament of tungsten, which emits electrons in an X-ray tube. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Caustic: An escharotic or corrosive agent. Called also cauterant. [EU] Celiac Disease: A disease characterized by intestinal malabsorption and precipitated by gluten-containing foods. The intestinal mucosa shows loss of villous structure. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell Extracts: Preparations of cell constituents or subcellular materials, isolates, or substances. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell motility: The ability of a cell to move. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell 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] Cellular adhesion: The close adherence (bonding) to adjoining cell surfaces. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Depressants: A very loosely defined group of drugs that tend to reduce the activity of the central nervous system. The major groups included here are ethyl alcohol, anesthetics, hypnotics and sedatives, narcotics, and tranquilizing agents (antipsychotics and antianxiety agents). [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cetirizine: A potent second-generation histamine H1 antagonist that is effective in the treatment of allergic rhinitis, chronic urticaria, and pollen-induced asthma. Unlike many traditional antihistamines, it does not cause drowsiness or anticholinergic side effects. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Cheilitis: Inflammation of the lips. It is of various etiologies and degrees of pathology. [NIH] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C

Dictionary 255

(chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] 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] Chest Pain: Pressure, burning, or numbness in the chest. [NIH] Chimera: An individual that contains cell populations derived from different zygotes. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] 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] 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 Disease: Disease or ailment of long duration. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Chymopapain: A cysteine endopeptidase isolated from papaya latex. Preferential cleavage at glutamic and aspartic acid residues. EC 3.4.22.6. [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] Clathrin: The main structural coat protein of coated vesicles which play a key role in the intracellular transport between membranous organelles. Clathrin also interacts with cytoskeletal proteins. [NIH] Clathrin-Coated Vesicles: Vesicles formed when cell-membrane coated pits invaginate and pinch off. The outer surface of these vesicles is covered with a lattice-like network of the protein clathrin. Shortly after formation, however, the clathrin coat is removed and the vesicles are referred to as endosomes. [NIH] Claviceps: A genus of ascomycetous fungi, family Clavicipitaceae, order Hypocreales, parasitic on various grasses. The sclerotia contain several toxic alkaloids. Claviceps purpurea on rye causes ergotism. [NIH]

256

Allergens

Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Coated Vesicles: Vesicles formed when cell-membrane coated pits invaginate and pinch off. The outer surface of these vesicles are covered with a lattice-like network of coat proteins, such as clathrin, coat protein complex proteins, or caveolins. [NIH] Cobalt: A trace element that is a component of vitamin B12. It has the atomic symbol Co, atomic number 27, and atomic weight 58.93. It is used in nuclear weapons, alloys, and pigments. Deficiency in animals leads to anemia; its excess in humans can lead to erythrocytosis. [NIH] Cochlea: The part of the internal ear that is concerned with hearing. It forms the anterior part of the labyrinth, is conical, and is placed almost horizontally anterior to the vestibule. [NIH]

Cochlear: Of or pertaining to the cochlea. [EU] Cochlear Diseases: Diseases of the cochlea, the part of the inner ear that is concerned with hearing. [NIH] Cockroaches: Insects of the order Dictyoptera comprising several families including Blaberidae, Blattellidae, Blattidae (containing the American cockroach Periplaneta americana), Cryptocercidae, and Polyphagidae. [NIH] Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (codon, terminator). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, transfer) complementary to all codons. These codons are referred to as unassigned codons (codons, nonsense). [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] Colic: Paroxysms of pain. This condition usually occurs in the abdominal region but may occur in other body regions as well. [NIH] Colitis: Inflammation of the colon. [NIH]

Dictionary 257

Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Colostrum: The thin, yellow, serous fluid secreted by the mammary glands during pregnancy and immediately postpartum before lactation begins. It consists of immunologically active substances, white blood cells, water, protein, fat, and carbohydrates. [NIH]

Competency: The capacity of the bacterium to take up DNA from its surroundings. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complement Activation: The sequential activation of serum components C1 through C9, initiated by an erythrocyte-antibody complex or by microbial polysaccharides and properdin, and producing an inflammatory response. [NIH] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as

258

Allergens

standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementation: The production of a wild-type phenotype when two different mutations are combined in a diploid or a heterokaryon and tested in trans-configuration. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Concomitant: Accompanying; accessory; joined with another. [EU] Condoms: A sheath that is worn over the penis during sexual behavior in order to prevent pregnancy or spread of sexually transmitted disease. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Conjunctivitis: Inflammation of the conjunctiva, generally consisting of conjunctival hyperaemia associated with a discharge. [EU] Conjunctivitis, Allergic: Conjunctivitis due to hypersensitivity to various allergens. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constriction: The act of constricting. [NIH] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Contact dermatitis: Inflammation of the skin with varying degrees of erythema, edema and

Dictionary 259

vesinculation resulting from cutaneous contact with a foreign substance or other exposure. [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] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]

Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Corneum: The superficial layer of the epidermis containing keratinized cells. [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] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Cotinine: 1-Methyl-5-(3-pyridyl)-2-pyrrolidinone antidepressant. Synonym: Scotine. [NIH]

fumarate.

Stimulant

proposed

as

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

260

Allergens

whether there is an associated hemorrhage. [NIH] Craniofacial Abnormalities: Congenital structural deformities, malformations, or other abnormalities of the cranium and facial bones. [NIH] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [NIH] Crowns: A prosthetic restoration that reproduces the entire surface anatomy of the visible natural crown of a tooth. It may be partial (covering three or more surfaces of a tooth) or complete (covering all surfaces). It is made of gold or other metal, porcelain, or resin. [NIH] Cryofixation: Fixation of a tissue by localized cooling at very low temperature. [NIH] Cryopreservation: Preservation of cells, tissues, organs, or embryos by freezing. In histological preparations, cryopreservation or cryofixation is used to maintain the existing form, structure, and chemical composition of all the constituent elements of the specimens. [NIH]

Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cyproheptadine: A serotonin antagonist and a histamine H1 blocker used as antipruritic, appetite stimulant, antiallergic, and for the post-gastrectomy dumping syndrome, etc. [NIH] Cystamine: A radiation-protective agent that interferes with sulfhydryl enzymes. It may also protect against carbon tetrachloride liver damage. [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]

Cytogenetics: A branch of genetics which deals with the cytological and molecular behavior of genes and chromosomes during cell division. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoskeletal Proteins: Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for

Dictionary 261

organelles and formed bodies, and make communication between parts of the cell possible. [NIH]

Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Dairy Products: Raw and processed or manufactured milk and milk-derived products. These are usually from cows (bovine) but are also from goats, sheep, reindeer, and water buffalo. [NIH] 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] Decubitus: An act of lying down; also the position assumed in lying down. [EU] Decubitus Ulcer: An ulceration caused by prolonged pressure in patients permitted to lie too still for a long period of time. The bony prominences of the body are the most frequently affected sites. The ulcer is caused by ischemia of the underlying structures of the skin, fat, and muscles as a result of the sustained and constant pressure. [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] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [NIH]

Dental Abutments: Natural teeth or teeth roots used as anchorage for a fixed or removable denture or other prosthesis (such as an implant) serving the same purpose. [NIH] Dental Materials: Materials used in the production of dental bases, restorations, impressions, prostheses, etc. [NIH] Dentures: An appliance used as an artificial or prosthetic replacement for missing teeth and adjacent tissues. It does not include crowns, dental abutments, nor artificial teeth. [NIH] Deoxyribonucleotides: A purine or pyrimidine base bonded to a deoxyribose containing a bond to a phosphate group. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Dermatitis: Any inflammation of the skin. [NIH]

262

Allergens

Dermatologist: A doctor who specializes in the diagnosis and treatment of skin problems. [NIH]

Dermis: A layer of vascular connective tissue underneath the epidermis. The surface of the dermis contains sensitive papillae. Embedded in or beneath the dermis are sweat glands, hair follicles, and sebaceous glands. [NIH] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Desensitisation: Gradually increasing the dose of a medicine in order to overcome severe allergic reactions. [NIH] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Detergents: Purifying or cleansing agents, usually salts of long-chain aliphatic bases or acids, that exert cleansing (oil-dissolving) and antimicrobial effects through a surface action that depends on possessing both hydrophilic and hydrophobic properties. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Developed Countries: Countries that have reached a level of economic achievement through an increase of production, per capita income and consumption, and utilization of natural and human resources. [NIH] Dextrans: A group of glucose polymers made by certain bacteria. Dextrans are used therapeutically as plasma volume expanders and anticoagulants. They are also commonly used in biological experimentation and in industry for a wide variety of purposes. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The dialyzer has two sections separated by a membrane. One section holds dialysate. The other holds the patient's blood. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] Dietary Proteins: Proteins obtained from foods. They are the main source of the essential amino acids. [NIH] Dietitian: An expert in nutrition who helps people plan what and how much food to eat. [NIH]

Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive 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] Dihydrotestosterone: Anabolic agent. [NIH]

Dictionary 263

Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer. [NIH] Diphtheria: A localized infection of mucous membranes or skin caused by toxigenic strains of Corynebacterium diphtheriae. It is characterized by the presence of a pseudomembrane at the site of infection. Diphtheria toxin, produced by C. diphtheriae, can cause myocarditis, polyneuritis, and other systemic toxic effects. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disease Vectors: Invertebrates or non-human vertebrates which transmit infective organisms from one host to another. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disposition: A tendency either physical or mental toward certain diseases. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Dissociative Disorders: Sudden temporary alterations in the normally integrative functions of consciousness. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Disulphides: A covalent bridge formed by the oxidation of two cysteine residues to a cystine residue. The-S-S-bond is very strong and its presence confers additional stability. [NIH]

Dithiothreitol: A reagent commonly used in biochemical studies as a protective agent to prevent the oxidation of SH (thiol) groups and for reducing disulphides to dithiols. [NIH] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Doxycycline: A synthetic tetracycline derivative with a range of antimicrobial activity and mode of action similar to that of tetracycline, but more effective against many species.

264

Allergens

Animal studies suggest that it may cause less tooth staining than other tetracyclines. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Dry Eye Syndrome: A common condition that occurs when the eyes do not produce enough tears to keep the eye moist and comfortable. Common symptoms of dry eye include pain, stinging, burning, scratchiness, and intermittent blurring of vision. [NIH] Duct: A tube through which body fluids pass. [NIH] Dumping Syndrome: Gastrointestinal nonfunctioning pylorus. [NIH]

symptoms

resulting

from

an

absent

or

Duodenum: The first part of the small intestine. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Ectopic: Pertaining to or characterized by ectopia. [EU] Eczema: A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents (Dorland, 27th ed). [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Effusion: The escape of fluid into a part or tissue, as an exudation or a transudation. [EU] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] 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

Dictionary 265

latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]

Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emollient: Softening or soothing; called also malactic. [EU] Emphysema: A pathological accumulation of air in tissues or organs. [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] Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Encephalomyelitis: A general term indicating inflammation of the brain and spinal cord, often used to indicate an infectious process, but also applicable to a variety of autoimmune and toxic-metabolic conditions. There is significant overlap regarding the usage of this term and encephalitis in the literature. [NIH] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the endocrine system. [NIH] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endosomes: Cytoplasmic vesicles formed when coated vesicles shed their clathrin coat. Endosomes internalize macromolecules bound by receptors on the cell surface. [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]

266

Allergens

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] Enema: The injection of a liquid through the anus into the large bowel. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Enterocolitis: Inflammation of the intestinal mucosa of the small and large bowel. [NIH] Enteropeptidase: A specialized proteolytic enzyme secreted by intestinal cells. It converts trypsinogen into its active form trypsin by removing the N-terminal peptide. EC 3.4.21.9. [NIH]

Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Environmental tobacco smoke: ETS. Smoke that comes from the burning of a tobacco product and smoke that is exhaled by smokers (second-hand smoke). Inhaling ETS is called involuntary or passive smoking. [NIH] Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [NIH] Eosinophil: A polymorphonuclear leucocyte with large eosinophilic granules in its cytoplasm, which plays a role in hypersensitivity reactions. [NIH] Eosinophilia: Abnormal increase in eosinophils in the blood, tissues or organs. [NIH] Eosinophilic: A condition found primarily in grinding workers caused by a reaction of the pulmonary tissue, in particular the eosinophilic cells, to dust that has entered the lung. [NIH] Eosinophilic Gastroenteritis: Infection and swelling of the lining of the stomach, small intestine, or large intestine. The infection is caused by white blood cells (eosinophils). [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic

Dictionary 267

vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]

Ergot: Cataract due to ergot poisoning caused by eating of rye cereals contaminated by a fungus. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophagitis: Inflammation, acute or chronic, of the esophagus caused by bacteria, chemicals, or trauma. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Ether: One of a class of organic compounds in which any two organic radicals are attached directly to a single oxygen atom. [NIH] Eucalyptus: A genus of Australian trees of the Myrtaceae family that yields gums, oils, and resins which are used as flavoring agents, astringents, and aromatics, and formerly to treat diarrhea, asthma, bronchitis, and respiratory tract infections. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excipients: Usually inert substances added to a prescription in order to provide suitable consistency to the dosage form; a binder, matrix, base or diluent in pills, tablets, creams, salves, etc. [NIH] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] 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] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]

Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and

268

Allergens

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 Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extracorporeal: Situated or occurring outside the body. [EU] Facial: Of or pertaining to the face. [EU] Faecal: Pertaining to or of the nature of feces. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] 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] Fetal Blood: Blood of the fetus. Exchange of nutrients and waste between the fetal and maternal blood occurs via the placenta. The cord blood is blood contained in the umbilical vessels at the time of delivery. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [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] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Fish Products: Food products manufactured from fish (e.g., fish flour, fish meal). [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

Dictionary 269

carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flatus: Gas passed through the rectum. [NIH] Flavoring Agents: Substances added to foods and medicine to improve the quality of taste. [NIH]

Flexor: Muscles which flex a joint. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Follow-Up Studies: Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease. [NIH]

Food Additives: Substances which are of little or no nutritive value, but are used in the processing or storage of foods or animal feed, especially in the developed countries; includes antioxidants, food preservatives, food coloring agents, flavoring agents, anti-infective agents (both plain and local), vehicles, excipients and other similarly used substances. Many of the same substances are pharmaceutic aids when added to pharmaceuticals rather than to foods. [NIH]

Food Coloring Agents: Natural or synthetic dyes used as coloring agents in processed foods. [NIH] Food Contamination: The presence in food of harmful, unpalatable, or otherwise objectionable foreign substances, e.g. chemicals, microorganisms or diluents, before, during, or after processing or storage. [NIH] Food Hypersensitivity: Gastrointestinal disturbances, skin eruptions, or shock due to allergic reactions to allergens ingested in food. [NIH] Food Preservatives: Substances capable of inhibiting, retarding or arresting the process of fermentation, acidification or other deterioration of foods. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Friction: Surface resistance to the relative motion of one body against the rubbing, sliding, rolling, or flowing of another with which it is in contact. [NIH] Fructose: A type of sugar found in many fruits and vegetables and in honey. Fructose is used to sweeten some diet foods. It is considered a nutritive sweetener because it has calories. [NIH] 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

270

Allergens

the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [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] 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 Neoplasms: Tumors or cancer of the gastrointestinal system. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gels: Colloids with a solid continuous phase and liquid as the dispersed phase; gels may be unstable when, due to temperature or other cause, the solid phase liquifies; the resulting colloid is called a sol. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Products, rev: Trans-acting nuclear proteins whose functional expression are required for HIV viral replication. Specifically, the rev gene products are required for processing and translation of the HIV gag and env mRNAs, and thus rev regulates the expression of the viral structural proteins. rev can also regulate viral regulatory proteins. A cis-acting antirepression sequence (CAR) in env, also known as the rev-responsive element (RRE), is responsive to the rev gene product. rev is short for regulator of virion. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes

Dictionary 271

may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Genes, env: DNA sequences that form the coding region for the viral envelope (env) proteins in retroviruses. The env genes contain a cis-acting RNA target sequence for the rev protein (= gene products, rev), termed the rev-responsive element (RRE). [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genetics, Biochemical: A branch of genetics which deals with the chemical structure of the genes and with the mechanisms by which the genes control and regulate the structure and synthesis of proteins. [NIH] Genital: Pertaining to the genitalia. [EU] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germline mutation: A gene change in the body's reproductive cells (egg or sperm) that becomes incorporated into the DNA of every cell in the body of offspring; germline mutations are passed on from parents to offspring. Also called hereditary mutation. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Gliadin: Simple protein, one of the prolamines, derived from the gluten of wheat, rye, etc. May be separated into 4 discrete electrophoretic fractions. It is the toxic factor associated with celiac disease. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glottis: The vocal apparatus of the larynx, consisting of the true vocal cords (plica vocalis) and the opening between them (rima glottidis). [NIH]

272

Allergens

Glucans: Polysaccharides composed of repeating glucose units. They can consist of branched or unbranched chains in any linkages. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] 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] Gluten: The protein of wheat and other grains which gives to the dough its tough elastic character. [EU] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycoside: Any compound that contains a carbohydrate molecule (sugar), particularly any such natural product in plants, convertible, by hydrolytic cleavage, into sugar and a nonsugar component (aglycone), and named specifically for the sugar contained, as glucoside (glucose), pentoside (pentose), fructoside (fructose) etc. [EU] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] Goats: Any of numerous agile, hollow-horned ruminants of the genus Capra, closely related to the sheep. [NIH] Goblet Cells: Cells of the epithelial lining that produce and secrete mucins. [NIH] Gonadal: Pertaining to a gonad. [EU] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Government Agencies: Administrative units of government responsible for policy making and management of governmental activities in the U.S. and abroad. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the

Dictionary 273

recipient. [NIH] Graft-versus-host disease: GVHD. A reaction of donated bone marrow or peripheral stem cells against a person's tissue. [NIH] Granule: A small pill made from sucrose. [EU] Granulocyte: A type of white blood cell that fights bacterial infection. Neutrophils, eosinophils, and basophils are granulocytes. [NIH] 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] 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] Hair Color: Color of hair or fur. [NIH] Hair Dyes: Dyes used as cosmetics to change hair color either permanently or temporarily. [NIH]

Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [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] Hay Fever: A seasonal variety of allergic rhinitis, marked by acute conjunctivitis with lacrimation and itching, regarded as an allergic condition triggered by specific allergens. [NIH]

Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Health Behavior: Behaviors expressed by individuals to protect, maintain or promote their health status. For example, proper diet, and appropriate exercise are activities perceived to influence health status. Life style is closely associated with health behavior and factors influencing life style are socioeconomic, educational, and cultural. [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 Services: Services for the diagnosis and treatment of disease and the maintenance of health. [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] Helminths: Commonly known as parasitic worms, this group includes the acanthocephala,

274

Allergens

nematoda, and platyhelminths. Some authors consider certain species of leeches that can become temporarily parasitic as helminths. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Hereditary mutation: A gene change in the body's reproductive cells (egg or sperm) that becomes incorporated into the DNA of every cell in the body of offspring; hereditary mutations are passed on from parents to offspring. Also called germline mutation. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] 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]

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] Histocompatibility: The degree of antigenic similarity between the tissues of different individuals, which determines the acceptance or rejection of allografts. [NIH] Histocompatibility Antigens: A group of antigens that includes both the major and minor histocompatibility antigens. The former are genetically determined by the major

Dictionary 275

histocompatibility complex. They determine tissue type for transplantation and cause allograft rejections. The latter are systems of allelic alloantigens that can cause weak transplant rejection. [NIH] Hoarseness: An unnaturally deep or rough quality of voice. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Horny layer: The superficial layer of the epidermis containing keratinized cells. [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] Hydration: Combining with water. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolases: Any member of the class of enzymes that catalyze the cleavage of the substrate and the addition of water to the resulting molecules, e.g., esterases, glycosidases (glycoside hydrolases), lipases, nucleotidases, peptidases (peptide hydrolases), and phosphatases (phosphoric monoester hydrolases). EC 3. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU]

276

Allergens

Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hydroxyzine: A histamine H1 receptor antagonist that is effective in the treatment of chronic urticaria, dermatitis, and histamine-mediated pruritus. Unlike its major metabolite cetirizine, it does cause drowsiness. It is also effective as an antiemetic, for relief of anxiety and tension, and as a sedative. [NIH] Hygienic: Pertaining to hygiene, or conducive to health. [EU] Hyperaemia: An excess of blood in a part; engorgement. [EU] Hyperlipidemia: An excess of lipids in the blood. [NIH] 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] Hyperreflexia: Exaggeration of reflexes. [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] 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] Hypnotics and Sedatives: Drugs used to induce drowsiness or sleep or to reduce psychological excitement or anxiety. [NIH] Hypotension: Abnormally low blood pressure. [NIH] Ichthyosis: Any of several generalized skin disorders characterized by dryness, roughness, and scaliness, due to hypertrophy of the stratum corneum epidermis. Most are genetic, but some are acquired, developing in association with other systemic disease or genetic syndrome. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Idiosyncrasy: An abnormal susceptibility to some drug, protein, or other agent which is peculiar to the individual. [EU] Idiotype: The unique antigenic determinant in the variable region. [NIH] Illusion: A false interpretation of a genuine percept. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Immersion: The placing of a body or a part thereof into a liquid. [NIH] Immune 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] Immunity:

Nonsusceptibility

to

the

invasive

or

pathogenic

effects

of

foreign

Dictionary 277

microorganisms or to the toxic effect of antigenic substances. [NIH] 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]

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] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulins: Glycoproteins present in the blood (antibodies) and in other tissue. They are classified by structure and activity into five classes (IgA, IgD, IgE, IgG, IgM). [NIH] 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] Immunosuppression: Deliberate prevention or diminution of the host's immune response. It may be nonspecific as in the administration of immunosuppressive agents (drugs or radiation) or by lymphocyte depletion or may be specific as in desensitization or the simultaneous administration of antigen and immunosuppressive drugs. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive 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] 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]

278

Allergens

Incision: A cut made in the body during surgery. [NIH] Incompetence: Physical or mental inadequacy or insufficiency. [EU] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Incubation period: The period of time likely to elapse between exposure to the agent of the disease and the onset of clinical symptoms. [NIH] 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] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Infestation: Parasitic attack or subsistence on the skin and/or its appendages, as by insects, mites, or ticks; sometimes used to denote parasitic invasion of the organs and tissues, as by helminths. [NIH] 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] Inflammation Mediators: The endogenous compounds that mediate inflammation (autacoids) and related exogenous compounds including the synthetic prostaglandins (prostaglandins, synthetic). [NIH] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]

Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Ingestion: Taking into the body by mouth [NIH] 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] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been

Dictionary 279

identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Inositol 1,4,5-Trisphosphate: Intracellular messenger formed by the action of phospholipase C on phosphatidylinositol 4,5-bisphosphate, which is one of the phospholipids that make up the cell membrane. Inositol 1,4,5-trisphosphate is released into the cytoplasm where it releases calcium ions from internal stores within the cell's endoplasmic reticulum. These calcium ions stimulate the activity of B kinase or calmodulin. [NIH] Insect Proteins: Proteins found in any species of insect. [NIH] Insecticide Resistance: The development by insects of resistance to insecticides. [NIH] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Integrins: A family of transmembrane glycoproteins consisting of noncovalent heterodimers. They interact with a wide variety of ligands including extracellular matrix glycoproteins, complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors, the leukocyte adhesion receptors, and the very-late-antigen receptors. Each family contains a common beta-subunit combined with one or more distinct alpha-subunits. These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development, hemostasis, thrombosis, wound healing, immune and nonimmune defense mechanisms, and oncogenic transformation. [NIH] 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-10: Factor that is a coregulator of mast cell growth. It is produced by T-cells and

280

Allergens

B-cells and shows extensive homology with the Epstein-Barr virus BCRFI gene. [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] Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestinal Mucosa: The surface lining of the intestines where the cells absorb nutrients. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intravascular: Within a vessel or vessels. [EU] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] 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] Irritants: Drugs that act locally on cutaneous or mucosal surfaces to produce inflammation; those that cause redness due to hyperemia are rubefacients; those that raise blisters are

Dictionary 281

vesicants and those that penetrate sebaceous glands and cause abscesses are pustulants; tear gases and mustard gases are also irritants. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isocyanates: Organic compounds that contain the -NCO radical. [NIH] Isoelectric: Separation of amphoteric substances, dissolved in water, based on their isoelectric behavior. The amphoteric substances are a mixture of proteins to be separated and of auxiliary "carrier ampholytes". [NIH] Isoelectric Point: The pH in solutions of proteins and related compounds at which the dipolar ions are at a maximum. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. [NIH] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [NIH] Keratosis: Any horny growth such as a wart or callus. [NIH] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Labyrinth: The internal ear; the essential part of the organ of hearing. It consists of an osseous and a membranous portion. [NIH] Laceration: 1. The act of tearing. 2. A torn, ragged, mangled wound. [EU] Lactation: The period of the secretion of milk. [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] Laryngitis: Inflammation of the larynx. This condition presents itself with dryness and soreness of the throat, difficulty in swallowing, cough, and hoarseness. [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]

282

Allergens

Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Latex Allergy: Hypersensitivity to products containing processed natural rubber latex such as rubber gloves, condoms, catheters, dental dams, balloons, and sporting equipment. Both T-cell mediated (delayed hypersensitivity) and IgE antibody-mediated (immediate hypersensitivity) allergic responses are possible. Delayed hypersensitivity results from exposure to antioxidants present in the rubber; immediate hypersensitivity results from exposure to a latex protein. [NIH] Lead Poisoning: Disease caused by the gradual accumulation of a significant body burden of lead. [NIH] Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]

Leukemia: Cancer of blood-forming tissue. [NIH] 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] 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] Lichenification: Hypertrophy of the epidermis, resulting in thickening of the skin with exaggeration of the normal skin markings, giving the skin a leathery barklike appearance, which is caused by prolonged rubbing or scratching. It may arise on seemingly normal skin, or it may develop at the site of another pruritic cutaneous disorder. [EU] 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] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligases: A class of enzymes that catalyze the formation of a bond between two substrate molecules, coupled with the hydrolysis of a pyrophosphate bond in ATP or a similar energy donor. (Dorland, 28th ed) EC 6. [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] Lip: Either of the two fleshy, full-blooded margins of the mouth. [NIH]

Dictionary 283

Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Liposome: A spherical particle in an aqueous medium, formed by a lipid bilayer enclosing an aqueous compartment. [EU] 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] 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] Lod: The lowest analyte content which, if actually present, will be detected with reasonable statistical certainty and can be identified according to the identification criteria of the method. If both accuracy and precision are constant over a concentration range. [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] Loratadine: A second-generation histamine H1 receptor antagonist used in the treatment of allergic rhinitis and urticaria. Unlike most classical antihistamines it lacks central nervous system depressing effects such as drowsiness. [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]

Lubricants: Oily or slippery substances. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B

284

Allergens

(with subpopulations of each); those with characteristics of neither major class are called null cells. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphokine: A soluble protein produced by some types of white blood cell that stimulates other white blood cells to kill foreign invaders. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lymphoproliferative: Disorders characterized by proliferation of lymphoid tissue, general or unspecified. [NIH] Lymphotoxin: Soluble substance released by lymphocytes activated by antigens or T-cell mitogens, that is cytotoxic to other cells. It is involved in allergies and chronic inflammatory diseases. Lymphotoxin is antigenically distinct from tumor necrosis factor-alpha (tumor necrosis factor), though they both share a common receptor, biological activities, and significant amino acid sequences. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Macrophage Colony-Stimulating Factor: A mononuclear phagocyte colony-stimulating factor synthesized by mesenchymal cells. The compound stimulates the survival, proliferation, and differentiation of hematopoietic cells of the monocyte-macrophage series. M-CSF is a disulfide-bonded glycoprotein dimer with a MW of 70 kDa. It binds to a specific high affinity receptor (receptor, macrophage colony-stimulating factor). [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Mammary: Pertaining to the mamma, or breast. [EU] 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] 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] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH]

Dictionary 285

Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Fusion: The adherence of cell membranes, intracellular membranes, or artifical membrane models of either to each other or to viruses, parasites, or interstitial particles through a variety of chemical and physical processes. [NIH] Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [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: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metamorphosis: The ontogeny of insects, i. e. the series of changes undergone from egg, through larva and pupa, or through nymph, to adult. [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] Methacrylate: A vinyl monomer. [NIH] Methoxsalen: A naturally occurring furocoumarin compound found in several species of plants, including Psoralea corylifolia. It is a photoactive substance that forms DNA adducts in the presence of ultraviolet A irradiation. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [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

286

Allergens

organisms, they are sometimes classified as microorganisms. [NIH] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microscopy, Confocal: A light microscopic technique in which only a small spot is illuminated and observed at a time. An image is constructed through point-by-point scanning of the field in this manner. Light sources may be conventional or laser, and fluorescence or transmitted observations are possible. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milk Hypersensitivity: Allergic reaction to milk (usually cow's milk) or milk products. In infants the hypersensitivity is manifested by colic, vomiting, diarrhea, rhinitis, wheezing, etc. Milk hypersensitivity should be differentiated from lactose intolerance, an intolerance to milk as a result of congenital deficiency of lactase. [NIH] Milligram: A measure of weight. A milligram is approximately 450,000-times smaller than a pound and 28,000-times smaller than an ounce. [NIH] Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same. [NIH] Mineralocorticoids: A group of corticosteroids primarily associated with the regulation of water and electrolyte balance. This is accomplished through the effect on ion transport in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by plasma volume, serum potassium, and angiotensin II. [NIH] Minor Histocompatibility Antigens: Allelic alloantigens often responsible for weak graft rejection in cases when (major) histocompatibility has been established by standard tests. In the mouse they are coded by more than 500 genes at up to 30 minor histocompatibility loci. The most well-known minor histocompatibility antigen in mammals is the H-Y antigen. [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] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular mass: The sum of the atomic masses of all atoms in a molecule, based on a scale in which the atomic masses of hydrogen, carbon, nitrogen, and oxygen are 1, 12, 14, and 16, respectively. For example, the molecular mass of water, which has two atoms of hydrogen

Dictionary 287

and one atom of oxygen, is 18 (i.e., 2 + 16). [NIH] Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monophosphate: So called second messenger for neurotransmitters and hormones. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Motor Neurons: Neurons which activate muscle cells. [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] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]

Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat

288

Allergens

(lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Multivalent: Pertaining to a group of 5 or more homologous or partly homologous chromosomes during the zygotene stage of prophase to first metaphasis in meiosis. [NIH] 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] 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] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Myalgia: Pain in a muscle or muscles. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocarditis: Inflammation of the myocardium; inflammation of the muscular walls of the heart. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Nasal Cavity: The proximal portion of the respiratory passages on either side of the nasal septum, lined with ciliated mucosa, extending from the nares to the pharynx. [NIH] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Nasal Septum: The partition separating the two nasal cavities in the midplane, composed of cartilaginous, membranous and bony parts. [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] 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] Needs Assessment: Systematic identification of a population's needs or the assessment of individuals to determine the proper level of services needed. [NIH] Neomycin: Antibiotic complex produced by Streptomyces fradiae. It is composed of neomycins A, B, and C. It acts by inhibiting translation during protein synthesis. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU]

Dictionary 289

Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. [NIH] Nephrology: A subspecialty of internal medicine concerned with the anatomy, physiology, and pathology of the kidney. [NIH] Nephrosis: Descriptive histopathologic term for renal disease without an inflammatory component. [NIH] Nephrotic: Pertaining to, resembling, or caused by nephrosis. [EU] Nephrotic Syndrome: Clinical association of heavy proteinuria, hypoalbuminemia, and generalized edema. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neurodermatitis: An extremely variable eczematous skin disease that is presumed to be a response to prolonged vigorous scratching, rubbing, or pinching to relieve intense pruritus. It varies in intensity, severity, course, and morphologic expression in different individuals. Neurodermatitis is believed by some to be psychogenic. The circumscribed or localized form is often referred to as lichen simplex chronicus. [NIH] 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] Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotoxins: Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutralization: An act or process of neutralizing. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophil: A type of white blood cell. [NIH] Nickel: A trace element with the atomic symbol Ni, atomic number 28, and atomic weight 58.69. It is a cofactor of the enzyme urease. [NIH] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in

290

Allergens

tobacco smoke. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nitrogen Dioxide: Nitrogen oxide (NO2). A highly poisonous gas. Exposure produces inflammation of lungs that may only cause slight pain or pass unnoticed, but resulting edema several days later may cause death. (From Merck, 11th ed) It is a major atmospheric pollutant that is able to absorb UV light that does not reach the earth's surface. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] 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] Nucleotidases: A class of enzymes that catalyze the conversion of a nucleotide and water to a nucleoside and orthophosphate. EC 3.1.3.-. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nurse Practitioners: Nurses who are specially trained to assume an expanded role in providing medical care under the supervision of a physician. [NIH] Nutritive Value: An indication of the contribution of a food to the nutrient content of the diet. This value depends on the quantity of a food which is digested and absorbed and the amounts of the essential nutrients (protein, fat, carbohydrate, minerals, vitamins) which it contains. This value can be affected by soil and growing conditions, handling and storage, and processing. [NIH] Nymph: The immature stage in the life cycle of those orders of insects characterized by gradual metamorphosis, in which the young resemble the imago in general form of body, including compound eyes and external wings; also the 8-legged stage of mites and ticks that follows the first moult. [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

Dictionary 291

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 Health: The promotion and maintenance of physical and mental health in the work environment. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Office Management: Planning, organizing, and administering activities in an office. [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] Oligodeoxyribonucleotides: A group of deoxyribonucleotides (up to 12) in which the phosphate residues of each deoxyribonucleotide act as bridges in forming diester linkages between the deoxyribose moieties. [NIH] 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] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Onychomycosis: Mycosis of the nails, possibly due to some extent to humidity. [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] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] 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] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Otitis: Inflammation of the ear, which may be marked by pain, fever, abnormalities of hearing, hearing loss, tinnitus, and vertigo. [EU] Otitis Media: Inflammation of the middle ear. [NIH] Otitis Media with Effusion: Inflammation of the middle ear with a clear pale yellowcolored transudate. [NIH] Otolaryngology: A surgical specialty concerned with the study and treatment of disorders of the ear, nose, and throat. [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]

292

Allergens

Ovalbumin: An albumin obtained from the white of eggs. It is a member of the serpin superfamily. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Ownership: The legal relation between an entity (individual, group, corporation, or-profit, secular, government) and an object. The object may be corporeal, such as equipment, or completely a creature of law, such as a patent; it may be movable, such as an animal, or immovable, such as a building. [NIH] Oxidants: Oxidizing agents or electron-accepting molecules in chemical reactions in which electrons are transferred from one molecule to another (oxidation-reduction). In vivo, it appears that phagocyte-generated oxidants function as tumor promoters or cocarcinogens rather than as complete carcinogens perhaps because of the high levels of endogenous antioxidant defenses. It is also thought that oxidative damage in joints may trigger the autoimmune response that characterizes the persistence of the rheumatoid disease process. [NIH]

Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxidative metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, cell respiration, or aerobic metabolism. [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic Juice: The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. [NIH] Papain: A proteolytic enzyme obtained from Carica papaya. It is also the name used for a purified mixture of papain and chymopapain that is used as a topical enzymatic debriding agent. EC 3.4.22.2. [NIH]

Dictionary 293

Paradoxical: Occurring at variance with the normal rule. [EU] 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] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Particle: A tiny mass of material. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Patch Tests: Skin tests in which the sensitizer is applied to a patch of cotton cloth or gauze held in place for approximately 48-72 hours. It is used for the elicitation of a contact hypersensitivity reaction. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Compliance: Voluntary cooperation of the patient in following a prescribed regimen. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

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] Peak Expiratory Flow Rate: Measurement of the maximum rate of airflow attained during a forced vital capacity determination. Common abbreviations are PEFR and PFR. [NIH] Peak flow: The maximum amount of air breathed out; the power needed to produce this amount. [EU] Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [NIH]

294

Allergens

Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] 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] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins. [NIH] Peptide Hydrolases: A subclass of enzymes from the hydrolase class that catalyze the hydrolysis of peptide bonds. Exopeptidases and endopeptidases make up the sub-subclasses for this group. EC 3.4. [NIH] Peptide Library: A collection of cloned peptides, or chemically synthesized peptides, frequently consisting of all possible combinations of amino acids making up an n-amino acid peptide. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Perennial: Lasting through the year of for several years. [EU] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [EU] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Peripheral blood: Blood circulating throughout the body. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneal Dialysis: Dialysis fluid being introduced into and removed from the peritoneal cavity as either a continuous or an intermittent procedure. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Pertussis: An acute, highly contagious infection of the respiratory tract, most frequently affecting young children, usually caused by Bordetella pertussis; a similar illness has been associated with infection by B. parapertussis and B. bronchiseptica. It is characterized by a catarrhal stage, beginning after an incubation period of about two weeks, with slight fever, sneezing, running at the nose, and a dry cough. In a week or two the paroxysmal stage begins, with the characteristic paroxysmal cough, consisting of a deep inspiration, followed by a series of quick, short coughs, continuing until the air is expelled from the lungs; the

Dictionary 295

close of the paroxysm is marked by a long-drawn, shrill, whooping inspiration, due to spasmodic closure of the glottis. This stage lasts three to four weeks, after which the convalescent stage begins, in which paroxysms grow less frequent and less violent, and finally cease. Called also whooping cough. [EU] Pest Control: The reduction or regulation of the population of noxious, destructive, or dangerous insects or other animals. [NIH] Pesticides: Chemicals used to destroy pests of any sort. The concept includes fungicides (industrial fungicides), insecticides, rodenticides, etc. [NIH] Petrolatum: A colloidal system of semisolid hydrocarbons obtained from petroleum. It is used as an ointment base, topical protectant, and lubricant. [NIH] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield combustible fuels, petrochemicals, and lubricants. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] Pharmaceutic Aids: Substances which are of little or no therapeutic value, but are necessary in the manufacture, compounding, storage, etc., of pharmaceutical preparations or drug dosage forms. They include solvents, diluting agents, and suspending agents, and emulsifying agents. Also, antioxidants; preservatives, pharmaceutical; dyes (coloring agents); flavoring agents; vehicles; excipients; ointment bases. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [NIH] Phosphodiesterase Inhibitors: Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases. [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

296

Allergens

function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphoric Monoester Hydrolases: A group of hydrolases which catalyze the hydrolysis of monophosphoric esters with the production of one mole of orthophosphate. EC 3.1.3. [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] 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] Photopheresis: A process in which peripheral blood is exposed in an extracorporeal flow system to photoactivated 8-methoxypsoralen (methoxsalen) and ultraviolet light - a procedure known as PUVA therapy. Photopheresis is at present a standard therapy for advanced cutaneous T-cell lymphoma; it shows promise in the treatment of autoimmune diseases. [NIH] Phototherapy: Treatment of disease by exposure to light, especially by variously concentrated light rays or specific wavelengths. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pigmentation: Coloration or discoloration of a part by a pigment. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pitch: The subjective awareness of the frequency or spectral distribution of a sound. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Placental tissue: The tissue intervening between fetal blood and maternal blood in the placenta; it acts as a selective membrane regulating the passage of substances from the maternal to the fetal blood. [NIH] Plant Oils: Oils derived from plants or plant products. [NIH] Plantago: Three different species of Plantago or plantain, P. psyllium, P. ovata and P. indica. The seeds swell in water and are used as laxatives. [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]

Dictionary 297

Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasma Volume: Volume of plasma in the circulation. It is usually measured by indicator dilution techniques. [NIH] Plasmids: Any extrachromosomal hereditary determinant. Plasmids are self-replicating circular molecules of DNA that are found in a variety of bacterial, archaeal, fungal, algal, and plant species. [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] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Policy Making: The decision process by which individuals, groups or institutions establish policies pertaining to plans, programs or procedures. [NIH] Pollen: The male fertilizing element of flowering plants analogous to sperm in animals. It is released from the anthers as yellow dust, to be carried by insect or other vectors, including wind, to the ovary (stigma) of other flowers to produce the embryo enclosed by the seed. The pollens of many plants are allergenic. [NIH] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [NIH]

Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation

298

Allergens

analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Polyneuritis: Inflammation of several peripheral nerves at the same time. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyunsaturated fat: An unsaturated fat found in greatest amounts in foods derived from plants, including safflower, sunflower, corn, and soybean oils. [NIH] Polyvalent: Having more than one valence. [EU] 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] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precipitation: The act or process of precipitating. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predictive Value of Tests: In screening and diagnostic tests, the probability that a person with a positive test is a true positive (i.e., has the disease), is referred to as the predictive value of a positive test; whereas, the predictive value of a negative test is the probability that the person with a negative test does not have the disease. Predictive value is related to the sensitivity and specificity of the test. [NIH] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH]

Dictionary 299

Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primary 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] Problem Solving: A learning situation involving more than one alternative from which a selection is made in order to attain a specific goal. [NIH] Proctocolitis: Inflammation of the rectum and colon. [NIH] Progeny: The offspring produced in any generation. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Promotor: In an operon, a nucleotide sequence located at the operator end which contains all the signals for the correct initiation of genetic transcription by the RNA polymerase holoenzyme and determines the maximal rate of RNA synthesis. [NIH] Prone: Having the front portion of the body downwards. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. [NIH] Prostaglandins: A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. [NIH] Prostaglandins, Synthetic: Compounds obtained by chemical synthesis that are analogs or derivatives of naturally occurring prostaglandins and that have similar activity. [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

300

Allergens

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 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] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Proteome: The protein complement of an organism coded for by its genome. [NIH] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritic: Pertaining to or characterized by pruritus. [EU] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH] Psoralen: A substance that binds to the DNA in cells and stops them from multiplying. It is being studied in the treatment of graft-versus-host disease and is used in the treatment of psoriasis and vitiligo. [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH]

Dictionary 301

Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Psychogenic: Produced or caused by psychic or mental factors rather than organic factors. [EU]

Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psyllium: Dried, ripe seeds of Plantago psyllium, P. indica, and P. ovata (Plantaginaceae). Plantain seeds swell in water and are used as demulcents and bulk laxatives. [NIH] 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 Housing: Housing subsidized by tax funds, usually intended for low income persons or families. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Ventilation: The total volume of gas per minute inspired or expired measured in liters per minute. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Purifying: Respiratory equipment whose function is to remove contaminants from otherwise wholesome air. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [NIH] 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] 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

302

Allergens

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] Radioactive: Giving off radiation. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radium: A radioactive element symbol Ra, atomic number 88, disintegration of uranium and is is used clinically as a source brachytherapy. [NIH]

of the alkaline earth series of metals. It has the atomic and atomic weight 226. Radium is the product of the present in pitchblende and all ores containing uranium. It of beta and gamma-rays in radiotherapy, particularly

Radon: A naturally radioactive element with atomic symbol Rn, atomic number 86, and atomic weight 222. It is a member of the noble gas family and released during the decay of radium and found in soil. There is a link between exposure to radon and lung cancer. [NIH] Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. [NIH] Randomization: Also called random allocation. Is allocation of individuals to groups, e.g., for experimental and control regimens, by chance. Within the limits of chance variation, random allocation should make the control and experimental groups similar at the start of an investigation and ensure that personal judgment and prejudices of the investigator do not influence allocation. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombinant Proteins: Proteins prepared by recombinant DNA technology. [NIH] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH]

Dictionary 303

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] 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] 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] Relaxant: 1. Lessening or reducing tension. 2. An agent that lessens tension. [EU] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]

Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Reperfusion: Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing reperfusion injury. [NIH] Reperfusion Injury: Functional, metabolic, or structural changes, including necrosis, in ischemic tissues thought to result from reperfusion to ischemic areas of the tissue. The most common instance is myocardial reperfusion injury. [NIH] Repressor: Any of the specific allosteric protein molecules, products of regulator genes, which bind to the operator of operons and prevent RNA polymerase from proceeding into the operon to transcribe messenger RNA. [NIH] Reproductive cells: Egg and sperm cells. Each mature reproductive cell carries a single set of 23 chromosomes. [NIH] Respirable: Dust particles smaller than 0. 005 mm, which are deposited in the respiratory region of the lungs. [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 Physiology: Functions and activities of the respiratory tract as a whole or of any of its parts. [NIH] Respiratory System: The tubular and cavernous organs and structures, by means of which

304

Allergens

pulmonary ventilation and gas exchange between ambient air and the blood are brought about. [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]

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] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rodenticides: Substances used to destroy or inhibit the action of rats, mice, or other rodents. [NIH]

Rubber: A high-molecular-weight polymeric elastomer derived from the milk juice (latex) of Hevea brasiliensis and other trees. It is a substance that can be stretched at room temperature to atleast twice its original length and after releasing the stress, retractrapidly, and recover its original dimensions fully. Synthetic rubber is made from many different chemicals, including styrene, acrylonitrile, ethylene, propylene, and isoprene. [NIH] Rural Population: The inhabitants of rural areas or of small towns classified as rural. [NIH] Ryanodine: Insecticidal alkaloid isolated from Ryania speciosa; proposed as a myocardial depressant. [NIH] Rye: A hardy grain crop, Secale cereale, grown in northern climates. It is the most frequent host to ergot (claviceps), the toxic fungus. Its hybrid with wheat is triticale, another grain. [NIH]

Salicylic: A tuberculosis drug. [NIH] Saline: A solution of salt and water. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Sanitation: The development and establishment of environmental conditions favorable to the health of the public. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics

Dictionary 305

when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Satellite: Applied to a vein which closely accompanies an artery for some distance; in cytogenetics, a chromosomal agent separated by a secondary constriction from the main body of the chromosome. [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] Scleroproteins: Simple proteins characterized by their insolubility and fibrous structure. Within the body, they perform a supportive or protective function. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Seafood: Marine fish and shellfish used as food or suitable for food. (Webster, 3d ed) shellfish and fish products are more specific types of seafood. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Sebaceous gland: Gland that secretes sebum. [NIH] Sebum: The oily substance secreted by sebaceous glands. It is composed of keratin, fat, and cellular debris. [NIH] Second Messenger Systems: Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [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] Semicircular canal: Three long canals of the bony labyrinth of the ear, forming loops and opening into the vestibule by five openings. [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.

306

Allergens

The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Sepsis: The presence of bacteria in the bloodstream. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sessile: Attached directly by the base, denoting a tumor without penduncle or stalk; in zoology, attached so that it is not possible to move about. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sexually Transmitted Diseases: Diseases due to or propagated by sexual contact. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Sinusitis: An inflammatory process of the mucous membranes of the paranasal sinuses that

Dictionary 307

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] Skin Care: Maintenance of the hygienic state of the skin under optimal conditions of cleanliness and comfort. Effective in skin care are proper washing, bathing, cleansing, and the use of soaps, detergents, oils, etc. In various disease states, therapeutic and protective solutions and ointments are useful. The care of the skin is particularly important in various occupations, in exposure to sunlight, in neonates, and in decubitus ulcer. [NIH] Skin test: A test for an immune response to a compound by placing it on or under the skin. [NIH]

Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sleep apnea: A serious, potentially life-threatening breathing disorder characterized by repeated cessation of breathing due to either collapse of the upper airway during sleep or absence of respiratory effort. [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]

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] Soaps: Sodium or potassium salts of long chain fatty acids. These detergent substances are obtained by boiling natural oils or fats with caustic alkali. Sodium soaps are harder and are used as topical anti-infectives and vehicles in pills and liniments; potassium soaps are soft, used as vehicles for ointments and also as topical antimicrobials. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Sciences: Disciplines concerned with the interrelationships of individuals in a social environment including social organizations and institutions. Includes Sociology and Anthropology. [NIH] Social Support: Support systems that provide assistance and encouragement to individuals with physical or emotional disabilities in order that they may better cope. Informal social support is usually provided by friends, relatives, or peers, while formal assistance is provided by churches, groups, etc. [NIH] 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] Sodium Channels: Cell membrane glycoproteins selective for sodium ions. Fast sodium

308

Allergens

current is associated with the action potential in neural membranes. [NIH] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Soybean Oil: Oil from soybean or soybean plant. [NIH] Spasmodic: Of the nature of a spasm. [EU] Spasmogenic: Capable of producing convulsions. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] 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] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [EU] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinous: Like a spine or thorn in shape; having spines. [NIH] Spirogram: A record of the amounts of air being moved in and out of the lungs. [NIH] Spirometry: Measurement of volume of air inhaled or exhaled by the lung. [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] Spores: The reproductive elements of lower organisms, such as protozoa, fungi, and cryptogamic plants. [NIH] Stabilization: The creation of a stable state. [EU] Standard therapy: A currently accepted and widely used treatment for a certain type of cancer, based on the results of past research. [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] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones,

Dictionary 309

bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stomatitis: Inflammation of the oral mucosa, due to local or systemic factors which may involve the buccal and labial mucosa, palate, tongue, floor of the mouth, and the gingivae. [EU]

Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Streptavidin: A 60kD extracellular protein of Streptomyces avidinii with four high-affinity biotin binding sites. Unlike AVIDIN, streptavidin has a near neutral isoelectric point and is free of carbohydrate side chains. [NIH] Streptomyces: A genus of bacteria that form a nonfragmented aerial mycelium. Many species have been identified with some being pathogenic. This genus is responsible for producing a majority of the antibiotics of practical value. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stringency: Experimental conditions (e. g. temperature, salt concentration) used during the hybridization of nucleic acids. [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] Students, Medical: Individuals enrolled in a school of medicine or a formal educational program in medicine. [NIH] Styrene: A colorless, toxic liquid with a strong aromatic odor. It is used to make rubbers, polymers and copolymers, and polystyrene plastics. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Sublingual: Located beneath the tongue. [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] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by

310

Allergens

means of a tube and a device that acts on negative pressure. [NIH] Sulfites: Inorganic salts of sulfurous acid. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]

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] 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] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. [NIH] Tea Tree Oil: Essential oil extracted from Melaleuca alternifolia (tea tree). It is used as a topical antimicrobial due to the presence of terpineol. [NIH] Tear Gases: Gases that irritate the eyes, throat, or skin. Severe lacrimation develops upon irritation of the eyes. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetani: Causal agent of tetanus. [NIH]

Dictionary 311

Tetanic: Having the characteristics of, or relating to tetanus. [NIH] Tetanus: A disease caused by tetanospasmin, a powerful protein toxin produced by Clostridium tetani. Tetanus usually occurs after an acute injury, such as a puncture wound or laceration. Generalized tetanus, the most common form, is characterized by tetanic muscular contractions and hyperreflexia. Localized tetanus presents itself as a mild condition with manifestations restricted to muscles near the wound. It may progress to the generalized form. [NIH] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thimerosal: A topical antiseptic used on skin and mucous membranes. It is also used as a preservative in pharmaceuticals. [NIH] Thioredoxin: A hydrogen-carrying protein that participates in a variety of biochemical reactions including ribonucleotide reduction. Thioredoxin is oxidized from a dithiol to a disulfide during ribonucleotide reduction. The disulfide form is then reduced by NADPH in a reaction catalyzed by thioredoxin reductase. [NIH] 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] Threshold Limit Values: Standards for limiting worker exposure to airborne contaminants. They are the maximum concentration in air at which it is believed that a particular substance will not produce adverse health effects with repeated daily exposure. It can be a timeweighted average (TLV-TWA), a short-term value (TLV-STEL), or an instantaneous value (TLV-Ceiling). They are expressed either as parts per million (ppm) or milligram per cubic meter (mg/m3). [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrush: A disease due to infection with species of fungi of the genus Candida. [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] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid

312

Allergens

metabolism. [NIH] Ticks: Blood-sucking arachnids of the order Acarina. [NIH] Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonus: A state of slight tension usually present in muscles even when they are not undergoing active contraction. [NIH] Topical: On the surface of the body. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Toxoid: The material resulting from the treatment of toxin in such a way that the toxic properties are inactivated whilst the antigenic potency remains intact. [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] Tractus: A part of some structure, usually that part along which something passes. [NIH] Tranquilizing Agents: A traditional grouping of drugs said to have a soothing or calming effect on mood, thought, or behavior. Included here are the anti-anxiety agents (minor

Dictionary 313

tranquilizers), antimanic agents, and the antipsychotic agents (major tranquilizers). These drugs act by different mechanisms and are used for different therapeutic purposes. [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] 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] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] Triamcinolone Acetonide: An esterified form of triamcinolone. It is an anti-inflammatory glucocorticoid used topically in the treatment of various skin disorders. Intralesional, intramuscular, and intra-articular injections are also administered under certain conditions. [NIH]

Trophic: Of or pertaining to nutrition. [EU] Trypsin: A serine endopeptidase that is formed from trypsinogen in the pancreas. It is converted into its active form by enteropeptidase in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4. [NIH] Trypsin Inhibitors: Serine proteinase inhibitors which inhibit trypsin. They may be endogenous or exogenous compounds. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body.

314

Allergens

Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tunica: A rather vague term to denote the lining coat of hollow organs, tubes, or cavities. [NIH]

Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] 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] Umbilical Arteries: Either of a pair of arteries originating from the internal iliac artery and passing through the umbilical cord to carry blood from the fetus to the placenta. [NIH] Umbilical Cord: The flexible structure, giving passage to the umbilical arteries and vein, which connects the embryo or fetus to the placenta. [NIH] Umbilical cord blood: Blood from the placenta (afterbirth) that contains high concentrations of stem cells needed to produce new blood cells. [NIH] Urban Health: The status of health in urban populations. [NIH] Urban Population: The inhabitants of a city or town, including metropolitan areas and suburban areas. [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Urease: An enzyme that catalyzes the conversion of urea and water to carbon dioxide and ammonia. EC 3.5.1.5. [NIH] 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] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] Urticaria: A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress. [NIH] Vaccination: Administration of vaccines to stimulate the host's immune response. This

Dictionary 315

includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vagal: Pertaining to the vagus nerve. [EU] Vagus Nerve: The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] 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] Vasodilator: An agent that widens blood vessels. [NIH] Vasomotor: 1. Affecting the calibre of a vessel, especially of a blood vessel. 2. Any element or agent that effects the calibre of a blood vessel. [EU] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venom: That produced by the poison glands of the mouth and injected by the fangs of poisonous snakes. [NIH] Venous: Of or pertaining to the veins. [EU] Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [EU] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Vestibule: A small, oval, bony chamber of the labyrinth. The vestibule contains the utricle and saccule, organs which are part of the balancing apparatus of the ear. [NIH] Vestibulocochlear Nerve: The 8th cranial nerve. The vestibulocochlear nerve has a cochlear part (cochlear nerve) which is concerned with hearing and a vestibular part (vestibular nerve) which mediates the sense of balance and head position. The fibers of the cochlear nerve originate from neurons of the spiral ganglion and project to the cochlear nuclei (cochlear nucleus). The fibers of the vestibular nerve arise from neurons of Scarpa's ganglion and project to the vestibular nuclei. [NIH] Vestibulocochlear Nerve Diseases: Diseases of the vestibular and/or cochlear (acoustic) nerves, which join to form the vestibulocochlear nerve. Vestibular neuritis, cochlear neuritis, and acoustic neuromas are relatively common conditions that affect these nerves. Clinical

316

Allergens

manifestations vary with which nerve is primarily affected, and include hearing loss, vertigo, and tinnitus. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vial: A small bottle. [EU] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Load: The quantity of measurable virus in the blood. Change in viral load, measured in plasma, is used as a surrogate marker in HIV disease progression. [NIH] 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] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] Vital Capacity: The volume of air that is exhaled by a maximal expiration following a maximal inspiration. [NIH] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitiligo: A disorder consisting of areas of macular depigmentation, commonly on extensor aspects of extremities, on the face or neck, and in skin folds. Age of onset is often in young adulthood and the condition tends to progress gradually with lesions enlarging and extending until a quiescent state is reached. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Voice Disorders: Disorders of voice pitch, loudness, or quality. Dysphonia refers to impaired utterance of sounds by the vocal folds. [NIH] Voice Quality: Voice quality is that component of speech which gives the primary distinction to a given speaker's voice when pitch and loudness are excluded. It involves both phonatory and resonatory characteristics. Some of the descriptions of voice quality are harshness, breathiness and nasality. [NIH] Vulgaris: An affection of the skin, especially of the face, the back and the chest, due to chronic inflammation of the sebaceous glands and the hair follicles. [NIH] Wart: A raised growth on the surface of the skin or other organ. [NIH] Wheezing: Breathing with a rasp or whistling sound; a sign of airway constriction or obstruction. [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]

Whooping Cough: A respiratory infection caused by Bordetella pertussis and characterized

Dictionary 317

by paroxysmal coughing ending in a prolonged crowing intake of breath. [NIH] Whooping Cough: A respiratory infection caused by Bordetella pertussis and characterized by paroxysmal coughing ending in a prolonged crowing intake of breath. [NIH] Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] 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]

319

INDEX A Abdominal, 4, 9, 148, 210, 211, 243, 256, 292, 294, 314 Abdominal Cramps, 4, 243 Abdominal Pain, 9, 210, 211, 243, 314 Ablate, 41, 243 Absenteeism, 33, 68, 243 Acceptor, 243, 283, 292 Acculturation, 64, 243 Acetylcholine, 243, 255, 289, 290 Acoustic, 6, 243, 315 Acrylonitrile, 243, 304 Actin, 61, 243, 288 Acylation, 30, 243 Adenine, 243, 301 Adenosine, 77, 243, 296 Adhesives, 204, 243 Adjuvant, 57, 243 Adolescence, 210, 243, 293 Adoptive Transfer, 15, 243 Adrenal Cortex, 243, 259, 299 Adrenal Medulla, 244, 253, 266, 290 Adrenergic, 17, 244, 266, 310 Adsorption, 59, 244 Adsorptive, 244 Adverse Effect, 178, 182, 208, 212, 244, 306 Aerosol, 153, 154, 244 Affinity, 14, 29, 37, 42, 60, 63, 146, 155, 157, 186, 190, 192, 244, 284, 307, 309 Agarose, 244, 277 Age of Onset, 229, 244, 314 Agonist, 46, 244, 289 Air Pollutants, 17, 31, 58, 244 Airway Obstruction, 19, 47, 244 Airway Resistance, 13, 244 Albumin, 162, 169, 203, 244, 292, 297 Algorithms, 245, 251 Alimentary, 245, 293 Alkaline, 150, 182, 245, 246, 250, 253, 302 Alkaloid, 245, 289, 304 Alkylation, 184, 245 Alleles, 93, 245 Allergic Rhinitis, 28, 29, 51, 79, 111, 131, 178, 179, 181, 187, 204, 211, 245, 254, 273, 283 Allo, 15, 35, 245 Allogeneic, 245, 272 Allograft, 245, 275

Alopecia, 10, 245, 260 Alpha Particles, 245, 302 Alpha-Amylase, 86, 91, 245 Alpha-helix, 245, 281 Alternative medicine, 209, 245 Alum, 19, 245 Aluminum, 189, 245 Alveoli, 245, 315 Ambulatory Care, 144, 245 Amine, 245, 274 Amino Acid Sequence, 53, 148, 163, 173, 184, 191, 192, 193, 194, 246, 247, 271, 284 Amino Acids, 148, 160, 246, 249, 256, 262, 271, 294, 298, 300, 306, 313, 314 Ammonia, 245, 246, 314 Amplification, 55, 63, 176, 246 Amylase, 161, 169, 246 Anaesthesia, 246, 278 Anal, 246, 266, 268 Analog, 53, 246 Analogous, 58, 246, 297, 313 Analytes, 152, 246 Anaphylactic, 8, 40, 61, 90, 146, 157, 164, 176, 178, 181, 187, 192, 246 Anaphylatoxins, 82, 246, 257 Anaphylaxis, 6, 14, 74, 87, 96, 132, 146, 148, 149, 157, 160, 190, 193, 226, 227, 230, 246 Anaplasia, 246, 289 Anatomical, 246, 252, 255, 265, 277, 305 Androgens, 243, 246, 259 Anemia, 246, 256 Anergy, 163, 164, 247 Anesthesia, 244, 247 Anesthetics, 247, 254, 267 Angina, 247 Anginal, 6, 247 Angioedema, 10, 132, 247 Animal model, 15, 54, 58, 247 Anions, 244, 247, 280 Annealing, 247, 297 Anode, 151, 247 Antiallergic, 247, 259, 260 Antibacterial, 247, 308 Antibiotic, 247, 288, 308, 311 Anticholinergic, 247, 254 Anticoagulant, 247, 300 Antidepressant, 247, 259

320

Allergens

Antiemetic, 247, 276 Antigen-Antibody Complex, 248, 257 Antigen-presenting cell, 13, 165, 248, 261 Antigens, Viral, 152, 248 Antihistamine, 170, 230, 248 Anti-infective, 248, 269, 275, 307 Anti-Infective Agents, 248, 269 Anti-inflammatory, 16, 22, 65, 248, 259, 272, 298, 313 Anti-Inflammatory Agents, 248, 259 Antimicrobial, 153, 154, 248, 262, 263, 310 Antineoplastic, 248, 259, 260 Antioxidant, 57, 248, 292 Antipruritic, 248, 260 Antiseptic, 248, 311 Antiserum, 248, 250 Anus, 246, 248, 250, 252, 257, 266, 302 Anxiety, 132, 248, 276, 312 Apnea, 6, 248 Apoptosis, 15, 22, 38, 46, 67, 248 Applicability, 179, 248 Approximate, 41, 248 Aqueous, 164, 167, 248, 250, 260, 265, 275, 283 Arachidonic Acid, 53, 249, 282, 299 Arginine, 246, 249, 290, 313 Arterial, 249, 276, 300 Arteries, 249, 251, 259, 288, 311, 314 Arterioles, 249, 251 Artery, 249, 259, 301, 303, 305, 314 Articular, 249, 313 Asbestos, 25, 249 Asbestosis, 249 Aspartame, 4, 249 Aspartic Acid, 249, 255 Aspergillosis, 70, 96, 97, 101, 249 Assay, 30, 36, 43, 48, 102, 106, 125, 152, 181, 249, 277 Astringents, 249, 267, 285 Atopic allergy, 146, 188, 249 Attenuation, 35, 249 Autacoids, 249, 278 Autoantibodies, 54, 249 Autoantigens, 15, 20, 34, 35, 194, 249 Autoimmune disease, 34, 35, 54, 249, 287, 296 Autoimmunity, 54, 249 Autologous, 44, 98, 249 Autolysis, 191, 249 Autopsy, 38, 250 Auxin, 191, 250 Avidity, 38, 250

B Bacterial toxin, 156, 250 Bactericidal, 48, 250 Bacterium, 250, 257, 258 Barium, 159, 250 Barium enema, 159, 250 Base, 85, 201, 243, 250, 261, 267, 271, 281, 295, 306, 310 Basement Membrane, 250, 268 Basophil, 146, 187, 250, 274 Baths, 227, 229, 250 Beer, 74, 143, 250 Benign, 39, 250, 273, 289 Bile, 250, 270, 275, 283, 309 Bile Acids, 250, 270, 309 Bilirubin, 244, 250 Binding Sites, 48, 154, 181, 184, 250, 309 Biochemical reactions, 250, 311 Biological response modifier, 251, 279 Biological Transport, 251, 262 Biomarkers, 57, 251 Biopsy, 10, 11, 251 Biosynthesis, 164, 249, 251, 295, 306 Biotechnology, 69, 71, 108, 200, 209, 221, 251 Biotin, 50, 176, 251, 309 Biotransformation, 17, 251 Bladder, 251, 258, 287, 299, 314 Blood Coagulation, 251, 253, 311 Blood Glucose, 4, 251, 279 Blood Platelets, 251, 306 Blood pressure, 149, 251, 253, 276, 287, 307 Blood transfusion, 86, 251 Blood vessel, 210, 251, 253, 254, 255, 265, 271, 281, 283, 285, 307, 309, 311, 315 Blot, 114, 251, 277 Blotting, Western, 251, 277 Body Burden, 252, 282 Body Fluids, 181, 251, 252, 264, 307, 313 Body Mass Index, 26, 252 Body Regions, 252, 256 Bone Density, 211, 252 Bone Marrow, 252, 260, 271, 273, 277, 283 Bowel, 134, 243, 246, 252, 262, 266, 278, 280, 294, 314 Bowel Movement, 252, 262 Bradykinin, 252, 290, 297 Breast Feeding, 39, 148, 252 Bronchi, 6, 252, 267, 312 Bronchial Provocation Tests, 92, 252 Bronchiseptica, 252, 294 Bronchitis, 12, 132, 203, 252, 267

321

Bronchoalveolar Lavage, 26, 37, 57, 252 Bronchoalveolar Lavage Fluid, 37, 252 Bronchopulmonary, 70, 96, 97, 101, 252 Bronchoscopy, 26, 252 Buccal, 253, 309 Burning Mouth Syndrome, 5, 253 C Calcium, 18, 47, 101, 187, 189, 249, 253, 257, 279, 306 Calcium Signaling, 18, 253 Callus, 253, 281 Calmodulin, 253, 279 Carbohydrate, 158, 162, 203, 253, 259, 272, 290, 298, 309 Carbon Dioxide, 168, 253, 261, 269, 270, 296, 303, 314 Carboxy, 35, 42, 253 Carcinogenic, 253, 278, 291, 299, 309 Carcinogens, 253, 288, 292 Cardiac, 6, 15, 253, 264, 267, 288, 308 Cardiopulmonary, 7, 253 Cardiovascular, 7, 27, 203, 253, 282, 306 Cardiovascular disease, 7, 27, 253 Carrier Proteins, 253, 297 Catecholamine, 253, 295 Catheters, 159, 177, 253, 282 Cathode, 247, 254, 264 Causal, 33, 87, 254, 266, 310 Caustic, 254, 307 Celiac Disease, 132, 254, 271 Cell Adhesion, 69, 254, 279 Cell Death, 248, 254, 288 Cell Differentiation, 48, 254, 306 Cell Division, 250, 254, 260, 284, 286, 296, 299, 305 Cell Extracts, 57, 254 Cell membrane, 53, 164, 251, 253, 254, 261, 267, 279, 285, 296, 307 Cell motility, 20, 254 Cell proliferation, 254, 280, 306 Cell Respiration, 254, 292, 303 Cellular adhesion, 47, 254 Central Nervous System, 7, 12, 243, 254, 270, 273, 282, 283, 287, 306 Central Nervous System Depressants, 7, 254 Cerebral, 254, 267 Cerebrovascular, 253, 254 Cetirizine, 10, 254, 276 Character, 254, 261, 272 Cheilitis, 228, 254 Chemokines, 20, 254

Chemotactic Factors, 255, 257 Chemotaxis, 49, 255 Chemotherapy, 155, 156, 255 Chest Pain, 6, 255 Chimera, 16, 255 Chin, 255, 285 Cholesterol, 27, 53, 203, 250, 255, 259, 309 Cholinergic, 13, 255, 289 Chromatin, 248, 255, 283 Chromosomal, 22, 38, 189, 246, 255, 305 Chromosome, 38, 55, 255, 258, 273, 282, 305 Chronic Disease, 26, 28, 31, 50, 56, 255 Chronic renal, 7, 255 Chymopapain, 255, 292 CIS, 255, 270, 271 Clathrin, 29, 255, 256, 265 Clathrin-Coated Vesicles, 29, 255 Claviceps, 255, 304 Clinical Medicine, 12, 256, 298 Clinical study, 256, 259 Clinical trial, 12, 35, 108, 147, 221, 256, 259, 260, 263, 287, 293, 300, 302 Cloning, 36, 69, 77, 86, 101, 126, 145, 163, 173, 191, 251, 256 Coagulation, 251, 256, 274, 297 Coated Vesicles, 255, 256, 265 Cobalt, 5, 256 Cochlea, 256, 278 Cochlear, 256, 312, 315 Cochlear Diseases, 256, 312 Cockroaches, 25, 45, 59, 62, 180, 256 Codon, 113, 173, 174, 256, 271 Cofactor, 256, 289, 300, 311 Cohort Studies, 256, 266 Colic, 39, 132, 256, 286 Colitis, 135, 210, 256 Collagen, 23, 243, 250, 257, 297, 299 Collapse, 246, 257, 307 Colloidal, 244, 257, 265, 295 Colon, 135, 250, 256, 257, 278, 281, 299, 314 Colostrum, 152, 257 Competency, 62, 257 Complement, 34, 163, 201, 246, 257, 258, 271, 279, 284, 297, 306 Complement Activation, 246, 257 Complementary and alternative medicine, 123, 138, 257 Complementary medicine, 123, 257 Complementation, 34, 258 Complete remission, 258, 303 Compliance, 59, 179, 258

322

Allergens

Computational Biology, 221, 258 Concomitant, 155, 258 Condoms, 159, 177, 258, 282 Congestion, 6, 8, 135, 258, 267 Conjugated, 105, 258 Conjugation, 251, 258 Conjunctiva, 258, 278 Conjunctivitis, 16, 48, 83, 132, 171, 181, 187, 192, 196, 258, 273 Conjunctivitis, Allergic, 187, 258 Connective Tissue, 252, 257, 258, 262, 268, 270, 283, 285 Consciousness, 258, 263, 301 Constriction, 42, 146, 258, 281, 305, 315, 316 Consultation, 6, 258 Contact dermatitis, 3, 8, 32, 44, 111, 124, 202, 229, 231, 258 Contamination, 143, 202, 259 Contraindications, ii, 259 Control group, 7, 21, 33, 39, 66, 259, 302 Controlled clinical trial, 71, 259 Controlled study, 33, 259 Coordination, 259, 287 Corneum, 259, 266, 276 Coronary, 253, 259, 288 Coronary heart disease, 253, 259 Coronary Thrombosis, 259, 288 Cortical, 259, 267 Corticosteroid, 17, 47, 259, 298 Cortisol, 244, 259 Cortisone, 229, 259, 298 Cotinine, 32, 56, 259 Craniocerebral Trauma, 259, 273, 312 Craniofacial Abnormalities, 7, 260 Crossing-over, 260, 302 Cross-Sectional Studies, 260, 266 Crowns, 260, 261 Cryofixation, 260 Cryopreservation, 41, 260 Curative, 203, 260, 311 Cutaneous, 5, 44, 55, 107, 204, 259, 260, 280, 282, 296 Cyclic, 253, 260, 273, 290, 295, 305 Cyclophosphamide, 10, 260 Cyclosporine, 204, 212, 260 Cyproheptadine, 10, 260 Cystamine, 161, 162, 260 Cysteine, 93, 174, 184, 255, 260, 263 Cystine, 161, 169, 260, 263 Cytogenetics, 260, 305

Cytokine, 17, 19, 21, 28, 29, 38, 40, 42, 43, 46, 54, 56, 65, 67, 76, 105, 157, 204, 260 Cytoplasm, 60, 248, 253, 254, 260, 261, 266, 279, 283 Cytoskeletal Proteins, 255, 260 Cytoskeleton, 187, 260, 261, 279 Cytotoxic, 14, 15, 61, 261, 284, 306 D Dairy Products, 4, 202, 261 De novo, 97, 261 Deamination, 261, 314 Decarboxylation, 261, 274 Decubitus, 261, 307 Decubitus Ulcer, 261, 307 Defense Mechanisms, 63, 261, 279 Degenerative, 261, 274 Deletion, 187, 248, 261 Delivery of Health Care, 261, 273 Denaturation, 261, 297 Dendrites, 261, 289 Dendritic, 13, 18, 22, 35, 37, 44, 98, 104, 146, 185, 261 Dendritic cell, 13, 18, 22, 35, 37, 44, 98, 104, 146, 185, 261 Dental Abutments, 261 Dental Materials, 204, 261 Dentures, 5, 261 Deoxyribonucleotides, 261, 291 Depolarization, 261, 306 Dermatologist, 231, 262 Dermis, 247, 262 DES, 246, 262 Desensitisation, 164, 262 Desensitization, 7, 14, 34, 164, 262, 277 Detergents, 231, 262, 307 Deuterium, 262, 275 Developed Countries, 179, 193, 262, 269 Dextrans, 155, 262 Diabetes Mellitus, 54, 262, 272 Diagnostic procedure, 141, 209, 262 Dialyzer, 262, 274 Diarrhea, 4, 9, 39, 70, 210, 226, 262, 267, 286 Diarrhoea, 155, 156, 262 Dietary Proteins, 203, 262 Dietitian, 230, 262 Diffusion, 156, 157, 251, 262, 277 Digestion, 57, 169, 192, 226, 245, 250, 252, 262, 280, 283, 309, 315 Digestive system, 202, 262, 270, 287 Dihydrotestosterone, 262, 302 Dimerization, 42, 263

323

Diphtheria, 30, 263 Diploid, 258, 263, 296 Direct, iii, 15, 17, 23, 44, 59, 68, 144, 171, 176, 202, 204, 213, 256, 263, 303, 310 Discrete, 36, 263, 271, 282 Disease Progression, 263, 316 Disease Vectors, 263, 279 Disinfectant, 153, 263 Disposition, 149, 263 Dissociation, 30, 82, 244, 263, 280 Dissociative Disorders, 263 Distal, 263, 264, 270, 300 Disulphides, 263 Dithiothreitol, 161, 162, 263 Dizziness, 263, 315 Dose-dependent, 51, 82, 263 Double-blind, 95, 148, 263 Doxycycline, 43, 263 Drive, ii, vi, 7, 13, 18, 117, 204, 264 Drug Interactions, 214, 264 Drug Tolerance, 264, 312 Dry Eye Syndrome, 48, 264 Duct, 264, 304 Dumping Syndrome, 260, 264 Duodenum, 250, 264, 292, 309 Dysplasia, 11, 264 E Ectopic, 145, 163, 264 Eczema, 39, 79, 100, 133, 154, 196, 199, 203, 211, 227, 228, 229, 230, 231, 264 Edema, 5, 6, 133, 203, 247, 258, 264, 280, 281, 288, 289, 290 Effector, 15, 18, 19, 22, 37, 54, 63, 65, 181, 187, 194, 243, 257, 264, 295 Effector cell, 15, 22, 54, 65, 181, 187, 264 Efficacy, 15, 19, 21, 33, 34, 35, 36, 43, 45, 55, 58, 167, 178, 264 Effusion, 264 Elastic, 47, 162, 179, 264, 272, 310 Elastin, 257, 264 Elective, 264 Electrode, 150, 174, 247, 254, 264 Electrolyte, 175, 259, 264, 286, 298, 307 Electrons, 248, 250, 254, 264, 280, 292, 302 Electrophoresis, 57, 104, 265, 277 Embryo, 254, 265, 278, 297, 314 Emollient, 265, 291 Emphysema, 203, 265 Emulsions, 90, 265 Enamel, 265, 281 Encephalitis, 265 Encephalomyelitis, 34, 195, 265

Endocrine System, 265 Endocrinology, 12, 265 Endocytosis, 30, 265 Endogenous, 14, 19, 34, 126, 191, 249, 264, 265, 278, 292, 313 Endosomes, 255, 265 Endothelium, 38, 265, 290 Endothelium, Lymphatic, 265 Endothelium, Vascular, 265 Endothelium-derived, 265, 290 Endotoxic, 265, 283 Endotoxin, 30, 33, 67, 79, 86, 109, 208, 265, 266, 314 End-stage renal, 7, 255, 266 Enema, 266 Enhancer, 266, 304 Enterocolitis, 39, 230, 266 Enteropeptidase, 266, 313 Environmental Exposure, 17, 24, 27, 50, 58, 266 Environmental Health, 23, 25, 28, 50, 64, 75, 86, 104, 109, 220, 222, 266 Environmental tobacco smoke, 24, 29, 31, 49, 56, 266 Enzymatic, 88, 163, 253, 257, 266, 274, 292, 297 Enzyme Inhibitors, 171, 266, 297 Eosinophil, 13, 83, 84, 266 Eosinophilia, 18, 43, 157, 266 Eosinophilic, 37, 39, 51, 146, 266 Eosinophilic Gastroenteritis, 39, 266 Epidemic, 26, 27, 37, 266 Epidemiologic Studies, 31, 266 Epidemiological, 27, 45, 178, 186, 266 Epidermal, 44, 55, 84, 126, 266, 281, 282 Epidermis, 44, 112, 259, 262, 266, 275, 276, 281, 282, 301 Epinephrine, 8, 10, 230, 244, 266, 289, 290, 314 Epithelial, 19, 39, 48, 53, 57, 58, 62, 65, 93, 110, 146, 156, 164, 251, 267, 272, 274 Epithelial Cells, 19, 39, 48, 53, 93, 267, 274 Epithelium, 19, 23, 48, 49, 53, 58, 63, 65, 112, 139, 155, 157, 250, 265, 267 Epitope, 14, 65, 145, 162, 178, 184, 191, 193, 194, 195, 267 Ergot, 267, 304 Erythema, 10, 149, 258, 267, 314 Erythrocytes, 246, 252, 267, 306 Esophageal, 267, 270 Esophagitis, 267, 270

324

Allergens

Esophagus, 203, 262, 267, 270, 283, 295, 303, 309 Ether, 118, 267 Eucalyptus, 123, 137, 267 Eukaryotic Cells, 260, 267, 277, 291, 314 Evoke, 267, 309 Excipients, 267, 269, 295 Excitatory, 13, 267, 272 Exocytosis, 60, 155, 267, 274 Exogenous, 19, 54, 191, 204, 244, 251, 264, 265, 267, 278, 313, 314 Expiration, 267, 303, 316 Extensor, 267, 300, 316 Extracellular, 34, 48, 60, 63, 65, 171, 258, 265, 267, 268, 279, 307, 309 Extracellular Matrix, 34, 60, 258, 267, 279 Extracellular Space, 267, 268 Extracorporeal, 204, 268, 296 F Facial, 8, 260, 268 Faecal, 153, 262, 268 Family Planning, 221, 268 Fat, 27, 29, 203, 249, 252, 257, 259, 261, 268, 283, 287, 290, 298, 305, 310 Fatigue, 185, 268 Fatty acids, 29, 244, 268, 299, 307 Feces, 171, 172, 268 Fermentation, 250, 268, 269 Fetal Blood, 268, 296 Fetus, 268, 296, 299, 314 Fibrinogen, 268, 297, 311 Fibrosis, 65, 96, 97, 268, 305 Filtration, 44, 142, 182, 268 Fish Products, 268, 305 Fixation, 260, 268, 306 Flatus, 269, 270 Flavoring Agents, 267, 269, 295 Flexor, 267, 269, 282 Fluorescence, 50, 269, 286 Fold, 5, 6, 14, 153, 186, 269 Follow-Up Studies, 148, 269 Food Additives, 4, 10, 226, 269 Food Coloring Agents, 269 Food Contamination, 202, 269 Food Hypersensitivity, 9, 39, 148, 269 Food Preservatives, 269 Forearm, 176, 251, 269 Free Radicals, 248, 263, 269 Friction, 167, 244, 269 Fructose, 162, 269, 272 Fungus, 267, 269, 304

G Gallbladder, 133, 243, 262, 270 Ganglia, 243, 270, 289 Gas, 44, 150, 195, 246, 253, 262, 269, 270, 275, 288, 290, 301, 302, 304, 309, 315 Gas exchange, 270, 304, 315 Gastrectomy, 260, 270 Gastric, 270, 274, 294 Gastroenterologist, 211, 270 Gastroenterology, 6, 270 Gastroesophageal Reflux, 203, 270 Gastroesophageal Reflux Disease, 203, 270 Gastrointestinal Neoplasms, 249, 270 Gastrointestinal tract, 9, 250, 270, 282, 306, 314 Gels, 60, 270 Gene Expression, 26, 48, 200, 270 Gene Products, rev, 270, 271 Gene Therapy, 183, 184, 270 Genes, env, 67, 271 Genetic Code, 271, 290 Genetic Engineering, 251, 256, 271 Genetic Markers, 22, 271 Genetic testing, 271, 298 Genetics, 17, 22, 31, 34, 64, 66, 75, 89, 161, 204, 228, 258, 260, 271 Genetics, Biochemical, 228, 271 Genital, 5, 271, 314 Genitourinary, 48, 62, 271, 314 Genotype, 26, 271, 295 Germline mutation, 37, 271, 274 Gestation, 271, 294, 296 Ginseng, 138, 271 Gland, 243, 244, 259, 271, 283, 292, 296, 299, 305, 309, 311 Gliadin, 162, 271 Glomerular, 203, 271, 303 Glomerulus, 271 Glottis, 271, 295 Glucans, 33, 272 Glucocorticoid, 204, 272, 298, 313 Glucose, 245, 251, 262, 272, 278, 279, 304 Glucose Intolerance, 262, 272 Glucuronic Acid, 272, 274 Glutamate, 8, 272 Gluten, 9, 121, 162, 200, 210, 254, 271, 272 Glycine, 272, 289, 306 Glycogen, 245, 272 Glycoprotein, 88, 172, 268, 272, 284, 287, 311, 314 Glycoside, 272, 275, 304 Glycosidic, 245, 272, 291

325

Goats, 261, 272 Goblet Cells, 22, 272 Gonadal, 272, 308 Governing Board, 272, 298 Government Agencies, 210, 272, 298 Grade, 31, 272 Graft, 15, 272, 273, 277, 286, 300 Graft Rejection, 15, 272, 277, 286 Graft-versus-host disease, 273, 300 Granule, 60, 83, 155, 273 Granulocyte, 70, 273 Grasses, 35, 142, 146, 160, 164, 190, 191, 193, 255, 273 Guanylate Cyclase, 273, 290 H Hair Color, 273 Hair Dyes, 229, 231, 273 Hair follicles, 262, 273, 316 Haploid, 273, 296 Haptens, 15, 82, 152, 192, 244, 273 Hay Fever, 6, 10, 34, 131, 133, 146, 190, 191, 193, 196, 229, 245, 273 Headache, 134, 273, 278 Health Behavior, 27, 273 Health Care Costs, 50, 68, 172, 273 Health Expenditures, 273 Health Services, 27, 261, 273 Health Status, 32, 33, 273 Heart attack, 253, 273 Helminths, 273, 278 Hemodialysis, 7, 262, 274, 281 Hemoglobinopathies, 271, 274 Hemorrhage, 260, 273, 274, 301, 309 Hemostasis, 274, 279, 306 Heparin, 146, 274 Hepatic, 244, 274 Hepatitis, 159, 177, 194, 274 Hepatocytes, 274 Hereditary, 211, 271, 274, 297 Hereditary mutation, 271, 274 Heredity, 229, 270, 271, 274 Heterodimers, 274, 279 Heterogeneity, 92, 244, 274 Histamine Release, 246, 274 Histidine, 274 Histocompatibility, 147, 274, 286 Histocompatibility Antigens, 147, 274 Hoarseness, 203, 275, 281 Homeostasis, 58, 203, 275 Homogeneous, 176, 275 Homologous, 42, 163, 190, 193, 245, 260, 270, 275, 288, 305, 306, 310

Hormonal, 156, 259, 275 Hormone, 245, 259, 262, 266, 275, 279, 285, 299, 305, 306, 310, 311 Horny layer, 266, 275 Humoral, 23, 46, 118, 184, 192, 272, 275 Humour, 275 Hybrid, 275, 304 Hybridization, 275, 309 Hybridoma, 42, 148, 275 Hydration, 11, 204, 275 Hydrogen, 167, 243, 245, 250, 253, 261, 262, 275, 283, 286, 287, 289, 292, 295, 300, 311 Hydrogen Peroxide, 167, 275, 283 Hydrolases, 165, 275, 296 Hydrolysis, 251, 275, 282, 294, 295, 296, 298, 300, 313 Hydrophilic, 262, 275 Hydrophobic, 182, 184, 262, 275 Hydroxylysine, 257, 276 Hydroxyproline, 257, 276 Hydroxyzine, 10, 276 Hygienic, 276, 307 Hyperaemia, 258, 276 Hyperlipidemia, 203, 276 Hyperplasia, 43, 276, 282 Hyperreflexia, 276, 311 Hypertension, 134, 253, 276, 280 Hypertrophy, 276, 282 Hypnotics and Sedatives, 254, 276 Hypotension, 39, 276 I Ichthyosis, 228, 276 Idiopathic, 10, 276 Idiosyncrasy, 226, 276 Idiotype, 15, 276 Illusion, 276, 315 Imidazole, 251, 274, 276 Immersion, 250, 276 Immune adjuvant, 245, 276 Immune Sera, 276, 277 Immunity, 20, 52, 65, 67, 70, 96, 157, 276, 277, 313 Immunization, 14, 63, 76, 158, 183, 184, 243, 277, 299, 305 Immunoassay, 59, 148, 149, 176, 277 Immunoblotting, 60, 95, 128, 159, 181, 277 Immunodiffusion, 277 Immunoelectrophoresis, 159, 277 Immunogenic, 165, 187, 277, 283 Immunoglobulins, 176, 181, 277, 297

326

Allergens

Immunologic, 11, 37, 39, 44, 55, 101, 124, 127, 201, 243, 255, 277 Immunosuppression, 277, 291 Immunosuppressive, 15, 19, 35, 260, 272, 277, 310 Immunosuppressive therapy, 15, 277 Impairment, 23, 277, 285 In situ, 70, 118, 150, 277 In Situ Hybridization, 70, 118, 277 Incision, 278, 280 Incompetence, 270, 278 Incubation, 278, 294 Incubation period, 278, 294 Induction, 15, 18, 19, 20, 35, 39, 43, 46, 48, 55, 61, 111, 155, 164, 246, 278 Infancy, 30, 61, 204, 210, 278 Infarction, 278, 303 Infestation, 196, 278 Inflammation Mediators, 188, 278 Inflammatory bowel disease, 73, 124, 210, 278 Influenza, 23, 42, 278 Ingestion, 40, 148, 176, 278, 297 Inhalation, 43, 51, 58, 97, 123, 130, 171, 176, 186, 203, 214, 244, 249, 252, 278, 297 Initiation, 20, 29, 278, 299, 313 Inner ear, 7, 256, 278 Inorganic, 150, 166, 167, 168, 182, 278, 287, 310 Inositol, 47, 278, 279, 305 Inositol 1,4,5-Trisphosphate, 47, 279 Insect Proteins, 174, 279 Insecticide Resistance, 45, 279 Insecticides, 45, 279, 295 Insight, 23, 279 Insulator, 279, 288 Insulin, 34, 54, 279, 314 Insulin-dependent diabetes mellitus, 279 Integrins, 20, 279 Interferon, 18, 29, 52, 279 Interferon-alpha, 279 Interleukin-1, 55, 65, 279 Interleukin-10, 65, 279 Interleukin-2, 279, 280 Interleukins, 52, 280 Intermittent, 264, 280, 294 Internal Medicine, 17, 21, 43, 51, 86, 265, 270, 280, 289 Interstitial, 252, 268, 280, 285, 303 Intestinal, 9, 39, 110, 155, 156, 210, 254, 266, 280 Intestinal Mucosa, 254, 266, 280

Intestine, 155, 252, 280, 281 Intoxication, 280, 317 Intracellular, 18, 253, 255, 278, 279, 280, 285, 290, 298, 302, 305, 306 Intracellular Membranes, 280, 285 Intracranial Hypertension, 273, 280, 312 Intramuscular, 280, 293, 313 Intravascular, 146, 280 Intravenous, 280, 293 Intrinsic, 46, 55, 65, 244, 250, 280 Invasive, 230, 276, 280 Involuntary, 266, 280, 288, 303, 307 Ion Channels, 280, 310 Ionization, 150, 280 Ionizing, 245, 266, 280 Ions, 135, 250, 253, 263, 264, 275, 279, 280, 281, 287, 307 Irritants, 4, 9, 10, 11, 32, 44, 48, 66, 67, 84, 180, 199, 202, 211, 227, 228, 229, 230, 280 Ischemia, 261, 281, 303 Isocyanates, 79, 281 Isoelectric, 281, 309 Isoelectric Point, 281, 309 K Kb, 220, 281 Keratin, 149, 281, 305 Keratinocytes, 44, 281 Keratosis, 228, 281 Kidney Failure, 266, 281 Kinetic, 30, 280, 281 L Labile, 71, 257, 281 Labyrinth, 256, 278, 281, 305, 315 Laceration, 281, 311 Lactation, 257, 281 Large Intestine, 262, 266, 280, 281, 302, 307 Laryngeal, 6, 281 Laryngitis, 6, 203, 281 Larynx, 203, 271, 281, 312, 315 Latent, 282, 298 Latex Allergy, 8, 177, 282 Lead Poisoning, 16, 282 Lectin, 158, 171, 282, 285 Lesion, 10, 282, 283 Lethal, 160, 250, 282, 288 Leucine, 282, 294 Leucocyte, 266, 282 Leukemia, 61, 271, 282 Leukotrienes, 146, 181, 249, 282 Lichen Planus, 5, 282 Lichenification, 228, 282 Life cycle, 282, 290

327

Ligands, 36, 43, 192, 279, 282 Ligases, 30, 282 Linkage, 22, 36, 38, 56, 271, 282 Lip, 211, 282 Lipid, 29, 53, 77, 95, 98, 203, 265, 279, 283, 288, 292 Lipid A, 29, 283 Lipid Peroxidation, 283, 292 Lipopolysaccharide, 26, 283 Liposome, 158, 283 Litter, 172, 283 Liver, 243, 244, 249, 250, 251, 260, 262, 268, 270, 272, 274, 283, 298, 314 Localization, 58, 283 Localized, 6, 196, 247, 260, 263, 268, 278, 282, 283, 289, 296, 311, 314 Locomotion, 283, 296 Lod, 55, 283 Loop, 44, 196, 283 Loratadine, 10, 283 Lower Esophageal Sphincter, 270, 283 Lubricants, 283, 295 Lymph, 18, 265, 275, 283 Lymph node, 18, 283 Lymphatic, 265, 278, 283, 285, 308, 311 Lymphatic system, 283, 308, 311 Lymphocytes, 13, 20, 42, 44, 54, 98, 194, 247, 261, 277, 279, 280, 282, 283, 284, 308, 310, 311, 316 Lymphoid, 18, 20, 35, 247, 282, 283, 284 Lymphokine, 147, 284 Lymphoma, 284, 296 Lymphoproliferative, 29, 100, 284 Lymphotoxin, 20, 284 Lysine, 276, 284, 313 M Macrophage, 23, 57, 70, 279, 284 Macrophage Colony-Stimulating Factor, 70, 284 Major Histocompatibility Complex, 16, 194, 275, 284 Malnutrition, 244, 284 Mammary, 257, 284 Manifest, 159, 164, 284 Mannans, 155, 269, 284 Mediate, 22, 29, 42, 46, 54, 57, 149, 186, 194, 278, 284 Mediator, 18, 164, 280, 284, 306 MEDLINE, 221, 284 Meiosis, 284, 288, 310 Melanin, 284, 295, 314 Membrane Fusion, 61, 285

Membrane Glycoproteins, 285 Membrane Proteins, 61, 285 Memory, 15, 37, 42, 203, 285 Meninges, 254, 259, 285 Mental, iv, 11, 24, 56, 220, 222, 255, 263, 268, 278, 285, 291, 299, 300, 301, 305, 314 Mental Disorders, 285, 299, 300 Mental Health, iv, 11, 24, 56, 220, 222, 285, 291, 299, 301 Mental Processes, 263, 285, 301 Mercury, 5, 285 Mesenchymal, 58, 284, 285 Metabolic disorder, 9, 204, 285 Metabolite, 251, 276, 285 Metamorphosis, 285, 290 Metaplasia, 37, 285 Metastasis, 285, 289 Methacrylate, 90, 285 Methoxsalen, 285, 296 Microbe, 48, 285, 312 Microorganism, 189, 256, 285, 293, 316 Micro-organism, 63, 150, 286 Microscopy, 13, 20, 29, 250, 286 Microscopy, Confocal, 13, 286 Migration, 18, 22, 53, 84, 286 Milk Hypersensitivity, 39, 286 Milligram, 286, 311 Milliliter, 252, 286 Mineralocorticoids, 243, 259, 286 Minor Histocompatibility Antigens, 274, 286 Mitochondrial Swelling, 286, 288 Mitosis, 248, 286 Mobilization, 61, 253, 286 Modeling, 12, 36, 67, 286 Modification, 16, 52, 58, 271, 286, 301 Molecular mass, 104, 286 Molecular Structure, 77, 287 Monitor, 59, 107, 287, 290 Monoclonal, 34, 54, 94, 148, 277, 287 Monoclonal antibodies, 34, 148, 277, 287 Monocyte, 37, 104, 284, 287 Mononuclear, 284, 287, 314 Monophosphate, 77, 287 Morphological, 13, 46, 265, 269, 287 Morphology, 47, 287 Motility, 20, 287, 306 Motion Sickness, 287, 288 Motor Neurons, 13, 287 Mucins, 48, 272, 287, 304 Mucociliary, 287, 307 Mucolytic, 252, 287

328

Allergens

Mucosa, 37, 149, 204, 287, 288, 309 Mucositis, 11, 287 Mucus, 22, 48, 51, 287, 314 Multicenter study, 101, 287 Multiple sclerosis, 195, 287 Multivalent, 164, 250, 288 Muscle Fibers, 288 Mustard Gas, 281, 288 Mutagenesis, 34, 36, 118, 288 Mutagens, 288 Myalgia, 278, 288 Myelin, 195, 287, 288 Myeloma, 275, 288 Myocardial infarction, 6, 259, 288 Myocarditis, 15, 263, 288 Myocardium, 288 Myosin, 15, 288 N Nasal Cavity, 6, 288, 293 Nasal Mucosa, 278, 288 Nasal Septum, 288 Nausea, 8, 226, 247, 288, 314 Necrosis, 211, 248, 278, 284, 288, 303 Needs Assessment, 17, 288 Neomycin, 229, 288 Neonatal, 20, 58, 73, 288 Neoplasms, 4, 243, 248, 253, 289 Nephrology, 6, 289 Nephrosis, 289 Nephrotic, 203, 289 Nephrotic Syndrome, 203, 289 Nervous System, 13, 156, 254, 284, 289, 309, 310 Networks, 38, 289 Neural, 13, 139, 275, 289, 308 Neurodermatitis, 196, 289 Neurons, 13, 261, 267, 270, 287, 289, 310, 315 Neurotoxic, 289 Neurotoxins, 45, 162, 169, 289 Neurotransmitter, 243, 249, 252, 272, 274, 280, 289, 290, 305, 306, 309, 310 Neutralization, 53, 167, 289 Neutrons, 245, 289, 302 Neutrophil, 49, 289 Nickel, 5, 229, 231, 289 Nicotine, 204, 289 Nitric Oxide, 85, 290 Nitrogen, 31, 40, 49, 244, 245, 246, 260, 269, 286, 290, 313 Nitrogen Dioxide, 31, 49, 290 Norepinephrine, 244, 289, 290

Nuclear, 42, 88, 256, 258, 265, 267, 270, 288, 290 Nuclei, 168, 245, 258, 264, 270, 271, 286, 289, 290, 300, 315 Nucleic acid, 146, 157, 159, 160, 162, 173, 183, 190, 193, 271, 275, 277, 288, 290, 301, 309 Nucleotidases, 275, 290 Nucleus, 13, 40, 248, 255, 260, 262, 267, 283, 284, 287, 289, 290, 299, 300, 309, 315 Nurse Practitioners, 10, 290 Nutritive Value, 269, 290 Nymph, 154, 285, 290 O Observational study, 49, 290 Occupational Health, 62, 291 Ocular, 16, 48, 291 Office Management, 6, 291 Ointments, 227, 230, 291, 307 Oligodeoxyribonucleotides, 36, 291 Oligosaccharides, 35, 245, 291 Oncogenic, 279, 291 Onychomycosis, 9, 10, 291 Operon, 291, 299, 303 Opportunistic Infections, 49, 291 Oral Health, 11, 291 Organ Culture, 291, 312 Organelles, 255, 260, 261, 291 Osmotic, 244, 286, 291 Otitis, 134, 227, 291 Otitis Media, 134, 227, 291 Otitis Media with Effusion, 227, 291 Otolaryngology, 6, 7, 97, 291 Outpatient, 27, 291 Ovalbumin, 15, 19, 46, 53, 57, 68, 80, 149, 194, 292 Ovary, 292, 297 Ownership, 79, 292 Oxidants, 31, 292 Oxidation, 44, 167, 243, 248, 251, 260, 263, 283, 292 Oxidation-Reduction, 251, 292 Oxidative metabolism, 282, 292 Oxidative Stress, 57, 292 Oxygen Consumption, 292, 303 P Palate, 200, 204, 292, 309 Palliative, 292, 311 Pancreas, 243, 251, 262, 270, 279, 292, 313, 314 Pancreatic, 270, 292 Pancreatic Juice, 270, 292

329

Papain, 90, 292 Paradoxical, 36, 293 Paranasal Sinuses, 293, 306 Parasite, 78, 293 Parasitic, 255, 273, 278, 293 Parenteral, 158, 182, 293 Paroxysmal, 293, 294, 317 Partial remission, 293, 303 Particle, 57, 62, 143, 166, 189, 283, 293, 313 Patch, 4, 5, 15, 29, 74, 79, 82, 102, 104, 105, 110, 111, 125, 128, 130, 202, 229, 231, 293 Patch Tests, 105, 130, 293 Pathogen, 43, 47, 49, 159, 278, 293 Pathologic, 48, 49, 248, 251, 259, 276, 293, 300, 315 Pathologic Processes, 248, 293 Pathophysiology, 42, 293 Patient Compliance, 178, 293 Patient Education, 10, 11, 21, 226, 236, 238, 242, 293 Patient Satisfaction, 66, 293 Patient Selection, 75, 293 Peak Expiratory Flow Rate, 83, 293 Peak flow, 20, 27, 293 Pediatrics, 23, 30, 35, 38, 39, 49, 64, 65, 66, 67, 68, 118, 119, 293 Penis, 258, 294 Pepsin, 161, 162, 169, 294 Pepsin A, 161, 294 Peptide, 14, 16, 40, 61, 65, 92, 145, 146, 165, 178, 193, 194, 266, 275, 281, 294, 298, 300 Peptide Fragments, 16, 92, 194, 294 Peptide Hydrolases, 275, 294 Peptide Library, 65, 294 Perception, 203, 294, 305 Perennial, 115, 171, 179, 191, 294, 313 Perforation, 142, 294 Perinatal, 29, 294 Peripheral blood, 44, 61, 204, 279, 294, 296 Peritoneal, 7, 294 Peritoneal Cavity, 294 Peritoneal Dialysis, 7, 294 Peritoneum, 294 Pertussis, 30, 76, 294, 316, 317 Pest Control, 16, 17, 33, 45, 295 Pesticides, 17, 24, 52, 279, 295 Petrolatum, 125, 295 Petroleum, 9, 143, 295 PH, 20, 252, 295 Phagocyte, 284, 292, 295 Phagocytosis, 23, 295 Pharmaceutic Aids, 269, 295

Pharmacologic, 19, 202, 247, 249, 295, 312 Pharmacotherapy, 10, 144, 171, 178, 295 Pharynx, 6, 270, 278, 288, 295, 315 Phenotype, 26, 31, 37, 44, 47, 51, 53, 54, 55, 67, 258, 295 Phenylalanine, 249, 294, 295, 314 Phosphodiesterase, 204, 295 Phosphodiesterase Inhibitors, 204, 295 Phospholipases, 53, 295, 306 Phospholipids, 268, 279, 295 Phosphoric Monoester Hydrolases, 275, 296 Phosphorus, 253, 296 Phosphorylated, 29, 296 Phosphorylation, 61, 296 Photopheresis, 204, 296 Phototherapy, 11, 228, 296 Physical Examination, 229, 230, 296 Physiologic, 47, 58, 244, 251, 296, 302 Physiology, 12, 69, 103, 119, 265, 270, 289, 296 Pigment, 250, 296 Pigmentation, 205, 296 Pilot study, 33, 296 Pitch, 203, 296, 316 Pituitary Gland, 259, 296 Placenta, 268, 296, 299, 314 Placental tissue, 100, 296 Plant Oils, 291, 296 Plantago, 80, 138, 193, 296, 301 Plasma, 14, 60, 152, 155, 203, 244, 247, 254, 262, 265, 268, 272, 274, 281, 286, 288, 297, 316 Plasma cells, 14, 247, 288, 297 Plasma protein, 60, 203, 244, 265, 297 Plasma Volume, 262, 286, 297 Plasmids, 21, 69, 297 Platelet Activation, 297, 306 Platelet Aggregation, 246, 290, 297, 311 Platelets, 290, 297 Pleated, 281, 297 Pneumonia, 259, 297 Poisoning, 17, 202, 267, 280, 285, 288, 297 Policy Making, 272, 297 Polyethylene, 164, 297 Polymerase, 112, 297, 299, 303 Polymerase Chain Reaction, 112, 297 Polymers, 34, 148, 149, 262, 298, 300, 309 Polyneuritis, 263, 298 Polypeptide, 190, 191, 246, 257, 268, 275, 294, 298, 300, 317 Polysaccharide, 244, 248, 298

330

Allergens

Polyunsaturated fat, 29, 203, 298, 311 Polyvalent, 155, 160, 298 Posterior, 246, 292, 298 Postnatal, 23, 58, 298, 308 Postsynaptic, 298, 306, 310 Potassium, 286, 298, 307 Potentiates, 279, 298 Potentiation, 298, 306 Practice Guidelines, 222, 298 Precipitation, 150, 182, 298 Precursor, 55, 249, 260, 264, 266, 290, 295, 298, 313, 314 Predictive Value of Tests, 59, 298 Predisposition, 34, 55, 146, 298 Prednisolone, 298 Prednisone, 10, 211, 298 Prenatal, 23, 265, 299 Prevalence, 5, 7, 8, 10, 22, 28, 30, 31, 45, 56, 64, 79, 129, 192, 201, 204, 211, 299 Primary Prevention, 64, 123, 299 Probe, 36, 299 Problem Solving, 36, 299 Proctocolitis, 39, 299 Progeny, 55, 258, 299 Progesterone, 299, 308 Progression, 6, 203, 247, 299 Progressive, 254, 255, 264, 288, 297, 299, 303 Projection, 261, 290, 299 Proline, 257, 276, 299 Promoter, 42, 48, 299 Promotor, 299, 304 Prone, 164, 231, 299 Prophase, 288, 299, 310 Prophylaxis, 21, 299, 315 Prospective Studies, 39, 299 Prostaglandins, 249, 278, 299 Prostaglandins, Synthetic, 278, 299 Prostate, 251, 299, 314 Protease, 19, 43, 93, 106, 127, 171, 300 Protein C, 29, 39, 47, 51, 53, 57, 162, 193, 244, 246, 255, 256, 281, 300, 314 Protein Conformation, 246, 281, 300 Protein S, 69, 183, 184, 251, 271, 288, 300, 311 Proteins, 8, 13, 16, 18, 19, 23, 30, 34, 39, 48, 51, 53, 57, 60, 61, 65, 81, 83, 98, 115, 127, 130, 145, 152, 155, 158, 159, 160, 161, 163, 167, 169, 171, 173, 177, 182, 183, 186, 187, 188, 189, 190, 191, 193, 194, 203, 246, 247, 251, 253, 254, 255, 256, 257, 262, 270, 271, 274, 275, 277, 279,

281, 285, 287, 290, 294, 297, 298, 300, 302, 305, 306, 311, 313 Proteinuria, 289, 300 Proteolytic, 63, 91, 165, 192, 257, 266, 268, 292, 300 Proteome, 57, 300 Protocol, 27, 62, 300 Protons, 245, 275, 280, 300, 302 Protozoa, 152, 258, 285, 300, 308 Proximal, 10, 263, 288, 300 Pruritic, 264, 282, 300 Pruritus, 4, 10, 204, 276, 289, 300 Psoralen, 11, 300 Psoriasis, 9, 10, 126, 134, 288, 300 Psychiatry, 268, 300, 315 Psychic, 285, 301 Psychoactive, 301, 317 Psychogenic, 289, 301 Psychology, 12, 263, 301 Psyllium, 138, 296, 301 Public Health, 16, 24, 26, 31, 50, 86, 144, 222, 301 Public Housing, 16, 301 Public Policy, 221, 301 Publishing, 3, 5, 8, 69, 146, 301 Pulmonary Artery, 251, 301 Pulmonary Ventilation, 301, 304 Pulse, 287, 301 Purifying, 150, 181, 182, 262, 301 Purines, 301, 306 Purpura, 210, 301 Pyrimidines, 301, 306 Q Quality of Life, 7, 27, 33, 36, 50, 62, 68, 228, 301 Quaternary, 153, 300, 301 R Race, 28, 29, 286, 301 Radiation, 155, 156, 260, 266, 269, 277, 280, 301, 302, 317 Radioactive, 252, 275, 280, 287, 290, 291, 302 Radiolabeled, 53, 252, 302 Radium, 302 Radon, 82, 168, 302 Random Allocation, 302 Randomization, 36, 302 Randomized, 21, 33, 36, 49, 56, 59, 68, 264, 302 Reactive Oxygen Species, 31, 302 Reagent, 54, 152, 188, 263, 302 Receptors, Serotonin, 302, 306

331

Recombinant, 19, 30, 34, 70, 71, 73, 75, 81, 82, 86, 96, 97, 98, 100, 101, 104, 105, 107, 108, 109, 113, 118, 129, 146, 160, 161, 173, 174, 178, 181, 182, 187, 190, 191, 192, 193, 194, 302, 315 Recombinant Proteins, 181, 182, 302 Recombination, 42, 258, 270, 271, 302 Rectal, 210, 302 Rectum, 248, 250, 252, 257, 262, 269, 270, 278, 281, 299, 300, 302 Recurrence, 202, 302 Reductase, 169, 302, 311 Refer, 1, 253, 257, 263, 268, 283, 289, 303, 312 Reflex, 13, 39, 303 Reflux, 270, 303 Refraction, 303, 308 Regeneration, 44, 303 Regimen, 164, 264, 293, 295, 303 Regurgitation, 270, 303 Relaxant, 46, 303 Reliability, 44, 50, 168, 303 Remission, 54, 302, 303 Renal failure, 203, 303 Reperfusion, 155, 156, 303 Reperfusion Injury, 303 Repressor, 194, 291, 303 Reproductive cells, 271, 274, 303 Respirable, 142, 303 Respiration, 168, 248, 253, 287, 292, 303 Respiratory Physiology, 97, 303, 315 Respiratory System, 9, 58, 183, 203, 287, 303 Response Elements, 42, 304 Retina, 304 Retrograde, 13, 304 Retroviral vector, 270, 304 Rheumatoid, 134, 292, 304 Ribose, 243, 304 Rigidity, 296, 304 Risk factor, 7, 8, 12, 20, 22, 27, 28, 31, 36, 51, 52, 56, 67, 97, 118, 178, 227, 266, 304 Rod, 151, 250, 304 Rodenticides, 295, 304 Rubber, 3, 8, 81, 102, 158, 177, 229, 231, 243, 282, 304 Rural Population, 74, 95, 304 Ryanodine, 18, 304 Rye, 91, 122, 128, 162, 255, 267, 271, 304 S Salicylic, 167, 304 Saline, 252, 304

Saliva, 152, 171, 189, 304 Salivary, 172, 262, 304 Salivary glands, 172, 262, 304 Sanitation, 143, 304 Saponins, 304, 309 Satellite, 32, 305 Schizoid, 305, 317 Schizophrenia, 305, 317 Schizotypal Personality Disorder, 305, 317 Scleroproteins, 281, 305 Sclerosis, 34, 134, 287, 305 Screening, 6, 127, 130, 147, 152, 256, 298, 305 Seafood, 108, 157, 230, 305 Sebaceous, 172, 262, 281, 305, 316 Sebaceous gland, 172, 262, 281, 305, 316 Sebum, 305 Second Messenger Systems, 305 Secretion, 18, 22, 34, 37, 42, 61, 157, 259, 274, 275, 279, 280, 281, 286, 287, 305, 315 Secretory, 18, 19, 48, 60, 65, 305, 310 Sedative, 276, 305 Segregation, 29, 302, 305 Selection Bias, 7, 305 Semicircular canal, 278, 305 Sepsis, 155, 156, 306 Sequencing, 36, 48, 145, 148, 173, 298, 306 Serine, 127, 306, 313 Serologic, 277, 306 Serotonin, 146, 170, 260, 289, 295, 302, 306, 313 Serous, 257, 265, 306 Sessile, 164, 306 Sex Characteristics, 243, 246, 306, 310 Sexually Transmitted Diseases, 49, 306 Shock, 8, 61, 134, 146, 149, 181, 187, 246, 269, 306, 313 Side effect, 4, 10, 35, 162, 192, 199, 211, 213, 244, 254, 260, 306, 312 Signal Transduction, 69, 192, 279, 306 Signs and Symptoms, 7, 210, 303, 306 Sinusitis, 50, 135, 203, 306 Skeletal, 18, 246, 307 Skeleton, 243, 307 Skin Care, 228, 229, 307 Skin test, 21, 22, 26, 32, 36, 41, 51, 52, 71, 129, 161, 169, 176, 293, 307 Skull, 259, 307, 310 Sleep apnea, 6, 203, 307 Small intestine, 264, 266, 275, 280, 307, 313 Smooth muscle, 42, 46, 47, 146, 246, 249, 274, 307, 309

332

Allergens

Sneezing, 185, 196, 226, 294, 307 Soaps, 9, 231, 307 Social Environment, 301, 307 Social Sciences, 12, 307 Social Support, 12, 307 Socioeconomic Factors, 147, 307 Sodium, 45, 104, 203, 286, 307 Sodium Channels, 45, 307 Soma, 308 Somatic, 42, 78, 243, 275, 284, 286, 308, 315 Soybean Oil, 298, 308 Spasmodic, 243, 295, 308 Spasmogenic, 246, 308 Specialist, 202, 232, 308 Specificity, 15, 42, 148, 244, 298, 308 Spectrum, 39, 160, 194, 308 Sperm, 41, 246, 255, 271, 274, 297, 303, 308 Sphincter, 281, 308 Spinal cord, 254, 255, 265, 285, 289, 303, 308 Spinous, 266, 281, 308 Spirogram, 32, 308 Spirometry, 21, 22, 33, 36, 56, 308 Spleen, 20, 275, 283, 308 Spores, 25, 44, 142, 150, 154, 168, 180, 196, 308 Stabilization, 161, 162, 308 Standard therapy, 296, 308 Stem Cells, 273, 308, 314 Sterility, 260, 308 Steroid, 211, 227, 230, 259, 304, 308 Stimulant, 259, 260, 274, 309 Stimulus, 18, 61, 264, 280, 303, 309, 311 Stomach, 135, 203, 243, 262, 266, 267, 270, 275, 283, 288, 294, 295, 303, 307, 308, 309 Stomatitis, 204, 309 Strand, 193, 297, 309 Streptavidin, 50, 176, 309 Streptomyces, 19, 288, 309, 310, 311 Stringency, 191, 309 Stroke, 220, 253, 309 Students, Medical, 24, 309 Styrene, 304, 309 Subacute, 278, 307, 309 Subclinical, 278, 309 Subcutaneous, 70, 164, 179, 247, 264, 293, 309 Sublingual, 172, 309 Subspecies, 308, 309 Substance P, 252, 285, 305, 309 Substrate, 171, 180, 266, 275, 282, 309 Suction, 168, 268, 309

Sulfites, 4, 8, 310 Suppression, 38, 149, 259, 310 Suppressive, 54, 310 Surfactant, 23, 75, 99, 105, 127, 310 Sympathomimetic, 266, 290, 310 Symptomatic, 4, 11, 31, 310 Symptomatology, 42, 149, 310 Synapse, 35, 244, 310, 313 Synaptic, 289, 306, 310 Synaptic Transmission, 289, 310 Systemic disease, 10, 276, 310 T Tacrolimus, 212, 310 Tea Tree Oil, 137, 183, 310 Tear Gases, 281, 310 Temporal, 31, 34, 61, 310 Terminator, 256, 310 Testosterone, 302, 310 Tetani, 310, 311 Tetanic, 311 Tetanus, 30, 39, 310, 311 Tetracycline, 263, 311 Therapeutics, 14, 158, 183, 184, 215, 311 Thermal, 44, 249, 263, 289, 297, 311 Thimerosal, 5, 311 Thioredoxin, 161, 169, 311 Threonine, 306, 311 Threshold, 73, 95, 276, 311 Threshold Limit Values, 73, 95, 311 Thrombin, 268, 297, 300, 311 Thrombomodulin, 300, 311 Thrombosis, 279, 300, 309, 311 Thromboxanes, 249, 311 Thrush, 11, 311 Thymus, 277, 283, 311 Thyroid, 311, 314 Thyroxine, 244, 295, 311 Ticks, 154, 278, 290, 312 Tinnitus, 7, 291, 312, 316 Tissue Culture, 57, 312 Tolerance, 32, 35, 39, 54, 68, 70, 157, 163, 164, 192, 208, 272, 312 Tomography, 252, 312 Tone, 13, 312 Tonus, 312 Toxicity, 45, 170, 264, 285, 312 Toxicology, 112, 114, 115, 124, 126, 222, 312 Toxin, 76, 161, 169, 263, 265, 266, 311, 312 Toxoid, 30, 39, 312 Trace element, 256, 289, 312 Trachea, 6, 13, 252, 281, 295, 311, 312

333

Tractus, 13, 312 Tranquilizing Agents, 254, 312 Transcription Factors, 304, 313 Transduction, 253, 306, 313 Transfection, 251, 270, 313 Transfer Factor, 277, 313 Transfusion, 313 Translating, 32, 313 Translation, 24, 270, 288, 313 Translational, 32, 47, 313 Translocation, 42, 156, 313 Transmitter, 243, 280, 284, 290, 313 Transplantation, 255, 275, 277, 284, 313 Trauma, 267, 288, 313 Trees, 142, 146, 164, 190, 193, 267, 304, 313 Triamcinolone Acetonide, 10, 313 Trophic, 58, 313 Trypsin, 147, 161, 169, 266, 313, 317 Trypsin Inhibitors, 161, 169, 313 Tryptophan, 257, 306, 313 Tuberculosis, 304, 313 Tumor marker, 251, 313 Tumor Necrosis Factor, 284, 314 Tunica, 287, 314 Type 2 diabetes, 27, 314 Tyrosine, 37, 164, 314 U Ubiquitin, 30, 314 Ulcerative colitis, 210, 278, 314 Umbilical Arteries, 314 Umbilical Cord, 105, 314 Umbilical cord blood, 105, 314 Urban Health, 21, 314 Urban Population, 24, 106, 314 Urea, 182, 314 Urease, 289, 314 Uremia, 281, 303, 314 Urethra, 294, 299, 314 Urinary, 203, 271, 314 Urine, 32, 52, 152, 171, 173, 180, 203, 251, 300, 314 Urogenital, 271, 314 Urticaria, 10, 39, 119, 228, 246, 254, 276, 283, 314 V Vaccination, 14, 43, 94, 158, 190, 193, 314 Vaccine, 14, 16, 20, 30, 58, 76, 183, 184, 195, 243, 245, 300, 315 Vacuoles, 265, 291, 315 Vagal, 13, 315 Vagus Nerve, 315

Vascular, 60, 246, 247, 262, 265, 278, 290, 296, 314, 315 Vasculitis, 10, 315 Vasoactive, 149, 315 Vasoconstriction, 267, 315 Vasodilator, 252, 274, 315 Vasomotor, 164, 315 Vector, 192, 313, 315 Vein, 280, 290, 305, 314, 315 Venom, 41, 78, 108, 127, 161, 169, 315 Venous, 300, 315 Ventilation, 31, 144, 315 Venules, 251, 265, 315 Vertigo, 7, 135, 291, 315, 316 Vestibule, 256, 278, 305, 315 Vestibulocochlear Nerve, 312, 315 Vestibulocochlear Nerve Diseases, 312, 315 Veterinary Medicine, 221, 316 Vial, 102, 316 Viral, 21, 23, 46, 47, 61, 69, 194, 265, 270, 271, 278, 291, 313, 316 Viral Load, 23, 316 Virulence, 312, 316 Virus, 21, 23, 266, 271, 279, 280, 304, 313, 316 Viscera, 308, 316 Viscosity, 155, 156, 316 Vital Capacity, 293, 316 Vitamin A, 278, 316 Vitiligo, 114, 300, 316 Vitro, 14, 15, 19, 35, 43, 45, 48, 49, 50, 53, 57, 58, 60, 63, 78, 82, 89, 112, 125, 126, 147, 162, 164, 169, 176, 177, 194, 271, 274, 277, 297, 310, 312, 316 Vivo, 13, 19, 23, 34, 35, 42, 43, 53, 57, 60, 63, 73, 125, 149, 164, 176, 177, 271, 274, 277, 292, 310, 311, 316 Voice Disorders, 6, 316 Voice Quality, 6, 316 Vulgaris, 114, 316 W Wart, 281, 316 Wheezing, 8, 56, 61, 100, 180, 185, 211, 286, 316 White blood cell, 247, 250, 257, 266, 273, 283, 284, 287, 288, 289, 297, 316 Whooping Cough, 295, 316, 317 Windpipe, 295, 311, 317 Withdrawal, 47, 317 Wound Healing, 49, 63, 279, 317

334

Allergens

X Xenograft, 247, 317 X-ray, 34, 250, 252, 254, 269, 290, 317

Y Yeasts, 269, 295, 317 Z Zymogen, 300, 317

335

336

Allergens