Contents:
1. Bacterial and Plant Toxins - General Mode of Action A.E. Frankel and P.D. Hall 2. Diphtheria Toxin-Structure, Function and its Therapeutic Use R.C. Ratts and J.C. VanderSpek 3. Ricin A-Structure, Function and its Clinical Applications M. Colmbatti 4. Pathways of Delivering Toxins into the Cytosol of Target Cells M. Lord, P.J. Day, M.E. Jackson, S.R. Owens, J.C. Simpson, D.C. Smith and L.M. Roberts 5. Engineering Immunotoxins for Improving their Therapeutic Activity Y. Reiter, G. Denkberg and C. Cohen 6. Ligand-receptor Interactions Studied with Chimeric Proteins H. Lorberboum-Galski 7. Chimeric Proteins: a Novel Approach for Eliminating Specific Cell Populations for Targeted Human Therapy A. Ben-Yehudah, R. Belostotsky, R. Aqeilan, Y. Azar, I. Steinberger, A. Fishman, A. Nechushtan, S. Yarkoni and H. Lorberboum-Gaski 8. Chimeric Neurotoxins - a Molecular Neurosurgery Approach P. Lazarovici 9. Targeted Immunotherapy of Autoimmune Diseases by Chimeric Toxins B.A. Holder and J.G. Krueger 10. Immunotoxins for Targeted Cancer Therapy R.J. Kreitman 11. Molecular Targeting of Brain Tumors with Cytotoxins W. Debinski 12. Toxins in the Development of Vaccines C.T. Hsu, C.Y. Ting and J. Hwang

Antisense technology may result in dramatic changes in the therapy of many diseases and may provide tools to dissect pharmacological processes and to confirm the roles of various genes. In this volume, progress in the understanding of antisense technology and its use in creating new drugs is discussed. Potential caveats, pitfalls and limitations of the technology are also presented. In the next few years the pace at which new molecular targets will be identified will increase exponentially as the sequencing of the human genome and of other genomes proceeds.

Considerable investment has been made by both pharmaceutical and biotechnology companies in pharmaceutical products of biotechnology. However, because relatively few of these products have been marketed, lack of relevant experience means that uncertainty still surrounds the most appropriate strategy for their safety evaluation. The 13th CMR International Workshop, held in February 1997, provided the opportunity for regulatory authority and industry experts from Europe, Japan and the USA to share their experiences of designing safety evaluation programmes for specific product classes: colony stimulating factors, growth factors, hormones, interferons, interleukins, monoclonal antibodies for therapeutic use, and gene therapy products. Participants worked together to recommend those studies that should be considered for such safety evaluation, and those that may be unnecessary. These recommendations subsequently made a valuable contribution to the ICH guideline Safety Studies for Biotechnological Products', which was finalised at ICH 4 in Brussels in July 1997. The Workshop proceedings not only describe the recommendations but also provide the reader with an appreciation of the science behind safety evaluation strategies used by experts, the influence of different regulatory systems on these strategies, and the type of data required by both toxicologists and clinicians before they have sufficient confidence to administer pharmaceutical products of biotechnology to humans.

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Hagley Perspectives on Business and Culture

Offering a basis for further research into the interactions of hosts and pathogens, this work gathers up-to-date findings, and details basic structures, functions and immunology. It provides descriptions of a variety of experimental endotoxin neutralizing agents, as well as a guide to clinical research initiatives and the latest treatments.

The Sapporo International Symposium on "Recent Advances in Nitric Oxide Research" was held in Sapporo, Japan, in 1997, following the Fifth International Meeting on the Biology of Nitric Oxide in Kyoto, Japan, organized by Dr. Salvador Moncada, Dr. Noboru Toda, and Dr. Hiroshi Maeda. The field of nitric oxide research continues to expand rapidly, and our understanding of the physiological and pathophysiological roles of NO has increased greatly. The Kyoto Meeting was stimulating and informative, providing impetus for the Sapporo Symposium, which I had the great honor to organize. To communicate the information from these events, Dr. Ichiro Sakuma and I decided to publish this book. The contents of its chapters were contributed by the participants who were active at the Sapporo symposium and cover the majority of the presentations made during that symposium. Dr. Csaba Szabo of Children's Hospital Medical Center in Cincinnati (U. S. A. ) reviews the roles of peroxynitrite and poly(ADP-ribose)synthetase in shock, inflammation, and reperfusion injury, and Dr. David A. Geller and his colleagues of the University of Pittsburgh (U. S. A. ) review the regulation and function of NO in the liver. As contributions from the Hokkaido University School of Medicine (Sapporo), Dr. Hiroko Togashi and colleagues present their data on transient cerebral ischemia and NO production, Dr.

Cell Culture Methods for in vitro Toxicology introduces the reader to a range of techniques involved in the use of in vitro cell culture in toxicological studies. It deals with major cell types studied in the field of toxicology and will be useful for anyone wishing to start work with animal cell cultures or to refresh their knowledge relating to in vitro cell models. Fundamental chapters deal with the general biology of cytotoxicity and cell immortalisation these are key issues for in vitro systems addressing the 3Rs' principle. Up-to-date overviews deal with the use of cells from liver, brain and intestine. In addition, biochemical analysis of cell responses, biotransformation pathways in cells and recombinant approaches to the early detection of cell stress are also covered in detail. Prominent features of in vitro technologies also include regulation, biosafety and standardisation. Dedicated chapters deal with these issues in a practical way in order to lead the reader to the right source of information. This book provides an up-to-date, informative and practical review of cell culture methods for in vitro toxicology. It will be of equal benefit to students and experienced toxicologists with little experience of in vitro cell culture.

Structure-Activity Relationships in Environmental Science is the first book of its kind that brings together information from a variety of sources into one document. It provides a comprehensive overview of the entire field of quantitative structure-activity relationships (QSARs) as well as being a reference for SAR experts. The book comprises three parts. Part One covers the theoretical background of structure-activity studies and Part Two deals with the practical applications of such methods in the environmental sciences. Part Three critically discusses SAR models with respect to their reliability and their aptness in environmental hazard and risk assessment. Recommendations are made as to which model to use and the case is presented for using QSARs in hazard assessment. The use of QSARs is becoming increasingly important since there is little experimental data available on environmentally relevant chemicals. Structure-Activity Relationships in Environmental Sciences will thus serve as an invaluable guide to both postgraduate and research scientists as well as professional ecologists.

The incidence of food poisoning continues to rise and now there is even greater interest in the subject of microbial food poisoning and food safety, than when the first edition of this popular book was published. As in the first edition of his book, Adrian Eley summarizes information on the principal agents that cause food poisoning and emphasizes their mode of action. Also discussed in chapters written by specially selected expert in the area are epidemilogical features of food poisoning, microbiological control of food production, mycoticoxic fungi and food safety legislation. Each chapter has been comprehensively updated to include any changes in for example laboratory practice, legislation, etc. Also included in this edition is a new chapter on food hygiene. Microbial Food Poisoning, Second Edition, appeals to students studying a wide range of courses, including medical microbiology, food science, and technology, nutrition, general microbiology and environmental health. This book will also be of use to professionals in a range of disciplines including food science, medicine, health sciences and environmental and public health.

This volume offers the most comprehensive presentation available on metal toxicology. It discusses not only metals but also the toxic endpoints, such as neurotoxicity, renal toxicity, and cancer induction. Chapters are written by experts in their respective fields, focusing on carcinogenesis and human exposures and highlighting the major aspects and issues of toxicity in general.

The volumes that comprise Chemical Sensitivity are the first major scientific books to be published on chemical sensitivity, a growing world-wide health problem. These volumes present clinical experiences in diagnosing and treating chemical sensitivity in over 20,000 patients under controlled conditions.

Biological Effects of Low-Level Exposures, more commonly referred to as BELLE, began as a conference in May 1990. Its members are committed to the enhanced understanding of low-dose responses of all types to human exposures to chemical and physical agents, whether of an expected or paradoxical nature.
The focus of BELLE encompasses dose-response relationships to toxic agents, pharmaceuticals, and natural products over wide dosage ranges in both in vitro systems and in vivo systems, including human populations. While BELLE promotes the scientific understanding of low-level effects, its primary goal is the scientific evaluation of existing literature and ways to improve research and assessment methods.

How to protect against ischemia/reperfusion damage is one of the most urgent problems in medicine. It is known that ischemic damage can be attenuated by improving the oxygen balance of the ischemic heart, but the damage-producing mechanism is not yet fully understood. This book provides the latest information on the pathophysiology of ischemia/reperfusion damage and presents new ideas for more effective methods for protection. In the first two sections, the roles of such factors as various ions and phospholipids that modulate ischemia/reperfusion damage are explored, providing a clear and updated explanation of the mechanisms involved. In the third section, the myocardial and vascular remodeling procedure in hearts that have undergone ischemia/reperfusion is explained in terms of signal transduction, enabling a new understanding of the remodeling process. In the final section, a new approach to protection against ischemia/reperfusion damage is presented.

Covers developments in food safety and foodborne illness, organizing information to provide easy access to many topics, both general and specific. Comprehensive summaries of important advances in food science, compiled from over 550 sources worldwide, are presented.

Chemical Sensitivity is the first major scientific book series on chemical sensitivity, an increasingly important worldwide health problem. This four-volume series features results from the study of more than 20,000 environmentally sensitive patients at the Environmental Health Center (EHC) in Dallas. Results from the study at EHC are supplemented by information accumulated from the treatment and study of an estimated 100,000 patients by other environmentally oriented physicians and scientists around the world.

Numerous reports demonstrate that the reproductive system could be affected by multiple potential toxicological agents. The volume includes different aspects of the development of new approaches to in vitro testing using sperm cells and systems involved on reproduction in mammals. Comparative analysis of in vivo and in vitro methods has been included to take steps towards the further development of and applications of new systems for germline toxicology.

The contributors provide a rich overview of the strengths and limitations of using risk assessment methods in the occupational health arena. This book brings together a distinguished group of experts in occupational health and risk assessment who express diverse views on the usefulness of risk assessment in the protection of worker health. Representatives from regulatory agencies, labor, industry, and academia consider both policy and technical issues, providing a rich overview of the strengths and limitations of using risk assessment methods in the occupational health arena. Both policy and technical issues are explored. Several contributors focus on the policy implications of regulatory agencies' increasing reliance on risk assessment to guide occupational and environmental risk reduction strategies. Others consider specific methodological issues relating to the application of state-of-the-art scientific developments to the evaluation of occupational risks. Chapters are organized to consider specific aspects of the field including current applications of risk assessment methods by federal regulatory agencies; approaches to improving the use of epidemiological data in risk assessment; the use of animal bioassay data to predict occupational risks; potential uses of cutting-edge scientific data on toxicological mechanisms, toxicokinetics, and biomarkers in risk assessment; specific issues including ethics, values, and sociopolitical aspects of the process, and a concluding chapter discussing future directions to the evaluation and regulation of risks to worker health and safety. Given the range of policy and technical issues explored, this collection will be invaluable to professionals as well as academics in the fields of occupational health and environmental risk assessment.

Papers from the Second International Conference on TDM Toxicology (date and place not stated) describe research on various aspects of therapeutic monitoring pharmacology, selected high-performance liquid chromatographic methods, antiepileptics, substances subject to abuse, inorganics. Over 100 contr

Mycotoxins produced by molds are common contaminants of many important crops, including wheat, corn, rice, and peanuts. Some mycotoxins are found in fruits and vegetables. These contaminants have a broad range of toxic effects, including carcinogenicity, neurotoxicity, and reproductive and developmental toxicity. The occurrence of mycotoxins in foods is an unavoidable worldwide problem. About 80 countries have imposed regulatory limits to minimize human and animal exposure to mycotoxins. Regulatory limits, including international standards, have tremendous economic impact and must be developed using science-based risk assessments. The purpose of Mycotoxin Protocols is to provide the scientific and technological basis for analytical methods for use in obtaining the exposure data needed for risk assessments. Mycotoxin Protocols is divided into four sections, which are interc- nected. The first section: Chapters 1-5 describe the general techniques for mycotoxin analysis with emphasis on the importance of method validation based on statistical parameters; sampling procedures for collecting a sample as representative as possible of a bulk lot; the isolation of mycotoxins for use as analytical standards or for toxicological studies; the evaluation of purity and preparation of standards; and the detection and identification of impu- ties in isolated mycotoxins. Sections 2-4: Chapters 6-19 describe the most current chromatographic and immunochemical methods for studies on the major mycotoxins.

This excellent book is a concise yet thorough examination of the important and emerging field of the study of biological risk factors in drug abuse. Historically, drug abuse research has concentrated on the contributions of environmental and behavioral factors as the major influences on addiction. The revelatory studies in this volume examine the genetic contributions to drug taking behavior through the use of animal models, cellular experiments and human clinical studies. Behavioral and Biochemical Issues in Substance Abuse provides for the first time in one volume, up-to-date, easily digested reviews of topics concerning biological and genetic factors in drug abuse. Medical researchers in all areas of alcoholism and drug abuse, researchers in pharmacology, psychology, psychiatry and neuroscience, and clinicians interested in biological approaches to alcoholism and drug abuse problems will benefit greatly from this valuable resource. Authoritative contributors clearly demonstrate the capability of genetic factors to modulate the reinforcing or rewarding effects of drugs, thereby altering their addictive potential. In addition to gaining comprehension of the biological factors affecting addiction, a greater understanding of genetics related to drug abuse will enable future research to control biological factors, leading to more accurate studies of behavioral and environmental influences on drug and alcohol abuse.

In 24 contributed chapters, 37 international specialists describe the latest developments in research on snake venom including different types of venoms and toxins, actions, antidotes, and applications and summarize what is known to date on Gila monster and frog toxins. Some 70 tables provide essent

This book tells the story of Agent Orange, its usage and the policies that surround it. Agent Orange contains a contaminant known as TCDD. It was the most widely used defoliant from 1965 - 1970 and became one of three major tactical herbicides used in Vietnam. More than 45 major health studies were conducted with Vietnam veterans from the United States, Australia, New Zealand, and Korea seeking a relationship between veterans' health and TCDD. Allegations of birth defects in the families of Vietnam veterans and the Vietnamese represented a case study in propaganda and deliberate misinformation by the government of Vietnam. The Policies of the US Government implemented by Congress and the Department of Veterans Affairs (DVA) identified 17 recognized associated presumptive diseases that failed the tests of "cause and effect" and common sense. This book tells the story of Agent Orange, its usage, the health studies and those policies from a diverse range of perspectives, delving into science, statistics, history, policy and ethics. It is of interest to scholars engaged in history, political and social philosophy and ethics.

This comprehensive treatise offers an in-depth discussion of natural toxicants in plants, emphasizing their effects as defenses against herbivory. Coevolution of plants and her-bivores are covered with a detailed treatment of toxicant metabolism and systemic effects in mammalian tissues. Con-sideration of the economic importance of plant toxins, modi-fication by plant breeding, management of toxico-sis, and toxicant problems in various geographic areas are in-cluded. Each volume offers an extensive description of chemistry, biosynthesis, analysis, distribution in plants, metabolism in mam-mals and insects, and practical problems in humans and livestock.