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It is only during the last decade that the functions of sinusoidal endothelial cells, Kupffer cells, hepatic stellate cells, pit cells and other intrahepatic lymphocytes have been better understood. The development of methods for isolation and co-culturing various types of liver cells has established that they communicate and cooperate via secretion of various intercellular mediators. This monograph summarizes multiple data that suggest the important role of cellular cross-talk for the functions of both normal and diseased liver. Special features of the book include concise presentation of the majority of detailed data in 19 tables. Original schemes allow for the clear illustration of complicated intercellular relationships. This is the first ever presentation of the newly emerging field of liver biology, which is important for hepatic function in health and disease and opens new avenues for therapeutic interventions.
In the two decades since the elusive "slow reacting substance of anaphylaxis" (SRS-A) was identified as a product of the action of the 5-lipoxygenase enzyme on arachidonic acid, it has been well established that the leukotrienes are key mediators of both alIergy and inflammation. Their release by alIergen or other challenge has been demonstrated in the lungs of asthmatic subjects, and measurement of urinary leukotriene concentrations in such patients has been shown to be a valuable, non invasive indicator. Significant progress has been made towards the characterization of the leukotriene receptor subtypes, exemplified by the cloning of the LTB4 receptor earlier this year. Coupled with this there has been a continued elucidation of signal transduction mechanisms underlying receptor activation. Consequent upon these advances has been the development of potent antagonists of the CysLT receptor, J and both these and inhibitors of leukotriene biosynthesis have entered clinical practice in the therapy of asthma. In this clinical setting antagonists of the CysLTJ receptor have been shown to be an effective therapy in chronic asthmatics, against antigen- and exercise-induced bronchoconstriction, and in aspirin-intolerant asthmatics. The advent of this new class of agents promises to change the way in which asthmatic patients are currently treated.
The Leukotrienes, Chemistry and Biology discusses the significant scientific progress of leukotrienes, from the discovery of slow-reacting substance to the chemical identification of a mixture of leukotrienes. Composed of 11 chapters, the book presents an enormous increase in research on the chemistry and biology of these and related substances, especially as they relate to the etiology of allergic and inflammatory diseases. After briefly discussing the continuing perspectives on the leukotriene biology, the book describes the structure, synthesis, formation, and biological actions of leukotrienes. This is followed by a discussion on arachidonic metabolism for the development of therapeutic agents specifically designed to either inhibit the synthesis or antagonize the effects of the leukotrienes. The book also looks into the biochemical and pharmacologic control of the synthesis and actions of leukotrienes. The information is considered in the context of the specific enzymes in the pathway that may be affected by any given agent. The in vivo studies on the pulmonary mechanical effect of leukotrienes, the pharmacologic activity of leukotriene receptors, and the antagonistic property of peptidoleukotrienes as an approach to allergic disease treatment are considered in the concluding chapters of the book. This book will be of value to scientists and researchers interested in hypersensitivity reactions, inflammation, and allergic diseases.
This study looks at the way the products of arachidonic acid metabolism are active both in normal and abnormal immune responses. While some of the fundamental issues such as whether lymphocytes are capable of producing prostaglandins and leukotrienes are still hotly debated, the evidence is overwhelming that many specific immunological problems and disease states are associated with alterations in the normal balance of arachidonic acid metabolism. This book provides a review of the history and chemistry of the arachidonic acid cascade as well as an exhaustive survey of the literature concerning the interaction of arachidonic acid metabolites with cells of the immune system. The author also presents and discusses the evidence demonstrating prostaglandin and leukotriene participation in response to injury and in malignancy, tissue and organ rejection, rheumatoid arthritis, autoimmunity and allergy.
Many new antileukotriene drugs are now marketed as antiasthma drugs and represent the first new drugs in this field since the 1970s. This book covers the steps that have led to the discovery and development of these new drugs and offers detailed descriptions of their clinical applications. The review chapters on the main aspects of basic and applied leukotriene research are written by leading specialists in the field, and the volume takes a new approach in presenting information of particular interest to both scientists and clinicians in the fields of asthma, inflammation and allergic diseases.
Prostaglandins, Leukotrienes, and Cancer is a multi-volume series that will focus on an emerging area of cancer research. In 1968, R.H. Williams first reported that elevated prostaglandin levels are present in human medullary car­ cinoma. Since that time, the concept that arachidonic acid metabolites may be in­ volved in cancer has expanded to include every aspect of the disease from cell transformation through metastasis. Prostaglandins and leukotrienes are generic terms used to describe a family of bioactive lipids produced from unsaturated fatty acids (principally from arachidonic acid) via the cyclooxygenase and lipoxygenase pathways, respec­ tively. Cyclooxygenase products consist of diverse products such as prosta­ glandin E, (POE,), prostacyclin (POI2) and thromboxane A2 (TXA2), whereas lipoxygenase products consist of hydroperoxy fatty acids and mono-, di- and tri-hydroxy acids including leukotrienes. The precursor fatty acids for the cyclooxygenase and lip oxygenase pathways are present in cellular phospholipids. This finding established an important control point in their biosynthesis-the release of substrate. This occurs in response to numerous stimuli that act at the cell surface. Dr. Bengt Samuelsson's extensive study of the metabolism of pros­ taglandins indicated that they are rapidly inactivated on a single pass through pulmonary circulation. Thus, they cannot act as circulating hormones and appear to be made on demand in or in the vicinity of target tissues leading to the concept that prostaglandins are local hormones or autocoids.
Eosinophils in Health and Disease provides immunology researchers and students with a comprehensive overview of current thought and cutting-edge eosinophil research, providing chapters on basic science, disease-specific issues, therapeutics, models for study and areas of emerging importance.
The increasing incidence and prevalence of allergic disease worldwide is one of the most remarkable phenomena of the past 50 years. One in three people in developed countries will experience an allergic condition at some point in their lives and advances in understanding the causes of this trend, and in allergy treatment and care, have captured the imagination of scientists, clinicians and the public. Landmark Papers in Allergy is a definitive collection of over 90 papers charting key discoveries and scientific advances in relation to allergy and the development of treatment and care for allergic disorders. Comprehensive in its coverage, the book includes the first clear descriptions of allergic diseases; the major advances in treatments, such as the discovery of antihistamines, cortisone, biological therapies and immunotherapy; the great immunological advances, such as the discovery of immunoglobulin E (IgE) and leukotrienes; the possible factors behind the increase in allergy, such as the house dust mite, changes in hygiene and diet; and the growing understanding of the social, psychological and quality-of-life consequences of allergy. Including authoritative commentaries from leading international experts providing reflections on the historical importance and current relevance of each landmark paper, Landmark papers in Allergy is essential reading for any clinician or academic with an interest in allergy.