Coronary circulation research is advancing at a rapid rate. Not only are inno vative techniques for studying myocardial perfusion being developed, new mechanisms related to coronary blood flow control and mechanics are also being discovered. The progress in this field justifies an update in the form of this new monograph. The book is divided into the following sections: "Measurement of Coronary Blood Flow and Assessment of Myocardial Per fusion" discusses advances in perfusion measurements in humans as well as nonradioactive microsphere methods. . "Coronary Flow Dynamics" elucidates the effect of heart contraction on coronary flow, perfusion, and reserve distribution as well as systolic-diastolic interaction. Models-a frequent topic of debate-are used to quantify hypotheses. "Models of Coronary Circulation" attempts to elucidate the concept of tissue pressure. "Regulatory Mechanisms of Coronary circulation and its Clinical Relevance" N u.merous mechanisms affecting coronary flow have been defined and studied at the level of isolated vessels and whole organs. The chapters in this section provide an in-depth analysis of a selection of these mechanisms and their inter actions. "Pathophysiology of Coronary Circulation in Ischemic Heart Disease" considers important aspects of factors which restrict perfusion of the myocardium in ischemic heart disease. An understanding these factors is of crucial importance in the management of patients. "Small Vessel Disorder in Coronary Circulation" describes circulatory flow and how it can be influenced by drugs."

In recent years, we have witnessed a rapid expansion of our knowledge regarding the role of the endothelium in the control of vascular tone (and organ perfusion) in health and disease. Physiology, pharmacology, and molecular biology have uncovered a wealth of information on structure and function of this heretofore largely neglected "organ". Clinical medicine is now called upon to define the clinical significance of these observa tions that imply the mechanisms of blood coagulation, e.g., the interaction of throm bocytes with the endothelium, vasomotor control, and specifically, the regulation of smooth muscle tone with consequences for vascular resistance and conductance and organ blood flow. Finally, metabolism of lipids with the everlasting problem of athero sclerosis is an important aspect. In a second step, implications regarding the improvement of current therapeutic con cepts, as well as the development of new modalities of pharmacotherapy will have to be discussed. The topic addressed by the 1990 Gargellen Conference: Endothelial Mechanisms of Vasomotor Control, clearly is of interest for both basic scientists and clinicians. It has been the aim of the organizers, the Society for Cooperation in Medical Science (SCMS) with this and the previous symposia to foster and support both basic science and clinical research. Research in medicine today shows two major directions of development: on the one hand, increasing involvement of the basic sciences and their methodology. On the other hand, statistical validation of concepts and therapeutic strategies in large scale population-and multicenter-studies.

Recent developments in recombinant DNA technology have led to the large-scale production of human erythropoietin and to the demonstration that it is effective in the treatment of renal and possibly some other anaemias. This has lent a new impetus to studies of the pathophysiology and pharmacology of the hormone which is reflected in this report of the proceedings of a meeting held in Liibeck in June 1988. In 15 papers, all from European centres, the broad topics covered are erythropoietin's physiology and chemistry, the patho- physiology of erythropoiesis and the use of erythropoietin in the treatment of anaemia. Several of the papers include up-to-date reviews of the literature. The field is now expanding rapidly, and this volume, though not comprehensive, usefully points up many areas of recent understanding as well as others of continuing un- certainty. Overall, it contains material likely to be of interest to biochemists and experimental haematologists as well as to phar- macologists, clinical haematologists and nephrologists.

The function of the vestibular system is not as obvious as those of vision, hearing, touch or smell. Vestibular dysfunction, however, is clearly apparent where lesions are present. It is probably for this reason that the vestibular sense was not discovered until the nineteenth century and that clinicians have continued to playa major role in basic vestibular research right up to the present. The relationship between basic and clinical research is certainly stronger in the vesti bular field than in that of tactile sensation, for instance, as testified by the work of clinicians as MENIERE, BREUER, BARANY, DEKLEIJN and FRENZEL. In this respect the situation is similar in vestibular physiology and in endocrinology, and for the same reason. This second part of the vestibular volume of the Handbook of Sensory Physio logy will be of interest to neurologists, otologists, neurosurgeons, ophthalmologists and physiotherapists on the one hand, and psychologists, physiologists, engineers and aviation specialists on the other. For a full understanding of Part 2, it is necessary to have assimilated the basic anatomy, physiology, and biochemistry of Part 1."

Dr. Elisabeth Bock (Photo Keenpress) This book contains review articles that produce a snapshot of recent developments in the field of the neural cell adhesion molecule NCAM. The chapters are grouped into sections reflecting various aspects of NCAM structure and function. The themes cover the structural basis of cell adhesion mediated by NCAM and NCAM interaction partners, NCAM-mediated signaling determinants of NCAM function under physiological conditions and in disease, and the therapeutic potential of NCAM mimetics. Section 1, "Structure and Ligands of NCAM," introduces the reader to the str- tural basis of NCAM-mediated cell adhesion, discussing the current knowledge of extracellular and intracellular NCAM ligands and the structural basis of NCAM int- actions with the fibroblast growth factor (FGF) receptor. Section 2, "NCAM and Polysialic Acid," focuses on NCAM polysialylation, discussing the structural and functional aspects of the most important posttranslational modifications of NCAM by the addition of a long linear homopolymer of sialic acid to the fifth Ig-like NCAM module. Section 3, "NCAM-mediated Signal Transduction," is devoted to signal v BookID 187530_ChapID FM1_Proof# 1 - 01/03/2011 BookID 187530_ChapID FM1_Proof# 1 - 01/03/2011 vi Preface transduction mechanisms associated with NCAM-mediated adhesion, with a focus on signaling pathways involved in NCAM-mediated neurite outgrowth, the role of growth-associated proteins, signaling through lipid microdomains, and signaling crosstalk with the epidermal growth factor (EGF) receptor. Section 4, "NCAM Metabolism," focuses on current knowledge about NCAM biosynthesis and the g- eration and role of soluble NCAM.

In the last few years, technologies that allow for monitoring and manipulating neuronal networks at a single cell resolution have been rapidly expanding. In Neuronal Network Analysis: Concepts and Experimental Approaches, experts in the field provide an overview of some of the most advanced techniques for the study of neuronal circuits, highlighting current technical limitations and providing a vision of what is yet to come. Broken into six convenient, interdependent section, this volume covers optical approaches, electrophysiological approaches, both in vitro and in vivo, optogenetics, morpho-functional approaches, and neuronal network analysis in humans. As a volume in the Neuromethods series, this work provides the kind of detailed description and implementation advice that is crucial for getting optimal results. Authoritative and cutting-edge, Neuronal Network Analysis: Concepts and Experimental Approaches will be useful for early career neuroscientists, as well as for experienced neuroscientists, by providing a practical framework for studying the brain as an organ while maintaining an appreciation for its cellular diversity.

This volume contains the manuscripts of the full papers and posters pre- sented at the conference "Dietary Phenylalanine and Brain Function," which took place at the Park Hyatt Hotel, Washington, D.C., on May 8-10, 1987. The conference was organized by a committee that included Drs. Louis Elsas (Emory University, Atlanta), William Pardridge (UCLA), Timothy Maher (Massachusetts College of Pharmacy), Donald Schomer (Harvard), and Richard Wurtman (MIT). It was sponsored by the Center for Brain Sciences and Metabolism Charitable Trust, a foun- dation which, during the past few years, had also organized seven other conferences related to interactions between circulating compounds (drugs, nutrients, hormones, toxins) and brain function. The Center's most recent other conferences were on "Melatonin in Humans" (Vienna, Austria; November 1985) and "The Pharmacology of Memory Disorders Associ- ated with Aging" (Zurich, Switzerland; January 1987). The decision to organize this conference was based on the perception that major changes had recently occurred in society's uses of phenylalanine and phenylalanine-containing products, and on the belief that a meeting of scientists and physicians who work on the amino acid's neurological effects could both catalyze additional research on these effects and assist regula- tory bodies in formulating appropriate public policies relating to the use of these products: phenylalanine, in both its L- and D-forms, has apparently become a popular sales item at "health-food" stores, and thus is now being consumed by a fairly large number of people, in the absence of the other

The recent interest in the pharmacology of the skin and the treatment of its diseases has come about for two reasons. The first is a realisation that many aspects of pharmacology can be studied as easily in human skin as in animal models, where they may be more relevant to human physiology and disease. Examples of this are the action of various vasoactive agents and the isolation of mediators of inflammation after UV irradiation and antigen-induced dermatitis. The second reason is the fortuitous realisation that a pharmacological approach to the treatment of skin disease need not always await the full elucidation of aetiology and mechanism. For example, whilst the argument continued un resolved as to whether the pilo-sebaceous infection which constitutes acne was due to a blocked duct or to a simple increase in sebum production, 13-cis retinoic acid, was found quite by chance totally to ablate the disease; again, whilst cyclosporin, fresh from its triumphs in organ transplantation, has been found able to suppress the rash of psoriasis, it has resuscitated the debate on aetiology. We are therefore entering a new era in which the pharmacology and clinical pharmacology of skin are being studied as a fascinating new way of exploring questions of human physiology and pharmacology as well as for the development and study of new drugs, use of which will improve disease control and at the same time help to define pathological mechanisms.

Anesthetics produce a reversible state of unconsciousness accompanied by ante- grade amnesia. This remarkable phenomenon brings great relief to surgical patients and wonder to clinicians and scientists. To date, we do not fully understand the mechanisms by which anesthetics ablate conscious sensation and memory. We are, however, making progress. This book presents original results as well as overviews of the current state of knowledge of the problem. It is authored by investigators who know the ?eld well; their research at a number of levels has contributed substantially to our c- rent understanding of anesthetic modulation of memory and consciousness. Most of the contributors were presenters at two workshops organized by Dr. Pearce and Dr. Hudetz at the 40th Annual Winter Conference on Brain Research, held at Snowmass Village, Colorado, from January 27 through February 2, 2007. One workshop focused on anesthetic modulation of consciousness and another on an- thetic modulation of memory. Seven of the chapters are based on material presented at these symposia - appropriately updated with new relevant ?ndings. This infor- tion is supplemented by chapters on anesthesia and sleep, computational analysis of the state of anesthesia, and the clinical phenomenon of "anesthesia awareness," a topic that has recently received much public attention. With these three additional contributions, the book thus includes 10 chapters.

Store-operated Ca2+ entry (SOCE) serves to control essential functions throughout the human body and represents a novel and attractive target for therapeutic intervention. This book provides an extensive overview of the role of SOCE pathways in Molecular Physiology and Cell Biology, as well as their clinical significance. (Patho)physiological principles and emerging therapeutic strategies are delineated in a way that is valuable both for the education of graduate students in advanced Cell Biology/Molecular Physiology and for the promotion of innovative research and developments in the clinical/therapeutic fields. A comprehensive, clear and elaborate representation of current concepts is provided, including a pathophysiological section arranged in a tissue/organ/system-oriented manner. The book is intended for basic researchers specializing in cell signaling, ion transport, or pharmacology, as well as biomedical scientists and clinicians with a focus on immunology, neurology or cardiology.

The International Society on Oxygen Transport to Tissue (ISOTT, www. isott. info) is an interdisciplinary society comprising about 250 members worldwide. Its purpose is to further the understanding of all aspects of the processes involved in the transport of oxygen from the air to its ultimate consumption in the cells of the various organs of the body. The annual meeting brings together scientists, engineers, clinicians and mathematicians in a unique int- national forum for the exchange of information and knowledge, the updating of participants on latest developments and techniques, and the discussion of controversial issues within the field of oxygen transport to tissue. Founded in 1973, the society has been the leading platform for the presentation of many of the technological and conceptual developments within the field both at the meetings themselves and in the proceedings of the society. These have been published first by Plenum Publishing (1973), then by Kluwer Academic/Plenum Publishers and presently by Springer Publishing, all in the Advances In Expe- mental Medicine and Biology Series. The 36th Annual ISOTT conference was held in Sapporo, Japan during August 3-7, 2008. It was the second occasion that the ISOTT meeting was held in Japan; the first one was held in the same place in 1987 organized by Professor Masaji Mochizuki.

A vast literature has been concerned with arteriosclerosis and yet, many aspects of pathogenesis and of the mechanism of development of the arteriosclerotic vascular lesion remain only poorly understood. In recent years, our knowledge of the earliest stages of arteriosclerosis have greatly improved. By now, we have learned to relate morphologic changes to disturbances in function. It has been of particular impor tance that components of the arterial wall could be analyzed in regard to dysfunction, for example, in the endothelium or the vascular smooth muscle. The interaction of the different morphological components of the vascular wall could thus be much bet ter understood. Likewise, the interaction between the arterial wall and the flowing blood could be much better described, including the intimate relationship between platelets and the endothelium, the coagulation system and the endothelium, the granulocytes and the endothelial cell layer, as well as processes of migration of blood cells into the subendothelial space. The recognition of functional and morphological disturbance has attained clinical significance not only because the arteriosclerotic diseases have quantitatively reached the dimensions of an epidemic, that is, of a magnitude never been witnessed. It is also because of the development of new drugs that interfere with the atherogenic process and thereby prevent the development of the disease or halt its progression. It is also becoming increasingly possible to inhibit the occurrence of complications in existing arteriosclerotic lesions in manifest disease, i. e.

The scientific literature has expanded dramatically in recent years, making entry into the structure of any given area extremely difficult; concurrent with this explosion more people are required to become acquainted with information outside their main line of expertise. For this reason there is a need for review articles which give an overall review of circumscribed areas. This volume reviews the subject of respiratory control mechanisms; the authors of each chapter are active research workers engaged in the area covered by their chapter. The first four chapters are concerned with the basic physiological mechanisms which sense changes in the respiratory system, in the standard physiology textbook parlance chemical and neural sensory receptors. The peripheral arterial chemoreceptors sense changes in arterial oxygen tension, carbon dioxide and pH. The first chapter describes the basic responses in the organ produced by changes in blood chemistry. Later chapters discuss changes in activity produced by exercise, chronic hypoxia and the possible role of the chemoreceptors in initiation of respiration in the new-born. In Chapter 1, a section considers the action of drugs on the peripheral chemoreceptors, and finally there is a discussion of the possible mechanisms whereby the organs sense changes in blood chemistry. This pattern is followed in subsequent chapters wherever possible; first a discussion of the basic physiological properties, followed by any clinical application and dis cussion of the mechanism whereby the receptor might operate. The remaining chapters are of a more applied nature.

Recent publications have addressed specific aspects of the endothelins, such as their roles in disease or the importance of endothelin receptors. However, in this book the entire field of endothelins is covered. This includes the pathways of endothelin production and their regulation, the local and systemic actions of endothelins, receptors for the endothelins and the signalling pathways employed, and the involvement of endothelins in a range of diseases. Attention is also paid to the development through chemistry, pharmacology and toxicology of endothelin antagonists and endothelin-converting enzyme inhibitors, with mention of all the important members of these drug classes. This leads to well-rounded discussions of the potential therapeutic benefit of endothelin inhibitors.

The sodium of animal cell membranes converts the chemical energy obtained from the hydrolysis of adenosine 5' -triphosphate into a movement of the cations Na + and K + against an electrochemical gradient. The gradient is used subse quently as an energy source to drive the uptake of metabolic substrates in polar epithelial cells and to use it for purposes of communications in excitable cells. The biological importance of the sodium pump is evident from the fact that be tween 20-70% of the cell's metabolic energy is consumed for the pumping pro cess. Moreover, the sodium pump is an important biological system involved in regulatory processes like the maintenance of the cells' and organism's water me tabolism. It is therefore understandable that special cellular demands are han dled better by special isoforms of the sodium pump, that the expression of the sodium pump and their isoforms is regulated by hormones as is the activity of the sodium pump via hormone-regulated protein kinases. Additionally, the sodium pump itself seems to be a receptor for a putative new group of hormones, the endogenous digitalis-like substances, which still have to be defined in most cases in their structure. This group of substances has its chemically well known coun terpart in steroids from plant and toad origin which are generally known as "car diac glycosides." They are in medical use since at least 200 years in medicine in the treatment of heart diseases."

Morphology and physiology are two fields which cannot be separated. This statement needs to be amplified: purely factual results of a morphological or physiological nature only have real value when they are gained in the context of certain guiding, embracing questions. By themselves they are mostly of little value, because only a guiding hypothesis or theory is of any importance. Equally, a physiological question will always raise questions as to the morphological substrate, and vice versa. Thus, Wiedemann's discovery, for instance, that the visual cells in each ommatidium of the dipterans have differing fields of vision has revived the question as to what the optical properties of individual visual cells, and the complete ommatidium, might be and how neighboring ommatidia interact. These questions in turn led to that of the morphological, neuronal wiring diagram of the visual cells in the optical ganglia. Within the realm of invertebrates, the morphological and physiological problems of visual perception have been resolved in very different ways on various levels, from the photo receptor to higher centers; despite many investigations, however, there remain unsolved problems. The first chapter of Vol. VII/6B deals with the neuroarchitecture in the visual system of two groups: crustaceans and insects. These systems are best known through recent investigations. The second chapter is devoted to the neural principles in the visual system of insects. It could not have been written without parallel research into morphology."

Several methods have been used to demonstrate the vasculature of different organs in man and other species. Many attempts to evaluate the precise microangioarchitecture of organ systems remained unproductive, others were controversial. The development of electron microscope in thirties opend new perspectives in researching microvascular systems. Transmission electron microscopy provided a two-dimensional view on microcirculatory system at higher magnifications, however, its standardization was delayed unnecessarily. The use of methyl methacrylate and related compounds for obtaining replicas of vascular beds, and their study in scanning electron microscope opened a new window in micromorphological research. For the first time, a three-dimensional image analysis of the vascular system was possible. The microvascular corrosion casting method has meanwhile attracted the interest of many contemporary scientists. Its application to medical and biological problems justify it to be used as a routine method for microvascular investigations. The first investigators who used this method, focused either on methodological details or they dealt with the normal microanatomy of organs. The advantages of this method in demonstrating pathological microvascular patterns are also evident.

This volume emphasizes the comparative approach to under standing vertebrate renal function. I am convinced that this approach is of particular value in understanding both the details of renal function at the cellular and subcellular levels and the renal role in regulating fluid volumes and solute concentrations. My exposure to this approach first occurred during a student research experience in the laboratory of Wilbur H. Sawyer, who also provided an introduction to the works of Homer W. Smith and August Krogh. The importance of this approach was reinforced by doctoral and postdoctoral research in the laboratory of Bodil Schmidt-Nielsen. It has been confirmed through years of personal experience since then. My research and my understanding of renal function have been aided through the years by collaboration and discussion with numerous students and associates. Of particular impor tance in developing my views on comparative renal function, and especially on the relationship of structure to function, has been my long association with my colleague and friend, Eldon J. Braun. Donald S. Farner, who suggested the writing of this volume, provided valuable editorial assistance. Much of my personal research in this area has been supported over the years by grants from the United States National Science Foundation and National Institutes of Health. The writing of this volume was completed while I was in Wiirzburg, Federal Republic of Germany, supported by a Senior U.S. Scientist Award from the Alexander von Humboldt Foundation."

This volume arose from the scientific program of the XIIth International Congress of Pharmacology, held in Montreal, Canada, July 24-29, 1994. The scientific program included plenary lectures and symposia, in addition to poster presentations and colloquia. The abstracts of the Congress presentations were published as .supplement 1 of volume 72 by the Cana dian Journal of Physiology & Pharmacology. The Congress organizers sought a more expansive treatment of the Congress proceedings and appointed Dr. A. Claudio Cuello to coordinate preparation of the present volume; Dr. Brian Collier was chair of the scientific program committee and, thus, also collaborated on this work. The objective that we pursued was to produce a volume of reasonable size which would feature all of the plenary lectures and symposia from those authors who agreed to participate. To this end, we solicited mini reviews from plenary lecturers and asked symposia organizers to coordi nate a single short-review covering the individual topics within their event. Those who accepted this challenge are evident in this volume. We express our gratitude to these authors for doing so, and for exercising considerable ingenuity in completing their task within a reasonable time."

(Director: Pierre J. COURTOY) Two years after its first gathering in Oeiras, Portugal, the European Endocytosis Group convened for a second workshop at the Pasteur Institute, Paris, on October 1-5, 1990. The meeting is reported in detail in this volume; a preliminary coverage, based on the overviews of each session, has appeared in the New Biologist (1991, 3:243-252). The three main objectives, to broaden the audience, to present a more comprehensive view of the multiple aspects of endocytosis, from basic biology to health, disease and therapy, as well as to clarify controversial issues, have been largely fulfilled. The Second European Workshop on Endocytosis was attended by more than tOO participants, originating from 18 countries. 59 lectures and 35 posters were presented. In addition, vivi~ roundtables allowed to thoroughly discuss the dynamics and the regulation of the endocytic apparatus, as well as the role of endocytosis in antigen presentation. Endocytosis is a general and distinctive property of all eukaryotic cells, including protists, plants and fungi.

We are pleased to present to our readers the Proceedings of the Second International Symposium "Proteases: Potential Role in Health and Disease" which was held in Rothenburg ob der Tauber (FRG) during May 17-20, 1987. The topics discussed included those dealing with the physiology and pathophysiology of proteases and their inhibitors, the inter- actions of proteases and hormones, the kallikrein-kinin, com- plement and coagulation system, the function of proteases in arthritis, malignoma, pancreatitis, intestinal tract, lung and kidney disease as well as in hypercatabolic states (acute renal failure, multiple trauma and septicemia). Furthermore some reports dealed with the role of proteases during extracorporeal circulation. The papers presented answered many questions, but raised many more concerning the significance of proteases and their in- hibitors in clinical medicine. It was unfortunately impossible in this volume, to include the extended, lively and stimulating discussions which were enjoyed by the participiants during the conference. The meeting has provided a unique framework for close inter- action between scientists from various disciplines, including molecular biology, biochemistry, physiology, surgery, anaesthe- siology, endocrinology, hematology, pneumatology and nephrology.

Having received the invitation from Springer-Verlag to produce a volume on drug-induced birth defects for the Handbook of Experimental Pharmacology, we asked ourselves what new approach could we offer that would capture the state of the science and bring a new synthesis of the information on this topic to the world's literature. We chose a three-pronged approach, centered around those particular drugs for which we have a relatively well established basis for understanding how they exert their unwanted effects on the human embryo. We then supplemented this information with a series of reviews of critical biological processes involved in the established normal developmental patterns, with emphasis on what happens to the embryo when the processes are perturbed by experimental means. Knowing that the search for mechanisms in teratology has often been inhibited by the lack of understanding of how normal development proceeds, we also included chapters describing the amazing new discoveries related to the molecular control of normal morphogenesis for several organ systems in the hope that the experimental toxicologists and molecular biologists will begin to better appreciate each others questions and progress. Several times during the last two years of developing outlines, issuing invitations, reviewing chapters, and cajoling belated contributors, we have wondered whether we made the correct decision to undertake this effort.

The volume Appetite Control provides a comprehensive description of the mechanisms controlling food intake, and thereby energy balance, in the mammalian organism. During the last decade, research in this area has produced a remarkable wealth of information and has characterized the function of numerous peptides, transmitters, and receptors in appetite control. Dysfunction of these circuits leads to obesity, a growing health concern. However, the plethora of mechanistic information is in marked contrasts to an almost complete lack of anti-obesity drugs that meet the safety standards required for the chronic therapy of morbid obesity. Consequently, ongoing research aims to identify additional targets and agents for a pharmacological intervention. Thus, the mechanisms of appetite control as well as all agents interfering with its control are of considerable practical interest.

The authors of the volume are distinguished scientists who are leading experts in the field, and who have contributed important, original data to our understanding of the mechanisms of appetite control. They have quite different scientific backgrounds and, together, they represent all relevant disciplines. Thereby, the topics are presented from different points of view, not exclusively from that of pharmacology and neuroendocrinology. Thus, the volume addresses all scientists who are interested in the field of obesity research and the pathophysiology of appetite control."

It is an exciting task to be the editor of the first monograph covering a new area of the biomedical sciences. Since the first report in 1980 by Robert Furchgott and colleagues (see Chapter 1) of the evidence of endothelium-dependent relaxation in isolated arteries, there are ever increasing numbers of vascular physiologists and pharmacologists who are scraping away the endothelium to look into its role in cardiovascular con trol. And the more one looks, the more one discovers. Not only is the list of substances that can induce endothelium-dependent relaxations im pressively long, but these intriguing cells can also secrete vasoconstrictor substances. The ability of the endothelium to modulate the degree of con traction of the underlying smooth muscle is an ancestral property of the blood vessel wall, illustrating the logic of nature, since the endothelial cells are located in the best possible strategic location to continuously monitor the properties (chemical or physical) of the blood. And more and more data emerge suggesting that in several cardiovascular diseases per turbations in endothelium-dependent responses are one of the early signs of the abnormal process. Thus, the importance of endothelium-dependent responses, triggered by the intellectual curiosity of one of the pioneers of vascular physiology and pharmacology, is now recognized not only by basic scientists, but also by all concerned with the cardiovascular diseases. The purpose of this monograph is to provide them with a reference work, so that they know where to start."

This volume forms part of a prestigious series and covers the latest advances in our understanding of the pathophysiology and treatment of asthma. Our understanding of asthma has changed dramatically in recent years, and much of this new information is brought together in this volume written by inter nationally recognised authorities. The aim of the book is to review in depth the changing concepts of inflammatory processes in asthma and to discuss the implications for research of this common chronic disease. Many of the advances in and future therapy our understanding of asthma have originated from a pharmacological approach, and this volume highlights the promising new options for pharma cological intervention. It is hoped this book will be invaluable for research scientists and clinic ians involved in asthma research and will be a major reference resource for chest physicians and those involved in the development of novel pharmaceu tical entities. Each chapter is extensively referenced, generously illustrated with clear diagrams and photographs, and represents a state-of-the-art review of this growing area. c.P. PAGE P.l. BARNES Contents CHAPTER 1 The Pathology of Asthma: An Overview L.A. LAmNEN and A. LAmNEN. With 10 Figures ...................... 1 A. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . 1 . . . . . . . . . . . . . . . B. Methods to Investigate the Pathology of Human Asthma ............ 1 C. Bronchial Epithelium and Inflammatory Cells in Asthmatic Patients Between Attacks ........................... 2 I. Mast Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . 4 . . . . . . . . . . . . . . II. Eosinophils ............................................... 7 III. Neutrophils.............................................. 10 D. Bronchial Epithelial Inflammation During an Asthma Attack. . . . . .. . 10 E. Epithelial Regeneration .... . . . . . . . . . . . . . . . . . . . . . . .. . . 12 . . . . . . . . ."