Coronary heart disease is one of the major health problems in indus trialized nations because of its high incidence and severity. Recent innovations in medical and surgical treatment of coronary heart dis ease have increased the importance of accurate diagnostic methods for determining the severity of coronary disease, identifying potential treatment alternatives, and evaluating the results of treatment. Great advances have also been made in basic research on coronary circula tion and its interaction with myocardial contraction and relaxation and neural and humoral control. With respect to these developments, the papers included in the present monograph deal with important topics concerned with the basic mechanism of coronary circulation as well as ones of clinical relevance. It is directed toward physicians (cardiologists, cardiac surgeons, cardiac radiologists, anestheologists, and others) and basic scientists (e.g., physiologists, bioengineers). We would like to em phasize the importance of a multidisciplinary approach in which basic scientists and clinicians work closely together. This volume consists of nine chapters. Chapter 1 contains macro scopic and microscopic descriptions of coronary vascular anatomy, which is closely related to the functions of coronary circulation. In Chap. 2 two methods in current use to evaluate phasic coronary blood velocity waveforms are presented, i.e., the laser Doppler and ultrasound Doppler methods. Chapter 3 describes the mechanical properties of coronary circulation, a knowledge of which is indispens able for an understanding of coronary arterial and venous blood flow velocity waveforms in relation to cardiac contraction and relaxation."

The development of a new antiarrhythmic drug involves many people with disparate skills. The organic chemist who makes it is guided not only by the structure-action relations of previous compounds, but by anticipation of a requirement for a particular type of action. In fact several of the best-known antiarrhythmics, including lidocaine, mexiletine, amiodarone and verapamil, were originally synthesized for other purposes. Physicians have to determine whether the new drug works, and pharma cologists how it works. For some years I have believed that there was room for a work which could be understood by all these groups and which could enlighten each about the point of view of the others. Thus when I was invited by Springer-Verlag to prepare a volume in their series Handbook of Experimental Pharmacology, I already had a firm conception of what its form should be. In any multi-author work there are two objectives which cannot always readily be reconciled. The first is to select topics which would relate to each other in a coherent manner. to give a logical and orderly shape to the volume as a whole. The second is to offer authors the greatest possible freedom to express themselves as they wish. When the general design was complete, prospective contributors were invited to write specific chapters, being provided with a complete list of their coauthors and chosen topics, so that they could avoid overlap."

This volume contains the lectures presented at the NATO Advanced Study Institute (ASI) on "Trafficking of Intracellular Membranes: From Molecular Sorting to Membrane Fusion", held in Espinho, Portugal, from June 19 to June 30,1994. The objective of this Institute was to survey recent developments and to discuss future directions in the rapidly advancing field of membrane cell biology, with particular emphasis on the dynamical properties and intracellular flow of membranes. A wide range of interrelated topics around the central theme of intracellular trafficking of membranes was covered, including lipid flow, membrane fusion, dynamics of membrane components, protein folding and assembly, vesicular transport in membrane biogenesis, exocytosis and endocytosis. A large variety of experimental techniques and systems, including the application of viruses and model systems, to study these processes was also considered. Membrane cell biology is a broad discipline which encompasses many scientific areas including cell biology, biochemistry, biophysics, virology, immunonology and genetics. Indeed, recent advances in the cell biology of membranes could not have been made without this multidisciplinary approach. Significant progress achieved during the last few years in understanding how newly synthesized lipids and proteins find their way to the cell organelles, how molecular sorting and the continuous flow of membranes allow each cellular membrane to maintain its own distinct molecular composition, and, thereby, the individuality of the various intracellular compartments, was discussed in considerable detail in this Institute.

This book attempts to present new aspects on electrophysiologi- cal mechanisms and catecholaminergic contributions in the set- ting of acute and chronic myocardial ischemia. Special emphasis is placed on the full scope from basic molecular and cellular mechanisms to experimental models of close clinical proximity. A number of internationally distinguished scientists present their latest findings in this significant research area within the peri- meter of cardiovascular disease which continues to lead mortality statistics in most industrialized countries. Contents of this book cover in addition to other subjects re- lease and uptake of catecholamines in ischemia, regulation of re- ceptors, adrenergic contribution to ventricular arrhythmias and mechanisms of ischemic malignant arrhythmias as well as un- derlying changes in membrane currents and the electrophysiolog- ical response to beta-adrenergic blocking drugs. In addition to original contributions, a number of editorial chapters are in- cluded for conclusions and future development in these areas. The main purpose of this book is to provide further inside in two traditionally separated research topics that are gravitating to more collaborative work and inspire more joint research ventures in the future. It provides a comprehensive view on clinically sig- nificant problems where basic research may stimulate further studies in man. Therefore this book may prove to be valuable to both cardiologists and interested clinicians as well as basic scien- tists.

A qualitative leap in the understanding of cardiovascular and n- ral regulation by the renin-angiotensin system, and of the role of this s- tem in tissue damage, has occurred as a result of the many recent advances in molecular genetic techniques. The cloning of the genes for the components of the renin-angiotensin system, the design of specific angiotensin receptor ligands, and the use of embryonic gene targeting te- niques for the creation of mutant strains have established that the renin- angiotensin system is important in blood pressure regulation, ion and fluid homeostasis, and tissue growth and remodeling Further investigation of the mechanisms by which this system p- ticipates in cardiovascular regulation may shed some light on the pat- genesis of several cardiovascular diseases, e. g. , hypertension, congestive heart failure, and chronic renal failure. Despite the promise of this system as a target for therapeutic interventions for these diseases, there are great challenges in the integration of the attempts to close the gap between the traditional literature of medicine and the explosion of information from the new technologies. This book's title, Angiotensin Protocols, reflects the authors' strong efforts to translate expert knowledge into easy-to-follow practice. The book opens with introductory chapters, and each specialty section provides detailed methods covering a wide variety of techniques, ranging from genetic manipulation of targeted genes to functional studies of the renin- angiotensin system.

The Editorial Board and the Publishers of the Handbook of Experimental Pharmacology wish to express their profound grief at the untimely death of Professor Peter Baker. Aware of his international recognition as an expert on the ubiquitous role of calcium in physiological processes and their pharma cological control, the Board was gratified when Professor Baker accepted its invitation to edit a new Handbook volume on "Calcium in Drug Actions". He went about this task with his usual energy and effectiveness so that, in the few months before his unexpected death, Professor Baker had mustered his distinguished contributors, got them to provide their manuscripts, and seen almost the entire material into the press. This achievement is all the more remarkable when one bears in mind the extraordinary number of his other commitments during the same time; they are mentioned in Sir Alan Hodgkin's preface to this volume. With so many other professional and personal responsibilities upon him, the Board of the Handbook wishes to record its grateful appreciation for the admirable way in which Professor Baker took on and carried out the additional work of bringing this fine book into existence; and the Board wishes it to be dedicated to the memory of Professor Peter Frederick Baker. The Editorial Board: G. V. R. BORN, P. CUATRECASAS, H. HERKEN, A.

The need for greater international collaboration is becoming increas. ingly clear. Practically every nation or people has, in addition to its own characteristics and history, its own medical tradition. Methods and ways of thinking that are successfully established in one place may not be accepted in another for some time. The medical tradition and training in different countries can take quite different forms. What would our present knowledge be - Without the creative, spontaneous ideas and contributions from the romance countries? - Without the opportunity of research, as it is practised on a large scale in the USA, where so many young Europeans took their first steps in experimental science? - Without the conscientious clinical work done in Central Europe and the valuable experience gained there? - Without, finally, the sober and critical scientific approach, as fostered in the cool heads of Northern Europe for generations? None of these qualities is sufficient without the others, but together they are a source of strength. Ultimately, we hope, through sensible con centration of efforts (while maintaining variety), to overcome the lack of an integrated approach in experimental science and to prevent repetition of painful mistakes. In this regard, the first two ESKA congresses have brought us great advances."

Mitochondrial transport systems are essential to mitochondrial function and therefore to energy homeostasis within the cell.
The book contains studies utilizing the techniques of biochemistry, physiology, molecular biology and genetics to reveal the structure and function of mitochondrial transport systems.
It is divided into the following six sections:
- Proton Translocation: The Uncoupling Protein and the ATPase; - Carriers and Transporters; - Mitochondrial Ion Channels; Structure of the Outer Mitochondrial Membrane Channel, VDAC; - VDAC, Peripheral Kinases and Energy Utilization; - Mitochondrial Channels in Humans and Relationship to Disease.

Together with the two previous volumes of the Handbook of Experimental Pharmacology on histamine and antihistamines the present publication yields a picture of a still rapidly developing field of research. New techniques and new experimental approaches have brought us new knowledge and deeper insight into the biomedical significance of histamine, even if many questions remain to be answered about the functional and medical implications of this old biogenic amine. The present volume covers the progress in histamine research during the past two decades. A significant chapter concerns techniques for histamine determination. As the result of a consensus meeting in Munich in December 1988, a panel of eminent specialists arrived at common recommendations as to the usefulness of the available histamine assays for the most common experimental biomedical conditions. The heterogeneity of mast cells, with great differences in their reactivity to various stimuli, has become apparent, not only among species but also among the tissues of a species. New informa tion is presented about the mechanism of exocytosis. The old questions about the role of histamine in the mechanism of gastric secretion and in cardio vascular and respiratory functions have been studied with new techniques, and the role of HI and H2 receptors discussed. New observations have been made on the occurrence and possible functions of histaminergic neurons and histamine receptors in CNS where a new type of receptor, the H, seems to 3 be widely represented."

Rhythms are a basic phenomenon in all physiological systems. They cover an enormous range of frequencies with periods from the order of milliseconds up to some years. They are described by many disciplines and are investigated usually in the context of the physiology of the respective function or organ. The importance given to the research on rhythmicity is quite different in different systems. In some cases where the functional significance is obvious rhythms are at the center of interest, as in the case of respiration or locomotion. In other fields they are considered more or less as interesting epiphenomena or at best as indicators without essential functional significance, as in the case of cardiovascular or EEG rhythms. Recently the study of physiological rhythms has attracted growing interest in several fields, especially with respect to rhythm research in humans and its rapidly spreading applications in basic behavioral research, and as a diagnostic tool in clinical medicine. This development was favored by two methodological and conceptual ad vances: on the one hand, the availability of non-invasive methods of continu ous recording of physiological parameters and their computer-assisted evaluation, and on the other, the rapid development of theoretical analyses, for example, the understanding of dynamic systems, the generation of coordinated macroscopic pro cesses in systems comprising many single elements, and the mathematical tools for treating nonlinear oscillators and their mutual coupling.

Understanding the mechanisms involved in intracellular movement and localization of proteins is a central issue in cell biology. This volume is concerned with the events involved in the transport of membrane proteins, and the contents of vesicular compartments, to their ultimate destinations. In several chapters, particular attention is given to studies with viruses that are assembled by budding at specific membrane sites within the cell or at the cell surface; studies with such viral systems have provided significant insights into membrane biogenesis.

This book is dedicated to the memory of Walter Brendel, late Professor of Experimental Surgery and Chairman of the Institute for Surgical Research at the University of Munich, Germany. For 20 years Walter Brendel organized the renowned Round Table Symposium on Applied Immunology, first in Kitzbiihel and later in Axams, Austria. On the occasion of the 20th symposium in January 1989 he gathered together a number of scientists who have been leaders in the field of transplantation immunology and clinical transplantation for the past two decades. All of them had participated at previous meetings, some on a regular basis. Many of the new discoveries in applied immunology and transplantation medicine were first presented and vividly dis cussed at the Round Table Symposia. The annual Kitzbiihel! Axams meetings became well-known and invitations much sought after, not only for this reason but also because of the uniquely intimate atmosphere that promoted the free exchange of research findings and theoretical cut and thrust.

Catecholamines are important transmitter substances in the autonomic and central nervous systems. These two volumes provide a comprehensive presentation of the state-of-the-art of catecholamine research and development in the past 15 years. The volumes present in-depth reviews of topical areas of catecholamine research in which substantial progress has been made and which are of current interest to various theoretical and clinical disciplines. Each topic has been dealt with by an established expert. Clinical subjects of relevant importance are included. Catecholamines are of interest in pharmacology, physiology, biochemistry, as well as in neurology, psychiatry, internal medicine (cardiology, hypertension, asthma), ophthalmology and anesthesiology.

Recent years have witnessed an explosion of knowledge lea- ding to a molecular understanding of the mechanisms of ac- tion of calcium on excitation and contraction coupling and its role in the regulation of contractility. This book highlights the most recent progress as well as providing a historial perspective of the field. It presents a concise and comprehensive overview of our current knowledge regar- ding calcium channels and regulatory proteins as well as in- tracellular calcium handling and the mechanisms underlying the activation of contractile proteins. It also describes how these basic mechanisms have been adapted in various types of muscle, especially in cardiac and smooth muscle.

th This volume contains selected lectures presented at the 12 International Conference on Advances in Prostaglandin, Leukotriene and Other Bioactive Lipid Research: Basic Science and Clinical Applications which was held in Istanbul, Turkey, on August 25-29, 2002. This meeting brought together basic and clinical scientists for the purpose of discussing advances in bioactive lipid research with.special attention to cancer, cardiovascular diseases, gastrointestinal diseases and respiratory diseases. Topics covered included: the role of leukotrienes and lipoxins in of inflammation, the cytochrome P450 pathway, the genetics and genomics bioactive lipids, lipid peroxidation, apoptosis, angiogenesis, isoprostanes, receptors and inhibitors, cyclooxygenase and lipoxygenase pathways and inhibitors, prostaglandin synthases and receptor signaling, phospholipases and inhibitors. Sessions included plenary lectures with expertise in particular areas, oral presentation on selected topics and general poster sessions. J.M. Drazen (Boston, USA) discussed anti-leukotriene treatment in asthma patients while C. Brink (paris, France) presented the recent advances in leukotriene receptors. The recent advances in cytochrome p450 pathway described in the session organized by J.C. McGiff (Valhalla, NY, USA). T. Shimizu (Tokyo, Japan) and M. Balazy (Valhalla, NY, USA) gave an update on phospholipases and arachidonic acid peroxydation. The editors are greatful to the Organizing, Programme and Advisory Committees for their valuable contributions. We greatfully acknowledge the generous financial support provided by PharmaciaIPfizer, Fako Pharmaceuticals Inc. and Novartis Pharmaceuticals Inc. ofthe contributors to this volume, in particular We are also greatful to all to those who delivered their manuscripts by or before the requested deadline.

The Taurine Symposium- "Taurine: Beginning the 21'' Century"- was held September 20-23, 2002, on the beautiful island of Kauai in Hawaii. The headquarters of the meeting was the Radisson Kauai Beach Resort. This international meeting was attending by approximately 80 individuals from 23 nations and 4 continents. Seventy-five papers were presented either as platform presentations or poster presentations. Taurine, first isolated from ox bile in 1827 by Tiedemann and Gmelin and named in 1838 by Demarcay, became of significant scientific interest in 1968 when the first extensive review article was published by Jacobsen and Smith. Interest in taurine grew exponentially after 1975 when the first taurine symposium was organized by Ryan Huxtable in Tucson, Arizona. Since that date, taurine symposia have been held approximately every two years held in various cities and resort areas around the world. Taurine investigators have had the privilege of attending these scientific meetings on three continents - Asia, Europe, and North America. Since the initial meeting in 1975, a central question addressed during many of the symposia has been: "What is physiological, pharmacological, nutritional, and pathological role of taurine?". Although taurine has been established as an important osmolyte, it appears to affect many other biological processes. However, the exact mechanism(s) by "which taurine acts" has not yet been definitively answered. In Kauai, the patticipants discussed many topics and asked many questions regarding the role and actions of taurine.

When survival is challenged by the cold, animals react by employing both behavioral and physiological solutions. Depending on the magni tude of the cold stress and the nature of the adjustment, simple avoidance or sophisticated capacity or resistance compensations may be used. Thus, migration, shelter seeking, metabolic and insulative compen sation, torpor, and freezing avoidance and tolerance are successful tac tics used by diverse groups of animals. To understand and appreciate the benefits of these tactics, it is necessary to examine not only the well being of the whole animal but also their basic underlying mechanisms. In ad dition, it is also of fundamental importance to grasp how seasonal cold affects the survivorship and reproductive success of populations when confronted by a general reduction in primary productivity and an elevated energy cost for maintenance (e. g. in endotherms). In this regard, a synthetic overview which integrates aspects of cell biology, biochem istry, physiology, neurobiology, behavior, and population biology should be a fruitful approach in providing a holistic understanding on how animals adapt to cold. The present volume is an attempt to achieve such an overview; its objective is to provide a depth and breadth of coverage that is essential to a full appreciation of animal adaptation to cold. It is the hope of the contributing authors that this book will serve as an effective reference text for all senior undergraduate and graduate students as well as research scientists with an interest in cold physiology."

At one time or another, everyone has said "I am thirsty". Yet what causes this sensation of thirst? It is obvious that a certain quantity of fluid must be present for the body to function normally. How does a water deficit in the body then influence drinking habits? But supposing the physiological need is met, what about the psychological need or social need? Water is certainly the most necessary fluid; then why do we humans often prefer other beverages, even at great cost of effort or money or health? The subject of thirst and drinking behavior are uniquely discussed in this book. For the first time both the physiological and the psychological aspects of water and beverage consumption are examined in one volume. The many recent developments concerning how a lack of water is signalled physiologically and processed neurally to affect drinking behavior are critically surveyed. Prospects for understanding the cultural and sensory influences on beverage consumption are mapped out. The thirty-one chapters by authorities in the field were all mutually reviewed and revised in the light of precirculated comments and round-table discussions. Together they provide a complete picture of the current state of knowledge on what determines fluid consumption in human beings and animals.

This second volume in Modern Methods of Plant Analysis, New Series concentrates on nuclear magnetic resonance (NMR) spectroscopy, a powerful technique that is now being used for plant studies in a major way. This is the first time that a series of chapters by leading experts on the application of NMR to plant cells has been assembled in a single volume. The methods are described in detail so that even beginners can apply them directly in the laboratory. Topics include general metabolism in higher plants and fungi, intercellular pH, energy status, DNA structure analysis, multiple quantum two-dimensional NMR spectroscopy, chloroplast orientation, rubber analysis, and the use of NMR to determine pollen viability. This volume should provide not only an excellent practical guide to the possibilities of NMR application to the plant sciences, but also give impetus to its future use.

Recent research has given great insight into the physiological and pharmaceutical effects of histamine on the central nervous system and especially on the brain. This volume focuses on these many new findings, including the role of brain histamine in the arousal system, learning, and memory. Also featured are the mechanisms of histamine release in bone marrow and mast cells and the role of histamine in neutrophil differentiation. These are analyzed using the most up-to-date techniques of molecular pharmacology and refined immunoelectroscopy. In addition, the pharmacological profiles of newly developed H1 antagonists are described, making this book invaluable to those who want to understand the very latest advances in histamine research.

Well over one decade has passed since the appearance of the original four volumes of Membrane Transport in Biology. Since the publication of the last volume there have been spectacular advances in this field. These advances have been in part the result of the application of exciting new methodologies, and in part the result of new insights into the regulation and integration of transport processes. This volume, as well as a sixth volume, which is in preparation, are intended to cover key areas in which the development has been particularly striking. For many years the trend in studies of membrane transport had been that of increasing specialization with regard to the transporter of interest and of the cell or tissue studied. This trend was supported by the enormous number of publications directed at understanding the cellular physiology of specific organ systems and tissues, and also by the fact that different tissues often seemed to react so differently to the same conditions that mechanisms unique to each appear to be at play. One of the happy developments in recent years has been the realization that this apparent disparity of behaviors in different tissues is based on varying combinations of a limited number of transport mechanisms, all mediated by the same or similar proteins. Some of these transport proteins have already been isolated and analyzed with respect to amino acid sequence whereas others are just entering this phase.

Major epidemiologists from the UK, USA and Europe contribute to the first ever, much needed comprehensive review of the epidemiology of peripheral vascular disease in the lower limbs.

During the last years much attention has been given to the investigation of the roles of specific growth modulators acting on liver cell populations. HGF functions as a pleotropic factor in the liver as well as in other extrahepatic tissues. The hepatic stem cell compartment is thought to play a major role in liver tissue restoration. Mechanisms of cell growth and cell death of the liver are described in detail, with particular emphasis on apoptosis. The functions of HBV-pX protein and the roles of hepatitis B virus gene expression relation to hepatocellular carcinoma are discussed. Techniques for obtaining human and nonhuman hepatocytes and other liver cell types and for efficient transfer and expression of genes in hepatocytes and liver-derived cell lines are presented.