Translational medicine underpins vascular medicine. It is fundamental to understanding how we treat patients with vascular disease and more importantly, how to prevent it. It is the rationale for drug design and production. Vascular medicine and translational medicine will take over and become the main reason for referring patients to hospital. Therefore, hospital-based clinicians working with basic scientists need to know about translational medicine, which educates and informs them about vascular medicine and how management should be based. This book is a primer for translational vascular medicine and discusses the evolving and exciting areas of basic science applied to vascular medicine. The book is based on the third vascular biology conference held at The Royal College of Physicians in 2008. It provides a large amount of new basic and clinical information and the contributors are world leaders.

In this volume of Reviews of Physiology we present three articles on modulation of PKC in antitumor treatment, compartment-specific functions of the ubiquitin-proteasome pathway and transgenic models of alpha2-adrenergic receptor subtype function.

Cardiovascular fluid mechanics is now used as a tool in determining diagnosis, treatment, and prognosis by physicians and surgeons working in the fields of cardiology and angiology. The text is based on a considerable amount of clinical and experimental data on blood flow in the heart and large vessels obtained using various methods such as ultrasound pulsed Doppler velocimetry (including Doppler color flow imaging), catheter-tip electromagnetic velocimetry, hot-film anemometry, and laser Doppler velocimetry. The book will introduce medical researchers and clinicians to this rapidly developing field and allow them to apply the knowledge and the methods of fluid mechanics to practical medicine.

Information flow as nerve impulses in neuronal circuits is regulated at synapses. The synapse is therefore a key element for information processing in the brain. Much attention has been given to fast synaptic transmission, which predominantly regulates impulse-to-impulse transmission. Slow synaptic transmission and modu lation, however, sometimes have been neglected in considering and attempting to understand brain function. Slow synaptic potentials and modulation occur with a considerable delay in response to the accumulation of synaptic and modulatory inputs. In these contexts, they are plastic in nature and play important roles in information processing in the brain. A symposium titled "Slow Synaptic Responses and Modulation" was held as the satellite symposium to the 75th Annual Meeting of the Physiological Society of Japan on March 30-31, 1998, in Kanazawa. The theme was selected not only for the reason mentioned above, but also because of the considerable involvement of many Japanese scholars in establishing the basic issues. Following the dawn of synaptic physiological research, as Sir John Eccles, Sir Bernard Katz, and Professor Stephen Kuffler carried out pioneer work, Professor Kyozou Koketsu and Professor Benjamin Libet, the students of Sir John Eccles, and their colleagues established the concept of slow synaptic responses and modulation by studying vertebrate sympathetic ganglia. Since then, the concept has been ex panded with detailed investigations of both peripheral and central synapses at the levels of single ion channels, intracellular Ca"+ dynamics, intracellular transduc tion mechanisms, and genes.

In this second special issue on signal transduction leading specialists in their fields again present overviews of topics related to the highly topicalsubject of signal transduction. The first contribution, by Keppler, deals with the biosynthesis, transport, inactivation, and analysis of leukotrienes. Mohr et al. present an excellent overview of the biology of the peptide hormone oxytocin and its role in signal transduction.The review by Holzer describes the significance of peptinergic sensory neurons in the control of vascular functions. In the contribution by Wolf etal the molecular biology of the Y chromosome is discussed.

In this volume of Reviews there are three outstanding articles, one on phspholipase D, an enzyme that is widely distributed in bacteria, protozoa, fungi, plants and animals. Phospholipase D carries out a transphosphatidylation reaction, which is unique to this enzyme. This review is focussed on mammalian PLDs. The second review deals with endotoxin tolerance, the term which describes the phenomenon that immune responses and metabolic changes are mitigated after repeated LPS administration. The third article summarizes the current knowledge relevant to understanding the molecular basis of GPCR function and focusses on the underlying mechanisms of GPCR malfunctions responsible for diferent human diseases.

It is becoming increasingly clear that the brain has an important role in the control and integration of the responses to injury and infection. This is the first volume to look in depth at the way the brain responds to trauma and subsequently integrates and influences behavioral, metabolic, neurohumoral, cardiovascular, and immune functions. It is well established that some of these responses, such as fever and neuroendocrine changes are directly influenced by the central nervous system. These, and other more recent advances, provide new insights into this area and provide a basis for more effective understanding and clinical management of trauma patients. The authors, all international authorities in their fields, discuss established and recent data from experimental and clinical studies and consider the implications of these findings for the treatment of the trauma patient. This book will serve as an excellent reference for professionals who deal with trauma or who work in accident and emergency medicine, neuroscience, neuroimmunology and physiology.

The primary goal of this book is to survey issues pertaining to coronary venous retroperfusion, a potentially beneficial treatment of myocardial ischemia. Since attention will be focused on the myocardium, its normal or deranged antegrade perfusion will be discussed first, along with factors affecting blood supply to region ally ischemic tissue. After pointing to coronary reperfusion and its rapidly expand ing applications, the principle of coronary venous interventions will be discussed. Recent anatomic observations are presented to clarify features of the coronary venous sytems, some of which remain inadequately defined, yet play a crucial role in determining effectiveness of all retrograde methods. The remainder of the text concentrates on the development of retroperfusion sytems designed for retrograde treatment of myocardium jeopardized by deficient ante grade blood delivery, sec ondary to coronary artery obstruction. Retroinfusion of contrast is also considered as a potential diagnostic tool. The final chapter of the book reports on recent efforts aimed at a mathematical modeling of mechanisms and effects of coronary venous interventions."

The study of signal transduction mechanisms has become one of the most important branches of biomedical science, indispensable to understanding the normal actions of hormones, neurotransmitters and other extracellular signaling molecules as well as many pathophysiological processes, including inflammation and cancer. In this volume, the various techniques for measuring Ca2+ in the cytosol, in the various organelles, and in the immediate surroundings of individual cells are described in practical detail by experts. Also included is a chapter on tracking calmodulin inside cells using fluorescence technology. A Springer Lab Manual

Book chapters are authored by participants in the International Meeting on "Staging Neuropsychiatric Disorders: Implications for Etiopathogenesis and Treatment," held in Mojacar (Almeria) Spain from 14-18 October 2009. Chapters are organized into four sections on themes encompassed by Staging Neuropsychiatric Disorders: 1) Clinical Staging in the Pathophysiology of Psychotic and Affective Disorders, 2) Staging Perspectives in Neurodevelopmental Aspects of Neuropsychiatry, 3) Epigenetics and Biomarkers in the Staging of Neuropsychiatric Disorders, and 4) Staging Neurodegenerative Disorders. This volume should serve as a resource for physicians and neuroscientists alike, highlighting the importance of staging neuropsychiatric disorders and the underlying mechanistic dysfunction, for prevention and treatment strategies at different stages of disease progression."

This is the first comprehensive volume to be published on the subject of electrical trauma in humans. Many of the world's leading experts describe the basic mechanisms of tissue injury in victims of electrical trauma, the complex and varied manifestations of electrical trauma, and state-of-the-art clinical treatment protocols. Promising new therapies still in the research stage are also discussed and assessed. The volume describes the basic physiochemical mechanisms responsible for tissue damage and explains the complex and variable ways in which electrical trauma manifests itself. An understanding of these underlying processes provides the basis for a rational and consistent approach to treatment which is highlighted in this volume. Electrical Trauma serves as a new and important source of information from a variety of perspectives that contributes to the understanding of the electrical injury problem. It is suitable for clinicians in plastic surgery, intensive care and burn units and for those with an academic and research interest in the mechanisms and causes of electrical trauma.

Originally published in 1992, this volume looks in detail at the important relationship, initially studied in 1871 by Bowditch, between the strength of the heartbeat and the interval between beats. The book draws together the work and experience of leading international research workers in this field. Collectively, the contributors illuminated the underlying mechanisms involved, their expression in both isolated muscle and the intact heart, and speculate on further avenues of research. The volume will be of interest to cardiologists, physiologists and all those concerned with the function of the heart.

The development and selection of ovarian follicles is one of the most active areas of contemporary reproductive research. Relevant experimental work extends from laboratory rodents, across a wide range of domestic species, to human clinical studies, especially as related to problems of fertility and in vitro fertilisation. This 2003 volume provides comprehensive coverage of the field, integrating research findings from animal and human studies and condensing the vast published literature into a meaningful and digestible physiological account which highlights the key role played by the oocyte in influencing all stages of follicular development.

Unique features of the present work include: Only authorized English translation of the original Spanish text, adhering as much as possible to the letter, with correction of the obvious errors already predicted by Cajal in his Preface. Added facts appearing in the French version, with correction of old as well as new errors, the latter probably due to inaccuracies in translating into French some nuances of the Spanish language. Uniform of nomenclature according to contemporary scientific English. Annotations on Cajal s changing concepts over time, the elucidation of certain structures that do not have present day equivalents, and explanations of the many symbols appearing in illustrations but not mentioned in the corresponding original legends. Most illustrations are reproductions of Cajal s original art work, still extant at the Cajal Museum in Madrid, with cross references to figure numbers of the Spanish and French versions. Citations are given by author and year in the text, with an alphabetical list at the end of the volume, completed and corrected for accuracy against original publications. Taxonomy glossary of species appearing in the text, with present scientific names, and their colloquial English counterparts."

Research centering on blood flow in the heart continues to hold an important position, especially since a better understanding of the subject may help reduce the incidence of coronary arterial disease and heart attacks. This book summarizes recent advances in the field; it is the product of fruitful cooperation among international scientists who met in Japan in May, 1990 to discuss the regulation of coronary blood flow.

In the series Reviews of Physiology, Biochemistry and Pharmacology three excellent contributions by Ruth Heidelberger (Houston, TX, USA) with Electrophysiological Approaches to the Study of Neuronal Exocytosis and Synaptic Vesicle Dynamics and Kay Truscott et al. (Freiburg, Germany) with Transport of Proteins Into Mitochondria and Randall K. Powers and Marc D. Binder (Seattle, WA, USA) with Input-Output Functions of Mammalian Motoneurons form another outstanding volume.

Protein transport events occurring at the endoplasmic reticulum (ER) of eukaryotic cells and the cytoplasmic membrane of prokaryotic organisms share many similarities. Resident proteins of both membranes span the lipid bilayer once or several times by a-helical stretches and their integration is usually mediated by uncleaved signal-anchor sequences. Proteins that are translocated across either membrane, collectively also termed secretory proteins, harbour cleavable N-terminal signal sequences. Prokaryotic and eukaryotic signal sequences have the same modular structure and are functionally exchangeable. Integration of membrane proteins and translocation of secretory proteins basically occur at the same sites (pores) within each membrane. In both types of membranes, these pores are c- posed of homologous components forming the Sec translocons. Parts of the Sec trans- cons are found populated by ribosomes, the membrane-bound ribosomes. Bacterial m- brane and eukaryotic secretory proteins are targeted to the Sec translocons by the same molecular mechanism involving signal recognition particle (SRP) and its receptor (SRP - ceptor, SR). Structure and assembly of the SRP The functional core of SRP The functional core of this ribonucleoprotein complex consists of the signal sequence binding subunit (SRP54 in eukaryotes and Ffh in prokaryotes) and the SRP RNA molecule (see Fig. 1). This core is conserved in all organisms, with the intriguing exception of chloroplasts, where the SRP lacks the RNA subunit.

This first volume in a projected series contains the proceedings of the first of the Keio University International Symposia for Life Sciences and Medicine under the sponsorship of the Keio University Medical Science Fund. As stated in the address by the President of Keio University at the opening of the 1996 symposium, the fund of Dr. Mitsunada Sakaguchi. The Keio was established by the generous donation University International Symposia for Life Sciences and Medicine constitute one of the core activities of the fund. The objective is to contribute to the international community by developing human resources, promoting scientific knowledge, and encouraging mutual exchange. Every year, the Executive Committee of the Interna tional Symposia for Life Sciences and Medicine selects the most interesting topics for the symposium from applications received in response to a call for papers to the Keio medical community. The publication of these proceedings is intended to publicize and distribute information arising from the lively discussions of the most exciting and current issues during the symposium. Weare grateful to Dr. Mitsunada Sakaguchi, who made the symposium possible, the members of the program committee, and the office staff whose support guaran teed the success of the symposium. Finally, we thank Springer-Verlag, Tokyo, for their assistance in publishing this work. Akimichi Kaneko, M. D. , Ph. D.

It has been known for over 150 years that hallmarks of inflammation can be observed in the wall of atherosclerotic vessels. It was, however, not clear if this inflammation is the cause or the consequence of atherogenesis. More recently, it has become evident that inflammation mediated both by innate and adaptive immunity is instrumental even in the earliest stages of the development of atherosclerotic lesions, i.e., that it plays an important pathogenetic role. In this volume, international experts in the field discuss the pathogenetic, diagnostic, preventive and possible therapeutic relevance of inflammation in atherogenesis. This book is intended for researchers and physicians in the fields of vascular biology, immunology and atherosclerosis.

Based on the 38th annual conference of the International Society on Oxygen Transport to Tissue (ISOTT), held in Ascona, Switzerland in July 2010, this volume covers all aspects of oxygen transport from air to the cells, as well as looking at organs and organism, instrumentation, and methods to sense oxygen and clinical evidence.

This book and CD-ROM package integrates the use of STELLA software into the teaching of health, nutrition and physiology, and may be used on its own in nutrition and physiology courses, or can serve as a supplement to introduce the role that simulation modelling can play. The author presents key subjects ranging from the theory of metabolic control, through weight regulation to bone metabolism, and gives readers the tools to simulate these using the STELLA software. Topics include methods for simulation of gene expression, a multi-stage model of tumour development, theories of ageing, circadian rhythms and physiological time, as well as a model for managing weight loss and preventing obesity.

Muscarinic acetylcholine receptors have played a key role in the advancement of knowledge of pharmacology and neurotransmission since the inception of studies in these fields, and the effects of naturally occurring drugs acting on muscarinic receptors were known and exploited for both therapeutic and non-therapeutic purposes for hundreds of years before the existence of the receptors themselves was recognized. This volume presents a broad yet detailed review of current knowledge of muscarinic receptors that will be valuable both to long-time muscarinic investigators and to those new to the field. It describes the detailed insights that have been obtained on the structure, function, and cell biology of muscarinic receptors. This volume also describes physiological analyses of muscarinic receptors and their roles in regulating the function of the brain and of a variety of peripheral tissues. This volume shows how the study of muscarinic receptors continues to provide new and surprising insights not just to the cholinergic system but to the broad areas of neurobiology, cell biology, pharmacology, and therapeutics.

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."