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 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.

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.

Speech sound production is one of the most complex human activities: it is also one of the least well understood. This is perhaps not altogether surprising as many of the complex neurological and physiological processes involved in the generation and execution of a speech utterance remain relatively inaccessible to direct investigation, and must be inferred from careful scrutiny of the output of the system -from details of the movements of the speech organs themselves and the acoustic consequences of such movements. Such investigation of the speech output have received considerable impetus during the last decade from major technological advancements in computer science and biological transducing, making it possible now to obtain large quantities of quantative data on many aspects of speech articulation and acoustics relatively easily. Keeping pace with these advancements in laboratory techniques have been developments in theoretical modelling of the speech production process. There are now a wide variety of different models available, reflecting the different disciplines involved -linguistics, speech science and technology, engineering and acoustics. The time seems ripe to attempt a synthesis of these different models and theories and thus provide a common forum for discussion of the complex problem of speech production. Such an activity would seem particularly timely also for those colleagues in speech technology seeking better, more accurate phonetic models as components in their speech synthesis and automatic speech recognition systems.

Cilia are tiny microtubule-based organelles projecting from the plasma membrane of practically all cells in the body. In the past 10 years a flurry of research has indicated a crucial role of this long-neglected organelle in the development and function of the central nervous system. A common theme of these studies is the critical dependency of signal transduction of the Sonic hedgehog, and more recently, Wnt signaling pathways upon cilia to regulate fate decisions and morphogenesis. Both primary and motile cilia also play crucial roles in the function of the nervous system, including the primary processing of sensory information, the control of body mass, and higher functions such as behavior and cognition, serving as "antennae" for neurons to sense and process their environment. In this book we describe the structure and function of cilia and the various tissues throughout the brain and spinal cord that are dependent upon cilia for their proper development and function.

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."

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."

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

This book summarizes present knowledge of different mechanisms involved in the development of positive and negative consequences of cardiac adaptation. Particular attention is paid to the still underestimated adaptive cardiac responses during development, to adaptation to the frequently occurring pressure and volume overload as well as to cardiac changes, induced by enduring exercise and chronic hypoxia. Cardiac Adaptations will be of great value to cardiovascular investigators, who will find this book highly useful in their cardiovascular studies for finding solutions in diverse pathological conditions; it will also appeal to students, fellows, scientists, and clinicians interested in cardiovascular abnormalities.

Natural killer (NK) cells have been at the forefront of immunology for two decades. During that time, a great amount of information about these cells has been obtained. They are important in antiinfectious and antitumoral defense and shape the adaptive immune response. In addition, they can act as immunoregulatory cells. In recent years, the therapeutic potential of NK cells in cancer immunotherapy has become increasingly evident. This book describes in detail current knowledge about NK cells and covers a broad range of NK cell-related topics, including those that are not frequently reviewed, e.g. NK cells and allergy or NK cells and skin diseases.

Oxygen-Ozone therapy is a complementary approach less known than homeopathy and acupuncture because it has come of age only three decades ago. This book clarifies that, in the often nebulous field of natural medicine, the biological bases of ozone therapy are totally in line with classical biochemistry, physiological and pharmacological knowledge. Ozone is an oxidizing molecule, a sort of super active oxygen, which, by reacting with blood components generates a number of chemical messengers responsible for activating crucial biological functions such as oxygen delivery, immune activation, release of hormones and induction of antioxidant enzymes, which is an exceptional property for correcting the chronic oxidative stress present in atherosclerosis, diabetes and cancer. Moreover, by inducing nitric oxide synthase, ozone therapy may mobilize endogenous stem cells, which will promote regeneration of ischemic tissues. The description of these phenomena offers the first comprehensive picture for understanding how ozone works and why. When properly used as a real drug within therapeutic range, ozone therapy does not only does not procure adverse effects but yields a feeling of wellness. Half the book describes the value of ozone treatment in several diseases, particularly cutanious infection and vascular diseases where ozone really behaves as a "wonder drug". The book has been written for clinical researchers, physicians and ozone therapists, but also for the layman or the patient interested in this therapy.

Induced pluripotent stem cells in cardiovascular research.- TRPs in the brain.- The channel physiology of the skin.

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 volume is unique to the existing literature in the Peptide Nucleic Acid field, in that it focuses on comparing and contrasting PNA with other available oligonucleotide homologues and considers areas in which these biomolecules could be profitably applied to clinical and diagnostic applications. Part I of the book addresses comparative strengths and weaknesses of various nucleoside homologues. Part II of the book addresses specific translational or clinical applications for PNA and related antisense biomolecules. The editors have succeeded in presenting a balanced yet broad view of the methods available for gene targeting and modification.

This edition of the companion volumes Muscle Pain: Understanding the Mech- isms and Muscle Pain: Diagnosis and Treatment is essential reading for those interested in clinical approaches to acute and chronic pain conditions involving muscle tissues and in the mechanisms underlying these conditions. The volumes cover a very important topic in pain medicine, since muscle pain is very common and can often be dif?cult to diagnose and treat effectively. Furthermore, chronic pain involving muscle and other components of the musculoskeletal system increases with age, such that it is a common complaint of those of us who are middle-aged or older. Indeed, as changing population demographics in "west- nized" countries result in higher proportions of the population living longer and being middle-aged and elderly, chronic muscle pain will likely become even more of a health problem. In the case of acute muscle pain, this can often be very intense, and in the short term can limit or modify the use of components of the musculoskeletal system associated with the sensitive muscle. Chronic muscle pain can also be intense, as well as unpleasant and disabling, and it is in many cases the over-riding symptom of most musculoskeletal disorders that are associated with long-term deleterious changes in musculoskeletal function.

This edition of the companion volumes Muscle Pain: Understanding the Mech- isms and Muscle Pain: Diagnosis and Treatment is essential reading for those interested in clinical approaches to acute and chronic pain conditions involving muscle tissues and in the mechanisms underlying these conditions. The volumes cover a very important topic in pain medicine, since muscle pain is very common and can often be dif?cult to diagnose and treat effectively. Furthermore, chronic pain involving muscle and other components of the musculoskeletal system increases with age, such that it is a common complaint of those of us who are middle-aged or older. Indeed, as changing population demographics in "west- nized" countries result in higher proportions of the population living longer and being middle-aged and elderly, chronic muscle pain will likely become even more of a health problem. In the case of acute muscle pain, this can often be very intense, and in the short term can limit or modify the use of components of the musculoskeletal system associated with the sensitive muscle. Chronic muscle pain can also be intense, as well as unpleasant and disabling, and it is in many cases the over-riding symptom of most musculoskeletal disorders that are associated with long-term deleterious changes in musculoskeletal function.

Volume I highlights the association of the cellular prion protein (PrPC) with copper and zinc, the potential roles of PrPC in Alzheimer's disease and cancers, insoluble PrPC, PMCA, molecular and cellular mechanisms of PrPSc formation and clearance, possible co-factors involved in the conversion of PrPC into PrPSc, infectious and pathogenic forms of PrP, cell biology of prions, prion strains and their interference, as well as yeast prions and their inheritable and structural traits. This unique volume will take you through the fascinating chronicle of prions in mammals, yeast, and fungi.

Cook et al.: Phospholipases C and D in Mitogenic Signal Transduction. Moolenaar et al: Lysophosphatidatic Acid: A Bioactive Phospholipid with Growth Factor-Like Properties. Kozma et al.: Serine/Threonine Kinases in thePropagation of the Early Mitogenic Response. Diringer et al: A Retrospective on Transformation, Growth Control, and some Peculiarities of Lipid Metabolism. Villereal et al.: Calcium Signals in Growth Factor Signal Transduction. Wakabayashi et al.: Structure Function of the Growth Factor-Activatable Na+/H+ Exchanger. Herrlich et al.: DNA Damage-Induces Gene Expression: Signal Transduction and Relation to Growth Factor Signaling. Lucibello et al.: Transcription Factor Encoding Oncogenes

As the title suggests, and unlike other existing books on sleep medicine, Neuroendocrine Correlates of Sleep/Wakefulness will be devoted primarily to endocrine regulation of the behavioral state control. It will address a wide spectrum of sleep./wakefulness phenomena (both animals and humans), including pathogenesis, diagnosis, and management. From molecular biology to applied clinical therapy, sleep research has been transformed in the last few years from a research backwater to an important interdisciplinary field. Anyone who regularly reads the literature on sleep, biological rhythms, or neuroendocrinology is aware that one of the subspecialties within sleep medicine, the neuroendocrine correlates of sleep/wakefulness, has in particular experienced a growth rate that is even faster than that of the field as a whole. To a significant extent this has been due to the introduction of new research technologies. The widespread adoption of a range of new methods in sleep research has opened a window into activities at the cellular and molecular level, which previously had been tightly closed. Consequently these activities are being characterized with a degree of precision and sensitivity that is without precedent. This volume invites the reader to explore the new vistas that have been opened onto the neuroendocrine frontier of sleep medicine. The editors have selectively identified a number of key articles having a citation frequency, which is considerably above the norm or which otherwise have contributed importantly to defining the neuroendocrine perspective. This new volume on Neuroendocrine Correlates of Sleep/Wakefulness is an up-to-date resource of research summaries and reviews written by major contributors to the fields of sleep, biological rhythms and neuroendocrinology. Its coverage is broad and its basic and clinical science reviews are detailed. In this volume, an international team of experts discuss their latest ideas, concepts, methods, and interpretations with supporting examples. This volume is intended for advanced students and specialists in psychobiology, neuroscience, neuroendocrinology, and psychiatry but might also be interest to anyone concerned with understanding the Neuroendocrine correlates of sleep/wakefulness. The contributions are directed more towards providing an integrated view of the field from the perspective of the authors, rather than being a compendium of recent results. The intent is to provide a reference book for recent and future workers in this and related areas of medicine and biology. Each topic in this volume has received the attention of a panel of authors who have responded to our request to review and place into perspective the major issues, which will undoubtedly confront newcomers to the field. The topics dealt with in Neuroendocrine correlates of Sleep/wakefulness are both diverse and complex. The editors hope that this volume will provide an authoritative summary of important issues in the neuroendocrine correlates of sleep/wakefulness. We also hope that it will motivate new researchers to join the quest for solutions to the problems that have been identified by our contributing authors.

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."