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.

The most recent research findings on the important genes, key molecules, and mechanisms in neural development and regeneration are presented in this volume. The papers collected here were delivered at the second of the Keio University International Symposia for Life Sciences and Medicine, held in Mita (Tokyo), Japan, and are in eight main sections: Early Neurogenesis and Pattern Formation, Regional and Cellular Specification, Trophic Factors, Adhesion Molecules, Glial Cell Lineage and Myelination, Circuit Formation, Synaptic Refinement and Neurotransmitter Release, and Neural Regeneration. Together, they present the concept of neural development and regeneration and its vital importance at the frontiers of medical science today.
Neural Development is an invaluable resource and reference for researchers, clinicians, and students in physiology and the medical sciences.

Interest in angiogenesis research remains strong in recent years and exciting new discoveries, about modulators of angiogenesis, their receptors, the transduction mechanisms and the angiogenic genes involved, have contributed to our present day understanding of this complex process. This knowledge has provided the basis and broadened the scope of angiogenesis - based therapy in oncology and many other clinical conditions. This monograph contains the contributions to the NATO Advanced Study Institute on "Angiogenesis: Models, Modulators and Clinical Applications," which was held in Rhodes, Greece, from June 20-30, 1997. This was the fourth of a series of NATO supported international meetings on Angiogenesis aiming to bring together basic scientists with clinicians to exchange ideas, disseminate new knowledge and discuss the present status and potential new directions in this fast moving area of biomedical research. The International Organising Committee that included Drs. E. Dejana, C Haudenschild, M. Hackel, H. Kleinman, P. Lelkes, M. Presta, P. Polverini, D. Thompson, has provided invaluable help with their insightful suggestions in the formulation of the scientific program for which I am grateful. I wish to thank all the participants for their enthusiastic participation and their complimentary comments on the success of the conference.

Novel Approaches into the Origins of Neurodevelopmental Disorders: The Fetal Physiology Foundation Over the past two decades, autism, a neurodevelopmental disorder that is defined by behavior and was once believed to be rare, became recognized in increasing numbers of children and recently received distinction as an "epidemic" [1]. While numbers of affected children have steadily increased, our knowledge is still ins- ficient to explain autism's diverse causes and broad range of presentations. Despite remarkable progress in research, available medical diagnostic testing applies only to a small minority of affected children. Thus, scientifically based explanations with which physicians can diagnose and treat the majority of children with autism and advise their parents are quite limited. Our society and scientific community were unprepared for the rise in autism, which explains our present inability to understand most of its causes. Researchers in neurodevelopmental disorders have long been aware of other disorders that, despite extensive efforts, have not yielded clear genetic or environmental origins, and autism has become symbolic of the need for new approaches to research into these complex conditions. Although autism has captured our attention in recent years, the prevalence of other neurodevelopmental disorders such as attention de- cit hyperactivity disorder (ADHD) and bipolar disorder, among others, also has been increasing [2-4].

Investigations involving incisive mechanistic dissection of various types of synaptic plasticity have revealed that it plays key roles in neural development, sensory information processing, cortical remapping following brain injury, perception, and behavioral learning and memory. Disruptions of synaptic plasticity may underlie neurological and behavioral disorders such as Alzheimer disease, Fragile-X syndrome, autism, and drug addiction. Multidisciplinary Tools for Investigating Synaptic Plasticity, therefore, assembles expert contributions that highlight techniques and strategies used in probing the cellular and molecular mechanisms of synaptic plasticity in the nervous systems of vertebrate and invertebrate species. Divided into three sections, this meticulous volume describes biochemical and genetic strategies for studying synaptic plasticity, behavior, neural development, and synaptogenesis, and also includes cellular electrophysiological and optical methods for interrogating a diverse array of mechanistic issues. As part of the Neuromethods series, this book contains the kind of detail and key implementation advice that maximizes successful results. Authoritative and invaluable, Multidisciplinary Tools for Investigating Synaptic Plasticity serves as an ideal primer for introducing researchers to specific techniques that will enhance their success at addressing novel questions in synaptic plasticity at the lab bench.

Year One of Practice Transition: The Necessary Guide to Success is a practical guide for both established physicians transitioning from one practice opportunity to another, and those transitioning from formal residency or fellowship training. This book is an up-to-date look at how to achieve a successful practice, offering insights from top experts who have navigated transition through various phases and circumstances.

Unique study of the human foot

Sole perspective on the human foot in the market

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.

Because of developments in powerful computer technology, computational techniques, advances in a wide spectrum of diverse technologies, and other advances coupled with cross disciplinary pursuits between technology and its greatly significant applied implications in human body processes, the field of biomechanics is evolving as a broadly significant area. The four volumes of Biomechanical Systems: Techniques and Applications presents the advances in widely diverse areas with significant implications for human betterment that occur continuously at a high rate. These include dynamics of musculo-skeletal systems; mechanics of hard and soft tissues; mechanics of muscle; mechanics of bone remodeling; mechanics of implant-tissue interfaces; cardiovascular and respiratory biomechanics; mechanics of blood flow, air flow, flow-prosthesis interfaces; mechanics of impact; dynamics of man machine interaction; and numerous other areas. The great breadth and depth of the field of biomechanics on the international scene requires at least four volumes for adequate treatment. These four volumes constitute a well integrated set that can be utilized as individual volumes. They provide a substantively significant and rather comprehensive, in-depth treatment of biomechanic systems and techniques that is most surely unique on the international scene.

Offers the best, practical approach to motor learning available which is written in language that is easy to understand. Includes market-leading ancillary material, such as an instructors' manual, lecture slides, laboratory activities and a test bank, to aid student learning Fully updated pedagogical features-Cerebral Challenges, Exploration Activities, Putting it into Practice and Research Notes-helping students to contextualise theory in practice and provides interactivity through online resources. Offers exceptional layout of the chapter with online resources, charts and outline of chapter and videos to include in the lecture

The bright colour of haemoglobin has, from the very beginning, played a significant role in both the investigation of this compound as well as in the study of blood oxygen transport. Numerous optical methods have been developed for measuring haemoglobin concentration, oxygen saturation, and the principal dyshaemoglobins in vitro as well as in vivo. Modern applications include pulse oximeters, fibre optic oximeters, multiwavelength haemoglobin photometers ('co-oximeters') and instruments for near infrared spectroscopy in vivo. Knowledge of the light absorption spectra of the common haemoglobin derivatives is a prerequisite for the development and understanding of these techniques.
In the 1960s a reference method based on the absorptivity of a single derivative (haemiglobincyanide; HiCN) at a single wavelength (540 nm) was established for measuring the total haemoglobin concentration. Thus an anchor value was provided on which the absorptivity spectra of all other haemoglobin derivatives could be based.
This monograph presents absorption spectra and absorptivity data in the wavelength range of 480 to 1000 nm of the major haemoglobin derivatives for human adult and foetal haemoglobin and for haemoglobin of several animals (cow, dog, horse, pig, rat, and adult and foetal sheep). A detailed description of the methods used to acquire these data has been included to allow future investigators to reproduce and expand on the data.
The second part of the monograph includes chapters on the principles and development, in historical perspective, of the principal methods for measuring total haemoglobin concentration for two, three, and multi-component analysis of haemoglobin derivatives, and for blood oxygen saturation measurement. Accurate quantitative data pertaining to haemoglobin in human blood are presented, together with a description of methods for measuring haemoglobin oxygen capacity and oxygen affinity. These chapters have been written with a view to foster knowledge and insight concerning the principles, purposes, and limitations of the various methods of all who use these methods in research and patient care.

This book presents cutting edge methods that provide insights into the pathways by which salt and water traverse cell membranes and flow in an orchestrated fashion amongst the many compartments of the body. It focuses on a number of molecular, cellular and whole animal studies that involve multiple physiological systems and shows how the internal milieu is regulated by multifactorial gene regulation, molecular signaling, and cell and organ architecture. Topics covered include: water channels, the urinary concentrating mechanism, angiotensin, the endothelin system, miRNAs and MicroRNA in osmoregulation, desert-adapted mammals, the giraffe kidney, mosquito Malpighian tubules, and circadian rhythms. The book highlights how different approaches to explaining the same physiological processes greatly increase our understanding of these fundamental processes. Greater integration of comparative, evolutionary and genetic animal models in basic science and medical science will improve our overall grasp of the mechanisms of sodium and water balance.

Free radicals and oxidative damage in biology and medicine: An introduction.- Oxidative metabolism in skeletal muscle.- Strategies to assess oxidative stress.- The course of exercise-induced skeletal muscle fibre injury.- Free radical mechanisms in exercise-related muscle damage.- The effects of exercise, ageing and caloric restriction on protein oxidation and DNA damage in skeletal muscle.- Antioxidant enzyme response to exercise and training in the skeletal muscle.- Glutathione: A key role in skeletal muscle metabolism.- Vitamin E and its effect on skeletal muscle.- Differential susceptibility of skeletal muscle proteins to free radical-induced oxidative damage in vitro.- Oxidative stress and Ca2+ transport in skeletal and cardiac sarcoplasmic reticulum.- Oxidative stress in skeletal muscle atrophy induced by immobilization.- Effect of growth hormone on oxidative stress in immobilized muscles of old animals.- The diaphragm and oxidative stress.- Oxidative damage after ischemia/reperfusion in skeletal muscle.- Oxidative damage in rat skeletal muscle after excessive L-tryptophan and atherogenic diets.- Oxidative stress and muscle wasting of cachexia.- Free radicals and antioxidants in the pathogenesis of alcoholic myopathy.- Drug-induced muscle damage.- Free radicals and diseases of animal muscle.- Therapeutic trials of antioxidants in muscle diseases.

Gastric acid plays a primary role in digestion as well as in the sterilization of food and water. Gastric juice contains the most concentrated physiological acid solution (pH~1) as a result + - of H and Cl ion secretion [hydrochloric acid (HCl) production] by parietal cells in the oxyntic mucosa of the stomach. The combined output of the parietal cells leads to the sec- tion of 1-2 l of HCl at a concentration of 150-160 mmol/l into the interior of the stomach. In order to facilitate the production of acid, the parietal cell relies on the generation of a high + concentration of H ions that are transported into the lumen of the gland. This process is fa- + + cilitated by activation of the gastric H ,K -ATPase, which translocates to the apical pole of + - the parietal cell. K as well as ATP hydrolysis and Cl all play critical roles in the activation + + of gastric H ,K -ATPase and are essential for the functioning of the enzyme (Reenstra and Forte 1990). This review will examine the classical proteins that have been linked to acid secretion as well as some recently identi?ed proteins that may modulate gastric acid secretion, in - dition we discuss the known secretagogues, and their receptors including a new receptor, which upon stimulation can lead to acid secretion.

The VIth World Symposium on Cardiac Pacing in Montreal 1979 opened with a course, meant to be an introduction for newcomers and an updating re fresher and link between the various fields of knowledge needed by experienced persons for cardiac pacing. Invited guest lecturers were selected for their world recognized expertise in the individual subjects. This book is a collection of the various presentations on historical, clinical, electrophysiological and technical aspects of cardiac pacing. Together they cover the fundamentals of cardiac stimulation. We hope that this book may become an introductory guide to the field of cardiac pacing and that it may contribute to a better understanding of the pacemaker system and a better treatment of the pacemaker patient. Claude C. Meere Hilbert J. Th. Thalen ACKNOWLEDGEMENT The editors of 'Fundamentals on Cardiac Pacing' acknowledge the under standing and support of their families, during the long nocturnal hours and weekends during which this book was prepared. A special note of appreciation is extended to our secretaries, especially Mrs. Carolyn Gaarenstroom-Arriens and Miss Katrien Schuurman for their 'emergency typing' and Miss Lynn Bacon and Mr. Boudewijn Commandeur from Martinus Nijhoff Publishers, who succeeded in completing the book in time for the Montreal meeting. Only those involved are able to realize the importance of their contribution. CONTRIBUTORS David L. Bowers, B.S.E.E., Vitarel Inc. San Diego, California, U.S.A. Guy Fontaine, M.D., Groupe Hospitalier, Pitie-Salpetriere, Paris, France."

Twenty years after its discovery, recombinant human leptin has been approved by the Food and Drug Administration for the treatment of patients with lipodystrophy. Beginning with a synthesis of the vast body of work on its discovery, dissection of mechanisms, and effects in experimental models , the focus of this book shifts to a consideration of the regulation and role of leptin in humans. The emphasis on human-level data is a unique feature of this book. The results of numerous studies indicate that leptin is indeed a regulated human hormone. Leptin provides a detailed account of the myriad physiological, hormonal, metabolic, immunological, mitogenic and inflammatory modulators and targets of leptin in a single volume. Next follows a comprehensive presentation of the therapeutic trials of recombinant leptin in patients with congenital leptin deficiency, lipodystrophy, hypothalamic amenorrhea, and other emerging areas, including leptin supplementation in leptin-replete subjects, leptin substitution for insulin in diabetic models, and novel combination regimens of leptin and other biogenic peptides. Unanswered questions and future directions in leptin research are highlighted in the Foreword by Dr. Jeffrey Friedman and throughout the volume. Identifying such questions helps direct research that could deepen understanding of the complex regulation of leptin under physiological and pathological conditions, a critical prerequisite to its rational deployment in the treatment of human disorders.

Advances in cellular physiology and molecular biology have now disclosed the metabolic changes and adaptational responses of the heart to various kinds of stresses. Topics covered in this volume include the regulation of myocardial proteins in mechanical overload, the alteration of adrenoceptors in the stressed heart, metabolic adaptation in cardiac hypertrophy, intracellular calcium metabolism in the ischemia-reperfused myocardium, calcium overload as a cause of myocardial stunning, acquisition of ischemic tolerance by ischemic preconditioning, factors that accelerate myocardial injury, and ventricular remodeling in the ischemic heart. As an update of the latest findings in basic cardiology, this book will benefit both researchers and clinical practitioners.

The Sapporo International Symposium on "Recent Advances in Nitric Oxide Research" was held in Sapporo, Japan, in 1997, following the Fifth International Meeting on the Biology of Nitric Oxide in Kyoto, Japan, organized by Dr. Salvador Moncada, Dr. Noboru Toda, and Dr. Hiroshi Maeda. The field of nitric oxide research continues to expand rapidly, and our understanding of the physiological and pathophysiological roles of NO has increased greatly. The Kyoto Meeting was stimulating and informative, providing impetus for the Sapporo Symposium, which I had the great honor to organize. To communicate the information from these events, Dr. Ichiro Sakuma and I decided to publish this book. The contents of its chapters were contributed by the participants who were active at the Sapporo symposium and cover the majority of the presentations made during that symposium. Dr. Csaba Szabo of Children's Hospital Medical Center in Cincinnati (U. S. A. ) reviews the roles of peroxynitrite and poly(ADP-ribose)synthetase in shock, inflammation, and reperfusion injury, and Dr. David A. Geller and his colleagues of the University of Pittsburgh (U. S. A. ) review the regulation and function of NO in the liver. As contributions from the Hokkaido University School of Medicine (Sapporo), Dr. Hiroko Togashi and colleagues present their data on transient cerebral ischemia and NO production, Dr.

Recent Advances in Prolactin Research summarizes the current knowledge of prolactin (PRL), PRL receptor, PRL-dependent signaling pathways, the role of PRL in oncogenesis and PRL crosstalk with other oncogenic factors. The chapters are written by experts in these fields and focus on identifying and reviewing timely experimental findings that provide new insights into the expanding role of PRL in the pathophysiology associated with a variety of human conditions. Prolactin is a peptide hormone that is best known for its role in lactation. Prolactin also has an influence on hematopoiesis and angiogenesis, and is involved in the regulation of blood clotting through several pathways. Although PRL was discovered more than 80 years ago, the understanding of PRL signaling and its relationship to various pathologies is still very incomplete. PRL is not only a pituitary hormone with an important role in reproduction, but PRL also acts as a cytokine, modulating a wide variety of physiological processes. For example, data gathered during the last decade have demonstrated that locally produced PRL acts as the autocrine/paracrine factor and plays a contributory role during breast oncogenesis. In fact, the scientific and clinical communities have suggested that the manipulation of the PRL axis may lead to the successful treatment of breast cancer. However, recent work has demonstrated that the role of the PRL axis is much more complex than first envisaged.

This book covers the tremendous progress in the current understanding of the molecular physiology of voltage-gated calcium channels. This book includes unparalleled insights into structural features of calcium channels due to X-ray crystallography and cryo-EM, which in turn yielded critical information into how these channels function under normal and pathophysiological conditions, and how they interact with calcium channel therapeutics. The chapters investigate how, with the advent of high throughput genome sequencing, numerous mutations in various calcium channel genes have been identified in patients with neurological, cardiovascular, neuropsychiatric and other disorders. This is further complemented through a much larger in vivo toolkit such as knock-out and knock-in mice. The chapters further discuss the increased complexity of calcium channel physiology that arises from mRNA editing and splicing. Finally, the book also provides an overview of the updated research on calcium channel inhibitors that can be used both in vivo and in vitro, and which may serve as a spring board for new calcium channel therapeutics for human disease. Voltage-Gated Calcium Channels is useful for academic researchers at all levels in neuroscience, biophysics, cell biology and drug discovery.

This second book of the three-volume collection "Ion Transport in Tumor Biology" helps readers gain comprehensive knowledge of the pathophysiology of cancer. The authors highlight that ion transport proteins, channels and transporters - collectively referred to as the transportome - are significantly involved in the development and progression of cancer. Nearly 90% of malignant tumor diseases originate from epithelial cells, the function of which, for the most part, is based on the transportome. This volume focuses on molecular principles by showing that dysregulated expression and/or function of ion transporters have been correlated with malignancy in the vast majority of tumor diseases. Within the story of the various chapters, the authors line out various malfunctions of the transportome and where they can be found at different stages of the metastatic cascade. The authors describe how the interactions between the tumor cells' transportome and the environment reinforce mesenchymal behaviour of cancer cells and contribute to their uncontrolled proliferation, migration, invasion, intra- and extravasation up to the formation of metastases. As part of a three-volume collection, this book will fascinate members of the active research community, as well as clinicians from the cancer field.

Those grieving the loss of a loved one who has died under traumatic circumstances form a special group of mourners. Separate from those going through "simple bereavement", these mourners must cope with a double-edged sword: the grief of the loss and the trauma of the knowledge of how the loved one may have had to endure traumatic stress during their final minutes of life. This addition to the "Series in Trauma and Loss" should enable mental health professionals to distinguish between those who are going through the "normal" grieving process in the aftermath of a traumatic event, and those who are suffering from post traumatic stress disorder. A byproduct of years of research and experience, this book helps buttress the theoretical bridge between thanatology and traumatology. It focuses on the unique features of death-related PTSD, its assessment, and treatment. With case examples that draw upon consistent concepts and definitions, and equal attention to scholarly and practical concerns, the book argues that traumatic elements must be worked through first before grief and loss accommodations are achieved. More importantly, the research and treatment methods presented by experts in t

Physical Activity and Health explains clearly, systematically and in detail the relationships between physical activity, health and disease, and examines the benefits of exercise in the prevention and treatment of a wide range of important conditions.

Now in a fully updated and revised third edition, and still the most complete and engaging textbook on this important subject, Physical Activity and Health offers a balanced examination of the very latest evidence linking levels of physical activity with disease and mortality. The book offers a wide-ranging assessment of the importance of inactivity as a factor in major diseases and health conditions such as cardiovascular disease, diabetes, obesity, cancer and osteoporosis, and now also includes a full chapter on exercise and mental health. The book is designed to help the reader evaluate the quality and significance of the scientific evidence, and includes an invaluable discussion of common study designs and the inherent difficulties of measuring physical activity. It explores every contemporary theme in the study of exercise and health, such as the hazards of exercise; exercise and the elderly; children s health and exercise; physical activity and public health policy; and also a critical appraisal of current recommendations for physical activity.

Containing useful features throughout, such as chapter summaries, study tasks, guides to supplementary reading and definitions of key terms, and richly illustrated with supporting tables, figures and plates, Physical Activity and Health is an essential course text. Now supported by a companion website featuring self-test questions, PowerPoint slides for lecturers, additional learning activities and web links, this book is vital reading for degree-level students of sport and exercise science, public health, physical therapy, medicine and nursing. "