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.

Volume 39, devoted solely to the vital research area on molybdenum and tungsten and their role in biology, offers a comprehensive and timely account of this fascinating topic by 40 distinguished international authorities. With more than 2200 references to assist further research, Molybdenum and Tungsten: Their Roles in Biological Processes is an essential resource for scientists and students in many disciplines, including bioinorganic, inorganic, and coordination chemistry; biochemistry; biophysics; molecular biology; enzymology; pharmacology; physiology; clinical chemistry; nutrition; toxicology; and environmental sciences.

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].

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 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.

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 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."

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.

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.

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.

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 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.

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.

This book for the first time comprehensively surveys the research investigating the Jak-Stat pathway and its role in normal blood development as well as its perturbation in disease. It draws on the expertise of world-renowned medical researchers to take the reader from basic biology through to recent therapeutic advances.

Rapid regeneration of city areas has placed the quality of urban design high on public and policy agendas worldwide. This work examines the achievement of quality in the urban environment, in a planning context. Tracing urban design from its roots, the authors draw on both historical and current practices to examine the key physical, political and economic forces at play and the social pressures and impacts brought about by both failures and achievements in urban design. This illustrated critique of towns and cities draws on examples from across Western Europe, South Africa and USA to examine both public and private sector development practices, controls and fiscal policies within a diverse range of localities. The authors indicate the need for a reinstitution of region-provincial approaches, for closer co-ordination bewteen sectors, and revised fiscal policies in planning and development in order to enhance the quality of urban social experience and environments.

The collection of chapters in this proceeding volume reflects the latest research presented at the Aegean meeting on Tumor Microenvironment and Cellular Stress held in Crete in Fall of 2012. The book provides critical insight to how the tumor microenvironment affects tumor metabolism, cell stemness, cell viability, genomic instability and more. Additional topics include identifying common pathways that are potential candidates for therapeutic intervention, which will stimulate collaboration between groups that are more focused on elucidation of biochemical aspects of stress biology and groups that study the pathophysiological aspects of stress pathways or engaged in drug discovery.

Carefully delineating each step in the formation of the lung, Lung Growth and Development examines prenatal and postnatal lung development...the regulation of surfactant protein gene expression and models for the analysis of epithelial gene transcription and function...cellular differentiation and the role of mesenchymal cells...airway gland growth and differentiation...growth regulation in the tracheobronchial epithelium and mucociliary differentiation...embryonic precursors of the pulmonary nervous system and the development of lung innervation...Clara cells, airway smooth muscle development, cell interactions in vessel formation, and the surfactant system...respiratory distress syndrome, bronchopulmonary dysplasia, and compensatory lung growth...and more. Written by over 30 international experts, Lung Growth and Development is a practical guide for pulmonologists and pulmonary disease specialists, physiologists, molecular and cellular biologists, pathologists, neonatalogists and pediatricians, anatomists, pathologists, and graduate-level and medical school students in these disciplines.

This monograph is dedicated to the lives and scientific achievements of the physiology pioneers Warren and Margaret Lewis. Their story spans the first half of the 20th century, from their respective educations through early, independent research to joint research from 1910 to 1955. Among the numerous developments they initiated, were the discovery of pinocytosis, the beginnings of video microscopy and the development of the first mammalian tissue cultures. Their research expanded the theoretical knowledge of cell structure and function. On a more practical level, they advanced many laboratory methods, like the first recipes for culture media. The text is beautifully enriched with personal anecdotes about their lives. This is the story of two scientific pioneers in the context of early 20th century biology and physiology. It is an inspiration for senior and aspiring researchers.

The maintenance of arterial blood pressure and the distribution of blood flow to the various organs of the body depends on the control of the pumping action of the heart and of the resistance of the vascular beds in the individual organs in accordance with their metabolic needs. These controls are achieved through the integrated actions of circulat ing hormones, humoral factors that are synthesized and released in the heart and blood vessels, and the autonomic nervous system. The heart, however, is not only the target for the direct and indirect actions of a number of hormones and humoral factors, it is also an endocrine organ in the traditional sense, synthesizing and secreting into the circulation chemical factors that act at distant sites. In this treatise, Hormones and the Heart in Health and Disease, we interpret "endocrinology" broadly and consider traditional hormones as well as autocoids that are secreted by the heart or that act on it. In this overview, the relevant chapters are indicated in parentheses. The discovery of atrial natriuretic peptide (ANP; atrial natriuretic factor, ANF) in the 1980s indicated that the heart does indeed function as an endocrine organ in the classic sense. ANP (Chapter I) is synthesized in the heart and secreted into the circulation for actions on the kidney, where it is a potent natriuretic agent, and on the vasculature, where it causes vasodilation. ANP can also affect myocardial contractility."

Quantitative ultrasound (QUS) of bone is a relatively recent research field. The research community is steadily growing, with interdisciplinary branches in acoustics, medical imaging, biomechanics, biomedical engineering, applied mathematics, bone biology and clinical sciences, resulting in significant achievements in new ultrasound technologies to measure bone, as well as models to elucidate the interaction and the propagation of ultrasonic wave in complex bone structures. Hundreds of articles published in specialists journals are accessible from the Web and from electronic libraries. However, no compilation and synthesis of the most recent and significant research exist. The only book on QUS of bone has been published in 1999 at a time when the propagation mechanisms of ultrasound in bone were still largely unknown and the technology was immature. The research community has now reached a critical size, special sessions are organized in major international meetings (e.g., at the World Congress of Biomechanics, the annual meetings of the Acoustical Society of America, International Bone Densitometry Workshop, etc...). Consequently, the time has come for a completely up to date, comprehensive review of the topic. The book will offer the most recent experimental results and theoretical concepts developed so far and is intended for researchers, graduate or undergraduate students, engineers, and clinicians who are involved in the field. The central part of the book covers the physics of ultrasound propagation in bone. Our goal is to give the reader an extensive view of the mathematical and numerical models as an aid to understand the QUS potential and the types of variables that can be determined by QUS in order to characterize bone strength. The propagation of sound in bone is still subject of intensive research. Different models have been proposed (for example, the Biot theory of poroealasticity and the theory of scattering have been used to describe wave propagation in cancellous bone, whereas propagation in cortical bone falls in the scope of guided waves theories). An extensive review of the models has not been published so far. We intend in this book to present in details the models that are used to solve the direct problem and strategies that are currently developed to address the inverse problem. This will include analytical theories and numerical approaches that have grown exponentially in recent years. Most recent experimental findings and technological developments will also be comprehensively reviewed.

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."

Learn, understand, and master pathophysiology! Corresponding to the chapters in McCance & Huether's Pathophysiology: The Biologic Basis for Disease in Adults and Children, 9th Edition, this study guide offers practical activities and detailed case studies to help you review and remember basic pathophysiology and make the connections between theory and practice. Interactive questions provide you with a working knowledge of disease etiology and disease processes - giving you practice applying what you've learned to clinical practice. Best of all, the answers are in the back of the book so that you can check your understanding as you go! More than 1,200 questions in a wide variety of challenging formats cover all areas of pathophysiology. Practice exams provide immediate feedback by helping you understand the rationale behind each answer. Concise chapter summaries highlight need-to-know information and help you quickly review content. Over 120 illustrations appear in active learning exercises to engage and reinforce understanding for visual learners. Answer key in the back of the study guide allows you to check answers and evaluate your progress. NEW! Thoroughly revised and updated information mirrors content from the 9th edition of the McCance & Huether's Pathophysiology textbook. NEW! Over 40 detailed case scenarios provide real-world examples of how pathophysiology is used in the clinical setting, helping you integrate knowledge, develop clinical judgment, and apply theory to practice.

Studies over the past decade have continued to bring tremendous advances to our understanding of bone biology. New pathways have been discovered and expanded our knowledge of the ways in which genes and gene products affect bone cells and thereby bone mass and bone strength. In Bone Research Protocols, Second Edition, expert researchers in the field detail many methods commonly used to study bone biology. Focusing mainly on in vitro methods, this volume gives techniques for isolation, culture and functional analysis of all bone cell types and details a range of imaging methods, including light and ultrastructural microscopy and live cell imaging. Some important in vivo techniques are included, such as analysis of bone resorption and imaging using X rays, fluorescent or luminescent techniques. Methods for study of proteins and nucleic acid are included and methods for analysis of bone composition, measurement of bone strength, and response to mechanical stimulation are described. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Bone Research Protocols, Second Edition seeks to aid scientists in the bone field to establish new techniques in their laboratories.