This volume features contributions from participants of an ESRF Workshop on "Systems Biology" held in Berkeley, USA, in November 2005. Significant progress has been made in developing technologies that enable systems interrogations at a molecular level. Recent successes and challenges of applying systems level measurements to the different steps of drug discovery and development in the pharmaceutical industry are summarized.

An essential reference for any laboratory working in the analytical fluorescence glucose sensing field. The increasing importance of these techniques is typified in one emerging area by developing non-invasive and continuous approaches for physiological glucose monitoring. This volume incorporates analytical fluorescence-based glucose sensing reviews, specialized enough to be attractive to professional researchers, yet appealing to a wider audience of scientists in related disciplines of fluorescence.

As a result of the rapidly growing rate of obesity worldwide, clinicians are struggling to provide the best strategies for treating obese patients with concomitant pulmonary conditions. Obesity does not simply change the epidemiology of pulmonary disease; obesity has a profound impact on the pathophysiology of common pulmonary diseases. Obesity affects the severity of asthma, response to treatment, and is likely a major modifier of the phenotype of asthma. Obesity also appears to affect response to pathogens, and as such has a major influence on response to pneumonia, and has a significant impact on outcomes pertaining to acute lung injury in the intensive care unit. Obesity and Lung Disease: A Guide to Management is the first text in the field to cover the full range of issues related to managing obese patients with pulmonary problems. All the relevant conditions, in the context of obesity, are covered, including airway inflammation, sleep apnea, asthma, pulmonary hypertension, obesity hypoventilation, as well as others. Written by an international group of experts, this important new volume is an invaluable resource for all clinicians and scientists concerned with the challenging problems surrounding obesity and lung diseases.

Kisspeptin has been shown to be both necessary and sufficient for activation of the reproductive axis, during puberty and later in adulthood. This makes kisspeptin a fundamental component of the reproductive axis. Kisspeptin has been deemed the single most potent stimulator of GnRH neurons yet known. The importance of kisspeptin has been documented in humans as well as non-human animal models, ranging from monkeys, sheep, and rodents to numerous fish species, thus signifying a highly conserved nature of its reproductive function. Importantly, kisspeptin neurons seem to mediate many of the regulatory effects of other signals, whether they are metabolic, circadian, hormonal, or stress. This places kisspeptin neurons in a unique position to be key nodal points and conduits for conveying numerous endogenous and exogenous signals to the reproductive axis.

The prevalence of hypertension is almost three times as high as that of diabetes mellitus type 2, with both conditions being major risk factors for stroke, ischemic heart disease, cardiac arrhythmias, and heart failure. The exact prevalence of hypertension related to hormonal derangements (endocrine hypertension) is not known but estimated to affect less than 15% of hypertensive patients. Recent scientific discoveries have increased the understanding of the pathophysiologic mechanisms of hypertension. In Endocrine Hypertension, a renowned panel of experts provides a comprehensive, state-of-the-art overview of this disorder, discussing when to assign an endocrine cause in one of many conditions that may present with hypertension. The first part of Endocrine Hypertension is dedicated to adrenal causes. The second part of the volume concerns potential nonadrenal causes of hypertension, such as growth hormone excess or deficiency, primary hyperparathyroidism, vitamin D deficiency, testosterone deficiency, insulin resistance, obesity-associated hypertension, and the role of central mineralocorticoid receptors and cardiovascular disease. An important contribution to the literature, Endocrine Hypertension is an indispensable reference not only for endocrinologists, diabetologists, and adrenal investigators, but also for translational scientists and clinicians from cardiology, internal medicine, pediatrics, family medicine, geriatrics, urology, and reproductive medicine / gynecology.

Since its ?rst description in 1942 in both serum and cerebrospinal ?uid, transthyretin (TTR) has had an eventful history, including changes in name from "prealbumin" to "thyroxine-binding prealbumin" to "transthyretin" as knowledge increased about its functions. TTR is synthesised in a wide range of tissues in humans and other eutherian mammals: the liver, choroid plexus (blood- cerebrospinal ?uid barrier), retinal pigment epithelium of the eye, pancreas, intestine and meninges. However, its sites of synthesis are more restricted in other vertebrates. This implies that the number of tissues synthesising TTR during vertebrate evolution has increased, and raises questions about the selection pressures governing TTR synthesis. TTR is most widely known as a distributor of thyroid hormones. In addition, TTR binds retinol-binding protein, which binds retinol. In this way, TTR is also involved with retinoid distribution. More recently, TTR has been demonstrated to bind a wide variety of endocrine disruptors including drugs, pollutants, industrial compounds, heavy metals, and some naturally occurring plant ?avonoids. These not only interfere with thyroid hormone delivery in the body, but also transport such endocrine disruptors into the brain, where they have the potential to accumulate.

Creating clinical guidelines is a modern trend. Published studies pertaining to a given theme are collected, their credibility evaluated, and then treatment options in the form of evidence-based guidelines are offered. There are a number of guidelines for the treatment of thyroid tumors that have established positions in clinical practice in North America and in Western European countries. In Japan, however, where radioisotope facilities are of limited availability, treatment plans for differentiated thyroid cancer differ considerably from those of America and Europe, and the associated clinical guidelines need modification before they can be adopted. In addition, although thyroid tumor is a common disease in endocrine practice, its management can differ even among specialists. Thus, a Japanese clinical guideline for the treatment of thyroid tumor was desired by many clinicians. As a combination of evidence-based and consensus-based guidelines for the treatment of thyroid tumor, this book offers alternatives to conventional approaches in the West. Ultimately, the authors hope the guideline will lead to the best possible treatment for patients all over the world in the not-distant future.

Why sex matters Among human and nonhuman animals, the prevalence and intensity of infection typically is higher in males than females and may reflect differences in exposure as well as susceptibility to pathogens. Elevated immunity among females is a double-edged sword in which it is beneficial against infectious diseases but is detrimental in terms of increased development of autoimmune diseases. The present book critically reviews the evolutionary origin and the functional mechanisms responsible for sexual dimorphism in response to infection. It emphasizes the value of examining responses in both males and females to improve our understanding about host-pathogen interactions in both sexes. The contributors are experts in their specific disciplines which range from microbiology and immunology to genetics, pathology, and evolutionary biology. The book aims at bringing insight to the treatment and management of infectious diseases; it delineates areas where knowledge is lacking and highlights future avenues of research.

Responding to a renewed interest in the growing problem of iodine deficiency worldwide, Drs. Charles Oxnard and Peter Obendorf, along with experienced translator and anatomist John Dennison, take a fresh look at the classic text, Der endemische Kretinismus, published in 1936 by Springer. Translated here for the first time into English, this landmark text will be a welcome resource for researchers confronting the problem of iodine deficiency. Oxnard and Obendorf point out that there is very little detailed knowledge or numerical data on cretinism available in the English-speaking world. In addition, highly-renowned Professor Basil S. Hetzel, recently-retired World Health Organization Chairman of the International Council for Control of Iodine Deficiency Disorders, published in 2009 with Dr Chen Zu-pei on the resurgence of iodine deficiency in China. Indeed, throughout the entire developing world there may be as many as two billion people at risk to iodine deficiency; perhaps three quarters of a billion have goiter, and ten million may be cretins. Even in developed countries, iodine deficiency is re-emerging (as in New South Wales in 19% of children) with the result of significantly reduced numbers of gifted children (though this is not cretinism per se). Certain to be of significant interest to a wide range of researchers, health providers and professionals, including government health administrators, this English translation of Endemic Cretinism is a major contribution to the literature.

Vassopressin, Volume 111, the latest release in the Vitamins and Hormones series, first published in 1943, covers the field of hormone action, vitamin action, X-ray crystal structure, physiology and enzyme mechanisms, with this release focusing on topics relating to hepcidin, bacterial infection, and iron overload, the role of heparan sulfates in hepcidin regulation, hepcidin CDNA and human gene sex hormones, growth factors and hepcidin, HFE gene polymorphisms and hereditary hemochromatosis, hepcidin and il-1beta, hepcidin-ferroportin axis, cardiomyocyte hepcidin, adipocyte iron, leptin and hepcidin, regulators of hepcidin expression, and much more.

Stjarne: The present review puts the emphasis on two important developments: the discovery that individual postganglionic sympathetic neurons may secrete multiple transmitter substances from different classes of vesicles and by different mechanisms, and the introduction of new techniques which may permit for the first time direct impulse by impulse analysis of transmitter secretion in individual sympathetic nerve varicosities. Illes: Exogenous and endogen opioid peptides elicit a number of effects in the organism, usually by modifying the function of transmitter and hormone systems, for example, activation of multiple opioid receptors. The effects of opioids on transmitter and hormone release have frequently been reviewed. This review gives a detailed overview on the involvement of multiple opioid receptors in these processes. Rothstein: This article gives an overview of the exchange in acidification and transepithelial salt and water transfer in nonepithelial cells. Delineating the exchanger's most important, common features, and concentrating particularly on its role in cell pH and volume regulation.

Originally presented as the author's thesis (doctoral--Technical University of Denmark).

The first report that rapid eye movements occur in sleep in humans was published in 1953. The research journey from this point to the realization that sleep consists of two entirely independent states of being (eventually labeled REM sleep and non-REM sleep) was convoluted, but by 1960 the fundamental duality of sleep was well established including the description of REM sleep in cats associated with "wide awake" EEG patterns and EMG suppression. The first report linking REM sleep to a pathology occurred in 1961 and a clear association of sleep onset REM periods, cataplexy, hypnagogic hallucinations and sleep paralysis was fully established by 1966. When a naive individual happens to observe a full-blown cataplexy attack, it is both dramatic and unnerving. Usually the observer assumes that the loss of muscle tone represents syncope or seizure. In order to educate health professionals and the general public, Christian Guilleminault and I made movies of full-blown cataplectic episodes (not an easy task). We showed these movies of cataplexy attacks to a number of professional audiences, and were eventually rewarded with the report of a similar abrupt loss of muscle tone in a dog. We were able to bring the dog to Stanford University and with this as the trigger, we were able to develop the Stanford Canine Narcolepsy Colony. Breeding studies revealed the genetic determinants of canine narcolepsy, an autosomal recessive gene we termed canarc1. Emmanuel Mignot took over the colony in 1986 and began sequencing DNA, finally isolating canarc1 in 1999.

captured for the published proceedings. Nevertheless, the two Supplements to this Journal (also available together as a hard-backed book) do, over the years, embrace many of the major aspects of the study of inborn errors of metabolism and can, particularly with the Short Communications section, be used as a way into the literature on specific new topics. We hope that with judicious selection of material these supplements will continue to provide, as did the Society's earlier annual publications, a balanced record of the present state of the subject in all its facets, a record of interest to those working in allied fields as well as to the specialist. R. J. Pollitt G. M. Addison R. A. Harkness The papers listed below were also presented at the meeting. Scripts were not available by the time of publication. 1. Tangier disease and related disorders of apolipoprotein Al. G. Assmann, Munster. 2. Contribution to Ethics Symposium by M. E. Pembrey, London.

The molecular era ushered in the cloning of the growth hormone (GH) gene and the production of unlimited amounts of GH through recombinant technology. The continuing momentum of research from basic science to clinical evaluation has brought unprecedented advances to the understanding of GH biology for the clinical endocrinologist. Growth Hormone Related Diseases and Therapy: A Molecular and Physiological Perspective for the Clinician distills all the new information of relevance to the endocrinologist over the last 20 years by offering five sections: physiology, molecular genetics, GH deficiency, acromegaly and pharmacotherapy. The first section on physiology focuses on GH action. A review on the structure and function of the GH receptor is followed by a perspective on the regulatory role of ghrelin on GH secretion. The second section on genetics covers pituitary function and adenomas, including new and fascinating information on familial pituitary adenomas, their genotype and phenotype. The adult GH deficiency section spans the epidemiology and diagnosis of GH deficiency with a strong reminder for the clinician that the transition period represents a critical time of somatic maturation, which continues for years after cessation of liner growth. The section on acromegaly focuses on management, giving practical guides to the value of GH and IGF-1 measurements, the place of somatostatin analogues and of radiotherapy while reminding the reader as to why evaluating quality of life is an important part of management. Finally, the section on GH pharmacology takes the reader through innovative developments of long-acting GH formulations with some products on the threshold of clinical use. This section provides a balanced evidence based review of the effects of GH supplementation in aging and in sports where recent data indicates an enhancing effect on a selective aspect of performance. Growth Hormone Related Diseases and Therapy: A Molecular and Physiological Perspective for the Clinician integrates a wealth of information and will prove an invaluable reference for pediatric endocrinologists, adult endocrinologists, endocrine scientists and internists interested in the human biology of GH.

Breast and prostate cancers are both hormone-dependent, at least in some stages of their progression. Hormonal manipulation represents an important therapeutic approach. Although most of breast and prostate cancers initially respond to hormone therapy, most tumors reinitiate to growth. Finally, hormone-resistant and metastatic breast and prostate cancers may develop. Thus, the challenge is the dissection of mechanisms by which steroid receptor signaling pathways continue to influence cell growth and invasiveness. Compelling evidence indicates that steroid hormones elicit non-genomic responses in extra-nuclear compartment of target cells. In this cellular location, steroid-coupled receptors rapidly recruit signaling effectors or scaffold proteins and activate multiple pathways leading to proliferation, survival, migration and invasiveness. The immediate challenge is the dissection of key events regulating the steroid response of target tissues to prevent progression and improve treatment of breast and prostate cancers.

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.

The scientific advances in the physiology and pathophysiology of adipose tissue over the last two decades have been considerable. Today, the cellular and molecular mechanisms of adipogenesis are well known. In addition, adipose tissue is now recognized as a real endocrine organ that produces hormones such as the leptin acting to regulate food intake and energy balance in the central nervous system, a finding that has completely revolutionized the paradigm of energy homeostasis. Other adipokines have now been described and these molecules are taking on increasing importance in physiology and pathophysiology. Moreover, numerous works have shown that in obesity, but also in cases of lipodystophy, adipose tissue was the site of a local low-grade inflammation that involves immune cells such as macrophages and certain populations of lymphocytes. This new information is an important step in the pathophysiology of both obesity and related metabolic and cardiovascular complications. Finally, it is a unique and original work focusing on adipose tissue, covering biology and pathology by investigating aspects of molecular and cellular biology, general, metabolic, genetic and genomic biochemistry.

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.

These two volumes are unique in that they take into consideration the enormous progress made in the field over the last few years. Expert knowledge is given by Professor Runnebaum, whose department was appointed WHO Collaboration Center for Research in Human Reproduction. These extensively illustrated books provide detailed information on the function and detection of new hormones and growth factors, on therapy with female sexual hormones, on environmental factors, and on the diagnostic and surgical techniques employed in reproductive medicine. This English edition of a standard German reference has been expanded to include an appendix containing a comprehensive list of pharmaceutical agents used in hormone therapy, including international and trade names and compositions.

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."

More than just coincidence connects a Tate & Lyle lawsuit and artificial sweetener to Jamaican-born Chemist Bert Fraser-Reid. From his first experience of Chemistry through his diabetic father, to his determination and drive as a Chemistry student in Canada, Fraser-Reid weaves a remarkable tale integrating science, law and autobiographical anecdotes. This book arises from the lawsuit brought by Tate & Lyle against companies accused of infringing its patents for sucralose, the sweet ingredient in the artificial sweetener SPLENDA which is made by chlorinating sugar. From a 1958 undergraduate intern witnessing the pioneering experiments on sugar chlorination, to being the 1991 recipient of the world's premiere prize for carbohydrate chemistry, Fraser-Reid was groomed for his role as expert witness in the mentioned lawsuit. Nevertheless, it seems more than his career links Fraser-Reid to the case.

Western knowledge of progress in biomedical research in Russia is severely limited by the scarcity of Russian journals available to us as well as the fact that few of us can read Russian. Therefore, it is of special significance that this recent contribution to the Russian scientific literature has been trans lated into English. This publication, Thyroid Hormones, brings to us a detailed analysis of recent work in Russia, and in particular in the Laboratory of Hormone Biochemistry, Institute of Biochemistry, Academy of Science of the Uzbek SSR and the Laboratory of Pathological Physiology, Institute of Experi mental Endocrinology and Hormone Chemistry, Academy Medical of Science of the USSR. The review illustrates the parallel pathways of inves tigation taken by investigators in Russia and in the West, indicating where the results have complemented each other or stimulated new questions and approaches. Consequently, the book provides an excellent review of the contributions made by Russian scientists in thyroid research and couples it with Western thought on these subjects to produce a complete review of the thyroid hormones. The large amount of data provided and the inclusion of multiple view points toward specific problems provides an excellent survey of the mecha nisms of biosynthesis and control of hormone formation, physiological effects of the hormones, and the molecular mechanisms involved in thyroid hormone action."

Gastroparesis is an increasingly recognized disorder. Treatment can be difficult due to the several mechanisms for symptom production. Gastroparesis: Pathophysiology, Presentation and Treatment serves as a concise reference on this disorder that allows clinicians to quickly access and evaluate the necessary information for treating and managing patients with gastroparesis. Each chapter is written byexperts in their respective area. The volume will enable the reader to better understand all aspects of this disorder. The book presents current concepts in a variety of areas opening with the epidemiology, clinical presentation and pathophysiology of gastroparesis. The natural history of patients is explored as well as evaluation of patients with suspected gastroparesis. This section includes chapters on Wireless Capsule Motility, Electrogastrography and Antroduodenal Manometry. This important resource concludes with a full section on treatment including dietary, prokinetic, antiemetic, sensory, electric stimulation, and surgical methods. New developments include the use of gastric electric stimulation for treatment, the use of SmartPill for diagnosis, and a number of new agents in development for this disorder. Gastroparesis: Pathophysiology, Presentation and Treatment is the ideal reference for gastroenterologists, and also for surgeons, endocrinologists, primary care physicians and nutritionists looking to keep pace with the latest information treatment options for their patients. "