The authors of this book have a goal-to describe the management of infertility from the perspective of physiology and anatomy gone awry. To accomplish this goal, the chapters devoted to the causes of infertil ity begin with a description of the normal structure and function of the organ or system causing the infertility. We believe that under standing the normal will result in rational and effective diagnosis and treatment of infertility. Our intent is that this book be a useful re source for those who care for infertile couples. For an infertile couple, success is the delivery of a normal and healthy infant. Chapters that describe the causes and treatment of habitual abortion and the reproductive performance of previously infertile couples emphasize the hazards that exist between conception and birth. Our environment is one of these hazards, one that may also affect reproduction before conception. A chapter is devoted to a de scription of environmental agents that affect reproduction, the mech anisms of their effect, and methods to predict those present and future environmental agents which might also affect reproduction."

The growth and function of many tissues are influenced by hormones. Therefore it is quite understandable that hormones play a role in the development and treatment of malignant tumors. Numerous publications address this topic; however, the results of many studies are controversial and have not been unequivocally accepted. For nearly 50 years the carcinogenic effect of steroid hormones has been under debate, and their therapeutic value a matter of discussion for equally as long. The present volume concentrates on substantiated data first obtained from the study of tumors developing from hormone regulated or hormone-producing tissue, e.g., the thyroid, adrenal glands, prostate, and the female genital tract. Through a joint approach from the field of molecular biology, biochemistry, and histopathology, advances in the management of these tumors have been elaborated. Another exciting example is the endo nuclear diagnosis of adrenal tumors. Antihormones, i.e. antian drogens or GnRH analogues have proved to be important indeed since they exhibit a destructive effect on prostate carcinomas and breast cancer. Further improvements can be expected in the localization of hormones in tumor tissue by specific antibodies. A special chapter is dedicated to the diffuse endocrine cell system (DECS), the clinical significance of which has mainly become obvious in the gastroenteropancreatic tract.

Die Beitrage dieses Buches beschaftigen sich mit Autoimmunitat, Immuntherapie des Typ-I Diabetes, Virusgenese, Insulintherapie und -allergie. Schwerpunkte liegen auf den dynamischen Aspekten der Insulinsubstitution unter Berucksichtigung einer angepassten Diat und der Therapie mit oralen Antibiotika, Insulinen und Pro-Insulinen. Gleichzeitig wird anhand der Makro-Angiopathie und der Neuropathie auf die Auswirkungen der dynamischen Insulinsubstitution bei Sekundarkomplikationen hingewiesen. Die Moglichkeit der computerunterstutzten Therapiefuhrung und glukosesensorgesteuerten Biofeedback-Kontrolle werden vorgestellt. Ein umfangreiches Kapitel vermittelt den aktuellen Stand der experimentellen Forschung und der klinischen Anwendung der Pankreas- und Inselzelltransplantation.

In the last decade, it has become increasingly evident that the clini- cal and morphologic changes underlying many of the complications of diabetes, including cataract formation, retinopathy, nephropathy, neuropathy, and macrovascular disease, are preceded by a variety of disturbances of biochemical and physiologic origin. Dr. Cohen has recently written a superb monograph, entitled Diabetes and Protein Glycosylation: Measurement and Biologic Relevance, in which she thoroughly explores how enhanced nonenzymatic glycosylation in uncontrolled diabetes underscores the pressing need for main- tenance of long-term euglycemia. In the present volume, The Polyol Paradigm and Complications of Diabetes, she reviews, in a most succinct and thorough manner, how another biochemical mechan- ism, involving the polyol pathway, is involved in the pathogenesis of such diabetes complications as retinopathy, neuropathy, nephropa- thy, and cataract formation. Dr. Cohen gives us a clearly written and comprehensive mono- graph, reviewing the chemistry of the polyol pathway and of the aldose reductase inhibitors, and the pathophysiologic significance of increased polyol pathway activity in a variety of tissues affected by Vlll Foreword diabetes mellitus. She insightfully describes the relationship of increased polyol pathway activity to altered metabolism of inositol- containing phospholipids and to changes in various tissue concentra- tions of myo-inositol. Finally, she provides us with a careful review of the existing experimental and clinical studies with a variety of different aldose reductase inhibitors that have been and are being performed in the hope of preventing or reversing long-term compli- cations of diabetes.

One of the hallmarks of aging is the decreased capacity to adapt to changes in the environment. In a constant, controlled environment, it is often difficult to distin guish the functioning of the young organism from that of the old. However, when stresses are applied-temperature stresses, dietary stresses, infection, emotional stresses-the differences are more apparent. Frequently, the response ofthe old is delayed and may never reach the same mag'nitude as the young. These responses, in most cases, are mediated by the neuroendocrine system, which communicates via hormones, neurotransmitters, and related substances. Thus, it is important to understand the age-related changes that take place in the secretion and act ion of these substances and how these changes relate to the well-being of the whole organism. Indeed, the "neuroendocrine theory of aging" proposes that almost all of the characteristics of aging can be accounted for by dysfunction of the neuroendocrine system. A book on endocrine function and aging is particularly relevant at this time. With the advent of the techniques of molecular biology, there has bee an explo sion of knowledge concerning hormone secretion and action. Hormones, pro hormones, hormone receptors, and "second messenger" mediators rapidly are being cloned and sequenced. Such knowledge gives us important insights into the molecular workings of these substances as well as into the genetic hasis of endo crine dysfunction. These new tools are now being applied to the problem of age related changes in endocrine function."

Key questions involved in the treatment of disseminated breast cancer are discussed in this well-presented overview. It is the result of an initiative taken by the Swiss Group for Clinical Cancer Research to reveal the most recent developments in experimental and clinical research. The topics discussed include: the comparison of in vitro cultures of epithelial cells with breast cancer cells, the effect of steroids and their antagonists, the involvement of suppressor genes in tumour progression, the modulation of transforming growth factors by estrogen, and prognostic factors such as cERB-2 and EGF-R in breast cancer.

The present monograph will concern itself with those disorders of the endocrine system, either associated with destruction, interference with function or hyper- function, which are considered to be due to auto-immune processes. Endocrinopathies Non-endocrine auto-immune disorders associated with the endocrinopathies Graves' (Basedow's, Parry's) disease Pernicious anaemia Hashimoto's thyroiditis Vitiligo Idiopathic Addison's disease Myaesthenia gravis Insulinopenic diabetes mellitus Sjogren's syndrome Auto-immune oophoritis and orchitis Rheumatoid arthritis Auto-immune hypoparathyroidism Idiopathic thrombocytopenic purpura Auto-immune hypophysitis Chronic active hepatitis Possibly some cases of infertility Primary biliary cirrhosis due to anti-sperm antibodies Reproduced with permission from Volpe (1977) The above table indicates those organ-specific endocrinopathies considered to be due to auto-immune factors, as well as those non-endocrine, organ-specific auto-immune disorders which may be associated with them (Volpe 1977). It is evident that such disorders, occurring without any obvious external cause, raise the very elementary question of how immune processes directed against self- constituents could be initiated. Generally, of course, the immune system acts as a regulatory and defence mechanism, and disorders of auto-immunity represent breakdowns in this regulatory system. The following chapters will be concerned with the individual components ofthe endocrine system so affected by auto-immune processes; it will first be necessary to provide an initial chapter for the purpose of summarizing some general principles of immunology, in order to place the immune disorders of the endocrine system in context.

Research on the hormonal control oflactation - the subject of this monograph - has long been the major interest of this laboratory. Studies were initiated in the mid 1930s by the late Professor S. 1. Folley, FRS, who directed the work with immense enthusiasm and devotion until his untimely death in 1970. This fruitful area of basic and applied research has, in recent years, attracted widespread attention; there have been many exciting events and developments with a dramatic increase in the number of publications. These events are diverse and include the identification, isolation and sequencing of human prolactin; the identification and isolation of placentallactogens in several ruminant species with recognition of their importance in mammary growth and differentiation; the introduction of highly sensitive bioassay, radioimmuno- and radioreceptor-assay techniques for mammotrophic hormones; the growing clinical appreciation of the immunological and nutritional importance of colostrum and milk to the newborn; the intensification of studies on normal mammogenesis to establish a sound basis for studies on mammary cancer; and the exploitation of the mammary gland, with its characteristic differentiation patterns and multiple synthetic abilities, as a valuable tissue for the investigation of basic mechanisms involved in the synthesis under hormonal control of enzymes and secretory proteins; and for the study of hormone - receptor interactions.

The European School of Oncology came into existence to respond to a need for informa tion, education and training in the field of the diagnosis and treatment of cancer. There are two main reasons why such an initiative was. considered necessary. Firstly, the teaching of oncology requires a rigorously multidisciplinary approach which is difficult for the Univer sities to put into practice since their system is mainly disciplinary orientated. Secondly, the rate of technological development that impinges on the diagnosis and treatment of cancer has been so rapid that it is not an easy task for medical faculties to adapt their curricula flexibly. With its residential courses for organ pathologies and the seminars on new techniques (laser, monoclonal antibodies, imaging techniques etc.) or on the principal therapeutic controversies (conservative or mutilating surgery, primary or adjuvant chemotherapy, radiotherapy alone or integrated), it is the ambition of the European School of Oncology to fill a cultural and scientific gap and, thereby, create a bridge between the University and Industry and between these two and daily medical practice. One of the more recent initiatives of ESO has been the institution of permanent study groups, also called task forces, where a limited number of leading experts are invited to meet once a year with the aim of defining the state of the art and possibly reaching a consensus on future developments in specific fields of oncology.

Progress in basic research has made it necessary to redetermine the possibility of classic endocrine therapy for the treatment of patients with breast cancer. Exemplary, close cooperation between biochemis try and animal and clinical research led to a truly interdisciplinary and international exchange of ideas and experience at a symposium held in autumn 1978 in Heidelberg. We owe our thanks to ICI-Pharma for the kind support of this sym posIUm. The participation of Charles Huggins in the meeting as honorary chairman signified to all participants the meaning of this joint endeavour. It was the same Charles Huggins who through experimental work laid the foundation stone for endocrine ther apy of prostate and breast cancer, and who applied his findings clinically. Thousands of patients owe to him relief from their suffering. He contributed greatly to the attempt to find and stabilize the endocrine therapy for breast cancer, for which we thank him sincerely. We hope that the following contributions will similarly serve the well-being of our patients."

This volume is the product of a symposium held on 14-16 February, 1985 in Ham- burg in honour of the 65th birthday of Prof. Hans-Joachim Schumann. Schumann was born on 28 December, 1919 in Stralsund. He studied medicine in Cologne, Greifswald and Rostock. The chair of pharmacology in Rostock was held at that time by Peter Holtz. It was he who first introduced Schumann to pharma- cology in 1944 and who was his Doktorvater (research supervisor). Mter the war, Schumann again worked with Holtz in Rostock and then in Frankfurt am Main. He received decisive stimuli during a research fellowship, in 1956, in Prof. J. H. Burn's department in Oxford, where he also worked with Prof. H. Blaschko. In 1964 he ac- cepted his present position as ordentlicher (full) Professor and Head of the Institute of Pharmacology and Toxicology of the then newly founded Medical Faculty of Es- sen. He has remained in Essen despite being offered the chair of pharmacology in G6ttingen in 1968. It is interesting to observe how in the main lines of his scientific work, which now spans 40 years, Schumann has followed the steps involved in autonomic neuro- transmission from transmitter release to transmitter-receptor interaction.

Publication of this monograph acknowledges great strides made in research on the zona pellucida during the past decade or so. The body of work presented testifies to a resurgence of interest in the zona pellucida, prompted largely by a renewed appreciation of its unique properties and its important functions during early mam malian development. It is gratifying to realize that the zona pellucida has at last achieved a well-deserved attention. Whereas extracellular coats of nonmammalian eggs have been studied intensively for many years, the zona pellucida by comparison, has until now taken a back seat. Fortunately, the research presented here signals an end to this situ ation. Many of the difficulties inherent in working with relatively small amounts of material have been overcome, paving the way for application of a wider variety of experimental approaches to the zona pellucida by a larger community of investigators. Hopefully, this monograph will serve as a catalyst in this regard. As revealed in these pages, application of contemporary experi mental methodologies has had significant impact on both pure and applied research on the zona pellucida. For example, modem im munological approaches have been used to assess molecular fea tures of zona pellucida structure and function, as well as to evalu ate the zona pellucida as a potential contraceptive target antigen."

A variety of new techniques that promise to revolutionize the clinical management of early pregnancy are fully detailed in this state-of-the-art book. Leading international researchers describe fast-moving topics such as embryo manipulation and the diagnosis of congenital abnormalities. The technology of assisted reproduction has made it possible to study living embryonic material for the first time, which has led to rapid advances in our understanding of the human embryo's early development. For example, study of the embryo in the test tube has pointed to early pregnancy loss as a possible cause of later infertility. Even more important, diagnostic tests using sophisticated techniques of molecular biology can be run on single cells before the embryo is replaced in the uterus. Another area of advance is the diagnosis of congenital abnormalities in the first and second trimesters of pregnancy. Great improvements have been made in the techniques of chorion villus biopsy and ultrasound imaging. A spectrum of simple biochemical tests performed on the mother's blood can greatly improve the detection of Down syndrome and other chromosome defects. Together with other developments in the fields of molecular biology and endocrinology, these new diagnostic techniques are the beginning of a new age in clinical human genetics and embryology.

THE STATE oF HoRMONE AcTioN levels were induced in concert with ligand occupa tion of certain membrane receptors and this second AND MoLECULAR REGULATION messenger (cAMP) was postulated to initiate intra cellular phosphorylation of unknown targets. At Molecular Endocrinology and Regulation is a this point, the field ofPeptide Hormone Action also burgeoning field, having experienced a remarkable came into being. period of growth since the late 1960s. At that time, These fields developed together for much ofthe there was no field of Hormone Action. The prevail next decade. Hormone Action Conferences invari ing view of how hormones worked ranged from ably contained talks on both types of receptors and effects on membrane transport of nutrients and progress was rapid and in concert with the explo precursors for RNA and protein synthesis, to effects sion molecular biology. In the steroid field, on the translation of mRN A at the level of ribo progress was more rapid initially, but by the mid somes. Therewas, however, asmallcadreofvoices 1980s, the peptide field attained equal mechanistic that predicted a possible nuclear action on mRN A status and the source of specialized conferences of synthesis. The first such paper was presented at the national endocrine meetings in 1967 and dealt with its own. Steroid hormone action investigators concen hormonal stimulation of oviductal protein synthe tratedonfirst understanding the "pathway" of action sis. It was about this time that a small group of for their hormones."

Physiological, pharmacological and molecular biological data generated over the past three decades have demonstrated the existence of two major families of extracellular receptors, the P1, a family of four G-protein coupled receptors and the P2, a family of at least 12 receptors responsive to purine (ATP, ADP) and pyrimidine (UTP) nucleotides through which adenosine and ATP can function as extracellular messengers. The present two-part volume represents an integrated compendium of invited chapters by leading researchers in the area focusing on advances in the understanding of purinergic and pyrimidinergic signaling systems, their role(s) in tissue function and pathophysiology and advances in developing potential new medications based on the modulation of P1 and P2 receptor signaling processes. The volumes will thus provide the reader with a topical, comprehensive and integrated overview of this important area.

Every year there are new and exciting developments in assisted human reproduction, but how much do we really know about the underlying causes of infertility? This volume explores recent progress in the understanding of the genetics of spermatogenesis and male infertility. Topics include fundamental advances and current problems in the development and function of the testis, an outline of clinical findings in male infertility and an overview of the role of the Y chromosome in male fertility. Comprehensive critiques of posttranscriptional control during spermatogenesis, mammalian meiotic sterility, and comparative genetics of human spermatogenesis from the perspective of yeast, Drosophila and mice provide a global overview of the field.

Quality of the Body Cell Mass presents proceedings of the International Symposium on Quality of the Body Cell Mass held in Fort Lauderdale , Florida. The text describes the states of the art of making measurements of body composition, including the methods and their interactions, and provides examples of applications that describe individual studies in the clinical areas of AIDS, obesity, osteoporosis, aging, wasting, and chronic disease. More than 50 illustrations complement the text.

This book brings together some of the results and ideas produced by a large number of people-colleagues and students with whom I am privileged to work in the laboratory at Rockefeller University. In terms of my personal history I see it as a confluence of creative forces persons from whom I have learned. I was instructed in neuroanatomy by Walle J. H. Nauta at M. I. T., and later in a course at Harvard Medical School under the direction of Richard Sidman. At Harvard Medical School, where M. I. T. graduate students were allowed to cross register, the superb neurophysiology course was under the guiding spirit of Stephen Kuffler. Later, I benefited greatly from participating in his summer course in electrophysiological techniques at Woods Hole. Eric Kandel and his colleagues have provided us with the most exciting contemporary approach to the conceptualization and study of cellular mechanisms for behavior. Here at Rockefeller, Carl Pfaffmann and Neal Miller have been leaders in every sense of the word. Not only did they provide me with opportunities to grow to scientific maturity; they also set an example of clear thinking about mechanisms for mammalian behavior patterns. I wrote this book to show how the systematic use of increasingly detailed electrophysiological, neuroanatomical, and neuroendocrine tech niques can explain the mechanism for a mammalian behavioral response. The behavior in question happens to be sensitive to steroid hormones and plays a central role in reproduction."

Neuroendocrine Perspectives, Volume 7, is part of an international book series designed to keep clinicians and researchers appraised of important trends and new data in basic and clinical neuroendocrinology. It focuses on four very rapidly evolving major topics: - the role of dopaminergic regulation of the intermediate pituitary lobe in elucidating intracellular signal transaction pathways and other regulatory mechanisms involved in transsynaptic regulation of peptide biosynthesis, post-translational processing, and hormone secretion; - the physiological and clinical implications of corticotropin releasing factor for such areas as diagnosing Cushing's syndrome, defining the hypothalamic and pituitary origins of secondary adrenal insufficiency, and distinguishing Cushing's syndrome from psychiatric states associated with hypercortisolism; - the large number of neurotrophic factors that affect CNS neurons and of neurite promoting factors that modulate neuronal performance, with emphasis on their mechanisms of action and their possible therapeutic applications to peripheral neuropathies and central diseases; - and the many factors that regulate changes in female reproductive cycles during middle age, with careful distinction between neuroendocrine and ovarian components and special attention to the possible cause-and-effect relationship within the cascade of events resulting in acyclicity and infertility.

Thyroid carcinoma is an uncommon malignan ing the available non-human lines, as models cy. In the vast majority of patients, if treated for cell cycle studies and oncogene/anti appropriately, it is associated with a benign oncogene regulation, because they are unaware clinical course. Why then does it hold a con of the often fundamental dichotomy between tinuing fascination for so many physicians? thyroid malignancy and prognosis. Third, the The answer is probably directly dependent very nature of the benign clinical course has suggested to the major health research fund on the very benign nature of most thyroid ing agencies that thyroid cancer is not worthy maligllancies. While there are terrible excep of study in a time of scarce resources. tions, the follicular and papillary thyroid can Nothing could be further from the truth. cers behave in a way quite alien to "common" This gratifying clinical course is the very reason neoplasia, since they grow and metastasize why the study of human thyroid cancer has the slowly. We believe that if only we could under potential for contributing further to our fun stand such a transformed state, we would be able to learn a great deal about the normal and damental understanding of malignancy and, abnormal regulation of the cell cycle and im perhaps more importantly, the mechanisms by prove our understanding of cancer. which the human body can resist neoplastic However, recent advances in the biology of cells."

In recent years, a series of excellent textbooks have been published dealing with pathology of the thyroid gland. The present volume of CURRENT TOPICS IN PATHOLOGY provides further information for both pathologists and clinicians interested in the thyroid gland. The contributions deal with surgical pathology of the thyroid as well as with basic aspects of thyroid metabolism, hormone transport, and growth factors in thyroid cells. The topics covered in this book should mainly be considered as adjuncts to common textbooks on thyroid pathology. The contributions should help pathologists in their routine diagnosis and should stimulate further thyroid research.

Obesity is a serious medical problem that affects millions of people, especially in Western societies. Although long considered a complicating factor in a variety of diseases, there is now widespread agreement that obesity itself should be classified and treated as a disease and that it has important conse quences for personal health, quality of life and cost to society. Understanding obesity and the means of treating it have been hampered in the past. There have been misperceptions that obesity is a behavioral disorder and that its treatments provides only cosmetic benefits. Pharmacologic approaches to treatment have suffered from problems of limited efficacy, reduced activity upon chronic use, and serious side effects, including abuse liability, cardiac disease, hypertension, and respiratory complications. Finally, there has been a proliferation of consumer and natural products with unproven benefits. This book attempts to address both the problems associated with obesity and the approaches to treating it. In the first section devoted to pathology, Drs. DIGIROLAMO, HARP, and STEVENS elaborate in Chap. 1 on how obesity and its medical complications develop. As described by Dr. PI-SUNYER in Chap. 2, obesity is a disease seen most often in affluent Western societies and is associated with the aforemen tioned medical problems, as well as Type II diabetes mellitus and gallbladder disease. Drs. CHAGNON, PERUSSE, and BOUCHARD review the human genetics of obesity in Chap. 3, and Drs."

Provides latest advances in diagnosis and management of bone and mineral disorders Part of the renowned Clinical Focus series Focus on skeletal and mineral homeostasis and the role of calcium and vitamin D as nutritional supplements Each chapter highly illustrated with tables and images Internationally recognised editor and author team led by US-based expert in the field

The fact that certain adrenal steroid hormones are immunosuppressive and anti-inflammatory has been known for many years, and is routinely exploited by physicians. These effects are attributable to glucocorticoid steroids such as cortisol. Pharmacological doses of glucocorticoids inhibit most or all T cell types. However we now know that the effect of exposure to raised physiological levels is mainly to drive developing lymphocyte responses towards a Th2 cytokine profile (interleukin-4 secreting) while suppressing the development ofThi (gamma interferon- secreting) lymphocytes. Only recently have two further regulatory mechanisms become appar- ent. First, these effects of cortisol are balanced by pro-inflammatory and ThI-enhancing effects of another adrenal steroid, dehydroepiandro- sterone sulfate (DHEAS). Second, the activity of cortisol is directly modulated by enzymes in the target organs and lymphoid tissues that convert it into inactive cortisone. This new information leads to the possibility that immunoregulatory steroids could be used by physicians in novel ways. We can envisage steroid combinations that exploit the anti-inflammatory effects of corti- sol, while the Thi-suppressing and Th2-promoting properties of these hormones are opposed by derivatives of DHEAS. Such therapies are already proving effective in animal models of infection, and could revol- utionize treatment of Th2-mediated diseases such as asthma, where the anti-inflammatory effects of cortisol are desirable but the effects on T lymphocyte differentiation are not.

A panel of leading experts integrate the latest findings from basic and clinical science to create a comprehensive treatment of the processes by which the brain acts as an endocrine organ, not only to control hormonal functions, but also to maintain homeostasis and regulate behavior. The authors-recognized both as leaders in their fields and as skilled teachers-provide systematic coverage of the analytical, anatomical, functional, clinical, and pathological aspects of neuroendocrinology. Topics range from the interactions between the nervous and endocrine systems to the regulation of reproduction, development, metabolism, fluid balance, and biological rhythms. Neuroendocrinology in Physiology and Medicine offers an unprecedented marriage of clinical and basic knowledge that has been missing from classical neuroscience, endocrinology, and physiology texts. It will teach today's medical students and serve researchers as a valuable reference to this rapidly growing field.