If you want practical information on how to use this book please refer to "Note to the Readers" p. VII. Histochemistry and cytochemistry are essential tools in biomedical research and routine service laboratories. Most texts on histochemistry fall into one of two categories: 1. Encyclopaedic texts covering all or nearly all information available on the whole or selected parts of histochemistry. 2. Reviews or surveys of methods found to be useful by the author(s). While the former category often appeals to the more philosophically inclined reader, direct guidance on the selection of technique may be difficult to find. In contrast, the latter category are often excellent sources for details on how to perform a particular method with a reasonable chance of success. Consideration of the exact mechanism of staining, of possible reasons for failure, and of alternative techniques are, however, frequently lacking. This book is an introduction to the scientific basis of histochemistry and is intended to provide a background for the selection and development of appro priate methods. It is not a "cook book" and readers expecting exhaustive methodological descriptions will be disappointed. Although most ofthe contributors to this book would not describe themselves as histochemists, they have all at some time found it essential to develop a basic understanding of histochemistry. This book contains the information they would have greatly appreciated ready access to at that time."

Both functions of the mammalian ovary, the endocrine and (synthesis and secretion of steroid hormones) and exocrine (production of ova), depend upon the presence and cyclic growth of follicles, as the depletion of primordial follicles from the ovary leads to cessation of these f-unctions or female reproduction in mammals, or to postmenopausal period in humans. Actually, various fertility and sterility problems at the ovarian level are related to follicles. Therefore, a thorough understanding of the biology of ovarian follicles in mammals is of fundamental interest to a wide variety of academic and scientific disciplines. Study of their structure, function, and control involves mor phology, including ultrastructure, cell biology, physiology, endocrinology, biochemis try, immunology, neurobiology and pharmacology. Zoologists take interest in comparative and evolutionary aspects of biology of ovarian follicles in many different groups of mammals. Agricultural scientists and wildlife biologists need a thorough knowledge of the biology of follicles to control more effectively fecundity in domestic animals and endangered species of mammals. Finally, clinical scientists, toxicologists and physicians want to know the normal and pathological features of ovarian follicles in women, especially in relation to health and the regulation of fertility. Having in view the great importance of studying various aspects of biology of ovarian follicles, numerous papers and reviews on several aspects of ovarian follicles are published annually in a wide variety of scientific journals."

This volume contains the Proceedings of the Serono Symposium on Pre implantation Embryo Development, held in Newton, Massachusetts, in 1991. The idea for the symposium grew out of the 1989 Serono Symposium on Fertilization in Mammals* at which preimplantation development was the predominant suggestion for a follow-up topic. This was indeed a timely subject in view of the recent resurgence of interest in this funda mental phase of embryogenesis and its relevance to basic research and applied fertility studies in humans, food-producing animals, and endangered species. The symposium brought together speakers from a broad range of disciplines in order to focus on key regulatory mechanisms in embryo development, using a wide variety of animal models, and on representative topics in human preimplantation embryogenesis. The culmination of preimplantation development is a blastocyst con taining the first differentiated embryonic tissues and capable of initiating and sustaining pregnancy. The central objective of the symposium was to throw light on the regulation of cellular and molecular events underlying blastocyst formation. It was particularly appropriate that the date of the symposium marked the 20th anniversary of the publication of the classic volume Biology of the Blastocyst, the proceedings of an international workshop held in 1970. This book, which summarized most of the information then available on this topic in mammals, was edited by the pioneer in blastocyst research, Dr. Richard B1andau, who was the guest speaker at the symposium."

Endocrinologic investigations during pregnancy have focused in the last decades on placental hormones, the maternal endocrine system and maternal fetal interactions. Less is known about the fetus itself and the interaction of fetal hormonal response and physiological parameters. In this book physiologists, pediatricians and obstetricians active in experimental studies in both physiology and endocrinology combine both aspects of investigations. Historical remarks on the endocrine development of the fetus are followed by observations of the hormonal control of the cardiovascular system. Basic mechanisms of fetal endocrine control such as brain development, fetal growth, fetal behaviour, and thermoregulation are given particular consideration. Finally, carbohydrate metabolism and the mechanism of parturition are outlined.

I was gratified by the most favorable reception and wide usage received by the first edition of this book. A decade seems to be a short period for a book on pathology, and yet it witnessed many important changes of concepts, along with a formidable growth of knowledge. The second edition required extensive reorganization. There are new chapters on mitochondriopathies, on peroxisomal diseases and on spongy myelino pathies. Major revisions and new additions were necessary in many chapters, for instance those on the dysplasias of the cerebral and of the cerebellar hemispheres, which were largely reorganized. The chapters on perinatal pathology were reordered and reorganized to give a more logical sequence of prenatal, perinatal and postnatal lesions. The entire text was worked over for brevity. A wealth of new references was added with the. aim of staying abreast with the literature up to summer 1988. All refer ences were double checked for errors. My gratitude goes to Mrs. Gisela Ropte and Mrs. Cynthia Bunker for their untiring, diligent help. As a result, this second edition is an essentially rewritten text. Advance in the prevention of human suffering is based on a thorough understand ing of the nature of disease. I hope that this text will continue to be of service in this behalf. Perhaps it may also reflect and foster the intellectual curiosity which makes the "reading of brains" so interesting an occupation. Gottingen, 1989 Reinhard L.

With the discovery of an ever increasing number of biogenetic polypeptides in the autonomic nervous system, it is evident that nervous transmission is controlled and modified not only by a series of classical transmitters but also by a variety of co-transmitters and modulators. Purifi- cation, characterization and synthesis of neuropeptides and peptide families allows the application of specific anti- bodies for radioimmunological, immunohistochemical and immunocytochemical localization. Transmitter interactions and phenotypic neuronal plasticity can be analyzed by pharmacological or surgical manipulations. Biochemical and autoradiographic determination of specific membrane receptors enables the recognition of peptide target struc- tures. In addition, neurophysiological techniques in combi- nation with histochemical methods result in functional interpretations. With regard to somatic manifestations of autonomic nervous disturbances these studies will offer fundamental insights for clinical medicine. This volume contains the refereed proceedings of recent investigations on histochemistry and cell biology of auton- omic neurons and paraganglia which were presented at an international colloquium on nervous transmission in Heidelberg in September 1986. The colloquium was origi- nally planned to be held under the presidency of Olavi Eranko but was continued by the editor after his death. It was sponsored by the German Research Foundation and took place on the occasion of the 600th anniversary of the Heidelberg University "Ruperto Carola" as part of the pro- gram in the international "Wissenschaftsforum". Hopefully, the information provided in this book will stimu- late new ideas and research strategies in the field of neu roscience.

A little picture is worth a million words. Chinese proverb Prenatal human development is an extremely complicated process related to genetics, biochemistry, anatomy, and physiology. There are no developmental changes, either chemical or morphologic, without simultaneous changes in molecular organization. The astonishing buildup ofbiostructures always precedes their proper function. The development of an embryo is genetically coded and is based on interactions related to the selective switching on and off of genes. Interactions are cell-to-cell mediated, mediated by extracellular fluids, or mediated by special pathways. Every substance involved in developmental is to be recognized by its target. interactions, before triggering a metabolic or a morphogenic event, Complex physical and immunologic recognitions are involved in the process of differentiation. Small pieces of evidence are collected to create a mosaic picture elucidating the development. This picture is fascinating and represents the biggest biological puzzle: the puzzle of development. There is no doubt that analysis of human prenatal development is a basis for understanding normal and pathologic relationships between structure and function. Today, there are approximately 2000 different inborn congenital anomalies and syndromes. This book attempts to present a complete realistic account of human morphogenesis, the differentiation of structures, using direct photographs of normal specimens obtained from legal medical abortions of unwanted pregnancies. Emphasis has been placed on contemporary techniques: histochemistry and scanning electron microscopy. The text is as simple as possible; meticulous detailed anatomic descriptions have been omitted.

Our knowledge of chromaffin tissue has increased enormously since the last comprehensive treatise in this series was published in 1943, chiefly as a result of the development of new histological methods and technical improve- ments. Less than 40 years have passed since the review by MAX WATZKA, and essentially only 25 years were required to accumulate an abundance of revolu- tionizing findings: it was not until 1957 that the carotid body was first studied successfully with the electron microscope. In 1962 the technique of formalde- hyde-induced fluorescence was introduced, yielding a view of adrenergic struc- tures that was completely new and far better than that obtained with the chro- maffin reaction. Immunohistochemistry made it possible to localize enzymes responsible for catecholamine synthesis and to detect peptide hormones. Autora- diographic techniques were used at the level of the electron microscope, the method of chemical sympathectomy was introduced and still other technical improvements could be mentioned. I myself have been interested in chromaffin cells and sympathetic neurons since 1965, when I entered the Department of Histology, University of Vienna, as a medical student. Therefore I have not followed the developments mentioned above retrospectively, but have actually experienced them. Anyone who experi- ences such a development comes to believe that he is well acquainted with the various results and interpretations and is thus capable of objectivity.

In 1980, the IVth International Cyclic Nucleotide Conference was held in Brussels. As this meeting attracted many investigators involved in cyclic nucleotides and calcium role in intracellular regulation, it was thought that this opportunity could be used to organize, prior to the Congress, an in-depth introductory course on the subject. This was carried out as a NATO Advanced Study Institute. The participants included Ph. D. students and M. D. s engaged in a research training, but also fully trained and well known researchers who wanted a refresher course on the whole subject. During the course, most of the participants and lecturers asked to be provided with a text summarizing the basic lectures of the course. This book was therefore conceived as a basic textbook on the regulation and action of intracellular signal molecules, concentrating mainly on cyclic nucleotides and calcium. It was deliberately kept at a basic level. We would therefore be happy if it could be used as an introduction for interested M. D. s or Ph. D. s working in other fields or entering this field and as a general refresher for researchers interested in the subject. For this reason, very general schemes have been asked of the authors, along with reading lists of available reviews rather than extensive bibliographies. The editors should like to thank the NATO Scientific Affairs Committee for having supported the course and Mrs. Gh. Wilmes who prepared the manuscripts. S. SWILLENS J. E.

Life is always intimately bound up with structure and with the continuous transformation which structures undergo. Modern science and technology have now made it possible to display these structures before our eyes, right up to the frontiers of molecular dimensions. When several years ago Dr. HANS LUDWIG, while working at the First Department of Obstetrics and Gynecology of the University at Munich, demonstrated to us some micrographs showing the human oviduct's surface pattern, my immediate reaction was: This is the environment that encom passes the very onset of an individual human life. In fact, scanning electron microscopy, superimposed upon classical micro morphology, has enabled us to get insight into the landscape of living structures, their intricate organization and their delicate beauty as well. At the same time this technique opens up an entirely new perspective in our three-dimensional view and comprehension of biological events. This becomes especially evident in the realm of reproductive processes within the human female reproductive tract. In this volume the authors give - for the first time systematically - a description of the surface patterns of the inside of the human vagina, ecto and endocervix, and the human uterus and oviduct; they depict ovulatory alterations of the ovarian surface and surface changes under various endo crine conditions, as well as in relation to the menstrual cycle, pregnancy, fetal growth, and the menopausal cessation of ovarian functional activity. of the placental intervillum, the In addition they describe surface structures basal plate and the amnion."

, Jean ANDRE Universite de Paris XI, ORSAY, France. Sperm cells have long been considered as the most highly specialized of all living cells. They surely are, being very diverse, very complex, containing organelles which do not exist in any other cell -such as acrosome or crystallized mitochondria- and being endowed with a very unique behaviour, that is to meet and recognize the ovum, pierce its protective envelopes and inject into its cytoplasm a most precious deposit, the haploid genome of the species. It is Baccio Baccetti's merit to have felt the need for a confrontation of the scientists working on sperm in order to clarify the apparent complexity of the enormous amount of knowledge accumulated on the subject. Thus, he successfully inaugurated the series of the InternationaZ Symposia on SpermatoZogy. The Seillac edition is the fourth in the series. After an initial stage during which morphology was predominant, our meetings have turned more and more towards function. It has been the will of the French Organizing Committee to devote this meeting mainly to Eutherians, and, among those, to man, in connection with the conflicting necessities to help the sterile couples and to contrul the population explosion at the surface of the world.

In the last two decades, investigations at the cellular level have progressively gained ground in the context of hypertension research. This choice of approach is due to some extent to the build up of know-how that molecular and cellular biology have been producing at a continuous rate. As the contents list of this volume shows, a large mass of work has been directed to gaining some insight into pathogenetic mechanisms. The pathogenesis of primary hypertension has been progressively categorized as a distinct biological problem, not amenable to the theoretical models that proved successful in understanding the nature of secondary forms of hypertension. At the same time, great efforts have been made to simplify this problem by sorting out, if possible, a few crucial mechanisms from the network of contributory factors in the regulation of blood pressure. The idea that what is to be sought is a primary structural and/or functional fault in arterial muscle has met with widespread acceptance. The strength of this argument lies in the fact that peripheral vascular resistance is increased in all forms of hypertension and, in turn, the diameter of resistance vessels is the dominant factor in the computation of total per ipheral resistance. On the basis of this, cardiovascular structural adaptation was proposed as a positive feedback mechanism tending to maintain hypertension, once begun, whatever the initiating factor is.

The hypothalamus is a vitally important component of the vertebrate nervous system, being involved in the regulation of the pituitary gland, the autonomic nervous system, and the central and peripheral motor systems; and implicated in such functions as reproduction, feeding, drinking, aggression, vigilance, and some other not clearly understood motivational processes. The development of the hypothalamus is generally recognized as an important field of inquiry, and many studies are available that deal with the biochemical, electrophysiologi- cal, morphological, and behavioral maturation of one or another component of this unique brain region. However, comprehensive studies of the development of the hypothalamus are scant. Some of the early attempts have been reviewed by Diepen (1962). Among the more recent studies, some in the context of de- scriptions of the development of the entire diencephalon, are those by Rose (1942) in the rabbit; Luyendijk (1944) and Niimi et al. (1962) in the mouse; Auer (1951) and Keyser (1972) in the hamster; Stroer (1956), Coggeshall (1964), and Hyyppa (1969) in the rat; and Gilbert (1953), Kahle (1956), and Richter (1965) in man. Thymidine radiography was utilized in the study by Ifft (1972) in the rat, Shimada and Nakamura (1973) in the mouse, and Wyss and Sripanid- ku1chai (1985) in the cat.

This volume documents our growing understanding of the human major histocompatibility complex. The application of this information is ever more important as the limits of transplantation continue to be reduced, including the recent success of bone marrow transplantation between unrelated but closely matched individuals. In addition, the need to transfuse platelets in the face of immunologic barriers continues to challenge transfusion services. Thus, the serologic information summarized in this volume is essential for optimal patient care. At the same time, recombinant DNA technology has led to a revolution in our understanding of many aspects of basic biology. Among the advances has been the initial characterization of the structure of some HLA loci. While this will ultimately improve clinical services, constant reference to serologic data is essential so that the powerful new techniques can be applied in the most effective ways. The timing of the First Red Cross International Histocompatibility Workshop is fortunate as it brings together experts from around the world to address the state of the art. We are all grateful to Dr. John Lee and his colleagues for organizing the workshop, and for bringing together in this volume the material to be presented in Beijing during October 17-23, 1990. Leon W. Hoyer, M.D.

During the past three decades, histology has seen enormous progress, thanks to new techniques and new investigation instruments. Numerous discoveries of important structures and morphofunctional phenomena have been described in a wealth of papers of ever increasing size and complexity. These publi cations have become difficult to follow, not only because of their number, but also because of a disparity of terminology and the multitude of synonyms employed by different authors. All of this makes reading and comprehension of the progress that has been achieved laborious, even for histologists, but especially for students, researchers in other basic branches of medicine, or clinicians who have to consult histological texts during their studies or investigations. In order to facilitate the orientation of all those interested in histology, a concise and practical volume in encyclopedic style, defining and, at the same time, illustrating fundamental histolog ical terms, enumerating synonyms, and describing morpho functional phenomena has become necessary, both because a work of this genre does not exist and because the list of Latin terms elaborated by the International Anatomical Nomenclature Committee in 1977 does not give illustrations or definitions of histological terms. The present work attempts to redress this deficiency."

Surgeons confronted with acute trauma are frequently under great pressure to act quickly. Only a few have an infallible three-dimensional memory as regards the different approaches necessary for treating fractures by inter nal fixation. Thus there is a real need for a reference book on the approaches to the shoulder, arm, pelvis, and leg which is instructive and based on clinical practice. This is true both for the emergency situation and for the "evening before" with the imperative preoperative planning. THOMAS RUEDI, himself a surgeon as well as a gifted illustrator, in coopera tion with ARTHUR VON HOCHSTETTER, a clinical anatomist, and excellently interpreted by the artist ROBERT SCHLUMPF, has created a novel and impres sive atlas. The surgical approaches are depicted in a manner which is ana tomically correct, limited to the essentials, and realistic. In addition, the attractive, black-and-white illustrations of the anatomy are successfully sup plemented by color schematic drawings. This luxuriously prepared edition may become a daily advisor to surgeons dealing with trauma. It deserves a widespread distribution in surgical depart ments and reference libraries.

The eye has fascinated scientists from the earliest days of biological in vestigation. The diversity of its parts and the precision of their interaction make it a favorite model system for a variety of developmental studies. The eye is a particularly valuable experimental system not only because its tissues provide examples of fundamental processes, but also because it is a prominent and easily accessible structure at very early embryonic ages. In order to provide an open forum for investigators working on all aspects of ocular development, a series of symposia on ocular and visual devel opment was initiated in 1973. A major objective of the symposia has been to foster communication between the basic research worker and the clinical It is our feeling that much can be learned on both sides from community. this interaction. The idea for an informal meeting allowing maximum ex change of ideas originated with Dr. Leon Candeub, who supplied the nec essary driving force that made the series a reality. Each symposium has on a different aspect of ocular development. Speakers have concentrated been selected to approach related topics from different perspectives."

Filling a gap in the anatomical and ENT literature, the authors show the various approaches to the middle ear which allow safe surgical manipulations, such as through the tympanic membrane or the Eustachian tube.

The eye has fascinated scientists from the earliest days of biological in vestigation. The diversity of its parts and the precision of their interaction make it a favorite model system for a variety of developmental studies. The eye is a particularly valuable experimental system not only because its tissues provide examples of fundamental processes, but also because it is a prominent and easily accessible structure at very early embryonic ages. In order to provide an open forum for investigators working on all aspects of ocular development, a series of symposia on ocular and visual devel opment was initiated in 1973. A major objective of the symposia has been to foster communication between the basic research worker and the clinical community. It is our feeling that much can be learned on both sides from this interaction. The idea for an informal meeting allowing maximum ex change of ideas originated with Dr. Leon Candeub, who supplied the nec essary driving force that made the series a reality. Each symposium has concentrated on a different aspect of ocular development. Speakers have been selected to approach related topics from different perspectives."

In 1974 The National Institute on Aging established a somatic cell genetic resource for aging research at the Institute for Medical Research in Camden, New Jersey. Within this program there is a yearly workshop to promote theory and concept develop ment in aging research with the specific purpose of addressing the use of genetically marked cells for aging research and to stimulate interest in aging research by workers in a variety of disciplines. This monograph, The Regulation of Cell Proliferation and Differentiation, is the result of the first workshop held May 15-17, 1975. The concept of the workshop was to consider two main areas: First, a discussion of clinical syndromes expressing as a major manifestation excessive growth, deficient growth or failure to thrive; and second, to present work in cellular and molecular biology on a model system suitable for in vitro study of regulation of cell proliferation and diff2rentiation. The model selected for this was skeletal muscle. It has been widely accepted that normal somatic cells from individual human donors display limited replicative lifespans when cultivated in vitro (1,2). That such "clonal senescence" may be related to in vivo aging is suggested by observations relating the replicative lifespans of cultures to donor age (3-5,13) donor genotype (4-7) and donor's tissue of origin (5,8). A variety of theories have been developed to explain in vitro clonal senescence (9)."

This volume of Molecular Biology of Hematopoiesis is dedicated to many inter national scientists and clinicians for their contribution to the field of Hematology/ Oncology presented at the 11th International Symposium on Molecular Biology of Hematopoiesis, which was held in Bormio, Italy, June 25-29, 1998. The continuous support of the Presidents of the meeting, Professor F. Takaku, President of Jichi University, and E. D. Thomas, Nobel Laureate, was greatly acknowledged, especially Professor Takaku, for his vision and support for development of gene therapy in Japan. New information on BMT for autoimmune disease and organ transplantation was presented at the symposium and is published in this volume. Several new findings on gene therapy/transfer into HSC were presented by E. F. Vanin and A. Nienhuis, K. Humphries, 1. A. Nolta, H. E. Heslop, and M. K. Brenner. Professors S. Asano and K. Tani presented new studies on gene transfer into primates. Among the highlights were the new papers on gene transfer presented by G. Wage maker, N. G. Abraham, and M. Onoderea from R. M. BJaese's group. The use of BMT for organ transplant and autoim mune disease was updated and a representative paper is presented in this volume."

Heme oxygenase is rapidly taking its place as the centerpiece of multiple inter acting metabolic systems. Only 25 years ago heme oxygenase and its metabolic prod ucts appeared to be merely a simple metabolic system-one substrate, heme; one enzyme, heme oxygenase; and one set of products, iron to be recycled, and bilirubin and carbon monoxide to be disposed. From a group of about 25 people in 1974, as judged by attendance at various Gordon conferences, heme oxygenase has, in the year 2000, attracted working scientists-and clinicians I might add-by the hundreds and has produced referenced publications by the thousands. It is well-deserved attention. Heme oxygenase system is now similar to the metabolic networks surrounding glucose in those complex maps of glycolytic and non-glycolytic metabolic pathways, which we had to memorize as students. The relevance of heme oxygenase to regulatory biology was recognized many years ago, but the work conducted over the past five years has created a new wave of emphasis focusing on genetic manipulation to alter heme oxygenase gene expression, the regulatory actions of heme oxygenase products including carbon monoxide, and the significance of changes in the heme oxygenase system. The physiological and pathological relevance of heme oxygenase in the brain, heart, liver, bone marrow, organ transplant, lung and kidney, opens many areas of investigation in various dis ciplines. Advances in the pharmacology of bilirubin and its ability as an antioxidant have provided a new avenue in clinical research.

This chart illustrates general shoulder and elbow anatomy. It shows anterior, posterior, lateral, and superior view of the shoulder. It also shows the socket of shoulder joint anterior and dislocation of humerus and illustrates impingement syndrome and acromioclavicular separation. It shows sagittal view of the elbow, as well as supination, pronation, and superior views of extension and flexion, and illustrates elbow fractures and tennis elbow.

We have considered it to be a demanding assignment to provide a complete exposition dealing with the nature of radiation, its effects, and protection against it to workers in health-related activities. "Radiation" (and more precisely "ionizing radiation") is emitted by X-ray machines, nuclear reactors, and nuclear weapons, but also comes from natural sources to which we are all exposed. It would have been easier to deal with this subject area with the terminology and mathematics employed by specialists. However, although most of the potential readers probably have obtained further pertinent knowledge, we assume no more than a high school education in science and mathematics and the challenge was to provide maximum information within this constraint. This book contains five sections: (A) Radiation Physics, (B) Radiological Physics, (C) Radiation Biology, (D) Radiation Effects on Human Populations, and (E) Radiation Protection. Each section is preceded by a synopsis covering its essential features. It provides sufficient information to enable readers to obtain a general under standing of the subject of the section and an adequate background for comprehension of other sections. The more detailed presentation in the bulk of each section is followed by appendixes that generally contain more advanced topics. This scheme necessarily involves some repetition but permits a more flexible approach for readers who are especially interested in the contents of particular sections.

Prior to the emergence of the sliding filament model, contraction theories had been in abundance. In the absence of the kinds of structural and biochemical information available today, it has been a simple matter to speculate about the possible ways in which tension generation and shortening might occur. The advent of the sliding filament model had an immediate impact on these theories; within several years they fell by the wayside, and attention was redirected towards mechanisms by which the filaments might be driven to slide by one another. In terms of identifying the driving mechanism, the pivotal observa tion was the electron micrographic indentification of cross-bridges extending from the thick filaments. It was quite naturally assumed that such bridges, which had the ability to split ATP, were the molecular motors, i.e., that they were the sites of mechanochemical transduction. Out of this presumption grew the cross-bridge model. in which filament sliding is presumed to be driven by the cyclic interaction of cross-bridges with complementary actin sites located along the thin filaments."