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.

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."

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."

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."

Histochemistry deals with the activities of chemical components in cells, and immunohistochemistry addresses the function of cell types in tissue or organs, such as those leading to acceptance or rejection of grafts or organs. This book is a methods volume focusing on antigen retrieval, particularly methods used in disease-related antigens. Because the book is a methods volume and a lab manual, it will have an audience of pathologists, biochemists, and lab technicians.

The present new version of this popular laboratory manual is at the same time the first one of this text in the English language - and this makes me even a little proud, as it reminds me of probably the first collection of monoclonal recipes in English, written by myself, which circulated for a couple of years in many laboratories. In the meantime many researchers have put enormous effort into improving methods for monoclonal antibody production. The proce dures have become more and more standardized and by this have more and more lost the character of magic secrets. Hinrich Peters and Horst Baumgarten, who had followed this good tradition already in the previous edition, written in German, suc ceeded in making laboratory tricks teachable. They had contributed their own experiences in cell culture and immunology, and were able to engage a number of experienced authors to contribute to the work. They were all willing to follow the general concept of this book, which contains a brief theoretical background for the methods described and presents the procedures in a highly organized structure. So the book has retained its shape as a "cook-book," which I especially like."

This volume is intended to cover research in the field of muscle morphology since publication of the previous edition by Haggquist in 1956. The development of new techniques, coupled with an intensified interest in muscle, has resulted in a vast literature which no single person could review, especially within the limitations of one volume. When I accepted the flattering offer to write a new edition, I quickly abandoned any hope of a comprehensive review. Instead, I tried to consider, within my limits, those lines of research which I believe to be important for the understanding of mammalian and ultimately human muscles under normal, experimental, and pathological conditions. It would be naive to suggest that muscle can be adequately described in purely morphologi cal aspects; I would characterize the results of my effort as "muscle as seen with the eyes of a morphologist." It gives me pleasure to acknowledge the help of several colleagues who read and commented on drafts of individual chapters: Dr. Brenda Eisenberg, Chicago; Dr. Else Nygaard, Copenhagen; Dr. Stefano Schiaffino, Padova; Dr. Michael Sjostrom, Umea; Dr. Lars Erik Thornell, Umea. None of these individ uals can be held responsible for any error or obscurity that persists. Indeed, without their assistance there would have been more. I also thank those col leagues who allowed me to include their published and unpublished material; their names, and also those of the publishers who kindly granted copyright permission, are given in the individual figure captions."

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.

, 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.

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."

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.

The new experimental tools and approaches of modern biology have allowed us to better understand many fundamental properties of the eukaryotic cells. These significant discoveries have drastically changed the diagnostic and therapeutic approaches of modern clinical practice. On April 18-22, 1988, an International Symposium on Cell Function and Disease was held in Monterrey, Nuevo Leon, Mexico, aimed at reviewing some of the most recent advances made in the following five areas: Genes and Human Diseases; Cellular and Molecular Pathology; Infectious Diseases; Brain Transplants and the New Approaches and Techniques with Potential Application to Cell Function and Disease. This book is based on the contributed papers of the symposium. To underline the importance of the clinical approach to the study of cell function and disease a section on this subject was added at the end of the book. The chapters in this volume include contributions by some of the leading scientists of the international scientific community and Mexico. During the course of this international conference, numerous discussions were held by the local and international representatives of the scientific community concerning the creation of an International Center of Molecular Medicine aimed at stimulating further interaction between molecular biologists, biochemists, biophyscists and clinicians. Such ideas received the endorsement and support of the Director General of the united Nations Educational and Scientific Organization (UNESCO), Federico Mayor, the Governor of the State of Nuevo Leon, Jorge Trevino, and the Secretary of Health of Mexico, Guillermo Soberon.

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."

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 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.

In the ever-expanding field of heart research the needs of established re searchers, students and general readers can vary considerably, making it difficult therefore to cater for all types of audience within a single volume. The aim of this book has been to provide a comprehensive and up-to-date review of the structure of the heart, including its cell biology. The ultrastructure of the working myocardium and all portions of the conduction system, together with their development, is covered in detail. Also included are chapters on the morphometry of cardiac muscle, the innervation of the heart, cardiac hyper trophy and regeneration, and the development of the coronary circulation. A detailed review of cardiac muscle in cell culture is also provided. It is to be hoped that readers, whatever their background, will find the information contained herein useful for their needs. This work was supported by a grant from the National Heart Foundation of Australia. The authors wish to gratefully acknowledge the following people for their invaluable assistance in preparation of the manuscript: Professor Yasuo Uehara, D'r. Takashi. Fujiwara, Dr. Peter Baluk, Dr. Seiji Matsuda and Bill Kaegi for providing unpublished micrographs; Fabian Bowers, Patricia Murphy and Janet Bennett for typing; and Lucy Popadynec, Nella Puglisi, Maggie Mackie, Mary Delafield and Liana Butera for assistance with references and figure preparation. THE AUTHORS Contents A. General Introduction 1 Morphology of Cardiac Muscle 8 B."

* The definitive reference work on arterial hemodynamics. * Fully updated and revised to cover all recent advancements in the field.

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.

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.

The 'Formation of the Heart and its Regulation' reviews in considerable detail the major events in heart development and their control via genes, cell-cell interactions, growth factors and other contributing elements. In addition, there is an extensive and useful overview of the field of heart development taken as a whole. The book will appeal to all students and researchers working on cardiovascular development and to pediatric cardiologists.

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.

Dr. Howard House, founder of the House Ear Institute and House Ear Clinic often uses the analogy of planting a seed when referring to establishing the House Ear Institute in 1946. Two grateful patients of Dr. House put forth the idea that his knowledge and innovative skills could be used to expand the understanding of hearing impairment and its treatment. Those two early patients provided the "seed money" to begin the Institute. Since that time, the growth has been phenomenal from a one-man laboratory to a multidisciplinary facility boasting over 175 scien tists, physicians, and support staff, all dedicated to the advancement of otologic research and education. Six years ago after a half-century of remarkable success with prosthetic and device research, the Institute began cultivating a new field of endeavor-cell and molecular biology. Don Nielsen, then the Institute's Executive Vice President for Research and Scientific Director, began exploring the potential for hair cell regen eration and presented his ideas to the Board of Trustees. For a period of six months, we did a lot of fact finding to assess what role the Institute might take in this excit ing new field.

The various chapters of this monograph were originally presented as papers in a Symposium on Joints and Bones which the editor organized for the VIII Inter national Congress of Anatomists held in Wiesbaden, Germany in August 1965. Each chapter represents original research on the structure and/or function of joints and bones. Preparing the manuscripts of these papers for publication required more time than originally anticipated and the editor hereby acknowledges his sincere appre ciation to the various authors for their help and patience. He also wants to express his special thanks to Mrs. ANTOINETTE CATRON, his editorial assistant, without whose help the task would still be unfinished. The interest and assistance of the staff of Springer-Verlag in the publication of this monograph is also greatly appreciated. Ann Arbor, Michigan, USA. February 1966 F. GAYNOR EVANS Contents Electron Microscopy of Normal Synovial Membrane. D. V. DAVIES, and A. J. PALFREY .............................. 1 Biomechanics and Functional Adaption of Tendons and Joint Ligaments. A. VnDIK . . . . . . . . . . . . . . . . . . . . . . . . .. . 17 . . . . Dynamic Considerations in Load Bearing Bones with Special Reference to Osteosynthesis and Articular Cartilage. J. M. ZAREK .. . . . . . . . 40 Intravital Measurements of Forces Acting on the Hip-Joint. N. RYDELL. .. 52 The Ergonomic Aspects of Articular Mechanics. M. A. MACCONAILL . . . . 69 A Longitudinal Vital Staining Method for the Study of Apposition in Bone. M. ]. BAER, and]. L. ACKERMAN. . . . . . . . . . . . . . . . . 81 . . . An Evaluation of the Use of Bone Histology in Forensic Medicine and Anthro pology. D. H. ENLOW. . . . . . . . . . . . . . . . . . . . . 93 . . . .

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.