There is a large and rapidly growing body of literature on the importance of mag nesium in biochemical and physiological processes. There is also much evidence that magnesium deficiency, alone and in combination with agents that interfere with its utilization, is associated with functional and structural abnormalities of mem branes, cells, organs, and systems. The manifestations of the changes caused by magnesium deficiency depend upon its extent and duration and on variable factors. Among the conditions that increase the risk of magnesium deficiency are (1) meta bolic factors that affect the absorption, distribution, and excretion of this mineral; (2) disease and therapy; (3) physiologic states that increase requirements for nutrients; and (4) nutritional imbalances. Excesses of nutrients that interfere with the absorption or increase the excretion of magnesium-such as fat, phosphate, sugar, and vitamin D-can contribute to long-lasting relative magnesium deficiency. All have been implicated in several of the diseases considered in this book. Whether their influence on the need for magnesium is a common denominator remains to be investigated further."

The present volume contains the scientific contributions to the Fifth International Symposium on "Current Trends in Sphingo lipidoses and Allied Disorders" under the auspices of the Isaac Albert Research Institute of the Kingsbrook Jewish Medical Center, the Department of Pathology, Downstate Medical Center, State Uni versity of New York, Brooklyn, New York, and the National Tay-Sachs and Allied Diseases Association, Inc., New York. A review of the four previous Symposia shows the increase in scope of the scientific exploration in this rapidly expanding field. The first meeting, held in 1958, was devoted to the discussion al most entirely of Tay-Sachs disease. The majority of the work emanated from local laboratories. The participants at the present Symposium came from many other domestic and foreign research in stitutions. The scope of the papers presented at these meetings and the interest shown in the Symposium demonstrates the signifi cance attached by the scientific community to the problems of these hereditary diseases. The reasons for this are apparent, when one considers the contributions during recent years to our basic know ledge by lipid and enzyme chemistry, genetics, and neuropathology. Partly because of the hereditary nature of these diseases any new discovery in this field has general meaning and permits cautious generalization well beyond its clinical significance."

Reproduction is, it would appear, a very simple biological event: the result of an act of love. In actual fact, it has always been, and still continues to be, one of the most complex, yet at the same time, most fascinating, problems, with which Science has ever been engaged. Physiopathology of human reproduction has always made use of investigations of a morphological nature, perhaps on account of the need to "see inside" the reproductive apparatus or within the gonads themselves in order to better understand how they function. Observation of spermatozoa practically coincided with the discovery of the microscope, and histological study of the testis and ovary was, for a very long time, the only means available with which to closely follow the evolution of gametes destined to their meeting. Improvement of techniques resulting from the evolution of endocrinology of reproduction has only apparently put aside morphological techniques, whilst at the same time there has been a gradual development of ultrastructural techniques, on the one hand, and, on the other, macroscopic diagnostic systems through images.

Experts from Europe, Japan and the United States have contributed to this in-depth volume on digestive disease pathology. Each chapter contains numerous electron micrographs, often supplemented byline drawings, and extensive references to the literature.The clear illustrations and text are an excellent aid for the diagnosis of pathological entities in the gastrointestinal tract.

In a condition of such complexity as bronchial carcinoma and at a time when the scientist's understanding of malignant disease is still incomplete, it is inevitable that views within the medical profession will proliferate. This book is an attempt to assemble these views in the light of 33 years of surgical experience and is intended for those specialists who will be concerned with the diagnosis and treatment of lung cancer in the foreseeable future. The wide clinical experience of the contributing authors has ena bled every aspect of this disease to be considered, with emphasis being placed on diagnostic techniques such as CT scanning and fine needle transpleural biopsy, as well as on the latest method of treatment by lasers. Bronchial carcinoma remains the major cause of cancer death in the United Kingdom, accounting for 60Jo of all deaths. While the incidence has decreased slightly in the male population, there has been an equivalent increase in the female population.

Biotargets of Cancer in Current Clinical Practice presents an updated and reasoned review of the current status of knowledge concerning the major cancer types with a special focus on the current biomarkers, genes involved and the potential future targets of innovative therapies. The volume includes for each major cancer type, a comprehensive although concise discussion of epidemiology, affirmed and innovative biomarkers for diagnosis, and descriptions of the relevant genes for prognosis and (individualized) therapy through biotarget-specific new molecular treatments, with the latest information on the validation status of each novel biomarker. Individual chapters are dedicated to the major cancer types, plus a special chapter on metastasis. The present debate on patentability of genetic information applied to diagnostics and therapeutics of cancer is also discussed.

Autoimmune myasthenia gravis (MG) is a classical autoimmune disease, for which the target antigen, nicotinic acetylcholine receptor, has been cloned, sequenced and biochemically characterized. Antibodies to acetylcholine receptors destroy acetylcholine receptor at the neuromuscular junction, thus leading to defective neuromuscular transmission, muscle fatigue, and weakness. In the last few years, rapid advances have been made in unraveling the cellular and molecular mechanisms involved in the pathogenesis of MG, both in the animal model, experimental autoimmune MG (EAMG), and in human MG. Significant advances are being made in characterizing the cells and molecules involved in the autoimmune response to the acetylcholine receptor (AChR). These advances are leading to the development of specific methods of immunointervention in EAMG. Further understanding of the intricate involvement of the major histocompatibility complex (MHC) and non-MHC genes, T cell receptors (TCR), costimulator molecules, and specific cytokines in the afferent and efferent autoimmune response of AChR should pave the way to future antigen/clone-specific therapy of MG. This book is the outcome of the MG workshop proceedings in Mysore, India, 1998. The majority of the chapters in this book are contributed by world-renowned authors and their students. The book not only contains a timely review of specific topics, but also up-to-date findings. Immunologists and neurologists will find, in this volume, the latest in MG/EAMG cutting-edge research. Clinicians will be interested in the applications of the various immunointervention strategies into clinical trials in MG patients. Finally, students will not only be interested in reading the latest in EAMG/MG research, but will also find information to help them develop a future strategy to unravel the precise mechanism of disease. To summarize, in this book, the readers should find up-to-date information related to immunological mechanisms involved in MG pathogenesis and various modalities for possible approaches to immunointervention to treat MG.

This atlas is a practical approach to problems commonly encountered in paediatric tumour diagnosis. It comprehensively covers a wide range of common and unusual entities. Over 300 full-colour illustrations are complemented by a text which is pragmatic and succinct. References have been carefully selected to reflect current thought and well-written reviews. New treatment strategies have led to considerable improvement in the salvage rate and prognosis in childhood neoplasia. Histological diagnosis in this area is fraught with problems and the demand invariably has been for a prompt and accurate histological reporting. The problems although wide-ranging, are particularly manifest in the area of the small round-cell tumours which constitute an important proportion of paediatric cancers. This atlas will be invaluable as a bench manual for the practising pathologist and as a study aid for the trainee. It will also be of interest to all oncologists and paediatricians.

The vasculature of the central nervous system (eNS) is characterized by the existence of the blood-brain barrier (BBB), which can be regarded as both an anatomical and physiological phenomenon. The BBB is formed by a complex cellular system of endothelial cells, astroglia, pericytes, perivascular macrophages and a basal membrane, although the anatomic substrate of the BBB is the interendothelial tight junctions that form a continuous sealing. The BBB serves as an exquisitely controlled, functional gate to the eNS. It not only protects the brain from agents in the blood that could impair neurological function, but also controls the influx and efflux of numerous substances to maintain proper homeostasis and provide the brain with necessary nutrients. The structural and functional integrity of the BBB was shown to be dramatically altered during various diseases of the eNS, including neoplasia, ischemia, trauma, hypertension, inflammation and epilepsy. Recent years research has partially elucidated the mechanisms underlying the development of some of these brain disorders as well as the pathways used by different pathogens, like bacteria and viruses, to initiate eNS infections. The development of in vitro models of the BBB had instrumental role in the understanding of the involvement of the BBB in the pathogenesis of several eNS diseases. The intimate, functional association between the function of the brain and the activity of the BBB makes the later a target for pharmacological modulation that will expand the therapeutic possibilities for a range of neurological diseases.

Toxicological and pharmacological effects arise when chemicals interact with biophysiological functions in discrete cell types. There is a continuing need to screen novel compounds for their potential therapeutic effects, and once these have been "discovered" to understand their molecular actions, as the basis of using such compounds safely and for rational drug design. Pharmacology now uses all of the sophisticated molecular research techniques that are available for the development of safer and more efficacious drugs. Histochemistry has been usefully applied to developing new drugs (and assessing chemical safley) and is potentially cost effective. The need to test novel substances for their potential adverse effects has raised many questions. Toxicological pathology has moved away from the cataloging of lesions towards understanding the basis of the events that underly cell injury, especially for those secondary consequences of chemical injury that lead to malignancy and chronic disease. The focal nature of toxicologic lesions de mands the use of microtechniques to provide data to help understand these questions. Histochemistry is under-utilized, but offers one of the key ap proaches necessary to address the problem of understanding interactions between a cell population and a chemical, the modulation of cellular biochem istryor the presence of a lesion in a test animal can be rationalised in terms of species differences that have no relevance to man as opposed to those that are of clinical significance or represent a warning of dire consequences to man.

This volume contains selected works from the 25th Anniversary of the International Conference on Intracranial Pressure (ICP) held in Williamsburg, Virginia. The theme of the meeting was Intracranial Pressure and Neuromonitoring and focused on all the current state of the art brain monitoring methodologies and their application to brain injury. The brain monitoring techniques covered a wide spectrum from neurochemical monitoring of the injured brain to specialized techniques for assessing shunt function in normal pressure hydrocephalus. It also includes the most recent advances in monitoring of the brain oxygen levels using electrodes or the less invasive Near Infrared Sprectroscopy devices. Controversial issues regarding the management of ICP and CPP or both are also addressed and there are several works dealing with this topic. Of particular interest is the group of papers describing diagnosis and outcome in normal pressure hydrocephalus. It is the first compilation of papers which covers all the latest brain monitoring studies in both ischemia, trauma and hydrocephalus. The manuscripts in this volume have been selected from over 300 abstracts submitted to this international symposium. The abstracts are also published in order to provide the most comprehensive view of the progress made in brain injury research.

Like all specialized areas of medicine, that of joint disease informative. The techniques, practical and interpretive, has become surrounded by a practical mystique and are highly reproducible and simple, allowing them to be applied in any laboratory. jargon specific to itself. The number of clinicians working Although we see this volume as being of value to all in the field is large but the number of pathologists small. interested in joint disease it is specifically aimed at It follows that the majority of pathologists are at somewhat laboratory staff wishing to offer a synovial fluid analytical of an immediate disadvantage when discussing and ana service. Like most cytology we believe much of the cell lysing articular problems with their rheumatological and and non-cell identification and quantitation can, and orthopaedic colleagues. should, be undertaken by trained technical staff. The book In the specific area of synovial fluid examination the is therefore aimed primarily at two groups: pathologists difficulties for the pathologist are compounded because who do not specialize in joint disease and technical staff to date there have been no basic texts that detail the who will be generating the data on which interpretation methods, findings and interpretation of the macroscopic will be based. It is therefore both a text book and a bench and microscopic characteristics of the fluid in the common reference manual. arthropathies. In this book we hope to go some way We do not believe our data or methodology represent towards rectifying this omission."

Alzheimer disease (AD) has become the most common form of dementia in industrialized countries and represents an increasing burden at the economic, social and medical level. In discussing both the biological aspects of AD as well as the cognitive functions involved, Alzheimer Disease - Neuropsychology and Pharmacology presents a comprehensive picture of the pathology and approaches to diagnosis and treatment. Basic research including animal models, molecular and genetic aspects is also taken into consideration. In part I, the biological correlates of AD are discussed. In part II the neuropsychological aspects such as cognitive impairment, loss of functional autonomy and emergence of neuropsychiatric disturbances of AD are outlined. In part III, strategies for effective treatment and prevention of AD are discussed. This book will be a useful source of information for clinicians as well as researchers in the area of neuropharmacology.

Enzymes are bio-catalysts which effect transformation of substrates to products with high specificity. The usage of enzymes in domestic and industrial applications is well known and has been well documented since the early history of civilization. With the advances in understanding of enzymology, usage of enzymes in industrial and biotechnological pro cesses and molecular medicine has proliferated. One of the key factors in the widespread application of enzymes in modern technologies is the development of enzyme immobilization tech niques, which overcome certain practical, functional and economic con straints. Many natural enzymes can be stabilized by immobilization on solid matrices, with most of the activity retained, for a variety of applica tions. An important application of immobilized enzymes is in liquid chromatography. In the last decade, post-column enzyme detection has become established as an important discipline in liquid chromatography. The new detection approach offers more sensitive and specific ways for measuring major classes of biomolecules. Reactors are fabricated by packing the immobilized enzymes into small columns, which can be placed immediately after an HPLC column."

These proceedings of the 5th Prouts Neck Meeting on Prostate Cancer, held in October, 1989, highlight the many advances in the understanding of prostatic growth and function at the cellular and molecular levels which have been registered since the first Prouts Neck Meeting in 1985, a meeting which also focused on the then current concepts and basic approaches to understanding prostate cancer. Inter vening Prouts Neck Meetings in 1986, 1987 and 1988 were devoted to treatment, image cytometry and clinical markers. As before, the Prouts Neck tradition of bringing together an international, multidiscipli nary group of experts for 3 days to exchange ideas and new data, in the relaxed atmosphere of an old iun on the scenic Maine coast, proved to be an ideal combination for a highly successful conference. Accordingly, the Organ System Program of the National Cancer Institute plans to use the Prouts Neck model for future conferences on other solid tumors (bladder in 1990 and kidney in 1991) and will return to the prostate in 1992. A new dimension was added to the current program through the inclusion of a poster session to recognize the research of pre-and postdoctoral investigators. The posters were judged by Drs. Collette Freeman, Frank French, Shutsung Liao, Robert Matusik and Henry Sun. The three winners, in alphabeti cal order, were John Fabian, Robert Getzenberg and Ming Fong-Lin."

In the front material of this book both a foreword and a preface appear. What the content of a preface should be is well understood. It is the author's retrospective account of intent, of the labors to accomplish that intent, and of the content of the book that resulted. What a foreword should be is less obvious. Most properly, it is perhaps the brief testimony of one who knows the accomplishments of the author and the scope of the field and who may direct readers to the book. On some basis, the writer is assumed to have earned the right to undertake such a task. To undertake the writing of a foreword for so considerable a researcher, teacher, and scholar as Alfred Evans can be seen not only as an honor but also as a daunting one. My first thought, in truth, is that this wine needs no blush and that no foreword is needed. As John Rodman Paul Professor of Epidemiology at Yale, Alfred Evans has an established reputation in the field of causality. We have learned from his insights about the evolution of causal thinking as epidemiology passed from the era of the germ theory into that of the search for causes of chronic noncontagious diseases. It was he who drew attention to the effect of specific context in that evolution.

Information is provided from the basic and clinical sciences on the mechanisms damaging the brain from trauma or ischemia. New aspects involve the endoplasmic reticulum, mitochondrial failure, pathobiology of axonal injury, molecular signals activating glial elements, or the emerging therapeutical role of neurotrophins. Experimental issues involve a better analysis of the ischemic penumbra, the salvagable tissue. Therapeutic contributions reach from the environmental influence to gene expression, including neuroprotection, such as hibernation - mother nature's experiment - or hypothermia which is reported to induce cell swelling. Treatment issues deal also with thrombolysis and combination therapies, or with the clearance of adverse blood components - LDL/fibrinogen - by a novel procedure using heparin. Other highlights are discussing the specificities of pediatric vs. adult brain trauma, or the evolving role of the Apolipoprotein-E e4 gene in severe head injury. An update is also provided on an online assessment of the patient management during the pre- and early hospital phase in Southern Bavaria. The empirical observation of neuroworsening is analyzed in further details, whether this is a specificity autonomously driving the posttraumatic course. Finally, the unsolved question why drug trials in severe head injury have failed so far in view of the promising evidence from the laboratory is subjected to an expert analysis.

Metastases determine malignancy. The main attention so far has been focused upon organ metastases. The molecular mechanisms thereof, while far from being totally elucidated, are increasingly well understood. Modern diagnostic tools now enable detection and precise localization of small lesions. In contrast, our knowl edge and diagnostic capabilities regarding metastatic spread to the'lymphatic system are rather limited. However, there have re cently been a number of interesting advances. It is the aim of this volume to submit these developments to detailed analysis. The therapeutic relevance of enhanced sensitivity in detection of lymph node metastases has to be considered in the light of in creased morbidity versus eventual prognostic improvements by modification of therapy. An interesting concept which might im prove diagnostic accuracy while reducing operative morbidity is the "sentinel node" technique. Surgical standards are lacking, however, and many fundamental questions pertaining to precise lymphatic mapping remain unanswered. Whether the sentinel node concept is of general relevance or whether it is applicable in only a few organs remains to be determined. This book offers intensive discussion of the concept from methodological and tu mor biological viewpoints. World-renowned experts with long term involvement in related basic and clinical research provide the reader with a broad survey of actual knowledge together with a critical appraisal of recent and future developments. We sincerely hope this book succeeds in providing an outlook as a reference for all clinicians on future prospects and serving and researchers in this extremely important field.

nd During June 13 -June 23 1996, the 2 EL. B. A. Foundation course on Genome, a NATO Advanced Study Institute, was held at Marcian Marina, Isle of Elba, Italy, - sponsored by the North Atlantic Treaty Organization and the EL. B. A. Fundation. The subject of the course was "Genome Structure and Function" with participants selected worldwire from 15 afferent countries. The purpose of the course and of the resulting book is the study of DNA structure (from the primary to the quintemary) and gene expression in the control of cell function and cell cycle progression; the topics were presented by top experts, covering both structural (cbwn to the atomic resolution) and functional (cbwn to gene level) aspects. The topics were presented by top experts and scientists active in the field, with the goal to give an insight into modm problems of genome study and recent ochievements in related fielm of molecular and cell biology, genetic engineering, biochemistry and biophysics, oncology and biotechnology. This resulting book is intenred to give a broad perspecti ve of the current stand of these fields. The major emphasis is towarm a reep unrerstanang of DNA structure and function in intetphase and metaphase chromosomes, originating by the parallel biophysical (namely NMR X-Ray and neutron scattering, spectropolarimetry, image analysis, calorimetry) and biochemical study conwcted on a wire range of cell systems placing the emphasis on either the higher orrer DNA structure or gene structure and function.

Larry L. Hench June Wilson OBJECTIVE Millions of people presently enjoy an improved quality of life due to prostheses which repair, augment or replace parts of their skeletal system: bones, joints, teeth, etc. However, all replacement parts have a finite probability of survival. The goal of this book is to compare the survivability data for various skeletal prosthesis systems. All data derive from previously published clinical studies. Where possible statistical comparisons are made and the reasons for failure are discussed. THE NEED FOR SKELETAL PROSTHESES We are an aging population with more than 100 million people in the U. S. and Europe over the age of 50 years. An unfortunate consequence of aging is a progressive deterioration of the quality of skeletal tissues. From the age of 30 years there is a decrease in bone mass for both men and women (Fig. 1. 1). However, for women it is much greater and between 40 and 60 years of age the rate of deterioration of long bones and vertebrae of women is especially severe due to hormonal changes. By the age of 70 most women will have lost from 35 to 60% of their bone mass. The loss of volume of cancellous or trabecular bone leads to a large decrease in mechanical compressive strength (Fig. 1. 2). The clinical consequence is an increasing incidence of vertebral collapse. Cortical bone decreases in tensile strength with age (Fig. 1.

How does dietary restriction affect the physiological and biochemical state of laboratory animals? How will the present conclusions affect further research? What are the implications for human health and safety assessment? These are the main questions asked in this book by leading international researchers. After a first look at feeding regimens and diets of laboratory animals, the book elaborates on a variety of age-associated toxicological and pathological endpoints including tumor development. The following sections detail the underlying mechanisms which may induce the broad spectrum of physiological and biochemical changes. This summary of current multidisciplinary research will enhance understanding of the practical applications and implications of dietary restriction.

Given the latest advances in cancer research, which includes basic research and its derived diagnostic, clinical, and therapeutic applications, the book New Trends in Cancer for the 21st Century is written by individuals such as molecular biologists, whose tasks are to decipher, after sequencing the human genome, those new genes and pathways involved in the carcinogenesis process; clinical and molecular pathologists, who apply these discoveries for the molecular diagnosis and characterization of the tumor; and clinical oncologists, who treat patients. Pharmacogenetics introduces new perspectives in the translational fields with the design of drugs against specific targets, which at this moment are in clinical trials phases. This book achieves a state of the art in every field of cancer research and discusses the new perspectives that will open the future for cancer treatment (basic research, new technologies, new drugs, therapies...). For this reason, the book is intended for pathologists, clinicians, and biologists, as well as fellows and students of physiology and medicine.

Glycotechnology brings together in one place important contributions and up-to-date research results in this fast moving area. Glycotechnology serves as an excellent reference, providing insight into some of the most challenging research issues in the field.

Rubin and Damjanov's latest volume of Pathology Reviews highlights the latest progress in the interface of biology and disease. Forefront techniques and experimental models that were once considered exotic or esoteric, are explored here in the context of understanding more fully the processes involved in human disease. Topics include: regulation of liver growth * contractile cells in lungs * mineral formation in bone * folate metabolism * the "riddle of the mast cell" * HLA antigens * interleukin 6 * IgA nephropathy * Goodpasture syndrome * anti-basement membrane glomerulonephropathy * molecular mechanisms of oncogenesis * molecular diagnosis of cancer * inhibition of intercellular communication in carcinogenesis * DNA repair and its pathogenetic implications * human and rat mammary tumorigenesis. Pathology Reviews * 1990 is essential reading for everyone concerned with the mechanisms of disease.