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.

The 1997 European Conference on Spectroscopy of Biological Molecules (ECSBM) is the seventh in a biennial series of conferences devoted to the applications of molecular spectroscopy to biological molecules and related systems. The interest of these conferences rests mainly on the relationship between the structure and physiological activity of biological molecules and related systems of which these molecular species form part. This volume ofECSBM contains articles prepared by the invited lecturers and those making poster presentations at the seventh ECSBM. The reader will find mainly applications of vibrational spectroscopy to protein structure and dynamics, biomembranes, molecular recognition, nucleic acids and other biomolecules and biological systems containing specific chromophors. Biomedical applications of vibrational spectroscopy are expanding rapidly. On the other hand, a significant number of the papers describe applications of other methods, such as NMR, circular dichroism, optical absorption and fluorescence, X-ray absorption and diffraction and other theoretical methods. One aim has been to achieve a well balanced, critically comparative review of recent progress in the field of biomolecular structure, bonding and dynamics based on applications of the above spectroscopic methods. A great part of the contributions included in this volume are devoted to biomedical and biotechnological applications and provide a broadly based account of recent applicationS in this field. The content of this book has been organized in sections corresponding mainly to the different types of biological molecules investigated. This book includes also another section related to theoretical methods where MO calculations of vibrational frequencies dominate clearly the topic.

The localized attachment of circulating leukocytes to endothelium has been recognized as the cellular hallmark of the inflammatory response. This adhesive interaction, a necessary antecedent to the emigration of leukocytes from the blood into the tissues, is mediated by vascular adhesion molecules. Leukocyte Recruitment, Endothelial Cell Adhesion Molecules and Transcriptional Control: Insights for Drug Discovery outlines some of the cellular and molecular mechanisms of inflammation with contributions from top researchers. This volume provides an overview of three of these endothelial adhesion molecules, as examples of key mediators of leukocyte recruitment. It reviews the structure and regulation of these cell surface proteins and focus on the rapidly expanding field of transcriptional regulation of these inducible proteins, and closes with a discussion of drug discovery possibilities that target the regulation of leukocyte recruitment. This book will be of interest for any researchers, in academia or industry, looking for an overview of leukocyte recruitment or novel approaches to drug discovery.

The goal of clinical laboratories is to produce accurate information for clinical decision making in medicine. More than half of the medical decisions made depend on clinical laboratory tests. Patient safety represents an important and critical problem for laboratories. They need to assure that the information they deliver to physicians is accurate, and therefore safe for clinicians to use. Endogenous compounds can interfere with laboratory tests, decreasing accuracy and threatening patient safety. Elevated bilirubin (bilirubinemia) and elevated lipids (lipemia) are common conditions that cause significant interferences with laboratory results. Clinicians depend on laboratories to detect these endogenous interferences. Laboratories must have a means to detect these endogenous interferences, make decisions about reporting results, and evaluate their impact. Most clinical pathology books provide only an abbreviated introduction to the subject, or provide a long list of references, without the necessary foundation for evaluating their significance. Package inserts typically provide scant information. This book provides the empirical and theoretical foundation for these interferences, describes the clinical settings where they occur, and explains their evaluation and detection, allowing the laboratory to interpret the available data on interferences and make the appropriate decision to effectively report test results while protecting patient safety.

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.

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.

Historically we have separated the disciplines of Chemistry and Biochemistry by recognizing that the distinguishing characteristic of Biochemistry is the catalysis of reactions by enzymes. Enzymes permit metabolic reactions which would otherwise require extremes of temperature, pressure or pH, often associated with Chemistry, to proceed under ambient conditions of the body. Under some conditions chemical reactions occur in vivo in which products of enzymatic reactions proceed to undergo further reactions non- enzymatically with cellular macromolecules. The results can often be seen as toxic or carcinogenic responses. The chemicals that initiate these reactions are termed "biological reactive intermediates. " The International Symposia on Biological Reactive Intermediates (BRI) began in 1975 at the University of Turku, Finland and have since convened at the University of Surrey, Guildford, The United Kingdom (1980), the University of Maryland, College Park, Maryland (1985), the University of Arizona, Tucson, Arizona (1990), the GSF Forschungszentrum and Technical University of Munich (1995) and, most recently, at the Universite Rene Descartes, Paris, France (2000). The Symposium was organized by an International Planning Committee co-chaired by P. Dansette (Paris, France) and TJ. Monks (Austin, Texas). The committee included: P. H. Beaune (Paris, France), M. De\aforge (Saclay, France), G. P. Gervasi (Pisa, Italy), G. G. Gibson (Guildford, UK), H. Greim (Munich, Germany), DJ. Jollow (Charleston, South Carolina), P. Moldeus (Sodertalje, Sweden), I. G. Sipes (Tucson, Arizona), R. Snyder PJ. van Bladderen (Zeist, The Netherlands). They were (Piscataway, New Jersey), and assisted by an International Scientific Program Advisory Committee which included: TJ.

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.

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.

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.

The Association Internationale de Recherche sur la Circulation Osseuse, A.R.C.O., was founded in London in December 1989 by a small group of doctors, surgeons and researchers in basic sciences who had been involved for many years in the study of bone circulation and its disorders. They had met several times in Toulouse, during the International Symposia on Bone Circulation held there since 1973 and they wished to carry their contacts further. In founding A.R.C.O., they established as their primary aims the encouragement and furtherance of research, organisation of meetings and promotion of knowledge on the subject. At the present time, the Association has over a hundred members from more than bone tissue twenty countries in Europe, America and Asia. All have the conviction that and its pathology can only be truly known and studied if one has an understanding of its vascular system and the way its circulation functions. This concept, apparently beyond question, has not yet been adopted by all physicians and scientists who are interested in bone. From time to time, one comes across teaching programmes on bone patho logy which make no mention of bone circulation.

Twenty years ago when Children's Cancer Association of Japan was born, the diagnosis of childhood leukemia amounted to a death sentence. Only 20% or so of children with leukemia survived more than 5 years. Since then, enormous improvements have been achieved regarding our understanding on the etiology, diagnosis, and the treatment of childhood leukemia. Now, 70% of children with leukemia survive and enter adult life. Even though the improved survival rate of children with leukemia represents a medical success story, we now face new problems. The first problem is the fact that we still lose 20-30% of patients with childhood leukemia. To address this problem, we need to understand the etiology, epidemiology, and biology of leukemia; to identify the patients at greater risk; and to develop adequate treatments. The second problem is the treatment itself. Even though efficacious, the modem treatment for leukemia is a grueling experience for children and their families. We should develop a total care system for families and children based on a deep understanding of their needs. The third problem is the aftereffects of the treatment and of cured leukemia. Extensive radiation and chemotherapy have an entirely different spectrum of long-term effects on children than on adults. These treatments in the early stage of life, when the mind and body are developing, create many physical and psychological problems. These are the present problems of childhood leukemia.

The study of cultured human tumor cells is a most obvious approach in experimental human cancer research. For many techniques in virology, immunology, biochemistry, and biophysics, for example, large amounts of cells may be required and such quantities are usually provided only when the cultures develop into established cell lines; when this happens, thorough characterization also becomes possible. The development of cell lines, therefore, is of prime importance. Recent major advances in research with animal cell systems see m to be a prologue for present and future efforts directed toward work with human tumor cells in culture. Conceivably, the most significant results in cancer research may develop from work with such cells, and so the time seemed right to define the present state of our knowledge. This is the first book dedicated exclusively to the subject: human tumor cells in vitro. Although so me of the fundamental aspects in the cultivation of human tumor ceIls, and the extent to which they represent human cancer in vivo are still unclear, I asked a number of the leading investigators in this area of research to collect and evaluate previous and present contributions, and to offer their thoughts on the questions to which answers are not yet available. Many of the chapters are concerned with techniques of cultivation. Cultures from some types of tumors have grown weIl; in many cases they have given rise to established cell lines.

Our understanding of inflammation has increased rapidly in recent years, due in large part to the impact of molecular biology and gene identification and cloning. This book brings together ideas from a number of different biochemical disciplines which are frequently not integrated. The first chapter gives a visual overview of the subject; the remaining chapters are organized into three themes: the affector molecules, the regulatory components and the processes of inflammation itself. This book is essential reading for the busy physician or pathologist who wants to be up-to-date with the latest developments in immunology as they affect the diagnosis and treatment of many conditions.

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.

The role of carcinogenic agents in the deveolopment of human cancers is now being defined using a variety of human cells as experi mental model systems. A workshop on "neoplastic transformation in human cell systems in vitro: mechanisms of carcinogenesis" was held at the Georgetown University Medical Center, Washington, DC, on April 25-26, 1991. The aims of the workshop were to present the state-of-the art in the transformation of human cells in culture, as well as to provide insight into the molecular and cellular changes involved in the conver sion of normal cells to a neoplastic state of growth. The following topics were closely related to the theme of the workshops: 1. Derivation of in vitro model systems (epithelial, fibroblastic, and hematopoietic). 2. Factors modulating cellular transformation. 3. Usefulness of defined in vitro model systems for viral, chemical, and radiation carcinogenesis. 4. Multistep nature of human cell carcinogenesis. 5. Role of activated and suppressor oncogenes in neoplastic trans formation. The workshop was organized by J. S. Rhim and A. Dritschilo (cochairmen), G. Jay, J. little, M. McCormick, R Tennant, and R R Weischelbaum. There were 32 speakers, 30 poster presentations, and about 190 participants."

Neurosurgery o/the Future: Computers and Robots in Clinical Neurosurgical Practice and in Training - a Philosophical Journey into the Future Many present day neurosurgeons believe that they already obtain good results in operative surgery with the benefit of the operating microscope and other aids which have become available in the last three decades and that the introduction of computers and robots to the operating theatre is superfluous. However, it is clear from analogy with the function of the airline pilot, another profession where there are great demands on manual skill and on spatial awareness, that these devices do have much to offer neurosurgery. Classical neurosurgery, in the time of Cushing, Dandy and Scarff, was based on a three dimensional picture of the patient's brain formed in the surgeon's mind and often illustrated in elegant drawings. Such pictures were based on neuroradiological studies by pneumoencephalography, ventriculography or by angiography. Generally these stud ies showed the presence and position of a lesion by displacement of normal brain structures and the picture was built up by interference. This was then converted by the experienced neurosurgeon into a plan for the craniotomy site and the trajectory of the surgical approach. Once the brain was exposed further pre-operative information was obtained by visual inspection and by palpation with the brain needle. These classical forms ofneuroradiology have largely been superseded by computerised tomography and by magnetic resonance imaging."

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.

Alcohol and other drugs of abuse are major contributing factors to liver disease and its pathology. Alcoholic cirrhosis causes thousands of deaths each year in the United States, and encourages liver replacement. A better understanding of the mechanisms of liver pathology will significantly aid basic researchers and physicians in treating and preventing liver damage. This book is designed especially for those researchers wishing to understand alcoholic liver disease. Therefore the role of alcohol in changing nutrition and its nutritional effects on liver disease are reviewed. The generation of free radicals during alcohol use has been found to be an important cause of membrane changes, of cancer development, and of lipid alterations-and thus of liver pathology. In addition to alcohol, other drugs of abuse, including morphine, cocaine, marijuana, and caffeine have also been shown to be significant contributors to liver pathology. The prevalence of drug and alcohol use and abuse today means that liver disease will continue as a major social and medical problem. The explanation of its biological origins cannot fail to help us better understand and treat the disease in the years to come.

Specialists from diverse disciplines discuss the important topics of Tissue Repair and Fibrosis. The Role of Myofibroblast. The Myofibroblast is implicated in many processes, such as tissue repair, fibrosis, and stromal reaction to tumors. This book seeks to provide an overview of the knowledge accumulated since this cell was first describes 25 years ago. Discussions focusses on three main topics: - Cellular and molecular biology of fibroblast and myofibroblasts - Wound healing: experimental models, and - Human fibrocontracted diseases

This comprehensive book, lavishly illustrated with over 700 colour pictures, addresses the subject of bone in internal medicine. It is based on biopsies of bone and first describes the normal range of physiological findings in iliac crest biopsies in young, middle-aged and elderly individuals. The book then deals systematically with the osseous disorders most frequently encountered in internal medicine, and some that would be considered in the differential diagnosis. Numerous up-to-date references are included. The clinical applications of biopsies of bone are emphasized as well as their clinical interpretation; sections on histomorphometry and functional aspects of bone cells are also included. The book will be of particular interest to specialists in internal medicine, endocrinology, nephrology, haematology and oncology, as well as being a bench manual for the practising pathologist.

Recent studies have shown that cells from adipose tissue are capable of trafficking to tumors, thus enabling paracrine action of adipokines from within the tumor microenvironment. Increased tumor vascularization, immune system suppression and direct effects on malignant cell survival and proliferation have been investigated as mechanisms regulated by adipokines. The goal of this book is to discuss data pointing to the role of adipose tissue in cancer and to dissect individual mechanisms through which adipose tissue excess or restriction could influence cancer progression.