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Par-4 is a tumor suppressor protein first discovered and identified in 1993 by Dr. Vivek Rangnekar's laboratory in prostate cancer cells undergoing apoptosis. Par-4 (later also known as PAWR) is a naturally occurring tumor suppressor. Studies have indicated that Par-4 selectively induces apoptosis in cancer cells while leaving normal, healthy, cells unaffected. Mechanisms contributing to the cancer-selective action of Par-4 have been associated with protein kinase A activation of intracellular Par-4 in cancer cells or GRP78 expression primarily on the surface of cancer cells. Par-4 is downregulated, inactivated or mutated in diverse cancers. This first of two volumes will be the first on the market on the topic of Par-4, and will provide the opportunity for researchers to discuss the future direction of studies, broaden the scope of research, and contribute a more complete understanding of the molecule's structural features, key functional domains, regulation and relevant basic and clinical/translational facets.

Metabolic programs of individuals are key determinants for disease susceptibility and immune response. This book, edited by experts in the field, summarizes epigenetic signaling pathways that regulate metabolic programs associated with cancer and cancer-related secondary diseases.The first part of the book highlights key metabolic pathways that are implicated in cancer and provides a comprehensive overview on the carbohydrate, protein, lipid, amino- and nucleic acid metabolic pathways that are deregulated in cancer. Special attention is paid to the altered tumor micro-environment that is influenced by the metabolic milieu. Furthermore, the fundamental relationship between the cellular metabolic environment and cell death-mediated autophagy is discussed.The second part of the book covers our understanding of the fundamental epigenetic regulations that are implicated in controlling the metabolic programs in cancer cells. Many aspects of epigenetic regulation of non-coding RNAs as well as DNA/RNA methylation, which influencing metabolic homeostasis in cancer, are discussed in detail. Special emphasis is placed on the epigenetic regulation of the amino acid, glucose/carbohydrate metabolism and epigenetic regulation during hypoxia and its connection to cancer.Last but not least, the third part of the book covers small molecule modulators of histone modifying enzymes, which can be used as therapeutic tools. The readers learn about the cross-talk between epigenetics and immunometabolims, as well as the epigenetic regulation of oncometabolites to combat cancer. Given its scope, the book will appeal to a broad readership interested in epigenetic, cancer and metabolic research.

This edited book helps researchers and practitioners to understand e-health, m-healthcare architecture through IoT and the state of the art in IoT counter measures. This book provides a comprehensive discussion on a functional framework for IoT-based healthcare systems, intelligent medicine box, RFID technology, HMI, cognitive interpretation, BCI, remote health monitoring systems, wearable sensors, WBAN, healthcare analytics, machine learning (ML) techniques for IoT-enabled healthcare services, security and privacy issues in IoT-based healthcare monitoring systems. The book discusses integration of IoT with big data and cloud computing for solving several real-time problems by the use of smart healthcare applications. In these applications, the cloud computing provides a common workplace for IoT and big data, big data provides data analytics technology and IoT provides the source of data. It serves as a reference resource for researchers and practitioners in academia and industry.

This book covers every aspect of radiation myelopathy and considers the evidence from all species in which it has been studied. The historical and current understanding of the pathogenesis of this rare but devastating injury is first discussed. The evidence regarding the role of a variety of factors in radiation myelopathy is then reviewed. Readers will find detailed information on the impacts of total radiation dose, radiation volume, dose fractionation, hyper fractionation, age, anatomic level, comorbidities, radiation modifiers, other therapies, and retreatment of the spinal cord. Given the similarity of the pathogenesis of radiation myelopathy in humans and experimental animals, the potential for cross-species modelling of dose response is explored, with attention to relevant species differences. Treatment of the condition is also fully considered. New theories are presented regarding retreatment, small volume response, and the final step in white matter necrosis. The final chapter addresses the medicolegal issues elicited by radiation myelopathy, which is often the result of treatment error. Radiation Myelopathy will be of high value for radiation oncologists, radiation physicists, dosimetrists, biologists, neurologists, medical oncologists, and attorneys.

This book presents an overview of the current state of research on ultrashort electric field pulses of high intensity and their use in biology and medicine. It examines in detail the most recent and exciting advances in how nanosecond and picosecond electric pulse research has grown and expanded into new areas of biology and medicine. Further, the book specifically focuses on electric pulses in the time domain, on intracellular effects as opposed to plasma membrane electroporation, and highlights the biological and medical applications of these unique pulse effects. Since the authors were initial innovators exploring nanosecond and picosecond pulses, their unique perspectives foreshadowed directions the research took, expanding into new areas that they continue to investigate today.

Microbial biosurfactant compounds are a group of structurally diverse molecules produced by microorganisms, and are mainly categorized according to their chemical structure. The diversity of microbial biosurfactants makes them versatile and means that they offer a range of capabilities, while at the same time being economically sustainable. As such, they have potential applications in environmental processes, as well as in food, biomedicine and other industries. This book discusses innovative approaches and cutting-edge research that utilize the various properties of biosurfactants. Drawing on research from around the globe, it provides an up-to-date review of biosurfactant applications and their importance in fields such as medicine, gene therapy, immunotherapy, antimicrobial bioremediation and agriculture. It also discusses their anti-adhesive properties. The book will appeal to academics and researchers in the field of microbiology, as well as policymakers. It also serves as additional reading material for undergraduate and graduate students of agriculture, ecology, soil science, and environmental sciences.

Recent developments in the field of nutrition have led to increased interest in herbs and medicinal plants as phytochemical-rich sources for functional food, nutraceuticals, and drugs. As research sheds light on the therapeutic potential of various bioactive phytochemicals, the demand for plant extracts and oils has increased. Black cumin or black seeds (Nigella sativa) have particularly widespread nutritional and medicinal applications. In traditional medicine, black seeds are used to manage fatigue and chronic headache. Black seed oil is used as an antiseptic and analgesic remedy and for treatment of joint's pain and stiffness and can be mixed with sesame oil to treat dermatosis, abdominal disorders, cough, headache, fever, liver ailments, jaundice, sore eyes, and hemorrhoids. Thymoquinone, the main constituent in black seed volatile oil, has been shown to suppress carcinogenesis. Black cumin (Nigella sativa) seeds: Chemistry, Technology, Functionality, and Applications presents in detail the chemical composition, therapeutic properties, and functionality of high-value oils, phytochemicals, nutrients, and volatiles of the Nigella sativa seed. Organized by formulation (seeds, fixed oil, essential oil, and extracts), chapters break this seed down into its chemical constituents and explore their role in the development of pharmaceuticals, nutraceuticals, novel food, natural drugs, and feed. Following numerous reports on the health-promoting activities of Nigella sativa, this is the first comprehensive presentation of the functional, nutritional, and pharmacological traits of Nigella sativa seeds and seed oil constituents.

This book deals with the paradoxical role of autophagy in tumor suppression and tumor promotion in cancer cells. Autophagy plays opposing, context-dependent roles in tumors; accordingly, strategies based on inhibiting or stimulating autophagy could offer as potential cancer therapies. The book elucidates the physiological role of autophagy in modulating cancer metastasis, which is the primary cause of cancer-associated mortality. Further, it reviews its role in the differentiation, development, and activation of multiple immune cells, and its potential applications in tumor immunotherapy. In addition, it examines the effect of epigenetic modifications of autophagy-associated genes in regulating tumor growth and therapeutic response and summarizes autophagy's role in the development of resistance to a variety of anti-cancer drugs in cancer cells. In closing, it assesses autophagy as a potential therapeutic target for cancer treatment. Given its scope, the book offers avaluable asset for all oncologists and researchers who wish to understand the potential role of autophagy in tumor biology.

The book provides current knowledge and research on the presence and effects of anticancer drug residues in the aqueous environment and covers all relevant aspects of the presence of these residues in wastewaters and natural aquatic systems, where numerous analogies between their pharmacokinetics and pharmacodynamics in humans and their effects in the environment can be drawn. This book comprises of 18 chapters and represents the combined work of leading scientists from different research institutions from across the globe. We present the state of the art in the field of anticancer drug residues in the aquatic environment while being cognizant of the many challenges that remain.

This book is an outcome of the keynote/lead papers presented by the experts from different disciplines in the Indian Ecological Society International Conference 2016 on “Natural Resource Management: Ecological Perspectives”, organized at the Sher-e-Kashmir University of Agricultural Sciences and Technology of Jammu, India. The book captures the essence of natural resource management from the intra and interdisciplinary perspectives of agricultural sciences (entomology, plant pathology, plant breeding and genetics, agronomy and soil sciences), social sciences (resource economics, agricultural extension education), medical sciences, and environmental sciences to stimulate discussion on the ecological perspectives of natural resource management. Wide-ranging topics on land and water resources, biodiversity, integrated farming system, role of microbes in agriculture, climate change and its impact on human health and crop pests, exploiting chemical ecology for pest management, human disease-causing pesticides, beneficial insects like lac insects, integrated pest management, resistance management in insect pests and Bt cotton, and diffusion and adoption of ecologically sustainable technologies at individual and organizational level are covered in the book.. The book will serve the professionals, researchers, academia, government, industry and students.

This book addresses the causes and effects of nutrient deficiencies along the cell-to-communities continuum. The book is primarily concerned with a lack or deficiency of one or more micro- or macronutrients in connection with malnutrition, under nutrition, and starvation. Embedded within the deficiency states is acute restriction whereby food is withdrawn completely for short periods, as when individuals are adhering to religious requirements or undergoing surgical procedures. Further downstream is the consumption of a fraction of the normal diet, as when individuals are dieting or when there is restriction in the amount or variety of food available. The causes of such reductions in dietary intake are varied and also include the social context of poverty, financial limitations, and famine. Refugees and displaced persons may also be vulnerable to under nutrition or total starvation. Diseases may also impact on the total food consumed, such as when there are physical impediments (intestinal obstruction or dysphagia) or anorexia (induced by organic disease or as a disease process per se, ie, anorexia nervosa). This book, organized as approximately 125 chapters in 17 major sections, covers the variable manifestations of dietary restrictions on cells, whole organs, the individual, and societies.

This book provides the most recent knowledge on almost all key aspects of the health impact of tobacco smoking. Its 21 chapters focus on both preclinical and clinical studies. The contents are broad, covering the epidemiology of tobacco smoking; genetic epidemiology; identification of susceptibility genomic regions, genes, and pathways as determined by both human and animal studies; evolutionary relations among the different nAChR subunit genes that are so important to the nicotine response; smoking-related diseases; E-cigarettes; and smoking cessation. Furthermore, each chapter includes a detailed and comprehensive list of key references. For both clinical and basic researchers, this book is a valuable resource on nicotine dependence and other addictions.

This book focuses on bioelectrics, a new multidisciplinary field encompassing engineering and biology with applications to the medical, environmental, food, energy, and biotechnological fields. At present, 15 universities and institutes in Japan, the USA and the EU comprise the International Consortium of Bioelectrics, intended to advance this novel and important research field. This book will serve as an introductory resource for young scientists and also as a textbook for use by both undergraduate and graduate students – the world's first such work solely devoted to bioelectrics.

This volume has gathered together some of the world's experts on cell death in liver diseases, covering topics on a variety of types of liver injury. Specifically, the chapters of this volume describe drug and virus-mediated hepatocyte injury, alcohol, lipid and bile acid-induced hepatocyte injury in addition to ischemia-reperfusion-mediated liver injury. The authors link these different types of liver injury to the commonly associated liver inflammation, fibrosis and tumorigenesis. Other topics explored include the various forms of cell death and cell survival pathways that have been identified in the liver, such as apoptosis, necroptosis, pryoptosis and autophagy. This book, along with its companion volume, Molecules, Systems and Signaling in Hepatic Cell Death, provides a thorough and comprehensive discussion on the topic of cell death and liver disease. Cellular Injury in Liver Diseases is an essential addition to the Cell Death in Biology and Diseases series and will appeal to scientists, clinicians and those doing research for drug discovery.

This essential volume presents comprehensive information on cell death and autophagy in liver diseases, including the role and molecular signaling pathways of cell death in alcohol and non-alcoholic fatty liver disease, bile acids, hepatitis C virus and drug-induced liver injury. The book starts with a discussion of lipotoxicity in non-parenchymal cells, followed by a discussion of cell death and autophagy in cholangiocytes, hepatic stellate cells and Kupffer cells in hepatic biliary diseases, fibrosis and liver inflammation. The book also covers Bcl-2 family proteins, beta-catenin and HMGB1 signaling in regulating cell death in the liver as well as mitochondria, ER stress and gut microbiota on liver injury. The Cell Death in Biology and Diseases series has recruited world experts ranging from basic scientists to clinicians on cell death in liver diseases. Likewise the contributors of this volume are leaders in their fields with worldwide expertise and perspective. Molecules, Systems and Signaling in Liver Injury is an essential companion to Hepatocytes and Non-Parenchymal Cells and Diseases. It is beneficial for both clinicians and basic scientists and is relevant to those working on drug discovery for preventing and treating liver diseases by targeting cell death and autophagy pathways.

This volume addresses hospital effluents in terms of their composition and the management and treatment strategies currently (being) adopted around the globe. In this context, one major focus is on pharmaceutical compounds: their observed concentration range, ecotoxicological effects, and the removal efficiency achieved by the different technologies. Another focus is on management strategies (dedicated hospital wastewater treatment, or a combined approach also involving urban wastewater) and currently adopted treatments to reduce the released pollutant load. Innovative and promising technologies under investigation at the lab and pilot scale are presented. A discussion of remaining knowledge gaps and future research requirements rounds out the coverage. The respective chapters, written by experts in the different fields, provide useful information for a broad audience: scientists involved in the management and treatment of hospital effluents and wastewater containing micropollutants, administrators and decision-makers, legislators involved in the authorization and management of healthcare structure effluents, and environmental engineers involved in the design of wastewater treatment plants, as well as newcomers and students interested in these issues.

This textbook presents concise chapters written by internationally respected experts on various important aspects of cancer-associated metabolism, offering a comprehensive overview of the central features of this exciting research field. The discovery that tumor cells display characteristic alterations of metabolic pathways has significantly changed our understanding of cancer: while the first description of tumor-specific changes in cellular energetics was published more than 90 years ago, the causal significance of this observation for the pathogenesis of cancer was only discovered in the post-genome era. The first 10 years of the twenty-first century were characterized by rapid advances in our grasp of the functional role of cancer-specific metabolism as well as the underlying molecular pathways. Various unanticipated interrelations between metabolic alterations and cancer-driving pathways were identified and currently await translation into diagnostic and therapeutic applications.Yet the speed, quantity, and complexity of these new discoveries make it difficult for researchers to keep up to date with the latest developments, an issue this book helps to remedy.

Autophagy principally serves an adaptive function to protect organisms against diverse human pathologies, including cancer and neurodegeneration. Recent developments using in vitro, ex vivo and in vivo models show the involvement of the autophagy pathway in immunity and inflammation. Moreover, direct interactions between autophagy proteins and immune signalling molecules have also been demonstrated. Defects in autophagy - similar to cancer, neurodegenerative diseases and aging - through autophagy gene mutation and/or microbial antagonism, may underlie the pathogenesis of many infectious diseases and inflammatory syndromes. In spite of the increasing awareness of the importance of autophagy in these pathophysiological conditions, this process remains underestimated and is often overlooked. As a consequence, its role in the initiation, stability, maintenance, and progression of these diseases are still poorly understood. This book reviews the recent advances regarding the functions ofthe autophagy pathway and autophagy proteins in immunity and inflammation, focusing on their role in self-nonself distinction, their implications in innate and adaptive immune responses and their dysregulation in the pathology of certain inflammatory and autoimmune diseases.

This volume will detail the current state and perspectives of autophagy-based cancer therapy. Covering a wide range of topics, it will include an overview of autophagy as a therapeutic target in cancer, autophagy modulators as cancer therapeutic agents, implications of micro-RNA-regulated autophagy in cancer therapy, modulation of autophagy through targeting PI3 kinase in cancer therapy, targeting autophagy in cancer stem cells, and roles of autophagy in cancer immunotherapy. In addition, the volume will review applications of system biology and bioinformatics approaches to discovering cancer therapeutic targets in the autophagy regulatory network. The volume will be beneficial for a variety of basic and clinical scientists, including cancer biologists, autophagy researchers, pharmacologists, and clinical oncologists who wish to delve more deeply into this field of cancer research.This volume will be the first book to focus solely on autophagy as a target in cancer therapy. As well, it will comprehensively discuss the roles of autophagy in most currently available cancer treatments.

Comprehensive overview of different aspects of autophagy as it relates to neurodegenerative diseases. The pathogenesis of the main neurodegenerative disorders includes either the accumulation of altered or misfolded proteins or exposure to several toxics. Autophagy constitute one of the two principal cellular pathways implicate in the clearance of these material and can serve as a neuroprotective mechanism. Topics include: the role of autophagy in the brain, the role of autophagy in the principal neurodegenerative disorders, and the mechanism by which different molecules cause neurotoxicity and the role autophagy plays.

This atlas provides a detailed insight into the complex structure and organization of cells and tissues, and highlights their specific functions as well as the dynamics of diverse intracellular processes. Highly informative electron micrographs are complemented by explanatory texts, selected references and schemes. The concept that subcellular organelles provide the structural foundation for fundamental processes of living organisms is emphasized. The first part covers the cellular organelles and changes caused by experiments or occurring under pathological conditions. The second part employs selected examples to illustrate the principles of functional tissue organization and typical changes resulting from experimental induction or pathological situations. The third edition of the atlas, revised and extended by 23 plates, thus provides an invaluable resource for scientists and students of medicine and biological sciences, particularly of histology, cell and molecular biology. Moreover, it will serve as a handy reference guide for diagnostic and research electron microscopy laboratories in clinical, industrial, and academic settings.

Environmental indicators are the first line of warning against hazards caused by humans or nature catastrophes to prevent diseases and death of living organisms. The present book covers a large variety of environmental indicators from physical-chemistry through economical, bioinformatics, electromagnetic irradiation and health aspects, all dealing with environmental pollution. This volume has been intended to environmentalists, engineers, scientists and policy makers as well to anybody interested in the latest development in the indicator field.

This book provides up-to-date information on the development and progression of hepatocellular carcinoma (HCC) with a review of the cellular and molecular mechanisms involved in the disease process. Recent research in HCC has led to significant progress in our understanding of the cellular processes and molecular mechanisms that occur during multi-stage events that lead to hepatocarcinogenesis. The emergence of micro RNAs and molecular targeted therapies have added a new dimension in our efforts to combat this deadly disease, Chapters include discussion and evaluation of current intervention strategies and therapeutic options and a focus on the novel approaches that are being pursued, such as micro-RNA based therapies and personalized medicine to treat liver cancer. This book will be of interest to basic and clinical researchers, as well as to drug developers.

This book provides a series of comprehensive views on various important aspects of vertebrate photoreceptors. The vertebrate retina is a tissue that provides unique experimental advantages to neuroscientists. Photoreceptor neurons are abundant in this tissue and they are readily identifiable and easily isolated. These features make them an outstanding model for studying neuronal mechanisms of signal transduction, adaptation, synaptic transmission, development, differentiation, diseases and regeneration. Thanks to recent advances in genetic analysis, it also is possible to link biochemical and physiological investigations to understand the molecular mechanisms of vertebrate photoreceptors within a functioning retina in a living animal.Photoreceptors are the most deeply studied sensory receptor cells, but readers will find that many important questions remain. We still do not know how photoreceptors, visual pigments and their signaling pathways evolved, how they were generatedand how they are maintained. This book will make clear what is known and what is not known. The chapters are selected from fields of studies that have contributed to a broad understanding of the birth, development, structure, function and death of photoreceptor neurons. The underlying common word in all of the chapters that is used to describe these mechanisms is “molecule”. Only with this word can we understand how these highly specific neurons function and survive. It is challenging for even the foremost researchers to cover all aspects of the subject. Understanding photoreceptors from several different points of view that share a molecular perspective will provide readers with a useful interdisciplinary perspective.

This book discusses the emergence of a new class of genes with a specific anticancer activity. These genes, recently defined as “Anticancer Genes”, are reviewed in individual chapters on their mode of action, the specific cell death signals they induce, and the status of attempts to translate them into clinical application.Anticancer Genes provides an overview of this nascent field, its genesis, current state, and prospect. It discusses how Anticancer Genes might lead to the identification of a repertoire of signaling pathways directed against cellular alterations that are specific for tumor cells.With contributions from experts worldwide, Anticancer Genes is an essential guide to this dynamic topic for researchers and students in cancer research, molecular medicine, pharmacology and toxicology and genetics as well as clinicians and clinical researchers interested in the therapeutic potential of this exciting new field.

​​​​This volume reviews disparities in cancer genetics, etiology, treatment and survivorship that are associated with differences in energy balance and how those differences and disparities may be affected by geography, socioeconomic status, ethnicity, biology, behavior and others. State-of-the-art strategies are outlined to alter these problems at the individual, community and policy levels. The book provides a comprehensive assessment of the multiple contributions of disparities in energy balance and how they affect cancer. this volume should constitute a valuable resource to disparity focused investigators at all levels and serves an important guide to professionals that deal with these issues, especially those who determine and implement policy.

This book is dedicated to Dr. Philip A. Schwartzkroin. The book has a novel format because it is not intended to be a set of reviews. Instead, it is an effort to explore important topics in the epilepsy research field. Because articles are written by leaders in the field who have years of experience and individuals with diverse expertise, articles are likely to have a long-lasting impact and be relevant for both epileptologists and neuroscientists. Authors address topics that are important, unresolved questions in the field of epilepsy research, drawing on available data from both the bench and the clinic to support their points. A given topic is addressed by one or more authors, each writing from his/her own unique perspective. For all of the individuals who have been trained or worked with Philip Schwartzkroin in the past and/or have appreciated his contributions to the epilepsy field, this volume is an excellent way to celebrate his achievements and look to the ways they have moved the field forward and continue to stimulate its growth.

Since the discovery of superoxide dismutase more than three decades ago, there has been rapid growth in the knowledge of oxidative stress and disease. This volume containing the proceedings of the 13th Yamaguchi Symposium on Liver Disease includes discussion of the direct cellular effects of hepatitis C virus (HCV) proteins on hepatocytes and reviews evidence that oxidative stress caused primarily by the HCV core protein plays a key role in disease pathogenesis. Also included are chapters on new aspects of oxidative stress and liver disease such as carbon monoxide as a regulator of liver microcirculation, hepatic iron accumulation and the incidence of hepatocellular carcinoma, and oxidative stress in the absence of inflammation in hepatocarcinogenesis. This collection of papers from the Yamaguchi Symposium creates a valuable reference resource for physicians and hepatologists.

In der Mortalitätsstatistik sind Krebserkrankungen nach den Herz-Kreislauferkrankungen am häufigsten. In der Behandlung von Tumorerkrankungen zeichnet sich neben klassischen chirurgischen, strahlen- und chemotherapeutischen Methoden durch die Anwendung molekularbiologischer Methoden ein grundlegender Wandel ab. Im vorliegenden Band werden an ausgewählten Beispielen neue molekulare und genetische Erkenntnisse über therapeutische, diagnostische und präventive Aspekte zur Behandlung von Krebserkrankungen und Möglichkeiten für eine klinische Anwendung der Gentherapie dargestellt. Gleichzeitig wird deutlich gemacht, welche Probleme bei der Übertragung von Ergebnissen der Grundlagenforschung in verantwortungsvolles therapeutisches Handeln noch zu bewältigen sind.

Seit Jahren wird in der Literatur eine Beteiligung der Prostaglandine an der Blutdruckregulation diskutiert. Dabei kommt dem vaskulären Prostacyclin eine besondere Bedeutung zu. Das vorliegende Buch beschreibt die physiologischen Funktionen des Prostacyclins sowie seine Beziehungen zu anderen vasoaktiven Hormonsystemen. Ein besonderes Augenmerk wird auf die mögliche Beteiligung des Prostacyclins an der Blutdruckregulation gerichtet. Seine Bedeutung für die Pathogenese der arteriellen Hypertonie wird diskutiert.

'Biologically Based Methods for Cancer Risk Assessment', an Advanced Research Workshop, (ARW) sponsored by the North Atlantic Treaty Organization (NATO) was held in Corfu, Greece in June, 1989. The intent of the workshop was to survey available pharmacokinetic and pharmacodynamic methods in cancer risk assessment and identify methodological gaps and research needs for biologically based methods in cancer risk assessment. Incorporation of such methods represents one of the most challenging areas for risk assessment. The workshop included an international group of invited experts in the field and provided for a dynamic exchange of ideas and accomplishments. Some of the major topics discussed were: • Inventory of available pharmacokinetic and pharmacodynamic methods for cancer risk assessment. • Identification of methodology gaps and research needs in biologically based methods in cancer risk assessment. • Development of a general framework to guide future cancer risk assessment research. This book is a compilation of the papers presented at the workshop and is intended to provide guidance for future research to reduce uncertainties in the cancer risk assessment process. The primary sponsorship of this ARW by NATO and the advice and cooperation of Dr. C. Sinclair of the Scientific affairs Division are gratefully acknowledged. Acknowledgement is also given to the National Science Foundation for its support. The organization of the ARW and the preparation of this book have required considerable help from many other sources.

Transforming growth factor-β (TGF-β) is a secreted polypeptide with multifunctional properties manifested during embryonic development, adult organ physiology, and pathobiology of major diseases, including cancer and fibrotic and cardiovascular diseases. The signaling pathway of TGF-β now is rather well understood. Continuing revelations in the mechanisms of action of TGF-β provide specific mechanistic examples of how human cells lose their controlled function and behave wrongly during the development of diverse diseases. Equally important, however, is the current promise of exploiting the TGF-β pathway in combating human disease. This book comprehensively covers major areas of human disease where the involvement of TGF-β is firmly established. Simultaneously, the book highlights major gaps in knowledge and the future directions of research that can benefit human medical science. The core set of diseases where TGF-β action is well documented and are included in the book are cancer and cardiovascular and fibrotic disorders. The central aim of the book is to stimulate young scientists to enter the prolific TGF-β field and find new solutions to the problems remaining in this area of study. For this purpose the book provides authoritative educational chapters that furnish a good introduction to the field for young doctoral students, postdocs, and clinical fellows. The book also serves as a valuable reference for the aficionados in the field, who can find accessible and well-illustrated material for their teaching and lecturing activities, via which the importance of TGF-β biology is disseminated to the world of science and to the public.

Four chapters represent the intense current effort to understand the way in which the mitochondrion controls the activation of the final stages of cell death. Another four articles attack the problem from the other side. How do specific insults in particular human or mouse neuro-degenerative diseases translate into mechanisms that will not only allow us to better understand what is happening in these patients but also, with luck, allow for development of more efficient and specific drugs in the future? Firstly, the concept of a central common cell death pathway, originally derived from studies on the nematode, has been an outstanding productive paradigm in bringing together different strands of research. Secondly, truly striking links have been made between results obtained in the culture dish (or even cell-free systems) and the diseased human brain.

The fifth Annual Pezcoller Symposium entitled, Apoptosis, was held in Trento, Italy, June 9-1I, 1993 and was focused on the specific phenomena leading to Programmed Cell Death (PCD) or Apoptosis, and the mechanisms involved. With presentations at the cutting edge of progress and stimulating discussions, this Symposium addressed the genetics and molecular mechanisms determining PCD and the role of this suicidal process in cancer and the immune system. The functions of pS3, c myc and bel 2 in affecting apoptosis in different cell types and the role of ions and intracellular pH changes and that of intranuelear endonueleases are given particular emphasis as are the effects of anticancer agents, hormone imbalances and growth factors. The role of pS3, a tumor suppressor gene, in inducing PCD is discussed in detail as pertinent to hematological and non-hernatological tumors. The requirement of pS3 for the induction ofapoptosis by ionizing radiation or adenovirus oncoproteins is outlined. Decision points during the cell cyele affecting the cascade ofevents leading to PCD are discussed as is their role as'switches'under the control of c-myc and bel-2 proteins or the influence of cyele specific drugs. The concurrent requirement of multiple signals in determining apoptosis is emphasized. The examples of the role of PCD in the regulation of hematopoiesis, and in the generation of antigen-specific immune repertoire are illustrated.

The fifth of the annual research conferences of the American Institute for Cancer Research was held September l-2, 1994, at the L'Enfant Plaza Hotel in Washington, DC. Appropriately, in view of current directions in research, the theme was'Diet and Cancer: Molecular Mechanisms of Interactions'. This proceedings volume contains chapters from the platform presentations and abstracts from the poster session held on the end of the first day. The subtopics for the tl;rree sessions held were'Retinoids, Vitamins A and Din Cancer Prevention and Therapy,''Choline and Lipids: Signal Transduction, Gene Expression and Growth Regulation,'and'Dietary Factors and Regulation of Oncogenes, Growth and Differentiation.'A general overview on vitamins A and D emphasized that A and D, in addition to their established roles in vision, reproduction, and bone mineral homeostasis, may play significant roles in regulating cell function. Vitamin A metabolites, trans-retinoic acid and 9-cis-retinoic acid, regulate growth and differentiation. Furthermore, vitamin A­ deprived animals were more susceptible to both spontaneous and carcinogen-induced tumors. Epidemiological studies showed a correlation between low A intake and higher incidences of certain types of human cancers. Conversely, all-trans retinoic acid is useful in treatment and control of certain types of cancer. Physiologically, Vitamin D is converted to the active form, l,25-dihydroxyvitamin D (VD). VD regulates hormone production and secretion, myocardial contractility, vascu­ 3 3 3 lar tone, and growth inhibition and differentiation.

Much of organic chemistry is based on the ability of suitably structured chemicals to bind together through the formation of covalent bonds. Biochemistry is replete with exam­ ples of enzymatically catalyzed reactions in which normal body constituents can be linked through covalent bonds during the process of intermediary metabolism. The finding that xenobiotic chemicals that enter the body from the environment, are metabolized to highly reactive species, and then covalently react with cellular macromolecules to induce toxic and carcinogenic effects was an observation that spawned the research featured in the Fifth International Symposium on Biological Reactive Intermediates (BRI V). The group of investigators that became fascinated with this process and its signifi­ cance in terms of human health began their discussions in Turku, Finland (J 975), and continued them at Guildford, England (1980), College Park, Maryland (1985), Tucson, Arizona (1990), and Munich, Germany (1995). Among the results were a series of reports listed below, as well as the book for which this serves as the Preface. • Jollow, DJ., Kocsis, J.J., Snyder, R. and Vainio, H. (eds), Biological Reactive Intermediates: Formation, Toxicity and Inactivation, Plenum Press, NY, 1975. • Snyder, R., Park, D.V., Kocsis, J.J., Jollow, D.V., Gibson, G.G. and Witmer, C.M. (eds), Biological Reactive Intermediates II: Chemical Mechanisms and Biological Effects, Plenum Press, N.Y., 1982.

The third edition of Geriatric Medicine appears at a crucial time for health profession­ als, a time when the values and goals of our overall American health care system are being reoriented to those values and goals that have long been at the core of geriatrics. It is likely that the readership of this highly respected textbook will be even substan­ tially greater than that for the two previous editions or, for that matter, for any other textbook on geriatric medicine published in the United States. This third edition continues what its predecessors began-the goal of closing the gap between our knowl­ edge of the proper care of older persons and our capacity to deliver that care. Numerous journal articles and forewords and prefaces to geriatrics textbooks claim that the field of geriatrics has matured. Geriatrics may have'matured'since the publication of the first edition of Geriatric Medicine in 1984, but the maturation process has been slow and is still incomplete. It is true that the field has advanced in many areas. It has been recognized as an area of added qualification by the American Board of Internal Medicine and the American Board of Family Practice, and they have certified thousands of fully qualified physicians in geriatrics over the past decade.

'What is a nongenotoxic carcinogen?'This question recurred through­ out the Ernst Schering Research Foundation Workshop on nongeno­ toxic carcinogenesis, underlining the complexity of the topic. The clarity of the view that all carcinogens act by mutating DNA, origin­ ally advocated by Bruce Ames nearly 20 years ago, has been clouded by the increasing numbers of compounds which are not genotoxic but which nevertheless can cause cancer. There is an urgent need to in­ crease our understanding of these compounds so that their risks can be evaluated realistically and decisions made from a position of knowl­ edge and strength, rather than in fear of the unknown. A nongenotoxic carcinogen can be defined as a compound which causes cancer, but which does not cause damage to DNA as its primary biological activity. This negative definition covers a range of carci­ nogens acting through a variety of mechanisms. Such chemicals often produce tumours only in a single organ species, and there are a few common locations which are affected most often. For example, in male rats, certain carcinogens bind to az globulin to form a complex which 11 accumulates in the kidney tubular cells, which is followed by necrosis and compensatory cell proliferation leading the neoplasia. Other com­ mon mechanisms include hormonal imbalance resulting in thyroid tu­ mours or peroxisome proliferation resulting in liver cancer. These and other examples are studied in some detail in the papers of this book.