Jamie A. Goode

Gregory R. Bock

Over the last several years, immunologists have re-discovered the importance of regulatory lymphocytes, formerly termed 'suppressor cells'. Many recent reports have documented their existence, effector functions and potential therapeutic benefits in autoimmunity and transplantation. However, even though modern techniques have allowed us to get a much more detailed picture of these cells, they are still highly controversial. Several unresolved issues responsible for this dilemma are discussed in this book: it is difficult to grow and clone such cells, their phenotypes and effector functions are diverse and can sometimes easily be lost, and it is not well understood how they interact with antigen-presenting cells. This book contains contributions from leading investigators from around the world, including lively discussion of the current state of the art in studies of regulatory lymphocytes. Topics featured are the physiological control of autoimmunity, the role of antigen-specific cells in various diseases and disease models and effector mechanisms. Therapeutic applications are considered, particularly for type 1 diabetes, tissue transplantation and the control of viral infection. This important and groundbreaking book should be of interest to all immunologists. Related Novartis Foundation symposia: 254 Immunoinformatics: bioinformatic strategies for better understanding of immune function Chair: Hans-Georg Rammensee 256 Cancer and inflammation Chair: Siamon Gordon

Generation and Effector Functions of Regulatory Lymphocytes

A multidisciplinary group of experts explore the pathophysiology of different types of anaphylactic and anaphylactoid reactions. Evidence is presented on the epidemiology of these conditions while problems relating to diagnosis, therapy and prevention are examined in detail. This coverage of the subject should be of great interest to all clinical immunologists, researchers and physicians who deal with this life-threatening condition.

Anaphylaxis

This book draws together contributions from some of the leading investigators in the field of autism to consider specific problem areas in current research. Each contributor brings expertise from a different field, providing a balanced view of the whole spectrum of study of this disorder. It covers four main areas: Twin and family studies indicate that the heritability of the underlying liability to autism exceeds 90% and point to a multifactorial causation, involving a relatively small number of susceptibility genes. The book discusses this issue in detail, along with the problem of why some additional symptoms are associated with autism while others are not. New techniques are available for examining the neurobiology of autism. The book contains results from imaging studies showing the contributions of different brain regions to autism. It includes neuropathological data and examines the neuropharmacology of autism. There is considerable discussion concerning the fundamental psychological deficit in children with autism. There is good evidence that "Theory of Mind" deficits are associated with autism and this issue is discussed in the book, as are other competing possibilities. The most important practical question facing medical and psychological practitioners is how to help children with autism. The evidence relating to possible psychological or psychiatric interventions for rehabilitation of children with autism is examined in detail. Drug treatments have generally been disappointing in this field and there is one chapter devoted specifically to this problem. The book focusses ultimately on intervention studies and so is of practical relevance to people interested in helping autistic children. In addition, it provides a very convenient summary of the principal controversies which currently exist in research on autism.

Neural Basis and Treatment Possibilities

Autism

The field of lymphokine research has grown in parallel to the exciting developments around the two sets of cells which defend the body. While lymphokines are the "property" of immunologists, the molecular regulators of hemopoiesis (CSFs) belong to the hematologists. This book offers the rare opportunity to examine these separate fields of expertise together.

The Molecular Basis of Cellular Defence Mechanisms

Heart failure is the main cause of death and disability in the industrialized world. There is a major need for novel therapeutics for prevention and reversal of cardiac pathology associated with heart failure and cardiac enlargement. Over recent years, dramatic progress has been made in unravelling the cellular circuitry involved in cardiac failure, as well as in normal cardiac growth, development and apoptosis. This work has revealed new and unexpected therapeutic targets in the heart. In addition, advances in understanding the role of stem cells in cardiac physiology have suggested strategies for cardiac repair and regeneration once thought impossible. This book describes the work of leading investigators studying the basic mechanisms of cardiac growth, function and dysfunction. There are also exciting contributions from researchers developing novel therapeutic strategies for cardiac disease. The unique feature is the discussions amongst the contributors, which always return to the same basic problem: how can new data from biological studies be used to design novel therapies for the treatment of cardiac dysfunction following myocardial infarction, hypertension and other disorders? With its strong emphasis on translational research, this book will appeal to both scientists and clinicians interested in diminishing the impact of the current epidemic of cardiac diseases.

Molecules, Mechanisms and Therapeutic Targets

Heart Failure

This book explores existing and potential strategies for using the genome sequences of human, mouse, other vertebrates and human pathogens to solve key problems in the treatment of immunological diseases and chronic infections. The assembled genome sequences now provide important opportunities for solving these problems, but a major bottleneck is the identification of key sequences and circuits controlling the relevant immune reactions. This will require innovative, interdisciplinary and collaborative strategies of a scale and complexity we are only now beginning to comprehend. Specific problems addressed include the following: What kinds of information are we lacking to understand how the genome sequence specifies the differentiation and response of immune system cells, and system behaviour such as immunological memory and tolerance? Which genome sequences and cellular circuits cause or prevent pathological immune responses to foreign pathogens, allergens or self-tissues? Which host and pathogen genome sequences and cellular circuits explain the failure of sterilizing immune responses to sophisticated human pathogens such as the agents of tuberculosis, malaria, metazoan parasites and chronic viruses? Containing contributions from a range of leading experts in the field, this book provides an important new perspective for clinical immunologists and basic researchers alike.

Decoding the Genomic Control of Immune Reactions

Derek J. Chadwick

Julie Whelan

As part of a continuing effort to tackle issues of major social concern, this 280th conference of internationally recognized experts from the fields of molecular biology, medicine, philosophy, theology, and the law looks into the scientific, legal, ethical, social, and economic issues confronting man and his ability to map and sequence the human genome. A wide variety of subjects are covered, including prenatal diagnosis, advances in the genetics of psychiatric disorders, the problems associated with polygenic disease, and the limits to genetic intervention in humans. The symposium also discusses genetic manipulation, commercial exploitation, and legal implications.

Science, Law and Ethics

Human Genetic Information

Foremost neurophysiologists and psychophysicists provide pertinent information on the nature of representation at the earliest stages as this will constrain the disposition of all subsequent processing. This processing is discussed in several different types of visual perception.

Higher-Order Processing in the Visual System

Gail Cardew

This new work contains the first integrated discussion of the role of olfaction in mosquito-host interactions. It covers the practical applications of this knowledge in attempting to control malaria as a problem for world health. The volume begins with a general overview of mosquito life cycle styles and how odour-mediated host location fits into the repertoire of behaviours that a specific species may exhibit. Certain aspects of insect olfaction and its underlying physiological mechanisms are incorporated within the book.

Olfaction in Mosquito-Host Interactions

Modern technology has made possible epidemiological studies that relate aspects of neonatal health to disease in adult life. This symposium is the first to draw together information from this new research area. Explores links between early growth and the risk of high blood pressure, stroke and coronary heart disease in adult life; poor growth of babies and inadequate growth and nutrition of mothers; and levels of blood cholesterol and clotting factors. Other chapters consider the connections between early nutrition and adult immunocompetence and risk of allergic diseases; critical periods in the development of both the brain and visual system; and possible origins of schizophrenia. Examines the consequences of adverse early experiences for adult psychosocial functioning.

The Childhood Environment and Adult Disease

This book features contributions from experts in cell biology, genetics, neurobiology, immunology and structural biology. The unifying element is that they all study processes of cell shape change and motility. Several key questions in this field of research are discussed: What are the organising principles behind cell shape change? Are there ‘master switches’ present in every cell type? How are extracellular signals interpreted by the cell in order to activate intracellular mechanisms? What is the influence of the extracellular matrix on cell movement and internal signalling pathways? How do pathogens subvert cellular systems in order to stimulate or block their uptake? The book addresses all of these important questions. Data are presented on the key proteins that regulate cell shape: the GTP binding proteins of the Rho family. There are also extensive discussions of the potential applications of the data to clinical problems, particularly that of cell motility in cancer.

Signalling Networks in Cell Shape and Motility

Cigarette smoking is estimated to lead to 4.9 million premature deaths per year worldwide. This is predicted to rise to 10 million by 2020. In western countries it kills half of all smokers who fail to stop. The prevailing model for tobacco addiction is that nicotine from cigarettes rewards smoking and punishes abstinence, tapping into a motivational system of operant conditioning that requires no conscious awareness. However, there are also accounts which involve cognitive biases and the effect of nicotine on impulse control. The brain pathways involved have been studied extensively, but the role of different nicotine receptor subtypes and other neurotransmitter systems is still subject to debate. In western countries, cigarette smoking as an adult has a heritability of 30-50% and candidate genes have been identified that may contribute in part to addiction susceptibility. Many socio-cultural correlates of cigarette smoking have been established, but a comprehensive model that accounts for these and links them with the psychobiological aspects of nicotine addiction has not been forthcoming. Structured behavioural support programmes aid cessation attempts, as do a number of pharmacotherapies, most notably nicotine replacement treatments and bupropion, but the underlying mechanisms are unclear. This book deals with the problems involved in understanding and treating nicotine and tobacco addiction. Topics covered include the nature of the worldwide health problem posed by cigarette smoking, the psychodynamics of cigarette addiction, and the basic pharmacology and biochemistry of nicotine and its effect on the brain. Further chapters analyse the genetic basis of susceptibility to nicotine addiction. Finally, the contributors address approaches to therapy. A continuing theme in the discussions throughout the book is how best to treat nicotine addiction, given that many smokers would like to stop smoking but are unable to do so because of their addiction. This book will be of great value to all psychologists and psychiatrists working on addiction, specifically to nicotine but also to other compounds and behaviours. It will also be of interest to neuroscientists and pharmacologists working on nicotine receptors and the brain pathways involved in dependence, as well as to biochemists, molecular biologist and to public health officials.

Understanding Nicotine and Tobacco Addiction

Dengue virus is a member of the Flaviviridae family, which includes viruses associated with human diseases such as yellow fever, Japanese encephalitis and hepatitis C. Dengue fever is transmitted by mosquitoes, principally Aedes aegypti. There are four serotypes of dengue virus, of which DENV-2 has been the most prevalent in many recent epidemics. Following primary infection, lifelong immunity develops, preventing repeated assault by the same serotype. However, the non-neutralizing antibodies from a previous infection or maternally acquired antibodies are thought to form complexes with a different serotype during a subsequent infection and cause dengue haemorrhagic fever/dengue shock syndrome, which can be fatal. There is no treatment or vaccine available today that can combat this emerging and uncontrolled disease. This book features contributions from the world’s leading researchers working on dengue and related flaviviruses who examine the current state of the art in the molecular biology of the dengue virus. Particular emphasis is placed on the structure and function of the virus and the targeting of virus proteins by potential antiviral agents. The pathogenesis of dengue and dengue haemorrhagic fever are discussed in detail, especially the target cells and the specific receptors on these cells, thereby developing a clear overview of host and viral factors that contribute to dengue haemorrhagic fever. Finally, the book reviews the therapeutic options, paying particular attention to ways in which vector, host and environment can play a critical role in the spread of this disease. With dengue fever and other emerging viral diseases becoming increasingly prevalent around the world, this book provides valuable insight into the virus that causes this disease and potential ways to manage it. It is essential reading for all those working in tropical diseases, public health and virology. Praise from the reviews: "The book provides an excellent summary of dengue/flavivirus research and is important for individuals and institutions interested in emerging infectious diseases." MICROBIOLOGY TODAY

New Treatment Strategies for Dengue and Other Flaviviral Diseases

Joan Marsh

Kate Widdows

Experts from a variety of areas compare and discuss IL-6 and LIF in order to provide a new understanding of their modes of action, the significance of their polyfunctionalization--why the body chooses to use one molecule to regulate various cell types--and their functional overlap. Covers such topics as actions of IL-6 and LIF on lymphoid populations, on megakaryocyte and platelet production, on bone metabolism, their effects on leukemic cells and much more. Includes contributions from researchers working on a variety of cell types and organ systems along with potential clinical applications regarding these two factors.

IL-6 and LIF

Polyfunctional Cytokines

Until recently a neglected disease syndrome, diarrhea is responsible for many millions of infant deaths in developing countries. The result of a 1987 symposium, this volume reflects advances in the aetiology of diarrhea while addressing such puzzling problems as the difficulty of growing viruses in a controlled setting. The volume is deliberately restricted to so-called ``novel'' diarrhea viruses and is not concerned with ``classical'' rotaviruses, which have formed the basis of previous symposia. Articles concentrate on: atypical rotaviruses; the enteric adenoviruses; small round viruses such as astroviruses, caliciviruses and Norwalk virus; and the Berne and Breda viruses, suggested as a new family Toroviridae. The contributions come from an interdisciplinary mix of virologists (both human and veterinary), epidemiologists, molecular biologists, and pathologists.

Novel Diarrhoea Viruses

Kate Ackrill

Written for psychologists, educational psychologists and developmental biologists, this volume explores the concept of giftedness, including its definition, origins and development. The author offers a balanced view of the topic and presents optimal educational strategies for various kinds of high ability. The effects of both environmental and biological/genetic factors on a student's level of giftedness are also discussed, as is the question of whether gifted people can be created.

The Origins and Development of High Ability

An invaluable book containing a series of interdisciplinary discussions between clinical and basic scientists. Biology of IGF-1: Its interaction with insulin and health and malignant states focuses on key issues such as: the definition of danger zones the development of methods for early recognition of malignant states linked to IGF-1 and/or insulin possible approaches to preventative intervention the relevance in this field of research to the development of novel therapeutic approaches to treating certain cancers.

Its Interaction with Insulin in Health and Malignant States

Biology of IGF-1

The potential lipotoxic effect of accumulation of fatty acids in non-adipose tissues is thought to be a major component in the development of insulin resistance. Chronic exposure to high concentrations of free fatty acids in the blood affects pancreatic β cell function, insulin secretion and lipid synthesis in the liver, and storage in adipose tissue. Maintaining the normal levels of fatty acids requires coordinated regulation between the liver, adipose tissue and skeletal muscle. This book deals with the molecular aspects of fatty acid action in obesity and insulin resistance. The topics include lipid metabolism and adipose tissue biology, and β cell function and insulin resistance. Chapters deal with the molecular genetics and molecular physiology of energy homeostasis.

Fatty Acid and Lipotoxicity in Obesity and Diabetes

Dietary supplements can contain a wide variety of ingredients, either singly or in combination, including nutrients, botanicals and 'bioactive components' commonly found in foods. They are marketed and used by consumers for a range of reasons: to enhance "well-being", as traditional medicines, for health promotion or disease risk reduction, and as alternatives or complements to conventional drug therapies. On a global basis, the dietary supplement industry has enjoyed rapid growth, becoming a multi-billion dollar enterprise over the last 10 years. This growth has been associated with significant changes in both the types of products available and the reasons for using these products. In many cases, these changes have occurred without the benefit of a sound scientific basis for evaluating the safety and efficacy of these products under the new conditions of use and frequently the same limited scientific evidence is used, even though current product composition, user populations, purported beneficial effects, and conditions of use may differ significantly from the available evidence or historical usage. This book presents systematic examinations of the scientific data that are available and/or needed to substantiate and evaluate the safety and efficacy of dietary supplements. A series of case studies that are illustrative of the types of scientific challenges that have been encountered in substantiating safety and efficacy for various product types are employed to point out some of the successes but also frustrations that have occurred in recent years. Discussions among presenters and participants identify the lessons learned from these experiences and formulate ideas for improved approaches to identifying research needs and for enhancing the quality and relevance of the scientific evidence available for policy decisions. Dietary Supplements and Health constitutes a useful resource for nutritionists, biochemists, public health researchers and anyone interested in herbal, alternative medicines.

Dietary Supplements and Health

Regulation of intracellular pH is vital to all living cells. This symposium covers the control of pH in muscle and nerve cells and the different mechanisms of acid transport across epithelial and other cell membranes. Papers describe the development and application of microelectrodes and various techniques in molecular biology to the study of the mechanisms of protein transport. Also discusses the significance of pH regulation for the action of hormones and growth factors.

Gregory R. Bock

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