Derek J. Chadwick

Jamie A. Goode

The book presents recent advances relating to the factors and mechanisms that regulate the growth, differentiation and function of mast cells and basophils; discussion of new technologies used to study these cells, and integration of the basic scientific findings in the context of therapeutic possibilities for the treatment of diseases such as allergic inflammation and autoimmune disease which are mediated, in part, by these granulocytes.

Development, Activation and Roles in Allergic / Autoimmune Disease

Mast Cells and Basophils

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

This book brings together contributions from key investigators in the area of Transient Receptor Potential (TRP) channel structure and function. It covers the structure, function and regulation of mammalian TRP channels and mechanisms of signal transduction. The discussions indicate research that would improve understanding of the role of TRP channels in normal cellular physiology, the involvement of TRP channels in disease states and their potential use as molecular targets for novel therapeutic agents.

Mammalian TRP Channels as Molecular Targets

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

Rice is the most important food crop for half the world's population. Over the last three decades, the imporvement in human nutrition and health in Asia has largely been attributable to a relatively stable and affordable rice supply. The challenge to produce enough rice for the future, however, remains daunting, as the current rate of population growth outpaces that of increases in rice production. Science has a central role to play in raising rice productivity and this book highlights areas of plant science that are particularly relevant to solving the major constraints on rice production. Examining molecular, genetic and cellular techniques, it considers recent advances in four research approaches for increasing yields and improving the nutritional quality of rice. Plant genomics: knowing the identity and location of each gene in the rice genome is of immense value in all aspects of rice science and cultivar improvement. Molecular biological approaches to increase yield: to produce more biomass by increasing photosynthetic rate and duration, and by improving grain filling. Enhancing tolerance to biotic and abiotic stresses: with new DNA array technologies, it is now possible to assess global genomic response to stresses. Understanding the relationships among stress pathways may create new opportunities for gene manipulation to enhance tolerance to multiple biotic and abiotic stresses. Improving nutritional quality in the grain: knowledge of the biosynthesis of micronutrients in plants permits genetic engineering of metabolic pathways to enhance the availability of micronutrients.

Improving Yield, Stress Tolerance and Grain Quality

Rice Biotechnology

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

Joan Marsh

Experts in their respective fields present papers concerned with the range of human diseases caused by defective or abnormal functioning of cell adhesion molecules. Discusses new therapeutic approaches to these maladies.

Cell Adhesion and Human Disease

Antibiotic Resistance: Origins, Evolution, Selection and Spread Chairman: Stuart B. Levy, 1997 Over the last 50 years, the rapid increase in the use of antibiotics, not only in people, but also in animal husbandry and agriculture, has delivered a selection unprecedented in the history of evolution. Consequently, society is facing one of its gravest public health problems-the emergence of infectious bacteria with resistance to many, and in some cases all, available antibiotics. This book brings together a multidisciplinary group of experts to discuss this problem. It begins by examining the origins of resistance and goes on to look at how the use of antibiotics in human medicine and farming/agriculture has selected for resistant bacteria. Separate chapters describe the evolution of resistance determinants and how these are spread both within and between bacterial species. Finally, the book contains discussions on strategies for countering the threat of antibiotic resistance. A major re-thinking of our approach to the treatment of infectious diseases is proposed-that antibiotic resistance should be seen as a problem created by the disruption of normal microbial ecology. To restore efficacy to earlier antibiotics, and to maintain the success of new antibiotics that are introduced, we need to use these drugs in a way that ensures an ecological balance that favours the predominance of susceptible bacteria.

Origins, Evolution, Selection and Spread

Antibiotic Resistance

Osteoarthritis is a chronic degenerative disease associated with joint pain and loss of joint function. It has an estimated incidence of 4 out of every 100 people and significantly reduces the quality of life in affected individuals. The major symptoms are chronic pain, swelling and stiffness; severe, chronic joint pain is often the central factor that causes patients to seek medical attention. Within the affected joint, there is focal degradation and remodelling of articular cartilage, new bone formation (osteophytes) and mild synovitis. Several mechanisms are thought to contribute to osteoarthritic joint pain. These include mild synovial inflammation, bone oedema, ligament stretching, osteophyte formation and cartilage-derived mediators. Changes in joint biomechanics and muscle strength also influence the severity and duration of joint pain in osteoarthritis. Within the nervous system, the relative contributions of peripheral afferent nociceptive fibres and central mechanisms remain to be defined, and there is limited information on the phenotype of sensory neurons in the OA joint. Importantly, there is no relation between clinical severity, as measured by radiographic changes, and the presence and severity of joint pain. Patients with severe joint pain may have normal joint architecture as determined by X-ray, whereas patients with considerable evidence of joint remodelling may not have significant joint pain. Treatments for osteoarthritic joint pain include non-steroidal anti-inflammatory compounds, exercise, corrective shoes and surgical intervention. There remains a critical need for improved control of joint pain in osteoarthritis. This book brings together contributions from key investigators in the area of osteoarthritic joint pain. It covers the clinical presentation of joint pain, the pathways involved in joint pain, osteoarthritis disease processes and pain, experimental models and pain control. The discussions provide insights into the nature of osteoarthritic joint pain, identify key studies needed to advance understanding of the problem, highlight possible intervention points and indicate future pathways towards a better treatment of osteoarthritic joint pain.

Osteoarthritic Joint Pain

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

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

Recent application of the techniques of molecular biology and patch-clamp physiology has led to rapid advances in understanding the molecular events in chemosensory transduction. In this book, the latest results are presented and discussed by leading scientists. The extensive coverage encompasses many important topics, including mucous domains; microchemical heterogeneity in the mucociliary complex of the olfactory epithelium; membrane currents and mechanisms of olfactory transduction, and genetic and pathological taste variation.

The Molecular Basis of Smell and Taste Transduction

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

Many different pathological conditions are currently under investigation as therapeutic targets of purines including cancer, cardiovascular conditions, behavioural disorders, inflammation, immunoregulation, and neuroendocrine function. This book draws together research on all aspects of P2 purinoceptors and discusses their use in different therapeutic areas.

Localization, Function and Transduction Mechanisms

P2 Purinoceptors

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

The ability at the molecular level to keep track of time is a property shared by organisms ranging from the simplest unicells to humans. The primary feature of these biological clocks is their ability to entrain to environmental stimuli. The dominant stimulus comes from environmental light cues, which requires the existence of photopigments sensitive to light. The exact identity of the molecules involved in circadian photoreception has remained elusive. The classical view of the circadian system is of diverse physiological rhythms regulated by a centralized clock structure. This book presents evidence that challenges this view. Experiments in both vertebrate and invertebrate systems demonstrate that the circadian timing system is dispersed throughout the animal and suggest that possibly every cell contains an autonomous clock mechanism. A variety of tissues and cells contain have been shown to maintain an oscillation when placed in vitro and removed from any external cues or signals that originate from the classical clock structures and/or the environment. This book draws together contributions from an international and interdisciplinary group of experts whose work is focused on all aspects of the topic. Coverage includes the mechanisms of light signalling to the vertebrate clock, the connections between central and peripheral clocks, circadian gene expression patterns and output pathways of clock mechanisms.

Jamie A. Goode

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