Книги автора: Jamie A. Goode

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

The past decade has seen mounting global concern regarding viral outbreaks such as SARS, avian influenza and West Nile virus. In 2004 and 2005, reports of bird-to-human, and possible human-to-human, transmissions of the H5N1 influenza viruses raised fears that these viruses could cause a pandemic on the scale of the Spanish flu pandemic of 1918. Previous to this, a novel coronavirus had been identified as the aetiological agent of the severe acute respiratory syndrome (SARS), a new respiratory viral disease that emerged at the end of 2002 and caused profound disturbances in over 30 countries worldwide in 2003. It is not known whether the SARS coronavirus will re-emerge, especially since its origins and potential reservoir(s) are unresolved. However, these outbreaks have shown that these viruses can emerge in any part of the world at any time. This book critically evaluates the latest scientific evidence on novel or re-emerging viral diseases and brings together contributions from world experts on this topic, explaining best practice in their area, and discussing lessons learned and how best to collaborate to prevent and control future outbreaks. Topics covered include: the latest advances in virology, particularly in the area of epidemiology diagnostics animal models for viral infection antiviral and vaccine development Novel and Re-emerging Respiratory Viral Diseases offers a comprehensive and interdisciplinary account of all aspects of the topic, from basic molecular biology to public health issues, and is therefore essential reading for virologists, infectious disease specialists, public health managers, researchers and epidemiologists, as well as those working in vaccine development, pharmaceutical medicine and drug discovery

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.

Evolutionary psychology and behavioural genetics are two successful and important fields in the study of human behaviour, but practitioners in these subjects have different conceptions of the nature of human intelligence. Evolutionary psychologists dispute the existence of general intelligence and emphasise the differences among species. They argue that natural and sexual selection would be expected to produce intelligences that are specialised for particular domains, as encountered by particular species. Behavioural geneticists consider general intelligence to be the most fundamental aspect of intelligence and concentrate on the differences between individuals of the same species. This exciting book features papers and discussion contributions from leading behavioural geneticists, evolutionary psychologists and experts on intelligence that explore the differences and the tensions between these two approaches. The nature of 'g' or general intelligence is discussed in detail, as is the issue of the heritability of intelligence. The alternative approaches that emphasise domain-specific intelligences are explored, alongside wide-ranging discussions on a broad range of issues such as the biological basis for intelligence, animal models and changes in IQ scores over time.

Retinal dystrophies are the major causes of incurable blindness in the Western world. Our insight into their aetiology has improved remarkably over the past decade and a number of key genes have been identified. Together with a more detailed understanding of disease processes, this knowledge is stimulating new approaches to therapeutic strategies involving gene therapy, growth factors and retinal cell transplantation. Molecular genetic studies have provided detailed information on the pathogenesis of retinal dystrophies. An important proof of principle that gene therapy holds great promise for the treatment of these conditions was demonstrated in the rds mouse: introduction of a functional copy of the peripherin gene subretinally resulted in complete rescue of rod outer segment structure. Novel approaches are being developed based on the manipulation of biochemical pathways that previously were not considered relevant to these diseases. For example, renewed interest in retinal dystrophy pathogenesis led to the successful use of high dose vitamin A treatment in Sorsby fundus dystrophy. This important new book covers all aspects of retinal dystrophies from the molecular and developmental biology of these disorders to possible therapeutic approaches, with special reference to gene therapy. Specific chapters deal with the molecular genetics of gene therapies, clinical genetic studies, molecular and cellular mechanisms of the development of the disease, functional genomics of retinal diseases, animal models of retinal dystrophies, and finally with studies on gene therapeutic approaches to correcting the disorder. With contributions by many of the leading researchers worldwide, this book is likely to be an important milestone in this rapidly developing field.

Understanding stem cells at the molecular level is essential to understanding their behaviour in a physiological context. This volume in our acclaimed Novartis Foundation series features animated discussion from the world’s experts in this topic on the important ethical issues that are raised by research on stem cells. They review the various regulatory regimes, which apply in different countries – a key factor in determining where future stem cell research is carried out. Potential clinical applications covered in the book include the production of cardiomyocytes to replace damaged heart tissue, the production of insulin-producing cells for patients with diabetes, and the generation of neurons for the treatment of patients with Parkinson’s disease or spinal cord injury. Particular attention is paid to the factors that maintain stem cells in a pluripotent state or which drive them to create differentiated and lineage-committed cells in vitro and in vivo. Nuclear reprogramming, the process by which a nucleus acquires developmental potential, is covered here as well. It is relevant to stem cell research generally, and also to research on the cloning of animals by nuclear transfer. This book is an essential purchase for all those engaged in stem cell research, whether in the laboratory, the clinic or the regulatory authorities. From the reviews: «…this book provides: a comprehensive overview of current issues in stem cell research, with contributions from leading figures…» —BRITISH SOCIETY OF CELL BIOLOGY

Anaphylaxis is an immediate-type allergic reaction involving the whole organism. It is the most life-threatening allergic condition. Although there are few exact epidemiological data regarding prevalence, estimates regarding insect sting anaphylaxis range from 1-3% in the general population, but much higher values have been reported by some authors for food and drug-induced anaphylaxis. Anaphylaxis is the main acute killer of allergic individuals. Although anaphylaxis was discovered at the beginning of the 20th century, there are still many unresolved issues. These include non-IgE-mediated anaphylactoid reactions, non-immunologically mediated anaphylactoid (pseudo-allergic) reactions, pathophysiological events at the microcirculatory level, appropriate therapy for the acute reaction, strategies for prevention, public education about the problem and new approaches to prevention and therapy at the IgE level. All these subjects are discussed in this book. Since anaphylaxis occurs acutely and is unforeseen, it is very difficult to organize controlled studies regarding therapy and prevention. The spectrum of symptomatology covers many clinical areas (skin, respiratory, cardiovascular and gastrointestinal system), therefore inter-disciplinary approaches are necessary for progress in the field. There is widespread uncertainty among physicians about therapy, especially concerning self-administered treatment. In this important book, an 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 thorough and up-to-date coverage of the subject will be of great interest to all clinical immunologists, researchers and physicians who deal with this life-threatening condition. Related Novartis Foundation symposia: 252 Generation and effector functions of regulatory lymphocytes Chair: Jean-François Bach Immunoinformatics: bioinformatic strategies for better understanding of immune function Chair: Hans-Georg Rammensee Cancer and inflammation Chair: Siamon Gordon

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.

A comprehensive volume examining the fundamental questions raised by reductionists' theory about levels of explanation necessary to understand biological systems. The book evaluates the enormously powerful techniques of molecular biology, and analyzes precisely how molecular information has improved our understanding of fundamental biological processes.

This book is a comprehensive and up-to-date account of where we stand in immunological strategies for preventing or treating type 1 diabetes (T1D). Brings together contributions from the leaders in the arena of clinical immunotherapy, not limited to the diabetes field exclusively, in order to delineate a road-map that would lead to future clinical trials. The book integrates information from human and animal studies. The book considers T1D within the broader context of autoimmune disease. The format contains several discussions, which address specific questions and provides guidelines for future strategies and solutions for discovering a cure.

Much recent research in evolutionary developmental biology has focused on the origin of new body plans. However, most evolutionary change at the population and species level consists of tinkering: small-scale alterations in developmental pathways within a single body plan. Such microevolutionary events have been well studied on a population genetic level and from the perspective of adaptive phenotypic evolution, but their developmental mechanisms remain poorly studied. This book explores both theoretical and practical issues of tinkering. It features a wide range of perspectives to address several fundamental questions. How does tinkering occur developmentally, and how is it manifested phenotypically? Are the developmental mechanisms by which tinkering occur different from those that underlie larger evolutionary changes? What are the developmental constraints on tinkering? And how do we test hypotheses about microevolutionary shifts in development from the fossil record? With contributions from experts in a range of fields, this fascinating book makes exciting reading for anyone studying evolution, developmental biology or genetics.

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.

Tissue engineering takes advantages of the combined use of cultured living cells and three-dimensional scaffolds to reconstruct adult tissues that are absent or malfunctioning. This book brings together scientists and clinicians working on a variety of approaches for regenerating of damaged or lost cartilage and bone to assess the progress of this dynamic field. In its early days, tissue engineering was driven by material scientists who designed novel bio-resorbable scaffolds on which to seed cells and grow tissues. This ground-breaking work generated high expectations, but there have been significant stumbling blocks holding back the widespread use of these techniques in the clinic. These challenges, and potential ways of overcoming them, are given thorough coverage in the discussions that follow each chapter. The key questions addressed in this book include the following. How good must cartilage repair be for it to be worthwhile? What is the best source of cells for tissue engineering of both bone and cartilage? Which are the most effective cell scaffolds? What are the best preclinical models for these technologies? And when it comes to clinical trials, what sort of outcome measures should be used? With contributions from some of the leading experts in this field, this timely publication will prove essential reading for anyone with an interest in the field of tissue engineering.

Over recent decades vast amounts of biological data have been accumulated. However, it is becoming increasingly difficult to apply traditional theoretical methods to the formulation of coherent pictures of cell and organ function because it is no longer possible for a human theorist to integrate all of the available information. Instead, computer technologies must now be used to perform this integration. This book brings together contributions from many different fields to summarize the current status of computer-assisted modelling of biological processes. The initial chapters deal with fundamental developments in hardware, software and mathematics that underlie current approaches to biological modelling. Next, different approaches to collating data on gene structure and function are presented. These databases form a vital resource for any investigator trying to construct an integrated picture of particular biological systems. Cell signalling systems form a particularly complicated aspect of all cellular function and are important both in the understanding of basic cellular processes and in selecting targets for drugs. Recent approaches to integrating data on cell signalling into computer models are covered. Further chapters build on these approaches to show how computerized models of intact cells can be developed. Finally, approaches to the computer modelling of whole organs such as the heart are presented. The role of computer modelling in drug design is the subject of the final chapter and is also touched on throughout the discussions.

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

Prominent clinicians and researchers from diverse disciplines discuss the basic cell and molecular biology of steroid action and sex steroids' effects on the nervous and immune systems. Provides an integrated evaluation of the advantages and disadvantages of hormone replacement therapy.

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.

Empathy is the process that allows us to share the feelings and emotions of others, in the absence of any direct emotional stimulation to the self. Humans can feel empathy for other people in a wide array of contexts: for basic emotions and sensation such as anger, fear, sadness, joy, pain and lust as well as for more complex emotions such as guilt, embarrassment and love. It has been proposed that, for most people, empathy is the process that prevents us doing harm to others. Although empathy seems to be an automatic response of the brain to others’ emotional reactions, there are circumstances under which we do not share the same feeling as others. Imagine, for example, that someone who does the same job as you is paid twice as much. In this case, that person might be very satisfied with their extra salary, but you would not share this satisfaction. This case illustrates the ubiquitous feeling of fairness and justice. Our sense of fairness has also become the focus of modern economic theories. In contrast to the prominent self-interest hypothesis of classic economy assuming that all people are exclusively motivated by their self-interest, humans are also strongly motivated by other-regarding preferences such as the concern for fairness and reciprocity. The notion of fairness is not only crucial in personal interaction with others in the context of families, workplace or interactions with strangers, but also guides people’s behaviour in impersonal economic and political domains. This book brings together work from a wide range of disciplines to explain processes underlying empathy and fairness. The expert contributors approach the topic of empathy and fairness from different viewpoints, namely those of social cognitive neuroscience, developmental psychology, evolutionary anthropology, economics and neuropathology. The result is an interdisciplinary and unitary framework focused on the neuronal, developmental, evolutionary and psychological basis of empathy and fairness. With its extensive discussions and the high calibre of the participants, this important new book is essential reading for anyone with an interest in this topic.

This title provides an extremely helpful analysis of genes that may be associated with autoimmunity, and answers questions such as how these genes can be identified, and how the functions of the gene products can be elucidated. Incorporating data on disease-associated chromosomal loci that has been accumulated from inbred mice, the title: descibes how some susceptibility loci may be common to many diseases, whereas others are relatively disease specific discusses the importance of developing criteria for establishing the significance of these different categories of disease-associated loci.

The astounding diversity of the immune system and the complexity of its regulatory pathways makes immunology a combinatorial science. Computational analysis has therefore become an essential element of immunology research and this has led to the creation of the emerging field of immunoinformatics. This book is the first to feature thorough coverage of this new field. Immunoinformatics facilitates the understanding of immune function by modelling the interactions among immunological components. Biological research provides ever deeper insights into the complexity of living organisms while computer science provides an effective means to store and analyse large volumes of complex data. Combining the two fields increases the efficiency of biological research and offers the potential for major advances in the study of biological systems. This book encompasses key developments in immunoinformatics, including immunological databases, sequence analysis, structure modelling, mathematical modelling of the immune system, simulation of laboratory experiments, statistical support for immunological experimentation and immunogenomics. The difficulties in effective application of bioinformatic tools in immunology arise at both ends of the spectrum: most immunologists have only a limited comprehension of sophisticated data analysis and applicability and limitations, while the average computer scientist lacks knowledge of the depth and complexity of biological data. The purpose of this book, therefore, is to present contributions from a multidisciplinary team of biologists and computer scientists to explore the issues related to better understanding of immune function and, in particular, to help apply new computer science methods to immunological research. Related Novartis Foundation symposia: 247 In Silico Simulation of Biological Processes Chair: Denis Noble 252 Generation and effector functions of regulatory lymphocytes Chair: Jean-François Bach