Книги автора: Jamie A. Goode

Part of the prestigious Novartis Foundation series, this volume uniquely addresses the use of innate immunity to treat or prevent infectious diseases of the lung. Innate Immunity to Pulmonary Infection: Provides a comprehensive overview of pulmonary infectious diseases, including basic pathology, current and potential therapies, and detailed consideration of the innate biological resistance mechanisms in the lung Thoroughly examines the major topic of innate immunity in immunology, which is now seen as key to the pathogenesis of and vaccination strategies for infectious diseases Describes the genetic and environmental factors which determine the outcome of infection, such as latency of Tuberculosis, blood stream invasion from local infection, and local target tissue damage Covers the roles of cells such as neutrophils, macrophages and dendritic cells and of molecular components such as Toll-like receptors Discusses the clinical applications of the new knowledge regarding innate immunity and how this can be used in both treatment and prevention (vaccination) strategies Includes contributions from an international and interdisciplinary group of experts Innate Immunity to Pulmonary Infection is an essential resource for researchers in both industry and academia. It is of interest for all those interested in the disciplines of immunology, virology, biology, biotechnology and genetics.

Part of the prestigious Novartis Foundation, this is the first book to review the pathology associated with acetaldehyde, a known toxic agent found in cigarette smoke and other pollutants and derived from ingested alcohol, amongst other sources. In the body, acetaldehyde affects several tissues, particularly the brain and liver, causing various diseases, including cancer, alcoholic liver disease and Alzheimer’s. Acetaldehyde-Related Pathology describes the toxic effects of acetaldehyde at the tissue and cellular levels, reviewing enzyme biochemistry, transgenic mouse models of alcohol dehydrogenase mutants, and the cell-signalling pathways implicated in alcohol-related pathology. It explores the mechanisms of acetaldehyde-induced damage to tissues, often a first step in carcinogenesis, including the oral cavity, the human airway, and the GI tract. The book considers pharmacological strategies and treatments for reducing oral and intestinal acetaldehyde. Acetaldehyde-Related Pathology features in-depth, round-table discussions by an international array of scientists from major laboratories worldwide involved in studies of acetaldehyde-related pathology. This book is essential reading for anyone interested in the effects of this compound – pathologists, biochemists, toxicologists, cell and molecular biologists.

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.

The field of neural transplantation is at a crucial stage, with important clinical trials on transplantation in patients with Parkinson's disease nearing completion and novel, alternative approaches to fetal transplantation being developed. This timely book brings together leading neuroscientists, clinicians, and cell and developmental biologists to discuss the use of neural transplants in neurodegenerative disorders, such as Parkinson's disease, Huntington's chorea, amyotrophic lateral sclerosis, multiple sclerosis and spinal cord injury. There is also extensive coverage of the potential alternatives to freshly derived fetal tissue as the source of transplants, for example xenografts, encapsulated cells and immortalized stem cells. With authoritative contributions and lively discussion sections, this book presents much new and exciting work in this field and identifies promising new research directions.

Smooth muscle contraction is a vital component of the functioning of blood vessels, the uterus, airways and the bladder. Its malfunction can lead to serious pathological conditions, such as hypertension and pre-term labour. The calcium ion plays a central role in smooth muscle function, increasing in concentration for contraction and decreasing for relaxation. Calcium entry into the cell is facilitated by the sarcoplasmic reticulum (SR). This book explores the latest research on the role of the sarcoplasmic reticulum (SR) in smooth muscle function. It examines the control and modulation of the SR and how this may vary among smooth muscle types. Potential therapeutic implications are also discussed. Discusses new and exciting work in this area and identifies promising new research directions. Considers the advances in this relatively unexplored field, offering new insights into the role of the SR muscle. Brings together contributions from key workers, both in basic and clinical science, whose studies range from physiological to pathological and molecular to whole animal.

Although normally thought of as a sex hormone, recent research has highlighted the numerous and significant effects that oestrogen has on the CNS, extending far beyond its important reproductive role. It has been shown that oestrogen acts as a neural growth factor with important influences on the survival, plasticity, regeneration and ageing of the mammalian brain. This exciting book brings together leading clinicians and researchers to discuss oestrogen's basic mechanisms of action, the extrahypothalmic brain regions it affects, and its influence on cognitive functions in animals and humans. Finally, recent research on the role of oestrogens in ageing and dementia, including the significance of oestrogen action in Alzheimer's disease, is discussed. The 15 papers contained in this book, together with the extensive discussion sessions that follow them, reveal much new and exciting work in this area, and identify promising new research directions.

The pacemaking and conduction system (PCS) is vital for generating and synchronizing the heart beat. Dysfunction of this system can be a direct cause of cardiac conduction disturbance, arrhythmias and sudden cardiac death. A wealth of information has been collected over many years on the unique histological, morphological and phenotypic characteristics of specialized cardiac tissues. The cellular and molecular mechanisms that govern development of the PCS are now starting to be understood. This book draws together contributions from an international and interdisciplinary group of experts working on both basic and clinical aspects of cardiac development. It features reviews of the structure and function of the developing PCS, discussion of the molecular and cellular mechanisms regulating embryological development of this system and studies on the fundamental basis of PCS pathology. The book also considers how novel therapeutic interventions based on understanding of the developmental biology of cardiac pacemaking and conduction tissues might ultimately impact on clinical medicine.

Both timely and topical, this book examines the most important aspects of the relationship between alcohol consumption and health. Drawing together much new and exciting work in this area, it reviews this emotive subject from a dispassionate perspective. It will provide a firm base for further research into the effects of alcohol on the cardiovascular system, and into public health attitudes to what is both a universal pleasure and problem.

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.

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.

This exciting book brings together an international and interdisciplinary group of experts to discuss the importance of pulsatile signalling in the induction of biological responses. Coverage includes the basic mechanisms involved in hormone pulsatility, the significance of pulsatility in normal and disease conditions, the relevance of circadian rhythms, changes with ageing, and detailed consideration of specific peptide hormone systems. This book includes contributions from professionals working in both basic and clinical research and reveals much new and exciting work in this area and promises new research directions.

A number of chronic respiratory diseases including chronic bronchitis, asthma, cystic fibrosis and bronchiectasis are characterized by mucus hypersecretion. Following damage to the airway epithelium, a repair process of dedifferentiation, regenerative proliferation and redifferentiation takes place that is invariably accompanied by mucus hypersecretion as a key element in the host defence mechanism. In chronic respiratory diseases, however, excessive mucus production leads to a pathological state with increased risk of infection, hospitalization and morbidity. An understanding of the mechanisms that underlie and maintain this hypersecretory phenotype is therefore crucial for the development of rational approaches to therapy. Despite a high and increasing prevalence and cost to healthcare services and society, mucus hypersecretion in chronic respiratory disease has received little attention until recently, probably because of the difficulties inherent in studying this pathology. Only in the last few years have some of the genes involved in mucus secretion been characterized. The recent availability of genomic sequence information and specific antibodies has led to an explosion of interest in this area making this publication particularly timely. This book draws together contributions from an international and interdisciplinary group of experts, whose work is focused on both basic and clinical aspects of the problem. Coverage includes epidemiology, airways infection and mucus hypersecretion, the genetics and regulation of mucus production, models of mucus hypersecretion, and the implications of new knowledge for the development of novel therapies.

Cl- absorption and HCO3- secretion are intimately associated processes vital to epithelial function, itself a key physiological activity. Until recently the transporters responsible remained obscure, but a breakthrough occurred with the discovery of the SLC26 transporters family. It is now clear that the SLC26 transporters have broad physiological functions since mutations in several members are linked to a variety of diseases. This book describes the properties of this family in detail, with contributions from the leading global researchers in the field. Complementary views from experts on other ion channels are offered in the discussions, which make fascinating reading. This family consists of at least 10 genes, each of which has several splice variants. Most members of the family are expressed in the luminal membrane of epithelial cells. Characterization of anion transport by three members has revealed that all function as Cl-/HCO3- exchangers, suggesting that SLC26 transporters are responsible for the luminal Cl-/HCO3- exchange activity. The SLC26 transporters are activated by the CF transmembrane conductance regulator and activate it in turn, leading to a model in which these molecules act together to mediate epithelial Cl- absorption and HCO3- secretion. The book includes chapters on the transport of other molecules by the SLC26 family, including oxalate in the kidney and sugars in cochlear hair cells amongst others. It also describes recent discoveries that most SLC26 transporters bind to scaffold proteins and that they all contain a conserved domain predicted to participate in protein-protein interactions. These suggest the SLC26 transporters exist in complexes with other Cl- and HCO3- transporters, and possibly other regulatory proteins. This book explores the functional role of these interactions, leading to better understanding of transepithelial fluid and electrolyte secretion and the diseases associated with it.

This book draws together contributions from cell and developmental biologists, structural biologists, geneticists and clinical scientists aimed at a better understanding of the cellular and molecular basis of these diseases. Topics include: How nuclear structure and location within a nucleus affect gene expression Chromatin organization and cell differentiation The nature of the interactions between the nuclear envelope and the cytoskeleton The extent to which the cytoskeleton mediates communication between the cell membrane and nucleus in regulating gene expression and whether disruption of such communication might underlie the disease processes It is hoped that a better understanding of the mechanisms leading to disease pathogenesis may ultimately lead to more rational and appropriate treatments.

The formation of blood vessels is an essential aspect of embryogenesis in vertebrates. It is a central feature of numerous post-embryonic processes, including tissue and organ growth and regeneration. It is also part of the pathology of tumour formation and certain inflammatory conditions. In recent years, comprehension of the molecular genetics of blood vessel formation has progressed enormously and studies in vertebrate model systems, especially the mouse and the zebrafish, have identified a common set of molecules and processes that are conserved throughout vertebrate embryogenesis while, in addition, highlighting aspects that may differ between different animal groups. The discovery in the past decade of the crucial role of new blood vessel formation for the development of cancers has generated great interest in angiogenesis (the formation of new blood vessels from pre-existing ones), with its major implications for potential cancer-control strategies. In addition, there are numerous situations where therapeutic treatments either require or would be assisted by vasculogenesis (the de novo formation of blood vessels). In particular, post-stroke therapies could include treatments that stimulate neovascularization of the affected tissues. The development of such treatments, however, requires thoroughly understanding the developmental properties of endothelial cells and the basic biology of blood vessel formation. While there are many books on angiogenesis, this unique book focuses on exactly this basic biology and explores blood vessel formation in connection with tissue development in a range of animal models. It includes detailed discussions of relevant cell biology, genetics and embryogenesis of blood vessel formation and presents insights into the cross-talk between developing blood vessels and other tissues. With contributions from vascular biologists, cell biologists and developmental biologists, a comprehensive and highly interdisciplinary volume is the outcome.

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.

Inflammatory bowel disease (IBD) comprises a group of idiopathic diseases of the intestine characterized by chronic inflammation of the bowel with periods of exacerbation and remission. Although the exact cause of IBD remains undetermined, the condition appears to be related to a combination of genetic and environmental factors resulting in an aberrant activation of the mucosal immune system. This book contains a series of interdisciplinary discussions between clinical and basic scientists focusing on key issues such as: Epithelial cell and molecular biology, including apoptosis, necrosis and cell survival The role of bacterial milieu and mucosal bacteria in the IBD and of prebiotic and probiotic therapy The progress towards the identification of susceptibility genes and phenotype-determining genes The pharmacogenetics of IBD Mucosal immunology and therapeutic strategies stemming therefrom

Chronic inflammation predisposes to some forms of cancer and the host response to malignant disease shows several parallels with inflammation and wound healing. The cells involved in inflammation are detected in a range of common cancers, together with the inflammatory cytokines and members of the chemokine ligand/receptor systems. Neutralization or deletion of the gene for some inflammatory cytokines confers resistance to tumour induction and experimental metastasis. Over-expression of such cytokines in tumour cells may enhance malignant potential. Certain chemokines are likely to subvert antitumour immunity by favouring development of ineffective Type 2 responses. Tumour cells may even utilize chemokine receptors in homing to lymph nodes and other organs. Thus, the cells, cytokines and chemokines found in tumours are more likely to contribute to tumour growth, progression and immunosuppression than they are to mount an effective host antitumour response. This book draws together contributions from an international group of scientists and clinicians from diverse disciplines, ranging from epidemiology to immunology, cell biology, molecular oncology, molecular medicine and pharmacology to debate these and related issues. Topics covered include the epidemiological links between cancer and inflammation, the parallels between inflammation and cancer, the role of inflammation in cancer, inflammatory genes as risk factors for cancer initiation and progression, inflammation and cancer angiogenesis, and preventative and therapeutic strategies. Related Novartis Foundation symposia: 252 Generation and Effector Functions of Regulatory Lymphocytes Chair: Jean-François Bach 254 Immunoinformatics: Bioinformatic Strategies for Better Understanding of Immune Function Chair: Hans-Georg Rammensee

The recent identification of susceptibility genes for schizophrenia, depression and learning and memory dysfunction suggest that psychiatric disorders may be influenced by a small number of genes with multiple actions. This is the first book to investigate the role of growth factors in these disorders, which should provide clues to the underlying biochemical mechanisms. For example, recent studies have substantiated the provocative finding that neuregulin 1 (NRG1)is a candidate gene for schizophrenia. Neuregulin and its receptors, the ErbB tyrosine kinases, are essential for development of the cardiovascular and nervous systems. Lack of NRG1 function may be involved in dysregulation of synaptogenesis and synaptic plasticity in the adult mediated through glutamate receptor function. Polymorphisms for BDNF (brain-derived neurotrophic factor) have also been implicated in the pathogenesis of schizophrenia. BDNF is a prevalent neurotrophic factor that plays an important role in the pathophysiology of depression, bipolar disease and other psychiatric disorders. Other topics addressed in this book include neuroplasticity and neurotrophic factors, signal transduction by neurotrophins, intracellular trafficking of growth factors, trophic factors and cognitive functions, neurotrophins and depression, and pharmacological treatments of schizophrenia.

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.