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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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