Книги автора: Derek J. Chadwick

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.

Microbial responses to acidic and alkaline pH are important in many areas of bacteriology. For example, the mechanisms of resistance to acidic pH are important in the understanding of the passage of human pathogens through the acid of the stomach; and an understanding of microbial degradation of alkaline industrial waste is important for the environment. Bringing together contributions from an international and interdisciplinary group of experts working on the many aspects of bacterial cellular responses to pH, this stimulating volume draws together new and innovative work in this area. It delineates both similarities and differences between mechanisms of tolerance and response, providing readers with an invaluable resource on the subject.

Asthma is a growing health problem throughout the developed world. This volume presents a critical review of all the possible factors for this rising trend and includes research that has not yet been published in the scientific literature. Discusses the basic biology of asthma and addresses genetic influences. Surveys the epidemiological evidence for the worldwide trends in morbidity and mortality.

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.

The increase in the world population and changes in welfare have led to an enormously expanding demand for food. In the industrialized world, food surpluses rather than shortages are a problem together with adverse environmental impacts from the overuse of chemicals and excessive exploitation of agricultural land. In the developing world, food production cannot keep up with population growth and the gap between demand and supply is growing. This book explores the theme of sustainable agricultural development in the developing world, with a particular focus on crop protection. Includes chapters on the ecology of food production, on sustainable agriculture and crop protection methods, on the economics of food production and more.

The mapping of human genes is proceeding rapidly. Genes associated with specific inherited diseases are being identified, often providing insight into the molecular cause of the disease. At the moment, however, little consideration is being given to the variation present in different human populations. Variation in the Human Genome discusses methods of analysing population genetic data and how contemporary genetic heterogeneity arises during the evolution and migration of human populations. Specific disorders such as cystic fibrosis, beta-thalassaemia, fragile X, phenylketonuria and tumour development susceptibility are used to illustrate this genetic variability and mechanisms of gene mutation and evolution.

Epigenetics pertains to the development of an organism from an undifferential cell, resulting in the successive formation and development of organs and parts that did not pre-exist in the fertilized egg. An exciting and stimulating volume which used the extensive knowledge of basic transcriptional control as a foundation to explore the more complex and interesting level at which genes can be regulated.

Details the application of positron emission tomography (PET) to the mapping of human cerebral cortical function. Coverage includes all aspects of PET technology. Includes chapters on somatosensory, motor and visual systems, and higher-order processes such as attention, memory, learning, intention and language. The clinical usefulness of PET is discussed in relation to psychiatric illness and to functional recovery after brain injury.

Working on Corticotropin-Releasing Factor in a variety of systems, experts present a coherent depiction of this peptide's role in the control and coordination of the response to stress-inducing situations.

The molecular mechanisms and protein species associated with the mineralization of mature dental enamel are active areas of research. This book focuses on specific areas of research including the structural chemistry, protein biochemistry and genetics of enamel development.

This book describes a diverse analysis of the five somatostatin receptors; somatostatin gene regulation; promatostatin processing; mechanisms of signal transduction; and the design and use of somatostatin analogues, including their possible clinical implications. The book will provide a comprehensive summary of the cellular and molecular biology of somatostatin and its recently isolated receptors. The book will review the design and use of specific somatostatin analogues both biochemically to characterize the specific functions of somatostatin and clinically in the treatment of various tumors.

Examines the establishment of the germ layers and other cell lineages in the early embryo including details of cell movements during the beginning stages of primitive streak formation. Discusses patterns of gene expression during the development of such tissues as the limb bud, skeletal, muscle and the central nervous systems placing special emphasis on commitment to particular cell types. Although it concentrates on the mouse as an example of mammalian development–chick, amphibian and Drosophila embryogenesis are employed whenever these organisms are more applicable to the study of a particular problem.

The heat shock, or cell stress, response was first identified in the polytene chromosomes of Drosophila. This was later related to the appearance of novel proteins within stressed cells, and the key signal stimulating this appearance was identified as the presence of unfolded proteins within the cell. It is now known that this is a key mechanism enabling cells to survive a multitude of physical, chemical and biological stresses. Since the promulgation of the ‘molecular chaperone’ concept as a general cellular function to control the process of correct protein folding, a large number of molecular chaperones and protein folding catalysts have been identified, and it has been recognized that not all molecular chaperones are stress proteins and vice versa. The discovery of molecular chaperones as folding proteins went hand-in-hand with their recognition as potent immunogens in microbial infection. It was subsequently shown that administration of molecular chaperones such as Hsp60, Hsp70 or Hsp90 could inhibit experimental autoimmune diseases and cancer. More recently evidence has accumulated to show that certain molecular chaperones are also present on the surface of cells or in extracellular fluids. A new paradigm is emerging: at least some molecular chaperones are secreted proteins with pro- or anti-inflammatory actions, regulating the immune response in human diseases such as coronary heart disease, diabetes and rheumatoid arthritis. In addition to having direct effects on cells, molecular chaperones can bind peptides and present them to T cells to modulate immune responses. This may be significant in the treatment of cancer. This is the first book bringing leading researchers in this field together to review and discuss: our current knowledge of cell stress response and molecular chaperones the changing paradigms of protein trafficking and function cell stress proteins as immunomodulators and pro- and anti-inflammatory signalling molecules the role of these proteins in various chronic diseases and their potential as preventative or therapeutic agents. The Biology of Extracellular Molecular Chaperones is of particular interest to immunologists, cell and molecular biologists, microbiologists and virologists, as well as clinical researchers working in cardiology, diabetes, rheumatoid arthritis and other inflammatory diseases.

This book brings together contributions from key investigators in the area of pathological pain. It covers the molecular basis of receptors and channels involved in nociception, the possible messages that cause neuropathic plasticity, spinal plasticity in neuropathy, plastic changes in opioid systems in neuropathy and opioid tolerance, and plastic changes related to pathological pain.

The use of oligonucleotides as therapeutic agents rests upon their ability to interfere, in a sequence-specific manner, with the fundamental machinery of protein synthesis either by binding to the mRNAs transcribed from a gene or by binding directly to a target gene. This approach can be used not only for inhibition of the synthesis of host proteins but also of those required by invading pathogens. Potential therapeutic applications are enormous, ranging over hypertension, cardiovascular disease, autoimmune disease, vital and other parasitic infections (especially HIV), and cancer. This book discusses the chemistry and pharmacokinetics of oligonucleotides and their analogues, and surveys the results of structure-activity studies and current clinical trials. It also critically reviews the problems with antisense therapy, such as the enzymatic destruction of oligonucleotides, the doses required for a therapeutic response, the difficulty in directing oligonucleotides to particular target tissues and cells, the need for parenteral administration, and doubts concerning the mechanism of action (especially problems associated with non-specific binding to proteins) and long-term effects.

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.

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.

Useful throughout history for their medical as well as other benefits, plant-derived compounds have gained particular importance recently, due to environmental factors. The isolation and characterization of plant products, the identification of their role in the plant, and ways of synthesizing identical compounds or more potent analogues are covered. Also includes methods of culturing plant tissues and genetic engineering as a means of increasing the yield of desired substances from plants. Special emphasis is placed on plants previously unknown to Western scientists.

Details the application of positron emission tomography (PET) to the mapping of human cerebral cortical function. Coverage includes all aspects of PET technology. Includes chapters on somatosensory, motor and visual systems, and higher-order processes such as attention, memory, learning, intention and language. The clinical usefulness of PET is discussed in relation to psychiatric illness and to functional recovery after brain injury.

With the recent renaissance in mitochondrial biology and increasing recognition of their role in many diseases, this book provides a timely summary of the current state-of-the-art in mitochondrial research. The book opens with the regulation of mitochondrial replication and biogenesis and reviews the mechanisms and functional consequences of mitochondrial fission and fusion. Further chapters address mitochondria and oxidative stress and their roles in cell signalling and cell death. The book includes extensive, fascinating discussion of the biochemistry of mitochondrial cell signalling (especially involving calcium) and of oxidative stress. The nature of the proteins engaged in these processes, many only recently discovered, is covered in detail. Mitochondria have been strongly implicated in neurodegenerative diseases such as Parkinson’s, Huntington’s and amyotrophic lateral sclerosis. They are also affected in cancer, ageing and cardiovascular disease. The final section of the book reviews mitochondrial mutations and their consequences in ageing and other phenotypic manifestations. The authors discuss how mitochondrial proteins might constitute important therapeutic targets and describe initial attempts to develop compounds that can regulate their function.