Search results for ""author derek j. chadwick""

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.

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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.

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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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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.

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This important book covers the structure and molecular biology of small round structured viruses (SSRVs) such as caliciviruses and astroviruses, and the basic pathology of infection. It provides readers with the knowledge needed to make progress in the prevention and treatment of these infections. Readers will also find an overview of gastroentitis vaccines, their structure and molecular biology, as well as the basic pathology of infection, epidemiology and surveillance. Provides an interdisciplinary approach, offering contributions from basic and clinical research Discusses the prevention and treatment of regimes Includes an overview of gastroentitis vaccines

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Chronic obstructive pulmonary disease (COPD) is the most common respiratory disorder of adults in the developed world and is the fourth main cause of death in the USA. It is also associated with high morbidity, and poses an enormous burden of suffering and expense. Despite this, the disease has received little attention compared with other respiratory conditions such as asthma and lung cancer. Current treatment can offer some marginal symptomatic relief but does not address the underlying disease process. Indeed, smoking cessation is the only intervention known to alter the rate of disease progression. There is clearly great need, and potential, for the development of superior therapies for symptomatic relief and disease modification. This book brings together leading researchers and physicians to discuss the most recent advances in our understanding of COPD, and draws together basic and clinical aspects relevant to the topic. Coverage includes the basic pathology, current and potential therapies, and detailed consideration of the major theories for the pathogenesis of COPD.

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Nature employs a wide variety of sex determining mechanisms and it is only comparatively recently that the tools have become available for these to be explored at the cellular and molecular levels. A major landmark was the discovery in 1990 of the SRY gene and the subsequent demonstration of its key role in triggering male sex determination in transgenic mice. This book reviews and discusses our current understanding of the molecular genetic pathways of sex determination, with special emphasis on vertebrates. It features comparisons with other modes of sex determination, consideration of the biology of sexual development and discussion of the evolution of sex-determining mechanisms. By bringing together an international and interdisciplinary group of experts who study many different aspects of the problem, the book highlights much new and exciting work in this area and serves to identify and stimulate promising new research directions.

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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.

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The field of neural transplantation is at a crucial stage in its development, with results of important clinical trials on transplantation in patients with Parkinson's disease expected soon and novel, alternative approaches to fetal transplantation being actively investigated. This timely book brings together leading neuroscientists, clinicians, and cell and developmenta; biologists to discuss the use of neural transplants in neurodegenerative diseases such as Parkinson's disease, Huntington's disease, 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, such as xenografts, encapsulated cells and immortalized stem cells. With authoritative contributions and lively discussion sections, this book draws together much new and exciting work in this field, and identifies promising new research directions.

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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.

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Seemingly simple behaviours turn out, on reflection, to be discouragingly complex. For many years, cognitive operations such as sensation, perception, comparing percepts to stored models (short-term and long-term memory), decision-making and planning of actions were treated by most neuroscientists as separate areas of research. This was not because the neuroscience community believed these operations to act independently—it is intuitive that any common cognitive process seamlessly interweaves these operations—but because too little was known about the individual processes constituting the full behaviour, and experimental paradigms and data collection methods were not sufficiently well developed to put the processes in sequence in any controlled manner. These limitations are now being overcome in the leading cognitive neuroscience laboratories, and this book is a timely summary of the current state of the art. The theme of the book is how the brain uses sensory information to develop and decide upon the appropriate action, and how the brain determines the appropriate action to optimize the collection of new sensory information. It addresses several key questions. How are percepts built up in the cortex and how are judgments of the percept made? In what way does information flow within and between cortical regions, and what is accomplished by successive (and reverberating) stages of processing? How are decisions made about the percept subsequently acted upon, through their conversion to a response according to the learned criterion for action? How does the predicted or expected sensation interact with the actual incoming flow of sensory signals? The chapters and discussions in the book reveal how answering these questions requires an understanding of sensory–motor loops: our perception of the world drives new actions, and the actions undertaken at any moment lead to a new ‘view’ of the world. This book is a fascinating read for all clinical and experimental psychologists and neuroscientists, as well as anyone interested in how we perceive the world and act within it.

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