Книги автора: Derek J. Chadwick

Classical studies of steroid hormones are concerned with their regulation of protein synthesis via the modulation of genomic transcription. But many of the actions of these hormones occur too rapidly to be explained in this manner, particularly their effects on the central nervous system. This text deals with recent discoveries showing that steroids can modulate the activity of some neurotransmitters. It explores the role of GABA as an important regulator of neuronal activity in the central nervous system and its inhibitory action as mediated via the GABA receptor and potentiated by steroids. In addition, the binding of steroids to cell membranes, the components involved and the outcome of such interactions are described. Also discusses possible uses of steroids as anesthetics and anticonvulsants.

T cells are a specialized population of immune cells that aid the immune system in combating various types of invading pathogens. This book presents up-to-the-minute data on the role of T cells in autoimmune diseases.

The ability at the molecular level to keep track of time is a property shared by organisms ranging from the simplest unicells to humans. The primary feature of these biological clocks is their ability to entrain to environmental stimuli. The dominant stimulus comes from environmental light cues, which requires the existence of photopigments sensitive to light. The exact identity of the molecules involved in circadian photoreception has remained elusive. The classical view of the circadian system is of diverse physiological rhythms regulated by a centralized clock structure. This book presents evidence that challenges this view. Experiments in both vertebrate and invertebrate systems demonstrate that the circadian timing system is dispersed throughout the animal and suggest that possibly every cell contains an autonomous clock mechanism. A variety of tissues and cells contain have been shown to maintain an oscillation when placed in vitro and removed from any external cues or signals that originate from the classical clock structures and/or the environment. This book draws together contributions from an international and interdisciplinary group of experts whose work is focused on all aspects of the topic. Coverage includes the mechanisms of light signalling to the vertebrate clock, the connections between central and peripheral clocks, circadian gene expression patterns and output pathways of clock mechanisms.

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.

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.

Prestigious contributors describe the genetic, molecular, anatomical and neurochemical mechanisms and pathways that operate to regulate and control circadian rhythmicity and functioning in organisms ranging from unicellular algae to human beings. Also considers the implications of the basic and clinical research for humans.

As part of a continuing effort to tackle issues of major social concern, this 280th conference of internationally recognized experts from the fields of molecular biology, medicine, philosophy, theology, and the law looks into the scientific, legal, ethical, social, and economic issues confronting man and his ability to map and sequence the human genome. A wide variety of subjects are covered, including prenatal diagnosis, advances in the genetics of psychiatric disorders, the problems associated with polygenic disease, and the limits to genetic intervention in humans. The symposium also discusses genetic manipulation, commercial exploitation, and legal implications.

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.

Prominent contributors address issues regarding the toxicity of aluminum which causes an encephalopathy in renal dialysis patients and is also known to damage animals and plants via acid rain. Examines the chemistry and biology of aluminum compounds focusing on the evidence for and against aluminum's role in Alzheimer's disease.

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.

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.

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.

Reviews recent basic research into IgE, mast cells, and the allergic response and the relevance of this work to human pathophysiology, and discusses new methods of treatment. This symposium is unique in the IgE field for its breadth of coverage and interdisciplinary nature, and it shows the benefits from the current rapid expansion of knowledge in cell biology, immunology, and molecular genetics, as well as the potential clinical significance of this research to clinical immunologists and allergologists.

Gramicidin channels have been studied intensively for more than 25 years. They serve as model transport systems for large protein ion channels, since it is difficult to glean high-resolution structural information on the latter. This book includes contributions from virtually all the major scientists studying gramicidin channels and is the only compilation of work in this field. It discusses crystallographic, spectroscopic, electrophysiological and computational studies, especially in the light of the recent availability of high-resolution structural data, and it compares these with insights derived from larger systems. As well as drawing together much new and exciting work in this field, it provides pointers to promising new research directions.

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.

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.

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.

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

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.

Contains the presentations and discussions that took place during a symposium at the CIBA Foundation on October 1-3, 1990 on the subject of catalytic antibodies. The recognition that monoclonal antibodies can possess catalytic activity is a recent advance with profound ramifications for chemistry. In addition to their potential commercial applications as catalysts for reactions, for which there are no known enzymes, antibodies promise to provide valuable insight into the detailed mechanisms of biological catalysis and organic chemistry.