Molecular and Cell Biology of Human Diseases Series – serie

Molecular and Cell Biology of Human Diseases reviews the status of research on a range of sexually transmitted diseases whose incidence has paralleled the increase in HIV infection and examines the ways in which new methods are influencing current practice and are likely to shape future management.

Molecular and Cell Biology of Muscular Dystrophy gives a series of accounts of various aspects of the remarkable breakthrough which has been achieved in our understanding of the Duchenne/Becker muscular dystrophies and of the consequences and ramifications of this breakthrough.

Over the last five years a great deal has been discovered about the neurochemistry, biochemistry and molecular genetics of neuropsychiatric diseases. The significance of all three approaches is reviewed in this volume by an internationally recognized team of authors. Providing a valuable statement of the position of current research, this book should be of considerable interest to psychiatrists and neuroscientists. This book should be of interest to graduate researchers and students in clinical biochemistry, molecular biology and neurosciences.

Written to inform not only basic research scientists and students, but also practising physicians, this volume reviews the evolution of gene transfer as a therapeutic strategy. The latest developments in viral and non-viral vectors for gene therapy are explained. The book then moves on to describe gene therapy applications in a comprehensive range of disease situations including cancer, AIDS, arthritis, cardiovascular and neuromuscular disorders, muscular dystrophy, cystic fibrosis and genetic vaccination. This book should be of interest to clinicians, clinical researchers and basic scientists interested in the development of genetic therapies.

The study of carbohydrates in biology is one of the longest-established aspects of the subject. In consequence, it is treated in most text­ books of biology and biochemistry~at least at an elementary level. However, certain areas of carbohydrate biochemistry have expanded rapidly over the past few years as a result of intense research activity. Such advances make this an opportune time to draw together the newer ideas of carbohydrate functions and to present them within a framework of established knowledge. This book describes the role of carbohydrates in biology at a level which is suitable for undergraduate students in biochemistry, biology and the medical sciences. The subject is treated to the final-year level although, inevitably, advanced students will wish to expand their knowledge of particular topics by use of the reading list provided as an appendix. Two areas are particularly emphasized. The first is the metabolic reactions of carbohydrates and the functions of such reactions in the organism. Here the regulation of metabolism in response to different physiological requirements is stressed, and concepts of compartmentation and transport are explored. The second area is concerned with the metabolism and functions of carbohydrate polymers. Here there has been a rapid expansion of research, particularly into the role of specific interactions of carbohydrates which occur, for example, at cell surfaces.

advanced metastatic disease of solid tumors, dictates that each tumor mass, indeed each individual metastasis, will have a unique antigen and cytokine environment and hence unique response to immune modu­ lation. A differential response to immunotherapy is thus inevitable. 4. Many of the human trials described are not randomized and report survival or response against historical controls. Most tumors described are immunogenic human tumors: renal cell cancer and melanoma are most common. In order to avoid the well-described inter-patient vari­ ation and rare incidence of spontaneous response among patient samples as well as selection bias and changes in practice over time, randomized trials are required. 5. Immunological treatment is unlike conventional chemotherapy in its endpoint. Most chemotherapeutic regimes require a complete response or a good partial response for cure or good palliation. There are now many cases where immunotherapy has provided long-term palliation without massive tumor reduction. Immunity may be stimulated to a degree which holds tumorigenicity in check and most importantly, pro­ vides good palliation for the patient in a manner that differs essentially from chemotherapy.

is"0l m 5-HT Ante-mortem (m = metabolite) . ". ~ Post-mortem m 0 Noradrenaline ,,-'-'-'-'0-J ,,-'-'-'-'-'-'- m Dopamine ~ . '-'-'-'-'- . " Somatostatin . '1 Plaques Tangles * . ". . ". . 'I Synapse loss * ChAT " ACh synthesis l"-,. '-'-'-'-'-'-'-'-'-'-'-'-'- ,,-'-'-'-'-'-'-'-'-'-'-'-'-'-'- * Neuronal loss ,,- ,,- . ". * o 0. 1 0. 2 0. 3 0. 4 0. 5 0. 6 0. 7 0. 8 0. 9 1. 0 Correlation coefficient with dementia rating Figure 2. 1 Various neurotransmitter and neuropathological measures on neocortex obtained either at diagnostic craniotomy (ante-mortem) or post-mortem and re- lationship to cognitive impairment (dementia rating). Asterisks identify significant correlations. Negative and positive correlations are not identified in this represen- tation of the data. Only the physiologically relevant measure of cholinergic neurones (acetylcholine synthesis) and indices of cortical pyramidal neurone degeneration (neuronal loss, synapse loss and tangles) correlate with severity of dementia. Note the lack of correlation with the structural marker of cholinergic neurones, ChAT activity. Loss of enzyme exceeded that of acetylcholine synthesis (Sims et al., 1983a), suggesting a compensatory increase in synthesis in the few remaining neurones. Data derived from Palmer (1987) and Terry et al. (1991). emission tomography (PET) and magnetic resonance, may some day pro- vide routine insight into differences in brain functioning. Success in developing rapid and reliable diagnostic procedures, perhaps based on changes in body fluid that reflect specific alterations in brain protein metabolism, should ultimately play an important role in the clinical development of new therapeutic agents.

Molecular and Cell Biology of Muscular Dystrophy gives a series of accounts of various aspects of the remarkable breakthrough which has been achieved in our understanding of the Duchenne/Becker muscular dystrophies and of the consequences and ramifications of this breakthrough.

Human immunodeficiency virus and AIDS have received much attention in the last decade. As the major cause of death in young adults, this concern is merited. AIDS has also ushered onto the clinical agenda a number of unusual and interesting pathogens. These have had considerably less attention than the virus itself, but are arguably as important. This book attempts to put into one volume a state of the art review of the basic biology of these opportunistic organisms. When compiling this book, the perceived difficulty was deciding how to restrict the number of chapters, as there is a large number of opportunistic organisms. It soon became clear, however, that the chapters would select themselves, as the work on many of these organisms was still in its infancy. We can be criticized for including Salmonella, which is not thought to be an opportunistic infection, and excluding Cryptococcus. Our defence is that the former has an interesting relationship with HIV and the latter is one of those organisms for which the basic biology is still in its early stages. The authors are all active researchers in their respective fields and we are grateful that they managed to review their subjects in the short turn-around time required for a book such as this not to be needlessly outdated on publication. We hope that, if nothing else, this book stimulates interest and more research on these agents: perhaps, in future editions, there will be much more to describe on their molecular biology.