In the last decade, remarkable advances have been made in bone marrow transplantation (BMT), which is now becoming a powerful tool in the treatment of diseases such as leukemia, aplastic anemia, and congenital immunodeficiency. In animal experiments, it has been found that BMT can be used to treat not only systemic autoimmune diseases but also organ-specific autoimmune diseases. In humans, it has recently been shown that rheumatoid arthritis, ulcerative colitis, and Crohn's disease can be successfully treated after BMT. This volume contains new information on how to prevent graft rejection, how T cell functions can be completely restored, and how concomitant BMT can prevent the rejection of organ allografts without the use of immunosuppressive agents. BMT will become an increasingly useful and powerful treatment for various currently intractable diseases, and this book will contribute by providing details of the latest research in the field.

Diabetes mellitus is rapidly increasing in prevalence throughout both developed and developing countries. The social and economic burden of this disease is estimated to cost 14 billion dollars worldwide. In the USA alone, 15 million individuals are diabetic, nearly half of them unaware of their condition. Complications of diabetes mellitus are the leading causes for blindness, limb amputation and chronic renal failure and kidney transplantation in industrialized countries. Further, diabetes mellitus per se and the metabolic derangement associated with diabetes are important risk factors for cardiovascular disease. Diabetes, as defined by an elevated fasting blood glucose level is presently subdivided in etiologically distinct groups. The most prevalent being type 2 (adult onset) diabetes characterized by insulin resistance and failure of the ~-cell to supply insulin in amounts sufficient to meet the body's needs. Type 1 (juvenile) diabetes, most commonly with an onset during childhood and adolescence, is caused by an auto-immune destruction of the pancreatic ~-cells. The causations of both type 1 and type 2 diabetes involve a combination of complex genetic traits and environmental influences. A third category are the mature onset diabetes of the young (MODY). This comparatively small group of patients (-10% of diabetes) presents relative early in life "30 years of age) compared to the more common late onset type 2 diabetes.

Ligand-gated ion channels mediate fast synaptic transmission in the central nervous s- tem (CNS) and at ganglionic and neuromuscular synapses. The nicotinic acetylcholine - ceptor (nAChR) is a member of the ligand-gated ion channel superfamily, which includes the 5-HT , glycine and GABA type A and C receptors. These receptors are known as Cys- 3 loop receptors, as all of them have a conserved sequence containing a pair of cysteines separated by 13 residues and linked by a disulfide bridge. nAChRs can be divided into two groups: muscle receptors, which are found at the skeletal neuromuscular junction where they mediate neuromuscular transmission, and neuronal receptors, which are found throughout the peripheral and central nervous system. Many of the early studies carried out on the subunit composition and structure of the nAChRs were performed on receptors isolated from the electric organ of Torpedo californica, as this tissue is very rich in nAChRs, and they were found to have a high degree of homology with the embryonic v- tebrate muscle type receptor. Muscle nAChRs are made up of five subunits arranged around a central pore (Fig. 1A, B). In Torpedo electric organ and vertebrate fetal muscle, the subunit composition is (a1) b1gd, and in adult muscle the g subunit is replaced by the e to give an (a1)b1ed 2 2 composition (Mishina et al. 1986).

RNA Interference: Challenges and Therapeutic Opportunities provides readers with recent advances in siRNA design, delivery, targeting and methods to minimize siRNA's unwanted effects. Preclinical and clinical use of synthetic siRNAs, the roles of miRNAs in cancer and the promise of extracellular miRNAs for diagnosis are also covered in this meticulous collection, along with novel methods for identifying endogenous siRNAs and the annotation of small RNA transcriptomes. Written for the highly successful Methods in Molecular Biology series, chapters include the kind of detail and key implementation advice that ensures successful results in the laboratory. Comprehensive and cutting-edge, RNA Interference: Challenges and Therapeutic Opportunities will aid researchers, clinicians, teachers and biotechnologists interested in the power of RNA-based therapies.

This book is a broadly historical account of a remarkable and very exciting scientific story-the search for the number of human chromosomes. It covers the processes and people, culminating in the realization that discovering the number of human chromosomes brought as much benefit as unraveling the genetic code itself. With the exception of red blood cells, which have no nucleus and therefore no DNA, and sex cells, humans have 46 chromosomes in every single cell. Not only do chromosomes carry all of the genes that code our inheritance, they also carry them in a specific order. It is essential that the number and structure of chromosomes remains intact, in order to pass on the correct amount of DNA to succeeding generations and for the cells to survive. Knowing the number of human chromosomes has provided a vital diagnostic tool in the prenatal diagnosis of genetic disorders, and the search for this number and developing an understanding of what it means are the focus of this book.

Principles of Anatomy according to the Opinion of Galen is a translation of Johann Guinter's textbook as revised and annotated by Guinter's student, Andreas Vesalius, in 1538. Despite Vesalius' fame as an anatomist, his 1538 revision has attracted almost no attention. However, this new translation shows the significant rewrites and additional information added to the original based on his own dissections. 250 newly discovered annotations by Vesalius himself, published here in full for the first time, also show his working methods and ideas. Together they offer remarkable insights into Vesalius' intellectual biography and the development of his most famous work: De humani corporis fabrica, 1543. An extensive introduction by Vivian Nutton also provides new information on Johann Guinter, and his substantial use of Vesalius' work for his own revised version of the text in 1539. Their joint production, a student textbook, is set against a background of the development of Renaissance anatomy, and of attitudes to their ancient Greek predecessor, Galen of Pergamum. This text will be of great interest to historians of science and medicine, as well as to Renaissance scholars.

The International Symposium on Prostaglandins and Related Compounds, first held in Vienna 1972, revisited the city after 24 years for the 10TH Symposium. For the many re searchers working in this multi-disciplinary field it was an opportunity to exchange their ex periences and share new data with colleagues from all around the world. This scientific exchange was largely encouraged by the unseasonably cold and rainy weather. For the first time, there was quite a large attendance from the former Communist countries. Eugene Garfield prepared a key note address delivered during the meeting (The Sci entist 1996, 12) reviewing the contribution of the Nobel Laureates U.S. von Euler, l.R. Vane, S.K. Bergstrom, and B.I. Samuelsson, discussing the relevance of the more than 40,000 pa pers in this area published since 1991. Overall, there is still a rapidly growing interest, and in particular a great variety of clinical applications of this family of compounds which were dis cussed in detail during the meeting. Beside the lectures there were 19 workshops covering nearly all the topics of key in terest. All the speakers were invited to prepare a manuscript which has resulted in the volume now in your hands. Special thanks to Dr. Patrick Wong and the new publisher of this series who helped to publish the proceedings in the usual quality and reasonable period of time. Looking forward to seeing all of you again in Florence in 1999, hopefully with much more sun."

The effort to sequence the human genome is now moving toward a c- clusion. As all of the protein coding sequences are described, an increasing emphasis will be placed on understanding gene function and regulation. One important aspect of this analysis is the study of how transcription factors re- late transcriptional initiation by RNA polymerase II, which is responsible for transcribing nuclear genes encoding messenger RNAs. The initiation of Class II transcription is dependent upon transcription factors binding to DNA e- ments that include the core or basal promoter elements, proximal promoter elements, and distal enhancer elements. General initiation factors are involved in positioning RNA polymerase II on the core promoter, but the complex - teraction of these proteins and transcriptional activators binding to DNA e- ments outside the core promoter regulate the rate of transcriptional initiation. This initiation process appears to be a crucial step in the modulation of mRNA levels in response to developmental and environmental signals. Transcription Factor Protocols provides step-by-step procedures for key techniques that have been developed to study DNA sequences and the protein factors that regulate the transcription of protein encoding genes. This volume is aimed at providing researchers in the field with the well-detailed protocols that have been the hallmark of previous volumes of the Methods in Molecular (TM) Biology series.

Since the publication of the popular first edition, the explosion of DNA sequence information, the access to bioinformatics and mutation databases coupled with the ability to readily detect and confirm mutations has cemented the role of molecular diagnostics in medicine and, in particular, mutation detection by the polymerase chain reaction (PCR). In PCR Mutation Detection Protocols, Second Edition, expert researchers bring the subject up-to-date with key protocols involving the PCR and its many various incarnations such as SSCP, CSGE, and dHPLC. The volume also addresses key areas such as Southern blotting, accurate diagnostics with high throughput, as well as microarray systems. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include brief introductions their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes which provide the often hard to find information that may mean the difference between the success and failure of the method. Authoritative and cutting-edge, PCR Mutation Detection Protocols, Second Edition aims to stimulate postgraduate scientists, researchers, and clinicians already engaged in the area and to provide an important first step for those new to this practice wanting to adopt the powerful and essential technique in their own laboratories.

Empirical data on neural control of motor action and perception have not yet been put into the context of a coherent theory. Dr. Feldman's goal for the proposed book is to illustrate that the field is now at a stage where the data can be used to formulate some core principles that underlie action and perception and to present the foundation of a scientific theory of motor control. Dr. Feldman is a well-known expert and has been active in the field for a long time. In the proposed book he will outline an approach to the analysis of action and perception that he and his colleagues have been using for the past 50 years or so. His theoretical approach will not only help to explain past empirical research, but should also help to inform and provide a structure for future empirical studies.

David Kuter and a host of leading international researchers summarize in one volume all the knowledge of thrombopoietins (TPO) available today. The distinguished experts review the history of the search to discover TPO, describe the molecular and biological characteristics of this new molecule, and present the results of the preclinical animal experiments that will guide clinical use of this new hormone. Along the way they provide the most recent and comprehensive guide to the biology of megakaryocytes and platelets.

This volume contains selected papers presented at the Sendai International Sympo sium on Molecular and Cellular Mechanisms of Cardiovascular Regulation held from May 10-12, 1995, to honor the contributions ofProfessorNorio Taira, Chairman of the Department of Pharmacology (1972-1995), Tohoku University School of Medicine, Sendai, Japan. The Department of Pharmacology at Sendai has a long tradition of significant contribution to the development of drug therapy for cardiovascular diseases. The late Professor Koroku Hashimoto, the predecessor of Professor Norio Taira, first suggested the mode of action of calcium antagonists and their potential usefulness in therapy of ischemic heart disease and hypertension at an early stage of their development. The need for greater understanding of the pathophysiology of cardiovascular dis eases is more critical now than ever before because modern advances in basic and clinical sciences have prolonged the average life expectancy. Using a wide range of molecular and electrophysiological techniques, major advances are occurring frequently in the field of cardiovascular physiology and pharmacology. Such multifaceted approaches are preferred because human cardiovascular diseases are complex, requiring multiple interventions and an in-depth understanding of molecular mechanisms underlying the disease. The first section of this book focuses on molecular mechanisms of ion channel regulation. Eight of ten chapters in this section are devoted to the recent advances in molecular characterization and regulation of various types of potassium channels in cardiac, vascular, and neuronal tissues. A discussion of the structure and function of sodium and calcium channels is also included.

Itisonlyrecently thatthe naturaloccurrenceoffree radicalsin biological tissue has become widely accepted, and that the suspi- cion with which biologists previously viewed the free radicals of radiationchemistryhas beenplacedin a broaderperspective. Now, oxygen-derived free radicals are considered respectable biochemi- cal intermediates, given always the caveat that unwanted tissue damage may arise if these active species are produced in such abundance that they overwhelm the natural antioxidant and free- radical defense mechanisms, or if these systems have become hypoeffective. Many factors, including several dietary manipula- tions, can lead toelevatedproductionofsuperoxide and may result in free radical overload, whereas a deficiency of those micronutri- ents associated with the antioxidant defense mec.hanisms may re- sult in substantially diminished antioxidant capacity. By now, antioxidants have become a household word and al- most everyone is aware of their imponance in protecting the body against attack by active oxygen species. Indeed, it is a paradox of nature that oxygen, which is so essential to sustain aerobic life, ul- timately contributes to its destruction. Not surprisingly, recogni- tion ofthis dilemma has generated a spate ofantioxidant strategies intended to reduce the risk of tissue damage by rampant oxygen radicals, some sadly based less on science than on speculation.

Knowledge about cancer genetics is rapidly expanding, and has implications for all aspects of cancer research and treatment, including molecular causation, diagnosis, prevention, screening, and treatment.

Additionally, while cancer genetics has traditionally focused on mutational events that have their primary effect within the cancer cell, recently the focus has widened, with evidence of the importance of epigenetic events and of cellular interactions in cancer development. The role of common genetic variation in determining the range of individual susceptibility within the population is increasingly recognized, and is now being widely addressed using information from the Human Genome Project. These new research directions will highlight determinants of cancer that lie outside the cancer cell, suggest new targets for intervention, and inform the design of strategies for prevention in groups at increased risk.

Today, the NCI is putting more and more money into research into the genetics of cancer. The very first of the NCI s stated research priorities is a project called The Cancer Genome Atlas. The Cancer Genome Atlas (TCGA) is a comprehensive and coordinated effort to accelerate the understanding of the molecular basis of cancer through the application of genome analysis technologies, including large-scale genome sequencing. The NCI and the NHGRI (National Human Genome Research Institute, where the series editor is employed) have each committed $50 million over three years to the TCGA Pilot Project.

This book proposes cover the latest findings in the genetics of male reproductive cancers; specifically cancers of the prostate and testes. The volume will cover the epidemiology of these cancers; model systems, pathology, molecular genetics, and inherited susceptibility."

Part I The Nano-Scale Biological Systems in Nature; Molecular bio-motors in living cells - by T. Nishizaka; The form designed by viral genome - by K. Onodera; Part II Detection and Characterization Technology; Atomic force microscopy applied to nano-mechanics of the cell - by A. Ikai; Design, synthesis and biological application of fluorescent sensor molecules for cellular imaging - by K. Kikuchi; Dynamic visualization of cellular signaling - by Q. Ni and J. Zhang; Part III Fabrication Technology; Surface acoustic wave atomizer and electrostatic deposition - by Y. Yamagata; Electrospray deposition of biomolecules by V.N. Morozov; Part IV Processing Technology; Droplet handling - by T.Torii; Integrated microfluidic systems - by S. Kaneda and T. Fujii; Part V Applications; A novel non-viral gene delivery system: Multifunctional envelope-type nano device - by H. Hatakeyama, H. Akita, K. Kogure, and H. Harashima; Biosensors - by M. Saito, H.M. Hiep, N. Nagatani, and E.Tamiya; Micro bioreactors - by Sato and T. Kitamori

In recent years much enthusiasm and energy has been directed toward the development of human gene therapies, especially for inherited conditions and cancers. However, current gene transfer technology is limited in its transduction efficiency and ability to permanently and safely correct genomic defects. Thus the promise of gene therapy for these conditions is as yet unrealized. The progression of gene transfer technology will eventually surmount these limitations. Gene Therapy for Acute and Acquired Diseases includes selected examples of ongoing studies in molecular genetics that have the potential to evolve into human therapies for acute illnesses. These chapters are intended to highlight lesser known applications of gene therapy for acquired disorders. It is expected that human gene therapy trials for these conditions will be forthcoming in the near future, leading to previously unimaginable therapies. Thus, this first-ever book about gene therapy for acute and acquired diseases is intended to serve as a glimpse into the future.

This volume details protocols that can be used for generation of knockout animals. Chapters guide the reader through basic protocols for three genome editing technologies, target design tools, and specific protocols for each animal. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Genome Editing in Animals: Methods and Protocols aims to ensure successful results in the further study of this vital field.

An integrated survey of best practices for the management of patients with implanted prosthetic devices and an insightful examination of the epidemiological, societal, and policy issues associated with their use. The devices covered range from breast, penile, vascular, and joint prostheses to cochlear, ossicular, and dental implants, and include cerebrospinal fluid shunts, cardiac valves, stents, and pacemakers. For each device, the authors consider its pros and cons, detail the best current strategies to keep implanted patients healthy, and evaluate the latest and most promising new diagnostic tests, Clinical counterpoints from distinguished authorities at major centers in the United States and Europe are offered throughout. Follow-up recommendations are summarized in a standardized format that allows comparative analysis and lays the foundation for controlled clinical trials and the eventual establishment of evidence-based guidelines.

Carbonic anhydrase (CA) is a seemingly ubiquitous enzyme of profound physiological importance, which plays essential roles in respiration, acid-base homeostasis, bone resorption, calcification, photosynthesis, several biosynthetic pathways and a variety of processes involving ion, gas and fluid transfer. This enzyme, which is present in at least three gene families (a, ss, ?), has found favour as a model for the study of evolution of gene families and for site-directed mutagenesis in structure/function relationships, for protein folding and for transgenic and gene target studies. Since the early use of CA inhibitors as diuretics and in treating congestive heart failure, the enzyme has been target of considerable clinical attention. Much of this is now focused on endeavours to produce a new generation of such drugs for the effective treatment of glaucoma and other potential applications. Recent data, suggesting links between CA and various disease processes, including cancer, have stimulated further...

This two-volume set focuses on the interface between physiologic mechanisms and diagnostic human engineering. Today numerous biomedical sensors are commonplace in clinical practice. The registered biosignals reflect mostly vital physiologic phenomena. In order to adequately apply biomedical sensors and reasonably interpret the corresponding biosignals, a proper understanding of the involved physiologic phenomena, their influence on the registered biosignals, and the technology behind the sensors is necessary. The first volume is devoted to the interface between physiologic mechanisms and arising biosignals, whereas the second volume is focussed on the interface between biosignals and biomedical sensors. The physiologic mechanisms behind the biosignals are described from the basic cellular level up to their advanced mutual coordination level during sleep. The arising biosignals are discussed within the scope of vital physiologic phenomena to foster their understanding and comprehensive analysis.

This monograph covers the entire field of blood group serology, with its main emphasis on the chemical and biochemical basis of blood group specificity. Full consideration is given to molecular biology investigations, in particular to studies on the structure of blood group genes and the molecular biological basis of alleles and rare blood group variants, whereby relevant literature up to the year 2000 is covered. The text is supplemented by numerous illustrations and tables, and detailed reference lists.

Beginning in 1970, the International Bile Acid Meeting has taken place every two years and each time new progress in our understanding of the complex role of bile acids in many metabolic processes of the liver and the intestine has been revealed by a selected group of leading scientists from all over the world. Although originally mainly physiological data on bile acid synthesis and transport were emphasized, and later on also the therapeutic benefit of bile acids in gallstone disease and cholestasis was discovered, we have come now to the molecular biology and genetic era with major discoveries in transport defects and related diseases. This book is the proceedings of Falk Symposium No. 120, held in The Hague, The Netherlands, on October 12-13, 2000 - the 16th International Bile Acid Meeting. One of the main discoveries recently has been the identification of nuclear receptors for bile acids, which gives them a much broader perspective than previously anticipated. It even suggests that bile acids can regulate their biosynthesis and enterohepatic circulation transcriptionally. It will therefore not be surprising that this topic, together with the molecular regulation of cholesterol 7alpha-hydroxylase and cholesterol homeostasis, has a dominant place in these proceedings. Another important topic is the progress in our molecular understanding of hepatic (both at the basolateral and canalicular sites), cholangiocytic and intestinal bile acid transport processes. Further insights into genetic defects causing cholestasis or intestinal malabsorption in animal models and in human diseases are also discussed by a number of well-known authors. Finally the last section deals with new findings on the role of bile acid therapy in cholestatic syndromes or chemoprevention and with the potential benefit of bile acid inhibitors. All contributors provide an update on the most recent developments in their field.