GABA (gamma-aminobutyric acid) is the main neurotransmitter regulating sleep. The majority of drugs presently in use for the treatment of sleep disorders act by enhancing GABAergic neuronal inhibition. The GABA system is, therefore, of prime clinical relevance for the therapy of insomnia. The focus of this volume is on the neuropsychopharmacology and the clinical impact of the GABA system in regulating sleep and wakefulness. It presents molecular, neuropharmacological, systems-biological and clinical approaches to the understanding of the mechanism of action of GABA and GABAergic drugs. It also explores the role of GABA in the basic drives that affect sleep, and the influences that adapt sleep and wakefulness to external events.

Pediatric Injury Biomechanics: Archive and Textbook consolidates and describes the current state of the art in pediatric injury biomechanics research in the automotive crash environment. Written by the most respected scientists in the field, the objective of this ground-breaking project is to provide a comprehensive archive and analysis of pediatric injury biomechanics research; to be the go-to reference for the epidemiology of motor vehicle related childhood injury data, pediatric anthropometry, pediatric biomechanical properties, tissue tolerance, and computational models. This book provides essential information needed by researchers working in the field of pediatric injury including those involved in rulemaking activities, injury criteria development, child dummy development, and child injury interventions development. In addition to the text, a companion archive will include valuable information and tools to assist in the identification of gaps in research and future research directions.This living document will be regularly updated with current research and advancements in pediatric injury biomechanics.

The term humanized mouse in this text refers to a mouse in which human tissues and cells have been transplanted and show the same biological function as they do in the human body. That is, the physiological properties and functions of tra- planted human tissues and cells can be analyzed in the mouse instead of using a living human body. It should therefore be possible to study the pathophysiology and treatment of human diseases in mice with good reproducibility. Thus, the hum- ized mouse can be used as a potent tool in both basic and clinical research in the future. The development of appropriate immunodeficient mice has been indispensable in the creation of the humanized mouse, which has been achieved through many years of efforts by several laboratories. The first stage on the road to the humanized mouse was the report on nude mice by Isaacson and Cattanach in 1962. Thereafter, nude mice were studied in detail by Falanagan and, in 1968, Pantelouris found that these mice have no thymus gland, which suggested that the mice lack transplan- tion immunity against xenografts such as human hematopoietic stem cells. At the Nude Mouse Workshops (organized by Regard, Povlsen, Nomura and colleagues) that were held nine times between 1972 and 1997, the possibility of creating a humanized mouse using nude mice was extensively examined. The results, however, showed that certain human cancers can be engrafted in nude mice, but unfortunately engraftment of normal human tissue was almost impossible.

Growth is a complex process that is essential to life. Not only does size play an important role in the process of cellular proliferation, but body size is also a critical factor in determining which organisms live longer. Evolution has been characterised by a dramatic increase in an organism's body size, which is not only limited to the size of the brain.

Regeneration, the homeostatic ability to maintain tissue structure in the face of normal cell turnover or loss of tissue damaged by trauma or disease, is an essential developmental process that continues throughout life. As recently as a decade ago, any serious discussion of the possibility of regeneration becoming a practical medical tool in the near future had the air of science fiction or over-optimistic speculation. The term "regenerative medicine" was certainly on many lips but few actually expected to soon see it applied in a clinical setting. A tidal wave of discovery has changed that and investigating the cellular mechanisms of natural regeneration has become one of the hottest topics in developmental biology and biomedicine in general. Many researchers entering the field find that the regeneration literature is still quite diffuse perhaps owing to the disparate biological systems that have been the object of study including hydra, planaria, newts, axolotls and more recently several mouse strains. The volume editors believe that an attempt to organize or systematize the literature is long overdue. In this volume, respected experts highlight the latest findings in vertebrate (including mammals) wound healing and regeneration. They present eleven reviews that cover a wide range of topics, from wound repair and its relationship to regeneration, through systems including lenticular, neural, and musculoskeletal tissues and limbs, to epigenetics and the role of the cell cycle. Nuclear reprogramming and cellular plasticity, which open the door for potential regenerative medical therapies for injury and degenerative disease, are recurring themes throughout the book. We are all now part of the regeneration revolution.

Developmental genetic studies of the spine and linkage and family-based association studies have led to recent advances in understanding the genetic etiology of idiopathic, neuromuscular, and congenital forms of scoliosis. The book is written by leaders in genetic and developmental research on scoliosis and developmental studies of the spine.

Research into gastrointestinal motility has received renewed interest in part due to recent advances in the techniques for measuring the structure and function of gastrointestinal cells, tissue and organs. The integration of this wealth of data into biophysically based computation models can aid in interpretation of experimental and clinical measurements and the refinement of measurement techniques. The contents of this book span multiple scales - from cell, tissue, organ, to whole body and is divided into four broad sections covering: i) gastrointestinal cellular activity and tissue structure; (ii) techniques for measuring, analyzing and visualizing high-resolution extra-cellular recordings; (iii) methods for sensing gastroelectrical activity using non-invasive bio-electro-magnetic fields and for modulating the underlying gastric electrical activity and finally (iv) methods for assessing manometric and videographic motility patterns and the application of these data for predicting the flow and mixing behavior of luminal contents by using computational fluid dynamic techniques. This book aims to provide both an overview of historical and existing research techniques as well as to highlight future directions and challenges for the community as a whole. It will be suitable for clinicians to understand the cellular and biophysical underpinnings of gastric emptying, gastroenterologists, surgeons, bioengineers and all scientists with interests in gastrointestinal motility research.

Of the approximately 640 muscles in the human body, over 10% of them are found in the craniofacial region. The craniofacial muscles are involved in a number of crucial non-locomotor activities, and are critical to the most basic functions of life, including vision, taste, chewing and food manipulation, swallowing, respiration, speech, as well as regulating facial expression and controlling facial aperture patency. Despite their importance, the biology of these small skeletal muscles is relatively unexplored. Only recently have we begun to understand their unique embryonic development and the genes that control it and characteristic features that separate them from the skeletal muscle stereotype. This book is the most comprehensive reference to date on craniofacial muscle development, structure, function, and disease. It details the state-of-the-art basic science of the craniofacial muscles, and describes their unique response to major neuromuscular conditions. Most importantly, the text highlights how the craniofacial muscles are different from most skeletal muscles, and why they have been viewed as a distinct allotype. In addition, the text points to major gaps in our knowledge about these very important skeletal muscles and identified key gaps in our knowledge and areas primed for further study and discovery.

The volume raises attention to the need of a completely new approach to breast cancer based on the knowledge collected on early breast cancer in the past two decades. The chapters are contributed by experts of all the fields participating in the clinical research and care of breast cancer. The practical importance of such a book is underlined by the increasing number of breast cancer cases, and also the increasing proportion of early stage-cases. The ultimate goal of the book is to point to the heterogeneous nature of the disease which is more striking and has more importance in care at the very early stages than at the more advanced stages. The book recommends the utilization of all the information provided by multimodality imaging and special pathological methods, a new classification system and therapeutic guidelines since early breast cancers should not be treated based on experience obtained with palpable tumors. No similar book has been yet released to the market. The book is written for all the members of the team participating in the diagnosis and treatment of breast cancer (radiologists, pathologists, surgeons, clinical and radiation oncologists), but may be useful for medical students and residents too. The chapters are illustrated with didactic pictures, and special emphasis is given to provide a peep into the practice of the special procedures for the careful examination and individualized therapy of each case.

Biomechanics applies the principles and rigor of engineering to the mechanical properties of living systems. This book integrates the classic fields of mechanics--statics, dynamics, and strength of materials--using examples from biology and medicine. Fundamentals of Biomechanics is excellent for teaching either undergraduates in biomedical engineering programs or health care professionals studying biomechanics at the graduate level. Extensively revised from a successful first edition, the book features a wealth of clear illustrations, numerous worked examples, and many problem sets. The book provides the quantitative perspective missing from more descriptive texts, without requiring an advanced background in mathematics. It will be welcomed for use in courses such as biomechanics and orthopedics, rehabilitation and industrial engineering, and occupational or sports medicine.

J.A. Roth: Membrane-Bound Catechol-O-Methyltreansferase: A Reevaluation of Its Role in the O-Methylation of the Catecholamine Transmitters. D.J. Benos, S. Cunningham, R.R. Baker, K.B. Beason, Y. Oh, and P.R. Smith: Molecular Characteristics of Amiloride-Sensitive Sodium Channels. D. Pette and G. Vrbov : Adaptation of Mammalian Skeletal Muscle Fibers to Chronic Electrical Stimulation.

Image-Based Computational Modeling of the Human Circulatory and Pulmonary Systems provides an overview of the current modeling methods and applications enhancing interventional treatments and computer-aided surgery. A detailed description of the techniques behind image acquisition, processing and three-dimensional reconstruction are included. Techniques for the computational simulation of solid and fluid mechanics and structure interaction are also discussed, in addition to various cardiovascular and pulmonary applications. Engineers and researchers involved with image processing and computational modeling of human organ systems will find this a valuable reference.

R. Levenson: Isoforms of the Na,K-ATPase: Family Members in Search of Function.- E. Petzinger: Transport of Organic Anions in the Liver. An Update on Bile Acid, Fatty Acid, Monocarboxylate, Anionic Amino Acid, Cholephilic Organic Anion and Anionic Drug Transport.- E. Schultz, K.M. McCormick: Skeletal Muscle Satellite Cells.

K.W. Bock: The Aryl Hydrocarbon or Dioxin Receptor: Biologic and Toxic Responses.- K. Grieshaber, I. Hardewig, U. Kreutzer, and H.-O. Poertner: Physiological and Metabolic Responses to Hypoxia in Invertebrates.- K.-W. Koch: Calcium as Modulator of Phototransduction in Vertebrate Photoreceptor Cells.

This reference provides a synthesis of the whole field of vascular biology, from the latest advances in the study of the structure and function of blood vessels to recent investigations of their interaction with blood cells, with non-cellular constituants of the blood, or with cells of the neighbouring tissue. The latest results from tumor angiogenesis to the latest advances in atherosclerosis research are discussed by leading experts in the field. Together with the CD-ROM this guarantees both researchers and clinicians quick and easy access to all relevant information.

The book reviews the literature on the regulation of NADPH oxidase, which is controversial in many areas, and refers specifically to relevant publications from the past 4 years. Main topics are catalytical properties, cofactor requirements and structural components of NADPH oxidase, activation of NADPH oxidase, inhibition of NADPH oxidase, reconstitution and regulation of NADPH oxidase activity in cell-free systems, and pathology of NADPH oxidase.

At the Fifth International Neuromuscular Meeting held in Tokyo in 1994, leading experts in the field came together to discuss the physiology and pharmacology of neuromuscular receptor sites and neuromuscular blocking agents (NBAs). The proceedings of the meeting present a review of the history of muscle relaxants and a comprehensive examination of recent research, with a primary focus on clinical considerations. Among the topics covered by specific chapters are aspects of the neuromuscular junction (NMJ), pharmacokinetics, metabolism and metabolites of neuromuscular blocking agents, and drug interaction. Presenting the most up-to-date knowledge of the physiology and pharmacology of the NMJ and NBAs, this volume will be highly valuable to clinicians and researchers in anesthesiology, physiology, and pharmacology.

P.J. Pearson, P.M. Vanhoutte: Vasodilator and Vasoconstrictor Substances Produced by the Endothelium. L. Dux: Muscle Relaxation and Sarcoplasmic Reticulum Function in Different Muscle Types. C.C. Ashley, P.J. Griffith, T.J. Lea, I.P. Mulligan, R.e. Palmer, and S.J. Simnett: Barnacle Muscle: Ca2+ Activation and Mechanics.

Knowledge of the juxtaglomerular apparatus (JGA) of the kidney and of the synthesis and secretion of renin has increased to such an extent over the past few years that it is now appropriate to summarize this knowledge in a monograph on the JGA, the first of its kind. It was the authors' special concern to demonstrate the association between structure and function for renin secretion, not only within the juxtaglomerular region, but also in the region of the renal cortex beyond the JGA. The description of the pathology of the human JGA, studded with references to experimental findings but nevertheless fully self-contained, should help to make this monograph also useful for clinicians.