Summary of Genes. Thirty years ago, the gene responsible for cystic fibrosis (CF), a recessive genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator gene, was identified. This progress has considerably changed our understanding of the pathophysiology of CF and has paved the way for the development of novel and specific therapies for the disease. The CFTR gene contains 27 exons and is characterized by a frequent three base pair deletion of the p.Phe508del. As a result of collaborative work, today more than 2000 mutations have been reported in the gene, and their impact on protein function is now more evident and useful in designing new strategies to correct the gene defect. The field of gene therapy, as illustrated by Ziying Yan in this book, has worked on identifying an efficient vector system for the delivery of the wild-type CFTR gene to the lung. At the same time, animal models have been developed in mice, rats, rabbits, zebrafish, ferrets, and pigs to establish the efficacity of gene delivery. These animals are also of the utmost importance in testing new molecules as modulators or correctors to improve the CFTR lung function. During the last three decades, the epidemiology of CF has dramatically changed, as today cystic fibrosis is now a chronic adult pulmonary disease.

Gene transfer within humans has been an obstacle until about 10 years ago. At that time, it was found that viral vectors were effective carriers of "healthy genes" into patients' cells. The problem, however, was that viral vectors proved unnecessarily harmful to humans: subjects experienced inflamatory activity and negative immunological responses to the genes. Viral vectors were also unable to meet the needs of the pharmaceutical community: they were not reproducible in large-scale proportions in cost-effective ways.Thus, research was undertaken to find a safer way to transfer genes to patients without jeopardizing the safety of the patient. And so non-viral vectors were discovered. This volume presents the various non-viral vectors currently under development. Although not methodologically oriented, it will provide the necessary details behind the development of the vectors. This information will prove useful to both researchers and clinicians.Key Features* Presents state-of-the art developments of nonviral vectors as tools for modern molecular medicine* Covers all types of nonviral vectors, from molecular structure to therapeutic applicationProvides a comprehensive review of synthetic vectors* Includes contributions from major investigators and leading experts in the field

This book describes the new imaging techniques being developed to monitor physiological, cellular and subcellular function within living animals. This exciting field of imaging science brings together physics, chemistry, engineering, biology and medicine to yield powerful and versatile imaging approaches. By combining advanced non-invasive imaging technologies with new mechanisms for visualizing biochemical events and protein and gene function, non-invasive vertebrate imaging enables the in vivo study of biology and offers rapid routes from basic discovery to drug development and clinical application. Combined with the availability of an increasing number of animal models of human disease, and the ability to perform longitudinal studies of disease evolution and of the long-term effects of therapeutic procedures, this new technology offers the next generation of tools for biomedical research. Well illustrated, largely in colour, the book reviews the most common and technologically advanced methods for vertebrate imaging, presented in a clear, comprehensive format. The basic principles are described, followed by several examples of the use of imaging in the study of living multicellular organisms, concentrating on small animal models of human diseases. The book illustrates: The types of information that can be obtained with modern in vivo imaging; The substitution of imaging methods for more destructive histological techniques; The advantages conferred by in vivo imaging in building a more accurate picture of the response of tissues to stimuli over time while significantly reducing the number of animals required for such studies. Part 1 describes current techniques in in vivo imaging, providing specialists and laboratory scientists from all disciplines with clear and helpful information regarding the tools available for their specific research field. Part 2 looks in more detail at imaging organ development and function, covering the brain, heart, lung and others. Part 3 describes the use of imaging to monitor various new types of therapy, following the reaction in an individual organism over time, e.g. after gene or cell therapy. Most chapters are written by teams of physicists and biologists, giving a balanced coherent description of each technique and its potential applications.

Within the framework of clinical internal medicine, they will gain critical knowledge of the many powerful molecular biology-based developments now so rapidly enhancing our understanding of the pathophysiology of disease, improving the feasibility and accuracy of diagnostic testing, and opening novel therapeutic avenues, including gene therapy. Readers will also gain a fuller understanding of the role played by genetic defects in a host of diseases, among them peripheral neuropathies, Alzheimer's disease, arrhythmias, leukemias and lymphomas, cystic fibrosis, hepatitis, HIV, autoimmune disorders, polycystic kidney disease, schizophrenia, affective disorders, alcoholism, Huntington's disease, and many more.

This Brief is devoted to the CFTR protein and cystic fibrosis, and it provides an updated perspective of the genetic, functional and cellular processes involved in this conformational disorder. Starting with a historical perspective on cystic fibrosis and its clinical features, the author departs into an in-depth description of the biology of the CFTR protein, ending with a discussion on the latest approaches aimed at developing corrective therapies for cystic fibrosis. First the basic aspects of cystic fibrosis as a disorder are addressed, focusing on genetics and mutation prevalence. Then the CFTR protein is discussed in detail: its structure and classification within the ABC transporter superfamily, its biogenesis with membrane insertion and chaperone assisted folding, its glycosylation and how it regulates the endoplasmatic reticulum quality control mechanisms that assess CFTR folding status. Extra attention is given to post-ER trafficking and regulation of membrane stability and anchoring, and to CFTR functions. This is linked to the molecular mechanisms through which different CFTR mutations cause cystic fibrosis. Finally, the different efforts aiming at rescuing the basic defect, most of which aim at repairing CFTR dysfunction, are covered. Through this integrated perspective, readers will obtain a unique insight into this fascinating membrane-bound protein and its associated disease. This Brief appeals to an audience interested in human genetics, protein folding, protein trafficking and physiology.

Now in its 6th edition, Cummings Otolaryngology remains the world's most detailed and trusted source for superb guidance on all facets of head and neck surgery. Completely updated with the latest minimally invasive procedures, new clinical photographs, and line drawings, this latest edition equips you to implement all the newest discoveries, techniques, and technologies that are shaping patient outcomes. Be certain with expert, dependable, accurate answers for every stage of your career from the most comprehensive, multi-disciplinary text in the field! Consult this title on your favorite e-reader, conduct rapid searches, and adjust font sizes for optimal readability. Overcome virtually any clinical challenge with detailed, expert coverage of every area of head and neck surgery, authored by hundreds of leading luminaries in the field. Experience clinical scenarios with vivid clarity through a heavily illustrated, full-color format which includes approximately 3,200 images and over 40 high quality procedural videos. Get truly diverse perspectives and worldwide best practices from a multi-disciplinary team of contributors and editors comprised of the world’s leading experts. Glean all essential, up-to-date, need-to-know information. All chapters have been meticulously updated; several extensively revised with new images, references, and content. Stay at the forefront of your field with the most updated information on minimally-invasive surgical approaches to the entire skull base, vestibular implants and vestibular management involving intratympanic and physical therapy-based approaches, radiosurgical treatment of posterior fossa and skull base neoplasms, and intraoperative monitoring of cranial nerve and CNS function. Apply the latest treatment options in pediatric care with new chapters on pediatric sleep disorders, pediatric infectious disease, and evaluation and management of the infant airway. Find what you need faster through a streamlined format, reorganized chapters, and a color design that expedites reference. Manage many of the most common disorders with treatment options derived from their genetic basis. Assess real-world effectiveness and costs associated with emergent technologies and surgical approaches introduced to OHNS over the past 10 years. Incorporate recent findings about endoscopic, microscopic, laser, surgically-implantable, radiosurgical, neurophysiological monitoring, MR- and CT-imaging, and other timely topics that now define contemporary operative OHNS. Take it with you anywhere! With Expert Consult, you'll have access the full text, video clips, and more online, and as an eBook - at no additional cost!