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This presentation describes various aspects of the regulation of tissue oxygenation, including the roles of the circulatory system, respiratory system, and blood, the carrier of oxygen within these components of the cardiorespiratory system. The respiratory system takes oxygen from the atmosphere and transports it by diffusion from the air in the alveoli to the blood flowing through the pulmonary capillaries. The cardiovascular system then moves the oxygenated blood from the heart to the microcirculation of the various organs by convection, where oxygen is released from hemoglobin in the red blood cells and moves to the parenchymal cells of each tissue by diffusion. Oxygen that has diffused into cells is then utilized in the mitochondria to produce adenosine triphosphate (ATP), the energy currency of all cells. The mitochondria are able to produce ATP until the oxygen tension or PO2 on the cell surface falls to a critical level of about 4–5 mm Hg. Thus, in order to meet the energetic needs of cells, it is important to maintain a continuous supply of oxygen to the mitochondria at or above the critical PO2 . In order to accomplish this desired outcome, the cardiorespiratory system, including the blood, must be capable of regulation to ensure survival of all tissues under a wide range of circumstances. The purpose of this presentation is to provide basic information about the operation and regulation of the cardiovascular and respiratory systems, as well as the properties of the blood and parenchymal cells, so that a fundamental understanding of the regulation of tissue oxygenation is achieved.
The goal of gene transfer is protein expression. a process brought about by the insertion of a gene coding for a foreign protein into target cells resulting in the synthesis of the foreign protein For gene therapy, a tmnsferred therapeutic gene must be expressed at a level beneficial for the patient. This chapter provides an introductory overview of the rapidly evolving field of non-viral approaches for gene delivery to rnarnrnalian cells. Although currently there are fewer ongoing clinical trials using non-viral approaches than those using viral based systems, the number of non-viral trials is increasing. The long range goal of some research groups is the development of a genetically engineered artificial virus targeted to specific cells in the human body. An arurual conference, organized by Cambridge Healthtech Institute entitled "Artificial Self-Assembling Systems for Gene Transfer", brings together researchers interested in this field [1]. Assembly of an artificial virus is very complex; other research groups aim to develop simpler delivery systems consisting of a plasmid combined with delivery agents. Viral-based systems are very successful for gene delivery, but despite their successes, viral-based systems have some geneml limitations and system-specific limitations. When employing a viml-based system, the following limitations should be considered: • size limitation of the inserted gene due to packaging constraints (e. g. adenovirus, retrovirus) . • potential tumorigenesis (e. g. retrovirus) • potential for insertional mutagenesis (greater than plasmid based systems) • potential imrnunogenicity (e. g.
Adenoviral Vectors for Gene Therapy, Second Edition provides detailed, comprehensive coverage of the gene delivery vehicles that are based on the adenovirus that is emerging as an important tool in gene therapy. These exciting new therapeutic agents have great potential for the treatment of disease, making gene therapy a fast-growing field for research. This book presents topics ranging from the basic biology of adenoviruses, through the construction and purification of adenoviral vectors, cutting-edge vectorology, and the use of adenoviral vectors in preclinical animal models, with final consideration of the regulatory issues surrounding human clinical gene therapy trials. This broad scope of information provides a solid overview of the field, allowing the reader to gain a complete understanding of the development and use of adenoviral vectors. - Provides complete coverage of the basic biology of adenoviruses, as well as their construction, propagation, and purification of adenoviral vectors - Introduces common strategies for the development of adenoviral vectors, along with cutting-edge methods for their improvement - Demonstrates noninvasive imaging of adenovirus-mediated gene transfer - Discusses utility of adenoviral vectors in animal disease models - Considers Federal Drug Administration regulations for human clinical trials
This detailed book provides methodological information on cardiac gene delivery, from classic to state-of-the-art technologies and techniques. Efficient, cardiac-specific, and safe vectors, as well as refined vector delivery methods, are key for successful cardiac gene transfer and eventually for improving patients’ outcomes. Newer vectors and more efficient vector delivery methods have the potential to dramatically improve gene transduction efficacy, while novel gene manipulation techniques enforce the therapeutic power and broaden disease targets. Written for the highly successful Methods in Molecular Biology series, 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, Cardiac Gene Therapy: Methods and Protocols serves as a valuable tool for molecular biologists and physiologists in the cardiology field conducting cardiac gene transfer research, which will ultimately lead to further advancements in the vital field.
This report considers the biological and behavioral mechanisms that may underlie the pathogenicity of tobacco smoke. Many Surgeon General's reports have considered research findings on mechanisms in assessing the biological plausibility of associations observed in epidemiologic studies. Mechanisms of disease are important because they may provide plausibility, which is one of the guideline criteria for assessing evidence on causation. This report specifically reviews the evidence on the potential mechanisms by which smoking causes diseases and considers whether a mechanism is likely to be operative in the production of human disease by tobacco smoke. This evidence is relevant to understanding how smoking causes disease, to identifying those who may be particularly susceptible, and to assessing the potential risks of tobacco products.
Gene transfer research is a rapidly advancing field that involves the introduction of a genetic sequence into a human subject for research or diagnostic purposes. Clinical gene transfer trials are subject to regulation by the U.S. Food and Drug Administration (FDA) at the federal level and to oversight by institutional review boards (IRBs) and institutional biosafety committees (IBCs) at the local level before human subjects can be enrolled. In addition, at present all researchers and institutions funded by the National Institutes of Health (NIH) are required by NIH guidelines to submit human gene transfer protocols for advisory review by the NIH Recombinant DNA Advisory Committee (RAC). Some protocols are then selected for individual review and public discussion. Oversight and Review of Clinical Gene Transfer Protocols provides an assessment of the state of existing gene transfer science and the current regulatory and policy context under which research is investigated. This report assesses whether the current oversight of individual gene transfer protocols by the RAC continues to be necessary and offers recommendations concerning the criteria the NIH should employ to determine whether individual protocols should receive public review. The focus of this report is on the standards the RAC and NIH should use in exercising its oversight function. Oversight and Review of Clinical Gene Transfer Protocols will assist not only the RAC, but also research institutions and the general public with respect to utilizing and improving existing oversight processes.
Angiogenesis and Cardiovascular Disease provides a comprehensive review of the basic scientific and clinical advances in the field of angiogenesis, and its role in the human cardiovascular system. The material presented draws from multiple disciplines, integrating information in a single source. Topics addressed focus first on aspects of development and normal biology of the vasculature, and then on angiogenesis and how it is involved in the pathophysiology and therapy of ischemic cardiovascular disease. Vascular development, endothelial cell biology, the vascular matrix, and growth factors are discussed. Up to date information on current clinical trials, and practical advice concerning application to cardiovascular therapeutic options, are also stressed.
Stem Cell and Gene Therapy for Cardiovascular Disease is a state-of-the-art reference that combines, in one place, the breadth and depth of information available on the topic. As stem cell and gene therapies are the most cutting-edge therapies currently available for patients with heart failure, each section of the book provides information on medical trials from contributors and specialists from around the world, including not only what has been completed, but also what is planned for future research and trials. Cardiology researchers, basic science clinicians, fellows, residents, students, and industry professionals will find this book an invaluable resource for further study on the topic. - Provides information on stem and gene therapy medical trials from contributors and specialists around the world, including not only what has been completed, but also what is planned for future research and trials - Presents topics that can be applied to allogeneic cells, mesenchymal cells, gene therapy, cardiomyoctyes, iPS cells, MAPC's, and organogenesis - Covers the three areas with the greatest clinical trials to date: chronic limb ischemia, chronic angina, and acute MI - Covers the prevailing opinions on how to harness the body's natural repair mechanisms - Ideal resource for cardiology researchers, basic science clinicians, fellows, residents, students, and industry professionals
Research centering on blood flow in the heart continues to hold an important position, especially since a better understanding of the subject may help reduce the incidence of coronary arterial disease and heart attacks. This book summarizes recent advances in the field; it is the product of fruitful cooperation among international scientists who met in Japan in May, 1990 to discuss the regulation of coronary blood flow.
During the past decades, with the introduction of the recombinant DNA, hybridoma and transgenic technologies there has been an exponential evolution in understanding the pathogenesis, diagnosis and treatment of a large number of human diseases. The technologies are evident with the development of cytokines and monoclonal antibodies as therapeutic agents and the techniques used in gene therapy. Immunopharmacology is that area of biomedical sciences where immunology, pharmacology and pathology overlap. It concerns the pharmacological approach to the immune response in physiological as well as pathological events. This goals and objectives of this textbook are to emphasize the developments in immunology and pharmacology as they relate to the modulation of immune response. The information includes the pharmacology of cytokines, monoclonal antibodies, mechanism of action of immune-suppressive agents and their relevance in tissue transplantation, therapeutic strategies for the treatment of AIDS and the techniques employed in gene therapy. The book is intended for health care professional students and graduate students in pharmacology and immunology.