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Author: Abul K. Abbas
Publisher: Springer Science & Business Media
ISBN: 1461223768
Category : Medical
Languages : en
Pages : 247
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Book Description
This book contains the proceedings of the Serono Symposia USA interna tional symposium on Genetic Models of Immune and Inflammatory Dis eases held on October 20 to 23, 1994, in Savannah, Georgia. The advent of methods for introducing genes into the germlines of mice, and for targeted disruption of particular genes by homologous recombination, has provided scientists in many disciplines with an extraordinarily powerful set of analyti cal tools. Some of the most informative applications of transgenic and gene knockout technology have been in studies of lymphocyte development and activation. The goal of this symposium was to bring together investigators using these genetic approaches for analyzing the immune system, with a view to defining common themes and novel directions. Transgenic mice have a wide variety of important applications in immu nology. Defined proteins can be expressed in selected tissues throughout development, thus acquiring the essential characteristic of "self" antigens. Such models have been used to study how immune responses to these artificially created "self" antigens are controlled. Antigen receptors of lym phocytes have been expressed as transgenes, and because lymphocytes are endowed with the unique property of allelic exclusion, such transgenic mice become essentially monospecific. Immunomodulatory agents have been expressed in defined tissues or throughout the body, providing tools for studying the functional consequences of dysregulated expression of biologi cal response modifiers.
Author: Abul K. Abbas
Publisher: Springer Science & Business Media
ISBN: 1461223768
Category : Medical
Languages : en
Pages : 247
Get Book Here
Book Description
This book contains the proceedings of the Serono Symposia USA interna tional symposium on Genetic Models of Immune and Inflammatory Dis eases held on October 20 to 23, 1994, in Savannah, Georgia. The advent of methods for introducing genes into the germlines of mice, and for targeted disruption of particular genes by homologous recombination, has provided scientists in many disciplines with an extraordinarily powerful set of analyti cal tools. Some of the most informative applications of transgenic and gene knockout technology have been in studies of lymphocyte development and activation. The goal of this symposium was to bring together investigators using these genetic approaches for analyzing the immune system, with a view to defining common themes and novel directions. Transgenic mice have a wide variety of important applications in immu nology. Defined proteins can be expressed in selected tissues throughout development, thus acquiring the essential characteristic of "self" antigens. Such models have been used to study how immune responses to these artificially created "self" antigens are controlled. Antigen receptors of lym phocytes have been expressed as transgenes, and because lymphocytes are endowed with the unique property of allelic exclusion, such transgenic mice become essentially monospecific. Immunomodulatory agents have been expressed in defined tissues or throughout the body, providing tools for studying the functional consequences of dysregulated expression of biologi cal response modifiers.
Author: Christopher H. Evans
Publisher: Birkhäuser
ISBN: 3034884788
Category : Medical
Languages : en
Pages : 278
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Book Description
Gene therapy for inflammatory diseases is a new , burgeoning field of medicine. Edited by the undisputed pioneers of this area of research, this volume is the first devoted to its topic. It contains thirteen chapters, each written by leaders in their respective fields, that summarize the state of the art in developing novel, gene based treatments for inflammatory diseases. As well as providing an introduction to the basic concepts of gene therapy and the use of naked DNA approaches, the book describes the advances that have been made in applying them to arthritis, lupus, multiple sclerosis, diabetes, Sjogren`s syndrome and transplantation.One chapter is devoted to discussing the first human clinical trials that apply gene therapy to the treatment of an inflammatory disease. As well as providing novel therapeutic approaches, gene therapy facilitates the development of new and improved animal models of disease; a chapter describing these advances is also included. As an up-to-date, timely book written by th
Author: Yuti Chernajovsky
Publisher: Springer Science & Business Media
ISBN: 3034601654
Category : Medical
Languages : en
Pages : 249
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Book Description
In this monograph about gene therapy of autoimmune and inflammatory d- orders we have gathered international experts and leaders from different fields to review the state of the art advances on topics ranging from disease entities to vectors and engineered cells. The different approaches described in each chapter take into consideration the biomedical knowledge of these diseases and address the complexities of delivering long-term genetic interventions. Gene therapy also serves as a testing ground for new therapeutic entities and helps provide proof of principle for their potential therapeutic role in animal models of disease. Scaling up from mice to men still remains an important h- dle not only from the quantitative point of view, but also for currently unknown and unexpected secondary effects of the vector or the transgene. Some of these approaches have already been tested in the clinic, but much more needs to be done to understand the human conditions treated and the n- ural history of their pathology. We are indebted to the secretarial assistance of Ms. Lin Wells (Bone and Joint Research Unit, London, UK) and the help of Hans Detlef Klüber for his help in getting this book published. We hope this book will be of interest to c- nicians and scientists and inspiring to students of the subject who will use their own ingenuity and knowledge to further forward this discipline into clinical use.
Author: A. N. Theofilopoulos
Publisher: Karger Medical and Scientific Publishers
ISBN: 3805568142
Category : Science
Languages : en
Pages : 304
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Book Description
Autoimmunity is one of the most highly investigated areas of immunologic research. The principle of immune system discrimination between self and foreign molecules is fundamental to the survival of the species, and the failure to establish or maintain this discrimination can lead to a wide spectrum of diseases. As a consequence of intensive studies, much has been learned with regard to the normal functioning of the immune system and the editing processes by which self-tolerance is established. Moreover, many theories and experimental models have been developed to explore the mechanisms of autoimmune disease pathogenesis. This book is the first volume of the new series 'Current Directions in Autoimmunity', which aims to consolidate current knowledge of autoimmunity focusing on both basic and clinical aspects. Given that these diseases have a strong genetic basis, it seems appropriate that the first volume addresses this topic. It reviews the most recent findings on genes affecting autoimmunity and genome-wide studies defining the multiple loci predisposing to prominent autoimmune diseases, such as lupus, arthritis, diabetes and multiple sclerosis. For each of these entities, studies in experimental models as well as humans are covered. The authoritative and timely material will be of interest to investigators in the fields of immunology and genetics, to clinicians with interest in rheumatology, endocrinology and neurology, and to those working to devise gene-specific therapies for a variety of inflammatory conditions.
Author: Abbas Raza
Publisher:
ISBN:
Category : Animal models in research
Languages : en
Pages : 596
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Book Description
Our understanding of genetic predisposition to inflammatory and autoimmune diseases has been enhanced by large scale quantitative trait loci (QTL) linkage mapping and genome-wide association studies (GWAS). However, the resolution and interpretation of QTL linkage mapping or GWAS findings are limited. In this work, we complement genetic predictions for several human diseases including multiple sclerosis (MS) and systemic capillary leakage syndrome (SCLS) with genetic and functional data in model organisms to associate genes with phenotypes and diseases. Focusing on MS, an autoimmune inflammatory disease of the central nervous system (CNS), we experimentally tested the effect of three of the GWAS candidate genes (SLAMF1, SLAMF2 and SLAMF7) in the experimental autoimmune encephalomyelitis (EAE) mouse model and found a male-specific locus distal to these loci regulating CNS autoimmune disease. Functional data in mouse suggests this male-specific locus modulates the frequency of immune cells including CD11b+, TCR[alpha beta]+CD4+Foxp3+, and TCR[alpha beta]+CD8+IL-17+ cells during EAE disease. Orchiectomy experiments demonstrate that this male specific phenotype is dependent on testis but not testosterone (T) or 5[alpha]-dihydrotestosterone (DHT). Using a bioinformatic approach, we identified SLAMF8 and SLAMF9 along with other differentially expressed genes in linkage with MS-GWAS predictions whose expression is testis-dependent, but not directly regulated by T or DHT, as potential positional candidates regulating CNS autoimmune disease. Further refinement of this locus is required to identify the causal gene(s) that may be targeted for prevention and/or treatment of MS in men. Using SCLS, an extremely rare disorder of unknown etiology characterized by recurrent episodes of vascular leakage, we identified and modeled this disease in an inbred mouse strain, SJL, using susceptibility to histamine- and infection-triggered vascular leak as the major phenotypic readout. This trait "Histamine hypersensitivity" (Histh/Histh) was mapped to a region on Chr 6. Remarkably, Histh is syntenic to the genomic locus most strongly associated with SCLS in humans (3p25.3). Subsequent studies found that the Histh locus is not unique to SJL but additional mouse strains also exhibit Histh phenotype. Considering GWAS studies in SCLS are limited by the small number of patients, we utilized interval-specific SNP-based association testing among Histh phenotyped mouse strains to predict Histh candidates. Furthermore, to dissect the complexity of Histh QTL, we developed network-based functional prediction methods to rank genes in this locus by predicting functional association with multiple Histh-related processes. The top-ranked genes include Cxcl12, Ret, Cacna1c, and Cntn3, all of which have strong functional associations and are proximal to SNPs segregating with Histh. Lastly, we utilized the power of integrating genetic and functional approaches to understand susceptibility to Bordetella pertussis and pertussis toxin (PTX) induced histamine sensitization (Bphs/Bphs), a sub-phenotype with an established role in autoimmunity. Congenic mapping in mice had earlier linked Bphs to histamine H1 receptor gene (Hrh1/H1R) and demonstrated that H1R differs at three amino acid residues in Bphs-susceptible and -resistant mice. Our subsequent studies identified eight inbred mouse strains that were susceptible to Bphs despite carrying a resistant H1R allele. Genetic analyses mapped the locus complementing Bphs to mouse Chr 6, in linkage disequilibrium with Hrh1; we have designated this Bphs-enhancer (Bphse). Similar to the approaches used for Histh, we utilized interval-specific SNP based association testing and network-based functional enrichment to predict nine candidate loci for Bphse including Atp2b2, Atg7, Pparg, Syn2, Ift122, Raf1, Mkrn2, Timp4 and Gt(ROSA)26Sor. Overall, these studies demonstrate the power of integrating genetic and functional methods in humans and animal models to predict highly plausible loci underlying QTL/GWAS data.
Author: Steven A. Frank
Publisher: Princeton University Press
ISBN: 9780691095950
Category : Medical
Languages : en
Pages : 364
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Book Description
Publisher Description
Author: National Research Council
Publisher: National Academies Press
ISBN: 0309220424
Category : Science
Languages : en
Pages : 200
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Book Description
For many years, experiments using chimpanzees have been instrumental in advancing scientific knowledge and have led to new medicines to prevent life-threatening and debilitating diseases. However, recent advances in alternate research tools have rendered chimpanzees largely unnecessary as research subjects. The Institute of Medicine, in collaboration with the National Research Council, conducted an in-depth analysis of the scientific necessity for chimpanzees in NIH-funded biomedical and behavioral research. The committee concludes that while the chimpanzee has been a valuable animal model in the past, most current biomedical research use of chimpanzees is not necessary, though noted that it is impossible to predict whether research on emerging or new diseases may necessitate chimpanzees in the future.
Author: Gerald J. Prud'homme
Publisher: Springer
ISBN: 9780306479915
Category : Medical
Languages : en
Pages : 149
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Book Description
Autoimmune diseases are diverse and responsible for considerable morbidity. Their etiology remains largely unknown, and current therapy with anti-inflammatory drugs is prone to adverse effects, and rarely curative. New therapies with anti-cytokine antibodies or receptors are promising, but require frequent administration of expensive protein drugs. Gene Therapy of Autoimmune Diseases comprehensively reviews research in gene therapy for autoimmune diseases with viral or non-viral vectors. Gene therapy offers the possibility of long-term, continuous delivery of a wide variety of immunosuppressive, anti-inflammatory, or tolerance-inducing agents. Moreover, highly specific genetically modified cells can be produced. This book discusses the most promising avenues in this exciting new field.
Author: Kenneth Murphy
Publisher: Garland Science
ISBN: 9780815344575
Category : Medical
Languages : en
Pages :
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Book Description
The Janeway's Immunobiology CD-ROM, Immunobiology Interactive, is included with each book, and can be purchased separately. It contains animations and videos with voiceover narration, as well as the figures from the text for presentation purposes.
Author: Irun R. Cohen
Publisher: Academic Press
ISBN:
Category : Medical
Languages : en
Pages : 360
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Book Description
Because autoimmune disorders can wreak havoc in both humans and animals, these disorders are now the objects of intense and focused research. This book details specific animal models for a variety of autoimmune disorders. The contributors are recognized authorities who deal with the panoply of experimentally induced autoimmune disorders, including encephalomyelitis, allergic neuritis, uveoretinitis, myocarditis, and hepatitis. Also included are discussions of spontaneously appearing diseases such as autoimmune thyroiditis and systemic lupus erythematosus. Many other disorders are also covered in this comprehensive guide. Certain to be an aid in the planning of individual experiments and broader research programs, this book will be a valuable addition to the library of all practicing immunologists interested in immune system function and dysfunction.
