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Two positive regulatory domains have been identified on the IFN-B gene promoter. One of the domains (PRDI) contains the binding site for two nuclear factors termed interferon regulatory factor (IRF)-1 and IRF-2. The second positive regulatory domain (PRDII) comprises a KB-like element. A high degree of homology exists between the IRF-1 and IRF-2 proteins in their N-terminal halves, which comprise the DNA binding domains, but the two factors differ significantly in their C-terminal halves. Some evidence suggested that, unlike IRF-1, IRF-2 acts as a negative regulator of IFN-B transcription.
Cytokines are polypeptides synthesized by many cells which act on a variety of tissues by changing gene expression and cellular metabolism. The pro-inflammatory cytokines are a particular group of cytokines with molecular weights between 8,000 - 25,000 Daltons which appear to be synthesized primarily in association with disease states or during host perterbation. Some 'normal' physiologic events such as strenuous exercise or normal ovulation result in the synthesis of the pro-inflammatory cytokines. These polypeptides are very potent molecules which, at picomolar or even femtomolar concentrations, trigger a variety of responses in cells in vitro but similar concentrations may be effective in vivo when one considers the half-life, clearance and distribution of parenterally administered cytokines.
Cytokines are regulatory polypeptides synthesized by a variety of cells in response to injury, inflammation or infection and which act on different tissues by changing gene expression and cellular metabolism. This book provides the results from recent in vitro studies of the structure and function of various cytokines. It offers an up-to-date overview of the latest advances in cytokine research, including research developments dealing with colony stimulating factors, interferons and growth and differentiation factors - as well as classical hormones such as insulin, neurokinin, somatomedin and parathormones. Several newly identified cytokine receptor structures are also discussed, as are certain activities of the recently discovered 8,000-10,000 m.w. cytokine family.
This volume deals with the in vivo activities of these compounds, focusing both on their relevance to normal physiology and their involvement in the pathophysiology of human disease states. The book contains information on cytokines as possible therapeutic agents and describes experimental procedures being explored by clinical researchers in this field. It provides an up-to-date summary of what is now understood about the biological functions of cytokines and anticipates the future directions for research in this area.
First multi-year cumulation covers six years: 1965-70.