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Exposure of Farage, a human B-cell line, to interleukin 4 (IL4) reduced the amount of CD38 antigen on the surface of the cells and in cell lysates. No evidence was obtained for accelerated breakdown, shedding, or internalization of CD38 molecules following IL4 treatment, nor the accumulation of CD38 molecules in the cell interior. The inhibition of protein synthesis with cycloheximide (CXM) diminished the down-regulation of CD38 induced by IL4. CXM decreased the expression of CD38 in Farage cells with arrested mitosis, and IL4 failed to further reduce CD38 expression. Staurosporine, an inhibitor of serine/threonine protein kinases, and H7 (1-(5-isoquinolinylsulfonyl)-2-methylpiperazine), a preferential inhibitor of protein kinase C (PKC), abrogated the effect of IL4 on CD38, while inhibitors of other serine protein kinases W7 (N-(aminohexyl)-5-chloro-1-naphthalenesulfoamide) and H8 (N-(2-[methylamino]ethyl)-5-isoquinolinesulfonamide) failed to interfere with the effect of IL4. Phorbol 12-myristate 13-acetate (PMA), an activator of PKC, resembled IL4 in decreasing the expression of CD38, and either staurosporine or H7 abolished this effect. Genistein, an inhibitor of tyrosine kinases, increased the expression of CD38, but failed to abrogate the inhibitory effect of IL4 on CD38. It is concluded that serine/threonine protein kinases mediated the IL4-induced down-regulation of the expression of CD38 molecules in B cells.  相似文献   
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To provide material suitable for structural studies of the nicotinic acetylcholine receptor, we have expressed and purified the NH2-terminal extracellular domain of the mouse muscle alpha subunit. Several constructs were initially investigated using Xenopus oocytes as a convenient small scale expression system. A fusion protein (alpha210GPI) consisting of the 210 NH2-terminal amino acids of the alpha subunit and a glycosylphosphatidylinositol anchorage sequence conferred surface alpha-bungarotoxin binding in oocytes. Coexpression of alpha210GPI with an analogous construct made from the delta subunit showed no evidence of heterodimer formation. The alpha210GPI protein was chosen for large scale expression in transfected Chinese hamster ovary cells. The alpha210GPI protein was cleaved from these cells and purified on an immunoaffinity column. Gel and column chromatography show that the purified protein is processed as expected and exists as a monomer. The purified protein also retains the two distinct, conformation-specific binding sites expected for the correctly folded alpha subunit. Circular dichroism studies of alpha210GPI suggest that this region of the receptor includes considerable beta-sheet secondary structure, with a small proportion of alpha-helix.  相似文献   
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Endurance training leads to an increase in the content of individual mitochondrial hemeproteins in skeletal muscle. To deduce the control mechanisms involved, cytochrome oxidase (COX) activity was compared with 1) the content of COX subunits III and IV and 2) 5-aminolevulinate synthase (ALAS) activity and mRNA content. In the plantaris muscle of female rats run daily for up to 28 days, ALAS activity was elevated 100% (P < 0.01) after 3 days and remained 150 and 125% higher (P < 0.001) after 7 and 28 days of running, respectively, than control. COX activity was also increased, but not until day 7 (40%; P < 0.05), and reached a maximal value 80% higher than control (P < 0.001) in the 28-day group. Compared with control, the content of COX subunit III and IV and ALAS mRNAs was not significantly changed by the training. The increased activities of COX and ALAS appear to be regulated by translational or posttranslational steps in the protein expression pathway. The induction of ALAS before COX suggests that the increased activity of COX may require increased synthesis of heme.  相似文献   
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Attention deficit/hyperactivity disorder (ADHD) and conduct disorder (CD) are both disorders of childhood and adolescence that all too frequently extend into adulthood. But just what is the relationship between these two disorders? This study explores the overlap between these two disorders as they relate to juvenile delinquency; both are significant risk factors for the development of antisocial behavior. But there is more significance to the presence or absence of ADHD or CD in later antisocial behavior. Higher levels of defiant and/or aggressive behavior lead to antisocial acts as compared with lower levels of defiance and antisocial acts. Boys diagnosed with ADHD have higher felony rates than normal control boys, yet ADHD is not nearly as strong a predictor of offending behavior as is CD in study subjects. The presence of both CD and ADHD contributes to illegal behavior, and it is likely that early intervention in both disorders will reduce the prevalence of antisocial behavior.  相似文献   
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