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排序方式: 共有1011条查询结果,搜索用时 20 毫秒
991.
992.
Edward G. McIver Justin Bryans Kristian Birchall Jasveen Chugh Thomas Drake Stephen J. Lewis Joanne Osborne Ela Smiljanic-Hurley William Tsang Ahmad Kamal Alison Levy Michelle Newman Debra Taylor J. Simon C. Arthur Kristopher Clark Philip Cohen 《Bioorganic & medicinal chemistry letters》2012,22(23):7169-7173
The design, synthesis and structure–activity relationships of a novel series of 2,4-diamino-5-cyclopropyl pyrimidines is described. Starting from BX795, originally reported to be a potent inhibitor of PDK1, we have developed compounds with improved selectivity and drug-like properties. These compounds have been evaluated in a range of cellular and in vivo assays, enabling us to probe the putative role of the TBK1/IKKε pathway in inflammatory diseases. 相似文献
993.
994.
1. An adenosine 3':5'-cyclic monophosphate (cyclic AMP)-dependent protein kinase, located predominantly in the cytosol, was studied in canine prostate. 2. The enzyme exhibited cyclic AMP-binding activity, and could be isolated by chromatography on diethylaminoethyl cellulose. 3. The enzyme was maximally stimulated (fourfold) by 1mum-cyclic AMP, and half-maximal activation of the enzyme was observed in presence of 50nm-cyclic AMP. 4. Equilibrium studies at pH5.0 indicated the presence of one major class of binding site for cyclic AMP, with an association constant of approx. 10(8)m(-1). 5. Stimulation of the enzyme was also observed with the 3':5'-cyclic monophosphate derivatives of cytidine, inosine, guanosine and uridine as well as with dibutyryl cyclic AMP, but higher concentrations of these cyclic nucleotides were required to provide the same degree of activation as that seen with cyclic AMP. 6. Comparing alpha-casein, protamine and different histone subfractions as substrates, highest cyclic AMP stimulation was demonstrated with histones. 7. Although maximum velocity of the enzyme was enhanced approximately fivefold in presence of cyclic AMP, kinetic studies indicated that the apparent K(m) for histone (0.5mg/ml) remained the same whether determined in the presence or absence of the cyclic nucleotide. 8. In addition, cyclic AMP did not significantly change the apparent K(m) for ATP (1.2x10(-5)m). 9. The purified enzyme showed an absolute requirement for bivalent metal ion. Substitution of Mn(2+) for Mg(2+) decreased basal protein kinase activity as well as the stimulation noted with cyclic AMP. Similarly, the basal activity was lowered when Mg(2+) was replaced by Ca(2+) and cyclic AMP produced only little stimulation of the prostatic enzyme. 相似文献
995.
The release of Vi antigens from three clinical isolates of Salmonella typhi was measured by a Vi-specific monoclonal antibody. Large quantities of Vi antigens were detected in the culture supernates from all three strains using either passive latex agglutination or rocket immunoelectrophoresis. Vi antigens were also detected in broth cultures of S. typhi containing about 10(5) cells/ml using the sandwich enzyme linked immunosorbent assay. The significance of this finding in relationship to the virulence and the diagnosis of S. typhi was discussed. 相似文献
996.
Ohtaka H.; Tsang J. Y.; Foster A.; Hogg J. C.; Schellenberg R. R. 《Journal of applied physiology》1987,63(2):582-588
The present study examined the effect of leukotrienes on porcine pulmonary vasculature both in vivo and in vitro. In vitro studies using isolated vascular strips demonstrated that pulmonary arterial smooth muscle contracted to leukotriene C4 (LTC4), whereas pulmonary vein smooth muscle did not. Pulmonary arterial contraction was due to both the direct action of LTC4 and secondarily generated thromboxane A2 (TxA2). In vivo, LTC4 injection caused a pronounced but transient increase in pulmonary arterial pressure and pulmonary arterial wedge pressure (Ppw), with a smaller effect on left ventricular end-diastolic pressure. Effects of LTD4 were smaller with comparable pressure changes at all three sites, suggesting a primary cardiac effect. Like LTC4, histamine caused a disproportionate increase in Ppw vs. left ventricular end-diastolic pressure. These observations suggest that LTC4 causes pulmonary venoconstriction in vivo despite its lack of effect on pulmonary vein smooth muscle in vitro. This discrepancy may be due to venoconstrictor effects of TxA2 generated from upstream pulmonary arterial vessels. 相似文献
997.
Divergent effects of 1-oleoyl-2-acetylglycerol and tumor-promoting phorbol ester on rat granulosa cell steroidogenesis in vitro 总被引:1,自引:0,他引:1
The present study was undertaken to compare the effects of diacylglycerol (synthetic 1-oleoyl-2-acetylglycerol; DG) and TPA (12-O-tetradecanoylphorbol 13-acetate) on FSH- and dibutyryl cyclic AMP ((Bu)2cAMP)-stimulated granulosa cell pregnenolone (P5), progesterone (P), and 20 alpha-hydroxypregn-4-en-3-one (20 alpha-OH-P) secretion. Granulosa cells from immature rats pretreated with pregnant mare's serum gonadotropin (PMSG) were incubated for up to 24 h with DG (0-80 micrograms/ml) or TPA (0-80 ng/ml) in the presence or absence of FSH (150 ng/ml) or (Bu)2cAMP (1.5 mM). DG, when continually present in the culture medium (MEM), significantly stimulated basal P5 (in the presence of 25 microM cyanoketone to block further metabolism), P, and 20 alpha-OH-P secretion during 6 h and 24 h of incubation. Pretreatment with TPA for 1 h caused a substantial increase in the subsequent progestin (P + 20 alpha-OH-P) secretion. However, the phorbol ester had little or no effect on steroid secretion during 6 h of incubation, significantly inhibited the secretion of P5 and P, but stimulated 20 alpha-OH-P production in 24 h. DG and TPA exerted divergent effects on FSH- and (Bu)2cAMP-stimulated progestin secretion. Accumulation of P5 throughout the culture periods (1-24 h) was markedly increased by DG (20 micrograms/ml) but significantly inhibited in the presence of TPA (40 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
998.
1-Chloroalkynes were successfully semihydrogenated to the corresponding cis-chloroalkenes in the presence of quinoline-poisoned palladised carbon. Chain extension of 1-chlorododec-cis-4-ene gave stereospecifically pure octadec-cis-10-en-5-ynoic acid. 相似文献
999.
1000.
Kwong-Y. Tsang G. Shashidhar Pai H. Hugh Fudenberg 《In vitro cellular & developmental biology. Plant》1981,17(4):308-314
Summary The characteristics of Cell Line LM-1, established from a human osteosarcoma, have been studied extensively. The cell produced
both bone-specific and placental-like alkaline phosphatases when treated with hydrocortisone 21-phosphate; they had specific
membrane antigens that reacted with sera from osteosarcoma patients. Injection of LM-1 cells into newborn hamsters treated
with antilymphocyte serum produced nodular tumors. The characteristics of LM-1 suggest that this tumor cell line has unique
features that may be useful in a variety of studies of human and animal osteosarcoma.
This research is supported in part by USPHS Grants HD-09938 and CA-25746. 相似文献