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排序方式: 共有181条查询结果,搜索用时 15 毫秒
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Activated protein C decreases plasminogen activator-inhibitor activity in endothelial cell-conditioned medium 总被引:12,自引:0,他引:12
van Hinsbergh VW; Bertina RM; van Wijngaarden A; van Tilburg NH; Emeis JJ; Haverkate F 《Blood》1985,65(2):444-451
Confluent cultures of endothelial cells from human umbilical cord were used to study the effect of activated human protein C (APC) on the production of plasminogen activators, plasminogen activator-inhibitor, and factor VIII-related antigen. Addition of APC to the cells in a serum-free medium did not affect the production of tissue-type plasminogen activator (t-PA) or factor VIII-related antigen; under all measured conditions, no urokinase activity was found. However, less plasminogen activator-inhibitor activity accumulated in the conditioned medium in the presence of APC. This decrease was dose dependent and could be prevented by specific anti-protein C antibodies. No decrease was observed with the zymogen protein C or with diisopropylfluorophosphate-inactivated APC. APC also decreased the t-PA inhibitor activity in endothelial cell-conditioned medium in the absence of cells, which suggests that the effect of APC is at least partly due to a direct effect of APC on the plasminogen activator- inhibitor. High concentrations of thrombin-but not of factor Xa or IXa-- had a similar effect on the t-PA inhibitor activity. The effect of APC on the plasminogen activator-inhibitor provides a new mechanism by which APC may enhance fibrinolysis. The data suggest that activation of the coagulation system may lead to a secondary increase of the fibrinolytic activity by changing the balance between plasminogen activator(s) and its (their) fast-acting inhibitor. 相似文献
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R. W. J. Meijers N. H. R. Litjens E. A. de Wit A. W. Langerak A. van der Spek C. C. Baan W. Weimar M. G. H. Betjes 《Clinical and experimental immunology》2013,174(3):424-432
Cytomegalovirus (CMV) infection has been implicated in accelerated T cell ageing. End‐stage renal disease (ESRD) patients have a severely immunologically aged T cell compartment but also a high prevalence of CMV infection. We investigated whether CMV infection contributes to T cell ageing in ESRD patients. We determined the thymic output by the T cell receptor excision circle (TREC) content and percentage of CD31+ naïve T cells. The proliferative history of the T cell compartment by determination of the relative telomere length (RTL) and the T cell differentiation status was determined by immunophenotyping. It appeared that CMV infection did not affect thymic output but reduced RTL of CD8+ T cells in ESRD patients. Moreover, increased T cell differentiation was observed with higher percentages of CD57+ and CD28null CD4+ and CD8+ memory T cells. These CD28null T cells had significantly shorter telomeres compared to CD28+ T cells. Therefore we concluded that CMV infection does not affect the decreased thymic output but increases T cell differentiation as observed in ESRD‐related premature T cell ageing. 相似文献
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The JB6 mouse epidermal cell system has been used extensively as an in
vitro transformation model for the study of tumor promotion. The standard
JB6 cell assay for promotion of transformation is carried out in soft agar
or other anchorage independent conditions. The present study was directed
to the development of an in vivo model to distinguish the promotion
resistant (P-) and promotion sensitive (P+) progression phenotypes. Results
indicate that the grafting assay distinguishes P- and P+ cells in vivo with
P+ but not P- cells forming tumors within 7-9 weeks. Expression of dominant
negative mutant jun TAM67 blocks both anchorage independent transformation
response and graft bed tumor formation by P+ cells, suggesting that the
requirement for AP-1 activation in transformation now applies in vivo.
Expression of mutated p53 produced a gain of P+ phenotype in P- cells in
vitro, but not in vivo. Histochemical and Northern blot analysis for
expression of various keratinocyte markers revealed no evidence for
expression, suggesting a loss of keratinocyte markers following
establishment in culture. In summary, the skin-grafting assay described in
this study appears to be a valid in vivo assay for distinguishing the
preneoplastic progression phenotypes represented by JB6 P- and P+ cells.
相似文献
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Litjens NH Burggraaf J van Strijen E van Gulpen C Mattie H Schoemaker RC van Dissel JT Thio HB Nibbering PH 《British journal of clinical pharmacology》2004,58(4):429-432
AIMS: To characterize the pharmacokinetics of fumarates in healthy subjects. METHODS: Ten subjects received a single fumarate tablet (containing 120 mg of dimethylfumarate and 95 mg of calcium-monoethylfumarate) in the fasted state and after a standardized breakfast in randomized order. Prior to and at fixed intervals after the dose, blood samples were drawn and the concentrations of monomethylfumarate, the biologically active metabolite, as well as dimethylfumarate and fumaric acid were measured using high-performance liquid chromatography. RESULTS: After a lag time, a transient increase in serum monomethylfumarate concentrations in the blood was observed, whereas dimethylfumarate and fumaric acid concentrations remained below the detection limit. The tlag was 240 min [range 60-603 min; 95% confidence interval (CI) 139, 471] shorter when the tablet was taken after an overnight fast (90 min; range 60-120 min; 95% CI 66, 107) than when taken with breakfast (300 min; range 180-723 min; 95% CI 0, 1002). The tmax was 241 min (range 60-1189 min, 95% CI 53, 781) shorter when the tablet was taken after an overnight fast (182 min; range 120-240 min; 95% CI 146, 211) than when taken with breakfast (361 min; range 240-1429 min; 95% CI 0, 1062). The mean Cmax for monomethylfumarate in the blood of fasting subjects was to 0.84 mg l(-1) (range 0.37-1.29 mg l(-1); 95% CI 0.52, 1.07) and did not differ from that in fed subjects (0.48 mg l(-1); range 0-1.22 mg l(-1); 95% CI 0, 5.55). CONCLUSIONS: The pharmacokinetics of monomethylfumarate in healthy subjects after a single tablet of fumarate are highly variable, particularly after food intake. Further experiments exploring the pharmacokinetics of oral fumarates are warranted in order to elucidate the mechanisms underlying variability in response in patients. 相似文献
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AI Zijlstra GD Offner NH Afdhal M van Overveld GN Tytgat AK Groen 《Gastroenterology》1996,110(6):1926-1935
BACKGROUND & AIMS: Many putative pronucleating proteins have been isolated from the biliary concanavalin A (con A)-binding fraction. The pronase resistance of the overall nucleating-promoting activity was almost never taken into consideration. The aim of this study was to identify the major pronase-resistant con A-binding glycoproteins. METHODS: Pronase-treated and -untreated con A-binding glycoproteins were separated on a Superose 12 gel permeation column (Pharmacia, Uppsala, Sweden) and tested in a crystal growth assay. Proteins were identified by amino-terminal sequencing. RESULTS: Con A-binding pronucleating activity eluted in two peaks on the Superose column. This activity was unaltered after pronase treatment. Activity peak I contained too little protein to allow amino-terminal sequencing. In activity peak II, the major pronase-resistant con A-binding glycoproteins were identified as alpha 1-antitrypsin and alpha 1- antichymotrypsin. The 130-kilodalton nucleation promoter was identified as aminopeptidase N, but the full pronase resistance of this protein, reported earlier, was not confirmed. Immunoabsorptive removal of alpha 1-antitrypsin and alpha 1-antichymotrypsin and immunopurification showed that only alpha 1-antichymotrypsin had pronucleating activity. CONCLUSIONS: The pronase resistance of the nucleating-promoting activity of the con A-binding glycoprotein fraction was confirmed. An important part of this activity could be attributed to alpha 1- antichymotrypsin. It is an acute-phase protein, as are many other pronucleating proteins, which might indicate a general mechanism of action in gallstone formation. (Gastroenterology 1996 Jun;110(6):1926-35) 相似文献