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排序方式: 共有5047条查询结果,搜索用时 281 毫秒
31.
Ning C Reynolds R Chen J Yager C Berry GT Leslie N Segal S 《Molecular genetics and metabolism》2001,72(4):306-315
Mice deficient in galactose-1-phosphate uridyltransferase (GALT) demonstrate abnormal galactose metabolism but no obvious clinical phenotype. To further dissect the pathways of galactose metabolism in these animals, galactose oxidation and metabolite levels were studied in 16-day-old sucklings and the effect of a 4 week prior exposure to a 40% glucose or 40% galactose diet was determined in 7-week-old mice. Suckling GALT-deficient (G/G) mice slowly oxidized [1-14C]galactose to 14CO2, 4.0% of the dose when fed and 7.9% when fasted compared to normal animals 38.3 and 36.4% in 4 h, respectively. Plasma of G/G sucklings contained 11.1 mM galactose and erythrocyte galactose 1-phosphate levels were 28.2 and 31.9 mg/dl packed cells. Galactose, galactitol, galactonate, and galactose 1-phosphate were found in G/G suckling mouse tissues. The tissue galactose concentrations were 10% or less of that in plasma, suggesting that there was limited cellular entry of galactose. In 7-week-old fasted mice with 4 weeks prior exposure to glucose or galactose-containing diet, 4-h oxidation was 12.9 and 15.0% of the administered radiolabeled galactose, respectively. Normal animals oxidized 33.9 and 37.9% of the dose when fed the same diets, respectively. The ability of G/G mice to oxidize galactose in the absence of GALT activity suggests the presence of alternate metabolic pathways for galactose disposition. G/G mice fed the galactose-free 40% glucose diet had erythrocyte galactose 1-phosphate levels ranging from 6.4 to 17.7 mg/dl packed cells and detectable galactose and galactose metabolites in tissues, suggesting that these animals endogenously produced galactose. The plasma of 40% galactose-fed G/G mice contained 9.1 mM galactose with red blood cell galactose 1-phosphate averaging 43.6 mg/dl. Tissues of these animals also contained high levels of galactose and galactose 1-phosphate. Liver contained over 4 micromol/g galactonate but little galactitol. Despite the elevated galactose and galactose 1-phosphate, the animals tolerated the high-galactose diet and were indistinguishable from normal animals, exhibiting no manifestations of galactose toxicity seen in human GALT-deficient galactosemia. The data suggest that high galactose 1-phosphate levels do not cause galactose toxicity and that high galactitol in combination with galactose 1-phosphate may be a prerequisite. Absence of GALT appears necessary but insufficient to produce human galactosemic phenotype. 相似文献
32.
Martin Steegmaier James E. Blanks Eric Borges Dietmar Vestweber 《European journal of immunology》1997,27(6):1339-1345
It has been shown recently that mast cells play an essential role as a source of tumor necrosis factor-α production during neutrophil recruitment to sites of bacterial infection. Increased numbers of mast cells are indeed noted at sites of wound healing and inflammation. These cells are either recruited from the bone marrow or proliferate locally under cytokine stimulation. Little is known about how mast cell progenitors extravasate into tissue. Using antibody-like fusion proteins of mouse E-selectin and P-selectin, we have analyzed the ability of immature mouse bone marrow-derived mast cells (BMMC) to interact with the endothelial selectins. The P-selectin glycoprotein ligand-1 (PSGL-1) was affinity-isolated from detergent extracts of surface biotinylated BMMC with both selectin-IgG fusion proteins. However, only P-selectin-IgG, but not E-selectin-IgG showed significant interaction with intact BMMC as tested by flow cytometry and cell attachment assays with the immobilized fusion proteins under flow and non-flow conditions at physiological shear stress. Thus, in spite of carrying the necessary carbohydrate modifications which enable solubilized PSGL-1 to bind avidly to E-selectin, PSGL-1 on the surface of BMMC is presented in a way that prevents it from interacting efficiently with E-selectin. Affinity-purified rabbit antibodies against mouse PSGL-1 almost completely blocked the interaction of BMMC with P-selectin-IgG in flow cytometry as well as in cell adhesion assays under static and under flow conditions. Our data reveal that PSGL-1 is the major binding site for P-selectin on mouse BMMC progenitors, but does not support efficient interactions with E-selectin. 相似文献
33.
Rus V Zernetkina V Puliaev R Cudrici C Mathai S Via CS 《Clinical immunology (Orlando, Fla.)》2005,117(1):48-56
Increased expression of TRAIL in membrane-bound and soluble form in patients with systemic lupus erythematosus (SLE) has been previously reported. In this study, we characterized the upregulation of T-cell-associated and soluble TRAIL (sTRAIL) in vivo and the modulation of TRAIL expression and soluble protein release in vitro following T cell activation and IFNalpha exposure. The expression of membrane-bound TRAIL as determined by flow cytometry was higher on CD4(+) and CD8(+) T cells from lupus patients compared to controls, particularly on activated CD69(+)CD8(+) T cells. Similarly, sTRAIL levels determined by ELISA were significantly elevated in serum from patients with active SLE and correlated with levels of IFNalpha. In vitro, both T-cell-associated and sTRAIL were maximally induced by T cell activation plus IFNalpha in patients and controls. By Western blot analysis, sTRAIL was detected in sera in both the monomeric and multimeric, functional form. Both forms of TRAIL were functional in vitro as determined by Annexin V staining and (51)Cr release assay but the apoptotic activity of membrane TRAIL was 2.5-fold higher compared to that of sTRAIL. These results indicate that IFNalpha-induced enhancement of TRAIL expression and of TRAIL-mediated apoptosis may amplify the abnormal apoptotic process in SLE. 相似文献
34.
文章通过特异的引物分别扩增出CTLA 4和FasL胞外区的cDNA ,将它们拼接后 ,克隆入真核表达载体pcDNA3 1( + )中 ,进行表达、纯化 ,获得CTLA 4 FasL融合蛋白。Westernblot分析显示了该融合蛋白具有CTLA4 胞外区和FasL胞外区的抗原性。体外试验表明 ,该融合蛋白可以结合Jurkat细胞表面的Fas受体和Raji细胞表面的B7分子 ,表明了该分子双特异性的特点。该融合蛋白能够直接诱导Jurkat细胞发生凋亡 ,且此凋亡效应伴随Raji细胞的参与而增强 ,初步证实了该分子的免疫抑制效应 ,从而为进一步研究该融合蛋白特性及应用奠定了基础。 相似文献
35.
Differential ability of Th1 and Th2 T cells to express Fas ligand and to undergo activation-induced cell death 总被引:22,自引:0,他引:22
Ramsdell Fred; Seaman Michael S.; Miller Robert E.; Picha Kathleen S.; Kennedy Mary K.; Lynch David H. 《International immunology》1994,6(10):1545-1553
Stimulation of previously activated T cells through the antigenreceptor can result in the apoptotic death of the respondingcell, a process referred to as activation-induced cell death(AICD). This process appears to involve Fas (CD95) and tts ligand(Fas-L). The distribution of Fas and Fas-L on various T cellsubsets has not been extensively characterized. We have thereforeanalyzed cells committed to a Th1- or Th2-type differentiationpattern for the expression and function of Fas-L. Using botha sensitive bloassay and flow cytometry, we demonstrate thatcloned Th1 cells express high levels of Fas-L, whereas clonedTh cells express only low levels. The expression of Fas-L byTh1 and Th2 cells correlates with the relative abilities ofthese two cell types to undergo AICD. Whereas AICD is readilyobserved in cultures of cloned Th1, but not Th2 cells, Th2 cellsare capable of undergoing apoptosls in the presence of Th1 cellsexpressing Fas-L The ability of T cells to undergo AICD appearsto be unrelated to the presence of various cytokines. Thus,the Fas/Fas-L pathway appears to be critical for the inductionof AICD and this pathway is differentially regulated in cellscommitted to either Th1 or Th2 differentiation. 相似文献
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39.
Leroy X Wacrenier A De la Taille A Gosset P Saint F Biserte J Gosselin B 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2001,109(6):469-473
Sarcomatoid renal cell carcinomas (SRC) are rare neoplasms associated with a very poor prognosis. The aim of this study was to evaluate biomarker expression and clinical significance in this uncommon renal cancer. Cytokeratin, epithelial membrane antigen, vimentin, desmin, smooth muscle actin, CD34, S-100 protein, MIB 1, p53, Fas and Fas ligand immunohistochemical expression was investigated in seven renal cell carcinomas with sarcomatoid changes. No significant difference between sarcomatoid and nonsarcomatoid areas was observed with the different biomarkers, excepted for Fas ligand. Fas expression was diffuse in sarcomatoid and nonsarcomatoid areas. However, Fas ligand had a higher expression in sarcomatoid in comparison to nonsarcomatoid areas. Our results showed that Fas and Fas ligand are both expressed in renal cancer. We suggest that the aggressive behavior of sarcomatoid carcinoma may be related to a higher expression of Fas ligand by tumor sarcomatoid cells. These findings may indicate that Fas ligand is a possible therapeutic molecular target for treatment of SRC. 相似文献
40.
Abstract: The effect of TGFβ1 and IL-12 on calcium-independent cytotoxic pathways was investigated. We have previously demonstrated that the regulatory effect of TGFβ1 and IL-12 on human alloreative CTL activity was associated with regulation of perform and granzyme B gene expression. To determine the effect of both cytokines on the alternative cytotoxic pathway involving FasL and mTNF, we first investigated the expression of both molecules on human primary alloactivated T cells. Our results show that human allostimulated T lymphocytes express FasL. Cell lysis experiments demonstrate that the FasL cytotoxic pathway is involved in the killing of specific target cells mediated by human alloreactive CTL. In addition, allogeneic stimulation induced significant mTNF expression on both CD4+ and CD8+ responder T cells. Using TNF-sensitive target cells, we also demonstrate that the mTNF-mediated cytotoxic pathway is involved in the cytotoxic activity of human primary allostimulated T lymphocytes. Neither TGFβ1 nor IL-12 had an effect on FasL or mTNF expression. Furthermore, addition of TGFβ1 or IL-12 at the initiation of the MLR had no significant effect on Fas- and mTNF-mediated cytotoxicity.
Taken together, our results provide a novel insight into the differences between regulation by cytokines of perforin-dependent and -independent cytotoxic mechanisms. Unlike their role in the perforin/granzyme B pathway, TGFβ1 and IL-12 do not appear to mediate any regulatory effect on FasL and mTNF cytotoxic pathways used by human alloreactive primary CTL. 相似文献
Taken together, our results provide a novel insight into the differences between regulation by cytokines of perforin-dependent and -independent cytotoxic mechanisms. Unlike their role in the perforin/granzyme B pathway, TGFβ1 and IL-12 do not appear to mediate any regulatory effect on FasL and mTNF cytotoxic pathways used by human alloreactive primary CTL. 相似文献