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排序方式: 共有114条查询结果,搜索用时 15 毫秒
1.
A minority of 46,XX true hermaphrodites are positive for the Y-DNA sequence including SRY 总被引:4,自引:0,他引:4
Ken McElreavey Raphaël Rappaport Eric Vilain Nacer Abbas François Richaud Stéphen Lortat-Jacob Roland Berger Maryvonne LeConiat Chafika Boucekkine Kiran Kucheria Samia Temtamy Claire Nihoul-Fekete Raja Brauner Marc Fellous 《Human genetics》1992,90(1-2):121-125
Summary A total of 30 cases of 46,XX true hermaphroditism was analysed for Y-DNA sequences including the recently cloned gene for male testis-determination SRY. In 3 cases, a portion of the Y chromosome including SRY was present and, in 2 cases, was localised, to Xp22 by in situ hybridisation. Since previous studies have shown that the majority of XX males are generated by an X-Y chromosomal interchange, the Xp22 position of the Yp material suggests that certain cases of hermaphroditism can arise by the same meiotic event. The phenotype in the 3 SRY-positive cases may be caused by X-inactivation resulting in somatic mosaicism of testis-determining factor expression giving rise to both testicular and ovarian tissues. Autosomal or X-linked mutation(s) elsewhere in the sex-determining pathway may explain the phenotype observed in the remaining 27 SRY-negative cases. 相似文献
2.
M Reboud-Ravaux A C Vilain N Boggetto J Maillard C Favreau J Xie J P Mazaleyrat M Wakselman 《Biochemical and biophysical research communications》1991,178(1):352-359
c[Arg-aB-(CH2+SCH3 phi)-Gly4] was designed and studied as a mechanism-based inactivator (suicide substrate) for plasminogen activators (u-PA and t-PA) and plasmin. This compound inhibited u-PA and fulfills criteria expected for the involvement of an enzyme-activated inhibitor: first-order and irreversible process, saturation kinetics, protection by substrate. The limiting first-order rate constant kinact and the apparent enzyme-inhibitor dissociation constant KI were 0.021 s-1 and 9 microM, respectively at pH 7.5 and 25 degrees C. The activation of plasminogen by u-PA is compromised after this enzyme has been treated by the reagent. Plasmin and t-PA were inactivated 40- and 2330-fold less efficiently than u-PA, respectively. 相似文献
3.
A C Vilain V Okochi I Vergely M Reboud-Ravaux J P Mazaleyrat M Wakselman 《Biochimica et biophysica acta》1991,1076(3):401-405
3-Benzyl-6-chloromethyl-3,4-dihydrocoumarin inhibits human leucocyte elastase (HLE) and porcine pancreatic elastase (PPE) through a mechanism-based process characterized by the following apparent enzyme-inhibitor dissociation constants, Ki, and limiting inactivation rate constants k2: 200 microM (HLE), 69 microM (PPE) and 5.10(-2) s-1 (HLE), 17.7.10(-2) s-1 (PPE) at pH 8.0, 37 degrees C. Bis(4-acyloxyphenyl)methane derivatives with a benzylic halogen as potential leaving group have also been synthesized and studied. They transiently inactivate PPE and HLE through the formation of an acyl-enzyme. 相似文献
4.
Bacillus cereus is believed to be a soil bacterium, but studied solely in laboratory culture media. The aim of this study was to assess the physiology of B. cereus growing on soil organic matter by a proteomic approach. Cells were cultured to mid-exponential phase in soil extracted solubilized organic matter (SESOM), which mimics the nutrient composition of soil, and in Luria-Bertani broth as control. Silver staining of the two-dimensional gels revealed 234 proteins spots up-regulated when cells were growing in SESOM, with 201 protein spots down-regulated. Forty-three of these differentially expressed proteins were detected by Colloidal Coomassie staining and identified by matrix assisted laser desorption ionization-time of flight MS of tryptic digests. These differentially expressed proteins covered a range of functions, primarily amino acid, lipid, carbohydrate and nucleic acid metabolism. These results suggested growth on soil-associated carbohydrates, fatty acids and/or amino acids, concomitant with shifts in cellular structure. 相似文献
5.
C Touvay B Vilain C Carré J M Mencia-Huerta P Braquet 《Biochemical and biophysical research communications》1988,152(2):527-533
The possibility that PAF is implicated in the alterations of the beta-adrenoceptor function observed during endotoxemia was investigated. Lung parenchymal strips (LPS) from endotoxin-treated guinea-pig demonstrated specific desensitization to low doses of PAF whereas the contractions induced by histamine and leukotriene D4 were slightly affected. In addition, histamine-contracted LPS from endotoxin-injected animals exhibited decreased responsiveness to isoproterenol, a phenomenon not observed with guinea-pigs also treated with the specific PAF antagonist, BN 52021. No alteration of the sensitivity to isoproterenol of LPS preincubated with PAF was noted, suggesting an indirect effect of the autacoid on beta-adrenoceptor function. 相似文献
6.
X Emonds-Alt P Vilain P Goulaouic V Proietto D Van Broeck C Advenier E Naline G Neliat G Le Fur J C Brelière 《Life sciences》1992,50(15):PL101-PL106
SR 48968 is a potent and selective non-peptide antagonist of the neurokinin A (NK2) receptor. SR 48968 selectively inhibited neurokinin A binding to its receptor and was a competitive antagonist of neurokinin A-mediated contraction of different isolated smooth muscle preparations from various species including human. In vivo, the compound inhibited the bronchoconstriction induced by neurokinin A in guinea pigs. SR 48968 can be used to study the physiological or pathological role of neurokinin A and may be useful in the treatment of neurokinin A-dependent pathology. 相似文献
7.
Activation of Xenopus eggs by the kinase inhibitor 6-DMAP suggests a differential regulation of cyclin B and p39(mos) proteolysis 总被引:17,自引:0,他引:17
Bodart JF Béchard D Bertout M Gannon J Rousseau A Vilain JP Flament S 《Experimental cell research》1999,249(2):413-421
The molecular mode of action of arsenic, a therapeutic agent employed in the treatment of acute promyelocytic leukemia, has been elusive. Here we provide evidence that arsenic compounds may act on mitochondria to induce apoptosis. Arsenite induces apoptosis accompanied by a loss of the mitochondrial transmembrane potential (Delta Psim). Inhibition of caspases prevents the arsenite-induced nuclear DNA loss, but has no effect on the Delta Psim dissipation and cytolysis induced by arsenite. In contrast, Bcl-2 expression induced by gene transfer prevents all hallmarks of arsenite-induced cell death, including the Delta Psim collapse. PK11195, a ligand of the mitochondrial benzodiazepine receptor, neutralizes this Bcl-2 effect. Mitochondria are required in a cell-free system to mediate arsenite-induced nuclear apoptosis. Arsenite causes the release of an apoptosis-inducing factor (AIF) from the mitochondrial intermembrane space. This effect is prevented by the permeability transition (PT) pore inhibitor cyclosporin A, as well as by Bcl-2, which is known to function as an endogenous PT pore antagonist. Arsenite also opens the purified, reconstituted PT pore in vitro in a cyclosporin A- and Bcl-2-inhibitible fashion. Altogether these data suggest that arsenite can induce apoptosis via a direct effect on the mitochondrial PT pore. 相似文献
8.
Vilain N Tsai-Pflugfelder M Benoit A Gasser SM Leroy D 《Nucleic acids research》2003,31(19):5714-5722
Epipodophyllotoxins are effective antitumour drugs that trap eukaryotic DNA topoisomerase II in a covalent complex with DNA. Based on DNA cleavage assays, the mode of interaction of these drugs was proposed to involve amino acid residues of the catalytic site. An in vitro binding study, however, revealed two potential binding sites for etoposide within human DNA topoisomerase IIα (htopoIIα), one in the catalytic core of the enzyme and one in the ATP-binding N-terminal domain. Here we have tested how N-terminal mutations that reduce the affinity of the site for etoposide or ATP affect the sensitivity of yeast cells to etoposide. Surprisingly, when introduced into full-length enzymes, mutations that lower the drug binding capacity of the N-terminal domain in vitro render yeast more sensitive to epipodophyllotoxins. Consistently, when the htopoIIα N-terminal domain alone is overexpressed in the presence of yeast topoII, cells become more resistant to etoposide. Point mutations that weaken etoposide binding eliminate this resistance phenotype. We argue that the N-terminal ATP-binding pocket competes with the active site of the holoenzyme for binding etoposide both in cis and in trans with different outcomes, suggesting that each topoisomerase II monomer has two non-equivalent drug-binding sites. 相似文献
9.
Tammy M. Rickabaugh Ruth M. Baxter Mary Sehl Janet S. Sinsheimer Patricia M. Hultin Lance E. Hultin Austin Quach Otoniel Martínez-Maza Steve Horvath Eric Vilain Beth D. Jamieson 《PloS one》2015,10(3)
Patients with treated HIV-1-infection experience earlier occurrence of aging-associated diseases, raising speculation that HIV-1-infection, or antiretroviral treatment, may accelerate aging. We recently described an age-related co-methylation module comprised of hundreds of CpGs; however, it is unknown whether aging and HIV-1-infection exert negative health effects through similar, or disparate, mechanisms. We investigated whether HIV-1-infection would induce age-associated methylation changes. We evaluated DNA methylation levels at >450,000 CpG sites in peripheral blood mononuclear cells (PBMC) of young (20-35) and older (36-56) adults in two separate groups of participants. Each age group for each data set consisted of 12 HIV-1-infected and 12 age-matched HIV-1-uninfected samples for a total of 96 samples. The effects of age and HIV-1 infection on methylation at each CpG revealed a strong correlation of 0.49, p<1 x10-200 and 0.47, p<1x10-200. Weighted gene correlation network analysis (WGCNA) identified 17 co-methylation modules; module 3 (ME3) was significantly correlated with age (cor=0.70) and HIV-1 status (cor=0.31). Older HIV-1+ individuals had a greater number of hypermethylated CpGs across ME3 (p=0.015). In a multivariate model, ME3 was significantly associated with age and HIV status (Data set 1: βage= 0.007088, p=2.08 x 10-9; βHIV= 0.099574, p=0.0011; Data set 2: βage= 0.008762, p=1.27x 10-5; βHIV= 0.128649, p= 0.0001). Using this model, we estimate that HIV-1 infection accelerates age-related methylation by approximately 13.7 years in data set 1 and 14.7 years in data set 2. The genes related to CpGs in ME3 are enriched for polycomb group target genes known to be involved in cell renewal and aging. The overlap between ME3 and an aging methylation module found in solid tissues is also highly significant (Fisher-exact p=5.6 x 10-6, odds ratio=1.91). These data demonstrate that HIV-1 infection is associated with methylation patterns that are similar to age-associated patterns and suggest that general aging and HIV-1 related aging work through some common cellular and molecular mechanisms. These results are an important first step for finding potential therapeutic targets and novel clinical approaches to mitigate the detrimental effects of both HIV-1-infection and aging. 相似文献
10.
Antoine AF Montpellier C Cailliau K Browaeys-Poly E Vilain JP Dubuisson J 《The Journal of membrane biology》2007,215(1):37-48
The Alphavirus Sindbis 6K protein is involved in several functions. It contributes to the processing and membrane insertion of E1 and PE2
viral envelope glycoproteins and to virus budding. It also permeabilizes Escherichia coli and mammalian cells. These viroporin-like properties have been proposed to help virus budding by modifying membrane permeabilities.
We expressed Sindbis virus 6K cRNA in Xenopus oocytes to further characterize the effect of 6K on membrane conductances and permeabilization. Although no intrinsic channel
properties were seen, cell shrinkage was observed within 24 h. Voltage-clamp experiments showed that 6K upregulated endogenous
currents: a hyperpolarization-activated inward current (I
in) and a calcium-dependent chloride current (I
Cl). 6K was located at both the plasma and the endoplasmic reticulum membranes. The plasma membrane current upregulation likely
results from disruption of the calcium homeostasis of the cell at the endoplasmic reticulum level. Indeed, 6K cRNA expression
induced reticular calcium store depletion and capacitative calcium entry activation. By experimental modifications of the
incubation medium, we showed that downstream of these events cell shrinkage resulted from a 6K -induced KCl efflux (I
Cl upregulation leads to chloride efflux, which itself electrically drives potassium efflux), which was responsible for an osmotic
water efflux. Our data confirm that 6K specifically triggers a sequential cascade of events that leads to cytoplasmic calcium
elevation and cell permeabilization, which likely play a role in the Sindbis virus life cycle. 相似文献