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41.
CM Lange S Bibert Z Kutalik P Burgisser A Cerny JF Dufour A Geier TJ Gerlach MH Heim R Malinverni F Negro S Regenass K Badenhoop J Bojunga C Sarrazin S Zeuzem T Müller T Berg PY Bochud D Moradpour;Swiss Hepatitis C Cohort Study Group 《PloS one》2012,7(7):e40159
Background
To perform a comprehensive study on the relationship between vitamin D metabolism and the response to interferon-α-based therapy of chronic hepatitis C.Methodology/Principal Findings
Associations between a functionally relevant polymorphism in the gene encoding the vitamin D 1α-hydroxylase (CYP27B1-1260 rs10877012) and the response to treatment with pegylated interferon-α (PEG-IFN-α) and ribavirin were determined in 701 patients with chronic hepatitis C. In addition, associations between serum concentrations of 25-hydroxyvitamin D3 (25[OH]D3) and treatment outcome were analysed. CYP27B1-1260 rs10877012 was found to be an independent predictor of sustained virologic response (SVR) in patients with poor-response IL28B genotypes (15% difference in SVR for rs10877012 genotype AA vs. CC, p = 0.02, OR = 1.52, 95% CI = 1.061–2.188), but not in patients with favourable IL28B genotype. Patients with chronic hepatitis C showed a high prevalence of vitamin D insufficiency (25[OH]D3<20 ng/mL) during all seasons, but 25(OH)D3 serum levels were not associated with treatment outcome.Conclusions/Significance
Our study suggests a role of bioactive vitamin D (1,25[OH]2D3, calcitriol) in the response to treatment of chronic hepatitis C. However, serum concentration of the calcitriol precursor 25(OH)D3 is not a suitable predictor of treatment outcome. 相似文献42.
Genetic determination and linkage mapping of Plasmodium falciparum malaria related traits in Senegal
Sakuntabhai A Ndiaye R Casadémont I Peerapittayamongkol C Peerapittayamonkol C Rogier C Tortevoye P Tall A Paul R Turbpaiboon C Phimpraphi W Trape JF Spiegel A Heath S Mercereau-Puijalon O Dieye A Julier C 《PloS one》2008,3(4):e2000
Plasmodium falciparum malaria episodes may vary considerably in their severity and clinical manifestations. There is good evidence that host genetic factors contribute to this variability. To date, most genetic studies aiming at the identification of these genes have used a case/control study design for severe malaria, exploring specific candidate genes. Here, we performed a family-based genetic study of falciparum malaria related phenotypes in two independent longitudinal survey cohorts, as a first step towards the identification of genes and mechanisms involved in the outcome of infection. We studied two Senegalese villages, Dielmo and Ndiop that differ in ethnicity, malaria transmission and endemicity. We performed genome-scan linkage analysis of several malaria-related phenotypes both during clinical attacks and asymptomatic infection. We show evidence for a strong genetic contribution to both the number of clinical falciparum malaria attacks and the asymptomatic parasite density. The asymptomatic parasite density showed linkage to chromosome 5q31 (LOD = 2.26, empirical p = 0.0014, Dielmo), confirming previous findings in other studies. Suggestive linkage values were also obtained at three additional chromosome regions: the number of clinical malaria attacks on chromosome 5p15 (LOD = 2.57, empirical p = 0.001, Dielmo) and 13q13 (LOD = 2.37, empirical p = 0.0014 Dielmo), and the maximum parasite density during asymptomatic infection on chromosome 12q21 (LOD = 3.1, empirical p<10(-4), Ndiop). While regions of linkage show little overlap with genes known to be involved in severe malaria, the four regions appear to overlap with regions linked to asthma or atopy related traits, suggesting that common immune related pathways may be involved. 相似文献
43.
Tétreault MP Chailler P Beaulieu JF Rivard N Ménard D 《Journal of cellular physiology》2008,214(2):545-557
Restitution is a crucial event during the healing of superficial injury of the gastric mucosa involving epithelial cell sheet movement into the damaged area. We demonstrated that growth factors promote the restitution of human gastric epithelial cells. However, the intracellular signaling pathways that transmit extracellular cues as well as regulate basal and growth factor-stimulated gastric epithelial cell migration are still unclear. Herein, confluent human gastric epithelial cell monolayers (HGE-17) or primary cultures of gastric epithelial cells were wounded with a razor blade and the migration response was analyzed in presence or absence of TGFalpha or of pharmacological inhibitors of signaling proteins. Kinase activation profile analysis and phase-contrast microscopy were also performed in parallel. We report that ERK1/2 and Akt activities are rapidly stimulated following wounding of HGE-17 cells. Treatment of confluent HGE-17 cells or primary cultures of gastric epithelial cells with the phosphatidylinositol 3-kinase inhibitor LY294002, but not the MEK1 inhibitor, PD98059, significantly inhibits basal and TGFalpha-induced migration following wounding. Conversely, treatment of wounded HGE-17 cells with phosphatidylinositol(3,4,5)-triphosphate is sufficient to stimulate basal cell migration by 235%. In addition, pp60c-src kinase activity and tyrosine phosphorylation of epidermal growth factor receptors (EGFR) are also rapidly enhanced after wounding and pharmacological inhibition of both these activities strongly attenuates basal and TGFalpha-induced migration as well as Akt phosphorylation levels. In conclusion, the present results indicate that EGFR-dependent PI3K activation promotes restitution of wounded human gastric epithelial monolayers. 相似文献
44.
Short-timescale variability of picophytoplankton abundance and cellular parameters in surface waters of the Alboran Sea (western Mediterranean) 总被引:1,自引:0,他引:1
Jacquet Stephan; Prieur Louis; Avois-Jacquet Carol; Lennon Jean-Francois; Vaulot Daniel 《Journal of plankton research》2002,24(7):635-651
The Alboran Sea (western Mediterranean) is characterized bya well-defined hydrological structure, the Almeria (Spain)Oran(Algeria) geostrophic front. During the Almofront-2 cruise (November22, 1997 to January 18, 1998), high frequency sampling ( 相似文献
45.
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47.
The past, present and future of childhood malaria mortality in Africa 总被引:11,自引:0,他引:11
During the past few years, there has been a historic series of declarations of renewed commitment to malaria control in Africa. Whether the burden of malaria is increasing in Africa is a moot point. This article attempts to re-construct the evidence for the trends in childhood mortality as a result of Plasmodium falciparum infection over the last century in Africa. 相似文献
48.
49.
Angiotensin II stimulates the production of NO and peroxynitrite in endothelial cells 总被引:12,自引:0,他引:12
Pueyo Maria E.; Arnal Jean-Francois; Rami Jacques; Michel Jean-Baptiste 《American journal of physiology. Cell physiology》1998,274(1):C214
Angiotensin II(ANG II) produces vasoconstriction by a direct action on smooth musclecells via AT1 receptors. Thesereceptors are also present in the endothelium, but their function ispoorly understood. This study was therefore undertaken to determinewhether ANG II elicits the release of nitric oxide (NO) from cultured rat aortic endothelial cells. NO production, measured by theaccumulation of nitrite and nitrate, was enhanced by107 M ANG II. Thebiological activity of the NO released by ANG II action was evaluatedby measuring its guanylate cyclase-stimulating activity in smoothmuscle cells. The guanosine 3',5'-cyclic monophosphate (cGMP) content of smooth muscle cells was significantly increased byexposure of supernatant from ANG II-stimulated endothelial cells. Theseeffects resulted from the activation of NO synthase, as they wereinhibited by the L-arginineanalogs. These ANG II actions were mediated by theAT1 receptor, as shown by theirinhibition by the AT1 antagonistlosartan. The cGMP production by reporter cells was inhibited by thecalmodulin antagonist W-7, suggesting that ANG II activates endothelialcalmodulin-dependent NO synthase. This hypothesis is also supported bythe increase of intracellular free calcium induced by ANG II inendothelial cells. ANG II also stimulated luminol-enhancedchemiluminescence in endothelial cells. This effect was inhibited byN-monomethyl-L-arginine andsuperoxide dismutase, suggesting that this luminol-enhancedchemiluminescence reflected an increase in peroxynitrite production.Thus ANG II stimulates NO release from macrovascular endothelium, whichmay modulate the direct vasoconstrictor effect of ANG II on smoothmuscle cells. However, this beneficial effect may be counteracted bythe simultaneous production of peroxynitrite, which could contribute toseveral pathological processes in the vascular wall. 相似文献
50.
Desaphy Jean-Francois; De Luca Annamaria; Camerino Diana Conte 《American journal of physiology. Cell physiology》1998,275(6):C1465
Although theskeletal muscle sodium channel is a good substrate for cAMP-dependentprotein kinase (PKA), no functional consequence was observed for thischannel expressed in heterologous systems. Therefore, we investigatedthe effect of 8-(4-chlorophenylthio)adenosine 3',5'-cyclicmonophosphate (CPT-cAMP), a membrane-permeable cAMP analog, on thenative sodium channels of freshly dissociated rat skeletal musclefibers by means of the cell-attached patch-clamp technique. Externallyapplied CPT-cAMP (0.5 mM) reduced peak ensemble average currents by~75% with no change in kinetics. Single-channel conductance andnormalized activation curves were unchanged by CPT-cAMP. In contrast,steady-state inactivation curves showed a reduction of the maximalavailable current and a negative shift of the half-inactivationpotential. Similar effects were observed with dibutyryl adenosine3',5'-cyclic monophosphate but not with cAMP, which doesnot easily permeate the cell membrane. Incubation of fibers for 1 hwith 10 µM H-89, a PKA inhibitor, did not prevent the effect ofCPT-cAMP. Finally, the -adrenoreceptor agonist isoproterenolmimicked CPT-cAMP when applied at 0.5 mM but had no effect at 0.1 mM.These results indicate that cAMP inhibits native skeletal muscle sodiumchannels by acting within the fiber, independently of PKA activation. 相似文献