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61.
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62.
Buckwalter MR Nga PT Gouilh MA Fiette L Bureau JF Laird ME Buchrieser J Ozden S Cheval J Eloit M Manuguerra JC Gessain A Brey PT Fontanet A Albert ML 《Journal of virology》2011,85(14):6893-6905
Theiler's murine encephalitis viruses (TMEV) are divided into two subgroups based on their neurovirulence. Persistent strains resemble Theiler's original viruses (referred to as the TO subgroup), which largely induce a subclinical polioencephalomyelitis during the acute phase of the disease and can persist in the spinal cord of susceptible animals, inducing a chronic demyelinating disease. In contrast, members of the neurovirulent subgroup cause an acute encephalitis characterized by the rapid onset of paralysis and death within days following intracranial inoculation. We report herein the characterization of a novel neurovirulent strain of TMEV, identified using pyrosequencing technology and referred to as NIHE. Complete coverage of the NIHE viral genome was obtained, and it shares <90% nucleotide sequence identity to known TMEV strains irrespective of subgroup, with the greatest sequence variability being observed in genes encoding the leader and capsid proteins. The histopathological analysis of infected brain and spinal cord demonstrate inflammatory lesions and neuronal necrosis during acute infection with no evidence of viral persistence or chronic disease. Intriguingly, genetic analysis indicates the putative expression of the L protein, considered a hallmark of strains within the persistent subgroup. Thus, the identification and characterization of a novel neurovirulent TMEV strain sharing features previously associated with both subgroups will lead to a deeper understanding of the evolution of TMEV strains and new insights into the determinants of neurovirulence. 相似文献
63.
64.
Yolanda K. Mueller Mathieu Bastard Patrick Nkemenang Eric Comte Geneviève Ehounou Sara Eyangoh Barbara Rusch Earnest Njih Tabah Laurence Toutous Trellu Jean-Francois Etard 《PLoS neglected tropical diseases》2016,10(4)
Background
Access to laboratory diagnosis can be a challenge for individuals suspected of Buruli Ulcer (BU). Our objective was to develop a clinical score to assist clinicians working in resource-limited settings for BU diagnosis.Methododology/Principal Findings
Between 2011 and 2013, individuals presenting at Akonolinga District Hospital, Cameroon, were enrolled consecutively. Clinical data were collected prospectively. Based on a latent class model using laboratory test results (ZN, PCR, culture), patients were categorized into high, or low BU likelihood. Variables associated with a high BU likelihood in a multivariate logistic model were included in the Buruli score. Score cut-offs were chosen based on calculated predictive values. Of 325 patients with an ulcerative lesion, 51 (15.7%) had a high BU likelihood. The variables identified for the Buruli score were: characteristic smell (+3 points), yellow color (+2), female gender (+2), undermining (+1), green color (+1), lesion hyposensitivity (+1), pain at rest (-1), size >5cm (-1), locoregional adenopathy (-2), age above 20 up to 40 years (-3), or above 40 (-5). This score had AUC of 0.86 (95%CI 0.82–0.89), indicating good discrimination between infected and non-infected individuals. The cut-off to reasonably exclude BU was set at scores <0 (NPV 96.5%; 95%CI 93.0–98.6). The treatment threshold was set at a cut-off ≥4 (PPV 69.0%; 95%CI 49.2–84.7). Patients with intermediate BU probability needed to be tested by PCR.Conclusions/Significance
We developed a decisional algorithm based on a clinical score assessing BU probability. The Buruli score still requires further validation before it can be recommended for wide use. 相似文献65.
Biochemical and Immunological Properties of the Mouse Brain Enolases Purified by a Simple Method 总被引:6,自引:4,他引:2
Angelica Keller Hélène Scarna Anne Mermet Jean-Francois Pujol 《Journal of neurochemistry》1981,36(4):1389-1397
Abstract: A simple and rapid purification method is presented for the two mouse cerebral isozymes of enolase (EC 4.2.1.11), E1 and E3. The purity of the preparations was ascertained by electrophoresis under two different conditions. The biochemical and immunological properties of E1 and E3 were compared. The molecular weight of the cerebral enolases was analysed by column chromatography on Sephadex G 150 and by electrophoresis in the presence of SDS. Both E1 and E3 are homodimers with a subunit of molecular weight of 50,000. The procedure also yields a semi-purified fraction of E2. Conditions of in vitro formation of E2 from pure or semi-purified fractions of E1 and E3 show that it is likely to be a real hybrid, rather than an aggregate and that it is probably not an artefact formed during the purification. The Km values (Km= 3–4·10?5 M) for the substrate are not significantly different amongst the three forms. However, E1 and E2 but not E3 are inhibited by excess substrate. Antisera against E1 and E3 have been obtained from rabbit and goat, respectively. Antibodies against each protein do not show any cross-reactivity with each other. There is, however, a broad species cross-reactivity, showing conservation of each enolase form during evolution. Both anti-E1 and anti-E3 sera react with the E2 enolase fraction, in agreement with its hybrid structure. Anti-E3 serum does not react with extracts of other tested organs. Brain enolase 1 resembles liver enolase in its biochemical and immunological properties. A slight cross-reactivity of anti-E1 serum with muscle extracts is observed. Heterogeneity of brain enolase 1 is observed by both biochemical and immunological methods; the nature of this heterogeneity is discussed. 相似文献
66.
A new disease-related mutation for mitochondrial encephalopathy lactic acidosis and strokelike episodes (MELAS) syndrome affects the ND4 subunit of the respiratory complex I. 总被引:5,自引:0,他引:5
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P Lertrit A S Noer M J Jean-Francois R Kapsa X Dennett D Thyagarajan K Lethlean E Byrne S Marzuki 《American journal of human genetics》1992,51(3):457-468
The molecular lesions in two patients exhibiting classical clinical manifestations of MELAS (mitochondrial encephalopathy, lactic acidosis, and strokelike episodes) syndrome have been investigated. A recently reported disease-related A----G base substitution at nt 3243 of the mtDNA, in the DHU loop of tRNA(Leu), was detected by restriction-enzyme analysis of the relevant PCR-amplified segment of the mtDNA of one patient but was not observed, by either restriction-enzyme analysis or nucleotide sequencing, in the other. To define the molecular lesion in the patient who does not have the A----G base substitution at nt 3243, the total mitochondrial genome of the patient has been sequenced. An A----G base substitution at nt 11084, leading to a Thr-to-Ala amino acid replacement in the ND4 subunit of the respiratory complex I, is suggested to be a disease-related mutation. 相似文献
67.
Zarei S Abraham S Arrighi JF Haller O Calzascia T Walker PR Kündig TM Hauser C Piguet V 《Journal of virology》2004,78(14):7843-7845
Control of a viral infection in vivo requires a rapid and efficient cytotoxic-T-lymphocyte response. We demonstrate that lentivirus-mediated introduction of antigen in dendritic cells confers a protective antiviral immunity in vivo in a lymphocytic choriomeningitis virus model. Therefore, lentiviral vectors may be excellent vaccine candidates for viral infections. 相似文献
68.
Next generation of elevated [CO2] experiments with crops: a critical investment for feeding the future world 总被引:1,自引:0,他引:1
Ainsworth EA Beier C Calfapietra C Ceulemans R Durand-Tardif M Farquhar GD Godbold DL Hendrey GR Hickler T Kaduk J Karnosky DF Kimball BA Körner C Koornneef M Lafarge T Leakey AD Lewin KF Long SP Manderscheid R McNeil DL Mies TA Miglietta F Morgan JA Nagy J Norby RJ Norton RM Percy KE Rogers A Soussana JF Stitt M Weigel HJ White JW 《Plant, cell & environment》2008,31(9):1317-1324
A rising global population and demand for protein-rich diets are increasing pressure to maximize agricultural productivity. Rising atmospheric [CO2 ] is altering global temperature and precipitation patterns, which challenges agricultural productivity. While rising [CO2 ] provides a unique opportunity to increase the productivity of C3 crops, average yield stimulation observed to date is well below potential gains. Thus, there is room for improving productivity. However, only a fraction of available germplasm of crops has been tested for CO2 responsiveness. Yield is a complex phenotypic trait determined by the interactions of a genotype with the environment. Selection of promising genotypes and characterization of response mechanisms will only be effective if crop improvement and systems biology approaches are closely linked to production environments, that is, on the farm within major growing regions. Free air CO2 enrichment (FACE) experiments can provide the platform upon which to conduct genetic screening and elucidate the inheritance and mechanisms that underlie genotypic differences in productivity under elevated [CO2 ]. We propose a new generation of large-scale, low-cost per unit area FACE experiments to identify the most CO2 -responsive genotypes and provide starting lines for future breeding programmes. This is necessary if we are to realize the potential for yield gains in the future. 相似文献
69.
70.
J Bussenius CM Blazey N Aay NK Anand A Arcalas T Baik OJ Bowles CA Buhr S Costanzo JK Curtis SC Defina L Dubenko TS Heuer P Huang C Jaeger A Joshi AR Kennedy AI Kim K Lara J Lee J Li JC Lougheed S Ma S Malek JC Manalo JF Martini G McGrath M Nicoll JM Nuss M Pack CJ Peto TH Tsang L Wang SW Womble M Yakes W Zhang KD Rice 《Bioorganic & medicinal chemistry letters》2012,22(17):5396-5404
With structural guidance, tropane-derived HTS hits were modified to optimize for HSP90 inhibition and a desirable in vivo profile. Through an iterative SAR development process 12i (XL888) was discovered and shown to reduce HSP90 client protein content in PD studies. Furthermore, efficacy experiments performed in a NCI-N87 mouse xenograft model demonstrated tumor regression in some dosing regimens. 相似文献