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31.
Ghosn J Galimand J Raymond S Meyer L Deveau C Goujard C Izopet J Rouzioux C Chaix ML;ANRS CO PRIMO cohort 《PloS one》2011,6(8):e23301
Our objective was to analyze the evolution of resistance mutations (RM) and viral tropism of multi-drug-resistant (MDR) strains detected at primary HIV-1 infection (PHI). MDR HIV strain was defined as the presence of genotypic resistance to at least 1 antiretroviral of the 3 classes. Tropism determinations (CCR5 or CXCR4) were performed on baseline plasma HIV-RNA and/or PBMC-HIV-DNA samples, then during follow-up using population-based sequencing of V3 loop and phenotypic tests. Clonal analysis was performed at baseline for env, RT and protease genes, and for HIV-DNA env gene during follow-up. Five patients were eligible. At baseline, RT, protease and env clones from HIV-RNA and HIV-DNA were highly homogenous for each patient; genotypic tropism was R5 in 3 (A,B,C) and X4 in 2 patients (D,E). MDR strains persisted in HIV-DNA throughout follow-up in all patients. For patient A, tropism remained R5 with concordance between phenotypic and genotypic tests. Clonal analysis on Month (M) 78 HIV-DNA evidenced exclusively R5 (21/21) variants. In patient B, clonal analysis at M36 showed exclusively R5 variants (19/19) using both genotypic and phenotypic tests. In patient C, baseline tropism was R5 by genotypic test and R5/X4 by phenotypic test. An expansion of these X4 clones was evidenced by clonal analysis on M72 HIV-DNA (12/14 X4 and 2/14 R5 variants). In patient D, baseline tropism was X4 with concordance between both techniques and HIV-RNA and HIV-DNA remained X4-tropic up to M72, confirmed by the clonal analysis. Patient E harboured highly homogenous X4-using population at baseline; tropism was unchanged at M1 and M18. In all patients, the initial MDR population was highly homogenous initially, supporting the early expansion of a monoclonal population and its long-term persistence. X4-tropic variants present at baseline were still exclusive (patients D and E) or dominant (at least one time point, patient C) far from PHI. 相似文献
32.
Arregui M Fisher E Knüppel S Buijsse B di Giuseppe R Fritsche A Corella D Willich SN Boeing H Weikert C 《Gene》2012,494(2):190-195
Background
rs2943634 C/A single nucleotide polymorphism (SNP), located in a non coding region of chromosome 2q36.3, has been associated with coronary artery disease in two genome wide association studies. Our goal was to investigate its relation with myocardial infarction (MI) and ischemic stroke (IS), as well as with 12 intermediate risk phenotypes, in a population-based prospective cohort study.Methods
rs2943634 was genotyped in a case-cohort study including a random sample of 1891 individuals (subcohort) and all incident MI (n = 211) and IS (n = 144) cases during a mean follow-up of 8.2 ± 2.2 years, nested within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort comprising 27,548 middle-aged men and women.Results
rs2943634 minor allele (A) was associated in an additive fashion with lower risk of IS but not with MI [hazard ratio (HR) = 0.66; 95% confidence interval (CI): 0.50-0.87; P = 0.003; HR = 1.02; 95% CI: 0.82-1.28; P = 0.83 respectively, for the age and sex adjusted model]. Furthermore, it was related to slightly higher levels of plasma adiponectin [CC 6.94, CA 7.27, AA 7.86 μg/ml, P = 0.0002] and high density lipoprotein (HDL)-cholesterol (CC 52.08, CA 53.05 and AA 55.27 mg/dl, P = 0.002), based on additive models. Adjustment for adiponectin and HDL-cholesterol did not attenuate the association between the SNP and IS risk. In contrast, adjustment for adiponectin abolished the association between the SNP and HDL-cholesterol and adjustment for HDL-cholesterol attenuated the association between the SNP and adiponectin.Conclusions
Our findings suggest that rs2943634 is associated with IS risk and with plasma levels of HDL-cholesterol and adiponectin in this German population. Further investigations are needed to confirm these results and to clarify the mechanisms underlying the association. 相似文献33.
34.
Arregui L Rathi R Zeng W Honaramooz A Gomendio M Roldan ER Dobrinski I 《Animal reproduction science》2008,106(1-2):65-76
Xenografting of testis tissue from immature males from several mammalian species to immunodeficient mouse hosts results in production of fertilization-competent sperm. However, the efficiency of testis tissue xenografting from adult donors has not been critically evaluated. Testis tissue xenografting from sexually mature animals could provide an option to preserve the genetic material from valuable males when semen for cryopreservation cannot be collected. To assess the potential use of this technique for adult individuals, testes from adult animals of six species (pig, goat, cattle, donkey, horse and rhesus monkey) were ectopically grafted to host mice. Grafts were recovered and analyzed at three time points: less than 12 weeks, between 12 and 24 weeks and more than 24 weeks after grafting. Histological analysis of the grafts revealed effects of species and donor tissue maturity: all grafts from species with greater daily sperm production (pig and goat) were found to have degenerated tubules or grafts were completely degenerated. None of the xenografts from mature adult bull and monkeys contained differentiated spermatogenic cells when examined more than 12 weeks post-grafting but tubules with Sertoli cells only remained. In grafts from a young adult bull, Sertoli cells persisted much longer than with the mature adult grafts. In grafts from a young adult horse, spermatogenesis proceeded to meiosis. In grafts from a young adult donkey and monkey, however, complete spermatogenesis was found in the grafts. These results show that testis tissue grafts from mature adult donors did not support germ cell differentiation but seminiferous tubules with Sertoli cells only survived in some species. The timing and progression of tubular degeneration after grafting of adult testis tissue appear to be related to the intensity of spermatogenesis at the time of grafting. Testis tissue from sub-adult donors survives better as xenograft than tissue from mature adult donors, and complete spermatogenesis can occur albeit with species-specific differences. 相似文献
35.
Violin M Forbici F Cozzi-Lepri A Velleca R Bertoli A Riva C Giannella S Manconi PE Lazzarin A Pasquinucci S Tacconi L Carnevale G Mazzotta F Bonazzi L Montroni M Chirianni A Capobianchi M Ippolito G Moroni M Perno CF D'Arminio-Monforte A;I.CO.N.A. Study Group. Italian Cohort of Antiretroviral Naive patients 《Journal of biological regulators and homeostatic agents》2002,16(1):37-43
36.
In this paper we describe the cloning of rat olfactory bulb tubulin tyrosine ligase (TTL) cDNA, and investigate the physiological role of TTL in cultured CHO-K1 cells. Comparison of the deduced amino acid sequence of rat TTL cDNA with those of bovine and pig showed approximately 90% of identity. Transient transfection of CHO-K1 cells with a dominant negative mutant of TTL that contains the binding site to the substrate (tubulin) but not the catalytic domain, significantly decreased the endogenous TTL activity as determined in vitro. Similar results were obtained using a construction encoding for the antisense sequence of TTL. The reduction in TTL activity is not accompanied by a decrease in the tyrosination levels of microtubules, as judged by immunofluorescence analysis. Strikingly, the number of cells in the plates transfected with the mutant TTL or the antisense TTL cDNA was, after 72 h of culture, two and three times higher, respectively, than the number of cells in the control plates. These results support the hypothesis that TTL may play a role in the regulation of the cell cycle in living cells. 相似文献
37.
Direct visualization of the microtubular cytoskeleton of ciliated protozoa with a fluorescent taxoid
Arregui L Muñoz-Fontela C Serrano S Barasoain I Guinea A 《The Journal of eukaryotic microbiology》2002,49(4):312-318
Visualization of the infraciliature, which is an essential tool for the identification of ciliate species, has traditionally been obtained with silver proteinate methods. Since infraciliature is mainly composed of microtubules, we used the synthetic fluorescent taxoid FLUTAX as a method for ciliate identification. The main advantages of this method are the facility and rapidity of its application and the fact that no previous fixation and permeabilization processes are required. FLUTAX may also be used as a probe to follow morphogenetical changes in the microtubular cytoskeleton during the ciliate life cycle. 相似文献
38.
39.
Valérie Potard Jacques Reynes Tristan Ferry Céline Aubin Laurent Finkielsztejn Yazdan Yazdanpanah Dominique Costagliola FHDH ANRS CO 《PloS one》2015,10(12)
Introduction
Limited data are available on the durability and effectiveness of maraviroc in routine clinical practice. We assessed the durability of maraviroc-containing regimens during a 30-month period, as well as their immunovirological and clinical efficacy, according to viral tropism in treatment-experienced individuals with viral load (VL) >50 copies/ml in the French Hospital Database on HIV.Methods
Virological success was defined as VL<50 copies/ml, immunological success as a confirmed increase of at least 100 CD4 cells/mm3 measured twice at least one month apart, and clinical failure as hospitalization for a non-AIDS event, an AIDS event, or death. Multivariable Cox regression models adjusted for potential confounders were used to assess the influence of viral tropism on durability, the immunovirological responses, and clinical outcome.Results
356 individuals started maraviroc with VL>50 copies/ml of whom 223 harbored R5 viruses, 44 non-R5 viruses and 89 viruses of unknown tropism. Individuals with non-R5 viruses were more likely than individuals with R5 viruses to discontinue maraviroc (75% vs 34%, p<0.0001). At 30 months, the estimated rates of virological and immunological success were respectively 89% and 51% in individuals with R5 viruses and 48% and 23% in individuals with non-R5 viruses. In multivariable analysis, non-R5 viruses were associated with a lower likelihood of both virological success (hazard ratio (HR): 0.42; 95% confidence interval (CI), 0.25–0.70) and immunological success (HR: 0.37; 95% CI, 0.18–0.77). No difference in clinical outcome was found between individuals with R5 and non-R5 viruses. The effectiveness of maraviroc-containing regimens in individuals with unknown viral tropism was not significantly different from that in individuals with R5 viruses. A limitation of the study is the absence of genotypic susceptibility score.Conclusion
In this observational study, maraviroc-containing regimens yielded high rates of viral suppression and immunological responses in individuals with R5 viruses in whom prior regimens had failed. 相似文献40.
Lukas Schwingshackl Georg Hoffmann Tamara Kalle-Uhlmann Maria Arregui Brian Buijsse Heiner Boeing 《PloS one》2015,10(10)