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51.
Lanoy E Rosenberg PS Fily F Lascaux AS Martinez V Partisani M Poizot-Martin I Rouveix E Engels EA Costagliola D Goedert JJ;FHDH-ANRS CO 《Blood》2011,118(1):44-49
Hodgkin lymphoma (HL) incidence with HIV infection may have increased with the introduction of combination antiretroviral therapy (cART), suggesting that immune reconstitution may contribute to some cases. We evaluated HL risk with cART during the first months of treatment. With 187 HL cases among 64 368 HIV patients in France, relative rates (RRs) and 95% confidence intervals (CIs) of HL were estimated using Poisson models for duration of cART, CD4 count, and HIV load, with and without adjustment for demographic/clinical covariates. HL risk was unrelated to cART use overall, but it was related to time intervals after cART initiation (P = .006). Risk was especially and significantly elevated in months 1-3 on cART (RR 2.95, CI 1.64-5.31), lower in months 4-6 (RR 1.63), and null with longer use (RR 1.00). CD4 count was strongly associated with HL risk (P < 10??), with the highest HL incidence at 50-99 CD4 cells/mm3. With adjustment for CD4 count and covariates, HL risk was elevated, but not significantly (RR 1.42), in months 1-3 on cART. HIV load had no added effect. HL risk increased significantly soon after cART initiation, which was largely explained by the CD4 count. Further studies of HIV-associated HL are needed. 相似文献
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Intrahepatic injection of adenovirus reduces inflammation and increases gene transfer and therapeutic effect in mice 总被引:2,自引:0,他引:2
Crettaz J Berraondo P Mauleón I Ochoa-Callejero L Ochoa L Shankar V Barajas M van Rooijen N Kochanek S Qian C Prieto J Hernández-Alcoceba R González-Aseguinolaza G 《Hepatology (Baltimore, Md.)》2006,44(3):623-632
Recombinant adenoviruses (Ad) are among the most extensively used vectors for liver gene transfer. One of the major limitations for the clinical application of these vectors is the inflammatory immune response associated with systemic administration of high dose of virus. We evaluated the effect of Ad administration route on the inflammatory immune response and liver transgene expression. We compared direct intrahepatic injection (IH) with the systemic administration via tail vein (IV). IH injection of Ad resulted in a lower inflammatory response and a higher transgene expression. When a relatively low dose of virus was used, IV administration resulted in no detectable protein expression but production of proinflammatory cytokines. In contrast, IH administration induced high levels of transgene expression and no inflammation, although we detected a transient hypertransaminemia, which fully resolved within days. Furthermore, IH injection resulted in a faster protein expression being more intense at the site of injection, whereas IV administration caused slower but diffuse liver expression. IH injection also reduced the spreading of the virus to other organs. Independently of the route, depletion of Kupffer cells significantly enhanced the transduction efficiency of Ad. This effect was stronger when using IV injection, indicating that IH injection partially overcomes Kupffer cell phagocytic activity. Moreover, the antitumor efficacy of high-capacity-Ad encoding murine interleukin-12 (IL-12) was significantly greater when the vector was administered by IH injection than when given IV. In conclusion, IH injection of adenovirus represents a safe and efficient administration route for clinical applications of gene therapy targeting the liver. 相似文献
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Thiébaut R Matheron S Taieb A Brun-Vezinet F Chêne G Autran B;immunology group of the ANRS CO HIV- cohort 《AIDS (London, England)》2011,25(6):865-867
Among 342 HIV-2-infected patients of the ANRS CO5 HIV-2 cohort, the prevalence of long-term nonprogressors (LTNPs) (i.e. asymptomatic for at least 8 years while maintaining CD4 cell count at least 500 cells/μl) and of HIV controllers (i.e. controlling HIV replication in the absence of antiretroviral treatment for at least 10 years) was 6.1% (95% confidence interval 3.9-9.1) and 9.1% (6.3-12.7), respectively. Most LTNPs (81%) were HIV controllers, whereas only 55% of HIV controllers were LTNPs. 相似文献
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Alegret M Cuberas-Borrós G Vinyes-Junqué G Espinosa A Valero S Hernández I Roca I Ruíz A Rosende-Roca M Mauleón A Becker JT Castell-Conesa J Tárraga L Boada M 《Journal of Alzheimer's disease : JAD》2012,30(1):109-120
The 15-Objects Test (15-OT) provides useful gradation of visuoperceptual impairment from normal aging through Alzheimer's disease (AD) and correlates with temporo-parietal perfusion. The objectives of this study were to analyze progression of 15-OT performance in mild cognitive impairment (MCI) and AD, and its correlates with cognition and single photon emission computerized tomography (SPECT), as well as to examine neuropsychological and SPECT differences between the MCI patients who developed AD and those who did not. From the initial 126 participants (42/group), 38 AD, 39 MCI, and 38 elderly controls (EC) were reassessed (SPECT: 35 AD, 33 MCI, 35 EC) after two years. The progression of cognitive and SPECT scores during this period was compared between groups, and baseline data between converters and non-converters. The 15-OT was the only measure of progression that differed between the three groups; worsening scores on 15-OT were associated with worsening in verbal and visual retention, and decreased perfusion on left postsubicular area. In the MCI patients, cerebral perfusion fell over the two years in medial-posterior cingulate and fronto-temporo-parietal regions; AD showed extensive changes involving almost all cerebral regions. No SPECT changes were detected in controls. At baseline, the MCI patients who developed AD differed from non-converters in verbal recognition memory, but not in SPECT perfusion. In conclusion, SPECT and 15-OT appear to provide a potential measure to differentiate between normal aging, MCI, and AD. Worsening on 15-OT was related to decreased perfusion in postsubicular area; but further longitudinal studies are needed to determine the contribution of 15-OT as a predictor of AD from MCI. 相似文献
58.
Sonia Moreno-Grau Itziar de Rojas Isabel Hernández Inés Quintela Laura Montrreal Montserrat Alegret Begoña Hernández-Olasagarre Laura Madrid Antonio González-Perez Olalla Maroñas Maitée Rosende-Roca Ana Mauleón Liliana Vargas Asunción Lafuente Carla Abdelnour Octavio Rodríguez-Gómez Silvia Gil Miguel Ángel Santos-Santos Agustín Ruiz 《Alzheimer's & dementia》2019,15(10):1333-1347
IntroductionLarge variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways.MethodsGenome Research at Fundacio ACE ([email protected]) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, [email protected] series were meta-analyzed with additional genome-wide association study data sets.ResultsWe classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444.DiscussionThe regulation of vasculature is a prominent causal component of probable AD. [email protected] meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series. 相似文献
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目的为提高乳糖酸阿奇霉素的效价指标,从而提高该产品质量。通过实验研究成盐反应过程各种参数对乳糖酸阿奇霉素效价的影响选择出最佳工艺条件,如控制成盐温度、终点PH值和反应时间,控制制备乳糖酸的PH值等工艺参数。用于指导大生产,使大生产中乳糖酸阿奇霉素的效价有很大的提高,提高了质量。经大生产实践,实验获得的工艺条件是最佳效价控制条件,达到了提高效价的目的。 相似文献