HIV-1 group O phenotypic susceptibility to integrase inhibitors

International audienc

Early-onset ventilator-associated pneumonia in adults randomized clinical trial: comparison of 8 versus 15 days of antibiotic treatment

International audiencePurposeThe optimal treatment duration for ventilator-associated pneumonia is based on one study dealing with late-onset of the condition. Shortening the length of antibiotic treatment remains a major prevention factor for the emergence of multiresistant bacteria.ObjectiveTo demonstrate that 2 different antibiotic treatment durations (8 versus 15 days) are equivalent in terms of clinical cure for early-onset ventilator-associated pneumonia.MethodsRandomized, prospective, open, multicenter trial carried out from 1998 to 2002.MeasurementsThe primary endpoint was the clinical cure rate at day 21. The mortality rate was evaluated on days 21 and 90.Results225 patients were included in 13 centers. 191 (84.9%) patients were cured: 92 out of 109 (84.4%) in the 15 day cohort and 99 out of 116 (85.3%) in the 8 day cohort (difference = 0.9%, odds ratio = 0.929). 95% two-sided confidence intervals for difference and odds ratio were [−8.4% to 10.3%] and [0.448 to 1.928] respectively. Taking into account the limits of equivalence (10% for difference and 2.25 for odds ratio), the objective of demonstrative equivalence between the 2 treatment durations was fulfilled. Although the rate of secondary infection was greater in the 8 day than the 15 day cohort, the number of days of antibiotic treatment remained lower in the 8 day cohort. There was no difference in mortality rate between the 2 groups on days 21 and 90.ConclusionOur results suggest that an 8-day course of antibiotic therapy is safe for early-onset ventilator-associated pneumonia in intubated patients

Regulation by protein kinase-C of putative P-type Ca channels expressed in Xenopus oocytes from cerebellar mRNA

AbstractXenopus oocytes injected with rat cerebellar mRNA expressed functional voltage-dependent Ca channels detected as an inward Ba current (IBa). The pharmacological resistance to dihydropyridines and ω-conotoxin together with the blockade obtained with Agelenopsis aperta venom suggest that these channels could be somehow assimilated to P-type Ca channels. The precise nature of the transplanted Ca channels was assessed by hybrid-arrest experiments using a specific oligonucleotide antisense-derivated from the recently cloned α1-subunit of P channels (BI-1 clone). In addition, we demonstrate that exogenous Ca channel activity was enhanced by two different PKC activators (a phorbol ester and a structural analog to diacylglycerol). The general electrophysiological and pharmacological properties of the stimulated Ca channels remain unchanged. This potentiation induced by PKC activators is antagonized by a PKC inhibitor (staurosporine) and by a monoclonal antibody directed against PKC. It is concluded that P-type Ca channels are potentially regulated by PKC phosphorylation and the functional relevance of this intracellular pathway is discussed

NETWOODRESIST - An international network of open laboratories between Europe and Latin America to develop new tools on wood adaptative traits on drought stress and climatic change studies

International audienc

Costimulation blockade with Belatacept in renal transplantation

Background: Renal transplantation is the standard of care for patients with end-stage renal disease. Although maintenance immunosuppression with calcineurin inhibitors yields excellent one-year survival, it is associated over the long term with high rates of death and graft loss, owing in part to the adverse renal, cardiovascular, and metabolic effects of these agents. The use of potentially less toxic agents, such as belatacept, a selective blocker of T-cell activation, may improve outcomes. Methods: We randomly assigned renal-transplant recipients to receive an intensive or a less-intensive regimen of belatacept or cyclosporine. All patients received induction therapy with basiliximab, mycophenolate mofetil, and corticosteroids. The primary objective was to demonstrate the noninferiority of belatacept over cyclosporine in the incidence of acute rejection at six months (with an upper bound of the 95 percent confidence interval around the treatment difference of less than 20 percent). Results: At six months, the incidence of acute rejection was similar among the groups: 7 percent for intensive belatacept, 6 percent for less-intensive belatacept, and 8 percent for cyclosporine. At 12 months, the glomerular filtration rate was significantly higher with both intensive and less-intensive belatacept than it was with cyclosporine (66.3, 62.1, and 53.5 ml per minute per 1.73 m2, respectively), and chronic allograft nephropathy was less common with both regimens of belatacept than with cyclosporine (29 percent, 20 percent, and 44 percent, respectively). Lipid levels and blood-pressure values were similar or slightly lower in the belatacept groups, despite the greater use of lipid-lowering and antihypertensive medications in the cyclosporine group. Conclusions: Belatacept, an investigational selective costimulation blocker, did not appear to be inferior to cyclosporine as a means of preventing acute rejection after renal transplantation. Belatacept may preserve the glomerular filtration rate and reduce the rate of chronic allograft nephropathy

Transcriptomic changes in human breast cancer progression as determined by serial analysis of gene expression

INTRODUCTION: Genomic and transcriptomic alterations affecting key cellular processes such us cell proliferation, differentiation and genomic stability are considered crucial for the development and progression of cancer. Most invasive breast carcinomas are known to derive from precursor in situ lesions. It is proposed that major global expression abnormalities occur in the transition from normal to premalignant stages and further progression to invasive stages. Serial analysis of gene expression (SAGE) was employed to generate a comprehensive global gene expression profile of the major changes occurring during breast cancer malignant evolution. METHODS: In the present study we combined various normal and tumor SAGE libraries available in the public domain with sets of breast cancer SAGE libraries recently generated and sequenced in our laboratory. A recently developed modified t test was used to detect the genes differentially expressed. RESULTS: We accumulated a total of approximately 1.7 million breast tissue-specific SAGE tags and monitored the behavior of more than 25,157 genes during early breast carcinogenesis. We detected 52 transcripts commonly deregulated across the board when comparing normal tissue with ductal carcinoma in situ, and 149 transcripts when comparing ductal carcinoma in situ with invasive ductal carcinoma (P < 0.01). CONCLUSION: A major novelty of our study was the use of a statistical method that correctly accounts for the intra-SAGE and inter-SAGE library sources of variation. The most useful result of applying this modified t statistics beta binomial test is the identification of genes and gene families commonly deregulated across samples within each specific stage in the transition from normal to preinvasive and invasive stages of breast cancer development. Most of the gene expression abnormalities detected at the in situ stage were related to specific genes in charge of regulating the proper homeostasis between cell death and cell proliferation. The comparison of in situ lesions with fully invasive lesions, a much more heterogeneous group, clearly identified as the most importantly deregulated group of transcripts those encoding for various families of proteins in charge of extracellular matrix remodeling, invasion and cell motility functions

PLoS Pathog

The low pathogenicity and replicative potential of HIV-2 are still poorly understood. We investigated whether HIV-2 reservoirs might follow the peculiar distribution reported in models of attenuated HIV-1/SIV infections, i.e. limited infection of central-memory CD4 T lymphocytes (TCM). Antiretroviral-naive HIV-2 infected individuals from the ANRS-CO5 (12 non-progressors, 2 progressors) were prospectively included. Peripheral blood mononuclear cells (PBMCs) were sorted into monocytes and resting CD4 T-cell subsets (naive [TN], central- [TCM], transitional- [TTM] and effector-memory [TEM]). Reactivation of HIV-2 was tested in 30-day cultures of CD8-depleted PBMCs. HIV-2 DNA was quantified by real-time PCR. Cell surface markers, co-receptors and restriction factors were analyzed by flow-cytometry and multiplex transcriptomic study. HIV-2 DNA was undetectable in monocytes from all individuals and was quantifiable in TTM from 4 individuals (median: 2.25 log10 copies/106 cells [IQR: 1.99-2.94]) but in TCM from only 1 individual (1.75 log10 copies/106 cells). HIV-2 DNA levels in PBMCs (median: 1.94 log10 copies/106 PBMC [IQR = 1.53-2.13]) positively correlated with those in TTM (r = 0.66, p = 0.01) but not TCM. HIV-2 reactivation was observed in the cells from only 3 individuals. The CCR5 co-receptor was distributed similarly in cell populations from individuals and donors. TCM had a lower expression of CXCR6 transcripts (p = 0.002) than TTM confirmed by FACS analysis, and a higher expression of TRIM5 transcripts (p = 0.004). Thus the low HIV-2 reservoirs differ from HIV-1 reservoirs by the lack of monocytic infection and a limited infection of TCM associated to a lower expression of a potential alternative HIV-2 co-receptor, CXCR6 and a higher expression of a restriction factor, TRIM5. These findings shed new light on the low pathogenicity of HIV-2 infection suggesting mechanisms close to those reported in other models of attenuated HIV/SIV infection models

Évolution et structures du roman maghrébin de langue française

Jusqu'à ce jour en effet le roman maghrébin a été l'objet de nombreuses études, diverses et intéressantes, mais jamais il n'a été analysé dans son ensemble et dans sa spécificité littéraire. Depuis les premiers travaux de Meade et Benouameur jusqu'à ceux, très importants, de Jean Déjeux, en passant par les thèses de Khatibi, Yétiv et Bonn, l'optique a toujours été sociologique et le corpus partiel, soit que l'on privilégiât une période, soit que l'on fît commencer le roman maghrébin en 1950, sans se soucier de tenir un compte précis des premiers romans. Nous avons voulu rompre avec ces méthodes et cette optique. Le roman maghrébin est d'abord une forme et, en tant que tel, il est susceptible de recevoir un traitement structural. Plutôt que de lire la société maghrébine à travers le roman, il nous est apparu que les structures sociologiques faisaient partie du texte romanesque à titre d'éléments formels. Sans doute, à l'origine, l'intérêt que nous portions au roman maghrébin était-il essentiellement sociologique. Mais il fallait dépasser ce sociologisme de base pour ouvrir la lecture à des considérations proprement littéraires. Comment était fait le roman maghrébin? Quelles étaient ses composantes élémentaires? Comment ces composantes se conjuguaient-elles dans des oeuvres concrètes? Toutes ces questions ont guidé notre démarche et nous ont imposé un plan de travail et d'exposition

Évolution et structures du roman maghrébin de langue française

Jusqu'à ce jour en effet le roman maghrébin a été l'objet de nombreuses études, diverses et intéressantes, mais jamais il n'a été analysé dans son ensemble et dans sa spécificité littéraire. Depuis les premiers travaux de Meade et Benouameur jusqu'à ceux, très importants, de Jean Déjeux, en passant par les thèses de Khatibi, Yétiv et Bonn, l'optique a toujours été sociologique et le corpus partiel, soit que l'on privilégiât une période, soit que l'on fît commencer le roman maghrébin en 1950, sans se soucier de tenir un compte précis des premiers romans. Nous avons voulu rompre avec ces méthodes et cette optique. Le roman maghrébin est d'abord une forme et, en tant que tel, il est susceptible de recevoir un traitement structural. Plutôt que de lire la société maghrébine à travers le roman, il nous est apparu que les structures sociologiques faisaient partie du texte romanesque à titre d'éléments formels. Sans doute, à l'origine, l'intérêt que nous portions au roman maghrébin était-il essentiellement sociologique. Mais il fallait dépasser ce sociologisme de base pour ouvrir la lecture à des considérations proprement littéraires. Comment était fait le roman maghrébin? Quelles étaient ses composantes élémentaires? Comment ces composantes se conjuguaient-elles dans des oeuvres concrètes? Toutes ces questions ont guidé notre démarche et nous ont imposé un plan de travail et d'exposition