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Olivier Leroy

Publications and source records attributed to Olivier Leroy.

At least 19 recordsLinked to original sources
PubMed2006

Different Polycomb group complexes regulate common target genes in Arabidopsis.

Polycomb group (PcG) proteins convey epigenetic inheritance of repressed transcriptional states. Although the mechanism of the action of PcG is not completely understood, methylation of histone H3 lysine 27 (H3K27) is important in establishing PcG-mediated transcriptional repression. We show that the plant PcG target gene PHERES1 is regulated by histone trimethylation on H3K27 residues mediated by at least two different PcG complexes in plants, containing the SET domain proteins MEDEA or CURLY LEAF/SWINGER. Furthermore, we identify FUSCA3 as a potential PcG target gene and show that FUSCA3 is regulated by MEDEA and CURLY LEAF/SWINGER. We propose that different PcG complexes regulate a common set of target genes during the different stages of plant development.

Amino Acid Sequence↗
PubMed2006

Polycomb-group proteins repress the floral activator AGL19 in the FLC-independent vernalization pathway.

Polycomb-group (PcG) proteins form a cellular memory by maintaining developmental regulators in a transcriptionally repressed state. We identified a novel flowering gene that is under PcG control in Arabidopsis--the MADS-box gene AGL19. AGL19 expression is maintained at very low levels by the PcG proteins MSI1, CLF, and EMF2, and AGL19 is partly responsible for the early flowering phenotype of clf mutants. AGL19 chromatin is strongly enriched in trimethylation of Lys 27 on histone H3 (H3K27me3) but not in H3K9me2. Repressive H3K27me3 marks were reduced by decreased CLF or MSI1 levels and by prolonged cold, suggesting that the PcG proteins MSI1 and CLF repress AGL19 in the absence of cold. Ectopic expression of AGL19 strongly accelerates flowering, and agl19 mutants have a decreased response to vernalization, the promotion of flowering by prolonged cold. Epistasis analyses revealed that AGL19 works in the poorly characterized FLC-independent vernalization pathway and does not require SOC1 to function. In this pathway, prolonged cold relieves AGL19 from PcG repression by a mechanism that requires VIN3 but not VRN2. Elevated AGL19 levels activate LFY and AP1 and eventually cause flowering.

Arabidopsis↗
PubMed2006

Procalcitonin kinetics in the prognosis of severe community-acquired pneumonia.

OBJECTIVES: Procalcitonin (PCT) kinetics is a good prognosis marker in infectious diseases, but few studies of community-acquired pneumonia (CAP) have been performed in intensive care units (ICU). We analyzed the relationship between PCT kinetics and outcome in ICU patients with severe CAP. DESIGN AND SETTING: Prospective observational study in a 16-bed university hospital ICU. PATIENTS: 100 critically ill patients with community-acquired pneumonia. MEASUREMENTS AND RESULTS: Median PCT was 5.2 ng/ml on day 1 and 2.9 ng/ml on day 3. It increased from day 1 to day 3 in nonsurvivors but decreased in survivors. In multivariate analysis four variables were associated with death: invasive ventilation (odds ratio 10-), multilobar involvement (5.6-), LOD score (6.9-), and PCT increase from day 1 to day 3 (4.5-). In intubated patients with a PCT level below 0.95 ng/ml on day 3 the survival rate was 95%. CONCLUSION: Increased PCT from day 1 to day 3 in severe CAP is a poor prognosis factor. A PCT level less than 0.95 ng/ml on day 3 in intubated patients is associated with a favorable outcome.

Aged↗
PubMed2006

ETR-3 represses Tau exons 2/3 inclusion, a splicing event abnormally enhanced in myotonic dystrophy type I.

Altered splicing of transcripts, including the insulin receptor (IR) and the cardiac troponin (cTNT), is a key feature of myotonic dystrophy type I (DM1). CELF and MBNL splicing factor members regulate the splicing of those transcripts. We have previously described an alteration of Tau exon 2 splicing in DM1 brain, resulting in the favored exclusion of exon 2. However, the factors required for alternative splicing of Tau exon 2 remain undetermined. Here we report a decreased expression of CELF family member and MBNL transcripts in DM1 brains as assessed by RT-PCR. By using cellular models with a control- or DM1-like splicing pattern of Tau transcripts, we demonstrate that ETR-3 promotes selectively the exclusion of Tau exon 2. These results together with the analysis of Tau exon 6 and IR exon 11 splicing in brain, muscle, and cell models suggest that DM1 splicing alteration of several transcripts involves various factors.

Alternative Splicing↗
PubMed2006

Epidemiology and prognostic factors of critically ill patients treated with hemodiafiltration.

PURPOSE: The objective of this study is to study the epidemiology, outcome, and prognostic factors of critically ill patients treated with continuous venovenous hemodiafiltration (CVVHDF). MATERIALS AND METHODS: Observational cohort was done in a French 16-bed intensive care unit (ICU) from a university-affiliated urban hospital. All patients requiring, in the opinion of the treating physician, the initiation of CVVHDF were included in the study. RESULTS: One hundred ninety-seven patients with acute renal failure (ARF) treated with CVVHDF were studied. The incidence of ARF treated with CVVHDF was 5.9% in the ICU with a mortality rate of 71.6%. A multivariate analysis identified 3 independent factors associated with fatal outcome: mechanical ventilation, sepsis, and septic shock requiring vasoactive drug. In contrast, 2 independent factors predicted a favorable outcome: nonoliguric ARF and serum creatinine concentration higher than 34 mg/L at CVVHDF initiation. A flowchart determined by the chi2 Automatic Interaction and Detection statistical method allowed for the identification of patients' subgroups with different mortality rates ranging from 25% to 100%. CONCLUSIONS: In our series, ARF treated with CVVHDF was associated with a high overall ICU mortality rate (71.6%). However, our prognostic flowchart identified patients with low mortality rates for which renal replacement therapy must be initiated with no discussion as soon as required.

Acute Kidney Injury↗
PubMed2006

Predictors of extubation failure in patients with chronic obstructive pulmonary disease.

Few studies have focused on extubation outcome in patients with chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation (MV). We conducted a study using prospectively collected data in a cohort of patients with COPD requiring invasive MV to identify variables associated with extubation failure. Use of noninvasive or invasive MV within 48 hours after extubation was defined as extubation failure. A total of 148 patients with COPD were studied. Extubation failure occurred in 35% of studied patients. Using multiple regression analysis, independent predictors of extubation failure were physiologic abnormalities measured by Simplified Acute Physiology Score II above 35 on intensive care unit (ICU) admission (odds ratio [OR], 3.88; 95% confidence interval [CI], 1.65-9.12), home noninvasive MV (OR, 12.99; 95% CI, 2.86-58.89), and sterile endotracheal aspirations on the day of extubation were predictors of success (OR, 0.23; 95% CI, 0.10-0.52). Despite high rate of extubation failure, survival to ICU discharge was 91% of the studied population. Extubation failure in patients with COPD remains high despite a successful spontaneous breathing on T piece. Simplified Acute Physiology Score II at ICU admission, home noninvasive MV, and isolated pathogens on quantitative cultures of tracheobronchial secretions within 72 hours preceding extubation were predictors of extubation failure in the study population.

APACHE↗
PubMed2006

An 18-case outbreak of drug-resistant Pseudomonas aeruginosa bacteriemia in hematology patients.

We retrospectively identified an outbreak of 18 episodes of P. aeruginosa bacteriemia in 17 patients with hematologic malignancies in 2004. All strains were ticarcillin I/R, 77% ciprofloxacin I/R, 72% ceftazidime I/R, 72% amikacin I/R and 50% imipenem I/R. The outbreak was multiclonal. Colistin was employed for documented therapy in ten cases including seven in which it was the only active drug. Outcomes were resolution of infection in 12 out of 18 episodes (67%), and death in six cases, five (25%) of which were attributable to the infection. Colistin was useful even in highly resistant strains and the efficacy of antibacterial therapy was similar (57%)in bacteriemia due to strains only susceptible to colistin.

Anti-Bacterial Agents↗
PubMed2005

Brain-specific change in alternative splicing of Tau exon 6 in myotonic dystrophy type 1.

Alternative splicing is altered in myotonic dystrophy of type 1 (DM1), a syndrome caused by an increase of CTG triplet repeats in the 3' untranslated region of the myotonic dystrophy protein kinase gene. Previously, we reported the preferential skipping of Tau exon 2 in DM1 brains. In this study, we analyze the alternative splicing of Tau exon 6 which can be inserted in three different forms (c, p and d) depending on the 3' splice site used. In fact, inclusion of exon 6c decreases in DM1 brains compared to control brains whereas inclusion of 6d increases. Alteration of exon 6 splicing was not observed in DM1 muscle although this exon was inserted in RNAs from normal muscle and DM1 splicing alterations were first described in this organ. In contrast, alteration of exon 2 of Tau mRNA was observed in both muscle and brain. However, co-transfections of a minigene containing exon 6 with CELF or MBNL1 cDNAs, two splicing factor families suspected to be involved in DM1, showed that they influence exon 6 splicing. Altogether, these results show the importance of determining all the exons and organs targeted by mis-splicing to determine the dysregulation mechanisms of mis-splicing in DM1.

Alternative Splicing↗
PubMed2005

Inhibition of bacterial RNA polymerase by streptolydigin: stabilization of a straight-bridge-helix active-center conformation.

We define the target, mechanism, and structural basis of inhibition of bacterial RNA polymerase (RNAP) by the tetramic acid antibiotic streptolydigin (Stl). Stl binds to a site adjacent to but not overlapping the RNAP active center and stabilizes an RNAP-active-center conformational state with a straight-bridge helix. The results provide direct support for the proposals that alternative straight-bridge-helix and bent-bridge-helix RNAP-active-center conformations exist and that cycling between straight-bridge-helix and bent-bridge-helix RNAP-active-center conformations is required for RNAP function. The results set bounds on models for RNAP function and suggest strategies for design of novel antibacterial agents.

Aminoglycosides↗
PubMed2005

Effect of gingival and dental plaque antiseptic decontamination on nosocomial infections acquired in the intensive care unit: a double-blind placebo-controlled multicenter study.

OBJECTIVE: To document the effect of gingival and dental plaque antiseptic decontamination on the rate of nosocomial bacteremias and respiratory infections acquired in the intensive care unit (ICU). DESIGN: Prospective, multicenter, double-blind, placebo-controlled efficacy study. SETTING: Six ICUs: three in university hospitals and three in general hospitals. PATIENTS: A total of 228 nonedentulous patients requiring endotracheal intubation and mechanical ventilation, with an anticipated length of stay > or =5 days. INTERVENTIONS: Antiseptic decontamination of gingival and dental plaque with a 0.2% chlorhexidine gel or a placebo gel, three times a day, during the entire ICU stay. MEASUREMENTS AND MAIN RESULTS: Demographic and clinical characteristics, organ function data (Logistic Organ Dysfunction score), severity of condition (Simplified Acute Physiologic Score), and dental plaque status were assessed at baseline and until 28 days. Bacteriologic sampling of dental plaque and saliva was done every 5 days, and blood, tracheal aspirate, and bronchoalveolar lavage cultures were performed when appropriate. The primary efficacy end point was the incidence of bacteremia, bronchitis, and ventilator-associated pneumonia, expressed as a percentage and per 1000 ICU days. All baseline characteristics were similar between the treated and the placebo groups. The incidence of nosocomial infections was 17.5% (13.2 per 1000 ICU days) in the placebo group and 18.4% (13.3 per 1000 ICU days) in the plaque antiseptic decontamination group (not significant). No difference was observed in the incidence of ventilator-associated pneumonia per ventilator or intubation days, mortality, length of stay, and care loads (secondary end points). On day 10, the number of positive dental plaque cultures was significantly lower in the treated group (29% vs. 66%; p < .05). Highly resistant Pseudomonas, Acinetobacter, and Enterobacter species identified in late-onset ventilator-associated pneumonia and previously cultured from dental plaque were not eradicated by the antiseptic decontamination. No side effect was reported. CONCLUSIONS: Gingival and dental plaque antiseptic decontamination significantly decreased the oropharyngeal colonization by aerobic pathogens in ventilated patients. However, its efficacy was insufficient to reduce the incidence of respiratory infections due to multiresistant bacteria.

Anti-Infective Agents, Local↗
PubMed2005

Comparison of levofloxacin and cefotaxime combined with ofloxacin for ICU patients with community-acquired pneumonia who do not require vasopressors.

STUDY OBJECTIVES: To evaluate the efficacy and tolerability of levofloxacin (L) as monotherapy in patients with severe community-acquired pneumonia (CAP) in comparison with therapy using a combination of cefotaxime (C) plus ofloxacin (O). DESIGN: Prospective, randomized 1:1, comparative, open, parallel-group study. SETTING: Multinational study with 149 sites. PATIENTS: A total of 398 randomized patients who had been admitted to the ICU with severe CAP without shock, including 308 patients in a modified intent-to-treat population and 271 patients in the per-protocol (PP) population (L group, 139 patients; C + O group, 132 patients). INTERVENTIONS: Therapy with levofloxacin (500 mg IV, q12h) vs therapy with a C + O combination (C, 1g IV, q8h; O, 200 mg IV, q12h) for 10 to 14 days. MEASUREMENTS AND RESULTS: The main end point was the clinical efficacy at the end of treatment (ie, the test-of-cure [TOC] visit). The statistical hypothesis was the noninferiority of L therapy to C + O therapy with a 2.5% alpha risk (unilateral) and a 15% maximum set difference. At the TOC visit, a clinical success was observed in 79.1% of patients (L group) and 79.5% of patients (C + O group) in the PP population (difference, -0.4%; 95% confidence interval [CI], -10.79 to 9.97% without adjustment for simplified acute physiology score [SAPS] II at inclusion; difference, -0.3%; 95% CI, -10.13 to 9.58% with adjustment for SAPS II). A satisfactory bacteriologic response was present in 73.7% of L group patients and 77.5% of C + O group patients, including responses of 75.7% and 70.3%, respectively, in the L group and C + O group in the Streptococcus pneumoniae-documented population. In the safety analysis, 20 patients in the L group (10.3%) and 16 patients in the C + O group (8.0%) experienced at least one adverse event that was considered to be treatment-related. CONCLUSION: L therapy was at least as effective as the combination therapy of C + O in the treatment of a subset of patients with CAP requiring ICU admission. This conclusion cannot be extrapolated to patients requiring mechanical ventilation or vasopressors (ie, those patients in shock).

Adult↗
PubMed2004

Substitutions in region 2.4 of sigma70 allow recognition of the sigmaS-dependent aidB promoter.

The strict dependence of transcription from the aidB promoter (PaidB) on the Esigma(S) form of RNA polymerase is because of the presence of a C nucleotide as the first residue of the -10 promoter sequence (-12C), which does not allow an open complex formation by Esigma(70). In this report, sigma(70) mutants carrying either the Q437H or the T440I single amino acid substitutions, which allow -12C recognition by sigma(70), were tested for their ability to carry out transcription from PaidB. The Gln-437 and Thr-440 residues are located in region 2.4 of sigma(70) and correspond to Gln-152 and Glu-155 in sigma(S). Interestingly, the Q437H mutant of sigma(70), but not T440I, was able to promote an open complex formation and to initiate transcription at PaidB. In contrast to T440I, a T440E mutant was proficient in carrying out transcription from PaidB. No sigma(70) mutant displayed significantly increased interaction with a PaidB mutant in which the -12C was substituted by a T (PaidB((C12T))), which is also efficiently recognized by wild type sigma(70). The effect of the T440E mutation suggests that the corresponding Glu-155 residue in sigma(S) might be involved in -12C recognition. However, substitution to alanine of the Glu-155 residue, as well as of Gln-152, in the sigma(S) protein did not significantly affect Esigma(S) interaction with PaidB. Our results reiterate the importance of the -12C residue for sigma(S)-specific promoter recognition and strongly suggest that interaction with the -10 sequence and open complex formation are carried out by different determinants in the two sigma factors.

Binding, Competitive↗
PubMed2004

[Lung diseases in the elderly. Assessment of guidelines for the probabilistic prescription of antibiotics in a department of geriatric care].

OBJECTIVE: We developed a prescribing guideline containing recommendations for the initial empirical antibiotic therapy in community or nosocomial pneumonia. The aim of the present study was to examine the impact of this measure. METHOD: The prescribing guideline was implemented in May 1999. We retrospectively reviewed the charts of all patients>65 years with community-, or nursing home- or hospital-acquired pneumonia hospitalised in our department of acute geriatric care between May 1999 and November 2000. The criteria assessed were: consistence with the guideline, clinical effectiveness within 72 hours, adequation with the isolated germs and intra-hospital mortality. RESULTS: Data were collected on 112 patients (63 women et 49 men; mean age=80 +/- 8 Years). The pneumonia was community-acquired in 52 cases (46%), nursing home acquired in 25 cases (22%) and hospital-acquired in 35 cases (31%). Antibiotic prescription was consistent with the guideline in 64 cases (57%). When the antibiotic therapy was consistent, the patients were more likely to improve within 72 hours (45/64 versus 23/48; p=0.01). Despite a tendency, the number of antimicrobial treatments adapted to the isolated microorganisms was not significantly higher in the consistent group (22/36 adapted treatments versus 10/20). The intra-hospital mortality (25%) was similar in the two groups consistent and not consistent with the guideline. SARM was the most frequent multiresistant bacteria that was isolated. CONCLUSION: The use of a prescribing guideline might improve the efficiency of empirical probabilistic antibiotic therapies. The impact of the guideline use on overall antibiotic costs and microbiological flora remains to be determined.

Aged↗
PubMed2004

Interactions between the 2.4 and 4.2 regions of sigmaS, the stress-specific sigma factor of Escherichia coli, and the -10 and -35 promoter elements.

The sigmas subunit of Escherichia coli RNA polymerase holoenzyme (EsigmaS) is a key factor of gene expression upon entry into stationary phase and in stressful conditions. The selectivity of promoter recognition by EsigmaS and the housekeeping Esigma70 is as yet not clearly understood. We used a genetic approach to investigate the interaction of sigmaS with its target promoters. Starting with down-promoter variants of a sigmaS promoter target, osmEp, altered in the -10 or -35 elements, we isolated mutant forms of sigmaS suppressing the promoter defects. The activity of these suppressors on variants of osmEp and ficp, another target of sigmaS, indicated that sigmaS is able to interact with the same key features within a promoter sequence as sigma70. Indeed, (i) sigmaS can recognize the -35 element of some but not all its target promoters, through interactions with its 4.2 region; and (ii) amino acids within the 2.4 region participate in the recognition of the -10 element. More specifically, residues Q152 and E155 contribute to the strong preference of sigmaS for a C in position -13 and residue R299 can interact with the -31 nucleotide in the -35 element of the target promoters.

Amino Acid Sequence↗