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F Caron

Publications and source records attributed to F Caron.

At least 19 recordsLinked to original sources

A high degree of macronuclear chromosome polymorphism is generated by variable DNA rearrangements in Paramecium primaurelia during macronuclear differentiation.

DNA rearrangements in Paramecium lead to the formation of macronuclear chromosomes, the sizes of which range from 50 and 800 kb (1 kb is 10(3) base-pairs). This process does not appear to be a simple size reduction of the micronuclear chromosomes by specific and reproducible DNA sequence elimination and chromosomal breakage followed by chromosomal amplification. On the contrary, this process generates a variety of different, but sequence-related, macronuclear chromosomes from a unique set of micronuclear chromosomes. This paper describes an attempt to understand the nature of the diversity of the macronuclear chromosomes and the mechanisms of their production. The structure of three macronuclear chromosomes, 480, 250 and 230 kb in size, have been determined utilizing chromosome-jumping and YAC-cloning techniques. The two smallest chromosomes correspond roughly to the two halves of the longest chromosome. The main contribution to the diversity arises from the chromosomal ends and is due to variable positions of the telomere addition sites and/or to variable rearrangements of DNA sequences. The 480 kb chromosome contains a region of variable length, which is likely to be due to a variable deletion, located at the position of telomerization seen in the two small chromosomes. A model of chromosomal breakage is proposed to rationalize this result where micronuclear DNA is first amplified, broken and degraded to various extent from the newly formed ends, which subsequently are either telomerized or religated. Potential implications of these processes for gene expression is discussed. Known phenotypes that have a macronuclear determinism could be explained by this type of process.

Animals

The differential expression of the G surface antigen alleles in Paramecium primaurelia heterozygous cells correlates to macronuclear DNA rearrangement.

The Paramecium primaurelia cell surface is covered with a high molecular weight protein called the surface antigen. Several genes encode alternative surface antigens, but only one is expressed at a time. In addition, each of these genes shows a high degree of allelic polymorphism. Paramecium primaurelia strains 156 and 168 have different alleles of the G antigen gene whose respective antigens can be distinguished in vivo using specific antibodies. An interallelic exclusion phenomenon has been previously described: 94% of the 156/168 heterozygotes express only the 156 allele of the G gene; 6% express both the 156 and the 168 alleles. The phenotype of the heterozygotes is determined at the time of macronuclear differentiation. We have investigated the molecular basis for the different heterozygous phenotypes. Both mRNAs are always produced, and the 156 mRNA is always more abundant than the 168 mRNA. The relative amounts of these messages, however, vary greatly between different heterozygotes and parallel their phenotype. Pushing the analysis further, we show that the copy number of each allele in the macronucleus correlates with the relative amounts of the mRNAs. However, allelic dosage alone is not sufficient to explain the variations of the mRNA ratio. The G antigen gene is located near a telomere in the macronucleus. We show that the distance between the 156G gene and the telomere is different in homozygotes and heterozygotes. It also varies among heterozygotes and is correlated with the mRNA ratio. Thus, we have identified two different parameters, both linked to the genome rearrangements occurring during macronuclear differentiation, that correlate with the relative expression of the two alleles. Two hypotheses concerning the influence of the telomere position on the expression of the gene are discussed.

Alleles

Short-term treatment of urinary tract infections: the French concept.

The indications for short-term treatment to cure urinary tract infections (UTIs) have been recently clarified in France by a "Consensus Conference". Short-term treatment essentially concerns young, non-pregnant women with symptomatic uncomplicated lower UTI of less than three days duration, with no other underlying severe illness or previous uro-nephrological history, and who accept the idea of clinical and possibly bacteriological control after treatment. Only antibiotics with prolonged urinary excretion are recommended, i.e. co-trimoxazole, fluoroquinolones or fosfomycin-trometamol. In pregnancy, in children, or in the elderly, indications for short-term treatment still remain controversial. As compared with conventional therapeutic strategies using urine cultures, the use of test strips for nitrite and leukocyte esterase for deciding on treatment and assessing its efficacy should allow considerable financial savings.

Anti-Infective Agents, Urinary

Daptomycin or teicoplanin in combination with gentamicin for treatment of experimental endocarditis due to a highly glycopeptide-resistant isolate of Enterococcus faecium.

Using an experimental endocarditis model, we studied the activity of daptomycin used alone or in combination with gentamicin against an Enterococcus faecium strain that was highly resistant to glycopeptides and susceptible to gentamicin. In vitro, the MIC of daptomycin was 1 micrograms/ml. In vivo, daptomycin appeared to be effective only when it was used in a high-dose regimen, i.e., 12 mg/kg of body weight every 8 h (-2.5 log10 CFU/g versus controls; P < 0.05), particularly when it was combined with gentamicin (-5.0 log10 CFU/g versus controls; P < 0.01). Since the distribution of daptomycin into cardiac vegetations, as evaluated by autoradiography, appeared to be homogeneous, the poor in vivo activity of daptomycin was considered to be related to its high degree of protein binding, as suggested by killing curves studies. Since the MIC of teicoplanin for the vancomycin-resistant E. faecium strain used in the study was only 64 micrograms/ml and since an in vitro synergy between teicoplanin at high dose and gentamicin was observed, a high-dose regimen of teicoplanin, i.e., 40 mg/kg every 12 h, was also assessed in vivo. This treatment provided marginal activity only when it was combined with gentamicin (-2.3 log10 CFU/g versus controls; P < 0.05). These results suggest that the levels of daptomycin or teicoplanin in serum required to cure experimental endocarditis caused by a highly glycopeptide-resistant strain of E. faecium would not be achievable in humans.

Animals

[Inflammatory polyp: a rare benign endobronchial tumor].

We report a case of inflammatory polyp in a male patient, which was totally obstructing the left main bronchus but could be removed by simple endoscopic traction. The polyp was responsible for an absence of left lung ventilation which in turn produced by reflex an absence of left lung perfusion completely reversible after removal of the polyp. Inflammatory polyp is a rare benign tumour. Its physiopathology is controverted, but it seems to result from local irritation of the bronchial mucosa. Bronchial endoscopy is the essential examination which in most cases make it possible to diagnose and treat the tumour.

Adult

Triple-combination penicillin-vancomycin-gentamicin for experimental endocarditis caused by a moderately penicillin- and highly glycopeptide-resistant isolate of Enterococcus faecium.

An in vitro bacteriostatic synergy between beta-lactam and glycopeptide antibiotics has been recently described against isolates of Enterococcus faecium moderately resistant to penicillin and highly resistant to vancomycin. The relevance of this synergy in a rabbit endocarditis model was evaluated. Penicillin was tested at low- (LoD) and high-dose (HiD) regimens, alone or combined with vancomycin and/or gentamicin. Compared with controls, after a 5-day treatment: LoD penicillin, vancomycin, gentamicin, LoD penicillin plus gentamicin or vancomycin, and vancomycin-gentamicin were not effective; LoD penicillin-vancomycin caused a small reduction of bacterial titers in vegetations that was strongly enhanced by adding gentamicin; HiD penicillin-gentamicin, the most effective regimen, was not significantly better than LoD penicillin-vancomycin-gentamicin. These results suggest that the relative in vivo inefficacy of penicillin-vancomycin might be related to the fact that this combination was poorly bactericidal, and the triple combination of LoD penicillin-vancomycin-gentamicin or the combination of HiD penicillin-gentamicin should be considered in the treatment of serious infections due to beta-lactam- and glycopeptide-resistant enterococci.

Animals

Effects of amoxicillin-clavulanate combination on the motility of the small intestine in human beings.

The amoxicillin-clavulanate combination (Augmentin) frequently induces gastric complaints and diarrhea by an unknown mechanism. The aim of this study was to assess the effects of two orally therapeutic regimens of amoxicillin-clavulanate on small bowel motility in human beings. Duodeno-jejunal manometric recordings were performed in six healthy subjects treated in a cross-over double-blind study with placebo; amoxicillin-clavulanate, 1 g plus 250 mg per os every 12 h for 3 days; or amoxicillin-clavulanate, 1 g plus 250 mg per os every 12 h on day 3 only (1-day regimen). Recordings were all performed on day 3 during a diurnal fasting period, a fed state after a standard dinner, and a nocturnal fasting period. Amoxicillin-clavulanate did not affect the motility of the small intestine during the diurnal fast or the fed state. During the nocturnal fast, amoxicillin-clavulanate significantly increased the motility index of the nonpropagated contractions and tended to increase the duration and the amplitude of the propagated contractions. The same digestive motor effect was already observed on the first day of treatment (1-day regimen). This study demonstrates that the oral administration of a therapeutic regimen of amoxicillin-clavulanate is associated, in most cases, with the occurrence of small intestinal motor disturbances.

Adult

Eucaryotic codes.

This article is a review of the rules used by eucaryotic cells to translate a nuclear messenger RNA into a polypeptide chain. The recent observation that these rules are not identical in two species of a same phylum indicates that they have changed during the course of evolution. Possible scenarios for such changes are presented.

Animals

Ceftriaxone-sulbactam combination in rabbit endocarditis caused by a strain of Klebsiella pneumoniae producing extended-broad-spectrum TEM-3 beta-lactamase.

We studied the activity of the combination of sulbactam and ceftriaxone against a Klebsiella pneumoniae strain producing TEM-3, a new extended-broad-spectrum beta-lactamase, in an endocarditis model. In vitro, ceftriaxone was strongly inactivated in the presence of TEM-3 (MBC, 128 micrograms/ml with an inoculum of 5 x 10(5) CFU/ml). A marked inoculum effect was demonstrated with sulbactam: effective concentrations of inhibitor needed to reduce the MIC and MBC of ceftriaxone to similar levels increased from 1 microgram/ml in the presence of an inoculum of 5 x 10(5) CFU/ml to 20 micrograms/ml in the presence of an inoculum of 1 x 10(7) CFU/ml. In vivo, sulbactam given at 200 mg/kg of body weight every 12 h, a dosage higher than that previously reported to be effective against rabbit endocarditis caused by other microorganisms, was not sufficient to restore the complete activity of ceftriaxone given at 30 mg/kg once daily for 4 days. This insufficient activity may be correlated with the presence of a high level of beta-lactamase inside the vegetations, as indicated by a quantitative in vitro assay of beta-lactamase activity in the cardiac vegetation, suggesting an insufficient inactivation of the extended-broad-spectrum beta-lactamase in vivo.

Animals

Activity of sulbactam in combination with ceftriaxone in vitro and in experimental endocarditis caused by Escherichia coli producing SHV-2-like beta-lactamase.

We studied the efficacy of sulbactam, a beta-lactamase inhibitor, in combination with ceftriaxone in vitro and in experimental endocarditis due to an Escherichia coli strain producing an extended-spectrum beta-lactamase most similar to SHV-2, a new mechanism of resistance to broad-spectrum cephalosporins among members of the family Enterobacteriaceae. In vitro, ceftriaxone demonstrated an important inoculum effect (MICs were 2 and 256 micrograms/ml with 5 X 10(5) and 5 X 10(7) CFU of inoculum per ml, respectively). Sulbactam inhibited the beta-lactamase degradation of ceftriaxone and enhanced the killing by ceftriaxone with both inocula tested. In vivo, sulbactam (100 mg/kg every 8 h) or ceftriaxone (15 or 30 mg/kg every 24 h) alone were ineffective after a 4-day therapy. The addition of sulbactam to ceftriaxone (15 mg/kg) or to the ceftriaxone (15 mg/kg)-netilmicin (6 mg/kg every 24 h) combination produced a reduction of 2 log10 CFU/g of vegetation greater than that produced by therapy without sulbactam. The sulbactam-ceftriaxone (30 mg/kg) combination produced a reduction of almost 5 log10 CFU/g of vegetation greater than that produced by single-drug therapy (P less than 0.01), sterilized five of eight vegetations (versus none of seven for ceftriaxone [30 mg/kg] alone; P less than 0.05), and was as effective as the ceftriaxone (15 mg/kg)-sulbactam-netilmicin combination. We concluded that (i) SHV-2 production was responsible for ceftriaxone failure in vivo, probably because of the high inoculum present in vegetations; (ii) sulbactam used in a regimen which provided levels in serum constantly above 4 micrograms/ml and a vegetation/serum peak ratio of approximately 1:3 enhanced the activity of a broad-spectrum cephalosporin in a severe experimental infection; and (iii) the highest dose of ceftriaxone in combination with sulbactam was as effective as the lowest dose of ceftriaxone plus sulbactam plus an aminoglycoside.

Animals

[Waardenburg's syndrome and severe cyanotic cardiopathy].

Waardenburg syndrome type I is transmitted as an autosomal dominant trait. The main features are dystopia canthorum, partial pigmentary disorder and perceptive deafness. Osteo-articular and intestinal malformations may be observed. In an affected family, the unusual combination of Waardenburg syndrome and severe congenital heart disease has been observed in a child.

Child, Preschool

Ceftriaxone-netilmicin combination in single-daily-dose treatment of experimental Escherichia coli endocarditis.

We evaluated the activities of ceftriaxone (15 mg/kg), netilmicin (6 mg/kg), and their combination given intramuscularly once daily for 4 days for the treatment of experimental Escherichia coli endocarditis in rabbits. In vitro, a greater rate of killing and an increased trough serum bactericidal titer (P less than 0.01) were achieved with the combination. In vivo, the combination had a greater bactericidal effect (P less than 0.01) and resulted in a greater number of sterile vegetations (P less than 0.05) than single-drug therapy. Thus, in vivo, an increased effect can be obtained despite a single daily dose of a long-acting cephalosporin and an aminoglycoside.

Animals

[A fosfomycin-gentamicin combination in the treatment of experimental endocarditis caused by Klebsiella pneumoniae producing type TEM-3 beta-lactamase].

The authors studied the activity of fosfomycin (FOS) and/or gentamicin (GEN) against a Klebsiella pneumoniae strain resistant to all beta-lactams--except cephamycins and imipenem--by production of a plasmid mediated extended broad-spectrum beta-lactamase-TEM-3, to all aminoglycosides--except gentamicin--by production of a plasmid mediated 6' aminoglycoside acetyltransferase IV, to sulfonamides and to tetracyclines. In vitro, the combination FOS (MIC = MBC = 32 mg/l) + GEN (MIC = MBC = 2) appeared indifferent (FIC = 0.75; FBC = 1). In vivo, on experimental endocarditis in rabbits, FOS alone was ineffective, GEN alone was active but only at high dose regimen, FOS - GEN combination was active as compared with controls. Fosfomycin - gentamicin combination may be an alternative in the therapy of severe infections due to multiresistant Enterobacteriacae.

Animals

Telomeric site position heterogeneity in macronuclear DNA of Paramecium primaurelia.

In Paramecium primaurelia, the macronuclear gene encoding the G surface protein is located near a telomere. In this study, multiple copies of this telomere have been isolated and the subtelomeric and telomeric regions of some of them have been sequenced. The telomeric sequences consist of tandem repeats of the hexanucleotides C4A2 or C3A3. We show that the location where these repeats are added, which we call the telomeric site, is variable within a 0.6-0.8-kb region. These results are discussed in relation with the formation of macronuclear DNA.

Animals