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Biomedical subjects

C Delorme

Publications and source records attributed to C Delorme.

At least 19 recordsLinked to original sources
PubMed2005

[Treatment interruption in HIV infected patients: clinical and biological evolution].

OBJECTIVE: The authors had for aim to evaluate the clinical and biological evolution in HIV-infected patients with viraemia lower than 30,000 copies/mL having decided to interrupt their treatment. PATIENTS AND METHODS: Patients with highly active antiretroviral therapy (HAART) for more than 3 months followed by treatment interruption longer than 1 month were included in a retrospective analysis. RESULTS: Forty-six patients having stopped treatment between November 1999 and July 2003 were included. The median duration of treatment interruption was 9.5 months. During the study, no clinical event occurred for 21 patients, and at least 1 clinical event occurred for the 25 others. The median CD4(+) cell counts (CD4) before and at the end of treatment interruption were 597/mm(3) and 437/mm(3), respectively (P<0.001). The median values of viral load before and at the end of treatment interruption were <50 and 23749 copies/mL, respectively (P<0.001). Among the 26 patients having started a new HAART, pre-treatment interruption and post-new HAART median CD4 (with a median delay after HAART of 9.7 months) were 548 and 432.5/mm(3) (P=0.02). Pre-treatment interruption and post-new HAART median viral load were 131.5 and 94.5 copies/mL (NS). CONCLUSIONS: Treatment interruption must be used with caution in spite of the absence of virological impact, because CD4 cell count after new HAART is lower than CD4 preceding treatment interruption. Treatment interruption is contraindicated for patients with AIDS. Physicians must carefully follow other patients who decide on a treatment interruption.

Adult↗
PubMed2002

Food-grade delivery system for controlled gene expression in Lactococcus lactis.

A food-grade system for the delivery of desired genes to Lactococcus lactis, their inducible expression, and their transfer to related strains was established. Based on the thermosensitive pG(+)host replicon, two types of plasmid vectors were constructed which contained sections of either the chromosomal leu operon of L. lactis or the tel operon from the lactococcal sex factor. Genes cloned into the leu or tel sequences of these vectors were delivered to the homologous regions of the chromosome or the sex factor through two single crossovers, leading to integration of the recombinant plasmids and subsequent excision of the vector portions. Inducible transcription of integrated genes was achieved by using the nisin-controlled expression (NICE) system. To establish the signal transduction genes nisRK in L. lactis, the vectors pLNG1363 (targeted to the chromosome) and pUK500 (targeted to the sex factor) were constructed. Fusions of six different peptidase genes (pep) from Lactobacillus delbrueckii with the nisin-inducible promoter P(nisA) were delivered to the sex factor with derivatives of the vector pUK300. Food-grade recombinants of L. lactis were constructed which had the nisRK genes and individual P(nisA)::pep fusions integrated either separately into the chromosome and the sex factor or simultaneously into the sex factor. With both types of recombinants, expression of P(nisA)::pep fusions after induction with nisin was demonstrated. Depending on the loci used for integration of nisRK, variable induction rates were observed. Furthermore, an engineered sex factor carrying a P(nisA)::pepI fusion was transfered by conjugation between two strains of L. lactis at a frequency of 4 x 10(-4).

Bacterial Proteins↗
PubMed2001

Pleiotropic transcriptional repressor CodY senses the intracellular pool of branched-chain amino acids in Lactococcus lactis.

Proteolysis is essential for supplying Lactococcus lactis with amino acids during growth in milk. Expression of the major components of the L. lactis proteolytic system, including the cell wall proteinase (PrtP), the oligopeptide transport system (Opp) and at least four intracellular peptidases (PepO1, PepN, PepC, PepDA2), was shown previously to be controlled negatively by a rich nitrogen source. The transcription of prtP, opp-pepO1, pepN and pepC genes is regulated by dipeptides in the medium. Random insertion mutants derepressed for nitrogen control in the expression of the oligopeptide transport system were isolated using an opp-lacZ fusion. A third of the mutants were targeted in the same locus. The product of the inactivated gene shared 48% identity with CodY from Bacillus subtilis, a pleiotropic repressor of the dipeptide permease operon (dpp) and several genes including genes involved in amino acid degradation and competence induction. The signal controlling CodY-dependent repression was searched for by analysing the response of the opp-lux fusion to the addition of 67 dipeptides with different amino acid compositions. Full correlation was found between the dipeptide content in branched-chain amino acids (BCAA; isoleucine, leucine or valine) and their ability to mediate the repression of opp-pepO1 expression. The repressive effect resulting from specific regulatory dipeptides was abolished in L. lactis mutants affected in terms of their transport or degradation into amino acids, showing that the signal was dependent on the BCAA pool in the cell. Lastly, the repression of opp-pepO1 expression was stronger in a mutant unable to degrade BCAAs, underlining the central role of BCAAs as a signal for CodY activity. This pattern of regulation suggests that, in L. lactis and possibly other Gram-positive bacteria, CodY is a pleiotropic repressor sensing nutritional supply as a function of the BCAA pool in the cell.

ATP-Binding Cassette Transporters↗
PubMed2001

Transcriptional pattern of genes coding for the proteolytic system of Lactococcus lactis and evidence for coordinated regulation of key enzymes by peptide supply.

The transcription of 16 genes encoding 12 peptidases (pepC, pepN, pepX, pepP, pepA, pepF2, pepDA1, pepDA2, pepQ, pepT, pepM, and pepO1), P(I) and P(III) proteinases (prtP1 and prtP3), and three transport systems (dtpT, dtpP, and opp-pepO1) of Lactococcus lactis MG1363 was analyzed in response to different environmental factors. Promoter fusions with luciferase reporter genes and/or mRNA analysis were used to study the effects of sugar sources, growth at 37 degrees C, and peptide supply on the transcription of these genes. Only transcription of the pepP gene is modulated by the source of sugar. The presence of potential catabolite-responsive element (CRE) boxes in its promoter region suggests that expression of this gene is directly controlled by catabolic repression. Elevated temperature had no significant effect on the level of transcription of these genes. prtP1, prtP3, pepC, pepN, pepX, and the opp-pepO1 operon are the most highly expressed genes in chemically defined medium, and their expression is repressed 5- to 150-fold by addition of peptide sources such as Casitone in the medium. Moreover, the transcription of prtP1, prtP3, pepC, pepN, and the opp-pepO1 operon is repressed two- to eight-fold by the dipeptides leucylproline and prolylleucine. The transcription of pepDA2 might also be repressed by the peptide sources, but this effect is not observed on the regulation of dtpT, pepP, pepA, pepF2, pepDA1, pepQ, pepT, pepM, and the dtpP operon. The significance of these results with respect to the functions of different components of the proteolytic system in L. lactis are discussed.

Artificial Gene Fusion↗
PubMed2001

Glycosphingolipid binding specificities of rotavirus: identification of a sialic acid-binding epitope.

The glycosphingolipid binding specificities of neuraminidase-sensitive (simian SA11 and bovine NCDV) and neuraminidase-insensitive (bovine UK) rotavirus strains were investigated using the thin-layer chromatogram binding assay. Both triple-layered and double-layered viral particles of SA11, NCDV, and UK bound to nonacid glycosphingolipids, including gangliotetraosylceramide (GA1; also called asialo-GM1) and gangliotriaosylceramide (GA2; also called asialo-GM2). Binding to gangliosides was observed with triple-layered particles but not with double-layered particles. The neuraminidase-sensitive and neuraminidase-insensitive rotavirus strains showed distinct ganglioside binding specificities. All three strains bound to sialylneolactotetraosylceramide and GM2 and GD1a gangliosides. However, NeuAc-GM3 and the GM1 ganglioside were recognized by rotavirus strain UK but not by strains SA11 and NCDV. Conversely, NeuGc-GM3 was bound by rotaviruses SA11 and NCDV but not by rotavirus UK. Thus, neuraminidase-sensitive strains bind to external sialic acid residues in gangliosides, while neuraminidase-insensitive strains recognize gangliosides with internal sialic acids, which are resistant to neuraminidase treatment. By testing a panel of gangliosides with triple-layered particles of SA11 and NCDV, the terminal sequence sialyl-galactose (NeuGc/NeuAcalpha3-Galbeta) was identified as the minimal structural element required for the binding of these strains. The binding of triple-layered particles of SA11 and NCDV to NeuGc-GM3, but not to NeuAc-GM3, suggested that the sequence NeuGcalpha3Galbeta is preferred to NeuAcalpha3Galbeta. Further dissection of this binding epitope showed that the carboxyl group and glycerol side chain of sialic acid played an important role in the binding of such triple-layered particles.

Animals↗
PubMed2000

[HIV risk behavior in prison and factors associated with reincarceration of injection drug users].

OBJECTIVES: The aim of this study was to estimate the frequency of risk behavior for HIV transmission in prison and to identify the factors associated with reincarceration. PATIENTS AND METHODS: An epidemiologic study was carried out in the penitentiary center of Marseilles between December 1995 and March 1997. Five hundred and seventy-four prisoners answered an anonymous voluntary questionnaire managed by independent interviewers. RESULTS: Among the 574 prisoners, 133 (23%) reported they had injected drugs (intravenous drug users, IDU) including 71 (53%) who had injected drugs during the three months preceding incarceration. Seven percent of the IDU received opiate substitutes before their imprisonment. Nine prisoners of the 120 who have responded to the question (7.5%: 3.7-14.2 95% CI) stated they had injected drugs during the first three months of incarceration. Multivariate analysis showed that reincarceration was significantly more frequent among men, HIV-infected and unemployed prisoners, and prisoners not receiving opiate substitutes at the time of their imprisonment. DISCUSSION: This study show that risk behaviors of HIV and hepatitis virus transmission are frequent among intravenous drug users, including during their incarceration. The relationship between opiate substitution treatment and reincarceration deserves to be studied further on larger samples in order to better evaluate its impact on social rehabilitation of drug addicts. This data also underline the need to strengthen prevention programs in prisons and the importance of social and health policies targeted on drug users especially opiate substitution programs.

Adult↗
PubMed2000

Association between high von willebrand factor levels and the Thr789Ala vWF gene polymorphism but not with nephropathy in type I diabetes. The GENEDIAB Study Group and the DESIR Study Group.

BACKGROUND: A genetic susceptibility for diabetic kidney disease is suspected since diabetic nephropathy occurs in only 30 to 40% of type I diabetic patients. As elevated von Willebrand factor (vWF) plasma concentrations have been reported to precede the development of microalbuminuria in type I diabetes, we addressed a possible implication of vWF as a genetic determinant for diabetic nephropathy. METHODS: Three known vWF gene polymorphisms were genotyped in a group of 493 type I diabetic subjects, all showing proliferative retinopathy, but with various stages of renal involvement, which ranged from no microalbuminuria, despite a mean duration of diabetes of 31 years, to advanced nephropathy (GENEDIAB Study): Thr789Ala (Rsa I), M-/M+ (Msp I) (intron 19), and Ala1381Thr (Hph I). Plasma vWF and factor VIII (F VIII) levels were also measured in this population. RESULTS: Plasma vWF and F VIII levels were increased in diabetic subjects with nephropathy (P < 0.001) or with coronary heart disease (CHD; P < 0.001), but there was no interaction of both conditions on plasma levels. The Msp I polymorphism (M-/M+) was weakly associated with nephropathy (P = 0. 04), but this association was not more significant when other risk factors were used in a logistic regression analysis. The vWF Thr789Ala polymorphism was associated with CHD (P = 0.002) and with plasma vWF levels. Logistic regression analysis indicated an independent and codominant effect of the Thr789Ala polymorphism on CHD, but not on nephropathy, with a maximal risk for Ala/Ala homozygotes (OR = 4.2, 95% CI, 1.8 to 9.9, P = 0.0008). CONCLUSION: It is unlikely that polymorphisms in the vWF gene contribute to the risk for nephropathy in type I diabetic patients. However, the Thr789Ala polymorphism might affect the risk for CHD in this population through modulation of plasma vWF levels.

Adolescent↗
PubMed1999

An aminoacyl-tRNA synthetase paralog with a catalytic role in histidine biosynthesis.

In addition to their essential catalytic role in protein biosynthesis, aminoacyl-tRNA synthetases participate in numerous other functions, including regulation of gene expression and amino acid biosynthesis via transamidation pathways. Herein, we describe a class of aminoacyl-tRNA synthetase-like (HisZ) proteins based on the catalytic core of the contemporary class II histidyl-tRNA synthetase whose members lack aminoacylation activity but are instead essential components of the first enzyme in histidine biosynthesis ATP phosphoribosyltransferase (HisG). Prediction of the function of HisZ in Lactococcus lactis was assisted by comparative genomics, a technique that revealed a link between the presence or the absence of HisZ and a systematic variation in the length of the HisG polypeptide. HisZ is required for histidine prototrophy, and three other lines of evidence support the direct involvement of HisZ in the transferase function. (i) Genetic experiments demonstrate that complementation of an in-frame deletion of HisG from Escherichia coli (which does not possess HisZ) requires both HisG and HisZ from L. lactis. (ii) Coelution of HisG and HisZ during affinity chromatography provides evidence of direct physical interaction. (iii) Both HisG and HisZ are required for catalysis of the ATP phosphoribosyltransferase reaction. This observation of a common protein domain linking amino acid biosynthesis and protein synthesis implies an early connection between the biosynthesis of amino acids and proteins.

ATP Phosphoribosyltransferase↗
PubMed1999

Reducing chorioretinal viral counts with intravitreal foscarnet injections in a rabbit model of Herpes simplex virus type-1 retinitis.

The efficacy of intravitreal foscarnet injections was evaluated in a rabbit model of Herpes simplex virus type-1 (HSV-1) retinitis. In untreated infected animals, viral titration revealed that the optic chiasm, vitreous and chorioretina were positive for HSV-1. On the other hand, foscarnet treatment significantly decreased the viral count in the chorioretina when compared to the untreated group. Immunolocalization of HSV in untreated infected animals clearly showed infected cells in the outer and inner layers of the retina and also in the ciliary body of the eye. Clinical examination by indirect ophthalmoscopy indicated an absence of optic nerve congestion and a lower level of vitritis in foscarnet treated animals compared to the untreated group. It is concluded that intravitreal injections of foscarnet reduced the viral titer in the chorioretina in a rabbit model of HSV-1 retinitis. This route of administration might be valuable for the treatment of CMV retinitis in AIDS patients with sight threatening lesions or intolerance to intravenous anti-CMV drugs.

Administration, Topical↗
PubMed1999

Regulation of expression of the Lactococcus lactis histidine operon.

In Lactococcus lactis, the his operon contains all the genes necessary for histidine biosynthesis. It is transcribed from a unique promoter, localized 300 bp upstream of the first gene. The region corresponding to the untranslated 5' end of the transcript, named the his leader region, displays the typical features of the T box transcriptional attenuation mechanism which is involved in the regulation of many amino acid biosynthetic operons and tRNA synthetase genes in gram-positive bacteria. Here we describe the regulation of transcription of the his operon by the level of histidine in the growth medium. In the absence of histidine, two transcripts are present. One covers the entire operon, while the other stops at a terminator situated about 250 bp downstream of the transcription start point. DNA sequences implicated in regulation of the his operon were identified by transcriptional fusion with luciferase genes and site-directed mutagenesis. In addition to the previously defined sequences necessary for effective T-box-mediated regulation, new essential regions were identified. Eighteen percent of the positions of the his leader region were found to differ in seven distantly related strains of L. lactis. Analysis of the variable positions supports the folding model of the central part of the his leader region. Lastly, in addition to the T-box-mediated regulation, the operon is regulated at the level of initiation of transcription, which is repressed in the presence of histidine. An operator site, necessary for full repression, overlaps the terminator involved in the T box attenuation mechanism. The functionality of the operator is altered on plasmids with low and high copy numbers, suggesting that supercoiling may play a role in the expression of the his operon. The extents of regulation at the levels of initiation and attenuation of transcription are 6- to 8-fold and 14-fold, respectively. Together, the two levels of control allow a 120-fold range of regulation of the L. lactis operon by histidine.

5' Untranslated Regions↗
PubMed1999

[Knowledge, beliefs and attitudes of inmates towards AIDS and HIV infection: a survey in a Marseille penitentiary center].

BACKGROUND: The objectives of our study were to evaluate knowledge, attitudes and beliefs of inmates toward HIV infection, and to compare them with those reported in the general population and according to injecting drug use. METHODS: Three hundred and seventy persons incarcerated in the prison of Marseille were invited, between December 1995 and March 1997, to answer a voluntary questionnaire offered by an independent staff. Odds ratios were estimated by logistic regression models adjusting for age, sex and type of questionnaire (self-administered for literate, face-to-face for illiterate inmates). The average scores among injecting and non injecting drug users (IDUs) were compared by analysis of variance adjusting for age, sex and type of questionnaire. These scores were also compared with those reported in a national survey (ACSF 1994), after adjustment for age, sex and educational level. RESULTS: The participation rate was 55%. Among the 202 participants, 152 answered a self-administered and 50 a face-to-face questionnaire; 45/202 (22%) were IDUs. The average scores of knowledge and tolerance towards HIV infected people were lower among inmates than in the general population. Furthermore, the scores of uncertainty towards HIV risk and unfavorable opinions about condom were higher than in the general population. While the average scores of knowledge, uncertainty towards HIV risk and unfavorable opinions did not differ between IDUs and non-IDUs, the score of tolerance towards HIV infected people was lower among non-IDUs than IDUs. CONCLUSION: That study shows that in spite of the high prevalence of at risk behaviors among people who are incarcerated, that population is not targeted enough by HIV prevention programs. Furthermore, the low level of tolerance towards HIV infected people among inmates, especially non-IDUs, is very likely an obstacle to health care management in that population with a high HIV prevalence. It is urgent to enhance the equality of access to care and prevention policy inside and outside prison.

Adult↗
PubMed1998

18-Vinyldeoxycorticosterone: a potent inhibitor of the bovine cytochrome P-450(11) beta.

18-Vinylprogesterone (18-VP) and 18-ethynylprogesterone (18-EP) have proved to be potent suicide inhibitors of P-450(11) beta, the last enzyme of aldosterone biosynthesis (Delorme, C.; Piffeteau, A.; Viger, A.; Marquet, A. Eur. J. Biochem. 1995, 232, 247; Delorme, C.; Piffeteau, A.; Sobrio, F.; Marquet, A. Eur. J. Biochem. 1997, 248, 252). This paper describes the synthesis of 18-vinyldeoxycorticosterone (18-VDOC), an analogue of deoxycorticosterone (DOC), the physiological substrate of the enzyme, and the evaluation of its reversible inhibiting properties for deoxycorticosterone and corticosterone oxidation by the bovine enzyme. 18-VDOC has been obtained by hydroxylation at C-21 of a 18-VP precursor. Its reversible Ki values are, respectively, 0.3 microM for the 11 beta-hydroxylation and 0.8 microM for the 18-hydroxylation. Hence, 18-VDOC is the strongest competitive inhibitor of bovine P-450(11) beta described so far, but in contrast with 18-VP, it does not inhibit more efficiently the 18-hydroxylation than the 11-hydroxylation.

Animals↗
PubMed1998

Use of luciferase genes as biosensors to study bacterial physiology in the digestive tract.

A method based on the use of the bacterial luciferase genes was developed in order to investigate Lactococcus lactis gene expression in the mouse digestive tract. Germfree mice were monoassociated with different strains containing transcriptional fusions of promoters with the luciferase genes. Our results demonstrate that this method is readily applicable to the study of promoter strength and physiology of bacteria in the digestive tract.

Animals↗
PubMed1998

Screening for diabetic retinopathy. Do family physicians know the Canadian guidelines?

OBJECTIVE: To assess whether family physicians and family medicine residents know what the Canadian guidelines for screening for diabetic retinopathy are, and to assess whether they believe they can perform this screening. DESIGN: Mailed survey with two mailed reminders. PARTICIPANTS: All general practitioners (N = 1038) listed in two health catchment areas, Québec and Chaudière-Appalaches administrative regions in the province of Québec, and all family medicine residents (N = 125) at Laval University Medical School. Response rate was 62% among general practitioners and 77% among residents. MAIN OUTCOME MEASURES: Knowledge of screening guidelines for diabetic retinopathy in type I and type II diabetes, including timing of the initial screening examination, risk factors, natural history, and treatment of ocular complications; and perception of ability to screen for diabetic retinopathy. RESULTS: Among GPs, 80% of respondents correctly chose the statement with the current guideline for first screening for diabetic retinopathy to be performed shortly after diagnosis of type II diabetes. Only 13% of respondents were familiar with the guideline for first screening 5 years after diagnosis of type I diabetes. Agreement with other correct guideline statements was also low. Overall, residents had higher scores than GPs. Most respondents were not confident in the accuracy of their eye examinations. CONCLUSIONS: General practitioners and family medicine residents have varying levels of knowledge about the Canadian guidelines for screening for diabetic retinopathy. These results will be useful in designing and improving educational programs for GPs in diabetic retinopathy screening.

Adult↗
PubMed1997

Mechanism-based inactivation of bovine cytochrome P-450(11beta) by 18-unsaturated progesterone derivatives.

Two 18-unsaturated progesterone derivatives, 18-vinylprogesterone (18-VP) and 18-ethynylprogesterone (18-EP) have proved to be potent inhibitors of the bovine cytochrome P-450(11beta), the enzyme involved in the last steps of aldosterone biosynthesis [Delorme, C., Piffeteau, A., Viger, A. & Marquet, A. (1995) Eur. J. Biochem. 232, 247-256]. In the present study, we demonstrate that these two compounds exhibit the characteristics of mechanism-based inactivators of this enzyme. Inactivation followed pseudo-first-order and saturation kinetics. The kinetic parameters of inactivation were k(i) = 0.11 min(-1) and Ki = 4 microM for 18-VP, and k(i) = 0.12 min(-1) and 22 microM for 18-EP. Inactivation of P-450(11beta) activity was strictly dependent on the presence of NADPH. Protection by the substrate deoxycorticosterone was observed, demonstrating a selective modification at the substrate-binding site. With radiolabeled 18-VP, inactivation was shown to be irreversible with a stoichiometry of 1.4 mol bound [3H]18-VP/mol inactivated cytochrome P-450(11beta). SDS/PAGE analysis of the [3H]18-VP-inactivated enzyme showed that, under conditions preventing heme dissociation, the P-450(11beta) band was labeled, while no labeling of the apoprotein was observed under denaturating conditions. Furthermore, the loss of catalytic activity could be correlated with the destruction of the P-450 chromophore evaluated by the FeII-CO versus FeII difference spectra. These arguments led us to propose that 18-vinylprogesterone inactivates cytochrome P-450(11beta) by heme destruction rather than by protein modification.

Animals↗
PubMed1996

Plasmid vectors for gram-positive bacteria switching from high to low copy number.

A set of vectors for Gram-positive bacteria was constructed with a new feature which enables the switching down of their copy number per cell. These vectors carry the replication region of pAM beta 1, containing a gene essential for replication, repE, and its regulator, copF. The latter gene was inactivated by inserting a linker into its unique KpnI site. Since copF downregulates the expression of repE, its inactivation leads to an increase in the plasmid copy number per cell. The original low copy state can be restored by removal of the linker via KpnI cleavage and ligation. The new replicon was used to build (i) vectors for studying gene regulation by transcriptional or translational fusion with the bacterial luciferase gene, (ii) vectors for gene expression, and (iii) cassettes of the replicon with different multiple cloning sites, which would facilitate construction of vectors for novel purposes.

Amino Acid Sequence↗