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C Delorme

Publications and source records attributed to C Delorme.

At least 37 records · Page 2Linked to original sources
PubMed1996

Specific inhibition of the last steps of aldosterone biosynthesis by 18-vinylprogesterone in bovine adrenocortical cells.

18-Vinylprogesterone (18-VP), designed for mechanism-based specific inhibition of the last steps of the aldosterone biosynthesis, was used to characterize the mechanism of the 11 - and 18-hydroxylase activities of bovine cytochrome P450(11beta). In the present work, its action was studied by observations on a primary culture of bovine adrenocortical cells. First, we investigated the effects of 18-VP on the different enzymatic steps of the biosynthesis of cortisol and aldosterone. The production of cortisol, baseline or hormone-stimulated (ACTH or AII), was inhibited by 18-VP in a dose-dependent manner with a maximal inhibition at 5 microM. Supply of different exogenous substrates to support steroidogenesis revealed an inhibition of the last step of cortisol or corticosterone biosynthesis. We then used specific blockers to measure individual activities and conclude that 11beta-hydroxylation was the only enzymatic activity affected. Aldosterone, as well as 18-hydroxycorticosterone, was also measured following addition of corticosterone. The 18-hydroxylation of corticosterone was inhibited by 18-VP, with 50% inhibition occurring at 0.04 microM compared with the 50% inhibition value of 0.3 microM obtained for 11-hydroxylation. Surprisingly, 18-ethynyl-progesterone (18-EP), which has a structure very similar to 18-VP, only weakly inhibits 11beta-hydroxylation. The inhibition of aldosterone formation was also much lower with 18-EP than with 18-VP. These studies demonstrate that 18-VP inhibits only the later steps of aldosterone biosynthesis and more specifically 18- than 11-hydroxylation activity.

Adrenal Cortex↗
PubMed1995

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

The last step of aldosterone biosynthesis, an 11 beta-hydroxylation followed by two 18-hydroxylations, are catalyzed, in the bovine system, by the same enzyme, the cytochrome P-450(11 beta) (deoxycorticosterone (DOC)-->corticosterone-->18-hydroxycorticosterone-->aldosterone). The 11 beta- and 18-hydroxylase activities were studied separately with a reconstituted enzymic system, using 11-deoxy[14C]corticosterone and [3H]corticosterone, respectively, as substrates. The inhibition of 11 beta-hydroxylase activity by corticosterone was competitive (Ki = 60 microM) showing that transformation of both substrates occurs at the same site. Double-label/double-substrate experiments, using an equimolar mixture of 11-deoxy[14C]corticosterone and [3H]corticosterone, suggested that 18-hydroxycorticosterone is directly formed from 11-deoxycorticosterone without the intermediate corticosterone leaving the enzyme. Inhibitions by 18-vinylprogesterone and 18-ethynylprogesterone, potent inhibitors of aldosterone biosynthesis [Viger, A., Coustal, S., Pérard, S., Piffeteau, A. & Marquet, A. (1989) J. Steroid Biochem. 33, 119-124], were characterized for both activities (11 beta- and 18-hydroxylase). The value of reversible Ki for the 18-hydroxylation (Ki = 5 microM for 18-vinylprogesterone and 30 microM for 18-ethynylprogesterone) is lower than that for the 11 beta-hydroxylation (30 microM and 100-150 microM, respectively); the former inhibitor is stronger than the latter for both steps. The binding of substrates and inhibitors to the active site was also examined by difference absorption spectroscopy. 18-Vinylprogesterone gave rise to a type I spectrum with a Ks value of 35 microM close to that of progesterone, while 18-ethynylprogesterone showed a reverse type I spectrum with a much higher Ks value (140 microM). Based on these results, a hypothetical model, involving a conformational change of the enzyme for the second step, is proposed.

Animals↗
PubMed1995

Metabolic operons in Lactococci.

The genes for the biosynthesis of histidine, tryptophan and branched-chain amino acids (ilv for isoleucine, leucine and valine) are clustered in large operons. In addition to genes encoding the pathway enzymes, the his and the ilv operons contain 4 and 3 other genes, respectively. The functions of two of these, orf3 and aldB are regulatory. The second gene of the his operon, orf3, encodes a protein homologous to the histidyl-tRNA synthetases. It is involved in transcription attenuation upstream of the his operon. This regulation is related to a new class of attenuation mechanisms controlling the expression of most tRNA synthetase genes and a few metabolic operons in Gram-positive bacteria. Gene aldB, the penultimate gene of the ilv operon, encodes acetolactate decarboxylase. This enzyme transforms acetolactate (AL), the first intermediate of leucine and valine biosynthesis, into acetoin. AL decarboxylase is positively controlled by the availability of leucine and possibly valine in the cell. This is the key enzyme for a new class of regulatory mechanisms, a metabolic shunt which guides the AL flux towards synthesis of amino acids or a secondary metabolite.

Amino Acid Sequence↗
PubMed1994

Mosaic structure of large regions of the Lactococcus lactis subsp. cremoris chromosome.

Lactococcus lactis subsp. lactis and Lactococcus lactis subsp. cremoris are closely related phenotypically and genetically. Here we report that certain regions of their chromosomes diverge considerably more than others. Conserved regions differ by less than 20%, whilst variable regions differ by more than 60%. This mosaic structure may have arisen by horizontal gene transfer from distantly related bacteria since in a particular region of the L. lactis subsp. cremoris chromosome the G+C content and the codon bias are not typical for lactococci. Such an exchange, which conserves the function of the gene and cannot be achieved under selective pressure, may be of considerable importance in the evolution of bacteria.

Amino Acid Sequence↗
PubMed1993

Conjugal transfer of the determinants for bacteriocin (lacticin 481) production and immunity in Lactococcus lactis subsp. lactis CNRZ 481.

The lacticin 481-producer (Lct+), L. lactis subsp. lactis (L. lactis) CNRZ 481 harbours 5 plasmids of 6.5, 7.5, 20, 37 and 69 kb. Novobiocin treatment of L. lactis 481 led to the appearance of lacticin 481 deficient variants which had all lost the 69 kb plasmid. Conjugal transfer of the lacticin 481 structural gene (lct) into the plasmid free strain L. lactis IL1441 yielded Lct+ transconjugants at a 10(-4) frequency, which carried a plasmid with an apparent size of 120-130 kb. Southern hybridization analyses showed that the lct gene was located on the 69 kb plasmid in L. lactis 481 and on the 120-130 kb plasmid in the transconjugants. The lct gene was in higher copy number in transconjugants than in the parental strain resulting in two-fold higher lacticin 481 production in the former strain.

Anti-Bacterial Agents↗
PubMed1993

Gene inactivation in Lactococcus lactis: branched-chain amino acid biosynthesis.

The Lactococcus lactis subsp. lactis strains isolated from dairy products are auxotrophs for branched-chain amino acids (leucine, isoleucine, and valine), while most strains isolated from nondairy media are prototrophs. We have cloned and sequenced the leu genes from one auxotroph, IL1403. The sequence is 99% homologous to that of the prototroph NCDO2118, which was determined previously. Two nonsense mutations and two small deletions were found in the auxotroph sequence, which might explain the branched-chain amino acid auxotrophy. Nevertheless, the leu genes from the auxotroph appear to be transcribed and regulated similarly to those from the prototroph.

Amino Acid Sequence↗
PubMed1993

Gene inactivation in Lactococcus lactis: histidine biosynthesis.

Lactococcus lactis strains from dairy and nondairy sources were tested for the ability to grow in the absence of histidine. Among 60 dairy strains tested, 56 required histidine, whereas only 1 of 11 nondairy strains had this requirement. Moreover, 10 of the 56 auxotrophic strains were able to grow in the presence of histidinol (Hol+), the immediate histidine precursor. This indicates that adaptation to milk often results in histidine auxotrophy. The histidine operon was detected by Southern hybridization in eight dairy auxotrophic strains tested. A large part of the histidine operon (8 kb, containing seven histidine biosynthetic genes and three unrelated open reading frames [ORFs]) was cloned from an auxotroph, which had an inactive hisD gene, as judged by its inability to grow on histidinol. Complementation analysis of three genes, hisA, hisB, and hisG, in Escherichia coli showed that they also were inactive. Sequence analysis of the cloned histidine region, which revealed 98.6% overall homology with that of the previously analyzed prototrophic strain, showed the presence of frameshift mutations in three his genes, hisC, hisG, and hisH, and two genes unrelated to histidine biosynthesis, ORF3 and ORF6. In addition, several mutations were detected in the promoter region of the operon. Northern (RNA) hybridization analysis showed a much lower amount of the his transcript in the auxotrophic strain than in the prototrophic strain. The mutations detected account for the histidine auxotrophy of the analyzed strain. Certain other dairy auxotrophic strains carry a lower number of mutations, since they were able to revert either to a Hol+ phenotype or to histidine prototrophy.

Amino Acid Sequence↗
PubMed1992

Divergence of Genomic Sequences between Lactococcus lactis subsp. lactis and Lactococcus lactis subsp. cremoris.

Relatedness between Lactococcus lactis subsp. cremoris and L. lactis subsp. lactis was assessed by Southern hybridization analysis, with cloned chromosomal genes as probes. The results indicate that strains of the two subspecies form two distinct groups and that the DNA sequence divergence between L. lactis subsp. lactis and L. lactis subsp. cremoris is estimated to be between 20 and 30%. The previously used phenotypic criteria do not fully discriminate between the groups; therefore, we propose a new classification which is based on DNA homology. In agreement with this revised classification, the L. lactis subsp. lactis and L. lactis subsp. cremoris strains from our collection have distinct phage sensitivities.

Journal Article↗
PubMed1992

Histidine biosynthesis genes in Lactococcus lactis subsp. lactis.

The genes of Lactococcus lactis subsp. lactis involved in histidine biosynthesis were cloned and characterized by complementation of Escherichia coli and Bacillus subtilis mutants and DNA sequencing. Complementation of E. coli hisA, hisB, hisC, hisD, hisF, hisG, and hisIE genes and the B. subtilis hisH gene (the E. coli hisC equivalent) allowed localization of the corresponding lactococcal genes. Nucleotide sequence analysis of the 11.5-kb lactococcal region revealed 14 open reading frames (ORFs), 12 of which might form an operon. The putative operon includes eight ORFs which encode proteins homologous to enzymes involved in histidine biosynthesis. The operon also contains (i) an ORF encoding a protein homologous to the histidyl-tRNA synthetases but lacking a motif implicated in synthetase activity, which suggests that it has a role different from tRNA aminoacylation, and (ii) an ORF encoding a protein that is homologous to the 3'-aminoglycoside phosphotransferases but does not confer antibiotic resistance. The remaining ORFs specify products which have no homology with proteins in the EMBL and GenBank data bases.

Amino Acid Sequence↗
PubMed1989

Are click-evoked BAEPs useful in case of neonate hyperbilirubinemia?

There is still controversy about the usefulness of click-evoked brainstem auditory evoked potentials (BAEPs) for the investigation of neonatal hyperbilirubinemia. The present work concerns the study of click-evoked BAEP responses in a population of 72 hyperbilirubinemic children (conceptional age between 33 and 42 weeks). Their bilirubinemia rates were between 219 and 600 mumol/l. The waves I, III and V were always present, and click BAEP thresholds were normal in all subjects. Latency anomalies were found only for 8 of the 72 subjects. The comparison of subjects having the higher (greater than 307 mumol/l) bilirubin levels with the group having the lower ones failed to show any significant differences for the I-III and I-V intervals. The influence of prematurity in BAEP alteration has not been demonstrated in this study. These data show, on the one hand, normal click-BAEP thresholds but, on the other hand, alterations of central conduction time in some hyperbilirubinemic newborns. It seems that other factors than hyperbilirubinemia might be operating.

Acoustic Stimulation↗
PubMed1988

Effect of stimulus intensity variation on brainstem auditory evoked potentials. Maturational changes.

The effect of stimulus intensity variation on brainstem auditory evoked potentials in premature and full-term neonates has been studied in two experiments. They show that the effects are different according to age and to waves. The variation of latencies is greater the younger the child and it is clearer with wave I than waves III and V. The findings are discussed in terms of the maturation of the basal part of the cochlea.

Acoustic Stimulation↗
PubMed1987

Effect of stimulus intensity variation on brain-stem auditory evoked potentials: comparison between neonates and adults.

Brain auditory evoked potentials (BAEPs) were recorded from 40 adult subjects and 40 neonates at 80 and 60 dB (nHL) to compare the effects of stimulus intensity variation on waves I, III and V and on intervals I-III, III-V and I-V. The results show that the changes in latency for wave, I, I-III and I-V intervals are significantly greater in neonates than in adults. So the effects of stimulus intensity variation on BAEPs are different in neonates and in adults and a major effect is in the peripheral auditory mechanism.

Acoustic Stimulation↗
PubMed1987

Brainstem auditory evoked responses alteration in twin neonates.

The authors obtained BAER recordings for 20 premature twins and 20 premature non-twins. The two groups were comparable as to conceptional age (36-37 weeks), gestational age, chronological age, birthweight, sex ratio and head size. The results showed a prolongation of the central conduction time (I-V interval) in the premature twins. This may be due to the intra-uterine growth retardation of twins.

Birth Weight↗
PubMed1987

Occupation and pregnancy outcome.

Over a two year period, 1982-4, 56067 women, delivered or treated for a spontaneous abortion in 11 Montreal hospitals covering 90% of such admissions, were interviewed in detail regarding their occupational, social, and personal characteristics in their most recent and past pregnancies--104,649 in all. These data were analysed in relation to four main adverse outcomes--spontaneous abortion, stillbirth (without defect), congenital defect, and low birth weight (less than or equal to 2500 g). For comparison with observed numbers, expected figures were calculated by logistic regression using up to eight potentially confounding variables. Sixty occupational groups in six main industrial sectors were examined in current and previous pregnancies, with tests for heterogeneity between these two estimates of risk. Women in managerial, health, and clerical sectors had little evidence of excess of any of the four outcomes, by contrast with those in sales, service, and manufacturing sectors. Substantial and statistically significant excesses of spontaneous abortion were observed in nursing aides, women in sales occupations and food and beverage service; of stillbirth in agriculture and horticulture, leatherwork, and certain sales occupations; of congenital defects in women in child care, certain service occupations, and the manufacture of metal and electrical goods; and of low birth weight in chambermaids, cleaners, and janitors, and in women employed in the manufacture of food and drink, metal and electrical goods, and clothing.

Abortion, Spontaneous↗
PubMed1987

[Cerebral aspergillosis. Apropos of 4 cases].

Four patients with aspergillosis of the central nervous system collected in less than two years are reported. Three patients had hematologic malignancies (acute myelogenous leukemia, Hodgkin's disease) and were treated with corticosteroids and chemotherapy. One patient received antimicrobial agents fort a post operative meningitis (after acoustic neuroma surgery). Analysis of these cases and review of literature available us to point out the increased frequency of invasive and cerebral aspergillosis particularly in immunocompromised hosts treated by cytotoxic drugs or broad spectrum antibiotic therapy. Diagnosis is very difficult because: --there are non specific radiologic features for aspergillus granuloma, abscess, aneurysm or meningitis, --blood and cerebrospinal fluid cultures are invariably negative, --serologic tests have limited value in immunosuppressed patients (poor capacity to elaborate antibodies). Diagnosis can be made only by surgical biopsy who isolate fungal elements. However diagnosis in greatest cases is only made at autopsy. Treatment consist by antifungal drugs administered intravenously and surgery when it is possible. Prognosis of cerebral aspergillosis is very poor and mortality rate very high about 70%.

Adult↗
PubMed1986

Visual display units and pregnancy: evidence from the Montreal survey.

Data on 56,012 current and 48,608 previous pregnancies were obtained by interview in 11 Montreal hospitals, 1982 to 1984, after delivery or spontaneous abortion. In 17,632 pregnancies in occupations with substantial use of visual display units (VDUs), users and nonusers had similar rates of congenital defects in both current and previous pregnancies and of abortions in previous pregnancies. In current pregnancies there was an excess of abortions in users which could have been due to biased recall. In a further analysis of all 42 occupational groups ranked according to percentage use of VDUs, the risk of spontaneous abortion in both current and previous pregnancies was the same irrespective of the amount of VDU use. Thus, the study does not support the suggestion that work with a VDU in pregnancy increases the risk of congenital defect or spontaneous abortion.

Abortion, Spontaneous↗
PubMed1986

Spontaneous abortion and occupation.

Occupational factors in spontaneous abortion were studied in the current and previous pregnancies of 56,012 women interviewed in 11 Montreal maternity departments, 1982 to 1984. Ratios of observed to expected abortions (RR), after allowance for nonoccupational confounders, were significantly increased (P less than .05) among nursing assistants and attendants (RR 1.24 in current and 1.13 in previous pregnancies), food and beverage servers (RR 1.31 in current and 1.11 in previous pregnancies) and sales persons (RR 1.18 in current and 1.12 in previous pregnancies). Women whose work entailed heavy lifting, other physical effort, long hours, exposure to noise, and exposure to cold had also significantly increased risk ratios. However, when occupational groups were ranked according to work demands, thus avoiding potential bias from prior knowledge of outcome, increased risks were associated consistently only with heavy lifting and other physical effort.

Abortion, Spontaneous↗