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L Mesnard

Publications and source records attributed to L Mesnard.

10 recordsLinked to original sources
PubMed1998

Genomic organisation, alternative splicing and polymorphisms of the human cardiac troponin T gene.

Troponin T (TnT) is a component of the troponin complex which regulates muscle contraction in response to alterations in intracellular calcium ion concentration. In human heart, multiple isoforms of cardiac TnT have been described on the basis of antibody studies and molecular cloning of corresponding cDNAs. These isoforms are all derived from the transcription of a single gene, TNNT2, located on chromosome 1q32, and generated by alternative splicing. We show here that isoform diversity is achieved by the use of both alternative exons and alternative acceptor sites and present the organisation of the human TNNT2 gene, which is composed of 17 exons spread over 17 kb. A potential structure of the promoter region is also presented. Several polymorphisms in both the exonic and intronic regions were identified, some of which may act as modulators of the expression of this gene.

Alternative Splicing↗
PubMed1996

Interactions between endothelin-1 and atrial natriuretic peptide influence cultured chick cardiac myocyte contractility.

We have previously shown that rat atrial natriuretic peptide (ANP) reduces the contractility of cultured, spontaneously beating chick embryo ventricular cells, an effect opposite to that of endothelin-1. Endothelin-1 has been described as a secretagogue for natriuretic peptides in vitro and in vivo. Natriuretic peptides can inhibit endothelin-1 secretion from cultured endothelial cells, suggesting a negative feedback mechanism between endothelial cells and cardiomyocytes. The aim of this study was to determine whether ANP attenuated the endothelin-1-induced increase in myocyte contractility. Using a video-microscopy system we studied the contractility of isolated cultured chick ventricular myocytes in response to endothelin-1, chicken natriuretic peptide (ChNP), and both. We also used Northern blot analysis to study the time course of ChNP expression in response to endothelin-1. Endothelin-1 (10(-8) M) increased chick cardiomyocyte contractility by 20-25% between 5 and 15 min (P < 0.05). Although ChNP (3 x 10(-7) M) did not significantly change the amplitude of contraction in basal conditions, it prevented the endothelin-1-induced increase in contractility (P < 0.05) when perfused prior to endothelin-1, and reversed it when perfused 5 min after endothelin-1 exposure (P < 0.05). Endothelin-1 significantly increased the accumulation of ChNP mRNA in chick ventricular myocytes as early as the 30 min after exposure (P < 0.05), with a maximal effect after 2 h of stimulation (P < 0.01); no effect was observed after 4 h. These data support an interaction between endothelin-1 and natriuretic peptides as autocrine/paracrine factors regulating the contractile function of chick cardiac myocytes, as well as their antagonistic effects on cardiac cell contractility. The early and transient expression of ChNP mRNA in response to endothelin-1 may be involved in this interaction.

Analysis of Variance↗
PubMed1995

Human cardiac troponin T: cloning and expression of new isoforms in the normal and failing heart.

Troponin T, like many myofibrillar proteins, exists as multiple isoforms encoded by distinct genes or generated by splicing of the same primary RNA transcript. We have previously cloned the first human cardiac troponin T (cTnT) cDNA and showed the differential expression of cTnT in cardiac and skeletal muscle during ontogenic development. In this work we located the human cTnT gene by means of fluorescent in situ hybridization to 1q32 and, by sequencing thirteen cDNAs isolated from a human fetal heart cDNA library, identified three new isoforms resulting from specific combinations of three variable regions in human cTnT cDNA. The first variable region is a 30-bp box located at the 5' end of the cDNA, which can be excised either totally or only from the first 3 bp onwards; the second is a codon which can be completely excised; and the third is a 9-bp box in the 3' half of the cDNA, which can also be excised either totally or only from the first 3 bp. The existence of the corresponding RNAs in fetal and adult ventricles was confirmed by RNase protection studies. No accumulation of the fetal isoforms was found in failing ventricles compared with controls.

Aged↗
PubMed1995

Genetic linkage heterogeneity in myotubular myopathy.

Myotubular myopathy is a severe congenital disease inherited as an X-linked trait (MTM1; McKusick 31040). It has been mapped to the long arm of chromosome X, to the Xq27-28 region. Significant linkage has subsequently been established for the linkage group comprised of DXS304, DXS15, DXS52, and F8C in several studies. To date, published linkage studies have provided no evidence of genetic heterogeneity in severe neonatal myotubular myopathy (XLMTM). We have investigated a family with typical XLMTM in which no linkage to these markers was found. Our findings strongly suggest genetic heterogeneity in myotubular myopathy and indicate that great care should be taken when using Xq28 markers in linkage studies for prenatal diagnosis and genetic counseling.

Chromosome Mapping↗
PubMed1994

A new human slow skeletal troponin T (TnTs) mRNA isoform derived from alternative splicing of a single gene.

A human muscle cDNA library was screened for slow skeletal troponin T (TnTs). Sequence analysis revealed that one of the selected clones had a cDNA coding sequence different from the two previously described. RNase protection assays confirmed the expression of this new isoform in adult skeletal muscle. In addition, results of the RNase protection assays strongly suggested the expression of a fourth isoform. These isoforms for human slow TnT most likely result from combinatorial alternative splicing of a single gene.

Adult↗
PubMed1993

Molecular cloning and developmental expression of human cardiac troponin T.

We have isolated a full-size cDNA coding for cardiac troponin T (cTnT) from a human adult heart library, using a slow skeletal TnT probe. This cDNA detected a 1.2 kb mRNA in fetal and post-natal human heart, the amount of which increased during ontogenic development. Interestingly, a similar transcript was coexpressed in fetal skeletal muscle, together with the 0.9 kb slow skeletal muscle mRNA, and its expression was down-regulated during further development.

Adult↗
PubMed1992

For a systematic policy of i.v. oxytocin inducted placenta deliveries in a unit where a fairly active management of third stage of labour is yet applied: results of a controlled trial.

The authors analysed the effect of the i.v. oxytocin induced third stage of labour in a controlled trial concerning 1000 patients. The appliance of such an policy in a unit that already had a fairly active management of delivery was very encouraging. The incidence of post-partum haemorrhage (greater than 500 ml) is significantly (P less than 0.001) less than in the control group; and the same for severe haemorrhage. The third stage is significantly (P less than 0.001) shorter in the oxytocin-injected group than in the control group. Moreover, there is no significant difference between the two groups for retained placenta. The economy of blood transfusion, which is a major concern nowadays, could be the real interest of this active management of the third stage of labour.

Female↗