Biomedical subjects

P Durand

Publications and source records attributed to P Durand.

At least 37 records · Page 2Linked to original sources

PubMed2004

Field and experimental evidence of preferential selfing in the freshwater mollusc Lymnaea truncatula (Gastropoda, Pulmonata).

We have conducted a thorough study of the mating system of Lymnaea truncatula, the intermediate host of the liver fluke, using three approaches: (i) a population genetics study, (ii) controlled pairings in the laboratory and (iii) a progeny-array analysis. The population genetics study revealed high levels of inbreeding in the studied populations, with strong clues that the extensive heterozygote deficiencies observed are due to selfing. However, Wahlund effects may also arise due to recolonisations from different source populations after bottleneck events. A breeding experiment helped to disentangle the mating system and the Wahlund effects, and showed that high levels of selfing occurred in isolation and in controlled pairings. However, the progeny-array analysis performed after a high-density culturing of the snails suggests that substantial outcrossing may also occur.

Animals↗

PubMed2004

Small effective population sizes in a widespread selfing species, Lymnaea truncatula (Gastropoda: Pulmonata).

We present here a spatial and temporal population genetic survey of a common freshwater snail, also a predominantly selfing species, Lymnaea truncatula. The rate of genetic diversity loss was quantified by estimating the effective size (Ne) of the snail populations, using two different methods. A temporal survey allowed estimation of a variance effective size of the populations, and a spatial survey allowed the estimation of an inbreeding effective size, from two-locus identity disequilibria estimates. Both methods were consistent and provided low Ne values. Drift due to (i) high amounts of selfing and (ii) fluctuations in population sizes because of temporary habitats, and also selection coupled to genome-wide linkage disequilibria, could explain such reductions in Ne. The loss of genetic diversity appears to be counterbalanced only very partially by low apparent rates of gene flow.

Analysis of Variance↗

PubMed2004

An E-box-containing region is involved in the tissue-specific expression of the human MC2R gene.

Expression of the melanocortin receptor (MC2R) gene is limited to adrenocortical cells and the aim of this study was to determine the factors responsible for this tissue specificity. We used different fragments of the human (h) MC2R gene promoter, inserted in a vector upstream of the luciferase reporter gene, to transiently transfect either bovine adrenocortical (BAC) cells or granulosa cells from bovine ovaries (B-Gran). Similar promoter activities were obtained in both cell types using constructs containing fragments up to 1017 bp of the hMC2R gene promoter. On the contrary, a 2-fold decrease was obtained after transfection of the B-Gran cells with vectors containing 1069 bp and more of the promoter. Results obtained here using BAC cells confirmed our previous data on human cells showing that steroidogenic factor 1 is the major transactivating factor involved in the basal expression of the hMC2R gene in adrenal cells. However, we showed that this factor did not permit, by itself, the expression of the hMC2R gene in B-Gran cells despite its expression in these cells. This study demonstrated for the first time that an E-box (located at -1020 bp) is involved in the repression of hMC2R gene expression in granulosa cells through interactions with several factors, such as activator protein 4, as suggested by electrophoretic mobility shift assay analyses.

Adrenal Cortex↗

PubMed2004

The effects of FSH and of testosterone on the completion of meiosis and the very early steps of spermiogenesis of the rat: an in vitro study.

The role of FSH and of testosterone in spermatogenesis has been a matter of controversy. In the present study, we addressed the involvement of these hormones in the regulation of the completion of meiosis of male rats under in vitro conditions. In the first series of experiments, middle/late pachytene spermatocytes were cocultured with Sertoli cells for 2 weeks in the absence or presence of FSH and/or testosterone. Treatment with both FSH and testosterone reduced slightly the percentage of apoptotic germinal cells in the cultures. Moreover, the number of round spermatids formed in vitro was enhanced by FSH or testosterone when compared with control cultures. Neither hormone influenced the half-life of round spermatids under the present culture conditions. The amounts of TP1 mRNAs in FSH- or FSH plus testosterone-treated cultures were higher than those of controls. In another series of experiments, round spermatids were incubated for 24 h in media conditioned by Sertoli cells cultured in the absence or presence of FSH and/or testosterone. TP1 mRNA contents of round spermatids incubated in media from Sertoli cells cultured in the presence of FSH and/or testosterone were two- to threefold higher than those of spermatids incubated in media from Sertoli cells cultured without hormones. These results indicate that FSH and testosterone have positive and somewhat overlapping effects on the meiotic divisions and the post-meiotic expression of a germ cell-specific gene, effects which cannot be related solely to their ability to reduce germinal cell apoptosis. Use of this culture system should help to test the effect of any hormone or factor on those steps in order to understand better their regulation.

Animals↗

PubMed2003

Synthesis and antioxidant efficiency of a new amphiphilic spin-trap derived from PBN and lipoic acid.

The synthesis of a new amphiphilic antioxidant called PBNLP and derived from both alpha-phenyl-N-tert-butyl nitrone (PBN) and lipoic acid was described. Grafting a lactobionamide moiety onto the aromatic group of the PBN provided the water solubility of this compound. In vitro preliminary biological evaluations of its antioxidant capacity were performed using the KRL biological test based on free radical-induced hemolysis. The PBNLP induces a protection of erythrocytes against exogenous free radicals higher than that measured with lipoic acid or PBN alone or with lipoic acid or PBN derivatives in admixtures.

Antioxidants↗

PubMed2003

Study of the alteration of gene expression in adipose tissue of diet-induced obese mice by microarray and reverse transcription-polymerase chain reaction analyses.

In the present study we developed a model of diet-induced obesity (DIO) in male C57 BL/6J mice using an 8-wk high fat diet. This model should better reflect the physiology of the majority of the human obese patients than mouse genetic models of obesity with defects in leptin or leptin signaling. At the end of the diet, DIO mice displayed an increased weight (20%) and higher leptin, insulin, glucose, and corticosterone plasma levels compared with mice fed a standard diet during the same period. Moreover, they became resistant to the central effect of peripheral administration of leptin. Oligonucleotide microarray studies were conducted in adipose tissue. They showed that a great number of genes are differentially expressed. The majority of these genes (69%) are down-regulated in DIO mice. Among those are genes encoding enzymes of the lipid metabolism or markers of adipocyte differentiation, enzymes involved in detoxification processes, as well as structural components of the cytoskeleton. Some other groups of genes displayed increased expression, such as those encoding inflammatory markers. The results of the microarray analysis were confirmed by semiquantitative RT-PCR studies run on a selected number of genes that were differentially expressed or not modified.

Adipose Tissue↗

PubMed2003

The Mott-Hubbard insulating state and orbital degeneracy in the superconducting C60(3-) fulleride family.

Electron correlation controls the properties of important materials such as superconducting and magnetoresistive transition metal oxides and heavy fermion systems. The role of correlation in driving metal-to-insulator transitions assumes further importance because many superconducting materials are located close to such transitions. The nature of the insulating ground state often reveals the dominant interactions in the superconductor, as shown by the importance of the properties of La2CuO4 in understanding the high-temperature-superconducting cuprates. The A3C60 alkali metal fullerides are superconducting systems in which the role of correlation in both the normal state and the superconducting pairing mechanism is controversial, because no magnetic insulator comparable to the superconducting materials has been identified. We describe the first example of a cubic C60(3-) system with degenerate orbitals that adopts the Mott-Hubbard insulating localized electron ground state. Electron repulsion is identified as the interaction that is suppressed on the transition to metallic and superconducting behaviour in the fullerides. This observation is combined with ab initio calculations to demonstrate that it is the orbital degeneracy that allows the superconducting cubic A3C60 fullerides to remain metallic while provoking electron localization in systems with lower symmetry.

Crystallization↗

PubMed2003

Rapid inactivation of the maize transposable element En/Spm in Medicago truncatula.

Transposable elements have been widely used as mutagens in many organisms. Among them, the maize transposable element En/Spm has been shown to transpose efficiently in several plant species including the model plant Arabidopsis, where it has been used for large-scale mutagenesis. To determine whether we could use this transposon as a mutagen in the model legume plant Medicago truncatula, we tested the activity of the autonomous element, as well as two defective elements, in this plant, and in Arabidopsis as a positive control. In agreement with previous reports, we observed efficient excision of the autonomous En/Spm element in A. thaliana. This element was also active in M. truncatula, but the transposition activity was low and was apparently restricted to the tissue culture step necessary for the production of transgenic plants. The activity of one of the defective transposable elements, dSpm, was very low in A. thaliana and even lower in M. truncatula. The use of different sources of transposases suggested that this defect in transposition was associated with the dSpm element itself. Transposition of the other defective element, I6078, was also detected in M. truncatula, but, as observed with the autonomous element, transposition events were very rare and occurred during tissue culture. These results suggest that the En/Spm element is rapidly inactivated in the regenerated plants and their progeny, and therefore is not suitable for routine insertion mutagenesis in M. truncatula.

Amino Acid Sequence↗

PubMed2003

Significant linkage disequilibrium and high genetic diversity in a population of Plasmodium falciparum from an area (Republic of the Congo) highly endemic for malaria.

A study based on 28 microsatellite loci was performed on 32 isolates of Plasmodium falciparum from Pointe Noire (Republic of the Congo) and compared with a cosmopolitan sample of 21 isolates collected from different countries in Africa, Latin America, and Asia. The Pointe Noire population exhibited very high genetic diversity (A = 7.8 +/- 2.6, He = 0.79 +/- 0.11). Significant linkage disequilibria were observed in 28 of 378 pairs of microsatellite loci. This result could be explained by two non-exclusive hypotheses: 1) uniparental propagation (i.e., selfing), leading to non-panmictic associations, and/or 2) a Wahlund effect (i.e., spatial population genetic heterogeneity). These observations are in agreement with data previously obtained from isozyme loci of the same isolates, but contrast with other population genetic analyses conducted in other hyperendemic zones.

Alleles↗

PubMed2002

In vitro anti-inflammatory and anti-proliferative activity of sulfolipids from the red alga Porphyridium cruentum.

A sulfoglycolipidic fraction (SF) isolated from the red microalga Porphyridium cruentum was analyzed for fatty acid composition and assayed for ability to inhibit, in vitro, the generation of superoxide anion in primed leucocytes and the proliferation of a panel of human cancer cell-lines. Results demonstrated that SF contained large amounts of palmitic acid (26.1%), arachidonic acid (C20: 4 omega-6, 36.8%), and eicopentaenoic (C20:5 omega-3, 16.6%) acids, and noticeable amounts of 16:1n-9 fatty acid (10.5%). It strongly inhibited both the production of superoxide anion generated by peritoneal leukocytes primed with phorbol myristate acetate (IC(50): 29.5 microg/mL), and the growth of human colon adenocarcinoma DLD-1 and to a lesser extent of human breast adenocarcinoma MCF-7, human prostate adenocarcinoma PC-3, and human malignant melanoma M4 Beu cell-lines, and therefore might have a chemopreventive or chemotherapeutic potential, or both. It was found markedly more cytotoxic than sulfoquinovosyldiacylglycerols from plant used as a standard (STD), due to a stronger ability to inhibit DNA alpha-polymerase (IC(50): 378 microg/mL, vs 1784 microg/mL for STD). After a 48-h continuous treatment, IC(50) values for growth inhibition were in the range of 20-46 microg/mL instead of 94 to >250 microg/mL for STD, and those for inhibition of metabolic activity were in the range of 34-87 microg/mL instead of >250 microg/mL for STD. The higher anti-proliferative effect was observed on colon adenocarcinoma DLD-1 cells, and the weaker effect was observed on breast adenocarcinoma MCF-7.

Adenocarcinoma↗

PubMed2002

Severe cardiac failure in newborns with VGAM. Prognosis significance of hemodynamic parameters in neonates presenting with severe heart failure owing to vein of Galen arteriovenous malformation.

OBJECTIVE: Neonatal vein of Galen malformation complicated by severe cardiac failure is a rare disease. The purpose was to assess the outcome of this life-threatening malformation and identify hemodynamic prognostic factors. DESIGN: Retrospective study. PATIENTS: Twenty-four newborns with cardiac failure requiring mechanical ventilation were consecutively admitted from 1986 to 2000. INTERVENTIONS: Cardiovascular evaluation including echocardiogram was performed in all cases. Eighteen transarterial shunt occlusions with glue were applied by the same team of three physicians. MEASUREMENTS AND RESULTS: Twelve babies survived and underwent one endovascular session at least (median age 20 days) with a mean 63 months follow-up. Embolization was not performed in 6 of the 12 nonsurvivors because of severe brain damage or profound hypotension Cardiogenic shock occurred in all nonsurvivors, but also in one long-term survivor (p<0.0001). Echocardiogram showed signs of right ventricular failure, most often in the dead babies (p=0.005). The pulmonary systemic arterial pressure ratio was significantly higher in the nonsurvivor group (p=0.031), and it decreased significantly after the first embolization only in patients who survived (p=0.01). Patent ductus arteriosus and a diastolic aortic reversed-flow were present in all nonsurvivors in contrast to 30% of the long-term survivors (p=0.003 ). There was no difference in the left ventricular contractility and mean cardiac output between the two groups. CONCLUSIONS: The outcome of vein of Galen malformation complicated by severe cardiac failure requiring mechanical ventilation remains poor. Neonatal embolization seems to be beneficial only in babies without suprasystemic pulmonary hypertension.

Arteriovenous Malformations↗

PubMed2002

Functional relationships between three novel homozygous mutations in the ACTH receptor gene and familial glucocorticoid deficiency.

Familial glucocorticoid deficiency (FGD) is an autosomal recessive disorder characterized by a glucocorticoid adrenal insufficiency without mineralocorticoid deficiency. Mutations of the ACTH receptor (MC2-R) gene have been reported in some FGD cases, but only a few of them have been functionally studied. We reported clinical features and MC2-R gene analysis in three families. For each proband, an homozygous mutation was identified after amplification and sequencing of the whole intronless MC2-R gene. One mutation converted Val-142 located in the second intracellular loop to Leu. Another mutation in the sixth transmembrane domain converted Ala-233 to Pro. The last mutation converted the negatively charged Asp-103 in the first extracellular loop to an uncharged Asn. Functional studies of these mutations as well as the S120R mutation were performed after stable transfection of M3 cells and measurement of ACTH-induced cAMP production. For the S120R, V142L, and A233P mutated MC2-R, cAMP production curves were similar to that obtained with M3 parental cells, confirming that these mutations are responsible for the FGD in the affected patients. The D103N-mutated MC2-R had an impaired cAMP response to physiological doses of ACTH, but the maximal response at very high concentrations of ACTH was similar to that obtained for the wild-type MC2-R. All these results demonstrated clear relationships based on functional studies between MC2-R homozygous mutations and FGD phenotype.

Adrenocorticotropic Hormone↗

PubMed2002

Genetic structure of Oestrus ovis populations in sheep and goats.

A genetic analysis using RAPD markers was performed on 12 natural populations of Oestrus ovis (Linné, 1761). Three-hundred and six O. ovis larvae (first, second and third instars) were randomly recovered in nasal cavities of sheep and goats naturally infected in Algeria, Ethiopia, France, Mauritania, Rumania and Tunisia and were analysed by 56 RAPD fragments. The results showed a high diversity within all samples. A significant genetic divergence was showed by discriminant analyses among the 12 populations sampled (p<0.0001). Moreover, discriminant analyses showed significant differentiation (p<0.0001) between O. ovis larva populations of sheep and goats and also among samples collected in the same region.

Animals↗

PubMed2002

Occurrence of a sibling species complex within neotropical lymnaeids, snail intermediate hosts of fascioliasis.

The delimitation of cryptic species within the genus Lymnaea, which are the main vectors of fascioliasis, remains a topic of controversy. An analysis of genetic variability based on 12 enzyme loci revealed different fixed alleles at 9 loci between two sympatric samples of Lymnaea viatrix at the type locality in Lima, Peru. The absence of heterozygotes within this locality indicates the presence of isolated populations or cryptic species within L. viatrix. Significant genetic differences were also found between these two L. viatrix samples from Lima and other populations of L. viatrix in South America and in addition to species such as L. truncatula, L. cubensis and L. columella. Moreover, the lack of variability within each Lymnaea samples studied indicates the existence of a high selfing rate in each species.

Animals↗

PubMed2002

[Severe Reye syndrome: report of 14 cases managed in a pediatric intensive care unit over 11 years].

UNLABELLED: Idiopathic Reye syndrome is a rare disease revealed by unexplained encephalopathy and microvesicular liver steatosis. Some clinical and epidemiological studies mainly performed in English speaking countries questioned the reality of Reye syndrome because numerous know inherited metabolic diseases, and some of them unrecognized, could mimick this disorder. We focused in our study on severe forms of Reye syndrome admitted to a pediatric intensive care unit. METHODS: Retrospective study over the last eleven years (1991-2001) included all the pediatric patients admitted to our tertiary referral center with the classical American Reye syndrome criteria (e.g. CDC). Extensive metabolic screening was performed in all cases, except for the ultimately dead patients. RESULT: Fourteen patients (mean age 52 months) were included. Fever always occurred before their admission and aspirin (n = 12) or acetaminophen (n = 7) was prescribed. Median Glasgow scale was 7 on admission. Mean amoniac plasma level was 320 mumol/L and alanine-aminotransferase peak plasma level 1475 +/- 1387 IU/L. Mechanical ventilation was started in ten children and six of them underwent continuous venovenous hemofiltration. Three patients ultimately died and 11 survived with a mean five years follow-up without relapses or neurological impairment. Any of them demonstrated inherited metabolic disease except for one infant with hereditary fructose intolerance. CONCLUSION: Unlike widespread opinion, severe Reye syndrome without identified metabolic disorders seems to not disappear in our country. Reye syndrome remains a potentially life threatening disease and raises for aggressive treatment of brain edema. If aspirin and Reye syndrome association are not formally documented in France, cautiousness must be kept in mind and all the aspirin adverse effects notifications should be addressed to the public drugs survey network.

Acetaminophen↗

PubMed2002

Sex-specific genetic structure in Schistosoma mansoni: evolutionary and epidemiological implications.

We studied the population genetic structure of 360 and 1247 adult Schistosoma mansoni using seven microsatellite and seven random amplified polymorphic DNA (RAPD) markers, respectively. Parasites were collected from their natural definitive host Rattus rattus in Guadeloupe (West Indies). We found a sex-specific genetic structure, a pattern never before reported in a parasitic organism. Male genotypes were more randomly distributed among rats than female genotypes. This interpretation was consistent with a lower differentiation between hosts for males relative to females, the higher genetic similarity between females in the same host and the observed local (i.e. within-individual-host) differences in allele frequencies between the two sexes. We discuss our results using ecological and immunological perspectives on host-parasite relationships. These results change our view on the epidemiology of schistosomiasis, a serious disease affecting humans in African and American intertropical zones.

Animals↗

PubMed2002

The human MC2-R gene expression: different aspects of its control.

Expression of the adrenocorticotropin receptor (MC2-R) is restricted to adrenocortical cells and is up-regulated by both adrenocorticotropin and angiotensin II through the activation of protein kinase A and protein kinase C pathways, respectively. After cloning of the promoter region of the human MC2-R gene (hMC2-R), we have shown that cyclic AMP-induced regulation of transcriptional activity of the gene is achieved through two SF1 binding elements located in the proximal promoter. On the other hand, regulation by angiotensin II partly involved two AP1 binding sites. Using different primary cell cultures, we have also been able to delineate a region inside the promoter which is responsible for part of the tissue-specific expression of the gene.

Angiotensin II↗

PubMed2002

Expression of the melanocortin receptors MC2-R (ACTH-receptor) and MC5-R during embryonic development of ovine adrenals.

Two melanocortin receptors MC2-R (ACTH-receptor) and MC5-R are expressed in the adult lamb adrenal cortex. In this work, we have studied the time-course of expression of these two receptors during ovine fetal development. MC2-R expression progressively increases from day 60 to day 140 of gestation (x3), then more rapidly before parturition and remains constant in the newborn. In contrast, the pattern of MC5-R expression is totally different. A strong increase is observed between days 60 and 120 (x7) then followed by a decrease until parturition and after birth. This peak of MC5-R expression precedes that of MC2-R, suggesting that MC5-R might be involved in alpha-MSH- and/or ACTH-stimulated corticosteroid synthesis during early embryonic life.

Adrenal Glands↗