Search PubMed⌕ Search

Biomedical subjects

A Couturier

Publications and source records attributed to A Couturier.

35 records · Page 2Linked to original sources

Physiological role of human placental growth hormone.

Placental growth hormone (PGH) is the product of the GH-V gene specifically expressed in the syncytiotrophoblast layer of the human placenta. PGH differs from pituitary growth hormone by 13 amino acids. It has high somatogenic and low lactogenic activities. Assays of PGH by specific monoclonal antibodies reveal that in the maternal circulation from 15-20 weeks up to term, PGH gradually replaces pituitary growth hormone which becomes undetectable. It is secreted by the placenta in a non-pulsatile manner. This continuous secretion appears to have important implications for physiological adjustment to gestation and especially in the control of maternal IGF1 levels. PGH secretion is inhibited by glucose in vitro and in vivo, and is significantly decreased in the maternal circulation in cases of pregnancies with intrauterine growth retardation. PGH does not appear to have a direct effect on fetal growth, as this hormone is not detectable in the fetal circulation. However the physiological role of PGH might also include a direct influence on placental development via an autocrine or paracrine mechanism as suggested by the presence of specific GH receptors in this tissue.

Cell Differentiation↗

The Xenopus protein kinase pEg2 associates with the centrosome in a cell cycle-dependent manner, binds to the spindle microtubules and is involved in bipolar mitotic spindle assembly.

By differential screening of a Xenopus laevis egg cDNA library, we have isolated a 2,111 bp cDNA which corresponds to a maternal mRNA specifically deadenylated after fertilisation. This cDNA, called Eg2, encodes a 407 amino acid protein kinase. The pEg2 sequence shows significant identity with members of a new protein kinase sub-family which includes Aurora from Drosophila and Ipl1 (increase in ploidy-1) from budding yeast, enzymes involved in centrosome migration and chromosome segregation, respectively. A single 46 kDa polypeptide, which corresponds to the deduced molecular mass of pEg2, is immunodetected in Xenopus oocyte and egg extracts, as well as in lysates of Xenopus XL2 cultured cells. In XL2 cells, pEg2 is immunodetected only in S, G2 and M phases of the cell cycle, where it always localises to the centrosomal region of the cell. In addition, pEg2 'invades' the microtubules at the poles of the mitotic spindle in metaphase and anaphase. Immunoelectron microscopy experiments show that pEg2 is located precisely around the pericentriolar material in prophase and on the spindle microtubules in anaphase. We also demonstrate that pEg2 binds directly to taxol stabilised microtubules in vitro. In addition, we show that the presence of microtubules during mitosis is not necessary for an association between pEg2 and the centrosome. Finally we show that a catalytically inactive pEg2 kinase stops the assembly of bipolar mitotic spindles in Xenopus egg extracts.

Amino Acid Sequence↗

[Comparison of endothelial reactivity of infrarenal and suprarenal aortic segments in rodents].

OBJECT: Human infrarenal aorta is prone to develop atherosclerotic lesions. Infrarenal aortic blood flow depends on lower limb muscular activity. Blood flow variations cause shear stress variations known to influence endothelial reactivity. The purpose of this study is to compare vascular reactivity of the suprarenal and infrarenal aorta. MATERIAL AND METHODS: Endothelium-dependent relaxation to acetylcholine (ACH) and calcium ionophore (Cal), and endothelium-independent relaxation to sodium nitroprussiate (SNP) in 3 aortic segments (thoracic, abdominal suprarenal and infrarenal) harvested from Sprague-Dawley rats (n = 12) were studied in organ chambers. RESULTS: Endothelium-dependent relaxations to ACH were similar for the 3 aortic segments. However, infrarenal aorta endothelial response to Cal was decreased compared to other segments whereas response to SNP was enhanced. Contractility to vasoconstrictor agonist (phenylephrine and KCl) was diminished compared to the suprarenal segments. CONCLUSION: Endothelial reactivity is not homogeneous throughout the rat aorta. Endothelial reactivity to Cal seems decreased in the infrarenal aorta which suggests a diminished nitric oxide synthase activity. The increased sensitivity of the infrarenal aorta to nitric oxide donor such as SNP suggests a compensatory mechanism.

Acetylcholine↗

Complex genetic predisposition to cancer in an extended HNPCC family with an ancestral hMLH1 mutation.

Hereditary non-polyposis colorectal cancer (HNPCC) is characterised by a genetic predisposition to develop colorectal cancer at an early age and, to a lesser degree, cancer of the endometrium, ovaries, urinary tract, and organs of the gastrointestinal tract other than the colon. In the majority of families the disease is linked to mutations in one of the two mismatch repair genes, hMSH2 or hMLH1. We have found a novel hMLH1 nonsense mutation in a Swiss family with Lynch syndrome, which has been transmitted through at least nine generations. A different tumour spectrum of neoplasms of the skin, soft palate, breast, duodenum, and pancreas was observed in three branches of this family, where there was a virtual absence of colonic tumours. The hMLH1 mutation could not be detected in members of these branches suggesting that at least a second genetic defect predisposing to cancer is segregating in part of the kindred.

Adaptor Proteins, Signal Transducing↗

Xenopus cyclin E, a nuclear phosphoprotein, accumulates when oocytes gain the ability to initiate DNA replication.

The capacity to initiate DNA replication appears during oocyte maturation in Xenopus. Initiation of S phase is driven by several components which include active cyclin/cdk complexes. We have identified three Xenopus cyclin E clones showing 59% amino acid identity with human cyclin E. The recruitment of cyclin E mRNA, like cdk2 mRNA, into the polysomal fraction during oocyte maturation, results in the accumulation of the corresponding proteins in unfertilized eggs. Cyclin E mRNA remains polyadenylated during cleavage and anti-cyclin E antibodies detect Xlcyclin E in embryonic nuclei at this time. Cdk2 protein is necessary for the phosphorylation of radiolabelled cyclin E added to egg extracts. Radiolabelled Xlcyclin E enters interphase nuclei and, though stable through interphase and mitosis, is not associated with condensed mitotic chromatin. In egg extracts, endogenous Xlcyclin E rapidly associates with nuclei before S phase and remains nuclear throughout interphase, becoming nucleoplasmic in G2/prophase. Under conditions where initiation of replication is limiting in extracts, Xlcyclin E associates only with those nuclei that undergo S phase. These features are entirely consistent with the view that Xlcyclin E is required for initiation of S phase.

Amino Acid Sequence↗

The prognosis of pregnancy in women with chronic hypertension.

OBJECTIVE: Our purpose was to assess pregnancy outcomes in women with chronic hypertension from a population with a perinatal mortality of 12 in 1000. STUDY DESIGN: A longitudinal cohort study was performed between 1987 and 1991 in Montreal, Quebec, Canada. RESULTS: A total of 337 pregnancies in 298 women with chronic hypertension were followed up. The following outcomes were statistically more frequent in the hypertensive women than in the general population (p < 0.01): perinatal mortality (45/1000 vs 12/1000), preeclampsia (21.2% vs 2.3%), premature delivery (34.4% vs 15.0%), small-for-gestational-age newborns (15.5% vs 6.3%), primary cesarean sections (29.6% vs 14.2%), and gestational diabetes (33.1% vs 12.0%). Preeclampsia was associated with prematurity, small-for-gestational-age newborns, cesarean section, and neonatal complications. Even without superimposed preeclampsia hypertensive women had significantly higher frequencies of perinatal death (29/1000) and small-for-gestational-age newborns (10.5%) than did normotensive women (p < 0.05). CONCLUSIONS: In our population women with chronic hypertension with or without superimposed preeclampsia, have a higher incidence of perinatal death and small-for-gestational-age newborns than the general population does.

Adult↗

Expression of RNA isolated from the water-shunting complex of a sap-sucking insect increases the membrane permeability for water in Xenopus oocytes.

The highly specialized membranes of the filter chamber found in the digestive tract of some homopteran insects could represent a favorable material for characterizing water channels. In order to demonstrate that membrane proteins of this epithelial complex serve as water channels, we have investigated the membrane permeability for water in Xenopus oocytes injected with RNA isolated from the filter chamber. Volumes of oocytes injected with filter chamber RNA were increased by 15% following a 16-min osmotic shock, while volumes of oocytes injected with RNA from midgut not of filter chamber or with water were increased only by 8.5 and 10%, respectively. This significant difference in oocyte swelling leads us to conclude that RNA isolated from the filter chamber contains mRNA coding for water channel proteins.

Animals↗

Cloning by differential screening of a Xenopus cDNA coding for a protein highly homologous to cdc2.

Fertilization of Xenopus laevis eggs triggers a period of rapid cell division comprising 12 nearly synchronous mitoses. Protein synthesis is required for these divisions, and new proteins appear after fertilization. Others proteins however, which are synthesized in the unfertilized egg, are no longer made in the early embryo. To identify such proteins, a differential screen of an egg cDNA library gave nine clones corresponding to mRNAs that are deadenylylated soon after fertilization. The sequence of one of these clones (Eg1) revealed a high homology to p34cdc2, the kinase subunit of maturation-promoting factor. Only 12 amino acids in the deduced amino acid sequence were unique to Eg1 when its sequence was compared to all other known examples of cdc2. Despite this strong similarity, however, Eg1 was unable to complement a yeast cdc2- mutant in Schizosaccharomyces pombe or a cdc28 mutant of Saccharomyces cerevisiae. Four Eg1 transcripts, two major and two minor, were found in Xenopus oocytes and early embryos. These RNAs appeared very early (stage I) in oogenesis and their level remained constant until the midblastula transition, at which time they declined. Eg1 RNA is found in the poly(A)+ fraction of oocytes only between the time of meiotic maturation and fertilization--that is to say, in the unfertilized egg. At fertilization the RNA loses its poly(A) tail and at the same time leaves the polyribosomes.

Amino Acid Sequence↗

Xenopus c-raf proto-oncogene: cloning and expression during oogenesis and early development.

We have isolated and characterized a cDNA which contains the entire coding sequence of Xenopus laevis raf protein. raf mRNA is identified as a member of the class of maternal RNAs. It is already relatively abundant at the beginning of oogenesis and is stable at least until the midblastula transition. The RNA is also detected later during embryogenesis in particular in gastrula, neurula, tailbud and feeding tadpole. We have also found the RNA in several adult tissues (skin, testis, stomach, intestine) at different levels.

Amino Acid Sequence↗

Cloning by differential screening of a Xenopus cDNA that encodes a kinesin-related protein.

By differential screening of a Xenopus egg cDNA library, we selected nine clones (Eg1 to Eg9) corresponding to mRNAs which are deadenylated and released from polysomes soon after fertilization. The sequence of one of these clones (Eg5) revealed that the corresponding protein has the characteristic features of a kinesin-related protein. More specifically, Eg5 was found to be nearly 30% identical to a kinesin-related protein encoded by bimc, a gene involved in nuclear division in Aspergillus nidulans.

Adenosine Triphosphatases↗

Detection of proto-oncogenes in the genome of the amphibian Xenopus laevis.

The Xenopus laevis genome was probed by Southern Blot analysis for the presence of sequences homologous to mammalian or avian proto-oncogenes. Hybridization conditions were strictly defined with a known proto-oncogene to detect a positive signal with DNA sequences having at least 60 to 64% homology. In such conditions thirteen genes representing different oncogene families exhibited positive hybridizations with specific DNA restriction fragments. Members of the protein kinase oncogene family were detected including abl, erbB, fes, fms, ros, raf and mos. Ets, rel, and the steroid hormone related receptor erbA also gave positive signals with specific Xenopus DNA fragments. Proto-oncogenes raf and the ras family, N-ras, H-ras and c-ral, gave the strongest hybridizations and the signals remained positive in high stringency wash conditions. This study confirms the relative conservation of these genes during evolution and opens the possibility of studying their role in one of the best characterized systems of embryonic development.

Animals↗

Changes in the polyadenylation of specific stable RNA during the early development of Xenopus laevis.

The distribution of four specific RNA species between the poly(A)+ and poly(A)- fractions has been studied during the first hours of Xenopus laevis development, before the mid-blastula transition (MBT). Two of these specific RNA species correspond to clones selected by differential hybridization from a Xenopus egg cDNA library. Another corresponds to Xenopus c-raf mRNA and the last one to RNA revealed by a mouse ornithine decarboxylase probe. We show that two of these RNAs are adenylated after fertilization and remain in the poly(A)+ population. During the same period, the other two RNAs are deadenylated and these new poly(A)- RNAs remain stable at least until the MBT. These results show (i) that polyadenylation of specific RNA species occurs after fertilization in Xenopus and (ii) that, in the absence of transcription, adenylation and deadenylation can occur simultaneously in the fertilized egg.

Animals↗

Further characterization of tumor-promoter-mediated activation of protein kinase C.

Tumor promoting phorbol esters are able to activate Ca2+-sensitive, phospholipid-dependent protein kinase (protein kinase C) in a reconstituted system. Indol alkaloid teleocidin, a tumor promoter, has been found to be as potent as tumor promoters from the series of phorbol esters and mezerein in activating the mouse brain enzyme. Chemically unrelated tumor promoters such as tetrachlorodibenzo-p-dioxin, anthralin and phenobarbital are devoid of effect. Diacylglycerol 1,2 diolein strongly activated the enzyme whereas 1,3 diolein like 1,2 distearin were poor activators and 1,3 distearin was inactive. Although tumor-promoter-or diacylglycerol-mediated activation of protein kinase C was observed in the presence of 0.5mM EGTA, the reaction requires traces of Ca2+. Tumor promoters did not prevent inhibitory action of antipsychotic phenothiazines and local anesthetics but appear to increase IC50 of these drugs.

Animals↗

Randomized, placebo-controlled, double-blind study of an ultra-low-dose aprotinin regimen in reoperative and/or complex cardiac operations.

BACKGROUND AND AIM OF THE STUDY: High-dose aprotinin is an effective but costly method to reduce transfusions after cardiopulmonary bypass (CPB). Very low doses of aprotinin have been shown to be effective in primary cardiac surgery, but not in patients undergoing procedures associated with the greatest usage of allogeneic blood products after CPB. We evaluated the efficacy of ultra-low-dose aprotinin in this patient population. METHODS: Aprotinin 1 million KIU or placebo was added to the priming solution of the CPB circuit of 52 patients undergoing a reoperation and/or a complex surgical procedure. Dryness of operative field, hemoglobin concentrations, coagulation parameters, chest drainage, and transfusion requirements were compared. RESULTS: Total chest drainage was not different between groups, but fewer patients in the aprotinin group required additional protamine postoperatively (35% vs 69% for controls, p = 0.03) and fewer received fresh frozen plasma (FFP; 19% vs 46% for controls, p = 0.04). Red cell transfusion was smaller in the aprotinin group compared to placebo (median 4 and 2 units, respectively, p = 0.04). Transfusion of FFP, platelets, cryoprecipitates was not different between groups. Total number of units transfused tended to be reduced in the aprotinin group compared to control (median 2 and 7 units, respectively, p = 0.06). CONCLUSIONS: Prophylactic administration of ultra-low-dose aprotinin reduced transfusions in patients undergoing repeat operations or complex procedures. Aprotinin could be used in a more economical manner, even in this patient population at high-risk of receiving allogeneic blood products.

Aged↗