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Biomedical subjects

M Philippe

Publications and source records attributed to M Philippe.

At least 91 records · Page 5Linked to original sources
PubMed1993

Effect of perindopril in rat cardiac volume overload.

The aortocaval fistula is a classic model of pure cardiac volume overload in rats. This model is characterized by dilation of the ventricular cavities and eccentric cardiac hypertrophy. There are also changes in peripheral arterial flow: high flow in the proximal part of the aorta, upstream of the shunt, and low flow in the distal aorta, downstream of the shunt. The chronic effects of converting enzyme inhibition in this model of volume overload have not yet been measured. We tested the effect of blood pressure and flow on cardiac mass and aortic dilatory pathway in normotensive Wistar and spontaneously hypertensive rats (SHR) with an aortocaval fistula. One half of the sham-operated rats and the normotensive and hypertensive rats with aortocaval fistulas were treated for 1 month with perindopril (2 mg/kg by daily gavage). Urine and plasma were collected at death, the heart was weighed, and the proximal (thoracic) and distal (abdominal) aortas were quickly removed and frozen in liquid nitrogen for measurement of cyclic guanosine monophosphate (cGMP). Blood pressure was always higher in SHR than in Wistar rats, in sham-operated rats than in those with aortocaval fistulas, and in untreated than in perindopril-treated rats. Similarly, the heart weight/body weight ratio was higher in SHR than in Wistar rats, in those with aortocaval fistulas than in sham-operated rats, and in untreated than in Wistar rats, in those with aortocaval fistulas than in sham-operated rats, and in untreated than in perindopril-treated rats. The aortocaval fistula increased the plasma atrial natriuretic factor and perindopril reduced it.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

N-acetylglucosamine-binding proteins on Plasmodium falciparum merozoite surface.

Plasmodium falciparum merozoite surface is specifically labelled with a neoglycoprotein bearing N-acetylglucosamine (GlcNAc) residues in a sugar-dependent manner, as shown by affinity cytochemistry in fluorescence and electron microscopy. To ascertain the nature of the sugar receptor, merozoite proteins were blotted and tested by a two-step method using biotinylated GlcNAc-bovine serum albumin (BSA) and streptavidin-peroxidase conjugate. Three parasite proteins were specifically revealed and designated as Pf 120, Pf 83 and Pf 45 GlcNAc-binding proteins. These proteins bind to a gel substituted with GlcNAc and are specifically eluted with 300 mM GlcNAc. Using a rabbit antiserum raised against Pf 83, the Pf 120 GlcNAc-binding protein, in addition to Pf 83, was labelled by Western blotting. Comparative analyses with an antibody against the Pf 83 MSP derived from the P. falciparum merozoite surface protein (Pf MSP) indicated that the Pf 83 GlcNAc-binding protein is not related to the fragment of the Pf MSP antigen. Similarly, the Pf 83 GlcNAc-binding protein is not related to the apical membrane antigen 1 (AMA 1) which also has the same molecular mass. Therefore the Pf 120, Pf 83 and Pf 45 GlcNAc-binding proteins which are located on the merozoite surface and recognize GlcNAc residues could be involved in the binding of merozoites to the glycoconjugates of the surface of the red blood cells.

Acetylglucosamine↗
PubMed1993

In Xenopus laevis, the product of a developmentally regulated mRNA is structurally and functionally homologous to a Saccharomyces cerevisiae protein involved in translation fidelity.

We have performed a differential screen of a Xenopus egg cDNA library and selected two clones (Cl1 and Cl2) corresponding to mRNA which are specifically adenylated and recruited into polysomes after fertilization. Sequence analysis of Cl1 reveals that the corresponding protein is 67.5% identical (83% similar) to the product of the Saccharomyces cerevisiae SUP45 (also called SUP1 or SAL4) gene. This gene, when mutated, is an omnipotent suppressor of nonsense codons. When expressed in a sup45 mutant, the Xenopus Cl1 cDNA was able to suppress sup45-related phenotypes, showing that the structural homology reflects a functional homology. Our discovery of a structural and functional homolog in Xenopus cells implies that the function of SUP45 is not restricted to lower eukaryotes and that the SUP45 protein may perform a crucial cellular function in higher eukaryotes.

Amino Acid Sequence↗
PubMed1993

An initiation codon mutation as a cause of beta-thalassemia in a Belgian family.

Nine asymptomatic members of a family of Belgian origin, spanning three generations, present typical features of heterozygous beta-thalassemia. Since no mutation was detected with a large panel of oligonucleotide probes, the thalassemia gene was investigated by direct sequencing of DNA segments amplified by the polymerase chain reaction. A T-->C transition was detected in the translation initiation codon (ATG). The mutation, which abolishes an Nco I restriction site, was further confirmed by enzymatic digestion as well as by dot-blot hybridization of the amplified products with allele-specific oligonucleotide probes. It produced a beta zero-thalassemia phenotype characterized by marked microcytosis and hypochromia, as well as by an in vitro beta/alpha chain synthesis ratio close to O.5. Search for haplotype linkage showed the mutation to be associated with haplotype IX [- + - + + + +].

Base Sequence↗
PubMed1993

Effects of converting enzyme inhibitor and neutral endopeptidase inhibitor on blood pressure and renal function in experimental hypertension.

Angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP) are implicated in the metabolism of several peptides involved in blood pressure and sodium homeostasis control, such as angiotensins, atrial natriuretic factor (ANF), bradykinin and endothelin. The effects of a highly selective NEP inhibitor (NEPI), retrothiorphan, of a converting enzyme inhibitor (CEI), enalaprilat, and of the combination, CEI + NEPI, were assessed in deoxycorticosterone acetate (DOCA)-salt hypertensive rats, spontaneously hypertensive rats (SHRs) and renovascular hypertensive rats. NEPI increased diuresis, natriuresis and urinary cyclic GMP (cGMP), ANF and bradykinin in the three models. NEPI decreased blood pressure in DOCA-salt hypertensive rats only, whereas CEI decreased blood pressure in SHRs and renovascular hypertensive rats only and increased plasma renin. CEI had no effect on urinary aldosterone or bradykinin in any of the three models. CEI + NEPI increased diuresis and natriuresis in DOCA-salt hypertensive rats and SHRs, and increased urinary cGMP, ANF and bradykinin and plasma renin levels. CEI and NEPI interacted significantly to decrease blood pressure and to increase urinary cGMP in SHRs only. Hence, NEPI increases diuresis, natriuresis and urinary cGMP, ANF and bradykinin in experimental hypertension, whereas CEI acts on blood pressure and increases in plasma renin in SHRs and renovascular hypertensive rats. The significant interaction between CEI and NEPI to decrease blood pressure in SHRs indicates that simultaneous blockade of the two metallopeptidases results in potentiation of the hypotensive effect and that the SHRs appear to be a good model for studying NEP and ACE coinhibition. Finally, NEP rather than ACE appears to be involved in bradykinin renal catabolism in experimental hypertension.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

Clonal rearrangement of the T-cell receptor beta-chain gene in the pleural fluid of a patient with thymoma.

Thymoma is generally considered as an epithelial malignancy surrounded by lymphocytes not belonging to the tumour. This report documents a case of malignant thymoma associated with a lymphocytic pleural effusion. The pleural lymphocytes were mature T-cells, a small proportion of which were shown to have a monoclonal rearrangement of the beta-chain of the T-cell receptor. On the contrary, the lymphocytes of peripheral blood exhibited a germline configuration. The nature of the monoclonal population found in the pleural fluid is discussed and if the cells are of thymic origin their clonal configuration may point to a neoplastic nature of lymphocytes infiltrating malignant thymoma. Alternatively, the clonal T-cell subpopulation may result from an aberrant immunological response to the thymoma.

Clone Cells↗
PubMed1992

Mitotic spindle organization by a plus-end-directed microtubule motor.

Intracellular microtubule motor proteins may direct the motile properties and/or morphogenesis of the mitotic spindle (reviewed in ref. 3). The recent identification of kinesin-like proteins important for mitosis or meiosis indicates that kinesin-related proteins may play a universal role in eukaryotic cell division, but the precise function of such proteins in mitosis remains unknown. Here we use an in vitro assay for spindle assembly, derived from Xenopus egg extracts, to investigate the role of Eg5, a kinesin-like protein in Xenopus eggs. Eg5 is localized along spindle microtubules, and particularly enriched near spindle poles. Immunodepletion of Eg5 from egg extracts markedly reduces the extent of spindle formation in extracts, as does direct addition of anti-Eg5 antibodies. We also demonstrate that Eg5 is a plus-end-directed microtubule motor in vitro. Our results suggest a novel mechanism for the dynamic self-organization of spindle poles in mitosis.

Animals↗
PubMed1992

A cdc2-related kinase oscillates in the cell cycle independently of cyclins G2/M and cdc2.

The Eg1 gene in Xenopus laevis is related in sequence to the cdc2+ gene. We show here that the Eg1 gene product (cdk2) possesses histone H1 protein kinase activity and binds to PSTAIR antibodies as well as to Sepharose beads linked to the 13-kDa product of the suc 1 gene (p13suc1). Eg1 protein kinase is active only in an Mr approximately 200,000 complex with other proteins but is not associated with any of the three known Xenopus mitotic cyclins or with any newly synthesized protein in egg extracts that exhibit cell cycle oscillations in vitro. The protein kinase activity of Eg1 oscillates in the mitotic cell cycle, being high in M-phase and low in interphase. Hyperactivation of cdc2 kinase by the addition of cyclin A has no effect on the activity or oscillatory behavior of Eg1. Inhibition of cdc2 kinase activation by emetine or RNase treatment of oscillating extracts does not inhibit the activation of Eg1 but does block deactivation normally seen during exit from mitosis. These results indicate that Eg1 is regulated by a cell cycle clock independently of cyclin and cdc2 kinase.

Amino Acid Sequence↗
PubMed1992

Expression of DNA ligases I and II during oogenesis and early development of Xenopus laevis.

We have analyzed the expression of DNA ligase I protein during oogenesis and early development of Xenopus laevis. The protein is already present in stage I oocytes and then accumulates throughout oogenesis to reach a steady state level by stage VI. It remains at this level at least until tadpole stage. In stage VI oocytes DNA ligase I protein is almost exclusively localized in the germinal vesicle. We have partially purified a DNA ligase II activity from stage VI oocytes, unfertilized eggs, and stage 8 embryos. An 80-kDa polypeptide can be specifically adenylated in all three purified extracts. It is not recognized by antibodies directed against DNA ligase I and is active on oligo(dT)-poly(rA) substrate. It could therefore represent DNA ligase II protein. The presence of both DNA ligases I and II in oocytes and embryos is inconsistent with the DNA ligase model that had been previously proposed for amphibia.

Animals↗
PubMed1992

Hepatic localization of a fibrosarcoma in a child with a liver transplant.

Two years after an orthotopic liver transplantation, a multifocal hepatic tumor with lymphonodular metastases, identified as a fibrosarcoma, developed in a 4-year-old girl being treated with cyclosporine. On a needle biopsy sample, genetic typing of the HLA-DR group revealed that tumoral cells were from the recipient.

Child, Preschool↗
PubMed1992

Cyclin A potentiates maturation-promoting factor activation in the early Xenopus embryo via inhibition of the tyrosine kinase that phosphorylates cdc2.

We have produced human cyclin A in Escherichia coli and investigated how it generates H1 kistone kinase activity when added to cyclin-free extracts prepared from parthenogenetically activated Xenopus eggs. Cyclin A was found to form a major complex with cdc2, and to bind cdk2/Eg1 only poorly. No lag phase was detected between the time when cyclin A was added and the time when H1 histone kinase activity was produced in frog extracts, even in the presence of 2 mM vanadate, which blocks cdc25 activity. Essentially identical results were obtained using extracts prepared from starfish oocytes. We conclude that formation of an active cyclin A-cdc2 kinase during early development escapes an inhibitory mechanism that delays formation of an active cyclin B-cdc2 kinase. This inhibitory mechanism involves phosphorylation of cdc2 on tyrosine 15. Okadaic acid (OA) activated cyclin B-cdc2 kinase and strongly reduced tyrosine phosphorylation of cyclin B-associated cdc2, even in the presence of vanadate. 6-dimethylamino-purine, a reported inhibitor of serine-threonine kinases, suppressed OA-dependent activation of cyclin B-cdc2 complexes. This indicates that the kinase(s) which phosphorylate(s) cdc2 on inhibitory sites can be inactivated by a phosphorylation event, itself antagonized by an OA-sensitive, most likely type 2A phosphatase. We also found that cyclin B- or cyclin A-cdc2 kinases can induce or accelerate conversion of the cyclin B-cdc2 complex from an inactive into an active kinase. Cyclin B-associated cdc2 does not undergo detectable phosphorylation on tyrosine in egg extracts containing active cyclin A-cdc2 kinase, even in the presence of vanadate. We propose that the active cyclin A-cdc2 kinase generated without a lag phase from neo-synthesized cyclin A and cdc2 may cause a rapid switch in the equilibrium of cyclin B-cdc2 complexes to the tyrosine-dephosphorylated and active form of cdc2 during early development, owing to strong inhibition of the cdc2-specific tyrosine kinase(s). This may explain why early cell cycles are so rapid in many species.

Amino Acid Sequence↗
PubMed1991

Human cyclin E, a new cyclin that interacts with two members of the CDC2 gene family.

A new human cyclin, named cyclin E, was isolated by complementation of a triple cln deletion in S. cerevisiae. Cyclin E showed genetic interactions with the CDC28 gene, suggesting that it functioned at START by interacting with the CDC28 protein. Two human genes were identified that could interact with cyclin E to perform START in yeast containing a cdc28 mutation. One was CDC2-HS, and the second was the human homolog of Xenopus CDK2. Cyclin E produced in E. coli bound and activated the CDC2 protein in extracts from human G1 cells, and antibodies against cyclin E immunoprecipitated a histone H1 kinase from HeLa cells. The interactions between cyclin E and CDC2, or CDK2, may be important at the G1 to S transition in human cells.

Amino Acid Sequence↗
PubMed1991

Reinvestigation of DNA ligase I in axolotl and Pleurodeles development.

We have recently shown that the exclusion process causing the replacement of DNA ligases II by DNA ligase I in amphibian eggs after fertilization does not occur in the case of Xenopus laevis [Hardy, S., Aoufouchi, S., Thiebaud, P., and Prigent, C., (1991) Nucleic Acids Res. 19, 701-705]. Since this result is in contradiction with the situation reported in axolotl and Pleurodeles we decided to reinvestigate such results in both species. Three different approaches have been used: (1) the substrate specificity of DNA ligase I; (2) the DNA ligase-AMP adduct reaction and (3) the immunological detection using antibodies raised against the X.laevis DNA ligase I. Our results clearly demonstrate that DNA ligase I activity is associated with a single polypeptide which is present in oocyte, unfertilized egg and embryo of both amphibians. Therefore, the hypothesis of a change in DNA ligase forms, resulting from an expression of the DNA ligase I gene in axolotl and Pleurodeles early development must be rejected. We also show that, in contradiction with published data, the unfertilized sea urchin egg contains a DNA ligase activity able to join blunt ended DNA molecules.

Adenosine Monophosphate↗
PubMed1991

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↗
PubMed1991

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↗