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M Philippe

Publications and source records attributed to M Philippe.

At least 127 records · Page 7Linked to original sources
PubMed1987

Consequences of renal morphologic damage induced by inhibition of converting enzyme in rat renovascular hypertension.

The consequences of morphologic changes in the kidney distal to a stenosis induced by chronic administration of a converting enzyme inhibitor were determined after induction of experimental renovascular hypertension in rats. The relationship between changes in morphology in the clipped kidney and diuresis, creatinine, and mortality was studied by converting a two-kidney, one-clip model into a one-kidney, one-clip model after 1 month of converting enzyme inhibition. The right renal artery was constricted with a clip of 0.2 mm diameter to increase blood pressure, the left kidney was left untouched. After 1 month, systolic blood pressure had increased to 173 +/- 27 mm Hg in the clipped animals (n = 47) compared with 139 +/- 8 mm Hg in sham-operated animals (n = 15; group 1). An inhibitor of angiotensin-converting enzyme, MK421 (2 mg/kg, po), or an equivalent volume of vehicle was then administered daily for 1 month. After treatment with the converting enzyme inhibitor, blood pressure (148 +/- 28 mm Hg) was virtually identical with that of a sham-operated, vehicle-treated control group (145 +/- 16 mm Hg, n = 15), and was significantly lower than that of untreated hypertensive rats (186 +/- 30 mm Hg, n = 17) (group 2). The weight of the left kidney was increased in the untreated hypertensive animals as compared with sham-operated controls (1260 +/- 168 mg for group 2 versus 1075 +/- 100 mg for group 1). After treatment with MK421, the weight of the contralateral kidney (1472 +/- 190 mg) was further increased. After 1 month of treatment with MK421 or vehicle, the unclipped left kidney was removed from all animals. The treated animals were then randomly divided into two groups: one in which treatment with MK421 was stopped (treated/untreated, n = 24; group 3) and a second in which the treatment was continued (treated/treated, n = 23; group 4). The ability of the rats to excrete a water load of 15 ml was then examined 12 hours after removal of the unclipped left kidney. In the two groups of treated rats, the urinary excretion of the water load was decreased and frequency of oliguria was increased as compared with controls and hypertensive untreated rats. Survival rates were affected by the treatment: 3 deaths occurred in the hypertensive untreated group 2, 10 in the treated/untreated group 3, and 12 in the treated/treated group 4. The majority of these deaths could be attributed to renal insufficiency.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Purification and characterization of Plasmodium berghei DNA topoisomerases I and II: drug action, inhibition of decatenation and relaxation, and stimulation of DNA cleavage.

It has recently been suggested that topoisomerases could be important targets for drugs used in several diseases. This prompted us to purify and characterize the topoisomerases I and II present in the erythrocytes of protozoan parasites of the genus Plasmodium, the causative agent of malaria, in order to later use these enzymatic systems in antimalarial drug assays. The topoisomerases were purified from Plasmodium berghei, a parasite of mouse red cells. The Plasmodium topoisomerase II consists of two subunits with a molecular weight of about 160K. The enzyme is ATP- and Mg2+-dependent. The conditions for the reactions of relaxation, unknotting, decatenation, and catenation were found to be similar to those observed with enzymes from other eukaryotic cells. The Plasmodium topoisomerase I is a monomeric enzyme with a Mr of 70K-100K. It is ATP-independent and K+- or Na-dependent. Mg2+ is not required for relaxation but stimulates the reaction. Topoisomerase II was more sensitive to drug action than topoisomerase I. The most active drugs were the ellipticine derivatives. The antimalarial drugs, currently used in human clinical therapy, were poor inhibitors. Some antitumoral drugs stimulated the double-stranded DNA cleavage activity of Plasmodium topoisomerase II, like that of mammalian topoisomerases II. Antimalarial drugs had no stimulating activity. It is therefore suggested that Plasmodium topoisomerases are not good targets for antimalarial drugs.

Alkaloids↗
PubMed1986

DNA polymerase alpha associated primase from rat liver: physiological variations.

A primase activity associated to DNA polymerase alpha from rat liver is described. Both activities were absent in normal adult rat liver but were concomitantly induced after partial hepatectomy. As previously shown for polymerase alpha and DNA topoisomerase II, primase activity reached a maximum value 40-43 h after the partial removal of the liver. Primase activity was shown to catalyze dNMP incorporation on unprimed single-stranded DNA template (M13 DNA) in the presence of rNTP. The activity was not detectable on poly(dA) or poly(dG) but was efficient on poly(dT) or poly(dC). However, the reliability of the primase assay in the presence of poly(dC) was dependent upon the degree of purification of the enzyme. The ribo primers were about 10 nucleotides long, and the reaction was completely independent of alpha-amanitin, a strong inhibitor of RNA polymerases II and III. Primase and polymerase were found tightly associated. A cosedimentation on a 5-20% sucrose gradient was always obtained, independent of the ionic strength. There was also a close coincidence between alpha-polymerase and primase activities during phosphocellulose, hydroxylapatite, and single-stranded DNA Ultrogel chromatography. It has been previously demonstrated by us and others that primase and alpha-polymerase are on separated polypeptides. The association of two activities in the replication complex and the conditions allowing their separation are discussed.

Animals↗
PubMed1986

Surface Plasmodium sugar-binding components evidenced by fluorescent neoglycoproteins.

A sugar-binding component was shown to be present at the surface of endoerythrocytic Plasmodium berghei and P. chabaudi stages and merozoites by means of a panel of neoglycoproteins using fluorescence microscopy and flow cytofluorometry. The protein nature of this material was ascertained by the loss of sugar-binding capacity upon trypsin treatment. This lectin-like protein primarily bound neoglycoprotein-borne N-acetylglucosamine and secondarily bound neoglycoprotein-borne alpha-D-glucose, beta-D-galactose and alpha-L-fucose. These results suggest the presence of at least one type of lectin-like protein with an extended binding site accomodating several sugar units, and define its localization on the parasite surface.

Animals↗
PubMed1986

[Kenacort retard].

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Delayed-Action Preparations↗
PubMed1984

Effects of glucocorticoids and antiglucocorticoid on angiotensinogen production by hepatoma cells in culture.

Angiotensinogen is synthesized in large amounts by Fao cells derived from the Reuber H35 rat hepatoma in a medium enriched with 5% fetal bovine serum (FBS). Treatment of FBS with dextran-coated charcoal removed endogenous steroids without modifying angiotensinogen production. This treatment allowed the study of the effects of steroids on angiotensinogen production. Hydrocortisone increased the angiotensinogen synthesis in a dose-dependent manner. The antiglucocorticoid RU 38486 did not change the basal rate of angiotensinogen production but inhibited the stimulation by hydrocortisone. Similar results were obtained with dexamethasone. Angiotensinogen biosynthesis seems to be regulated by two distinct mechanisms: (a) glucocorticoid independent, controlling the basal rate of angiotensinogen production and (b) glucocorticoid dependent, mediating the increased rate of angiotensinogen production upon glucocorticoid treatment.

Angiotensinogen↗
PubMed1984

Diabetes and insulin: actions and interactions upon the glucose metabolism of rat aorta.

We studied the glucose oxidation to CO2 and the incorporation of glucose into lipids by thoracic aorta from streptozotocin-diabetic rats in two circumstances: 9 minutes exposure of the isolated aorta to insulin, perfused in situ; and one-week treatment with either low--4 units (U)--or high--12 U--daily doses of insulin. Diabetes inhibited the glucose metabolism of media and adventitia. Perfusion with insulin did not influence the depressed metabolism of media but increased that of adventitia. Four units insulin treatment normalized the synthesis of glucose-derived lipids by the media, whereas 12-U treatment brought it to levels significantly higher (+23%) than those found in nondiabetic rats. We conclude that: (a) a haemodynamic explanation cannot account for the in vitro insulin resistance of media found in diabetes; (b) insulin treatment exerts a dose-dependent lipogenic effect upon the media, which might favour an atherogenic role for therapeutic hyperinsulinaemia in insulin-dependent diabetics.

Animals↗
PubMed1983

DNA-polymerases in neuron and glial cells of developing and aging mouse brain.

DNA-polymerases alpha and beta were studied in neuron and glial cells of mouse during developing and aging brain. Maximum activity of alpha-enzyme was found to be prenatal, though a very low but significant level could be detected in aging brain. Furthermore, this pattern was found to be dependent upon cell types that shift in peak activity just before birth in glial cells in contrast to neurons. DNA-polymerase-beta remained high throughout the period studied though a second peak of activity was also observed at day 30 in both cell types, suggesting a possible role in DNA-replication in addition to DNA-repair. It was found that beta-enzyme from glial cells behaves differently than the same enzyme from neurons.

Animals↗
PubMed1983

The three cortical membranes of the gregarines. I. Ultrastructural organization of Gregarina blaberae.

Gregarines, parasitic protozoa of invertebrates, possess a highly differentiated cell surface, with three cortical membranes and associated structures. Transmission electron microscopy and freeze-fracture reveal the presence of two cytomembranes lying uniformly under the plasma membrane. The density and the distribution of the intramembraneous particles (IMPs) in the plasma membrane of Gregarina blaberae are similar to those reported for other eukaryotic cells. The IMP density is lower in the cytomembranes than in the plasma membrane. The distribution of IMPs in the different fracture faces of the two cytomembranes suggests that they are in topological continuity, forming either side of a flattened vesicle or cisterna. The sizes of the cytomembrane IMPs show a high variability. The nature of the IMPs, both for the plasma membrane and the cytomembrane, is discussed with regard to the integral proteins and glycoproteins of the ghost. The cell surface of G. blaberae exhibits numerous longitudinal folds with three types of cortical membrane-associated structures: 12 nm filaments, an internal lamina, and homogeneous structures described as 'rippled dense structures'. The 12 nm filaments, running under the cytomembranes along the longitudinal axis of each fold, exhibit the properties of intermediate filaments. Their distribution in mature cells and during the growth process suggests a participation in cell surface morphogenesis. The internal lamina, also localized under the cytomembranes, would stabilize each fold and assure a scaffolding function between the numerous folds. The rippled dense structures, settled on the external cytomembrane, show a regular distribution at the top of each fold. The membrane-associated structures are discussed with regard to the gliding movement mechanism.

Apicomplexa↗
PubMed1983

Role of the 1-amino group in aminocyclitol antibiotics: synthesis of 1-deaminogentamicin C2.

The synthesis of 1-deaminogentamicin C2 described here, uses 3,2',6',3"-tetrakis-N-tert-butoxycarbonylgentamicin C2 (2) as intermediate. N-Formylation of 2 followed by per-O-acetylation and dehydration furnished the isocyanide 5. Radical-induced deamination of the latter using tri-n-butylstannane and removal of the protecting groups afforded the target 1-deaminogentamicin C2 (7). Its in vitro antibacterial activity is less than that of the parent gentamicin C2. The behaviour of 7 towards aminoglycoside-inactivating enzymes was also examined; interestingly, it was found to be neither substrate nor inhibitor for such enzymes. These results strongly suggest that the substitution pattern of the 1-position determines the biological properties of the aminoglycoside antibiotics.

Gentamicins↗
PubMed1982

The three cortical membranes of the gregarines (parasitic protozoa). Characterization of the membrane proteins of gregarina blaberae.

GREGARINES, WHICH ARE PARASITIC PROTOZOA LIVING IN INVERTEBRATES, POSSESS A CORTICAL STRUCTURE SPECIFIC TO THEIR VEGETATIVE STAGE: namely two additional cytomembranes are lying just under the plasma membrane. This cortical complex has been isolated by centrifugation on discontinuous sucrose gradients and characterized chemically. Its integrity was tested by electron microscopy. Ghost proteins were resolved by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. About 30 polypeptides of mol.wt. 15000-300000 were present in this fraction and four glycoproteins were detected after periodate/Schiff staining. Ten major proteins were labelled after lactoperoxidase-catalysed iodination. The GP(2) glycoprotein (41000-49000 apparent mol.wt.) appears to be a major component of the cell surface. Effects of trypsin and Pronase digestion on ghosts and cells were monitored by gel electrophoresis and by electron microscopy. Ghosts treated with low trypsin or Pronase concentrations (10-25mug/ml) became drastically disorganized; many proteins were vigorously attacked in comparison with those of control ghosts. Variations in proteinase-sensitivity of proteins are pointed out. The GP(3) glycoprotein (130000-160000 apparent mol.wt.) seemed to be the only glycoprotein released from the cell surface by trypsin. Whole cells treated under the same conditions or with higher proteinase concentrations (up to 1mg/ml) do not exhibit morphological modifications of the cell surface; furthermore, no discernible cleavage of membrane proteins was indicated by electrophoretograms. It is postulated that cell-surface proteins are protected by the dense carbohydrate cell coat. By using various different methods (change of ionic strength, detergent, denaturing agent, labelling experiment) it was possible to localize several major proteins within the protozoon cortical membranes.

Animals↗
PubMed1982

1-N-acylation of gentamicin C1a by a cyclic, chiral gamma-amino-alpha-hydroxy acid related to the (S)-4-amino-2-hydroxybutyric acid.

A semisynthetic aminoglycoside antibiotic 15, containing a cyclic gamma-amino-alpha-hydroxy acid, related to the 1-N-4-amino-2-hydroxybutyric acid (AHBA) side chain of butirosins and amikacin, has been prepared. Conveniently protected 3,2',6'-tris-N-tert-butoxycarbonylgentamicin C1a (12) was condensed with the phtalimido active ester 10 to give after catalytic reduction and deprotection, the hitherto unknown 1-N-substituted gentamicin C1a 15. The requisite side chain was synthesized from the readily available D-(-)-quinic acid. The antibacterial properties of 15 are given.

Acylation↗
PubMed1980

Study of dogfish (Scyliorhinus caniculus) deoxyribonucleic acid polymerase alpha and beta. Extraction, separation, characterization and changes during spermatogenesis.

DNA polymerase activity was extracted from testis cells of the dogfish Scyliorhinus caniculus. On a sucrose gradient, two main peaks could be separated, corresponding to DNA polymerases beta (3.8 S) and alpha (7.5 S). DNA polymerase gamma could also be detected when poly(A) . (dT)12 was used as template. The properties of alpha and beta polymerases of this primitive vertebrate were similar to those generally described, especially in mammals. The beta enzyme was highly sensitive to N-ethylmaleimide, however, and could use poly(dT) . poly(A) as template. Polymerase alpha was present in spermatogonia, spermatocytes and spermatids. Activity was maximal in spermatocytes. DNA polymerase beta was present in all testis cells with similar activities in spermatogonia and spermatocytes. Decreased activities were observed during spermiogenesis. Some activity remained associated with the chromatin fraction of mature sperm cells.

Animals↗
PubMed1980

Evidence for an unusual multifunctional protoreceptor in hormone action.

Contrary to the techniques of mere association, column chromatography has revealed a 'protoreceptor' that accepts aldosterone agonists and antagonists only in the physiological target, the kidney, and is absent in non-targets, liver and serum; it is furthermore different from the aldosterone specific receptor in renal cytosol.

Aldosterone↗