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Biomedical subjects

F Joly

Publications and source records attributed to F Joly.

At least 55 records · Page 3Linked to original sources
PubMed1988

Biosynthesis of paf-acether. XI. Regulation of acetyltransferase by enzyme-substrate imbalance.

Acetyl-CoA:1-O-alkyl-sn-glycero-3-phosphocholine acetyltransferase is the key enzyme in paf-acether (paf) biosynthesis, since it yields the active mediator from its nonacetylated precursor, lyso-paf. In microsomal fractions obtained from the ionophore A23187-stimulated human polymorphonuclear neutrophils, the optimal conditions allowing the full acetylation of lyso-paf were: 2-2.5 mg.ml-1 bovine serum albumin, 40 microM lyso-paf, 200 microM acetyl-CoA and acetyltransferase of high specific activity, at least 18 nmol.min-1.mg protein- -1. The reaction frequently stopped before the substrate was consumed due to spontaneous decay of the enzyme activity at 37 degrees C and inhibition of the enzyme by the paf formed in the reaction. However, low concentrations of acetyltransferase substrates (lyso-paf or lysophosphatidylcholine) and the antioxidant dithiothreitol, but not the inhibitors of proteinases or phosphatases, protected the enzyme against decay. In contrast, high concentrations of those lyso substrates inhibited the enzyme activity in the assay. This inhibition as well as that due to paf was overcome by raising the concentration of the enzyme contained in the microsomal fraction or the bovine serum albumin in the assay. These results suggest that the biosynthesis of paf in cell-free assay and most probably in intact cells might be controlled to a larger extent by the acetyltransferase concentration rather than by that of its substrates.

Acetyltransferases↗
PubMed1988

[Efficacy of halofantrine in Plasmodium falciparum or Plasmodium vivax malaria in a resistance area (French Guiana)].

Halofantrine (WR 171.669) is a phenanthrene methanol derivative effective against the multidrug resistant strains of Plasmodium falciparum. One hundred and one patients, 48 men and 53 women, 53 adults and 48 children (less than or equal to 12 years old) aged from 1.5 to 57 years were treated. Fifty-one patients received a single 16 mg/kg dose and 50 patients received 24 mg/kg/day in 3 doses at 6-hour intervals. Parasite counts with examination of both thin and thick smears were performed twice daily for 5 to 6 days following treatment, or until smears were negative for parasites for 24 hours, and then weekly for 4 weeks. Thirteen patients reported clinical side effects. Six treated patients had no parasites. One patient had mixed parasitemia. Eighty three patients had P. falciparum malaria, with mean parasitemias between 26,850 +/- 36,679 and 35,412 +/- 50,527 per cubic millimeter. Halofantrine was very effective in the two doses tested from 87.5 to 100 p. 100. Eleven patients had in vivo resistant strains; ten in vitro tests were successful and nine were resistant to chloroquine. Thirteen patients with P. vivax and a mean parasitemia of 13,858 +/- 10,835 per cubic millimeter were cured but 3 had a relapse 3 to 4 weeks after treatment. At the 2 dosage levels tested halofantrine proved highly effective in the treatment of malaria caused by resistant and sensitive strains to P. falciparum.

Adolescent↗
PubMed1987

Ketotifen inhibits paf-acether biosynthesis and beta-hexosaminidase release in mouse mast cells stimulated with antigen.

Acetyl-CoA acetyltransferase (1-O-alkyl-sn-glycero-3-phosphocholine) is a key enzyme in paf-acether biosynthesis. Its immunological activation as related to paf-acether formation was investigated in mast cells derived from mouse bone marrow. The action of ketotifen, a prophylactic anti-asthma drug, on the antigen-induced activation of acetyltransferase and on the release of paf-acether and beta-hexosaminidase was studied in mast cells. Mast cells were sensitized with dinitrophenyl-specific monoclonal IgE and preincubated for 15 min at 37 degrees C with various concentrations of ketotifen or vehicle prior to challenge with dinitrophenyl coupled to bovine serum albumin (40 ng/ml). Acetyltransferase activity and mediator formation and release were measured. Ketotifen inhibited dose dependently the antigen-induced paf-acether formation and release, beta-hexosaminidase release and acetyltransferase stimulation. The IC50 values were 20.0 +/- 4.4, 11.8 +/- 6.2, 8.8 +/- 3.8 and 20.5 +/- 3.4 microM (mean +/- S.E.M., n = 3) respectively. Mast cells were preincubated with 50 microM ketotifen for 15 min at 37 degrees C then washed prior to antigen challenge. The release of paf-acether and beta-hexosaminidase and the stimulation of acetyltransferase were inhibited by 90.0 +/- 15.0, 91.0 +/- 15.0 and 88.0 +/- 11.0% (n = 3) respectively. In addition, Ca2+ entry was inhibited by 100% as assessed from Quin-2 fluorescence. Thus, the release of a preformed granular enzyme beta-hexosaminidase is inhibited by ketotifen together with the enzymatic formation of a newly formed mediator.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetyltransferases↗
PubMed1987

Biosynthesis of paf-acether. IX. Role for a phosphorylation-dependent activation of acetyltransferase in antigen-stimulated mouse mast cells.

Mouse bone marrow-derived mast cells passively sensitized with monoclonal IgE released paf-acether (platelet-activating factor) and beta-hexosaminidase when challenged with the specific antigen. The formation and the release of paf-acether followed an early increase in the activity of the acetyltransferase, the main enzyme in paf-acether biosynthesis. The antigen-induced activation of the acetyltransferase was dependent on physiologic temperature and on the presence of Ca2+. By using microsomal fractions from unchallenged and challenged mast cells, the Vmax values were 3.5 and 12.0 nmol/min/mg of protein, respectively, whereas in both cases a Km value for acetyl-coenzyme A of 172 microM was measured. The stimulation of acetyltransferase could be mimicked in vitro under experimental conditions which favor phosphorylation, i.e. adding ATP and Mg2+ to lysates from unchallenged mast cells. In contrast, ATP and Mg2+ were uneffective on lysates from challenged cells that exhibited high level of acetyltransferase activity, suggesting that phosphorylation of the enzyme already took place at the time of cell stimulation. Moreover, addition of alkaline phosphatase to microsomal fraction obtained from either antigen-challenged mouse bone marrow-derived mast cells or unchallenged cells, resulted in 52% and 43% loss of acetyltransferase activity, respectively. Phorbol myristate acetate treatment of cells doubled the enzyme activity supporting the phosphorylation hypothesis. Thus, we report on the immunologic activation of a key enzyme for paf-acether synthesis and on the mechanism of this activation in a pure mast cell population. A link between bridging of IgE receptors and the activation of an enzyme critical to the formation of a lipid mediator is thereby evidenced.

Acetyltransferases↗
PubMed1978

[Mitral commissurotomy under direct vision. 37 cases].

1 188 mitral commissurotomies were carried out between 1962 and 1976, 37 of them (3.1%) being under direct vision. The two operative deaths (5.4%) occurred early in the series. Longer term follow-up showed that 3 cases died secondarily, and 3 had revision surgery. The main complication was mitral incompetence (51% of operated cases had a systolic murmur). The varying indications and results are presented; these justify a prospective study, but not a recommendation for the systematic adoption of mitral commissurotomy by an open heart technique.

Adult↗
PubMed1977

[Long-term anticoagulant therapy in subjects over 75 years of age. 100 cases].

100 patients (median age 79 years) were given anticoagulant therapy (ACT) for a period of time averaging 5 years 3 months (522 follow-up years).--Out of 3 522 Quick tests, converted into prothrombin times and all carried out in the same laboratory, the prothrombin time was at or less than 32% in 60.5%, and 34% in 69.6% of the tests.--The mean therapeutic doses were less than 27% of those for adults, and were decreased by 3 mg of phenindione per year over the age of 75, only the actively treated cases being retained.--The risks are the same as those for the middle-aged adult. They depend more on the quality of the investigations than upon age. In the group which has been studied, slight or frank haemorrhagic complications (0.05/year/patient) were the result of a demonstrable overdosage in only one case in four. They were not responsable for any deaths in this series.--because of the referral patterns, the patients studied consisted of 79 with ischaemic heart disease, 27 with peripheral vascular disease, 9 cerebrovascular accidents, and 6 with thrombo-emoblic problems, not counting the 23 complications during the course of the study. In those patients with ischaemic heart disease, well-regulated anticoagulant treatment was associated with a favourable clinical course, and the correlation was significant.--there is not argument against the administering of a full and prolonged course of ACT to a patient of more than 75 years of age.

Age Factors↗
PubMed1975

[Course of telesystolic mitral insufficiency. Apropos of a case followed for 7 years and operated on].

One case followedup for 7 years with progressive intensification of regurgitation, requiring a surgical operation at the age of 48 years, brings its contribution to knowledge of the natural history of late systolic mitral incompetence and of the anatomical lesions causing it. The presence of prolapsed posterior leaflet, of stretched chordae tendinae, of both septal and parietal muscle hypertrophy with biloculation of the ventricular cavity were suggested by angiocardiography and confirmed by operation. A review of the literature reporting the cases with operative or post-mortem verification poses the unresolved question of the diagnostic criteria of late systolic mitral incompetence at the stage of cardiac failure.

Adult↗