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Biomedical subjects

M C Prevost

Publications and source records attributed to M C Prevost.

30 records · Page 2Linked to original sources

Signal transducing mechanisms in human platelets stimulated by cotton bract tannin.

Cotton bract tannin is a potent stimulus for platelet aggregation and secretion. Tannin has been shown to stimulate the phosphorylation of two 19-kD and 47-kD cytosolic proteins in platelets, but earlier steps in signal transducing mechanisms of platelet activation are unknown. In this study, measurements of 32P-labeled phospholipids, 14C-labeled arachidonic acid, and levels of intracellular free calcium (Ca2+) were performed before and after the addition of thrombin (1 U/ml) or various concentrations of tannin to human platelets. The results showed that tannin induced a dose-dependent synthesis of phosphatidic acid, an early and transient hydrolysis of phosphatidylinositol monophosphate and bisphosphate, a transient synthesis of diacylglycerol, and a release of arachidonic acid metabolites. The kinetics of phosphatidic acid, diacylglycerol, and arachidonic acid metabolite synthesis were similar after platelet stimulation by tannin (75 micrograms/ml) or thrombin. Tannin also induced a reversible rise of intracellular Ca2+ due to a mobilization of the internal stores and an influx of extracellular Ca2+. These results suggest that cotton bract tannin, as thrombin, activates human platelets by phospholipase C and A2 activations, release of diacylglycerol, and mobilization of intracellular free Ca2+.

Arachidonic Acids↗

Amiodarone-induced pulmonary toxicity. Immunoallergologic tests and bronchoalveolar lavage phospholipid content.

Amiodarone (A) is a widely-used antiarrhythmic drug. Pulmonary toxicity is the most serious adverse effect with an estimated mortality of 1 to 33 percent. In order to determine an element helpful for diagnosis, we examined four patients with amiodarone-induced pulmonary toxicity, three patients treated with A, without evidence of pulmonary toxicity but with a main underlying pulmonary disease, and four healthy volunteers. Daily and cumulative doses or duration of treatment were similar in the first two groups. Pulmonary function tests (spirometry, CO-diffusing capacity, arterial blood gases), roentgenographic examinations, pulmonary biopsies or immunoallergologic tests (skin reaction, lymphoblastic transformation test and human basophile degranulation test) did not provide any discriminatory element. In APT+, we observed an increased cellularity of the bronchoalveolar lavage. Neither the differential cell count nor the presence of foamy macrophages were distinguishable between APT+ and APT-. The phospholipid composition of BAL fluid showed a decreased total phospholipid and phospholipid/protein ratio in all patients compared to normal subjects. These changes reflect more the severity of pulmonary disease than the specificity of the causative agent. However, we observed that the unique PL which decreases in APT- and remains normal in APT+ is phosphatidyl-serine + phosphatidylinositol (PS + PI). This has to be confirmed and should be evaluated at different stages of the disease to determine an eventual specific element. We conclude that there are no data currently available to establish the diagnosis of APT except perhaps for the analysis of BAL PL content.

Aged↗

Effects of hypergravity on adherent human cells.

In recent years, accumulating evidence has shown that microgravity or hypergravity may affect cell growth and differentiation. Since it is not easy to carry out researches in space or to simulate weightlessness on earth, we conducted experiments on simulated hypergravity (2 to 15 g) by using a centrifuge (radius: 80 cm; speed motor: 180 rpm). We looked for the effects of chronic hypergravity (7 to 10 days) on cultures of three human cell lines: lung or dermic fibroblasts and lung adenocarcinoma A 549 cells. The results showed a significant decrease (10-20%, P<0.05) in cell proliferation connected to a significant decrease (20-50%, P<0.01) in culture DNA content under hypergravity, but only for lung fibroblasts. The protein content was never disturbed. Dermic fibroblast elastase activity was enhanced (8-13%, P<0.02) under 15 g. Total phospholipid content as well as relative amounts of phospholipid components, analysed by thin layer chromatography, were unchanged in A 549 cells.

Adenosarcoma↗

Activity of cilofungin (LY 121019), a new lipopeptide antibiotic, on the cell wall and cytoplasmic membrane of Candida albicans. Structural modifications in scanning and transmission electron microscopy.

Cilofungin, a new biosemisynthetic analog of echinocandin B, inhibits the synthesis of beta-(1,3)-glucan resulting in severe modifications of the cell wall and cytoplasmic membrane of sensitive organisms. The morphological modifications to budding yeast cells, pseudomycelium, mycelium and germ tubes of Candida albicans were studied by scanning and transmission electron microscopy after 3 and 16 h exposure to cilofungin. Changes in yeast cell morphology were apparent after 3 h in 0.1 microgram ml-1 cilofungin but were more marked in 1 and 10 micrograms ml-1 cilofungin. Most of the yeasts failed to separate and formed aggregates. Cracks and discontinuities were present in the cell wall and the cell membrane became undulated and fractured. Inclusions into the periplasmalemma space were observed, along with a release of cellular components. An important inhibition of germ tube formation was noted and the structure of true mycelium and pseudomycelium was severely modified. The budding area of yeast cells was particularly susceptible to damage by cilofungin.

Antifungal Agents↗

Effects of hypergravity on lung carcinoma cells maintained in continuous organotypic culture.

The effects of hypergravity levels ranging from 1 to 15 g were studied on A549 lung adenocarcinoma cell line, cultivated as nodules. This organotypic culture model preserves as closely as possible the cellular structures and differentiation functions of the in vivo situation. Nodules submitted to hypergravity conditions for 27 d did not show any change of cell growth, protein and DNA contents, compared with controls. Also, cellular differentiation, as regards intracellular phospholipid composition and more particularly phosphatidylcholine content, appeared undisturbed. The only obvious effect of hypergravity was a modification of the structural organization, with a disappearance of the large alveoli present at the surrounding of control nodules and the development of a dense cellular mass instead.

Adenocarcinoma↗

Wood degradation by white rot fungi: cytochemical studies using lignin peroxidase-immunoglobulin-gold complexes.

Using an anti-lignin peroxidase antiserum-protein A-gold complex, we found lignin peroxidase mainly intracellularly in several white rot fungi colonizing sawdust under laboratory conditions. This enzyme was also present in fungi found in naturally decayed wood. However, in all cases, lignin peroxidase was located mainly inside the fungal cells. Labeled lignin peroxidase did not bind to the lignocellulosic samples tested, with the exception of poplar milled-wood lignin. These results are discussed in relation to the role of lignin peroxidase during wood degradation.

Journal Article↗

Platelet activating factor (PAF-acether) is released into rat pulmonary alveolar fluid as a consequence of hypoxia.

Hypoxia provokes pulmonary constriction and because PAF-acether is a very strong pulmonary constrictor, we looked for PAF-acether in lung alveolar lavage (LAL) with a biological method based on the measurement of rabbit platelet aggregation. We first demonstrated a PAF-acether secretion during bronchoalveolar lavage with sterile isotonic NaCl (pH 7.2). PAF-acether secretion was completely suppressed with isotonic NaCl containing 5 mM EDTA but lyso-PAF-acether was still present (1.9 +/- 0.55 nmoles). Upon hypobaric hypoxia, PAF-acether was detected in LAL (1.05 +/- 0.25 10(-2)nmoles). The amount of lyso-PAF-acether increased by 6 times (12.1 +/- 4.1 nmoles). These results are given for 10(4) nmoles phospholipids of LAL. They indicate that alveolar macrophages might be activated by hypobaric hypoxia, so they produce PAF-acether in the alveole. Such a process could be involved in the well-known bronchoconstriction accompanying hypoxia.

Animals↗

Renal effect of clonidine during acute hypobaric pressure breathing in normal and diabetes insipidus rats.

The renal effects of clonidine (100 and 500 micrograms/kg s.c.) during acute hypobaric pressure breathing (i.e. a protocol which induces an increase in intrathoracic blood volume) were studied in normal and diabetes insipidus rats. In normal rats, clonidine enhanced the increase in urine flow and urea concentration elicited by hypobaric breathing without change in urinary creatinine level. By contrast, in Brattleboro diabetes insipidus rats, clonidine reinforced the hypoxia-induced mechanisms: oliguria, decrease in both urinary urea and creatinine excretions. During normobaric and hypobaric conditions in normal rats administration of clonidine induced an increase in electrolytes (Na+, K+, Cl-) excretion. In Brattleboro rats, clonidine potentiated the decrease in electrolytes excretion elicited by the hypobaric pressure breathing. Since the diuretic reflex elicited by the hypobaric pressure breathing is due to an inhibition of vasopressin release, the present data show that clonidine induces an inhibition of vasopressin release. However, it is suggested that beside this property clonidine also possesses direct vasoconstrictor actions during hypobaric pressure breathing.

Animals↗

Biochemical modifications of pulmonary surfactant after bromhexine derivate injection.

The authors study the influence of bromhexine metabolite VIII on phospholipid and fatty acid composition comparatively to controls. The subcutaneous injection of NA 872 produces on pulmonary surfactant an increase of 43% of total phospholipids. This change in the distribution of phospholipids is shown by the increase of 53% of phosphatidylcholines. A rise of 61.9--74.4% of palmitic acid appears in the phosphatidylcholines of the pulmonary surfactant. It can be noticed that the specific activity of the phosphatidylcholines rises by 31%.

Animals↗

Pulmonary surfactant and dog lung transplant.

The pulmonary sufactant was studied in the dog after crossed lobe autotransplantation and the influence of graft preservation time before reimplantation was considered. 1) The phospholipid composition of the grafted lobe is unchanged. 2) The incorporation of 32P orthophosphate in phosphatidylcholines is increased in the entire grafted lung (transplanted and ungrafted lobes). 3) Conservation of the graft for 48 hrs before the autograft changes neither surfactant composition nor 32P incorporation.

Animals↗

Guinea pig tracheal epithelial cells in primary culture: morphological and metabolic characterization.

The tracheo-bronchial epithelial cells are the first cells of the respiratory tract to encounter inhaled pathogens or allergens. In order to study these interactions in vitro we developed a culture of epithelial cells from guinea pig trachea which were kept as a primary culture for 3-13 days. Electron microscopy showed that the specific ultrastructure of epithelial cells was maintained, particularly cytokeratin intermediate filaments detected by immunofluorescence. The cells in culture produced eicosanoid metabolites, mainly leukotriene B4 and prostaglandin E2 spontaneously and upon calcium ionophore A23187 stimulation.

Animals↗