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E Favre

Publications and source records attributed to E Favre.

31 records · Page 2Linked to original sources
PubMed1992

Structure-activity relationships in platelet-activating factor (PAF antagonists). 6. Synthesis and in vitro antagonistic activities of 2-substituted 5-oxotetrahydrofurans.

The synthesis of 2,5-disubstituted tetrahedrofuran compounds as potential in vitro PAF antagonists is described. Results demonstrate that the structural requirements for potent PAF antagonist activity are: a moderate lipophilic group or a trimethoxyphenyl group in position-5, and a long aliphatic chain terminated by a cationic polar head in position-2. The cis-trans configuration does not induce any difference in biological activity. Some conformational features of the putative PAF receptor are proposed in light of the present findings.

Animals↗
PubMed1987

Orientation and vertical fluctuations of spin-labeled analogues of cholesterol and androstanol in phospholipid bilayers.

We have used ESR and NMR linewidth broadening by spin-labels to determine the overall orientation of spin-labeled analogues of cholesterol and androstanol in egg lecithin bilayers. While the cholesterol analogues were found to have a single orientation in each monolayer, with the acyl chain pointing towards the center of the bilayer, the androstanol analogue appeared, at least in sonicated vesicles, to experience two opposite orientations in the same monolayer, very likely with a rapid reorientation. The possibility of rapid vertical fluctuations of the sterol molecules within the phospholipid bilayer is also discussed.

Androstanols↗
PubMed1986

Interaction of cytochrome c with mixed dimyristoylphosphatidylcholine-dimyristoylphosphatidylserine bilayers: a deuterium nuclear magnetic resonance study.

Deuterium nuclear magnetic resonance (2H NMR) was used to study the interaction of cytochrome c (from horse heart) with bilayers of mixed dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylserine (DMPS). Three types of labeled lipids were used: chain-perdeuterated phosphatidylcholine (DMPC-d54), chain-perdeuterated phosphatidylserine (DMPS-d54), and phosphatidylserine labeled at the alpha-position of the head group (DMPS-d2). Liposomes containing equimolar mixtures of DMPC and DMPS were found to bind cytochrome c with a maximum ratio of about 1 mg of cytochrome c per 1 mg of DMPS. The 2H NMR spectra of equimolar mixtures of DMPC-d54-DMPS and DMPC-DMPS-d54 were examined with and without cytochrome c. No change of the NMR spectra of either DMPC or DMPS could be detected after protein addition, for temperatures both above and below the phospholipid phase transition region. On the other hand, in the liquid-crystalline state, the transverse relaxation time, T2e, was reduced by 30-40% after protein addition. Measurements of the spin-lattice relaxation time, T1, showed, under all circumstances, multiple components. For simplicity, we have examined the shape of the relaxation curves at short and long times. Addition of protein increased by 2-fold the value of the slow T1 component of DMPS-d54 but not that of DMPC-d54. Partially relaxed spectroscopy allowed us to assign this slow component (at least in part) to the methyl group and C2H2 groups near the methyl end of the chains, i.e., far from the binding sites of the extrinsic protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Outside-inside translocation of aminophospholipids in the human erythrocyte membrane is mediated by a specific enzyme.

When human erythrocytes are incubated with spin-labeled analogues of sphingomyelin, phosphatidylcholine, phosphatidylserine, or phosphatidylethanolamine, with a short beta chain (C5) bearing a doxyl group at the fourth carbon position, the labeled lipids incorporate readily in the outer monolayer. The incorporation is followed in fresh erythrocytes by a selective inward diffusion of the amino derivatives. This observation led us to postulate the existence of a selective ATP-dependent system that would flip aminophospholipids from the outer to the inner monolayer [Seigneuret, M., & Devaux, P. F. (1984) Proc. Natl. Acad. Sci. U.S.A. 81, 3751-3755]. This study further examines the nature of this selective transport and demonstrates that it is mediated by a specific membrane protein. By measurement of the initial rate of transverse diffusion of spin-labeled lipids incorporated at various concentrations in the membrane outer leaflet of packed erythrocytes, apparent Km values were determined for the phosphatidylserine and phosphatidylethanolamine analogues. A ratio of approximately equal to 1/9.4 [corrected] was obtained (KmPS/KmPE). Using spin-labels bearing either a 14N or a 15N isotope, we have carried out competition experiments allowing us to measure simultaneously the transport of two different phospholipids. By this procedure, we show that phosphatidylserine and phosphatidylethanolamine compete for the same transport site but that phosphatidylserine has a higher affinity, in agreement with a lower apparent Km. On the other hand, the slow diffusion of the phosphatidylcholine or sphingomyelin analogues has no influence on the transport of phosphatidylserine or phosphatidylethanolamine. Experiments carried out in ghosts loaded with ATP enabled us to determine the activation energies for phosphatidylserine and phosphatidylcholine transverse diffusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Transport↗
PubMed1986

[Energy-dependent translocation of amino-phospholipids in the erythrocyte membrane].

In this review, we show how the stability of the asymmetric transverse distribution of phospholipids and the physiological role of the asymmetric distribution can be explained. Experiments with paramagnetic or fluorescent lipids enabled us to show that in fresh red blood cells, i.e. containing ATP, and in resealed ghosts containing ATP (1 mM) the amino derivatives (phosphatidylserine and phosphatidylethanolamine) are selectively transported from the outer monolayer to the inner monolayer of the membranes. On the other hand, phosphatidylcholine and sphingomyelin are not carried and diffuse spontaneously with a very long characteristic time. The ATP-dependent carrier mechanism can be inhibited by protein reacting groups (N-ethyl maleimide and ortho-vanadate), which very probably implies a transmembrane protein specific for amino phospholipids. The affinity for phosphatidylserine seems slightly higher than that for phosphatidylethanolamine. In addition we show the close parallel between the transverse distribution of phospholipids and cell shape. This leads us to suggest that the phospholipid translocation would be used to maintain the natural discoid shape of red blood cells. A possible generalisation of this mechanism to other cells and its implications for endocytosis are discussed.

Adenosine Triphosphate↗
PubMed1985

Strong interactions between a spin-labeled cholesterol analog and erythrocyte proteins in the human erythrocyte membrane.

We have used a spin label analog of cholesterol bearing a nitroxide on the alkyl chain (26-nor-25-doxylcholestanol) to study cholesterol-protein interactions in the human erythrocyte membrane. As judged from the ESR spectrum, the spin label is readily incorporated into the membrane when added from a concentrated ethanolic solution to a cell or ghost suspension. With intact erythrocytes or white ghosts in isotonic buffer, the ESR spectrum is a superposition of a mobile component and a strongly immobilized component (outer hyperfine splitting 61-63 G). The latter corresponds to approx. 45% of the signal, a percentage which is barely affected by varying the temperature between 5 and 37 degrees C. Removal of the cytoskeletal proteins spectrin and actin by low ionic strength treatment or of all extrinsic proteins by alkali treatment of ghosts reduces the immobilized fraction to approx. 25%. The effect of controlled proteolysis of intrinsic proteins was also tested. Pre-treatment of cells with chymotrypsin or pre-treatment of unsealed ghosts with trypsin has no effect on the ESR spectrum obtained with alkali-treated membranes. On the other hand, after chymotrypsin treatment of unsealed ghost, which reduces the band 3 protein to a 17.5 kDa membrane fragment, the strongly immobilized component is no longer observable. These data show that the cholesterol analog 26-nor-25-doxylcholestanol interacts strongly with one or several proteins of the erythrocyte membrane. That the intrinsic protein band 3 is involved is suggested by the disappearance of the immobilized fraction occurring upon chymotrypsin digestion of this protein. Our results are thus consistent with the proposal of a selective cholesterol-band 3 interaction in the erythrocyte membrane (Schubert, D. and Boss, K. (1982) FEBS Lett. 150, 4-8). Our data also suggest that this interaction is influenced by cytoskeletal proteins, an effect which can be explained considering the known linking of band 3 to the erythrocyte cytoskeleton via ankyrin. Experiments have also been carried out with 3-doxylandrostanol, a more commonly used cholesterol spin-label analog. With this spin label, at all temperatures investigated, we found it impossible to demonstrate unambiguously the existence of two spectral components. It is suggested that 26-nor-25-doxylcholestanol is a better reporter of cholesterol behavior in membranes.

Anion Exchange Protein 1, Erythrocyte↗
PubMed1977

[Operative mortality, mortality and late results in bronchial carcinoma].

457 patients with a bronchial carcinoma of the years 1947--1962 are compared with 126 patients of the years 1969--1970 and set up in comparison to the whole clinical material of the years 1960--1975. In the period between 1969 and 1970 radical resections were performed in 20% more patients than in the first period (1947--1962). Older patients were in the last period (1970--1974) more frequent. 8% of all patients in which lobectomy was performed and 5.5% of the patients in which pneumonectomy was performed were older than 70 years of age. Overall mortality has remained unchanged for exploratory thoracotomy (19%), palliative resection (17.5%) and "radical" resection (14%). For simple pneumonectomy the overall mortality went down from 19.2% (1960--1964) to 9.6% (1970-1974) and for simple lobectomy from 14.4% to 3.8%. The five-year survival rate after radical resections was 8% (first period 0%) and after simple resections 26% (26.2%). Patients with stage I epidermoid carcinoma had a five-year survival rate of 46%. Those with stage II (spread to ipsilateral hilar nodes) a five-year survival rate of 14.3% Patients with palliative resections and exploratory thoracotomy died within 16 months.

Aged↗