Search PubMed⌕ Search

Biomedical subjects

E Lebrun

Publications and source records attributed to E Lebrun.

33 records · Page 2Linked to original sources

Differential effects of transforming growth factor-beta and epidermal growth factor on the cell cycle of cultured rabbit articular chondrocytes.

We examined the effect of transforming growth factor (TGF-beta) on the proliferative rate and cell cycle of cultured rabbit articular chondrocytes using cell counting, cytofluorometry, and [3H]-thymidine incorporation. In the presence of 2% or 10% FCS (fetal calf serum), TGF-beta at 0.01, 0.1, 1, and 10 ng/ml had an inhibitory effect on cell proliferation after 24 h exposure with a dose dependence only for 2% FCS. Flow cytometric analysis of cell DNA content at that time showed that a high proportion of cells were arrested in late S-phase (SQ or G2Q) in either 2% or 10% FCS-containing medium. In both cases, a disappearance of the cell blockage occurred between 24 and 48 h after TGF-beta addition. However, whereas a stimulation of cell proliferation rate was observed at that time in cultures containing 10% FCS, a dose-dependence inhibition of cell growth was detected, in contrast, for 2% FCS-treated cells. Presence of TGF-beta during the last 24 h was not necessary to release the arrested cells. Furthermore, platelet-poor plasma at 10% produced the same effects as FCS, suggesting that platelet-derived factors, such as platelet-derived growth factor (PDGF), could not be responsible for the release of blocked cells in this case. We compared the effect of TGF-beta to that of epidermal growth factor (EGF), used at an optimal concentration (10 ng/ml). In both slowly growing (2% FCS) and proliferating chondrocytes (10% FCS), EGF caused a significant increase of cell proliferation as early as 24 h. No arrest in late S-phase but an augmentation of the percentage of cells in S- and G2M-phases were observed. When combined, TGF-beta and EGF did not induce synergistic effect on the chondrocyte proliferation, as estimated by cell counting. [3H]-thymidine labeling showed that the factors induced identical maxima of incorporation but the peak occurred earlier for TGF-beta than for EGF (approximately 6 h versus 12 h, respectively). Although both factors induce similar cell-number increases at 48 h in 10% FCS-containing medium, these proliferative effects were due to different actions on the cell cycle. The present study indicates that TGF-beta induces first a recruitment of chondrocytes in noncycling SQ- or G2Q-blocked cells. The, the release of these cells may produce either apparent stimulation of cell proliferation if sufficient levels of an unknown serum factor are present (10% FCS) or an inhibition of growth rate when only reduced amounts of this factor are available (2% FCS).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

[Comparative topography of the catalytic sites of chromosomal dihydrofolate reductases and that of the enzyme encoded in R 67 plasmid from E. coli].

The trimethoprim-resistant dihydrofolate reductase specified in E. coli by plasmid R 67, when compared, with other enzymes catalyzing the same reaction, to have a dissimilar primary, secondary, tertiary and quaternary structure. In regard to the tertiary structure, we show here that the pteridine binding site, in the plasmid-encoded enzyme, has a geometrical similarity with that of other chromosomal specified reductases.

Binding Sites↗

[Heterogeneity of large granular lymphocyte leukemia. 2 cases].

Large cell granulocytic leukemia (LCGL) or proliferative lymphocyte T gamma disease, characterized cytologically by the presence of lymphocytes with intracytoplasmic azurophil granules, raises the problem of whether or not it is monoclonal in character. However, although it may resemble a chronic lymphoid T leukemia or Felty's syndrome, it differs by the constant finding of infiltration of the splenic red pulp by large granular lymphocytes. Studies of their immunologic phenotype and functional activity produce heterogeneous results. The disease course varies considerably: the serious nature of the infections, knowledge of the physiopathologic mechanism of the neutropenia and the importance of the tumoral syndrome could represent therapeutic indications the modalities of which have still to be defined.

Adult↗

[Pediatric emergencies in the Grenoble Medical Center].

In the Grenoble Medical Centre, pediatric emergency admissions have been drastically influenced by the opening of an Emergency Unit in May 1983. Our work was carried out one year after the opening in order to study the characteristics of the admitted children. The enquiry was done over 4 months, one month for each season of that year. A total of 1,382 children were included in the study. Thirty-four percent were seen for a medical advice (66% hospitalized). Children seen for medical advice are younger and mostly migrants. They live close to the hospital and are brought most often for fever. Fifty one per cent directly brought to the hospital by their parents for a first pediatric advice (49% were sent by their personal physician). Children directly brought by their parents are in majority infants and migrants. They are mostly admitted at night and morning and during the week-end. They are more frequently followed within the public mother-child health protection system ("Service de Protection Maternelle et Infantile", PMI).

Child↗

[Assignment, by proton magnetic resonance, of histidines of dihydrofolate reductase from chicken liver].

The effects of pH and temperature upon C epsilon 1 H resonances of the four histidyl residues of chicken liver dihydrofolate reductase in binary complex with methotrexate were studied by 500-MHz 1H NMR spectroscopy. The four histidines labelled a, b, c, d are distinguishable by their pK values and the chemical shifts of their C epsilon 1H protons. The local electromagnetic environment as deduced from X-ray studies at 2.9 A resolution was used as a basis for proposed assignment of the four histidines. The assignments were a: H42, b: H140, c: H131, d: H87. Furthermore the histidyl residue labelled c was shown to be upfield shifted in its C epsilon 1H proton in the enzyme-methotrexate complex compared to the native enzyme. The hypothesis of a conformational change of the protein is discussed.

Animals↗

[Chronic lymphocytic leukemia, erythroblastopenia, thymolipoma].

The association of B cell chronic lymphocytic leukemia and pure red cell aplasia in a 42 year-old patient led to the discovery of a thymic enlargement. After six weeks treatment including steroids, cyclophosphamide and three courses of plasma exchange without improvement, surgical thymectomy was followed by a reticulocytosis and remission of the red cell aplasia. The tumor was a thymolipoma. Characteristics of this are thymic tumor, his connections with pure red cell aplasia and in vitro differentiation of erythroid progenitors are discussed.

Adult↗

Image analysis of the heavy form of the acetylcholine receptor from Torpedo marmorata.

The structure of the heavy (H) form of the acetylcholine receptor, which comprises two covalently linked 250,000 Mr oligomers, has been investigated by numerical analysis of electron microscope images. Na-cholate solubilized Torpedo marmorata H-form receptor was reintegrated into artificial lipid vesicles and negatively stained with uranyl acetate prior to imaging in a conventional transmission microscope. The reconstituted preparations exhibited the standard polypeptide composition of the purified receptor (alpha 2 beta gamma delta) and the same transmembrane arrangement as in the native subsynaptic membrane. Covalent disulfide linkage between the two oligomers took place exclusively through the delta chains. In agreement with previous work (Cartaud et al., 1980) the H-form appeared as "doublets" of two coplanar 9 nm rosettes at a center-to-center distance of 9.2 +/- 1.1 nm. The relative angular orientation of the two rosettes in a doublet was examined by correlation analysis in the real space. It exhibited a marked variability, few of the doublets featuring any kind of symmetry, suggesting that the two oligomers of a doublets are connected via an extended and flexible chain or loop. The area of contact between the two rosettes of a doublet therefore does not necessarily represent a reliable clue as to the location of the delta chain within the structure. Averaged images obtained after reorientation and summation of up to 132 rosettes revealed the three major peaks and the two grooves already observed in previous studies. Two additional smaller peaks were identified. Tentative assignment of structural details to individual subunits was deduced from an examination of alpha-bungarotoxin-labeled doublets. The alpha subunits, which carry part or all of the acetylcholine binding sites, are probably located in nonadjacent positions in the vicinity of the newly found peaks. This assignment is consistent with the image analysis of receptor-toxin complexes recently reported by Zingsheim et al. (1982b).

Animals↗

[Cleidocranial dysostosis. Contribution to its study apropos of 2 personal cases (an isolated and a familial form)].

Cleidocranial dysostosis is a rare embryopathy affecting the whole osseous system. Anomalies predominate on skull, chest and dentition but the whole skeleton can be affected especially pelvic girdle and spine. An autosomal transmission is often demonstrable; isolated forms are very uncommon. We present two cases fortuitously diagnosed in our ward: a familial cleidocraniopelvic major form and an incomplete isolated form. The treatment must be especially oriented towards dental malformations.

Adolescent↗

[Relative orientation of the two oligomers composing the heavy form of the acetylcholine receptor from Torpedo marmorata].

The morphology of the heavy form (H) of the nicotinic acetylcholine receptor reintegrated into lipid vesicles after purification in the presence of sodium cholate is studied by numerical analysis of electron microscopy images obtained after negative staining. The analysis discloses a large variability in the relative orientation of the two alpha 2 beta gamma delta oligomers (L), suggesting a flexible mode of association between oligomers through the delta chains.

Animals↗

The structure of the lentil (Lens culinaris) lectin. Amino acid sequence determination and prediction of the secondary structure.

The subunit structure and complete amino acid sequence of the lectin extracted from Lens culinaris (LcL) seeds was determined. In previous studies, the primary structure of the alpha-chain (Mr = 5,710) was shown to be homologous to the alpha-chain of the lectin from Pisum sativum, the Vicia cracca glucose-specific lectin, and a region in the middle of the concanavalin A sequence (residues 70-121). The complete amino acid sequence of the beta-chain (Mr = 17,572) has been determined from 11 tryptic peptides, 4 peptides derived by chemical cleavage of the beta-chain at its three tryptophan residues, 11 peptides obtained after digestion with Staphylococcus aureus protease, and 5 tryptic peptides from the succinylated polypeptide chain. The extensive homologies by alignment of the alpha- and beta-chains of the L. culinaris lectin with portions of concanavalin A situated between 1 to 45 and 70 to 237, suggest that the L. culinaris and Canavalia ensiformis lectins have evolved from each other. A comparison was made between the secondary structure of the C. ensiformis lectin and the probable secondary structure of the L. culinaris lectin as predicted by two different methods. The results indicate that the folding of these two polypeptides has been particularly well conserved during evolution. It is suggested that the L. culinaris lectin is synthesized as a single polypeptide chain and cleaved subsequently into two or possibly three fragments, two of which would be alpha and beta and the third a fragment homologous to portion 46 to 69 in concanavalin A. As in favin, the amino acids postulated to be involved in the formation of the hydrophobic cavity and the sugar and metal binding sites are highly conserved in L. culinaris lectin.

Amino Acid Sequence↗

[Changes in pacemakers and the wearers of pacemakers as a result of the use of different electromagnetic energy sources].

Over the past decade there have been considerable advances in cardiac electrostimulation technologies. However, there are still reports of electromagnetic interference with pacemakers and pacemaker patients. We have studied the effects of various electromagnetic sources (short-wave diathermy, electrosurgical knives, electrotherapy and radiofrequencies) on both humans and animals. The results of the studies were completely negative and, therefore, we are convinced that today's pacemakers are much more reliable and hence less subject to interference from external electromagnetic sources. We performed the following tests: (a) Short-wave diathermy: various electrode positions in pigs and 8 patients with pacemakers. (b) Electrosurgical knives: several tests on pigs with unipolar electrosurgical knife; 6 tests on humans during automatic defibrillator implantation using two-pole electrosurgical knives; 23 pacemaker patients underwent abdominal surgery (3 inguinal hernias, 12 gastric resections; 6 cholecystotomies, 2 aortic aneurysms-with two-pole electrosurgical knives). (c) Electrotherapy (TENS): on pigs. (d) Radiofrequency (RF) for transcatheter ablation-several tests on pigs.

Animals↗