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Biomedical subjects

E Nègre

Publications and source records attributed to E Nègre.

At least 19 recordsLinked to original sources
PubMed1996

Specific induction of fibronectin binding activity by hemoglobin in Candida albicans grown in defined media.

Fibronectin (FN) is a major component of host extracellular matrix that may play an important role in the initiation and dissemination of Candida albicans infections. Expression of FN binding requires growth of C albicans blastoconidia in complex medium, and the regulation of FN receptor expression is poorly understood. We now demonstrate that hemoglobin is a potent and specific inducer of FN receptor expression and describe a defined medium supplemented with hemoglobin that greatly and stably enhances the binding activity of C. albicans for soluble FN. Enhancement of FN binding by hemoglobin in strain 44807 was concentration dependent and was maximal at 0.1% hemoglobin with 20- to 80-fold enhancement. The hemoglobin-induced FN binding to C. albicans was saturable, with a Kd of 2.7 X 10(-8) M. Enhancement required growth of C. albicans in hemoglobin-containing medium, since simply exposing blastoconidia to hemoglobin in a nongrowing status did not enhance binding. Induction was reversible following removal of hemoglobin from the growth medium and not associated with germination. Inorganic or protein-bound iron was not sufficient for the induction, since other iron-containing proteins or inorganic iron salts were inactive. Growth in the simple medium yeast nitrogen base supplemented with hemoglobin increased cell adhesion to immobilized FN and to cultured monolayers of bovine corneal endothelial cells. These data suggest that hemoglobin may be an important regulator of FN binding activity in C. albicans and thus may play a role in its pathogenesis.

Animals↗
PubMed1994

The collagen binding domain of fibronectin contains a high affinity binding site for Candida albicans.

A 30-kDa proteolytic fragment from the gelatin/collagen-binding domain of fibronectin is a potent inhibitor of fibronectin binding to Candida albicans, with a molar inhibition constant equal to that of intact fibronectin. Recombinant and proteolytic fragments from the cell-, the fibrin I-, and the heparin II-binding domains also inhibit fibronectin binding, but are 13-1000-fold less active. In suspension, binding of fibronectin to C. albicans is regulated by growth conditions and is specific, saturable, time-dependent, reversible, and divalent cation-independent. Scatchard plot analyses indicate the presence of high affinity (Kd = 1.3 x 10(-9) M) and low affinity (Kd = 1.2 x 10(-7) M) receptors. Recombinant or proteolytic fragments from four binding domains of fibronectin promote adhesion of C. albicans. A recombinant fragment corresponding to the cell-binding domain but with the sequence Arg-Gly-Asp-Ser deleted promotes C. albicans adhesion and inhibits fibronectin binding to C. albicans with the same activity as the natural sequence. Furthermore, four peptides containing the Arg-Gly-Asp-Val sequence and the peptides CS-1 and Arg-Glu-Asp-Val did not block the binding of fibronectin to C. albicans. Thus, in contrast to the specific binding of soluble fibronectin, recognition of immobilized fibronectin by C. albicans is mediated by several domains of the protein. Interactions with the cell-binding domain are not mediated by the Arg-Gly-Asp or other known recognition sequences as it has been suggested. Binding of fibronectin also did not correlate with C3d binding to the avirulent clones of C. albicans strain H12 or with iC3b binding to variants of the strain 4918.

Amino Acid Sequence↗
PubMed1993

Inhibition of fibronectin binding and fibronectin-mediated cell adhesion to collagen by a peptide from the second type I repeat of thrombospondin.

The platelet and extracellular matrix glycoprotein thrombospondin interacts with various types of cells as both a positive and negative modulator of cell adhesion, motility, and proliferation. These effects may be mediated by binding of thrombospondin to cell surface receptors or indirectly by binding to other extracellular matrix components. The role of peptide sequences from the type I repeats of thrombospondin in its interaction with fibronectin were investigated. Fibronectin bound specifically to the peptide Gly-Gly-Trp-Ser-His-Trp from the second type I repeat of thrombospondin but not to the corresponding peptides from the first or third repeats or flanking sequences from the second repeat. The two Trp residues and the His residue were essential for binding, and the two Gly residues enhanced the affinity of binding. Binding of the peptide and intact thrombospondin to fibronectin were inhibited by the gelatin-binding domain of fibronectin. The peptide specifically inhibited binding of fibronectin to gelatin or type I collagen and inhibited fibronectin-mediated adhesion of breast carcinoma and melanoma cells to gelatin or type I collagen substrates but not direct adhesion of the cells to fibronectin, which was inhibited by the peptide Gly-Arg-Gly-Asp-Ser. Thus, the fibronectin-binding thrombospondin peptide Gly-Gly-Trp-Ser-His-Trp is a selective inhibitor of fibronectin-mediated interactions of cells with collagen in the extracellular matrix.

Amino Acid Sequence↗
PubMed1992

Heparin-binding peptides from the type I repeats of thrombospondin. Structural requirements for heparin binding and promotion of melanoma cell adhesion and chemotaxis.

Synthetic peptides derived from the type I repeats of human platelet thrombospondin containing a consensus sequence Trp-Ser-Xaa-Trp bind to heparin, promote cell adhesion, and inhibit heparin-dependent interactions of melanoma cells with extracellular matrix components (Guo, N. H., Krutzsch, H. C., Nègre, E., Vogel, T., Blake, D. A., and Roberts, D. D. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 3040-3044). In the present study, we further examined the structural requirements for activity of these peptides. The minimal active sequence for heparin or sulfatide binding based on inhibition studies is Trp-Ser-Pro-Trp, although an octapeptide is required for optimal activity. The 2 Trp residues and the Ser residue are essential. Peptides with more than 2 residues between the Trp residues are inactive. The Pro residue is essential for activity of the pentapeptide Trp-Ser-Pro-Trp-Ser, but some larger peptides with substitutions for the Pro residue are active. For direct high affinity binding to heparin, both the consensus sequence and a flanking sequence of basic amino acids are essential. Peptides containing the consensus sequence promote cell adhesion and act cooperatively with the adjacent basic amino acid sequence to promote cell spreading. Chemical modification of the Trp residues in the peptides with amino-terminal basic amino acids abolished both cell adhesion and heparin-binding. Peptides containing the consensus sequence and basic amino acids are chemotactic for A2058 human melanoma cells. The functional importance of this novel heparin and sulfatide-binding motif is suggested by its conservation in other members of the thrombospondin gene family, complement components, and in many members of the cytokine receptor and transforming growth factor beta superfamilies.

Amino Acid Sequence↗
PubMed1992

Heparin- and sulfatide-binding peptides from the type I repeats of human thrombospondin promote melanoma cell adhesion.

Peptides from the three type I repeats of human endothelial cell thrombospondin, containing the consensus sequence-Trp-Ser-Xaa-Trp-, bind to sulfated glycoconjugates including heparin and sulfatide. The peptides are potent inhibitors for the binding of thrombospondin, laminin, or apolipoprotein E to these ligands. The thrombospondin peptides that inhibit heparin binding, but not adjacent peptides from the thrombospondin sequence containing the previously identified adhesive motif Val-Thr-Cys-Gly, promote melanoma cell adhesion when immobilized on plastic. Melanoma cell adhesion to the immobilized peptides is inhibited by soluble recombinant heparin-binding fragment of thrombospondin. The peptides also inhibit heparin-dependent binding of thrombospondin or laminin to human melanoma cells. The active peptides lack any previously identified heparin-binding consensus sequences and most do not contain any basic amino acids. Studies with homologous peptides showed that the tryptophan residues are required for binding. Adjacent basic residues in the second type I repeat enhance binding to heparin but not to sulfatide. Thus the type I peptides of thrombospondin define a distinct class of heparin-binding peptides.

Amino Acid Sequence↗
PubMed1992

Antileishmanial drug targeting through glycosylated polymers specifically internalized by macrophage membrane lectins.

Antileishmanial chemotherapy is hampered by the location of the parasite within the phagolysosome of the macrophage, which restricts the bioavailability of many potentially useful antileishmanial drugs. In this study, the possibility of using antileishmanial drugs targeted to the infected macrophages by means of a chemical linkage to a neutral mannose-substituted poly-L-lysine carrier molecule was explored. The study was performed in an in vitro model with Leishmania donovani-infected murine macrophages. The antileishmanial activities of various synthetic constructs were compared with those of the free drugs and the pentavalent antimonial Pentostam, which was used as the positive control. The 50% effective dose of allopurinol riboside linked to the mannosylated poly-L-lysine was below 7.5 x 10(-6) M, while it was up to 3 x 10(-4) M for the free drug, indicating that the drug bound to the polymer was 50 times more active than the free drug. Control experiments with other constructs (e.g., allopurinol riboside linked to the mannose-free polymer) confirmed that the enhancement of activity was indeed achieved by means of the mannose homing device.

Animals↗
PubMed1989

Muramyl dipeptide bound to poly-L-lysine substituted with mannose and gluconoyl residues as macrophage activators.

Poly-L-lysine modified with mannose derivatives, the residual cationic charges of which being neutralized by N-acylation, were synthesized and used as carriers of a macrophage activator (N-acetylmuramyl dipeptide, MDP). The influence of the acylating agent on the targeting efficiency was investigated: a hydrosolubilizing group such as a gluconoyl moiety led to very efficient carrier conjugates, while an acetyl group did not. The effect of sugar and acyl content of the polymers was assessed using these compounds as inhibitors of red blood cell agglutination by Concanavalin A. The binding and specific endocytosis of poly-L-lysine substituted with several mannose derivatives and gluconoyl residues (GlcAx-, Man(y)-PLK) have been determined by a quantitative flow cytometry analysis. MDP bound to these conjugates was much more efficient in vitro than free MDP in macrophage cytostasis assays.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1983

[Reinforcement cerclage of dystrophic aortic rings].

Reinforcement of a dystrophic aortic ring with a purse string suture makes it possible to obtain perfect coaptation between prosthesis and ring whilst inducing sclerosis. The technique described here was used by the authors in 30 patients operated upon since June, 1980, and none of these needed reoperation for leakage. These results contrast most favourably with those previously obtained in similar anatomical conditions with conventional prosthesis insertion.

Aortic Valve Insufficiency↗
PubMed1981

[Long-term course of patients with Smeloff-Cutter aortic valve prosthesis].

The long-term results (5 to 12 years) of 77 patients with Smeloff-Cutter aortic valve prostheses are reported. These patients were comparable in age, preoperative clinical condition and type of aortic valve replacement. The postoperative follow-up period of this series was however significantly longer. The 5 year survival rate was of 87%. The causes of death included thromboembolism, infectious endocarditis and cardiac failure. Mortality was higher in the first 5 postoperative years : 2,4% patient-years compared to 1,5% patient-years in the following years. Thromboembolism and neurological complications were particularly rare, representing a risk of 1,04% patient-years but these complications were lethal in half the cases in which they occurred. No haemolytic complications were observed. Infective endocarditis always occurred in patients with a history of infection, the complication usually being late (after 3 years). The life expectancy of patients seen after 5 years is at least 5 additional years in 80% of cases. The haemodynamic profile of the prosthesis did not degrade with time. After 5 years, 58,6% of patients in functional Class IV at operation were in Class I or II afterwards. 84,4% of patients operated in functional Class III were in Class I or II, and 93% operated in functional Class II were in Class I or III. A control of 3 prostheses carried out by the Cutter laboratory after 10 and 11 years' function shows practically no deterioration of the prosthesis. The low incidence of thromboembolism, the absence of haemolysis and long-term deterioration of the prosthesis are particularly valuable characteristics of this prosthesis in the aortic position.

Adult↗
PubMed1976

[Pre-operative irradiation in the treatment of cancers of thoracic esophagus].

The authors analyse an homogeneous series (2 operators) of 650 patients operated on for thoracic oesophageal carcinoma, of which 185 were submitted to pre-operative irradiation with cobalt. Irradiation led to a definite increase in the resectability rate 74 p. 100 as against 62 p. 100. There was an increase in the mid-term survival rate, especially an increase of 5 p. 100 at 2 years, 8 p. 100 at 3 years, 6 p. 100 at 4 years; The 5 survival rate was little modified. It was 12 p. 100 for 290 cases, resection alone, and 15 p. 100 for 137 resections after irradiation.

Esophageal Neoplasms↗
PubMed1975

[Cancers of the thoracic esophagus in gastrectomized patients. Technical problems].

The authors report three cases of carcinoma of the thoracic part of the esophagus who had previously undergone gastrectomy. They study, in the absence of a stomach, the possibilities of restoration of digestive continuity after esophagectomy and describe three possibilities: -- mobilisation and use of the remaining gastric stump; --esophageal resection and anastomosis restoring continuity; -- colonic interposition. Of the three procedures used, only the first and last are advised by the authors.

Bronchial Fistula↗