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Biomedical subjects

C Moreau

Publications and source records attributed to C Moreau.

213 records · Page 12Linked to original sources

The insulin-like growth factor axis in cell cycle progression.

Emerging evidence suggests that members of the Insulin-like Growth Factors (IGFs) family, including IGF-I, IGF-II, the IGF-I receptor (IGF-IR), and the IGF-binding proteins (IGFBPs) play a central role in the development and progression of cancer. Cancer cells exhibit an increased and deregulated proliferative activity. Abnormalities in many positive and negative modulators of the cell cycle are also frequent in many cancer types. Recent advances in the understanding of cell-cycle control mechanisms have been applied to outline the molecular mechanism through which IGFs regulate cell cycle progression. In this review, we will provide a brief overview of the role of the IGF system as a regulator of some components of the cell cycle.

Animals↗

Chronic nitric oxide inhibition aggravates hypertension in erythropoietin-treated renal failure rats.

Alterations in nitric oxide (NO) and endothelin-1 (ET-1) production have recently been reported in erythropoietin (r-HuEPO)-induced hypertension in renal failure rats. The present study was designed to evaluate the effect of NO synthase inhibition with the L-arginine analog NG-nitro-L-arginine methyl ester (L-NAME) on blood pressure (BP) and ET-1 production in control and in uremic rats treated or not treated with r-HuEPO. Renal failure was induced by a two-stage 5/6 nephrectomy. Control and uremic rats were studied separately and subdivided into four groups: vehicle, r-HuEPO, L-NAME + vehicle and L-NAME + r-HuEPO. L-NAME (100 mg/kg/day), r-HuEPO (100 U/kg, subcutaneously, three times per week), the vehicle or both were administered during 4 weeks in control rats and during 2 weeks in uremic rats. Systolic BP was recorded before and after the onset of treatment at weeks 2 and 4 in control rats and at weeks 1 and 2 in uremic rats. Hematocrit, serum creatinine, plasma, blood vessel (thoracic aorta and mesenteric artery bed) and renal cortex immunoreactive (ir) ET-1 concentrations were measured at the end of the protocol. L-NAME enhanced BP in control and uremic rats and the increase was significantly higher in uremic rats under r-HuEPO therapy (222 +/- 7 mmHg vs 198 +/- 6 mmHg, p<0.05). L-NAME induced an increase in thoracic aorta ir-ET-1 concentrations in control and uremic rats. In contrast, ir-ET-1 concentrations were unchanged in the mesenteric arterial bed and the renal cortex of control and uremic animals. R-HuEPO increased thoracic aorta ir-ET-1 contents in L-NAME treated control and uremic rats. These results underline the important role of NO release in opposing the action of vasopressors on blood vessel tone which appears more important in uremic rats treated with r-HuEPO. L-NAME treatment increased large vessel, but not small resistance artery ir-ET-1 concentrations, suggesting differential regulation of ET-1 production in different vascular beds under chronic NO synthase inhibition.

Animals↗

The two SH2-domain-containing inositol 5-phosphatases SHIP1 and SHIP2 are coexpressed in human T lymphocytes.

The activation of many hematopoietic cells via cytokine receptors, as well as B and T cell receptors, leads to the tyrosine phosphorylation of Shc and its association with both Grb2-Sos1 complexes and with a 145 kDa protein referred to as the SH2 containing inositol 5-phosphatase (SHIP1). In a search of putative 5-phosphatase isoenzymes, we have isolated a second SH2 domain containing inositol 5-phosphatase, referred to as (SHIP2). Both SHIP1 and SHIP2 are coexpressed in human T lymphocytes. This was shown at the protein level by Western blot analysis in transformed T cell lines and in peripheral blood T lymphocytes either unstimulated or after in vitro activation through TCR-CD3 complex. SHIP1 protein level was not modulated after activation of T lymphocytes, in contrast to SHIP2, which was increased after long-term stimulation. SHIP1 was tyrosine phosphorylated in resting naive T cells. This was not observed in the transformed T cell lines. T lymphocyte is therefore a model of coexpression of the two SH2-containing inositol 5-phosphatases SHIP1 and SHIP2.

Amino Acid Sequence↗

Drug-induced transmembrane lipid scrambling in erythrocytes and in liposomes requires the presence of polyanionic phospholipids.

The asymmetric transmembrane distribution of phospholipids between the two bilayer halves of erythrocyte can be modified upon addition of cationic amphiphilic drugs, such as chlorpromazine or verapamil. We studied this phenomenon in erythrocytes and in lipid vesicles using spin-labelled analogues of the endogenous phospholipids. The extent of the rapid disappearance of the analogues from the erythrocyte outer leaflet depended on the concentration of the drug. Up to 40% of spin-labelled sphingomyelin moved to the inner erythrocyte leaflet in 10 min in the presence of 1.5 mm chlorpromazine. Verapamil or vinblastine gave similar results. On the other hand, the inside-outside movement of the aminophospholipid analogues was less evident, and did not exceed 10%. This apparent discrepancy between inward and outward movements could result from the formation of an endovesicle which is known to occur upon drug addition at high concentration. A fraction of lipids would be trapped in the intravesicular leaflet, corresponding to the cell outer leaflet, and be inaccessible both from the cytoplasm and the extracellular medium. In cells submitted to a metabolic depletion of cellular ATP the intensity of the scrambling induced by the amphipaths was drastically lowered. We attribute this effect to the important reduction of the membrane content in phosphatidylinositol-4,5-bisphosphate (PIP2). The involvement of the latter lipid in triggering scrambling was partly confirmed by experiments carried out with artificial membranes. Indeed, in large unilamellar vesicles PIP2 is required in order to obtain a rapid redistribution of phospholipids between the two leaflets upon addition of drugs. However, the extent of phospholipid redistribution was limited to 15-20%. This redistribution was also induced when the vesicle membrane contained di-anionic phospholipids (phosphatidylinositol-4-monophosphate or diphosphatidylglycerol), but did not occur when it contained mono-anionic phospholipids (phosphatidylserine or phosphatidylinositol). Some drugs such as methochlorpromazine, active in artificial membranes, were ineffective in erythrocyte membranes, probably because they could not cross the membrane and reach PIP2 molecules at the cytoplasmic leaflet.

Adenosine Triphosphate↗

[Anti-Gram-negative bacterial antibodies in alcoholic cirrhosis. Study of 58 patients].

Gram-negative bacterial infections are frequent and severe in cirrhotic patients. Existence of endotoxemia in cirrhosis is controversial. The demonstration of Gram-negative bacterial antibodies could be an alternative approach to the pathogenic role of these bacteria. In 58 patients with alcoholic cirrhosis, the immunoglobulin G specifically directed against the Gram-negative bacteria lipopolysaccharide expressed by the J5 mutant of Escherichia coli 0111:B4 was measured. Antibody titres were compared to those of a control group of blood donors. The distributions of antibody titres were similar in cirrhotic patients and in control subjects. No correlation was found between antibody titres and biological parameters of liver function. These results seem to confirm previous reports on the absence of latent endotoxemia in cirrhotic patients, and they suggest that antibody production against Gram-negative bacteria lipopolysaccharides is not enhanced in these patients.

Antibodies, Bacterial↗

[Implantation of a strain of "Escherichia coli" in the digestive tract of human new-borns: barrier effect against antibioresistant "E. coli" (author's transl)].

Twenty-two healthy human new-borns were inoculated within two hours of birth with a strain of Escherichia coli. This strain was isolated from the faecal flora of an healthy adult and was plasmid-free, nontoxigenic in vitro or in vivo, and sensitive to all usual antibiotics. This strain became established at a high population level within two days in all new-borns and remained at a very high level during the following days in almost all cases (86%). Strains of E. coli resistant to ampicillin or tetracycline were found in 6 of 22 inoculated infants as well as in 7 of the 24 control infants. These resistant strains remained at a very high level in the control infants but disappeared, or decreased to a subdominant level, in the inoculated infants. These results show that a totally innocuous strain of E. coli can exert in holoxenic conditions a barrier effect on antibiotic resistant E. coli strains. They also suggest the interest of inoculating such a strain at birth in order to prevent proliferation of potentially pathogenic bacteria.

Adult↗

[Anti-tumour cytostatic and cytotoxic properties of peritoneal exudate cells of conventional and germ-free mice, stimulated or not by "Corynebacterium parvum" (author's transl)].

The treatment by Corynebacterium parvum induced an increase of peritoneal cell number in conventional mice but no modifications in germ-free mice. Against YC8 tumoral target cells, cytostatic properties of peritoneal cells were of the same intensity in conventional and germ-free after C. parvum treatment. Against K.BALB cells, C. parvum treatment induced an increase of cytostatic properties from 9 to 93% in conventional mice and from 51 to 84% in germ-free mice. Cytotoxic properties were increased by C. parvum in conventional mice but were unchanged in germ-free mice. The bacterial flora could play a role in the cytotoxic and cytostatic properties of peritoneal cells in conventional mice.

Animals↗