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Biomedical subjects

A Lemoine

Publications and source records attributed to A Lemoine.

90 records · Page 5Linked to original sources

[Vitamins and aging].

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Age Factors↗

[Molecular biology and hepatocellular carcinoma: current status and future prospects].

Hepatocellular carcinoma (HCC) is among the fifth most common cancers worldwide. Its incidence is still rising in part because of the high level of hepatitis C virus infection. Tumor markers currently used such as serum alpha-foetoprotein are not sufficient for diagnosis of the tumor and satisfying follow-up of the patients. Mechanisms of hepatocarcinogenesis ar not completely understood although several altered genes have been described in HCC. The genetic changes involved can be divided in at least 4 different pathways, each pathway contributing to a limited number of tumors. These are: 1) the p53 pathway involved in response to DNA damage, 2) the retinoblastoma pathway involved in the control of the cell cycle, 3) the transforming growth factor-beta (TGF-beta) pathway involved in growth inhibition, and 4) the Wnt pathway involved in cell-cell adhesion and signal transduction. Alterations of the epigenetic regulation of gene expression have also been described. Evolution of molecular biology methods tends to the development of more global genomic approaches; microsatellite instability analysis, chromosomal instability analysis or gene expression profile analysis have been used to investigate HCC. Finally, attempts to develop molecular biomarkers based on peripheral blood analysis more easily accessible in clinical routine patients have also been developed.

Biomarkers, Tumor↗

Effects of genetic or chemically induced diabetes on imipramine metabolism. Respective involvement of flavin monooxygenase and cytochrome P-450-dependent monooxygenases.

Imipramine metabolism has been studied in both type I (streptozotocin-induced insulin-deficient) and type II (genetically insulin-resistant) diabetes in mice. In both types of diabetes, the formation of imipramine N-oxide is increased. In type I diabetes, desmethyl- and 2-hydroxyimipramine are additionally increased. The inhibition of imipramine metabolism by anti-cytochrome P-450 reductase antibodies led to the conclusion that cytochrome P-450-dependent monooxygenases are not involved in the N-oxidation of imipramine. This metabolic route is only supported by the flavin monooxygenase, whose activity is increased by diabetes. The pharmacological implications of altered imipramine metabolism in diabetic states are discussed in relation to the drug metabolism in human diabetes.

Animals↗

Computer analysis of ocular results following selective blockade of growth-hormone in diabetic retinopathy. A collaborative study.

Computer storage and analysis of ocular data (visual acuity, fundus photographs and fluorescein angiographies) in diabetic retinopathy (DR) was used before and 1, 3 and 5 years after "Stereo-GIHF". This radiobiological procedure results in the selective inhibition of growth-hormone (GH) release. A series of 107 eyes were analyzed after division into 2 categories A and B (A: progressing background DR, n = 53, B: proliferative DR, n = 54). All patients treated by laser photocoagulation before and/or after stereo-GIHF were excluded from the present study; in contrast complications that impair visual acuity (VA), mainly vitreous hemorrhages, diabetic maculopathy and cataracts, were not discarded. In groups A and B, mean VA was stable showing no significant differences before and 5 years after treatment. In both groups microaneurysms are improved or stable in all cases. Hard exudates were improved in 66% of cases. In group B preretinal new-vessels and neovascularisation on the disc are improved or stable in 90% of cases. The same percentage is observed for extramacular and macular transudations 3 years after Stereo-GIHF. The present data strongly suggest that the selective suppression of GH improves the prognosis of DR. However the prognosis for vision remains poor in macular degenerations; in addition a rapid evolution of new-vessel formations should indicate a combined treatment with argon laser photocoagulation.

Adult↗

[Relationship between hepatic cytochrome P-450 3A and acute cyclosporine toxicity in liver transplantation].

Despite the availability of whole blood cyclosporine assays, the different response of individual patients to its administration following transplantation continue to pose clinical problems, particularly in respect of toxicity. The aim of this study was to know if the inter-individual variations in the hepatic concentration of cytochrome P-450 3A, that metabolizes cyclosporine into several metabolites with very limited immunosuppressive activity, could be associated with cyclosporine toxicity. 59 consecutive liver transplant recipients were studied. Immunosuppression was with cyclosporine, azathioprine and methylprednisolone. The relative concentration of P-450 3A was assessed by immunoblot analysis using a specific monoclonal antibody on liver graft biopsy. Twelve patients experienced toxic neurological and renal complications. Six of these patients had cyclosporine levels in the therapeutic range. There was an excellent correlation between the occurrence of complications and cyclosporine whole blood levels (P < 10(-4), the first day post-op after a standard dose of cyclosporine (1 mg/kg). Cytochrome P-450 3A hepatic content assessed in a groups of 34 patients exhibited a 10-fold variation (m = 94 +/- 47 AU (Arbitrary Units)/mg). Eight of these patients who developed cyclosporine toxicity had a lower graft P-450 3A levels (m = 52 +/- 19 AU/mg, P = 3.10(-4), cf. patients with no toxicity). This highlights the importance of the first dose of cyclosporine and indicates that cytochrome P-450 3A can provide information which should allow individualized immunosuppression with cyclosporine maintaining therapeutic levels but avoiding toxicity in susceptible individuals.

Acute Disease↗