Progression of familial adenomatous polyposis (FAP) colonic cells after transfer of the src or polyoma middle T oncogenes: cooperation between src and HGF/Met in invasion.

Little is known about the the signalling pathways driving the adenoma-to-carcinoma sequence in human colonic epithelial cells. Accumulation and activation of the src tyrosine kinase in colon cancer suggest a potential role of this oncogene in this early progression. Therefore, we introduced either activated src (m-src), polyoma-MT alone or combined with normal c-src in the adenoma PC/AA/C1 cell line (PC) to define the function and phenotypic transformations induced by these oncogenes in familial adenomatous polyposis (FAP) colonic epithelial cells. Functional expression of these oncoproteins induced the adenoma-to-carcinoma conversion, overexpression of the hepatocyte growth factor (HGF) receptor Met, but failed to confer invasiveness in vivo and in vitro, or to produce alterations in cell proliferation and differentiation. In contrast, PC-msrc cells became susceptible to the HGF-induced invasion of collagen gels and exhibited sustained activation of the pp60src tyrosine kinase and Tyr phosphorylation of the 120-kDa E-cadherin, which was further increased by HGF Transcripts of HGF were clearly identified by reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot in the parental and transformed PC cells, suggesting an autocrine mechanism. Taken together, the data indicate that: (1) experimental activation of src and PyMT pathways directly induces tumorigenicity and Met upregulation in a colon adenoma cell line; (2) HGF-activated Met and src cooperate in inducing invasion; (3) in view of the molecular associations between catenins and cadherin or the tumour-suppressor gene product APC, the cell adhesion molecule E-cadherin may constitute a downstream effector of src and Met

Socioeconomic determinants of psychotropic drug utilisation among elderly: a national population-based cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Psychotropic drugs are commonly utilised among the elderly. This study aimed to analyse whether two socioeconomic determinants - income and marital status - are associated with differences in utilisation of psychotropic drugs and potentially inappropriate psychotropic drugs among elderly in Sweden.</p> <p>Methods</p> <p>All individuals aged 75 years and older who had purchased a psychotropic drug in Sweden during 2006 were included (68.7% women, n = 384712). Data was collected from national individual-based registers. Outcome measures were utilisation of three or more psychotropic drugs and utilisation of potentially inappropriate psychotropic drugs, as classified by the Swedish National Board of Health and Welfare.</p> <p>Results</p> <p>Individuals with low income were more likely to utilise three or more psychotropic drugs compared to those with high income; adjusted odds ratio (aOR) 1.12 (95% confidence interval [CI] 1.10-1.14). The non-married had a higher probability for utilising three or more psychotropic drugs compared to the married (aOR 1.22; CI 1.20-1.25). The highest probability was observed among the divorced and the never married. Potentially inappropriate psychotropic drugs were more common among individuals with low compared to high income (aOR 1.14; CI 1.13-1.16). Compared to the married, potentially inappropriate psychotropic drug utilisation occurred more commonly among the non-married (aOR 1.08; CI 1.06-1.10). The never married and the divorced had the highest probability.</p> <p>Conclusions</p> <p>There was an association between socioeconomic determinants and psychotropic drug utilisation. The probability for utilising potentially inappropriate psychotropics was higher among individuals with low income and among the non-married.</p

Psychotropes et dépendance: profils de consommateurs et trajectoires de leur consommation

Observatoire Français des Drogues et Toxicomanie

Évaluation des connaissances sémantiques de la temporalité au cours du vieillissement normal et de la maladie d’Alzheimer aux stades légers à modérés, étude préliminaire

National audienceDes processus tant épisodiques que sémantiques sous-tendent la temporalité de la vie quotidienne. La mémoire épisodique situe un événement dans le temps. Les connaissances sur sa segmentation et sa représentation symbolique appartiennent à la mémoire sémantique. Ce domaine de la mémoire sémantique est peu exploré dans la maladie d’Alzheimer (MA) faute d’outil adapté. L’originalité du travail présenté dans cet article est la mise au point d’une évaluation exploratoire de la sémantique de la temporalité (EST) par la lecture de l’heure, la capacité à utiliser le cadran, la connaissance de la segmentation temporelle du calendrier, l’estimation de durée. La validation de l’EST a été réalisée auprès d’un groupe témoin avant d’être proposée à des patients atteints de MA légère à modérée. Les résultats montrent que l’âge et le niveau culturel influencent les scores qui sont indépendants du genre chez les témoins et les patients. Il existe une altération des processus sémantiques liés à la temporalité dans la MA, corrélée avec l’évaluation globale du degré de sévérité de la maladie, l’attention, les fonctions exécutives. La dépression n’est pas apparue influencer les résultats en sémantique de la temporalité. Une version modifiée de l’EST, utilisable en pratique courante, est proposée à l’issue de ce travail. L’évaluation présentée permet le repérage et le suivi des troubles sémantiques de la temporalité. Elle apprécie les sources de difficultés dans la relation que les patients MA entretiennent au temps dans leur vie quotidienne. En outre, ce constat ainsi établi, ce travail débouche sur la possibilité de proposer aux professionnels et aux aidants des adaptations environnementales en adéquation avec les besoins des patients dans ce domaine

Health impact assessment of artificial ultraviolet radiation from sunbeds on cutaneous melanoma in France

International audienceno abstrac