[The public health department of the Western French Guiana Hospital: a 5-year return of experience]. / Le département de santé publique du centre hospitalier de l'ouest guyanais : un retour d'expérience à cinq ans.

INTRODUCTION: The western French Guiana hospital (Chog) is atypical. The creation of a public health department (PSP) is the result of a willingness of the institution to respond to public health issues on its territory. The main objective of this article is to identify the levers and impediments for the development of public health activities within this hospital, after five years of implementation. METHOD: This article was based on the analysis of documents produced within the PSP, the institution and at the regional level (2013-2018), and on interviews conducted in 2017 with PSP professionals, and chiefs of other departments of the Chog (N = 16). RESULTS: The added value of the PSP is based on the pooling of human resources and technical skills, the coexistence of clinical activities, prevention, research, teaching and international cooperation with Suriname, and the development of multidisciplinary and evaluative approaches. The lack of a set of public health objectives in the establishment project, the lack of place for these activities in its new hospital, and the difficult mobilization of financial resources, however, limit the prospects. CONCLUSION: This analysis has shown difficulties in developing public health activities within this hospital, in an overseas territory with nonetheless multiple and complex needs. The authors invite politics and health authorities to value, and develop these activities, conditions necessary for the positioning of the hospital as an actor of the “turn in prevention”.

[The public health department of the Western French Guiana Hospital: a 5-year return of experience] / Le département de santé publique du centre hospitalier de l'ouest guyanais : un retour d'expérience à cinq ans.

INTRODUCTION: The western French Guiana hospital (Chog) is atypical. The creation of a public health department (PSP) is the result of a willingness of the institution to respond to public health issues on its territory. The main objective of this article is to identify the levers and impediments for the development of public health activities within this hospital, after five years of implementation. METHOD: This article was based on the analysis of documents produced within the PSP, the institution and at the regional level (2013-2018), and on interviews conducted in 2017 with PSP professionals, and chiefs of other departments of the Chog (N = 16). RESULTS: The added value of the PSP is based on the pooling of human resources and technical skills, the coexistence of clinical activities, prevention, research, teaching and international cooperation with Suriname, and the development of multidisciplinary and evaluative approaches. The lack of a set of public health objectives in the establishment project, the lack of place for these activities in its new hospital, and the difficult mobilization of financial resources, however, limit the prospects. CONCLUSION: This analysis has shown difficulties in developing public health activities within this hospital, in an overseas territory with nonetheless multiple and complex needs. The authors invite politics and health authorities to value, and develop these activities, conditions necessary for the positioning of the hospital as an actor of the “turn in prevention”.

Le département de santé publique du centre hospitalier de l'ouest guyanais : un retour d'expérience à cinq ans.

INTRODUCTION: The western French Guiana hospital (Chog) is atypical. The creation of a public health department (PSP) is the result of a willingness of the institution to respond to public health issues on its territory. The main objective of this article is to identify the levers and impediments for the development of public health activities within this hospital, after five years of implementation. METHOD: This article was based on the analysis of documents produced within the PSP, the institution and at the regional level (2013-2018), and on interviews conducted in 2017 with PSP professionals, and chiefs of other departments of the Chog (N = 16). RESULTS: The added value of the PSP is based on the pooling of human resources and technical skills, the coexistence of clinical activities, prevention, research, teaching and international cooperation with Suriname, and the development of multidisciplinary and evaluative approaches. The lack of a set of public health objectives in the establishment project, the lack of place for these activities in its new hospital, and the difficult mobilization of financial resources, however, limit the prospects. CONCLUSION: This analysis has shown difficulties in developing public health activities within this hospital, in an overseas territory with nonetheless multiple and complex needs. The authors invite politics and health authorities to value, and develop these activities, conditions necessary for the positioning of the hospital as an actor of the "turn in prevention".

Effect of laminin-1 on intestinal cell differentiation involves inhibition of nuclear nucleolin.

Intestinal epithelial cells are characterized by continuous renewal and differentiation events, which may be influenced by the basement membrane, and in particular laminins, which are major components of this specialized extracellular matrix. The function and signaling pathways of laminins in these processes are still poorly documented. In this study, we investigated the possible role and the subcellular localization of nucleolin, a nuclear shuttling protein, in relation to differentiation of human intestinal epithelial Caco2/TC7 cells triggered by exogenous laminin-1. Immunofluorescence and Western blot analysis indicated that laminin-1 induced early differentiation of the cells concomitantly to a decrease in nuclear nucleolin and its a cell surface location. We also showed that both effects of laminin-1 on Caco2/TC7 cells--induction of the differentiation marker sucrase-isomaltase and redistribution of nucleolin--could be mediated by a beta1-integrin dependent cascade that implicated activation of the p38 MAPK pathway. In addition, knock-down of nucleolin expression by the small interfering RNA strategy mimicked the effect of laminin-1 as it resulted in the induction of cell polarization and differentiation. Thus, our study suggests that changes in the subcellular distribution and expression level of nucleolin play an important role in intestinal cell differentiation and relay the signaling pathway induced by laminin-1.

Laminin isoforms: biological roles and effects on the intracellular distribution of nuclear proteins in intestinal epithelial cells.

Laminins are structurally and functionally major components of the extracellular matrix. Four isoforms of laminins (laminin-1, -2, -5 and -10) are expressed in a specific pattern along the crypt-villus axis of the intestine. Previous works indicated that expression of these isoforms is developmentally regulated and that laminins could modulate the behaviour of intestinal cells, but the exact role of each isoform remained unclear. Here, we report the first systematic analysis of the cellular functions of the four isoforms using the human colon adenocarcinoma Caco2/TC7 cell line as a model. We compared the respective abilities of each isoform to modulate adhesion, proliferation and differentiation of intestinal epithelial cells. We found that the isoforms were functionally distinct, with laminin-10 being the most adhesive substratum, laminin-2, laminin-5 and laminin-10 enhancing cellular proliferation and at the opposite, laminin-1 stimulating intestinal cell differentiation. To begin to characterise the molecular events induced by the different isoforms, we examined by immunofluorescence the intracellular distribution of several nuclear proteins, recently highlighted by a nuclear proteomic approach. We observed clear nucleocytoplasmic redistribution of these proteins, which depended on the laminin isoform. These results provide evidence for a distinct functional role of laminins in intestinal cell functions characterised by specific localisation of nuclear proteins.

Proteomic analysis of nuclear proteins from proliferative and differentiated human colonic intestinal epithelial cells.

Self-renewing tissues such as the intestine contain progenitor proliferating cells which subsequently differentiate. Cell proliferation and differentiation involve gene regulation processes which take place in the nucleus. A human intestinal epithelial cell line model (Caco2/TC7) which reproduces these dynamic processes has been used to perform proteomic studies on nuclear proteins. Nuclei from Caco2/TC7 cells at proliferative and differentiated stages were purified by subcellular fractionation. After two-dimensional gel electrophoresis separation and ruthenium staining, 400 protein spots were detected by image analysis. Eighty-five spots corresponding to 60 different proteins were identified by matrix-assisted laser desorption/ionization mass spectrometry in nuclei from proliferative cells. Comparison of nuclear proteomes from proliferative or differentiated cells by differential display resulted in the identification of differentially expressed proteins such as nucleolin, hnRNP A2/B1 and hnRNP A1. By using Western blot analysis, we found that the expression and number of specific isoforms of these nuclear proteins decreased in differentiated cells. Immunocytochemistry experiments also showed that in proliferative cells nucleolin was distributed in nucleoli-like bodies. In contrast, hnRNPs A2/B1 and A1 were dispersed throughout the nucleus. This study of the nuclear proteome from intestinal epithelial cells represents the first step towards the establishment of a protein database which will be a valuable resource in future studies on the differential expression of nuclear proteins in response to physiological, pharmacological and pathological modulations.

Resveratrol analog (Z)-3,5,4'-trimethoxystilbene is a potent anti-mitotic drug inhibiting tubulin polymerization.

Resveratrol (3,5,4'-trihydroxystilbene) a natural polyphenol present in medicinal plants, grapes and wines, has potent chemopreventive properties on intestinal carcinogenesis. A methylated derivative (Z-3,5,4'-trimethoxystilbene: R3) was synthesized. R3 at 0.3 microM exerted a 80% growth inhibition of human colon cancer Caco-2 cells and arrested growth completely at 0.4 microM (R3 was 100-fold more active than resveratrol). The cis conformation of R3 was also 100-fold more potent than the trans isomer. R3 (0.3 microM) caused cell cycle arrest at the G2/M phase transition. The drug inhibited tubulin polymerization in a dose-dependent manner (IC50=4 microM), and it reduced also by 2-fold ornithine decarboxylase and s-adenosylmethionine decarboxylase activities. This caused the depletion of the polyamines, putrescine and spermidine, which are growth factors for cancer cells. R3 inhibited partially colchicine binding to its binding site on tubulin, indicating that R3 either partially overlaps with colchicine binding or that R3 binds to a specific site of tubulin that is not identical with the colchicine binding site modifying colchicine binding by allosteric influences. The resveratrol derivative (Z)-3,5,4'-trimethoxystilbene (R3) is an interesting anti-mitotic drug that exerts cytotoxic effects by depleting the intracellular pool of polyamines and by altering microtubule polymerization. Such a drug may be useful for the treatment of neoplastic diseases.

Cdx1 homeobox gene during human colon cancer progression.

The Cdx1 homeobox gene encodes an intestine-specific transcription factor with a pro-oncogenic function in vitro. Here we have analysed the pattern of Cdx1 in human colon cancer progression. Cdx1 expression remains at a high level in the majority of the polyps and it is even overexpressed in more than one-third of the specimens, consistent with the fact that the gene is an intestine-specific target of oncogenic pathways. However, Cdx1 decreases in one-fifth of the polyps, which is reminiscent of the loss of expression previously reported in the majority of carcinomas. Allelic imbalance analysis demonstrates that the Cdx1 locus located on chromosome 5q is a major site of genomic rearrangement in colorectal cancers, and that the frequency of the rearrangements increases during polyps to carcinoma progression. Allelic imbalance at the Cdx1 locus occurs in relation to, although not invariably in association with, the rearrangements at the APC locus on the same chromosomal arm. Xenografts of primary human colon carcinomas indicate that the level of Cdx1 mRNA correlates with the intensity of allelic imbalance. Together, these data show that Cdx1 exhibits a complex pattern during colorectal cancer progression. Given that Cdx1 has a pro-oncogenic function in vitro, the maintenance of a high level of expression in polyps, and even its overexpression in one-third of the specimens, suggest that this homeobox gene may be an important factor in the process toward malignant transformation during the first steps of tumorigenesis.

Expression and distribution of distinct variants of E-MAP-115 during proliferation and differentiation of human intestinal epithelial cells.

Epithelial cell proliferation and differentiation occur concomitant with striking remodeling of the cytoskeleton. Microtubules (MTs) play important roles in these processes, during which the MTs themselves are reorganized and stabilized by microtubule-associated proteins (MAPs). Among the proteins classified as structural MAPs, E-MAP-115 (also named ensconsin) is preferentially expressed in cells of epithelial origin. The aims of this study were, first, to determine if E-MAP-115, like other MAPs, is expressed as different isoforms during differentiation and, second, to perform a detailed analysis of the expression and distribution of any E-MAP-115 variants detected in intestinal epithelial cells during their polarization/differentiation. It was our expectation that these data would help us to develop hypotheses concerning the role of this MAP in epithelial development. We report the expression of three E-MAP-115 transcripts encoding isoforms of 115, 105, and 95 kDa; two display an expression gradient inverse to the third one as Caco-2 cells progress from proliferation through the stages of differentiation. To monitor the proteins produced from each transcript, we used purified polyclonal antibodies against synthetic peptides contained within the 115, 105, and 95 kDa isoforms to assay proliferating and differentiating CaCo-2 cells. Our results indicate that the expression and MT-binding capacity of the 115, 105, and 95 kDa isoforms vary upon proliferation/differentiation of the cells. E-MAP-115 proteins colocalize with MTs in proliferative and differentiated Caco-2 cells; in vivo, they are expressed in both crypt and villus epithelial cells where they are mainly concentrated at the apical pole of the cells.