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Robitaille, Hubert

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Université Laval. Département de biologie moléculaire, de biochimie médicale et de pathologie
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  • Publication
    Accès libre
    Assessments of the extent to which health-care providers involve patients in decision making : a systematic review of studies using the OPTION instrument
    (John Wiley & Sons Ltd, 2015-07-22) Turcotte, Stéphane; Robitaille, Hubert; Vaillancourt, Hugues; LeBlanc, Annie; Couët, Nicolas; Desroches, Sophie; Elwyn, Glyn; Légaré, France
    Background: We have no clear overview of the extent to which health-care providers involve patients in the decision-making process during consultations. The Observing Patient Involvement in Decision Making instrument (OPTION) was designed to assess this. Objective: To systematically review studies that used the OPTION instrument to observe the extent to which health-care providers involve patients in decision making across a range of clinical contexts, including different health professions and lengths of consultation. Search strategy: We conducted online literature searches in multiple databases (2001–12) and gathered further data through networking. Inclusion criteria: (i) OPTION scores as reported outcomes and (ii) health-care providers and patients as study participants. For analysis, we only included studies using the revised scale. Data extraction: Extracted data included: (i) study and participant characteristics and (ii) OPTION outcomes (scores, statistical associations and reported psychometric results). We also assessed the quality of OPTION outcomes reporting. Main results: We found 33 eligible studies, 29 of which used the revised scale. Overall, we found low levels of patient-involving behaviours: in cases where no intervention was used to implement shared decision making (SDM), the mean OPTION score was 23 ± 14 (0–100 scale). When assessed, the variables most consistently associatedwith higher OPTION scores were interventions to implement SDM (n = 8/9) and duration of consultations (n = 8/15). Conclusions: Whatever the clinical context, few health-care providers consistently attempt to facilitate patient involvement, and even fewer adjust care to patient preferences. However, both SDM interventions and longer consultations could improve this.
  • Publication
    Accès libre
    Approaches to considering sex and gender in continuous professional development for health and social care professionals : an emerging paradigm
    (Taylor & Francis, 2018-07-28) Bilodeau, André.; Borduas, Francine; Dogba, Maman Joyce; Monette, Céline; Blair, Louisa; Robitaille, Hubert; Rhugenda, Sylvie-Marianne; Stacey, Dawn; Gagnon, Marie-Pierre; Tanguay, Dominique; Bélanger, Annie-Pierre; Tremblay, Marie-Claude; Bussières, André; Desroches, Sophie; Gosselin, Hélène.; Roch, Geneviève; Jose, Caroline; Légaré, France
    Consideration of sex and gender in research and clinical practice is necessary to redress health inequities and reduce knowledge gaps. As all health professionals must maintain and update their skills throughout their career, developing innovative continuing professional education programs that integrate sex and gender issues holds great promise for reducing these gaps. This article proposes new approaches to partnership, team development, pedagogical theory, content development, evaluation and data management that will advance the integration of sex and gender in continuing professional development (CPD). Our perspectives build on an intersectoral and interprofessional research team that includes several perspectives, including those of CPD, health systems, knowledge translation and sex and gender.
  • Publication
    Human epithelial stem cells persist within tissue-engineered skin produced by the self-assembly approach
    (Mary Ann Liebert, 2013-02-15) Germain, Lucie; Goyer, Benjamin; Larouche, Danielle; Kim, Dong Hyun; Paquet, Claudie; Fugère, Claudia.; Dunnwald, Martine; Robitaille, Hubert; Sauvé, Sarah; Desgagné, Maxime; Fradette, Julie; Lavoie, Amélie; Beauparlant, Annie.; Pouliot, Roxane
    To adequately and permanently restore organ function after grafting, human tissue-engineered skin substitutes (TESs) must ultimately contain and preserve functional epithelial stem cells (SCs). It is therefore essential that a maximum of SCs be preserved during each in vitro step leading to the production of TESs such as the culture process and the elaboration of a skin cell bank by cryopreservation. To investigate the presence and functionality of epithelial SCs within the human TESs made by the self-assembly approach, slow-cycling cells were identified using 5′-bromo-2′-deoxyuridine (BrdU) in the three-dimensional construct. A subset of basal epithelial cells retained the BrdU label and was positive for the SC-associated marker keratin 19 within TESs after a chase of 21 days in culture post-BrdU labeling. Moreover, keratinocytes harvested from TESs gave rise to SC-like colonies in secondary monolayer subcultures, indicating that SCs were preserved within TESs. To evaluate the effect of cryopreservation with dimethyl sulfoxide and storage in liquid nitrogen on SCs, human epithelial cells were extracted from skin samples, amplified in culture, and used to produce TESs, before cryopreservation as well as after thawing. We found that the proportion and the growth potential of epithelial SCs in monolayer culture and in TESs remained constant before and after cryopreservation. Further, the functionality of these substitutes was demonstrated by successfully grafting human TESs on athymic mice for 6 months. We conclude that human epithelial skin SCs are adequately preserved upon human tissue reconstruction. Thus, these TESs produced by the self-assembly approach are suitable for clinical applications.
  • Publication
    Accès libre
    The mitogen-activated protein kinase kinase kinase dual leucine zipper-bearing kinase (DLK) acts as a key regulator of keratinocyte terminal differentiation.
    (American Society for Biochemistry and Molecular Biology, 2005-01-28) Germain, Lucie; Proulx, Roxanne; Robitaille, Hubert; Robitaille, Karine; Blouin, Richard
    In the skin, epithelial cells undergo a terminal differentiation program leading to the formation of the stratum corneum. Although it is expected that the last phases of this process must be tightly regulated since it results in cell death, the signaling pathways involved in this induction remain ill defined. We now report that a single kinase, the mitogen-activated protein kinase kinase kinase dual leucine zipper-bearing kinase (DLK), acts in the epidermis to promote the terminal differentiation of human keratinocytes. In support of this notion, we showed that DLK expression was restricted to the granular layer in situ. In addition, cultured keratinocytes infected with a recombinant adenovirus expressing DLK exhibited morphological and biochemical changes, including a suprabasal localization, altered cell shape, compacted cytoplasm, DNA fragmentation, and the up-regulation of filaggrin, that are reminiscent of a terminally differentiated phenotype. Moreover the expression of wild-type DLK in keratinocytes stimulated transglutaminase activity and the consequent formation of the cornified cell envelope, while a kinase-inactive variant of DLK did not. Together these results identify DLK as a signaling molecule implicated in the regulation of keratinocyte terminal differentiation and cornification.
  • Publication
    Accès libre
    Tissue-engineered ACL : from the laboratory to the knee Joint
    (Association canadienne d'orthopédie, 2006-08-01) Cloutier, Réjean; Germain, Lucie; Bouchard, Ludovic; Robitaille, Hubert; Auger, François A.; Lamontagne, Jean; Goulet, Francine
  • Publication
    Applications of human tissue-engineered blood vessel models to study the effects of shed membrane microparticles from T-Lymphocytes on vascular function
    (Mary Ann Liebert, Inc. Publishers, 2008-10-15) Pricci, Maria; Germain, Lucie; Robitaille, Hubert; Bourget, Jean-Michel; Porro, Chiara; Auger, François A.; Soleti, Raffaella; Mostefai, Ahmed; Martinez, Carmen; Andriantsitohaina, Ramaroson
    Microparticles (MPs) are membrane vesicles harboring cell surface proteins and containing cytoplasmic components of the original cell. High levels of circulating MPs have been detected in pathological states associated with vascular dysfunction. We took advantage of the self-assembly method of tissue engineering to produce in vitro three vascular constructs from human vascular smooth muscle cells and fibroblasts to investigate the role of the adventitia in the modulation of vascular tone by MPs, comparing the contractile response of each of these constructs to histamine. The first two were composed of an adventitia (tissue-engineered vascular adventitia (TEVA)) or a media (tissue-engineered vascular media (TEVM)) solely, and the third one contained a media and an adventitia (tissue-engineered vascular media and adventitia (TEVMA)). In the three constructs, the results show that histamine induces contraction insensitive to blockade of inducible nitric oxide (NO) synthase (iNOS) and cyclooxygenase-2 (COX-2) and not affected by MP treatment. MPs decreased NO production and nuclear factor (NF)-kB expression but did not affect superoxide anion (O2) release in TEVA. MPs enhanced NF-kB expression but did not affect iNOS and COX-2 expression or NO or O2 release in TEVM. In TEVMA, MPs did not enhance NF-kB expression, but COX-2 expression was higher, and O2 release was lower. Thus, MPs affected NO, O2, NF-kB, and COX-2 in a subtle fashion to maintain the contractile response to histamine. The use of tissue-engineered vascular constructs results in a better understanding of the effect of MPs on human adventitia and media.
  • Publication
    Accès libre
    Fonction de la Dual leucine-zipper protéine kinase DLK dans la différenciation des kératinocytes épidermiques
    (2008) Robitaille, Hubert; Germain, Lucie; Blouin, Richard
    La différenciation épidermique est un processus complexe qui requiert une régulation fine, chronologique et précise. La régulation de ce processus de différenciation dépend d'un grand nombre de voies de signalisation et d'activateurs qui doivent intervenir à des moments précis. Les différents processus et acteurs moléculaires qui sont impliqués dans la différenciation des kératinocytes sont encore mal connus. Étant donné la complexité de ce programme de différenciation, la mise en lumière de ces processus moléculaires revêt un grand défi. La DLK est un élément régulateur potentiel du processus de cornification des kératinocytes puisqu'elle n'est exprimée que dans les cellules les plus différenciées de l'épiderme. L'expression de DLK dans des kératinocytes humains normaux peu différenciés à l'aide d'un système adénoviral de transfert de gènes a révélé un rôle clé de DLK dans la différenciation épidermique. Cette expression de DLK engendre en effet divers processus primordiaux à la phase tardive de la différenciation des kératinocytes comme l'expression de la filaggrine, l'activation de la transglutaminase, l'accumulation de la protéine p21 cipl/WAFl et la dégradation de l'ADN. La différenciation épidermique s'accompagne également de l'expression de protéines de la famille des Hsp, entre autres la Hsp 27. L'expression de DLK dans des kératinocytes normaux humains entraîne la colocalisation de Hsp 27 avec l'enveloppe cornée ainsi que son insolubilisation, un phénomène observé dans la phase tardive de la différenciation épidermique. Finalement, le calcium est un important régulateur de la différenciation des kératinocytes. L'augmentation du niveau de calcium intracellulaire engendre une augmentation de l'activité de DLK et une re-localisation aux membranes tel qu'observé dans la couche granuleuse de l'épiderme. La localisation membranaire de DLK est aussi un reflet de son rôle important dans la cornification des kératinocytes. Ces travaux montrent donc le rôle important de DLK dans la différenciation épidermique. Ainsi, ils ont permis d'identifier un nouveau régulateur de ce programme de différenciation terminale.
  • Publication
    Tissue engineering of skin and cornea : Development of new models for in vitro studies
    (Academy of Sciences, 2010-06-02) Guérin, Sylvain; Germain, Lucie; Larouche, Danielle; Bisson, Francis; Paquet, Claudie; Robitaille, Hubert; Auger, François A.; Gaudreault, Manon.; Martel, Israël; Duranceau, Louise; Proulx, Stéphanie; Carrier, Patrick; Simard-Bisson, Carolyne; Fradette, Julie
    Human beings are greatly preoccupied with the unavoidable nature of aging. While the biological processes of senescence and aging are the subjects of intense investigations, the molecular mechanisms linking aging with disease and death are yet to be elucidated. Tissue engineering offers new models to study the various processes associated with aging. Using keratin 19 as a stem cell marker, our studies have revealed that stem cells are preserved in human skin reconstructed by tissue engineering and that the number of epithelial stem cells varies according to the donor's age. As with skin, human corneas can also be engineered in vitro. Among the epithelial cells used for reconstructing skin and corneas, significant age-dependent variations in the expression of the transcription factor Sp1 were observed. Culturing skin epithelial cells with a feeder layer extended their life span in culture, likely by preventing Sp1 degradation in epithelial cells, therefore demonstrating the pivotal role played by this transcription factor in cell proliferation. Finally, using the human tissue-engineered skin as a model, we linked Hsp27 activation with skin differentiation.
  • Publication
    The small heat-shock protein Hsp27 undergoes ERK-dependent phosphorylation and redistribution to the cytoskeleton in response to dual leucine zipper-bearing kinase expression
    (Elsevier Science, 2015-12-08) Germain, Lucie; Larouche, Danielle; Tanguay, Robert; Robitaille, Hubert; Blouin, Richard; Simard-Bisson, Carolyne
    Hsp27, a small heat-shock protein, has important roles in many cellular processes, including cytoskeleton dynamics, cell differentiation, and apoptosis. Its expression in normal epidermis correlates with differentiation; however, little is known about the regulatory mechanisms involved. In this study, we report that Hsp27 undergoes upregulation, phosphorylation, and redistribution to the cytoskeleton during the late phase of epidermal keratinocyte differentiation. Our results also show that the expression of the dual leucine zipper-bearing kinase (DLK), an upstream activator of the MAP kinase pathways, is sufficient by itself to induce Hsp27 phosphorylation, cell periphery localization, and redistribution to the insoluble protein fraction (cytoskeleton) in poorly differentiated keratinocytes. This redistribution correlates with the insolubilization of cornified envelope-associated proteins such as involucrin. Interestingly, the effects of DLK on Hsp27 were blocked by PD98059, a selective inhibitor of the extracellular signal-regulated protein kinase (ERK) pathway. Moreover, downregulation of Hsp27 by small interfering RNA in epithelial cells expressing DLK was accompanied by attenuated expression of involucrin in the cytoskeleton. Thus, these observations suggest that the DLK–ERK signaling pathway may act as a regulator of the interaction that occurs between Hsp27 and the cytoskeleton during the formation of the cornified cell envelope, a process conferring to the skin its crucial barrier function.
  • Publication
    The mixed lineage kinase leucine-zipper protein kinase exhibits a differentiation-associated localization in normal human skin and induces keratinocyte differentiation upon overexpression
    (Elsevier Science Pub. Co., 2015-12-08) Germain, Lucie; Robitaille, Hubert; Nadeau, André; Guignard, Rina; Grondin, Gilles; Blouin, Richard; Fradette, Julie
    Leucine-zipper protein kinase/dual leucine zipper bearing kinase/mitogen-activated protein kinase-upstream kinase is a recently described protein serine/threonine kinase which belongs to the mixed lineage kinase family. The overall pattern of expression of the leucine-zipper protein kinase/dual leucine zipper bearing kinase/mitogen-activated protein kinase-upstream kinase gene in embryonic and adult mouse tissues suggested that this kinase could be involved in the regulation of epithelial cell proliferation and differentiation. In order to get more insights into the potential role of leucine-zipper protein kinase in these cellular processes, we characterized its expression in normal human skin, both at the mRNA and protein levels. In situ hybridization, western blotting, and indirect immunofluorescence studies were conducted to localize leucine-zipper protein kinase on various human skin tissues. This is one of the first reports that leucine-zipper protein kinase has a very precise pattern of expression in human skin epithelia, as both mRNA and protein are restricted to the granular layer of the epidermis and inner root sheath of hair follicles. Detection of leucine-zipper protein kinase protein on skin from various body sites, donors of different ages as well as on reconstructed human skin always reveals that leucine-zipper protein kinase is present only in the very differentiated keratinocytes of epidermis and hair follicles. To determine directly whether leucine-zipper protein kinase exhibits any effect on cell growth and differentiation, keratinocytes were transfected with an expression vector harboring the leucine-zipper protein kinase cDNA. The presence of this construct in keratinocytes results in growth arrest together with a concomitant increase in filaggrin expression. Collectively, our results indicate that leucine-zipper protein kinase plays an active part in cellular processes related to terminal differentiation of epidermal keratinocytes.