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Le Touquet – Paris-Plage, France

Buffet C.,University of Paris Descartes | Buffet C.,Institute E3M | Catelli M.-G.,University of Paris Descartes | Hecale-Perlemoine K.,University of Paris Descartes | And 6 more authors.
PLoS ONE | Year: 2015

Serum stimulation of mammalian cells induces, via the MAPK pathway, the nuclear protein DUSP5 (dual-specificity phosphatase 5), which specifically interacts with and inactivates the ERK1/2 MAP kinases. However, molecular mechanisms underlying DUSP5 induction are not well known. Here, we found that the DUSP5 mRNA induction depends on a transcriptional regulation by the MAPK pathway, without any modification of the mRNA stability. Two contiguous CArG boxes that bind serum response factor (SRF) were found in a 1 Kb promoter region, as well as several E twenty-six transcription factor family binding sites (EBS). These sites potentially bind Elk-1, a transcription factor activated by ERK1/2. Using wild type or mutated DUSP5 promoter reporters, we demonstrated that SRF plays a crucial role in serum induction of DUSP5 promoter activity, the proximal CArG box being important for SRF binding in vitro and in living cells. Moreover, in vitro and in vivo binding data of Elk-1 to the same promoter region further demonstrate a role for Elk-1 in the transcriptional regulation of DUSP5. SRF and Elk-1 form a ternary complex (Elk-1-SRF-DNA) on DUSP5 promoter, consequently providing a link to an important negative feedback tightly regulating phosphorylated ERK levels. © 2015 Buffet et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Source

Miyara M.,CNRS Immunology and Infectious Disease Center | Chader D.,CNRS Immunology and Infectious Disease Center | Sage E.,Departement de Chirurgie Thoracique et de Transplantation Pulmonaire | Sugiyama D.,Osaka University | And 14 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2015

CD4+ regulatory T (Treg) cells expressing CD25 and the transcription factor forkhead box P3 (FOXP3) are indispensable for immunological self-tolerance and homeostasis. FOXP3+CD25+CD4+ T cells in humans, however, are heterogeneous in function and differentiation status, including suppressive or nonsuppressive cells as well as resting or activated Treg cells. We have searched for cell surface markers specific for suppression-competent Treg cells by using a panel of currently available monoclonal antibodies reactive with human T cells. We found that CD15s (sialyl Lewis x) was highly specific for activated, terminally differentiated, and most suppressive FOXP3high effector Treg (eTreg) cells and able to differentiate them in various clinical settings from nonsuppressive FOXP3+ T cells secreting inflammatory cytokines. For example, CD15s+FOXP3+ eTreg cells were increased in sarcoidosis, whereas it was nonsuppressive CD15s-FOXP3+ T cells that were expanded in lupus flares. FOXP3+ cells induced from conventional CD4+ T cells by T-cell receptor stimulation hardly expressed CD15s. CD15s+CD4+ T-cell depletion was sufficient to evoke and enhance in vitro immune responses against tumor or viral antigens. Collectively, we have identified CD15s as a biomarker instrumental in both phenotypic and functional analysis of FOXP3+CD4+ T-cell subpopulations in health and disease. It allows specific targeting of eTreg cells, rather than whole FOXP3+CD4+ T cells, in controlling immune responses. © 2015 PNAS. Source

Interested, since she first qualified as a nurse, in the complex care of people with chronic diseases, Marina Vignot has focused on the coordination of care pathways throughout her career. She now shares her expertise by teaching the follow-up of patients with cardio-metabolic diseases. © 2014 Elsevier Masson SAS. All rights reserved. Source

Grimaldi A.,Institute E3M | Penfornis A.,University Paris - Sud | Consoli S.,University of Paris Descartes | Falissard B.,University Paris - Sud | And 3 more authors.
Advances in Therapy | Year: 2016

Background: The OPTIMA© (MSD, Courbevoie, France) questionnaire was developed to promote shared decisions and the set-up of specific micro-objectives in clinical practice by optimizing communication between type 2 diabetes (T2DM) patients and their physicians. The present study aimed to assess OPTIMA in clinical practice. Methods: A cross-sectional multicenter observational study was conducted in France from 2012 to 2014. During routine consultation, patients completed one of the five modules of the OPTIMA questionnaire (Physical activity, Diet, Treatment, Knowledge of the disease or Self-monitoring of blood glucose). The rate of SMART (specific, measurable, acceptable, realistic, timely) micro-objective set-up following the use of the questionnaire was assessed. Data on how patients felt about their diabetes management (beliefs concerning actions, how easy they were to do and how often they were done in practice) were gathered. Finally, patients’ and physicians’ opinions on OPTIMA were assessed using the PRAgmatic Content and face validity Test (PRAC-Test© (Mapi, Lyon, France) evaluation questionnaire. Results: Overall, 807 patients were included by 186 physicians. While 92.7 % of consultations led to the set-up of a micro-objective, only 22.3 % were SMART micro-objectives: Physical activity module (34.3 %), Diet module (9.6 %), Treatment module (16.4 %), Knowledge of the disease module (25.2 %), and self-monitoring of blood glucose module (29.5 %). Among patients completing the Physical activity module, 79.0 % reported that they believed physical activity was useful, 35.0 % that it was easy, and 25.8 % that they regularly practised it. PRAC-Test results showed that OPTIMA was a useful and easy-to-use questionnaire that promotes communication between physicians and their patients according to 92.8 % of patients and 69.4 % of physicians. Conclusion: The OPTIMA questionnaire facilitates communication between patients and their physicians and promotes the set-up of micro-objectives concerning T2DM management. The Physical activity module was the most likely of the five modules in the questionnaire to lead to the set-up of SMART micro-objectives. Funding: MSD France. © 2016, The Author(s). Source

Jublanc C.,Institute E3M | Bruckert E.,Institute E3M
Revue de Medecine Interne | Year: 2016

Adrenal insufficiency is a rare but life-threatening disorder. Clinical manifestations include fatigue, weight loss, gastrointestinal manifestations and skin hyperpigmentation, the latter being specific of primary adrenal failure. Because of non-specific clinical features of this rare disorder, diagnosis can be delayed and adrenal failure be revealed by an acute crisis. Adrenal insufficiency can be primary (Addison disease), most frequently autoimmune, or secondary, resulting from long term administration of exogenous glucocorticoids or more rarely from pituitary disorders. Monitoring of substitutive treatment is now well codified. Patient education is very important in this chronic disease that remains associated with a persistent high risk of adrenal crisis. © 2016 Société nationale française de médecine interne (SNFMI). Source

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