Paris Descartes University

About: Paris Descartes University is a government organization based out in Paris, France. It is known for research contribution in the topics: Population & Transplantation. The organization has 20987 authors who have published 37456 publications receiving 1206222 citations. The organization is also known as: Université Paris V-Descartes & Université de Paris V.

Reactive Oxygen Species Controls Endometriosis Progression

Abstract: Endometriosis is associated with chronic inflammation, and reactive oxygen species (ROS) are proinflammatory mediators that modulate cell proliferation. We have investigated whether the dysregulation of ROS production in endometriotic cells correlates with a pro-proliferative phenotype and can explain the spreading of this disease. Stromal and epithelial cells were purified from ovarian endometrioma and eutopic endometrium from 14 patients with endometriosis to produce four primary cell lines from each patient. ROS production, detoxification pathways, cell proliferation, and mitogen-activated protein kinase pathway activation were studied and compared with epithelial and stromal cell lines from 14 patients without endometriosis. Modulation of the proliferation of endometriosis by N-acetyl-cysteine, danazol, and mifepristone was tested in vitro and in 28 nude mice implanted with endometriotic tissue of human origin. Endometriotic cells displayed higher endogenous oxidative stress with an increase in ROS production, alterations in ROS detoxification pathways, and a drop in catalase levels, as observed for tumor cells. This increase in endogenous ROS correlated with increased cellular proliferation and activation of ERK1/2. These phenomena were abrogated by the antioxidant molecule N-acetyl-cysteine both in vitro and in a mouse model of endometriosis. Human endometriotic cells display activated pERK, enhanced ROS production, and proliferative capability. Our murine model shows that antioxidant molecules could be used as safe and efficient treatments for endometriosis.

Large genomic rearrangements in the hepatocyte nuclear factor-1β (TCF2) gene are the most frequent cause of maturity-onset diabetes of the young type 5

Abstract: Maturity-onset diabetes of the young (MODY) 5 is caused by mutations in the TCF2 gene encoding the transcription factor hepatocyte nuclear factor-1β. However, in 60% of the patients with a phenotype suggesting MODY5, no point mutation is detected in TCF2. We have hypothesized that large genomic rearrangements of TCF2 that are missed by conventional screening methods may account for this observation. In 40 unrelated patients presenting with MODY5 phenotype, TCF2 was screened for mutations by sequencing. Patients without mutations were then screened for TCF2 rearrangements by the quantitative multiplex PCR of short fluorescent fragments (QMPSF). Among the 40 patients, the overall detection rate was 70%: 18 had point mutations, 9 had whole-gene deletions, and 1 had a deletion of a single exon. Similar phenotypes were observed in patients with mutations and in subjects with large deletions. These results suggest that MODY5 is more prevalent than previously reported, with one-third of the cases resulting from large deletions of TCF2. Because QMPSF is more rapid and cost effective than sequencing, we propose that patients whose phenotype is consistent with MODY5 should be screened first with the QMPSF assay. In addition, other MODY genes should be screened for large genomic rearrangements.

IRAP Identifies an Endosomal Compartment Required for MHC Class I Cross-Presentation

Abstract: Major histocompatibility complex (MHC) class I molecules present peptides, produced through cytosolic proteasomal degradation of cellular proteins, to cytotoxic T lymphocytes. In dendritic cells, the peptides can also be derived from internalized antigens through a process known as cross-presentation. The cellular compartments involved in cross-presentation remain poorly defined. We found a role for peptide trimming by insulin-regulated aminopeptidase (IRAP) in cross-presentation. In human dendritic cells, IRAP was localized to a Rab14+ endosomal storage compartment in which it interacted with MHC class I molecules. IRAP deficiency compromised cross-presentation in vitro and in vivo but did not affect endogenous presentation. We propose the existence of two pathways for proteasome-dependent cross-presentation in which final peptide trimming involves IRAP in endosomes and involves the related aminopeptidases in the endoplasmic reticulum.

A systematic literature review of drug therapies for the treatment of psoriatic arthritis: current evidence and meta-analysis informing the EULAR recommendations for the management of psoriatic arthritis

Abstract: Objectives To review the available evidence for the efficacy and safety of non-steroidal anti-inflammatory drugs (NSAIDs), synthetic and biological drug therapies for the different clinical manifestations of psoriatic arthritis (PsA) in order to provide data for the development of treatment recommendations by the European League Against Rheumatism (EULAR) taskforce. Methods A systematic literature review (SLR) of available treatments for PsA was performed using the largest electronic databases (MEDLINE, EMBASE and COCHRANE) by two working groups formed within the EULAR taskforce. This comprised a comprehensive sample of rheumatologists, dermatologists, epidemiologists and patients. The available evidence was reviewed for NSAIDs, synthetic disease modifying antirheumatic drugs (DMARDs), local and systemic corticosteroids and biologic drugs. All articles and abstracts published between 1962 and January 2010 were reviewed and considered and a meta-analysis of data on biological therapies was performed. Results While little data are available on NSAIDs, glucocorticoids and synthetic DMARDs, the available evidence suggests an acceptable efficacy and safety profile of both NSAIDs and synthetic DMARDs (methotrexate, cyclosporine A, sulfasalazine and leflunomide) in PsA. More evidence is available (level 1B) supporting the efficacy of anti-tumour necrosis factor (anti-TNF) agents (adalimumab, etanercept, golimumab and infliximab) in treating the signs and symptoms of PsA as well as reducing radiographic progression. Registry data show no new safety concerns, although the numbers studied to date are relatively small. Conclusions This SLR reveals some evidence to support the use of NSAIDs and synthetic DMARDs and good evidence for the efficacy of anti-TNF therapy in PsA.