Analyse discriminante de la sévérité de l'allergie à l'arachide

International audienceL'allergie à l'arachide est un problème de santé publique. La sévérité des réactions, parfois très graves, est évaluée par un score lors d'un Test de Provocation Orale (TPO), qui nécessite l'hospitalisation du patient, souvent un enfant, et peut s'avérer dangereux. Afin de s'en affranchir, ont été réalisées des analyses discriminantes concernant trois mesures de la sévérité de l'allergie à l'arachide : le score du TPO, la dose réactogène et le score de sévérité du premier accident, à partir de 2 groupes de variables explicatives par patient ($n=93$) : 6 dosages immunologiques et 30 tests cutanés. Une Analyse Factorielle Multiple a été implémentée afin d'équilibrer l'influence des deux groupes de variables sur les modèles prédictifs, avec les règles de classement linéaire et quadratique, les $k$-NN, CART, et AdaBoost, précédés par une phase de sélection de variables et testés par validation croisée. De plus, un algorithme permettant simultanément de regrouper les doses réactogènes en classes et de sélectionner les caractères discriminants est proposé

Complete exon sequencing of all known Usher syndrome genes greatly improves molecular diagnosis

<p>Abstract</p> <p>Background</p> <p>Usher syndrome (USH) combines sensorineural deafness with blindness. It is inherited in an autosomal recessive mode. Early diagnosis is critical for adapted educational and patient management choices, and for genetic counseling. To date, nine causative genes have been identified for the three clinical subtypes (USH1, USH2 and USH3). Current diagnostic strategies make use of a genotyping microarray that is based on the previously reported mutations. The purpose of this study was to design a more accurate molecular diagnosis tool.</p> <p>Methods</p> <p>We sequenced the 366 coding exons and flanking regions of the nine known USH genes, in 54 USH patients (27 USH1, 21 USH2 and 6 USH3).</p> <p>Results</p> <p>Biallelic mutations were detected in 39 patients (72%) and monoallelic mutations in an additional 10 patients (18.5%). In addition to biallelic mutations in one of the USH genes, presumably pathogenic mutations in another USH gene were detected in seven patients (13%), and another patient carried monoallelic mutations in three different USH genes. Notably, none of the USH3 patients carried detectable mutations in the only known USH3 gene, whereas they all carried mutations in USH2 genes. Most importantly, the currently used microarray would have detected only 30 of the 81 different mutations that we found, of which 39 (48%) were novel.</p> <p>Conclusions</p> <p>Based on these results, complete exon sequencing of the currently known USH genes stands as a definite improvement for molecular diagnosis of this disease, which is of utmost importance in the perspective of gene therapy.</p

Kyphoplasty for the Treatment of Painful Vertebral Hemangioma

peer reviewedVertebral angiomas are frequent and often asymptomatic. Sometimes although they do not seem invasive radiologically, they are responsible for local pain. If there is concordance between pain and vertebral angioma localisation, surgery such as vertebroplasty or cyphoplasty can be proposed. These techniques lead to a quick and complete removal of symptoms

Overview of a decade of advances in ophtalmology

This review summarizes the most important advances that occurred in ophthalmology during the last decade, with a focus on corneal pathology, cataract surgery, glaucoma and retinal diseases

Interaction between climate forcing and plankton communities in a pristine NW Mediterranean site, the Bay of Calvi (Corsica) : a long term study

In the Mediterranean coastal areas, most of the long-term studies of plankton dynamics concern highly urbanized areas, where long-term variability reflects the combined effects of climate and anthropogenic forcing. Here we use a unique long-term time series (1979-) performed in a NW Mediterranean coastal area unbiased by local anthropogenic pressure (Bay of Calvi, Corsica) to understand how climate variation drives changes in plankton communities. From high-frequency field data, we describe a mechanism that links winter physics, nutrient replenishment of the surface layer and plankton biomass and composition under the different combinations of meteorological conditions that occurred during the 4 decades of observations. Focusing on phytoplankton, we point out how climate variation affected (i) the timing, duration and magnitude of the winter-spring phytoplankton blooms, (ii) the mean yearly biomasses, (iii) the abundance of phytoplankton functional groups. We identify threshold values of physical variables below and above which they strongly impact nutrient availability, phytoplankton bloom characteristics and seasonal succession of functional groups. We show that food webs are resource controlled. Striking similarities between our observations and events elsewhere in the NW Mediterranean Sea are presented. We explore ecological consequences of changes occurring at the base of the food webs on services provided by plankton in the Mediterranean coastal waters

3-Aryl-2-quinolone derivatives: synthesis and characterization of in vitro and in vivo antitumor effects with emphasis on a new therapeutical target connected with cell migration

Among 25 3-aryl-2-quinolone derivatives synthesized, the antitumor activity of some of them was characterized both in vitro and in vivo. In this series, no compound appeared to be cytotoxic in vitro, as was known by the colorimetric MTT assay carried out on 12 distinct human cancer cell lines obtained from the American Type Culture Collection. Indeed, the concentration values decreasing the growth of the 12 cell lines by at least 50% (IC(50) index) were always higher than 10(-5) M. We then made use of a computer-assisted phase-contrast videomicroscopy system to quantitatively determine in vitro the level of migration of living MCF-7 human breast cancer cells. For example, at 10(-7) M, compounds 7, 13, 16, and 28 markedly decreased the migration level of these MCF-7 human breast cancer cells. The in vivo determination of the maximum tolerated dose showed that all compounds tested were definitively nontoxic. When the nontoxic, antimigratory compound 16 was combined with either doxorubicin or etoposide, two cytotoxic compounds routinely used in the clinic, this led to additive in vivo benefits from this treatment (as compared to individual administrations of the drugs) when the MXT mouse mammary adenocarcinoma was used. Thus, nontoxic antimigratory compounds, including the 2-quinolone derivatives synthesized here, can actually improve the efficiency of antitumor treatment when combined with conventional cytotoxic agents.Journal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Synthesis and in vitro antitumor activity of ring C and D-substituted phenanthrolin-7-one derivatives, analogues of the marine pyridoacridine alkaloids ascididemin and meridine.

A series of cycle C and D-substituted phenanthrolin-7-ones, analogues of the marine pyridoacridines meridine and ascididemin have been synthesized on the basis of Diels-Alder reactions involving quinoline-5,8-dione and 2- (or un)-substituted-N,N-dimethylhydrazones. All the compounds were evaluated for in vitro cytotoxic activity against 12 distinct human cancer cell lines. They all exhibit cytotoxic activity with IC(50) values at least of micromolar order.Journal Articleinfo:eu-repo/semantics/publishe

Deciphering the Crosstalk Between Myeloid-Derived Suppressor Cells and Regulatory T Cells in Pancreatic Ductal Adenocarcinoma

International audiencePancreatic ductal adenocarcinoma (PDAC) is a fatal disease with rising incidence and a remarkable resistance to current therapies. The reasons for this therapeutic failure include the tumor's extensive infiltration by immunosuppressive cells such as myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs). By using light sheet fluorescent microscopy, we identified here direct interactions between these major immunoregulatory cells in PDAC. The in vivo depletion of MDSCs led to a significant reduction in Tregs in the pancreatic tumors. Through videomicroscopy and ex vivo functional assays we have shown that (i) MDSCs are able to induce Treg cells in a cell-cell dependent manner; (ii) Treg cells affect the survival and/or the proliferation of MDSCs. Furthermore, we have observed contacts between MDSCs and Treg cells at different stages of human cancer. Overall our findings suggest that interactions between MDSCs and Treg cells contribute to PDAC immunosuppressive environment

MT4-MMP and EGFR expression levels are key biomarkers for breast cancer patient response to chemotherapy and erlotinib.

BACKGROUND: Triple-negative breast cancers (TNBC) are heterogeneous cancers with poor prognosis. We aimed to determine the clinical relevance of membrane type-4 matrix metalloproteinase (MT4-MMP), a membrane type matrix metalloproteinase that interacts with epidermal growth factor receptor (EGFR) overexpressed in >50% of TNBC. METHODS: We conducted a retrospective immunohistochemical analysis on human TNBC samples (n=81) and validated our findings in in vitro and in vivo assays. RESULTS: Membrane type-4 matrix metalloproteinase and EGFR are produced in 72.5% of TNBC samples, whereas those proteins are faintly produced by healthy tissues. Unexpectedly, tumour relapse after chemotherapy was reduced in samples highly positive for MT4-MMP. Mechanistically, this is ascribed to a higher sensitivity of MT4-MMP-producing cells to alkylating or intercalating chemotherapeutic agents, as assessed in vitro. In sharp contrast, MT4-MMP expression did not affect tumour cell sensitivity to paclitaxel that interferes with protease trafficking. Importantly, MT4-MMP expression sensitised cancer cells to erlotinib, a tyrosine kinase EGFR inhibitor. In a pre-clinical model, the growth of MT4-MMP overexpressing xenografts, but not of control ones, was reduced by epirubicin or erlotinib. The combination of suboptimal drug doses blocked drastically the growth of MT4-MMP-producing tumours. CONCLUSIONS: We demonstrate that MT4-MMP defines a sub-population of TNBC sensitive to a combination of DNA-targeting chemotherapeutic agents and anti-EGFR drugs.British Journal of Cancer advance online publication 14 February 2017; doi:10.1038/bjc.2017.23 www.bjcancer.com