Utilisation du SCF après échec du G-CSF pour des autogreffes (à propos de deux cas en pédiatrie)

Le SCF est une cytokine essentielle à une hématopoïèse normale qui agit aux stades précoces de l'hématopoïèse en permettant la prolifération et la survie des progéniteurs pluripotents. En combinaison avec le C-CSF, le SCF augmente la prolifération, la différenciation et la survie de la cellule hématologiques. L'utilisation de fortes doses de chimiothérapie myéloablative associée à une transplantation de cellules souches du sang périphériques a rapidement remplacé la greffe de moelle osseuse dans le traitement des cancers chimiosensibles. Le SCF combiné au G-CSF constitue une alternative lors de l'échec de transplantation de cellules souches de sang périphérique après administration de G-CSF seul. Dans cette étude, le SCF est administré à deux enfants atteints de maladies cancéreuses, qui ont échoué pour la transplantation de cellules souches du sang périphérique après administration du G-CSF seul.ROUEN-BU Médecine-Pharmacie (765402102) / SudocSudocFranceF

Histoire de radars

International audienceIn 1970, Henri Dessens, director of the Clermont-Fd Observatory, wanted to use radar to study the physics of the atmosphere. The idea became a reality with Serge Godard, who took over from Dessens at the head of the Observatory. He succeeded in recovering a military radar that was diverted from its original function to become a study and research instrument called ANATOL (ANAlyse et Trajectoire d'Orages Locaux). ANATOL's long career came to an end in 1995 after more than 45 years of good and loyal service in atmospheric research. However, the idea of using radars continued to grow and in 1993, under the direction of Daniel Ramon, an ST (Stratosphere-Troposphere) radar was installed with Météo-France. Then, in the mid-1990s, Jacques Kornprobst, director, launched the Observatory on the design and technical production of a prototype "volcanological" Doppler radar, VOLDORAD-1. Responding to volcanological needs, it was tested in a pioneering way at Etna in 1998. This success led to the construction of two other unique volcanological radars (VOLDORAD-2 and 2B) and a third (VOLDORAD-3). Since 2002, these radars have been combined into a dedicated observation service within the OPGC and are used for monitoring volcanic eruptions but also for atmospheric studies.En 1970, Henri Dessens, directeur de l'Observatoire de Clermont-Ferrand, souhaite utiliser des radars pour l'étude de la physique de l'atmosphère. L'idée se concrétise avec Serge Godard, qui prend la suite de Dessens à la tête de l'Observatoire. Il réussit à récupérer un radar militaire qui va être détourné de sa fonction première pour devenir un instrument d'étude et de recherche baptisé ANATOL (ANAlyse et Trajectoire d'Orages Locaux). La longue carrière d'ANATOL s'achève en 1995 après plus de 45 ans de bons et loyaux services dans la recherche atmosphérique. Mais l'idée d'utiliser des radars poursuit son chemin et dès 1993, sous la direction de Daniel Ramon, c'est l'installation d'un radar ST (Stratosphère-Troposphère) menée avec Météo-France. Puis, au milieu des années 1990, Jacques Kornprobst, directeur, lance l'Observatoire sur la conception et la réalisation technique d'un prototype de radar « volcanologique » à effet Doppler, VOLDORAD-1. Répondant à des besoins en volcanologie, il fut testé de façon pionnière sur le site de l’Etna en 1998. Ce succès conduisit dans la foulée à la construction de deux autres radars uniques en volcanologie (VOLDORAD-2 et 2B) puis d'un troisième (VOLDORAD-3). Réunis en un service d’observation dédié au sein de l’OPGC depuis 2002, ces radars sont utilisés pour la surveillance des éruptions volcaniques mais également pour des études atmosphériques

Adaptation of Arterial Wall Viscosity to the Short‐Term Reduction of Heart Rate: Impact of Aging

Background Changes in arterial wall viscosity, which dissipates the energy stored within the arterial wall, may contribute to the beneficial effect of heart rate (HR) reduction on arterial stiffness and cardiovascular coupling. However, it has never been assessed in humans and could be altered by aging. We evaluated the effect of a selective HR‐lowering agent on carotid arterial wall viscosity and the impact of aging on this effect. Methods and Results This randomized, placebo‐controlled, double‐blind, crossover study performed in 19 healthy volunteers evaluated the effects of ivabradine (5 mg BID, 1‐week) on carotid arterial wall viscosity, mechanics, hemodynamics, and cardiovascular coupling. Arterial wall viscosity was evaluated by the area of the hysteresis loop of the pressure‐lumen cross‐sectional area relationship, representing the energy dissipated (WV), and by the relative viscosity (WV/WE), with WE representing the elastic energy stored. HR reduction by ivabradine increased WV and WE whereas WV/WE remained stable. In middle‐aged subjects (n=11), baseline arterial stiffness and cardiovascular coupling were less favorable, and WE was similar but WV and therefore WV/WE were lower than in youth (n=8). HR reduction increased WV/WE in middle‐aged but not in young subjects, owing to a larger increase in WV than WE. These results were supported by the age‐related linear increase in WV/WE after HR reduction (P=0.009), explained by a linear increase in WV. Conclusion HR reduction increases arterial wall energy dissipation proportionally to the increase in WE, suggesting an adaptive process to bradycardia. This mechanism is altered during aging resulting in a larger than expected energy dissipation, the impact of which should be assessed. Registration URL: https://www.clinicaltrials.gov; Unique identifier: 2015/077/HP. URL: https://www. eudract.ema.europa.eu; Unique identifier: 2015‐002060‐17

Therapeutic Management of Pyriform Sinus Cancer: Results of a Single-Center Study of 122 Patients

International audienceObjective. To analyze the survival rate of a nonselected pyriform sinus cancer population. Study Design. Case series with chart review. Setting. University hospital. Subjects and Methods. A total of 122 patients were included in this study covering the 2002-2008 period. All patients had squamous cell carcinoma originating from the pyriform sinus. Survival and prognostic factors were analyzed. Results. The 3-and 5-year overall survival rates were 39.7% and 2.4%, respectively. The 3-and 5-year survival rates without recurrence were 34% and 27%, respectively. The median survival rates by UICC stage were as follows: stage 1 and 2 patients, 60 months; stage 3, 40 months; stage 4, 19 months. Stage 4 patients had a lower median survival rate than other stages (P =.039). The 5-year survival rate was 46% for patients having T3-T4 operable cancers treated by surgery vs 45% for patients treated by laryngeal conservation protocol (not significant). The 5-year survival rate for patients having nonoperable T4 cancers was 17.2%. The 3-and 5-year overall survival rates of N0 patients was significantly higher than N1 patients (P =.042). N2 and N3 patients had 100% 5-year mortality. Conclusion. This study showed that overall survival and therapeutic management depend on the initial stage of pyriform sinus cancer, notably on the N status. In particular, nonoperable T4 pyriform sinus cancer and N2 and N3 patients had a very poor prognosis. A laryngeal conservation protocol seemed as effective as surgical management in terms of survival

Rabbit targeted genomic sequences after heterologous hybridization using human exome

International audienceAbstract Objective Causal mutations for major genes that underlie a broad range of morphological traits are often located within exons of genes that then affect protein functions. Non-model organism genetic studies are not easy to perform due to the lack of genome-wide molecular tools such as SNP genotyping array. Genotyping-By-Sequencing (GBS) methods offer an alternative. Consequently, we used this approach that is focused on the exome to target and identify major genes in rabbit populations. Data description We used a heterologous enrichment method before sequencing, allowing us to capture the rabbit exome using the marketed human panel since mammal protein coding genes are well conserved across the phylogenic tree of species. This targeted strategy was performed on 52 French rabbits from 5 different French strains (Californian, New-Zealand, Castor, Chinchilla and Laghmere). We generated 3.4 billion sequencing reads and approximately 29–140 million of reads per DNA sample. The expected exome coverage per sample ranged between 118 and 566X. The present dataset could be useful for the scientific community working on rabbit species in order to (i) improve the annotation of the rabbit reference genome Oryctolagus cuniculus (OryCun2.0), (ii) enrich the characterization of polymorphisms segregating in rabbits and (iii) evaluate the genetic biodiversity in different rabbit strains. Raw sequences were deposited in the European Nucleotide Archive (ENA) at the European Molecular Biology Laboratory- European Bioinformatics Institute (EMBL-EBI) data portal under bioproject accession number PRJEB37917

TGF-β signaling intersects with CD103 integrin signaling to promote T lymphocyte accumulation and antitumor activity in the lung tumor microenvironment

International audienceHoming of CD8+ T lymphocytes to the tumor microenvironment is an important step for mounting a robust antitumor immune response. TGF-β is responsible for CD103 (αEβ7) integrin induction in activated intraepithelial CD8+ T lymphocytes. However, the interplay between TGF-β and CD103 and their contribution to T-cell infiltration and antitumor activity remain unknown. Here, we used viable human lung tumor slices and autologous tumor antigen-specific T-lymphocyte clones to provide evidence that CD103 is directly involved in T-lymphocyte recruitment within epithelial tumor islets and intratumoral early T-cell signaling. Moreover, TGF-β enhanced CD103-dependent T-cell adhesion and signaling, whereas it inhibited leukocyte function-associated antigen (LFA)-1 (αLβ2) integrin expression and LFA-1-mediated T-lymphocyte functions. Mechanistic investigations revealed that TGF-β bound to its receptors (TGFBR), which promoted the recruitment and phosphorylation of integrin-linked kinase (ILK) by TGFBR1. We further show that ILK interacted with the CD103 intracellular domain, resulting in protein kinase B (PKB)/AKT activation thereby initiating integrin inside-out signaling. Collectively, our findings suggest that the abundance of TGF-β in the tumor microenvironment may in fact engage with integrin signaling pathways to promote T-lymphocyte antitumor functions, with potential implications for T-cell-based immunotherapies for cance

Beneficial Effect of Alcohol Withdrawal on Gut Permeability and Microbial Translocation in Patients with Alcohol Use Disorder

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Volume reduction and automation of DNAprep libraries for low pass sequencing

International audienceTo characterize a population's haplotypic variability, low pass sequencing represents an interesting alternative to genotyping DNA-microarrays. Although this new technology is also costly, it offers greater precision of genetic information. We have therefore reduced reagent and DNA volumes by automating our Illumina DNA Prep library preparation protocol with the Mosquito HV (SPT LabTech, UK). For this purpose, we intend to evaluate this strategy for the porcine species. We used a family F2 protocol based on crossbreeds between Large White (LW) and Meishan (MS) individuals. It comprises around 1000 pigs, including 12 F0 (6 LW and 6 MS), 30 F1 (6 males and 24 females) and 1000 F2. In addition to the evaluation of bioinformatic phasing methods for the imputation and reconstruction of haplotypes. The exploitation of these data will enable the precise characterization of recombination sites. This will provide an understanding of the reasons why a large region of the X chromosome recombines or not. The SeqOccIn porcine pilot project gave us the opportunity to (i) automate the DNA prep protocol to significantly reduce volumes with very good results and (ii) generate good quality low pass sequencing data for genotype imputation (validated by Mendelian compatibility