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101.
Vincent Morinière Karin Dahan Pascale Hilbert Marieline Lison Said Lebbah Alexandra Topa Christine Bole-Feysot Solenn Pruvost Patrick Nitschke Emmanuelle Plaisier Bertrand Knebelmann Marie-Alice Macher Laure-Hélène Noel Marie-Claire Gubler Corinne Antignac Laurence Heidet 《Journal of the American Society of Nephrology : JASN》2014,25(12):2740-2751
Alport syndrome is an inherited nephropathy associated with mutations in genes encoding type IV collagen chains present in the glomerular basement membrane. COL4A5 mutations are associated with the major X-linked form of the disease, and COL4A3 and COL4A4 mutations are associated with autosomal recessive and dominant forms (thought to be involved in 15% and 1%–5% of the families, respectively) and benign familial hematuria. Mutation screening of these three large genes is time-consuming and expensive. Here, we carried out a combination of multiplex PCR, amplicon quantification, and next generation sequencing (NGS) analysis of three genes in 101 unrelated patients. We identified 88 mutations and 6 variations of unknown significance on 116 alleles in 83 patients. Two additional indel mutations were found only by secondary Sanger sequencing, but they were easily identified retrospectively with the web-based sequence visualization tool Integrative Genomics Viewer. Altogether, 75 mutations were novel. Sequencing the three genes simultaneously was particularly advantageous as the mode of inheritance could not be determined with certainty in many instances. The proportion of mutations in COL4A3 and COL4A4 was notably high, and the autosomal dominant forms of Alport syndrome appear more frequently than reported previously. Finally, this approach allowed the identification of large COL4A3 and COL4A4 rearrangements not described previously. We conclude that NGS is efficient, reduces screening time and cost, and facilitates the provision of appropriate genetic counseling in Alport syndrome. 相似文献
102.
Homologous Recombination (HR) plays an essential role in cellular proliferation and in maintaining genomic stability by repairing DNA double-stranded breaks that appear during replication. Rad51, a key protein of HR in eukaryotes, can have an elevated expression level in tumor cells, which correlates with their resistance to anticancer therapies. Therefore, targeted inhibition of Rad51 through inhibitor may improve the tumor response to these therapies. In order to identify small molecules that inhibit Rad51 activity, we screened the Prestwick Library (1120 molecules) for their effect on the strand exchange reaction catalyzed by Rad51. We found that Chicago Sky Blue (CSB) is a potent inhibitor of Rad51, showing IC50 values in the low nanomolar range (400 nM). Biochemical analysis demonstrated that the inhibitory mechanism probably occurs by disrupting the Rad51 association with the single-stranded DNA, which prevents the nucleoprotein filament formation, the first step of the protein activity. Structure Activity Relationship analysis with a number of compounds that shared structure homology with CSB was also performed. The sensitivity of Rad51 inhibition to CSB modifications suggests specific interactions between the molecule and Rad51 nucleofilament. CSB and some of its analogs open up new perspectives in the search for agents capable of potentiating chemo- and radio-therapy treatments for cancer. Moreover, these compounds may be excellent tools to analyze Rad51 cellular functions. Our study also highlights how CSB and its analogs, which are frequently used in colorants, stains and markers, could be responsible of unwanted side effects by perturbing the DNA repair process. 相似文献
103.
Hematopoietic stem cell transplantation for de novo erythroleukemia: a study of the European Group for Blood and Marrow Transplantation (EBMT)
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Fouillard L Labopin M Gorin NC Polge E Prentice HG Meloni G Reiffers J Pigneux A Willemze R Schattenberg A Sica S Lagrange M Fenneteau O Perot C Frassoni F;Acute Leukemia Working Party of the EBMT 《Blood》2002,100(9):3135-3140
De novo erythroleukemia (EL) is a rare disease. Reported median survival are poor and vary from 4 to 14 months. The value of hematopoietic stem cell transplantation (HSCT) for EL is unknown. This EBMT registry study reports on the largest series of patients with EL treated with HSCT in first complete remission-103 autologous and 104 HLA identical sibling allogeneic HSCT. Outcome and identification of prognostic factors for each type of transplantation were evaluated. For autologous HSCT, outcome at 5 years showed a leukemia-free survival (LFS) of 26% +/- 5%, a relapse incidence (RI) of 70% +/- 6%, and a transplant-related mortality (TRM) of 13% +/- 4%. By multivariate analysis, the only prognostic factor was age. For allogeneic HSCT, outcome at 5 years showed an LFS of 57% +/- 5%, an RI of 21% +/- 5%, and a TRM of 27% +/- 5%. By multivariate analysis, prognostic factors were graft-versus-host disease and age. This study represents the largest series of de novo EL treated with HSCT and shows that allogeneic HSCT is by far the most effective treatment. 相似文献
104.
Clinical characteristics and prognostic factors of sinonasal undifferentiated carcinoma: a multicenter study
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Guillaume de Bonnecaze MD MSc Benjamin Verillaud MD PhD Leonor Chaltiel PhD Sylvestre Fierens MD Mark Chapelier MD Cécile Rumeau MD MSc Olivier Malard MD PhD Marie Gavid MD MSC Xavier Dufour MD PhD Christian Righini MD PhD Emmanuelle Uro‐coste MD PhD Michel Rives MD Christine Bach MD Bertrand Baujat MD PhD François Janot MD PhD Ludovic de Gabory MD PhD Sebastien Vergez MD PhD 《International forum of allergy & rhinology》2018,8(9):1065-1072
Background
Sinonasal undifferentiated carcinoma (SNUC) is a very rare entity with a poor prognosis. Due to the lack of studies on the subject, evidence is lacking concerning its management.Methods
A multicenter collaborative study was conducted to assess treatment strategy, oncological outcome, and prognostic factors.Results
Definitive analyses focused on 54 patients with a majority of advanced stage; the 3‐year overall survival (OS) and 3‐year recurrence‐free survival (RFS) rates were, respectively, 62.4% and 47.8%. During the follow‐up, 18 patients (33.3%) died, 10 (18.5%) developed metastases, 7 had lymph‐node involvement (13%), and 12 (22.2%) showed recurrence or local progression. In univariate analyses, treatment modalities associated with improved RFS were induction chemotherapy (p = 0.02) and intensity‐modulated radiotherapy (p = 0.007). In the multivariate analyses, only induction chemotherapy (p = 0.047, hazard ratio [HR] = 0.39) was significantly associated with improved RFS.Conclusion
Multimodal therapies including induction chemotherapy and intensity‐modulated radiotherapy may improve the prognosis of SNUC; surgery might improve local control. Further multicenter studies are required.105.
Hemorheological aspects of the metabolic syndrome: markers of insulin resistance, obesity or hyperinsulinemia? 总被引:1,自引:0,他引:1
The metabolic syndrome is a major health problem in western countries, due to the deleterious metabolic consequences of sedentarity and rich diet in the large part of the population who exhibits the so-called "thrifty phenotype". This syndrome, which is at high risk for diabetes and atherothrombosis is associated with hemorheologic abnormalities. Initially, insulin resistance was considered as the core of the syndrome. However, it becomes clear that the syndrome is a cluster in which the combined effects of obesity, insulin resistance, and hyperinsulinemia can be inconstantly associated. Thus, we investigated in 157 nondiabetic subjects (53 males and 104 females, age 35.6+/-1.1 yr, mean BMI 29.2+/-0.6 kg/m2) the respective importance of each of these factors. Subjects were divided in 6 groups according to BMI (cut-off point 25 kg/m2) and insulin sensitivity (SI) measured with the minimal model (lowest quartile SI<1.1 min(-1)/(microU/ml) x 10(-4), highest quartile SI>9.5, middle zone between 1.1 and 9.5). Results show that whole blood viscosity at high shear rate is higher in obese subjects (p<0.01). Plasma viscosity is also higher in obese subjects 1.41+/-0.02 vs 1.34+/-0.012 (p<0.01), and, in addition, in lean subjects, is lower when SI is in the upper quartile. RBC rigidity index "Tk" is higher in obese subjects. A worsening effect of insulin resistance (SI<1.1) on Tk is found only in obese subjects. The aggregability index "M1" is increased when SI<1.1 in both obese and nonobese subjects. No clear effect of either SI or obesity on hematocrit is observed. On the whole, obesity and insulin resistance both impair blood rheology by acting on red cell rigidity and plasma viscosity. Whole blood viscosity at high shear rate reflects rather obesity than insulin resistance. Myrenne "M1" aggregation is rather a marker of hyperinsulinemia. Thus, the hemorheologic picture of the metabolic syndrome is far to be only a reflect of insulin resistance alone. 相似文献
106.
Anne Jolivet Emmanuelle Cadot Olivier Angénieux Sophie Florence Sophie Lesieur Jacques Lebas Pierre Chauvin 《Journal of immigrant and minority health / Center for Minority Public Health》2014,16(4):586-594
Few data exist on the health status and heath care utilization of the undocumented migrants in France. Data are particularly scarce in French overseas territories where this population is numerous. We aimed to describe the characteristics of undocumented patients who use the emergency department of Saint-Laurent du Maroni Hospital (SLMH) in French Guiana, and to identify factors associated with their subsequent hospitalization. In a random sample of 177 patients, we used logistic regression models to test the mediational role of health-care system utilization and medical characteristics at admission in the association between residency status and hospitalization. More than a quarter of patients (27.7 %) were undocumented migrants, who were subsequently hospitalized more often than the others [OR 3.11, 95 % CI (1.32–7.34)]. More-severe symptoms at admission, a poorer access to health insurance, a greater distance between their home and SLMH, and poorer French language skills partially explained this higher hospitalization rate. Despite the fact that France has instituted a specific insurance program for the undocumented, an increasing number of barriers to accessing health care is being reported for these people. Our results suggest that these obstacles have some impacts in the utilization of hospital care. 相似文献
107.
108.
109.
Suzanne Ho-wai So Emmanuelle Roisin Peters Joel Swendsen Philippa Anne Garety Shitij Kapur 《Psychiatry research》2014
It has been suggested that different aspects of delusions (conviction, distress, preoccupation) respond to treatment at different rates, and that the cognitive bias of ‘Jumping to Conclusions’ (JTC) may predict treatment outcome. This study investigates changes in delusion dimensions using Experience Sampling Methodology (ESM) and the role of JTC as a predictor of change during the initial 2 weeks of antipsychotic treatment on admission to hospital. Sixteen acute patients with delusions were assessed seven times per day for 14 days using computerised ESM. ESM assessed moment-by-moment experiences of affect, psychotic symptoms, and delusion dimensions. Clinical ratings were completed at baseline, 1 week and 2 weeks later. The 'beads' task was used to measure JTC at baseline. Delusion dimensions improved over the two weeks of antipsychotic treatment and admission to hospital. Different delusional dimensions changed at different rates, with distress and disruption being more responsive than conviction and preoccupation on both PSYRATS and ESM ratings. Eight out of 16 participants showed a JTC bias on the beads task at baseline. Exploratory analyses showed that JTC predicted changes in the ESM ratings of delusion conviction and distress, suggesting that reasoning biases may predict treatment response. 相似文献
110.
Mathilde His Laurent Zelek Mélanie Deschasaux Camille Pouchieu Emmanuelle Kesse-Guyot Serge Hercberg Pilar Galan Paule Latino-Martel Jacques Blacher Mathilde Touvier 《European journal of epidemiology》2014,29(2):119-132
Experimental studies provided evidence about mechanisms by which cholesterol, especially high density lipoprotein cholesterol (HDL-C), could influence carcinogenesis, notably through antioxidant and anti-inflammatory properties. However, prospective studies that investigated the associations between specific lipid metabolism biomarkers and cancer risk provided inconsistent results. The objective was to investigate the prospective associations between total cholesterol (T-C), HDL-C, low density lipoprotein cholesterol, apolipoproteins A1 (apoA1) and B, and triglycerides and overall, breast and prostate cancer risk. Analyses were performed on 7,557 subjects of the Supplémentation en Vitamines et Minéraux Antioxydants Study, a nationwide French cohort study. Biomarkers of lipid metabolism were measured at baseline and analyzed regarding the risk of first primary incident cancer (N = 514 cases diagnosed during follow-up, 1994–2007), using Cox proportional hazards models. T-C was inversely associated with overall (HR1mmol/L increment = 0.91, 95 % CI 0.82–1.00; P = 0.04) and breast (HR1mmol/L increment = 0.83, 95 % CI 0.69–0.99; P = 0.04) cancer risk. HDL-C was also inversely associated with overall (HR1mmol/L increment = 0.61, 95 % CI 0.46–0.82; P = 0.0008) and breast (HR1mmol/L increment = 0.48, 95 % CI 0.28–0.83; P = 0.009) cancer risk. Consistently, apoA1 was inversely associated with overall (HR1g/L increment = 0.56, 95 % CI 0.39–0.82; P = 0.003) and breast (HR1g/L increment = 0.36, 95 % CI 0.18–0.73; P = 0.004) cancer risk. This prospective study suggests that pre-diagnostic serum levels of T-C, HDL-C and ApoA1 are associated with decreased overall and breast cancer risk. The confirmation of a role of cholesterol components in cancer development, by further large prospective and experimental studies, may have important implications in terms of public health, since cholesterol is already crucial in cardiovascular prevention. 相似文献