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81.
Loss of heterozygosity in 7q myeloid disorders: clinical associations and genomic pathogenesis 总被引:1,自引:0,他引:1
Jerez A Sugimoto Y Makishima H Verma A Jankowska AM Przychodzen B Visconte V Tiu RV O'Keefe CL Mohamedali AM Kulasekararaj AG Pellagatti A McGraw K Muramatsu H Moliterno AR Sekeres MA McDevitt MA Kojima S List A Boultwood J Mufti GJ Maciejewski JP 《Blood》2012,119(25):6109-6117
Loss of heterozygosity affecting chromosome 7q is common in acute myeloid leukemia and myelodysplastic syndromes, pointing toward the essential role of this region in disease phenotype and clonal evolution. The higher resolution offered by recently developed genomic platforms may be used to establish more precise clinical correlations and identify specific target genes. We analyzed a series of patients with myeloid disorders using recent genomic technologies (1458 by single-nucleotide polymorphism arrays [SNP-A], 226 by next-generation sequencing, and 183 by expression microarrays). Using SNP-A, we identified chromosome 7q loss of heterozygosity segments in 161 of 1458 patients (11%); 26% of chronic myelomonocytic leukemia patients harbored 7q uniparental disomy, of which 41% had a homozygous EZH2 mutation. In addition, we describe an SNP-A-isolated deletion 7 hypocellular myelodysplastic syndrome subset, with a high rate of progression. Using direct and parallel sequencing, we found no recurrent mutations in typically large deletion 7q and monosomy 7 patients. In contrast, we detected a markedly decreased expression of genes included in our SNP-A defined minimally deleted regions. Although a 2-hit model is present in most patients with 7q uniparental disomy and a myeloproliferative phenotype, haplodeficient expression of defined regions of 7q may underlie pathogenesis in patients with deletions and predominant dysplastic features. 相似文献
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Victoria C. Wing Mera S. Barr Caroline E. Wass Nir Lipsman Andres M. Lozano Zafiris J. Daskalakis Tony P. George 《Brain stimulation》2013,6(3):221-230
BackgroundTobacco smoking is the leading cause of preventable deaths worldwide, but many smokers are simply unable to quit. Psychosocial and pharmaceutical treatments have shown modest results on smoking cessation rates, but there is an urgent need to develop treatments with greater efficacy. Brain stimulation methods are gaining increasing interest as possible addiction therapeutics.ObjectivesThe purpose of this paper is to review the studies that have evaluated brain stimulation techniques on tobacco addiction, and discuss future directions for research in this novel area of addiction interventions.MethodsElectronic and manual literature searches identified fifteen studies that administered repetitive transcranial magnetic stimulation (rTMS), cranial electrostimulation (CES), transcranial direct current stimulation (tDCS) or deep brain stimulation (DBS).ResultsrTMS was found to be the most well studied method with respect to tobacco addiction. Results indicate that rTMS and tDCS targeted to the dorsolateral prefrontal cortex (DLPFC) were the most efficacious in reducing tobacco cravings, an effect that may be mediated through the brain reward system involved in tobacco addiction. While rTMS was shown to reduce consumption of cigarettes, as yet no brain stimulation technique has been shown to significantly increase abstinence rates. It is possible that the therapeutic effects of rTMS and tDCS may be improved by optimization of stimulation parameters and increasing the duration of treatment.ConclusionAlthough further studies are needed to confirm the ability of brain stimulation methods to treat tobacco addiction, this review indicates that rTMS and tDCS both represent potentially novel treatment modalities. 相似文献
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International Ophthalmology - Report the foveal avascular zone (FAZ) area imaged by OCT angiography (OCTA) using a full spectrum probabilistic algorithm in eyes of healthy individuals from Costa... 相似文献
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Ana M. Ramos-Levi Andres Sanchez-Pernaute Lucio Cabrerizo Pilar Matia Ana Barabash Carmen Hernandez Alfonso L. Calle-Pascual Antonio J. Torres Miguel A. Rubio 《Obesity surgery》2013,23(12):2020-2025
Background
Remission of type 2 diabetes (T2D) is a desired outcome after bariatric surgery (BS). Even if this goal is not achieved, individuals who do not strictly fulfill remission criteria experience an overall improvement. The aim of this study was to evaluate the metabolic control status in patients considered as diabetes “non-remitters.”Methods
A retrospective study of 125 patients (59.2 % women) with preoperative diagnosis of T2D who underwent BS in a single center (2006–2011) was conducted. We collected anthropometric and metabolic parameters before surgery and at 1-year follow-up. T2D remission was defined according to the 2009 consensus statement: glycosylated hemoglobin (HbA1c) <6 %, fasting glucose (FG) <100 mg/dLs, and absence of pharmacologic treatment. We evaluated metabolic status of non-remitters, according to the American Diabetes Association's (ADA) target recommendations: HbA1c <7 %, LDL-c <100 mg/dL, triglycerides <150 mg/dL, and HDL-c >40 (male) or >50 mg/dL (female). Statistics: analysis of variance.Results
Baseline characteristics (mean ± SD): age 53.5?±?9.7 years, BMI 43.5?±?5.6 kg/m2, time since diagnosis of T2D 7.7?±?7.9 years, FG 162.0?±?56.3 mg/dL, HbA1c 7.7?±?1.6 %. ADA's target recommendations were present in 12 patients (9.6 %) preoperatively, and in 45 (36.0 %) at 1-year follow-up (p <0.001). Sixty-two (49.6 %) patients did not achieve diabetes remission; 26 (41.9 %) had now diet treatment, 30 (48.4 %) oral medications, and 6 (9.7 %) required insulin. Of the non-remitters, 57 (91.9 %) had HbA1c <7 % and 18 (40.0 %) achieved ADA's target recommendations. There were no differences between remitters and non-remitters in the number of individuals reaching ADA's combined metabolic control.Conclusions
Although almost 50 % of the patients may not be classified as diabetes remitters, their significant improvement in metabolic control should be regarded as a success, according to most scientific societies' target recommendations. 相似文献87.
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