Search results for "ERAS"
showing 10 items of 4431 documents
NDST1 missense mutations in autosomal recessive intellectual disability.
2014
NDST1 was recently proposed as a candidate gene for autosomal recessive intellectual disability in two families. It encodes a bifunctional GlcNAc N-deacetylase/N-sulfotransferase with important functions in heparan sulfate biosynthesis. In mice, Ndst1 is crucial for embryonic development and homozygous null mutations are perinatally lethal. We now report on two additional unrelated families with homozygous missense NDST1 mutations. All mutations described to date predict the substitution of conserved amino acids in the sulfotransferase domain, and mutation modeling predicts drastic alterations in the local protein conformation. Comparing the four families, we noticed significant overlap in …
Differential expression of specific microRNA and their targets in acute myeloid leukemia
2010
Acute myeloid leukemia (AML) the most common acute leukemia in adults is characterized by various cytogenetic and molecular abnormalities. However, the genetic etiology of the disease is not yet fully understood. MicroRNAs (miRNA) are small noncoding RNAs which regulate the expression of target mRNAs both at transcriptional and translational level. In recent years, miRNAs have been identified as a novel mechanism in gene regulation, which show variable expression during myeloid differentiation. We studied miRNA expression of leukemic blasts of 29 cases of newly diagnosed and genetically defined AML using quantitative reverse transcription polymerase chain reaction (RT-PCR) for 365 human miR…
Clonal evolution in relapsed NPM1-mutated acute myeloid leukemia.
2013
Mutations in the nucleophosmin 1 (NPM1) gene are considered a founder event in the pathogenesis of acute myeloid leukemia (AML). To address the role of clonal evolution in relapsed NPM1-mutated (NPM1mut) AML, we applied high-resolution, genome-wide, single-nucleotide polymorphism array profiling to detect copy number alterations (CNAs) and uniparental disomies (UPDs) and performed comprehensive gene mutation screening in 53 paired bone marrow/peripheral blood samples obtained at diagnosis and relapse. At diagnosis, 15 aberrations (CNAs, n = 10; UPDs, n = 5) were identified in 13 patients (25%), whereas at relapse, 56 genomic alterations (CNAs, n = 46; UPDs, n = 10) were detected in 29 patie…
End-plate dysfunction in acute organophosphate intoxication.
1989
Acute organophosphate intoxication resulting from suicide attempts in 14 patients produced a series of electrophysiologic abnormalities that correlated with the clinical course. Spontaneous repetitive firing of single evoked compound muscle action potentials (CMAP) was the earliest and most sensitive indicator of the acetylcholinesterase inhibition. A decrement of evoked CMAP following repetitive nerve stimulation was the most severe abnormality. At the height of the intoxication no CMAP was evoked after the first few stimuli. The decrement-increment phenomenon occurred only at milder stages of intoxication and its features are characteristic of acetylcholinesterase inhibition. These electr…
Relaxation and cyclic GMP levels in response to sildenafil in human pulmonary arteries from donors.
2005
We measured cyclic GMP formation and relaxation response to sildenafil given either alone or in combination with sodium nitroprusside (SNP) in pulmonary arteries obtained from 13 multi-organ donors. Sildenafil (10(-9)-10(-4) M) caused concentration-dependent relaxations and amplified the relaxation induced by SNP. Relaxation was unaffected by endothelium removal or by pre-treatment with the inhibitor of nitric oxide synthase L-NMMA (10(-4) M). SNP (10(-7) M) caused elevation of cyclic GMP levels that was potentiated by sildenafil (10(-6) M). Thus, the enhancement of SNP-induced relaxation by sildenafil is mainly due to an increase in cyclic GMP accumulation.
MGMT promoter methylation status and prognosis of patients with primary or recurrent glioblastoma treated with carmustine wafers
2013
The prognostic role of O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation in glioblastoma patients treated with carmustine (BCNU) wafer implantation is unclear. Here, we report on a retrospective study of 47 patients with either newly diagnosed (30 patients) or recurrent (17 patients) glioblastoma (WHO grade IV) treated with BCNU (bis-chloroethylnitrosourea) wafers. Thirteen of the newly diagnosed patients received local BCNU and irradiation only (first-line BCNU), while 17 patients additionally received concomitant and adjuvant temozolomide (TMZ) radiochemotherapy (first-line BCNU + TMZ). Of the 17 patients treated for recurrent glioblastoma (second-line BCNU), 16 had rec…
Therapy-related acute myeloid leukemia developing 14 years after allogeneic hematopoietic stem cell transplantation, from a persistent R882H- DNMT3A …
2018
Abstract Background Therapy-related acute myeloid leukemia (t-AML) develops in patients with prior exposure to cytotoxic therapies. Selection of a pre-existing TP53 mutated clone prone to acquire additional mutational events has been suggested as the main pathogenic mechanism of t-AML. Here, we report a unique case of t-AML which developed from a pre-existing DNMT3A mutated clone that persisted in the patient for more than 10 years despite treatment with intensive chemotherapy and allogeneic hematopoietic stem cell transplantation (alloHSCT). Case presentation A 42-year-old male was diagnosed with AML harboring a normal karyotype and mutations in the NPM1 (c.863_864ins, p.W288 fs*12), DNMT3…
Phenotypic and genetic analysis of biofilm formation by Staphylococcus epidermidis.
2012
Objective. The most important virulence factor of Staphylococcus epidermidis is their capability to form a biofilm on the surfaces of implanted medical devices. The accumulative phase of biofilm formation is linked to the production of intercellular adhesin encoded by the icaADBC operon and accumulation-associated protein by the aap gene. The aim of the study was to investigate biofilm formation phenotypically and genetically in clinical strains of S. epidermidis in comparison with commensal strains. Material and Methods. The study was carried out in 4 hospitals in Riga, Latvia. In total, 105 clinical strains of Staphylococcus epidermidis isolated from patients’ blood (n=67) and intravenous…
Somatic loss of an EXT2 gene mutation during malignant progression in a patient with hereditary multiple osteochondromas
2015
Multiple osteochondromas (MO) is an autosomal-dominant skeletal disorder caused by mutations in the exostosin-1 ( EXT1 ) or exostosin-2 ( EXT2 ) genes. In this study, we report the analysis of the mutational status of the EXT2 gene in tumor samples derived from a patient affected by hereditary MO, documenting the somatic loss of the germline mutation in a giant chondrosarcoma and in a rapidly growing osteochondroma. The sequencing of all exons and exon–intron junctions of the EXT1 and EXT2 genes from blood DNA of the proband did not reveal any mutation in the EXT1 gene but did demonstrate the presence of the transition point mutation c.67C > T in the EXT2 gene, determining the introduction …
Gene-environment interaction as a predictor of early adjustment in first episode psychosis.
2017
Abstract Background This study aims to explore the gene-environment interaction hypothesis applied to pre-symptomatic neurodevelopmental phenotypes of first episode psychosis (FEP), that is, genetic factors might increase vulnerability to the effects of environmental adverse conditions occurring at later stages of development. Methods We constructed a schematic ‘two-hit’ model, with Val/Val homozygosity for the catechol- O -methyltransferase ( COMT ) Val158Met polymorphism as the ‘first hit’ and history of obstetric complications and parental socioeconomic status as ‘second hits’. Early adjustment, measured using the Premorbid Adjustment Scale, was considered the main outcome. The study pop…