Search results for "Somatic"
showing 10 items of 305 documents
BCL6: somatic mutations and expression in early-stage chronic lymphocytic leukemia
2009
BCL6 somatic mutations affect normal and tumoral post germinal center B-lymphocytes. Our objective was to analyse expression, mutations and polymorphisms in the BCL6 gene and to correlate those variables with the clinical outcome in early-stage chronic lymphocytic leukemia (CLL). CLL samples were used for characterisation of the mutational status of BCL6/ immunoglobulin variable heavy chain (IGHV) genes, and expression of BCL6 was determined by real time PCR and immunoblot. Out of 68 cases, 29% show somatic mutations on BCL6 which occur exclusively in IGHV mutated cases. They are single nucleotide substitutions located mainly in two short mutational hot spots. CLL cells express different le…
A Putatively Functional Haplotype in the Gene Encoding Transforming Growth Factor Beta-1 as a Potential Biomarker for Radiosensitivity
2011
Purpose To determine whether genetic variability in TGFB1 is related to circulating transforming growth factor-β1 (TGF-β1) plasma concentrations after radiotherapy and to radiosensitivity of lymphoid cells. Patients and Methods Transforming growth factor-β1 plasma concentrations ( n = 79) were measured in patients 1 year after radiotherapy and chromosomal aberrations ( n = 71) ex vivo before therapy start. Furthermore, TGF-β1 secretion and apoptosis were measured in isolated peripheral blood mononuclear cells of 55 healthy volunteers. These phenotypes were analyzed in relation to five germline polymorphisms in the 5′ region of the TGFB1 gene. Because of high linkage disequilibrium, these fi…
Clinical relevance of postzygotic mosaicism in Cornelia de Lange syndrome and purifying selection of NIPBL variants in blood.
2021
Postzygotic mosaicism (PZM) in NIPBL is a strong source of causality for Cornelia de Lange syndrome (CdLS) that can have major clinical implications. Here, we further delineate the role of somatic mosaicism in CdLS by describing a series of 11 unreported patients with mosaic disease-causing variants in NIPBL and performing a retrospective cohort study from a Spanish CdLS diagnostic center. By reviewing the literature and combining our findings with previously published data, we demonstrate a negative selection against somatic deleterious NIPBL variants in blood. Furthermore, the analysis of all reported cases indicates an unusual high prevalence of mosaicism in CdLS, occurring in 13.1% of p…
Dipole source analyses of laser evoked potentials obtained from subdural grid recordings from primary somatic sensory cortex
2011
The cortical potentials evoked by cutaneous application of a laser stimulus (laser evoked potentials, LEP) often include potentials in the primary somatic sensory cortex (S1), which may be located within the subdivisions of S1 including Brodmann areas 3A, 3B, 1, and 2. The precise location of the LEP generator may clarify the pattern of activation of human S1 by painful stimuli. We now test the hypothesis that the generators of the LEP are located in human Brodmann area 1 or 3A within S1. Local field potential (LFP) source analysis of the LEP was obtained from subdural grids over sensorimotor cortex in two patients undergoing epilepsy surgery. The relationship of LEP dipoles was compared wi…
Functional polymorphism in the neuropeptide Y gene promoter (rs16147) is associated with serum leptin levels and waist-hip ratio in women
2013
<b><i>Objective:</i></b> The neuropeptide-Y (NP-Y) gene is a strong candidate gene in the pathophysiology of obesity-linked behavior, and several single-nucleotide polymorphisms of NP-Y have already been linked to body weight and appetite. However, the results from current studies remain inconclusive. The aim of the present study was to test whether a certain functional genetic variant (SNP rs16147) in the NP-Y promoter gene is associated with serum leptin levels and body fat distribution. <b><i>Method:</i></b> We genotyped and measured the serum leptin levels of the NP-Y rs16147 polymorphism in 1,097 Caucasian subjects in the context of a pop…
Intrathecal somatic hypermutation of IgM in multiple sclerosis and neuroinflammation
2014
Intrathecal oligoclonal bands of the cerebrospinal fluid are considered the most important immunological biomarkers of multiple sclerosis. They typically consist of clonally expanded IgG antibodies that underwent affinity maturation during sustained stimulation by largely unknown antigens. In addition, ∼40% of patients with multiple sclerosis have oligoclonal bands that consist of expanded IgM antibodies. We investigated the molecular composition of IgM- and IgG-chains from cerebrospinal fluid of 12 patients with multiple sclerosis, seven patients with other neurological diseases, and eight healthy control subjects by high-throughput deep-sequencing and single-cell PCR. Further, we studied …
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…
Blunted Electrodermal and Psychological Response to Acute Stress in Family Caregivers of People with Eating Disorders.
2016
AbstractCaring for an offspring with an eating disorder (ED) is associated with high levels of distress, and health problems. Indeed, ED caregivers have to cope with a range of challenges related to their caring role, which represents a chronic stress situation. This tends to alter body homeostasis and caregivers’ health status. This study aimed to analyse the electrodermal reactivity and psychological response to acute stress in ED caregivers compared to non-caregivers. As expected, caregivers showed lower electrodermal (p < .001, η2partial = .269 for SCL and p < .01, η2partial = .214 for NSCRs) and psychological response (p < .05, η2partial = .198) to acute stress than non-caregi…
Psychodynamic focal group treatment for psychosomatic inpatients--with an emphasis on work-related conflicts.
2006
Conflicts arising from the work setting have remained a neglected issue in psychotherapy. To address this, the present study investigated the effectiveness of a manualized focal group treatment for psychotherapeutic inpatients suffering from vocational strains and conflicts and identified predictors of outcome. Cohorts of patients were assigned either to a treatment (N=144) or control condition (N=135). The group therapy intervention was found to be highly accepted by participants who were also more optimistic about returning to work and more favorable in their evaluations of treatment than patients in the treatment-as-usual condition. Group climate was found to be a predictor of favorable …
Depression and religiosity in older age
2011
Abstract We investigated the hypothesis that religious commitment could help counter general affective distress, accompanying depressive symptoms, in older age. A total of 34 older adults, all catholic believers, completed self-reported questionnaires on the presence of depressive symptoms, religiosity, health, worry, and the style of coping with stress. The depressive and non-depressive subgroups were then created. The prevalence of depressive symptoms was 50%, with the substantial predominance of females. Regression analyses indicate that health expectations and worry significantly worsen with increasing intensity of depressive symptoms. The results further show that religious engagement …