Search results for "abnormal"
showing 10 items of 761 documents
Pluripotent stem cells to model Hutchinson-Gilford progeria syndrome (HGPS): Current trends and future perspectives for drug discovery
2015
Progeria, or Hutchinson-Gilford progeria syndrome (HGPS), is a rare, fatal genetic disease characterized by an appearance of accelerated aging in children. This syndrome is typically caused by mutations in codon 608 (p.G608G) of the LMNA, leading to the production of a mutated form of lamin A precursor called progerin. In HGPS, progerin accumulates in cells causing progressive molecular defects, including nuclear shape abnormalities, chromatin disorganization, damage to DNA and delays in cell proliferation. Here we report how, over the past five years, pluripotent stem cells have provided new insights into the study of HGPS and opened new original therapeutic perspectives to treat the disea…
Epigenetic involvement in Hutchinson-Gilford progeria syndrome: a mini-review.
2013
Hutchinson-Gilford progeria syndrome (HGPS) is a rare human genetic disease that leads to a severe premature ageing phenotype, caused by mutations in the <i>LMNA</i> gene. The <i>LMNA</i> gene codes for lamin-A and lamin-C proteins, which are structural components of the nuclear lamina. HGPS is usually caused by a de novo <i>C1824T</i> mutation that leads to the accumulation of a dominant negative form of lamin-A called progerin. Progerin also accumulates physiologically in normal ageing cells as a rare splicing form of lamin-A transcripts. From this perspective, HGPS cells seem to be good candidates for the study of the physiological mechanisms of ageing…
Cytoprotective effects of the antioxidant phytochemical indicaxanthin in beta-thalassemia red blood cells
2006
Antioxidant phytochemicals are investigated as novel treatments for supportive therapy in beta-thalassemia. The dietary indicaxanthin was assessed for its protective effects on human beta-thalassemic RBCs submitted in vitro to oxidative haemolysis by cumene hydroperoxide. Indicaxanthin at 1.0-10 microM enhanced the resistance to haemolysis dose-dependently. In addition, it prevented lipid and haemoglobin (Hb) oxidation, and retarded vitamin E and GSH depletion. After ex vivo spiking of blood from thalassemia patients with indicaxanthin, the phytochemical was recovered in the soluble cell compartment of the RBCs. A spectrophotometric study showed that indicaxanthin can reduce perferryl-Hb ge…
Sporadic and Familial Variants in NF1: An Explanation of the Wide Variability in Neurocognitive Phenotype?
2020
Background: Cognitive impairment is the most common neurological manifestation in NF1 and occurs in 30-70% of NF1 cases. The onset and severity of each specific cognitive deficit varies greatly from child to child, with no apparent external causes. The wide variability of phenotype is the most complex aspect in terms of management and care. Despite multiple research, the mechanism underlying the high heterogeneity in NF1 has not yet been elucidated. While many studies have focused on the effects of specific and precise genetic mutations on the NF1 phenotype, little has been done on the impact of NF1 transmission (sporadic vs. familial cases). We used a complete neuropsychological evaluation…
Safety of tiotropium and olodaterol fixed-dose combination for COPD in patients on β-blockers
2015
Introduction: The TONADO studies (NCT01431274; NCT01431287) established the efficacy and safety of a new once-daily fixed-dose combination (FDC) with tiotropium (T), a long-acting muscarinic antagonist, and olodaterol (O), a long-acting β 2 -agonist, for the treatment of COPD. This post hoc analysis evaluates T+O safety in the subgroup of patients (pts) receiving β-blockers (BBs) in these studies. Methods: These were randomised, double-blind, parallel-group, 52-week, Phase III trials comparing T+O FDC (2.5/5 µg; 5/5 µg) with the monocomponents. Adverse events (AEs) and serious AEs (SAEs) were recorded and SAEs independently adjudicated. Pooled safety data from pts receiving BBs at baseline …
Absence of mutation at the GAP-related domain of the neurofibromatosis type 1 gene in sporadic neurofibrosarcomas and other bone and soft tissue sarc…
1995
The NF1 gene encodes neurofibromin, a GTPase-activating protein containing a GAP-related domain (NF1-GRD) that is capable of downregulating ras by stimulating ras intrinsic GTPase activity. We tested 44 sarcomas, nine of which corresponded to sporadic neurofibrosarcomas, for mutations at the NF1-GRD by the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) technique, finding no mutation in every sample tested. We suggest that inactivation of the NF1-GRD by gene mutation seems not to be an important event in the tumorigenesis of sarcomas.
In the literature: April 2020
2020
Deficient DNA mismatch repair (dMMR) may be caused by germline or somatic mutations in mismatch repair genes ( MLH1 , MSH2 , MSH3 , MSH6 and PMS2 ) or through epigenetic silencing of MLH1 .1 dMMR induces a hypermutator phenotype, also known as microsatellite instability (MSI). Next-generation sequencing identifies MSI in 12 cancer types. The highest prevalence is seen in endometrial cancer (31.4%), followed by colorectal cancer (19.7%) and gastric cancer (GC, 19.1%). MSI was related to better prognosis for colorectal cancer and GC . Moreover, the dMMR/MSI hypermutator phenotype is thought to produce large numbers of immunogenic neoantigens that can be recognised by immune cells, leading to …
First analysis of the National Lung Cancer Register in Spain (RTT).
2018
e13608Background: The Spanish Lung Cancer Group (GECP) initiated a Tumor Thoracic Register (RTT) in September 2016 with the aim of evaluating accurate, basic data concerning this oncological pathol...
A ceRNA analysis on LMNA gene focusing on the Hutchinson-Gilford progeria syndrome
2013
Background: Hutchinson-Gilford progeria syndrome is a rare dominant human disease of genetic origin. The average life expectancy is about 20 years, patients’ life quality is still very poor and no efficient therapy has yet been developed. It is caused by mutation of the LMNA gene, which results in accumulation in the nuclear membrane of a particular splicing form of Lamin-A called progerin. The mechanism by which progerin perturbs cellular homeostasis and leads to the symptoms is still under debate. Micro-RNAs are able to negatively regulate transcription by coupling with the 3’ UnTranslated Region of messenger RNAs. Several Micro-RNAs recognize the same 3’ UnTranslated Region and each Micr…
Tissue‐dependent differences in Bardet–Biedl syndrome gene expression
2019
BACKGROUND INFORMATION Primary cilia are highly conserved multifunctional cell organelles that extend from the cell membrane. A range of genetic disorders, collectively termed ciliopathies, is attributed to primary cilia dysfunction. The archetypical ciliopathy is the Bardet-Biedl syndrome (BBS), patients of which display virtually all symptoms associated with dysfunctional cilia. The primary cilium acts as a sensory organelle transmitting intra- and extracellular signals thereby transducing various signalling pathways facilitated by the BBS proteins. Growing evidence suggests that cilia proteins also have alternative functions in ciliary independent mechanisms, which might be contributing …