Search results for "3a"

A total of 220 patients with autosomal dominant spastic paraplegia do not display mutations in the SLC33A1 gene (SPG42).

2010

The most frequent causes of autosomal dominant (AD) hereditary spastic paraplegias (HSP) (ADHSP) are mutations in the SPAST gene (SPG4 locus). However, roughly 60% of patients are negative for SPAST mutations, despite their family history being compatible with AD inheritance. A mutation in the gene for an acetyl-CoA transporter (SLC33A1) has recently been reported in one Chinese family to cause ADHSP-type SPG42. In this study, we screened 220 independent SPAST mutation-negative ADHSP samples for mutations in the SLC33A1 gene by high-resolution melting curve analysis. Conspicuous samples were validated by direct sequencing. Moreover, copy number variations affecting SLC33A1 were screened by …

CYP2D6 increases toxicity of the designer drug 4-methylthioamphetamine (4-MTA)

2006

4-Methylthioamphetamine (4-MTA) belongs to a group of new amphetamine derivatives that is usually sold as "ecstasy" or "flatliners" on the illicit drug market. Large interindividual differences in 4-MTA mediated toxicity have been reported in humans. Therefore, we tested whether CYP2D6 or its variant alleles as well as CYP3A4 influence the susceptibility to 4-MTA. For this purpose, we used the colony formation assay with Chinese hamster lung fibroblast V79 cells expressing human wild-type CYP2D6 (CYP2D6*1), the low activity alleles CYP2D6*2, CYP2D6*9, as well as human CYP3A4. The obtained results showed that the expression of wild type CYP2D6*1 clearly enhanced the susceptibility to the cyt…

Pharmacogenetic considerations for optimizing tacrolimus dosing in liver and kidney transplant patients

2013

The introduction of tacrolimus in clinical practice has improved patient survival after organ transplant. However, despite the long use of tacrolimus in clinical practice, the best way to use this agent is still a matter of intense debate. The start of the genomic era has generated new research areas, such as pharmacogenetics, which studies the variability of drug response in relation to the genetic factors involved in the processes responsible for the pharmacokinetics and/or the action mechanism of a drug in the body. This variability seems to be correlated with the presence of genetic polymorphisms. Genotyping is an attractive option especially for the initiation of the dosing of tacrolim…

Effect of CYP3A5*3 on kidney transplant recipients treated with tacrolimus: a systematic review and meta-analysis of observational studies

2014

The highly variable pharmacokinetics of tacrolimus can hamper the optimal management of kidney transplant patients. This variability has been attributed to the genetic polymorphism of CYP3A5 6986A>G, but the evidence is not clear. We conducted a meta-analysis of studies evaluating the effect of CYP3A5 polymorphism on kidney transplant recipients with tacrolimus plasma concentration divided by daily dose per body weight (C/D) and clinical outcomes. We searched in MEDLINE and EMBASE. We found evidence suggesting a significantly lower C/D among CYP3A5*1 allele carriers compared with carriers of the CYP3A5*3/*3 genotype at weeks 1 and 2, and months 1, 3, 6 and 12. We demonstrated that the expre…

La Perdita di Funzione del Complesso di Deacetilazione Istonica Sin3A/Rpd3 Causa Fusioni Telomeriche

2008

The probability that $x$ and $y$ commute in a compact group

2010

We show that a compact group $G$ has finite conjugacy classes, i.e., is an FC-group if and only if its center $Z(G)$ is open if and only if its commutator subgroup $G'$ is finite. Let $d(G)$ denote the Haar measure of the set of all pairs $(x,y)$ in $G \times G$ for which $[x,y] = 1$; this, formally, is the probability that two randomly picked elements commute. We prove that $d(G)$ is always rational and that it is positive if and only if $G$ is an extension of an FC-group by a finite group. This entails that $G$ is abelian by finite. The proofs involve measure theory, transformation groups, Lie theory of arbitrary compact groups, and representation theory of compact groups. Examples and re…

$n$-harmonic coordinates and the regularity of conformal mappings

2014

This article studies the smoothness of conformal mappings between two Riemannian manifolds whose metric tensors have limited regularity. We show that any bi-Lipschitz conformal mapping or $1$-quasiregular mapping between two manifolds with $C^r$ metric tensors ($r > 1$) is a $C^{r+1}$ conformal (local) diffeomorphism. This result was proved in [12, 27, 33], but we give a new proof of this fact. The proof is based on $n$-harmonic coordinates, a generalization of the standard harmonic coordinates that is particularly suited to studying conformal mappings. We establish the existence of a $p$-harmonic coordinate system for $1 < p < \infty$ on any Riemannian manifold.

Mutant p53 gain of function can be at the root of dedifferentiation of human osteosarcoma MG63 cells into 3AB-OS cancer stem cells

2014

Osteosarcoma is a highly metastatic tumor affecting adolescents, for which there is no second-line chemotherapy. As suggested for most tumors, its capability to overgrow is probably driven by cancer stem cells (CSCs), and finding new targets to kill CSCs may be critical for improving patient survival. TP53 is the most frequently mutated tumor suppressor gene in cancers and mutant p53 protein (mutp53) can acquire gain of function (GOF) strongly contributing to malignancy. Studies thus far have not shown p53-GOF in osteosarcoma. Here, we investigated TP53 gene status/role in 3AB-OS cells-a highly aggressive CSC line previously selected from human osteosarcoma MG63 cells-to evaluate its involv…

Human osteosarcoma 3AB-OS cancer stem cells is a model to study microRNA-29b-1 involvement in self-renewal and fate decisions of stem cells

2014

Caracterización molecular de las leucemias mieloides agudas de novo

2013

La secuenciación es la técnica de elección para identificar mutaciones. Sin embargo, tiene un coste elevado, es laboriosa y su sensibilidad es limitada. Recientemente, el nuevo método de análisis de alta resolución con curvas de fusión (High Resolution Melt, HRM) permite detectar de forma rápida y específica mutaciones, polimorfismos y cambios epigenéticos. La leucemia mieloide aguda (LMA) son enfermedades heterogéneas con distintos comportamientos clínicos. El 40-50% de los pacientes no presentan alteraciones cromosómicas específicas y los mecanismos moleculares que subyacen en su patogenia son en su mayor parte desconocidos. Avances en la caracterización molecular han permitido la identif…