Biomedical subjects

Juan R González

Publications and source records attributed to Juan R González.

10 recordsLinked to original sources

PubMed2007

Brain-derived neurotrophic factor Val66Met and psychiatric disorders: meta-analysis of case-control studies confirm association to substance-related disorders, eating disorders, and schizophrenia.

BACKGROUND: There is an increasing recognition that the pathophysiology of mental disorders could be the result of deregulation of synaptic plasticity with alterations of neurotrophins. The valine (Val)66-to-methionine (Met) variant, located in the pro brain-derived neurotrophic factor (BDNF) sequence, has been extensively studied through linkage and association approaches in several psychiatric disorders. METHODS: We performed a meta-analysis restricted to individual case-control studies in different categories of mental disorders and BDNF Val66Met polymorphism. We included data from 39 case-control studies encompassing psychiatric phenotypes: eating disorders, substance-related disorders, mood disorders, and schizophrenia, among others. RESULTS: The association of Val66Met was confined to three diagnoses: substance-related disorders, eating disorders, and schizophrenia. The Val/Met and the Met/Met genotypes increase the risk for eating disorders up to 33%, while these same genotypes confer a 21% protective effect in substance-related disorders. The homozygous carriers Met/Met showed a 19% increased risk of schizophrenia with respect to the heterozygous state. CONCLUSIONS: The study confirms the association of Val66Met to substance-related disorders, eating disorders, and schizophrenia. It remains to be determined if other variants in tight linkage disequilibrium with Val66Met could configure an extended functional haplotype that would explain observed discrepancies in risk estimations across studies.

Adult↗

PubMed2006

Global variation in copy number in the human genome.

Copy number variation (CNV) of DNA sequences is functionally significant but has yet to be fully ascertained. We have constructed a first-generation CNV map of the human genome through the study of 270 individuals from four populations with ancestry in Europe, Africa or Asia (the HapMap collection). DNA from these individuals was screened for CNV using two complementary technologies: single-nucleotide polymorphism (SNP) genotyping arrays, and clone-based comparative genomic hybridization. A total of 1,447 copy number variable regions (CNVRs), which can encompass overlapping or adjacent gains or losses, covering 360 megabases (12% of the genome) were identified in these populations. These CNVRs contained hundreds of genes, disease loci, functional elements and segmental duplications. Notably, the CNVRs encompassed more nucleotide content per genome than SNPs, underscoring the importance of CNV in genetic diversity and evolution. The data obtained delineate linkage disequilibrium patterns for many CNVs, and reveal marked variation in copy number among populations. We also demonstrate the utility of this resource for genetic disease studies.

Chromosome Mapping↗

PubMed2006

[Time trend of breast cancer incidence in Catalonia].

BACKGROUND AND OBJECTIVE: Time trend of breast cancer incidence in Catalonia in the last 20 years is evaluated by a age-period-cohort model. POPULATION AND METHOD: Women older than 25 years diagnosed with breast cancer between 1980 and 1999 in the population covered by Tarragona and Girona population-based cancer registries. To investigate the age, period and birth cohort effect in the time trends of breast cancer incidence, Decarli and La Vecchia and Holdford's methods were used. RESULTS: The world age-standardized rate (25 to > or = 85 years old) has increased from 53.9 cases per 100,000 women-year in the period 1980-1984 to 83.9 per 100,000 women-year in the period 1995-1999. The annual percentage change was 2.2% (95% confidence interval, 1.8-2.6). According to age-period-cohort model an increment of the incidence exists depending on age and birth cohort, being the period effect less important. CONCLUSIONS: Breast cancer incidence has significantly increased in Catalonia. The birth cohort seems to be more important than the period effect in this increment, which supposes a change on the prevalence of the risk factor, although the use of screening diagnosis techniques might explain a part of the period effect.

Adult↗

PubMed2006

A recessive Mendelian model to predict carrier probabilities of DFNB1 for nonsyndromic deafness.

Mutations in the DFNB1 locus, where two connexin genes are located (GJB2 and GJB6), account for half of congenital cases of nonsyndromic autosomal recessive deafness. Because of the high frequency of DFNB1 gene mutations and the availability of genetic diagnostic tests involving these genes, they are the best candidates to develop a risk prediction model of being hearing impaired. People undergoing genetic counseling are normally interested in knowing the probability of having a hearing impaired child given his/her family history. To address this, a Mendelian model that predicts the probability of being a carrier of DFNB1 mutations, using family history of deafness, has been developed. This probability will be useful as additional information to decide whether or not a genetic test should be performed. This model incorporates Mendelian mode of inheritance, the age of onset of the disease, and the current age of hearing family members. The carrier probabilities are obtained using Bayes' theorem, in which mutation prevalence is used as the prior distribution. We have validated our model by using information from 305 families affected with congenital or progressive nonsyndromic deafness, in which genetic analysis of GJB2 and GJB6 had already been performed. This model works well, especially in homozygous carriers, showing a high discriminative power. This indicates that our proposed model can be useful in the context of clinical counseling of autosomal recessive disorders.

Adult↗

PubMed2006

Opioid-induced hyperalgesia in a murine model of postoperative pain: role of nitric oxide generated from the inducible nitric oxide synthase.

BACKGROUND: Opioid-induced delayed hyperalgesia and allodynia have been reported in human and animal models. The authors evaluated the influence of different opioids used during clinical anesthesia on nociceptive sensitivity and incisional pain in mice. The role of the inducible nitric oxide synthase on surgical pain and opioid-induced pronociception also was investigated. METHODS: CD1 mice were used to study the efficacy of opioids inducing pronociception and enhancing incisional pain. The implication of nitric oxide generated from the inducible nitric oxide synthase was investigated using knockout mice (C57/BL6) for its gene. Mice underwent right hind paw surgery under sevoflurane anesthesia combined with subcutaneous administration of saline or the opioids fentanyl (0.05 mg/kg), alfentanil (1 mg/kg), and remifentanil (0.04 mg/kg). Nociception was evaluated daily for 7 days using paw-pressure, plantar, and von Frey tests. RESULTS: The antinociceptive effect of opioids was followed by long-lasting thermal hyperalgesia and mechanical allodynia (each lasting between 2 and 7 days), but not mechanical hyperalgesia. Intraoperative infusion of opioids significantly enhanced incisional pain in all tests. The most prominent effects were observed with remifentanil. The inducible nitric oxide synthase gene deletion attenuated both remifentanil- and incision-induced pronociceptive effects. In mutant mice for the inducible nitric oxide synthase gene, remifentanil was still efficient in enhancing incisional pain, but the global pronociceptive effect was attenuated significantly as compared with wild-type mice. CONCLUSIONS: The authors' study demonstrates that the intraoperative administration of fentanyl or remifentanil enhances the extent and duration of postoperative pain. The results suggest a role of the nitric oxide systems in the cause of acute postoperative pain and opioid-induced pronociception.

Analgesics, Opioid↗

PubMed2005

Modelling intervention effects after cancer relapses.

This article addresses the problem of incorporating information regarding the effects of treatments or interventions into models for repeated cancer relapses. In contrast to many existing models, our approach permits the impact of interventions to differ after each relapse. We adopt the general model for recurrent events proposed by Peña and Hollander, in which the effect of interventions is represented by an effective age process acting on the baseline hazard rate function. To accommodate the situation of cancer relapse, we propose an effective age function that encodes three possible therapeutic responses: complete remission, partial remission, and null response. The proposed model also incorporates the effect of covariates, the impact of previous relapses, and heterogeneity among individuals. We use our model to analyse the times to relapse for 63 patients with a particular subtype of indolent lymphoma and compare the results to those obtained using existing methods.

Female↗

PubMed2005

Murine segmental duplications are hot spots for chromosome and gene evolution.

Mouse and rat genomic sequences permit us to obtain a global view of evolutionary rearrangements that have occurred between the two species and to define hallmarks that might underlie these events. We present a comparative study of the sequence assemblies of mouse and rat genomes and report an enrichment of rodent-specific segmental duplications in regions where synteny is not preserved. We show that segmental duplications present higher rates of molecular evolution and that genes in rearranged regions have evolved faster than those located elsewhere. Previous studies have shown that synteny breakpoints between the mouse and the human genomes are enriched in human segmental duplications, suggesting a causative connection between such structures and evolutionary rearrangements. Our work provides further evidence to support the role of segmental duplications in chromosomal rearrangements in the evolution of the architecture of mammalian chromosomes and in the speciation processes that separate the mouse and the rat.

Animals↗

PubMed2004

Hla-DPB1 mismatch in HLA-A-B-DRB1 identical sibling donor stem cell transplantation and acute graft-versus-host disease.

BACKGROUND: The role of human leukocyte antigen (HLA)-DPB1 as a transplantation antigen is controversial. A higher incidence of acute graft-versus-host disease (aGVHD) has been described after unrelated donor bone marrow transplant when both HLA-DPB1 alleles were mismatched. METHODS: We investigated the impact of a single HLA-DPB1 mismatch after HLA-A-B-DRB1 identical sibling donor transplantation on aGVHD. We analyzed 627 adult patient-donor pairs and identified 30 pairs without HLA-DPB1 identity (4.78%). In 17 cases, the patient had an allele that was not shared by the donor. RESULTS: The cumulative incidence of grades II-IV aGVHD was higher in the HLA-DPB1 mismatched group (66.7% vs. 35.7%, p=0.012). The HLA-DPB1 mismatch was identified by multivariate analysis as an independent risk factor for aGVHD (p=0.020, RR=2.68, 95% CI: 1.73-3.62). CONCLUSIONS: HLA-DPB1 can mediate alloreactive responses. A single HLA-DPB1 mismatch increases the risk of aGVHD after sibling donor stem cell transplantation.

Acute Disease↗

PubMed2003

Suitability of oligonucleotide-mediated cystic fibrosis gene repair in airway epithelial cells.

BACKGROUND: Non-viral vector-mediated targeted gene repair could become a useful alternative to classical gene addition strategies. The methodology guarantees a physiologically regulated and persistent expression of the repaired gene, with reported gene conversion and phenotypic correction efficiencies approaching 40-50% in some in vitro and in vivo models of disease. This is particularly important for cystic fibrosis (CF) because of its complex pathophysiology and the cellular heterogeneity of the cystic fibrosis transmembrane conductance regulator (CFTR) gene expression and function in the lung. METHODS: A cell-free biochemical assay was applied to assess the ability of CF airway epithelial cells to support chimeraplast-mediated repair. In addition, a methodology allowing the relative quantification of the percentage of W1282X mutation repair in a heterozygous background using the PCR/oligonucleotide ligation assay (PCR/OLA) was developed. The performance of different chimeraplast and short single-stranded oligonucleotide structures delivered by non-viral vectors and electroporation was evaluated. RESULTS: Chimeraplast-mediated repair competency was corroborated in CF airway epithelial cells. However, their repair activity was about 5-fold lower than that found in liver cells. Moreover, regardless of the corrector oligonucleotide structure applied to our CF bronchial epithelial cells, of compound heterozygous genotype (F508del/W1282X), the percentage of their resulting wild-type allele in the W1282X (exon 20) locus of the CFTR gene was not significantly different from that of the control untreated cells by our PCR/OLA assay (confidence interval at 95% +/- 4 allele wild-type). CONCLUSIONS: Oligonucleotide-mediated CFTR gene repair is an inefficient process in CF airway epithelial cells. Further improvements in oligonucleotide structure, nuclear delivery and/or the capability for mismatch repair stimulation will be necessary to achieve therapeutic levels of mutation correction in these cells.

Base Sequence↗

PubMedDate not supplied

[Non-parametric estimation of survival function for recurrent events data].

Recurrent events when we deal with survival studies demand a different methodology from what is used in standard survival analysis. The main problem that we found when we make inference in these kind of studies is that the observations may not be independent. Thus, biased and inefficient estimators can be obtained if we do not take into account this fact. In the independent case, the interocurrence survival function can be estimated by the generalization of the limit product estimator (Peña et al. (2001)). However, if data are correlated, other models should be used such as frailty models or an estimator proposed by Wang and Chang (1999), that take into account the fact that interocurrence times were or not correlated. The aim of this paper has been the illustration of these approaches by using two real data sets.

Data Interpretation, Statistical↗