R497K polymorphism in epidermal growth factor receptor gene is associated with the risk of acute coronary syndrome

Background  

Previous studies suggested that genetic polymorphisms in the epidermal growth factor receptor (EGFR) gene had been implicated in the susceptibility to some tumors and inflammatory diseases. EGFR has been recently implicated in vascular pathophysiological processes associated with excessive remodeling and atherosclerosis. Acute coronary syndrome (ACS) is a clinical manifestation of preceding atherosclerosis. Our purpose was to investigate the association of the EGFR polymorphism with the risk of ACS. In this context, we analyzed the HER-1 R497K and EGFR intron 1 (CA)_n repeat polymorphisms in 191 patients with ACS and 210 age- and sex-matched controls in a Chinese population, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) strategy and direct sequencing.     

The intron 4c allele of the NOS3 gene is associated with ischemic stroke in African Americans

Background  

Ischemic stroke is the most common cause of disability in North America and in addition to the generally accepted risk factors, there is increasing evidence for the potential pathophysiological role of genes. One of these genes, the endothelial nitric oxide synthase gene (NOS3) has been reported as a genetic risk factor for ischemic stroke. To independently confirm and extend the results of these previous reports, we investigated this gene as a risk factor for stroke in an ethnically diverse study population.     

Evaluation of RGS4 as a candidate gene for schizophrenia.

Several studies have suggested that the regulator of G-protein signaling 4 (RGS4) may be a positional and functional candidate gene for schizophrenia. Three single nucleotide polymorphisms (SNP) located at the promoter region (SNP4 and SNP7) and the intron 1 (SNP18) of RGS4 have been verified in different ethnic groups. Positive results have been reported in these SNPs with different numbers of SNP combinatory haplotypes. In this study, these three SNP markers were genotyped in 218 schizophrenia pedigrees of Taiwan (864 individuals) for association analysis. Among these three SNPs, neither SNP4, SNP7, SNP18 has shown significant association with schizophrenia in single locus association analysis, nor any compositions of the three SNP haplotypes has shown significantly associations with the DSM-IV diagnosed schizophrenia. Our results fail to support the RGS4 as a candidate gene for schizophrenia when evaluated from these three SNP markers.     

CFTR 5T variant has a low penetrance in females that is partially attributable to its haplotype.

PURPOSE: The study's purpose was to understand the molecular basis for different clinical phenotypes of the 5T variant, a tract of 5 thymidines in intron 8 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which disrupts processing of CFTR mRNA and reduces synthesis from the corresponding CFTR alleles. METHOD: We analyzed the polymorphic TG dinucleotide repeat adjacent to the 5T variant in intron 8 and the codon 470 in exon 10. Patients selected for this study were positive for both the 5T variant and the major cystic fibrosis mutation, Delta F508. Almost all Delta F508 mutation alleles occur in a 10TG-9T-470M haplotype. Therefore, it is possible to determine the haplotype of the 5T variant in trans. RESULTS: Of the 74 samples analyzed, 41 (55%) were 11TG-5T-470M, 31 (42%) were 12TG-5T-470V, and 2 (3%) were 13TG-5T-470M. Of the 49 cases for which we had clinical information, 17.6% of females (6/34) and 66.7% of males (10/15) showed symptoms resembling atypical cystic fibrosis. The haplotype with the highest penetrance in females (42% or 5/12) and more than 80% (5/6) in males is 12TG-5T-470V. We also evaluated 12 males affected with congenital bilateral absence of vas deferens and positive for the 5T variant; 10 of 12 had the 12TG-5T-470V haplotype. CONCLUSION: Overall, the 5T variant has a milder clinical consequence than previously estimated in females. The clinical presentations of the 5T variant are associated with the 5T-12TG-470M haplotype.     

Do adults in contact with Australia's public sector mental health services get better?

This paper describes the outcomes of episodes of care for adults in public sector mental health services across Australia, with a view to informing the debate on service quality. Health of the Nation Outcome Scales (HoNOS) change scores and effect sizes were calculated for 14,659 acute inpatient episodes and 23,692 community episodes. The results showed that people in contact with public sector mental health services generally do get better, although the magnitude of improvement depends on the setting and episode type. This confirmatory finding is particularly positive, given current community concerns about the quality and effectiveness of mental health services.     

Optimization of Ga-67 imaging for detection and estimation tasks: dependence of imaging performance on spectral acquisition parameters

We have compared the use of two (93 and 185 keV) and three (93, 185, and 300 keV) photopeaks for Ga-67 tumor imaging and optimized the placement of each energy window. METHODS: The bases for optimization and evaluation were ideal and Bayesian signal-to-noise ratios (SNR) for the detection of spheres embedded in a realistic anthropomorphic digital torso phantom and ideal SNR for the estimation of their size and activity concentration. Seven spheres of radii ranging from 1 to 3 cm, located at several sites in the torso, were simulated using a realistic Monte Carlo program. We also calculated the ideal SNR for the detection from simple phantom acquisitions. RESULTS: For detection and estimation tasks, the optimum windows were identical for all sphere sizes and locations. For the 93 keV photopeak, the optimal window was 84-102 keV for the detection and 87-102 keV for estimation; these windows are narrower than the 20% window often used in the clinic (83-101 keV). For the 185 keV photopeak, the optimal window was 170-220 keV for the detection and 170-215 keV for estimation; these are substantially different than the 15% window used in our clinic (171-199 keV). For the 300 keV photopeak, the optimal window for detection was 270-320 keV, and for estimation, 280-320 keV. Using the three optimized, rather than only the two lower-energy, windows yielded a 9% increase in the SNR for the detection of the 3 cm diam sphere (a 12% increase for a 2 cm diam sphere) and a 7% increase in the SNR for estimation of its size. For the acquired phantom data, detection also increased by 9%-12% when using three, rather than two, energy windows.     

B cells regulate autoimmunity by provision of IL-10

To assess the importance of B cell control of T cell differentiation, we analyzed the course of the T helper type 1 (T(H)1)-driven disease experimental autoimmune encephalomyelitis in mice with an altered B cell compartment. We found that recovery was dependent on the presence of autoantigen-reactive B cells. B cells from recovered mice produced interleukin 10 (IL-10) in response to autoantigen. With a bone marrow chimeric system, we generated mice in which IL-10 deficiency was restricted to B cells but not T cells. In the absence of IL-10 production by B cells, the pro-inflammatory type 1 immune response persisted and mice did not recover. These data show that B cell-derived IL-10 plays a key role in controlling autoimmunity.     

Gain of 1q and loss of 22 are the most common changes detected by comparative genomic hybridisation in paediatric ependymoma

Ependymomas are the third most common brain tumour in the paediatric population. Although cytogenetic and molecular analyses have pinpointed deletions of chromosomes 6q, 17, and 22 in a subset of tumours, definitive patterns of genetic aberrations have not been determined. In the present study, we analysed 40 ependymomas from paediatric patients for genomic loss or gain using comparative genomic hybridisation (CGH). Eighteen of the tumours (45%) had no detectable regions of imbalance. In the remaining cases, the most common copy number aberrations were loss of 22 (25% of tumours) and gain of 1q (20%). Three regions of high copy number amplification were noted at 1q24-31 (three cases), 8q21-23 (two cases), and 9p (one case). Although there was no association with the loss or gain of any chromosome arm or with benign versus anaplastic histologic characteristics, the incidence of gain of 7q and 9p and loss of 17 and 22 was significantly higher in recurrent versus primary tumours. This study has identified a number of chromosomal regions that may contain candidate genes involved in the development of different subgroups of ependymoma.