Three hundred cDNAs containing putatively entire open reading frames (ORFs) for previously undefined genes were obtained from CD34+ hematopoietic stem/progenitor cells (HSPCs), based on EST cataloging, clone sequencing, in silico cloning, and rapid amplification of cDNA ends (RACE). The cDNA sizes ranged from 360 to 3496 bp and their ORFs coded for peptides of 58-752 amino acids. Public database search indicated that 225 cDNAs exhibited sequence similarities to genes identified across a variety of species. Homology analysis led to the recognition of 50 basic structural motifs/domains among these cDNAs. Genomic exon-intron organization could be established in 243 genes by integration of cDNA data with genome sequence information. Interestingly, a new gene named as HSPC070 on 3p was found to share a sequence of 105bp in 3Ј UTR with RAF gene in reversed transcription orientation. Chromosomal localizations were obtained using electronic mapping for 192 genes and with radiation hybrid (RH) for 38 genes. Macroarray technique was applied to screen the gene expression patterns in five hematopoietic cell lines (NB4, HL60, U937, K562, and Jurkat) and a number of genes with differential expression were found. The resource work has provided a wide range of information useful not only for expression genomics and annotation of genomic DNA sequence, but also for further research on the function of genes involved in hematopoietic development and differentiation.
Graves' disease (GD) is one of the most common human autoimmune diseases, and recent data estimated a prevalence of clinical hyperthyroidism of 0.25-1.09% in the population. Several reports have linked GD to the region 5q12-q33; and a locus between markers D5s436 and D5s434 was specifically linked to GD susceptibility in the Chinese population. In the present study, association analysis was performed using a large number of single-nucleotide polymorphisms (SNPs) at this locus in 2811 patients with GD recruited from different geographic regions of China. The strongest associations with GD in the combined Chinese Han cohorts were mapped to two SNPs in the promoter (pSNP) of SCGB3A2 [SNP76, rs1368408, P = 1.43 x 10(-6), odds ratio (OR) = 1.28 and SNP75, -623 - -622, P = 7.62 x 10(-5), OR = 1.32, respectively], a gene implicated in immune regulation. On the other hand, pSNP haplotypes composed of the SNP76 (rs1368408)+SNP74 (rs6882292) or SNP76+SNP75 (-623 approximately -622, AG/T) variants are correlated with high disease susceptibility (P = 0.0007, and P = 0.0192, respectively) in this combined Chinese Han cohort. Furthermore, these haplotypes were associated with reduced SCGB3A2 gene expression levels in human thyroid tissue, while functional analysis revealed a relatively low efficiency of SCGB3A2 promoters of the SNP76+SNP75 and SNP76+SNP74 haplotypes in driving gene expression. These results suggest that the SCGB3A2 gene may contribute to GD susceptibility.
Background Chronic insomnia is common in patients with arteriosclerotic cerebral small vessel disease (CSVD) and aggravates the cognitive impairment caused by CSVD. Low-dose trazodone is effective in treating insomnia, but it is unclear whether it can also improve cognitive function in CSVD patients. This study was performed to explore the effects of trazodone on sleep quality and cognitive function in CSVD comorbid with chronic insomnia. Methods This was a randomized, double-blind, placebo-controlled pilot study. Forty patients suffering from arteriosclerotic CSVD and insomnia were recruited from an outpatient clinic. Participants were randomized individually to receive either trazodone (study group) or a placebo (control group) for 4 weeks. The primary outcome was the cognitive score on the Montreal Cognitive Assessment scale (MoCA). Secondary outcomes included sleep parameters measured with polysomnography (PSG) and the Pittsburgh Sleep Quality Index. Results Trazodone caused significantly better improvements in concentration and recall abilities, measured with MoCA, as well as in PSG parameters such as sleep efficiency, N3 sleep ratio, and sleep continuity than the placebo, with no significant differences in the occurrence of side effects. The improvement of sleep quality was correlated with increased concentration and recall abilities. Conclusions A low dose of trazodone seems acceptable and effective in reducing insomnia severity and improving concentration and recall abilities in this pilot study. The improvement of cognition could be achieved by alleviation of insomnia severity. Considering the high incidence of insomnia in CSVD patients, the results of this preliminary study support the use of low-dose trazodone to deal with insomnia and cognitive impairment in CSVD.
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