The PROGINS progesterone receptor gene polymorphism and idiopathic recurrent miscarriage.

OBJECTIVE: Progesterone inhibits lymphocyte cytotoxicity, natural killer cell degranulation, and release of proinflammatory cytokines and has been shown to protect against spontaneous miscarriage. We investigated the association between idiopathic recurrent miscarriage (IRM) and the PROGINS 306 base pair insertion polymorphism in intron G of the progesterone receptor gene, which is known to segregate with progesterone-dependent neoplasms. METHODS: In a case-control study we investigated 125 women with a history of three or more consecutive pregnancy losses before 20 weeks' gestation and 79 healthy controls with at least two live births and no history of pregnancy loss. Peripheral venous puncture, DNA extraction, and polymerase chain reaction were used to genotype women for the presence of the PROGINS polymorphism. RESULTS: Allele frequencies among women with IRM and controls were 85.2% and 89.2%, respectively, for allele T1 (wild type) and 14.8% and 10.8%, respectively, for allele T2 (mutant). No association between allele T2 and the occurrence of IRM was found (P =.3; odds ratio [OR] 0.69; confidence interval [CI] 0.34, 1.40). Genotype frequencies were not significantly different between the study group (T1/T1 73.6%, T1/T2 23.2%, T2/T2 3.2%) and the control group (T1/T1 79.7%, T1/T2 19%, T2/T2 1.3%) (P =.4). Between women with primary and secondary IRM, there were no statistically significant differences with respect to allele frequencies (82% versus 87%, P =.4 for allele T1 and 12% versus 13%, P =.6 for allele T2). CONCLUSIONS: We found that the PROGINS polymorphism in the progesterone receptor gene was not associated with IRM in white women.     

No association of common VCP variants with sporadic frontotemporal dementia

Mutations in the gene for valosin containing protein (VCP) cause autosomal dominant inclusion body myopathy associated with Paget disease and frontotemporal dementia (IBMPFD). To investigate the role of this novel gene in sporadic forms of frontotemporal dementia (FTD), we genotyped 27 single nucleotide polymorphisms covering the entire VCP genomic region in 198 patients with sporadic FTD and 184 matched controls from Germany. No significant association could be demonstrated. There is no evidence, that common variants in VCP confer a strong risk to the development of sporadic FTD.     

应用荧光高效液相法检测心肌磷脂酶D的活性

 目的：为心肌磷脂酶D活性的检测提供新的可靠、灵敏的实验方法。方法：提取心肌膜脂质，以荧光标记的磷脂酰胆碱及乙醇为底物。高效液相色谱条件：LiChrosphere 100色谱柱（250 mm×4 mm, 5 μm）为固定相，流动相A液为正已烷-丙醇-冰醋酸（82∶17∶1, V∶V∶V），流动相B液为丙醇-水-冰醋酸（85∶14∶1, V∶V∶V），柱温 45 ℃，流速1 mL/min，梯度洗脱。荧光检测：激发波长475 nm，发射波长515 nm。结果：PLD标准品在0.625-40 pmol范围含量与峰面积呈线性关系，相关系数0.999；孵育时间在0-45 min，磷脂酰乙醇生成量与孵育时间呈直线相关；日内及日间变异系数分别为5.6%、6.9%。小鼠心肌样品色谱图见二酯酰甘油、磷脂酰乙醇、磷脂酸3个峰，心肌磷脂酶D活性检测水平为nmol·h^-1·g^-1。结论：荧光高效液相法是检测心肌磷脂酶D活性的简便、快速、准确、灵敏的实验方法。     

A functionalized THz sensor for marker-free DNA analysis

We report on a novel resonant THz sensor for the label-free analysis of DNA molecules. The sensor allows the direct detection of DNA-probe molecules at functionalized electrodes via hybridization. Subsequent time resolved photoconductive sampling of the THz transmission identifies the binding state between probe and target DNA. Integrating neighbouring sensors on a chip, this technique can be extended to a parallel analysis of multiple DNA sequences. A clearly readable sensor response is obtained with less then 40 fmol of 20-mer single-stranded DNA molecules, indicating at least a sevenfold sensitivity increase compared to previous approaches.     

Genetic variation at a splicing branch point in intron 9 of the low density lipoprotein (LDL)-receptor gene: a rare mutation that disrupts mRNA splicing in a patient with familial hypercholesterolaemia and a common polymorphism

Mutations in the coding sequence, splice junctions or promoter of the gene for the low density lipoprotein (LDL) receptor are known to be the underlying cause of familial hypercholesterolaemia (FH), but mutations of this type cannot be identified in all patients with a clinical diagnosis of FH. We show here that minor sequence changes elsewhere in introns can be deleterious. A minor rearrangement 30 bp upstream from the junction of intron 9 with exon 10 was detected as a heteroduplex in amplified genomic DNA from one out of 300 heterozygous FH patients. The mutation destroys the only consensus sequence for a splicing branch point in intron 9 and analysis of mRNA from cells from the patient showed that it causes retention of intron 9 or, more rarely, in the use of cryptic splice sites in exon 10. The effect of the mutation on mRNA splicing was confirmed by analysis of mRNA in cells transfected with LDL-receptor mini-gene constructs expressing exons 9 and 10, together with the normal or mutant intron 9. A common C/T polymorphism within this branch point in intron 9 of the LDL-receptor gene does not affect mRNA splicing in vitro and is not associated with significant differences in mean plasma cholesterol concentration in a healthy population.      

Association study suggests opposite effects of polymorphisms within IL8 on bronchial asthma and respiratory syncytial virus bronchiolitis

BACKGROUND: IL-8 is a strong inductor of inflammation. Accordingly, it plays a pivotal role in acute inflammatory responses during respiratory syncytial virus (RSV) infections and in chronic inflammatory diseases such as bronchial asthma and juvenile idiopathic arthritis. Recently, 2 studies have found association of the polymorphism -251A of IL8 with RSV bronchiolitis. Furthermore, epidemiologic studies have demonstrated an increased risk for the development of asthma after RSV bronchiolitis, and a common genetic background for the 2 diseases is currently being discussed. OBJECTIVE: This study investigated whether IL-8 is in association with asthma and/or arthritis and whether the results can confirm a common genetic background of RSV bronchiolitis and asthma. METHODS: The polymorphisms -A251T, C781T, C1633T, and A2767T within IL8 were genotyped in the following 4 populations: children with asthma, atopic children, children with juvenile idiopathic arthritis, and control subjects. Statistical analysis made use of the Armitage trend test and the software program Arlequine. RESULTS: Association of all polymorphisms was found with asthma ( P =.008 to P =.03). Surprisingly -251T was associated with asthma, which is the opposite allele as described in association with RSV bronchiolitis. Furthermore, all polymorphisms were significantly more common in children with arthritis than in asthmatic children ( P =.006 to P =.02). No association was seen with the diagnosis of arthritis per se or with atopy. CONCLUSION: This is the first study to describe association of IL-8 with asthma and a significant inverse distribution of the polymorphisms in juvenile idiopathic arthritis. In addition, the results of this study might suggest that RSV bronchiolitis and bronchial asthma have at least some different genetic factors.     

Twelve-month outcomes of an Internet-based diabetes self-management support program

Objective

Internet-based programs offer potential for practical, cost-effective chronic illness self-management programs.

Methods

We report 12-month results of an Internet-based diabetes self-management program, with and without additional support, compared to enhanced usual care in a 3-arm practical randomized trial. Patients (n = 463) were randomized: 77.3% completed 12-month follow-up. Primary outcomes were changes in health behaviors of healthy eating, physical activity, and medication taking. Secondary outcomes were hemoglobin A1c, body mass index, lipids, blood pressure, and psychosocial factors.

Results

Internet conditions improved health behaviors significantly vs. usual care over the 12-month period (d for effect size = .09–.16). All conditions improved moderately on biological and psychosocial outcomes. Latinos, lower literacy, and higher cardiovascular disease risk patients improved as much as other participants.

Conclusions

The Internet intervention meets the reach and feasibility criteria for a potentially broad public health impact. However, 12-month magnitude of effects was small, suggesting that different or more intensive approaches are necessary to support long-term outcomes. Research is needed to understand the linkages between intervention and maintenance processes and downstream outcomes.

Practice implications

Automated self-management interventions should be tailored and integrated into primary care; maintenance of patient self-management can be enhanced through links to community resources.     

The human Achaete-Scute homologue 2 (ASCL2,HASH2) maps to chromosome 11p15.5, close to IGF2 and is expressed in extravillus trophoblasts

Here we describe the cloning of the human Achaete Scute Homologue 2 (HASH2) gene, officially designated ASCL2 (Achaete Scute complex like 2), a homologue of the Drosophila Achaete and Scute genes. In mouse, this gene is imprinted and maps to chromosome 7. We mapped the human homologue close to IGF2 and H19 at 11p15.5, the human region syntenic with mouse chromosome 7, indicating that this imprinted region is highly conserved in mouse and man. HASH2 is expressed in the extravillus trophoblasts of the developing placenta only. The lack of HASH2 expression in non-malignant hydatidiform (androgenetic) moles indicates that HASH2 is also imprinted in man.