MDR1 基因单靶点双荧光素酶报告基因系统的建立

目的通过构建以MDR1启动子为启动序列的双荧光素酶报告基因系统并进行活性分析，为MDR1基因表达的单靶点调控研究和逆转剂的筛选提供一种有效的方法。方法从HCT-8细胞中提取DNA并克隆含有MDR1基因启动子中Y—box序列。将该序列重组到萤光素酶报告基因载体pGL-3．Basic的启动区域中，从而构建报告基因载体pGL-MDR1。将pGL-MDR1和pRL-TK载体共转染到HCT-8和HCT-8／VCR细胞中。通过调节不同载体的比例来优化转染效率。利用MDRI基因激活剂（热诱导）和抑制剂（EGCG）等处理来分析其启动转录活性受外界因素的影响。结果通过直接测序法验证了pGL-MDR1含有MDR1基因启动子Y—box序列且没有出现碱基突变。在pGL-MDR1和pRL-TK的转染比例为5：5时，转染效率最高并具有最高的萤光素酶活性。通过MDR1基因激活处理后表现为时间依赖性地激活MDR1基因的表达，而MDR1基因抑制剂的作用则相反。结论MDR1启动子为启动序列的双荧光素酶报告基因系统建立成功。该系统不但可以用于研究活体生物发光成像和MDRI基因表达的机理，而且可用于单靶点的多药耐药抑制剂的筛选。     

4p16.3 haplotype modifying age at onset of Huntington disease

Huntington disease (HD) is caused by an expanded CAG repeat sequence in the HD gene. Although the age at onset is correlated to the CAG repeat length, this correlation only explains approximately half of the variation in onset age. Less variation between siblings indicates that the variation is, in part, explained by genetic modifiers. We analyzed polymorphic loci within or close to the HD gene on the HD chromosome in Danish HD patients. We found one specific haplotype segregating with later age at onset, compared with patients with similar CAG repeat length and another haplotype. The nine Danish families in the study carrying this haplotype most likely have a common founder. Several of the polymorphic loci displayed alleles that may be specific to the late-onset haplotype, implicating that from this study we cannot determine which of the loci tested (or other polymorphic loci in this chromosomal area) do in fact contain genetic modifiers of age at onset.     

Cardiorespiratory fitness and body mass index values in 9-year-old rural Norwegian children

Aim: To describe cardiorespiratory fitness and body mass index (BMI) values in a representative population of 9-year-old Norwegian children in two rural communities and compare present values with previous findings.
Methods: Two hundred and fifty-nine 9-year-old children were invited, and 256 participated in this study. Maximal oxygen uptake was directly measured during a continuous progressive treadmill protocol. Body mass and height were also measured.
Results: The mean ± SD relative maximal oxygen uptake was 52.8 ± 6.5 for boys and 46.9 ± 7.2 mL/kg/min for girls. Eight percent of the boys and 16.8% of the girls were classified as overweight, and 1.6% of the boys and 6.9% of the girls as obese. Mean age, body mass, height and Ponderal index were not significantly different between sexes. Girls had a higher BMI than boys (p = 0.05).
Conclusion: Compared to earlier Norwegian studies, children's BMI values seem to have increased substantially. This increase is most pronounced in girls. When assessing these differences using the PI, this increase is less marked. Comparing maximal oxygen uptake data with that in earlier Nordic studies, there is no evidence that fitness has declined among 9-year olds. However, the limitations of the few earlier studies make reliable comparisons difficult.     

Percutaneous cecostomy: controlled transperitoneal approach

The authors present two cases of percutaneous cecostomy performed with a modified approach previously described for percutaneous gastrostomy and cholecystostomy. T-fastener devices were used to affix the cecum to the anterior abdominal wall; thus, the potential problem of fecal spillage was prevented. In both cases, adequate fecal drainage was provided without complication.     

Association between palmoplantar pustulosis and cigarette smoking in Brazil: a case–control study

Background  Palmoplantar pustulosis (PPP) discloses some differences compared to vulgar psoriasis (PV) in terms of age of onset, female predominance and low occurrence of psoriasis lesions elsewhere. Cigarette smoking has been associated to PPP in international studies; nevertheless, these studies were never performed among Brazilian.
Objectives  To compare prevalence of smoking among PPP, PV and other dermatologic patients (NPD).
Methods  Case–control study involving 25 PPP patients from a reference psoriasis centre. Two control groups were matched according to gender and age: 50 patients with PV and 50 NPD. Confounders were adjusted by conditional multiple logistic regression.
Results  Among cases, 84.0% were female and PPP age of disease onset (41.4 years) was greater than PV (34.5 years). Prevalence of ever smoking was higher among cases (92.0%) than PV (52.0%) and NPD (30.0%). Adjusted odds ratio of PPP ever smoking compared to PV and NPD was 9.5 and 36.2, respectively. All smokers reported the onset of their habit before the development of PPP.
Conclusions  There was significant association between PPP and smoking. However, the impact of giving it up in the clinical course of the disease remains to be established.     

Cognitive impairment in rapid‐onset dystonia‐parkinsonism

Rapid‐onset dystonia‐parkinsonism (RDP) is caused by mutations in the ATP1A3 gene. This observational study sought to determine if cognitive performance is decreased in patients with RDP compared with mutation‐negative controls. We studied 22 familial RDP patients, 3 non‐motor‐manifesting mutation‐positive family members, 29 mutation‐negative family member controls in 9 families, and 4 unrelated RDP patients, totaling 58 individuals. We administered a movement disorder assessment, including the Burke‐Fahn‐Marsden Dystonia Rating Scale (BFMDRS) and the Unified Parkinson's Disease Rating Scale (UPDRS) and a cognitive battery of memory and learning, psychomotor speed, attention, and executive function. The cognitive battery was designed to evaluate a wide range of functions; recognition memory instruments were selected to be relatively pure measures of delayed memory, devoid of significant motor or vocal production limitations. Comparisons of standardized cognitive scores were assessed both with and without controlling for psychomotor speed and similarly for severity of depressive symptoms. A majority of RDP patients had onset of motor symptoms by age 25 and had initial symptom presentation in the upper body (face, mouth, or arm). Among patients, the BFMDRS (mean ± SD, 52.1 ± 29.5) and UPDRS motor subscore (29.8 ± 12.7) confirmed dystonia‐parkinsonism. The affected RDP patients performed more poorly, on average, than mutation‐negative controls for all memory and learning, psychomotor speed, attention, and executive function scores (all P ≤ 0.01). These differences persisted after controlling for psychomotor speed and severity of depressive symptoms. Impaired cognitive function may be a manifestation of ATP1A3 mutation and RDP. © 2014 International Parkinson and Movement Disorder Society     

尿道狭窄患者围手术期尿液TGF-β1变化的分析研究

目的:探讨尿道狭窄患者围手术期尿液TGF-β1浓度变化情况以及影响该浓度的相关因素.方法:使用ELISA试剂盒对29例尿道狭窄患者术前1个月及术后1个月尿液中TGF-β1进行测定及记录.同期取泌尿系统其他手术的14例患者作为对照组,测定其术后1个月尿液中TGF-β1浓度.结果:检测结果显示实验组在接受手术治疗后尿液中TGF-β1含最较对照组有显著增高(P＜0.05).同时实验组患者术前和术后尿液TGF-β1浓度也存在明显差异(P＜0.05).在相关性因素的分析中,前尿道狭窄患者术后尿液中TGF-β1含量的变化幅度较后尿道狭窄患者更为显著(P＜0.05),同时采用自体组织替代技术较传统端端吻合技术以及内镜切开技术更能引起尿液中TGF-β1的明显变化(P＜0.05).但年龄、既往手术次数均未能引起患者术后TGF-β1的变化.结论:狭窄部位、手术方式都与患者尿液中 TGF-β1的含量存在一定的联系,而年龄及既往手术史等因素未发现与患者体内TGF-β1含量有较大的联系.