Missense mutation in a von Willebrand factor type A domain of the alpha 3(VI) collagen gene (COL6A3) in a family with Bethlem myopathy

The Bethlem myopathy is a rare autosomal dominant proximal myopathy characterized by early childhood onset and joint contractures. Evidence for linkage and genetic heterogeneity has been established, with the majority of families linked to 21q22.3 and one large family linked to 2q37, implicating the three type VI collagen subunit genes, COL6A1 (chromosome 21), COL6A2 (chromosome 21) and COL6A3 (chromosome 2) as candidate genes. Mutations of the invariant glycine residues in the triple-helical domain-coding region of COL6A1 and COL6A2 have been reported previously in the chromosome 21-linked families. We report here the identification of a G-->A mutation in the N-terminal globular domain-coding region of COL6A3 in a large American pedigree (19 affected, 12 unaffected), leading to the substitution of glycine by glutamic acid in the N2 motif, which is homologous to the type A domains of the von Willebrand factor. This mutation segregated to all affected family members, to no unaffected family members, and was not identified in 338 unrelated Caucasian control chromosomes. Thus mutations in either the triple-helical domain or the globular domain of type VI collagen appear to cause Bethlem myopathy.      

乐脉颗粒促进鸡胚绒毛尿囊膜血管的生成

目的:乐脉颗粒在缺血性心脑血管病的治疗中具有较好的效果,其是否通过促进血管生成而发挥作用还不清楚。观察乐脉颗粒对鸡胚绒毛尿囊膜血管生成的影响。方法:实验于2005-03/08在江西省重点实验室南昌大学第二附属医院分子中心完成。①实验材料:新西兰大白兔8只,体质量2～2.5kg;新鲜白皮种蛋70只,质量50～60g。②实验方法:种蛋在(37.5±0.5)℃条件下孵育,种蛋受精率90%以上。第7天开窗暴露鸡胚绒毛尿囊膜建立鸡胚绒毛尿囊膜模型。将60枚存活鸡胚随机分为生理盐水组、正常血清组、乐脉血清组、内膜损伤血清组、内膜损伤乐脉治疗组以及血管内皮生长因子(20mg/L)组,每组10枚鸡胚。新西兰大白兔腹主动脉用球囊导管损伤建立血管内膜损伤模型,乐脉血清组及内膜损伤乐脉治疗组给予乐脉颗粒25mg/(kg·d)喂饲,各组7d后取血清。第8天,在鸡胚绒毛尿囊膜上放一直径为5mm的滤膜作为载体,分别加样5μL,1次/d,连续3d,③实验评估:第11天取鸡胚绒毛尿囊膜,数码相机拍照后平铺于载玻片上,计数载体周围血管数目及滤膜周围0.5cm范围内的血管分支点数并进行比较。结果:纳入大白兔8只,存活鸡胚60枚,均进入结果分析,无脱落。与正常血清组相比较,乐脉血清组鸡胚绒毛尿囊膜周围血管总数明显增多,血管以载体为中心呈辐辏状生长,差异具有显著性意义(P<0.05);与正常血清组相比较,内膜损伤血清组血清载体周围血管数量明显增多,差异具有极显著性意义(P<0.01);与内膜损伤乐脉治疗组相比较,血管总数差异无显著性。结论:①兔乐脉颗粒血清能够明显促进鸡胚绒毛尿囊膜上血管生成。②血管内膜损伤7d后的血清能够促进鸡胚绒毛尿囊膜上血管生成。     

Determining the minimum number of detectable cardiac-transplanted 111In-tropolone-labelled bone-marrow-derived mesenchymal stem cells by SPECT

In this work, we determined the minimum number of detectable 111In-tropolone-labelled bone-marrow-derived stem cells from the maximum activity per cell which did not affect viability, proliferation and differentiation, and the minimum detectable activity (MDA) of 111In by SPECT. Canine bone marrow mesenchymal cells were isolated, cultured and expanded. A number of samples, each containing 5x10(6) cells, were labelled with 111In-tropolone from 0.1 to 18 MBq, and cell viability was measured afterwards for each sample for 2 weeks. To determine the MDA, the anthropomorphic torso phantom (DataSpectrum Corporation, Hillsborough, NC) was used. A point source of 202 kBq 111In was placed on the surface of the heart compartment, and the phantom and all compartments were then filled with water. Three 111In SPECT scans (duration: 16, 32 and 64 min; parameters: 128x128 matrix with 128 projections over 360 degrees) were acquired every three days until the 111In radioactivity decayed to undetectable quantities. 111In SPECT images were reconstructed using OSEM with and without background, scatter or attenuation corrections. Contrast-to-noise ratio (CNR) in the reconstructed image was calculated, and MDA was set equal to the 111In activity corresponding to a CNR of 4. The cells had 100% viability when incubated with no more than 0.9 MBq of 111In (80% labelling efficiency), which corresponded to 0.14 Bq per cell. Background correction improved the detection limits for 111In-tropolone-labelled cells. The MDAs for 16, 32 and 64 min scans with background correction were observed to be 1.4 kBq, 700 Bq and 400 Bq, which implies that, in the case where the location of the transplantation is known and fixed, as few as 10,000, 5000 and 2900 cells respectively can be detected.     

激光小角光散射仪测定右旋糖酐分子量

激光小角光散射仪(LALLS)由于采用了激光光源,具有光强度高、单色性强、准直性好等特点,可以在微量样品池及很低浓度的溶液中进行小角度(3°～7°)散射光强的测量,溶质的瑞利系数与其分子量有如下关系:     

雪灵芝对二乙基亚硝胺诱导大鼠肝癌组织细胞的抑制作用

目的：验证雪灵芝是否具有抑制大鼠肝癌的功效。方法：实验于2003—09/2004—08在广西疾病预防控制中心SPF级动物实验室完成。选用健康成年SD大鼠160只。按体质量分层随机分为5组：空白对照组、模型组、雪灵芝高剂量组、雪灵芝中剂量组和雪灵芝低剂量组，每组32只。雪灵芝高、中、低剂量组大鼠分别灌胃2．500，1．250，0．625mL/kg雪灵芝溶液，阴性对照组和模型组灌胃等量蒸馏水，1次／d，连续60d。第61天开始雪灵芝高、中、低剂量组和模型组灌胃二乙基亚硝胺溶液，对照组灌胃等量的生理盐水。于停止灌胃90d后各组处死一半受试大鼠（雌雄各半），检测血常规及血清主要生化指标，观察各脏器大体形态改变、脏器的癌变程度。1周后给剩余大鼠灌胃雪灵芝溶液（不含二乙基亚硝胺）。7周后处死余下的一半雄性大鼠，进行相同操作。8周后处死余下的全部大鼠，操作及检测方法同前。结果：纳入的160只SD大鼠，145只进入结果分析，15只脱落。①病理切片检查结果：除阴性对照组，其他各组大鼠肝组织均发生癌变或癌前病变。雪灵芝高、中、低剂量组的癌前病变发生率与模型组相近（P〉0．05）；癌变的发生率均低于模型组，差异有显著性意义（P〈0．05，0．01）。②大体标本检查结果：阴性对照组大鼠肝脏的大体标本均无异常改变，其他各组大鼠的肝脏有些可见表面粗糙等病理改变。模型组大体标本病理改变的阳性率高于雪灵芝高、中、低剂量组，差异有显著性意义（P〈0．05）。肉眼观模型组癌变发生率高于其他各组。③其他脏器检查结果：模型组2只大鼠有肝癌肺转移。结论：以较大剂量的二乙基亚硝胺连续灌胃30d可以复制大鼠肝癌模型；雪灵芝对二乙基亚硝胺诱导的大鼠肝癌具有预防和抑制的作用。     

Adverse events and treatment completion for latent tuberculosis in jail inmates and homeless persons

BACKGROUND: Recently, a short-course treatment using 60 daily doses of rifampin and pyrazinamide was recommended for latent tuberculosis (TB) infection (LTBI). STUDY OBJECTIVES: To determine the acceptability, tolerability, and completion of treatment. DESIGN: Observational cohort study. SETTING: Five county jails and TB outreach clinics for homeless populations in three cities. PATIENTS: Study staff enrolled 1,211 patients (844 inmates and 367 homeless persons). INTERVENTIONS: Sites used 60 daily doses of rifampin and pyrazinamide, an approved treatment regimen for LTBI. MEASUREMENTS: Types and frequency of drug-related adverse events and outcomes of treatment. RESULTS: Prior to treatment, 25 of 1,178 patients (2.1%) had a serum aminotransferase measurement at least 2.5 times the upper limit of normal. Patients who reported excess alcohol use in the past 12 months were more likely than other patients to have an elevated pretreatment serum aminotransferase level (odds ratio, 2.1; 95% confidence interval, 1.1 to 6.1; p = 0.03). Treatment was stopped in 66 of 162 patients (13.4%) who had a drug-related adverse event. Among 715 patients who had serum aminotransferase measured during treatment, 43 patients (6.0%) had an elevation > 5 times the upper limits of normal, including one patient who died of liver failure attributed to treatment. In multivariate analyses, increasing age, an abnormal baseline aspartate aminotransferase level, and unemployment within the past 24 months were independent risk factors for hepatotoxicity. Completion rates were similar in jail inmates (47.5%) and homeless persons (43.6%). CONCLUSIONS: This study detected the first treatment-associated fatality with the rifampin and pyrazinamide regimen, prompting surveillance that detected unacceptable levels of hepatotoxicity and retraction of recommendations for its routine use. Completion rates for LTBI treatment using a short-course regimen exceeds historical rates using isoniazid. Efforts to identify an effective short-course treatment for LTBI should be given a high priority.     

毛茛甙的抗诱变作用及代谢转化

研究表明,毛茛甙可显著抑制MMC和MMS等诱变剂对沙门氏菌TA_(100)和TA_(102)回复突变作用;对MMC诱发的小鼠PEC徽核抑制率达56.5%。代谢研究表明:毛茛甙抑制DNA生物合成的作用可被肝微粒体酶和胞浆液分别降低46和12%;RP-HPLC测定显示,体外毛茛甙可被肝微粒代谢转化。     

Comparison of the myocardial clearance of endothelial progenitor cells injected early versus late into reperfused or sustained occlusion myocardial infarction

Stem cell transplantation following AMI has shown promise for the repair or reduction of the amount of myocardial injury. There is some evidence that these treatment effects appear to be directly correlated to cell residence time. This study aims to assess the effects of (a) the timing of stem cell injection following myocardial infarction, and (b) flow milieu, on cell residence times at the site of transplantation by comparing three time points (day of infarction, week 1 and week 4–5), and two models of acute myocardial infarction (sustained occlusion or reperfusion). Twenty-one dogs received 2 injections of 30 million endothelial progenitor cells. The first injections were administered by epicardial (n = 8) or endocardial injection (n = 13) either on the day of infarction (n = 15) or at 1 week (n = 6). The second injections were administered by only endocardial injection (n = 18) 4 weeks following the first injection. Cell clearance half-lives were comparable between early and late injections. However, transplants into sustained occlusion infarcts resulted in slower cell clearance 77.1 ± 6.1 (n = 18) versus reperfused 59.4 ± 2.9 h (n = 21) p = 0.009. Sustained occlusion infarcts had longer cell retention in comparison to reperfusion whereas the timing of injection did not affect clearance rates. If the potential for myocardial regeneration associated with cell transplantation is, at least in part, linked to cell residence times, then greater benefit may be observed with transplants into infarcts associated with persistent coronary artery occlusion.     

The response of the human circulatory system to an acute 200-��T, 60-Hz magnetic field exposure

Purpose

Recent research by the authors on the effects of extremely low-frequency (ELF) magnetic field (MF) exposure on human heart rate (HR), heart rate variability (HRV), and skin blood perfusion found no cardiovascular effects of exposure to an 1,800-??T, 60-Hz MF. Research from our group using rats, however, has suggested a microcirculatory response to a 200-??T, 60-Hz MF exposure. The present pilot study investigated the effects of 1?h of exposure to a 200-??T, 60-Hz MF on the human circulation. Microcirculation (as skin blood perfusion) and HR were measured using laser Doppler flowmetry. Mean arterial pressure was monitored with a non-invasive blood pressure system.

Methods

Ten volunteers were recruited to partake in a counterbalanced, single-blinded study consisting of two testing sessions (real and sham exposure) administered on separate days. Each session included four consecutive measurement periods separated by rest, allowing assessment of cumulative and residual MF effects.

Results

A within-subjects analysis of variance did not reveal session by time period interactions for any of the parameters which would have been suggestive of a MF effect (p?>?0.05). Perfusion, HR, and skin surface temperature decreased over the course of the experiment (p?<?0.05).

Conclusions

The MF used in this experiment did not affect perfusion, HR, or mean arterial pressure. Decreasing perfusion and HR trends over time were similar to our previous results and appear to be associated with a combination of inactivity (resulting in decreasing body temperatures) and reduced physiological arousal.