干扰素γ基因内含子1+874位点多态性与乙型肝炎病毒感染关系的研究

目的 研究干扰素γ（IFN-γ）基因内含子1＋874位点多态性与乙型肝炎病毒（HBV）感染、转归的关系,探讨慢性HBV感染的遗传易感因素.方法 采用序列特异性引物-聚合酶链反应（PCR-SSP）技术检测231例慢性HBV携带患者、165例自限性HBV感染者和135名正常对照者IFN-γ基因内含子1＋874位点T/A单核苷酸多态性.结果 慢性HBV感染组IFN-γ基因＋874位点AA基因型频率（TT、TA、AA频率分别为9.1%、12.1%、78.8%）高于正常对照组（TT、TA、AA频率分别为12.6%、23.0%、64.4%）（x2=9.60,P=0.008）;而自限性HBV感染组（TT、TA、AA频率分别为13.9%、23.7%、62.4%）和对照组之间差异无显著性（x2=0.16,P=0.92）.结论 IFN-γ基因内含子1＋874位点多态性与慢性HBV感染有关,该位点多态性可能在决定个体HBV感染遗传易感性方面有一定意义.     

Genotyping of presenilin-1 polymorphism in amyotrophic lateral sclerosis

The mechanisms underlying motor neuron degeneration in amyotrophic lateral sclerosis are not fully understood. Recent studies suggest that apoptosis is involved in the abnormal neural death that occurs in this devastating disease. Presenilin-1, a transmembrane protein, seems to be implicated in apoptosis. To determine whether presenilin-1 intron 8 polymorphism has an influence in the course of amyotrophic lateral sclerosis, we examined this polymorphism genotypes in a large group of patients (n=72) with amyotrophic lateral sclerosis and in a random sample of 213 healthy individuals. The results showed a significant difference in genotype (P < 0.04) and allele (P < 0.03) distribution between patients and controls. These results suggest a possible intervention of presenilin-1 in the pathogenesis of amyotrophic lateral sclerosis. Received: 14 February 2000 / Received in revised form: 20 April 2000 / Accepted: 4 June 2000     

Autosomal recessive progeroid syndrome due to homozygosity for a TOMM7 variant

Multiple genetic loci have been reported for progeroid syndromes. However, the molecular defects in some extremely rare forms of progeria have yet to be elucidated. Here, we report a 21-year-old man of Chinese ancestry who has an autosomal recessive form of progeria, characterized by severe dwarfism, mandibular hypoplasia, hyperopia, and partial lipodystrophy. Analyses of exome sequencing data from the entire family revealed only 1 rare homozygous missense variant (c.86C>T; p.Pro29Leu) in TOMM7 in the proband, while the parents and 2 unaffected siblings were heterozygous for the variant. TOMM7, a nuclear gene, encodes a translocase in the outer mitochondrial membrane. The TOMM complex makes up the outer membrane pore, which is responsible for importing many preproteins into the mitochondria. A proteomic comparison of mitochondria from control and proband-derived cultured fibroblasts revealed an increase in abundance of several proteins involved in oxidative phosphorylation, as well as a reduction in abundance of proteins involved in phospholipid metabolism. We also observed elevated basal and maximal oxygen consumption rates in the fibroblasts from the proband as compared with control fibroblasts. We concluded that altered mitochondrial protein import due to biallelic loss-of-function TOMM7 can cause severe growth retardation and progeroid features.     

Lifespan extension by n-butanol extract from seed of Platycladus orientalis in Caenorhabditis elegans

Aim of the study

As a traditional Chinese medicine, seed of Platycladus orientalis(Linnaeus) Franco has been extensively used as a tonic and sedative remedy. The present study was conducted to investigate whether lifespan was extended and the mechanisms of n-butanol extract from seed of Platycladus orientalis (BSPO) in Caenorhabditis elegans. The findings could provide the pharmacological basis for a treatment in traditional medicine.

Materials and methods

Lifespan extension by BSPO was evaluated under normal culture conditions and in a stress test. A possible mechanism of the anti-aging effect of BSPO, a change in the stress-resistance of related proteins, was also investigated in C. elegans.

Results

It has been shown that BSPO could significantly extend lifespan of C. elegans in a concentration dependent manner under normal culture conditions and stress. Further studies demonstrated that BSPO treatment significantly decreased reactive oxygen species (ROS) accumulation, up-regulated resistance to stress of related proteins, including glutathione S-transferase-4 (GST-4) and heat shock protein-16.2 (HSP-16.2), and reduced the amount of lipofuscin in transgenic C. elegans.

Conclusion

These results indicated that BSPO extended the lifespan, which could be attributed to its direct ROS scavenging activity, reducing the amount of lipofuscin and increasing the expression of gens associated with resistance to stress. These obtained data provided valuable support for traditional clinical practice to extend lifespan and to provide tonic remedy.     

遗传、肥胖与妊娠糖尿病的关系

目的 探讨遗传、肥胖与妊娠糖尿病(GDM)的关系。方法 1997年2月～1998年12月在我院产科门诊确诊为GDM孕妇92例为GDM组;随机抽取同期孕24～28周及孕38～40周糖筛查阴性孕妇70例为对照组。两组分别于产前初诊时详细询问糖尿病家族史及孕前体重、身高,计算孕前体重指数(BMI);并分别于孕28～34周、孕38～40周、产时胎盘娩出后及产后2个月空腹静脉血测血浆胰岛素。结果①GDM组平均孕前体重指数(23.44±3.98)kg/m~2,与对照组平均孕前体重指数(19.38±3.13)kg/m~2相比,差异有显著性(P<0.01);GDM组糖尿病家族史阳性率为25.00%,与对照组1.43％相比,差异有显著性(P<0.01)。②GDM组中糖尿病家族史(+)性者,孕38～40周、产后2个月胰岛素水平明显高于(-)性者,差异有显著性(P<0.01)。孕28～34周、产时两组间差异无显著性(P>0.05)。GDM组中BWI≥kg/m~2者于孕38～40周胰岛素水平明显高于BWI正常者,差异有显著性(P<0.05);孕28～34周、产后2个月两组之间差异无显著性(P>0.05);产时BWI偏高者,胰岛素水平明显低于BWI正常组(P<0.05)。结论 糖尿病是由遗传因素及环境因素共同参与和(或)相互作用引起的,其中肥胖与遗传占重要地位。     

斑马鱼动物模型在眼科及视觉科学研究中的应用:历史与现状

近年来,斑马鱼凭借其体型小、繁殖力强、生长发育快、胚胎透明等独特的生物学特性,成为人类疾病动物模型的理想选择,加之与人类眼部结构和基因的高度保守性,使斑马鱼受到眼科学和视觉科学领域工作者的关注.本文主要以斑马鱼模型在视觉研究中的文献为基础,对目前常用和新近发展的基因调控和编辑技术在这一领域的应用进行综述.     

Elucidation of genomic origin of synchronous endometrial and ovarian cancer (SEO) by genomic and microsatellite analysis

ObjectiveElucidation of clonal origin of synchronous endometrial and ovarian cancers (SEOs).MethodsWe reviewed 852 patients who diagnosed endometrial and/or ovarian cancer. Forty-five (5.3%) patients were diagnosed as SEOs. We evaluated blood and tissue samples from 17 patients. We analyzed the clonal origins of 41 samples from 17 patients by gene sequencing, mismatch microsatellite instability (MSI) polymerase chain reaction assay and immunohistochemical (IHC) staining of 4 repair genes.ResultsSixteen of 17 patients had at least 2 or more trunk mutations shared between endometrial and ovarian cancer suggesting the identical clonal origins. The shared trunk mutation are frequently found in endometrial cancer of the uterus, suggesting the uterine primary. Four out of 17 (24%) SEOs had mismatch repair (MMR) protein deficiency and MSI-high (MSI-H) states. One case was an endometrial carcinoma with local loss of MSH6 protein expression by IHC staining, and the result of MSI analysis using the whole formalin-fixed, paraffin-embedded specimen was microsatellite stable. In contrast, ovarian tissue was deficient MMR and MSI-H in the whole specimen. This indicated that MMR protein deficiency could occur during the progression of disease.ConclusionMost SEOs are likely to be a single tumor with metastasis instead of double primaries, and their origin could be endometrium. In addition, SEOs have a high frequency of MMR gene abnormalities. These findings not only can support the notion of uterine primary, but also can help to expect the benefit for patients with SEOs by immuno-oncology treatment.