Smith-Fineman-Myers综合征的候选基因GPC4分析

目的:探讨GPC4基因与中国山东Smith-Fineman-Myers综合征(SFMS)的关系,并分析SFMS患者GPC4基因突变。方法:利用primer3设计扩增GPC4全部编码序列及内含子和外显子接头序列的引物,采用PCR扩增结合PCR产物直接测序方法检测GPC4基因开放性阅读框架区域基因突变。结果:在GPC4基因开放性阅读框架区域内并未检测到导致疾病的基因突变。结论:山东SFMS家系患者不是由于GPC4基因编码区域基因突变所致。     

A clinical and genetic study of 56 Saudi Wilson disease patients: identification of Saudi-specific mutations

Wilson disease (WD) is a hereditary disorder, with recessive transmission and genetic heterogeneity. Several mutations of ATP7B, the gene underlying WD, were reported in many ethnic groups. In this study, mutation screening in ATP7B of 56 Saudi Arabian WD patients was undertaken. The clinical data of all patients were recorded. The entire ATP7B coding sequence, including intron-exon boundaries were screened for mutation by the polymerase chain reaction (PCR)-based mutation detection technique and DNA sequencing. Thirty-nine patients were symptomatic at presentation and 17 subjects were pre-symptomatic siblings of affected patients. Fourteen patients had neurological, 11 patients had mixed (hepatic and neurological), and 14 patients had hepatic presentations. Family history suggestive of WD was present in 72% of cases and 68% had consanguineous parents. Genetic analysis showed disease-causing mutations in three exons (exons 8, 19 and 21) of the ATP7B gene in 28 patients (50%). Mutations in exons 21 (18 cases) and 19 (one case) were unique for Saudis. This large series of Saudi patients with WD has shown wide variability in the genomic substrate of WD. There is no correlation between genotype and clinical presentation.     

荧光偏振检测HBV DNA C区BCP双突变

目的：建立简便、灵敏的HBV DNA序列中BCP双突变点的检测方法．方法：采用终点终止法和偏振光检测技术进行点突变的检测．首先对HBV C区基因进行PCR扩增，然后用特异探针与扩增产物中待测核苷酸的下游序列杂交，使探针的3’端可以在DNA聚合酶的催化下，依据其互补链上的待测核苷酸连接上一个标有特定荧光素的ddNTP，然后检测该3’端带有荧光素的探针，根据检测到的荧光素种类和偏振光的强度可以判定待测点是何种核苷酸．结果：该方法可以检测出HBV基因序列中BCP双突变核苷酸类型以及检测1个拷贝的模板，并且可以从BCP野性株DNA序列中检出5％BCP双突变DNA序列．结论：该技术可以检测血清中HBV DNA C区BCP双突变．     

G2019S LRRK2 mutation in familial and sporadic Parkinson's disease in Russia.

Among mutations associated with autosomal dominant and sporadic Parkinson's disease (PD) the G2019S substitution in the leucine-rich repeat kinase 2 (LRRK2) gene is the most frequently identified. To estimate its frequency in Russia, we analyzed 208 patients with PD from the Northwestern region of Russia. Of these, 51 patients were probands from families with PD compatible with autosomal dominant inheritance. The control group represented 161 subjects without neurological disorders settled in the same region. The frequency of the G2019S mutation was greater in familial PD (2 [3.9%] of 51) than in sporadic PD (1 [0.6%] of 157). In addition, this mutation was found in the proband's father, who also had PD, in 1 PD family, and in 1 carrier without signs of PD at age 40 in another PD family. All carriers were heterozygous for the G2019S mutation and reported the Ashkenazi Jewish origin. The mutation was not found in the control group.     

Inhibition of hepatitis B virus DNA replicative intermediate forms by recombinant interferon-γ

AIM: To evaluate the in vitro anti-HBV activity of recombinant human IFN-γ, alone and in combination with lamivudine. METHODS: A recombinant baculovirus-HBV/HepG2 culture system was developed which could support productive HBV infection in vitro. Expression of HBsAg and HBeAg in infected HepG2 culture medium was detected by commercial enzyme immunoassays. HBV DNA replication intermediates were detected in infected cells by Southern hybridization and viral DNA load was determined by dot hybridization. RESULTS: IFN-γat 0.1 to 5μg/L efficiently down regulated HBsAg expression in transduced HepG2 cells. At 5μg/L, IFN-γalso suppressed HBV DNA replication in these cells. While treatment with a combination of lamivudine and IFN-γshowed no additive effect, sequential treatment first with lamivudine and then IFN-γwas found to be promising. In this culture system the best HBV suppression was observed with a pulse of 2μmol/L lamivudine for two days, followed by 1μg/L IFN-γfor another four days. Compared to treatment with lamivudine alone, the sequential use of 0.2μmol/L lamivudine for two days, followed by 5μg/L IFN-γfor six days showed a 72% reduction in HBV cccDNA pool. CONCLUSION: This in vitro study warrants further evaluation of a combination of IFN-γand lamivudine, especially in IFN-αnon-responder chronic hepatitis B patients. A reduced duration of lamivudine treatment would also restrict the emergence of drug-resistant HBV mutants.     

HBsAg阳性患者中HBV-DNA(PCR)与其它HBV复制标志物的关系

本文应用聚合酶链反应(PCR)对125例乙型肝炎病毒患者血清进行了HBV-DNA检测,根据其检测结果与乙型肝炎病毒的其它复制标志物HBcAg(检测125例)、HBeAg(检测115例)、PreS_2Ag(检测92例)、PHSA-R(检测114例)、Anti—HBclgM(检测118例)进行比较。HBV-DNA阳性血清中HBcAg、HBeAg、PreS_2Ag、PHSA-R、Anti-HBcIgM的检出率分别为83.75％(67/80)、62.34％(48/77)、61.02％(39/59)、74.03％(57/77)、72.97％(54/74)。经统计学处理,显示五项复制标志物与HBV-DNA的相关关系应是:HBcAg>PHSA-R>Anti-HB-cIgM>HBeAg>PreS_2Ag。在HBV-DNA(PCR)阳性血清中,HBcAg的检出率为最高。提示在除HBV-DNA(PCR)外,上述五项标志物中,HBcAg可能是HBV-DBA复制的最佳指标。HBeAg在HBV复制过程中的地位仍有待今后进一步探讨。     

北京地区361名孕妇乙型肝炎流行病学研究

从1985年4月到1986年4月对361名孕妇进行的乙型肝炎流行病学横断面研究以及196名产妇一年随访研究的结果表明,361例孕妇的HBsAg阳性率为2.5%,抗-HBs阳性率为23.8%,抗-HBc阳性率为22.1%,HBV总感染率为31.3%;抗-HBs阳性、抗-HBs和抗-HBc共存阳性者占总阳性者的76.1%,说明人群感染HBV后大多产生了免疫力.1986年4月复查了196例产妇,133名在1985年HBV标记阴性者中有6人获得了HBV标记,HBV新感染率为4.5%;1例为急性乙型肝炎病人,5例为亚临床感染.HBV新感染者的感染途径不明,但医源性传播不能排除.1986年检查的148对夫妇中,男性HBsAg阳性率是女性的3.1倍(6.1%对2.0%),男性单独抗-HBc阳性率是女性的2.3倍(6.1%对2.7%),抗-HBs、抗-HBs和抗-HBc共存以及HBV感染率男女性间都无显著差异.     

871名学龄前儿童乙肝感染情况调查分析

目的:探讨学龄前儿童乙肝感染情况,为制定有效的干预措施提供可靠的依据。方法:采用酶联免疫(ELISA)法对871名2~6岁学龄前儿童乙肝感染情况进行调查分析。结果:871名学龄前儿童中HBsAg阳性63名,阳性率为7.23%。男女儿童乙肝患病率无显著性差异;4岁以前儿童患乙肝率随年龄增长而逐渐上升;农村儿童HBV感染率高于城区。结论:对学龄前儿童定期进行健康体检是及早发现HBV感染的有效途径;加强对公共卫生、环境污染的管理,提高易感人群的预防接种率,严格规范输血操作及注射用具的一次性使用等是预防HBV感染和切断乙肝传播的有效措施。     

反义寡核苷酸抗乙型肝炎病毒的研究进展

反义寡核苷酸(ASODN)是近十年来迅速发展起来的一种新的生物技术。它为乙型肝炎病毒(HBV)治疗提供了一种新的基因治疗途径。本文就ASODN抗HBV的研究进展:ASODN抗HBV的反义与非反义作用机制研究;ASODN的化学修饰;针对HBV各基因区关键位点的ASODN抗HBV效果评价以及利用联合或串联ASODN和靶向技术抗HBV作用的研究分三部分进行综述。