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.     

病毒白细胞介素-10转基因在造血干细胞中的表达

目的　观察逆转录病毒转病毒白细胞介素 10 (vIL 10 )基因在体内的表达。方法　用MSCVneo vIL 10重组体在体外转导CBA (H 2 K)小鼠的造血干细胞 (HSCs) ,给经致死照射(90 0rads)的 2 0只同基因CBA(H 2 K)小鼠注入经MSCVneo vIL 10转染的HSCs ,2× 10 6HSCs/只。酶联免疫吸附测定 (ELISA)、逆转录 聚合酶链反应 (RT PCR )、Westernblot分析vIL 10的表达。结果　移植MSCVneo vIL 10转染HSCs的 2 0只小鼠 ,移植后 8周用ELISA检测 ,其中 15只小鼠血清的vIL 10浓度为 :2 70～ 13 40ng/L ,5只小鼠血清的vIL 10为阴性。 12周后有 2只小鼠vIL 10测不出 ,13只小鼠长时间表达vIL 10达 6个月。对照组小鼠血清vIL 10均为阴性。RT PCR和Westernblot证实小鼠的器官均有vIL 10的mRNA和蛋白的表达。结论　逆转录病毒能有效地将vIL 10基因导入造血干细胞并在体内长时间表达。     

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.     

雌激素及其受体对心血管系统保护作用实验研究进展

雌激素对心血管系统具有重要的保护作用。雌激素及其受体主要通过调节血管舒张功能、抑制血管平滑肌细胞增殖和迁移以及影响肾素 -血管紧张素等介导这一保护作用。但临床上雌激素替代治疗尚未得到肯定 ,需进一步研究     

中国人不同C4基因型时血中C4浓度的定量检测

用神经氨酸酶及羧肽酶B处理血浆,依次经C4高压琼脂糖电泳、免疫固定、薄层激光扫描等步骤,并结合血浆免疫火箭电泳定量法对我国武汉地区随机人群的血浆C4总量及C4两种同种型,主要别型,单、双QO,重复座位等时的血浆C4含量进行了检测与分析。结果发现:遗传因素明显影响血浆C4水平,因而在群体中表现宽广的C4浓度范围,特别在有C4QO与C4重复基因座位时差异特别明显。这一研究提示,不同的C4基因型,循环C4含量表现明显差异。临床上检测C4含量时应该考虑患者的C4基因型别。     

Increase of prolactin mRNA in the rat hypothalamus after intracerebroventricular injection of VIP or PACAP

Vasoactive intestinal peptide (VIP), the structurally homologous pituitary adenylate cyclase-activating peptide (PACAP) and the pituitary hormone, prolactin (PRL) enhance rapid eye movement sleep (REMS). VIP and PACAP are both inducers of PRL gene expression and release in the pituitary gland. Little is known about PRL regulation in the brain although it is hypothesized that the REMS-promoting activity of i.c.v. administered VIP may be mediated via the activation of cerebral PRL. To test whether VIP or PACAP in fact increase intracerebral mRNA, the peptides (VIP: 30 or 300 pmol; PACAP: 220 pmol) were injected i.c.v. into rats at dark onset. 1 h later, cDNA was synthesized from purified hypothalamic mRNA. Standardized amounts were analysed for PRL using the polymerase chain reaction followed by Southern blotting and hybridization. Compared with β-actin mRNA levels, both VIP and PACAP increased PRL mRNA levels in a dose-dependent fashion though VIP was more effective on a molar basis. The previously reported alternatively spliced PRL mRNA (lacking exon 4) was not detected. The data support the hypothesis that the REMS-promoting activity of central VIP and PACAP might be mediated by cerebral PRL.     

p53基因与肝癌

p53肿瘤抑制基因突变与多数恶性肿瘤的发生发展有关,包括肝细胞癌(hepatocelluar carcinoma,HCC)在内的人类恶性肿瘤中至少有50%发生了p53基因改变。因此,以正常p53基因治疗肿瘤就成了研究热点,随着介入放射学(inter-ventional radiology)向纵深发展,经介入放射方法进行肝癌的基因治疗令人关注。本文介绍了p53基因的结构与功能,其与肝癌的病理联系以及在肝癌治疗中的应用。     

变形链球菌表面蛋白和葡糖基转移酶基因疫苗对唾液变形链球菌和牙菌斑的影响

目的　了解变形链球菌表面蛋白和葡糖基转移酶基因疫苗单独及联合免疫对定菌鼠唾液变链菌和牙面菌斑的影响。方法　 2 8d龄 Wistar大鼠 3 6只 ,随机分为 pc DNA3 - pac组、pc DNA3 - gtf B组、pc DNA3 - pac联合pc DNA 3 - gtf B组、变形链球菌灭活全菌组、pc DNA3空载体组和 PBS液组 ,进行三次双侧颌下腺腺周注射免疫 ,建立定菌鼠模型 ,作诱龋实验 3个月。唾液变链菌计数和菌斑计分。结果　唾液变链菌菌落计数和牙面菌斑计分在 pc D-NA3与 PBS组最高 ,其次为单基因疫苗免疫组 ,联合基因疫苗和灭活全菌细胞免疫组最低 ,各组间有显著性差异 ( P<0 .0 5 )。结论　 pc DNA3 - gtf B和 pc DNA3 - pac具有明显的免疫抑菌作用 ,联合基因疫苗免疫优于单基因疫苗     

聚合酶链反应单链构象多态性检测乳腺癌中P53基因突变

应用聚合酶链反应单链构象多态性方法，对２４例原发性乳腺癌肿瘤组织基因组ＤＮＡ进行了分析，结果表明：其中７例存在Ｐ５３基因的突变，突变频率约为３０％。同时对其中１０例进行Ｓｏｕｔｅｒｎｂｌｏｔ分析，有２例在ｃｈｒ１７Ｐ上存在等位基因的缺失，而其另一等位基因上均存在基因突变。