Recurrent and novel mutations of GCDH gene in Chinese glutaric acidemia type I families

Glutaric acidemia type I is caused by mutations of the glutaryl-CoA dehydrogenase (GCDH) gene resulting in loss of GCDH enzyme activity. Patients present with progressive dystonia and lesions in basal ganglia. Dietary treatment, when instituted from the early neonatal period, markedly reduces dystonia and morbidity. Early diagnosis and prenatal diagnosis will be facilitated by knowledge of locally prevalent GCDH mutations. Several common GCDH mutations have been found in different ethnic groups. GCDH mutations were studied in 5 Chinese glutaric acidemia type I families. We detected two novel recurrent mutations (A219T and IVS10-2A>C) which were found in two unrelated families. An asymptomatic carrier of IVS10-2A>C was also found on screening of 120 individuals. Other mutations were identified, including two other novel (R386G & IVS3+1G>A) and two known mutations (G178R & R355H). Fibroblasts from patients carrying the novel mutations were confirmed to be deficient for GCDH activity. This is the first report of GCDH mutations describing recurrent mutations in Chinese patients. The carrier rate of IVS10-2A>C may be particularly high in Chinese.     

重复电刺激前肢神经引起成年大鼠运动皮层的可塑性改变

为了了解成年大鼠运动皮层的功能可塑性，利用皮层内微刺激方法测定ＭＩ代表区并观察重复电刺激前肢神经对ＭＩ代表区的影响。实验组大鼠（９例）持续１．２－２小时的前肢神经电刺激导致前肢运动区与面部触须运动区边界向ＶＩ方向，移动２６３．３±９０．９μｍ并同时伴有运动阈值的改变；ＦＬ内ＭＴ降低５．０±１３．３μＡ，而在ＶＩ内ＭＴ升高９．６±１１．６μＡ对照组大鼠间隔１．５－２小时的两次测定结果，ＦＬ－ＶＩ边界     

HLA-DR、DQ等位基因与精神分裂症相关性的研究

目的 证明HLA-DR、DQ等位基因与精神分裂症的发病密切相关。方法 HLA-DR、DQ等位基因检测：PCR-SSP分型。结果 发现在大连地区随机选择的精神分裂症患者的HLA-DQ8基因的频率(9．0％)明显高于正常对照(2．5％)。精神分裂症患者的HLA-DR、DQ等位基因的某些位点与免疫指标的改变有相关性。结论 ①HLA-DQ8基因与精神分裂症有关联，可以认为HLA-DQ8基因可能是精神分裂症的易感基因。②HLA-DR、DQ等位基因的某些组合可能是精神分裂症发病的危险组合模式，对预测精神分裂症的基因易感性具有潜在的应用价值。③精神分裂症的免疫指标的改变与HLA-DR、DQ等位基因的某些位点有相关性，说明精神分裂症与它的免疫指标的变化可能有内在的联系。     

Molecular cytogenetic characterization of nasopharyngeal carcinoma cell lines and xenografts by comparative genomic hybridization and spectral karyotyping

Nasopharyngeal carcinoma (NPC) cell lines and xenografts represent valuable models for functional and therapeutic studies on this common malignancy in Southeast Asia. The karyotypic information in most NPC cell lines and xenografts, however, remains largely unclear to date. We have characterized the chromosomal aberrations in six commonly used human NPC cell lines and xenografts using the molecular cytogenetic technique of comparative genomic hybridization (CGH). Genomic imbalances identified in cell lines were further correlated with structural abnormalities indicated from spectral karyotyping (SKY) analysis. CGH revealed consistent overrepresentations of 8q (six out of six cases) with a smallest overlapping region identified on 8q21.1q22. Other common gains included 7p (4/6 cases), 7q (4/6 cases), 12q (4/6), and 20q (4/6 cases), where minimal overlapping regions were suggested on 7p15p14, 7q11.2q21, and 12q22q24.1. Common losses were detected on 3p12p21 (4/6 cases) and 11q14qter (4/6 cases). Although SKY analysis on cell lines revealed predominantly unbalanced rearrangements, reciprocal translocations that involved chromosome 2 [i.e., t(1;2), t(2;3), and t(2;4)] were suggested. Furthermore, SKY examination illustrated additional breakpoints on a number of apparently balanced chromosomes. These breakpoints included 3p21, 3q26, 5q31, 6p21.1p25, 7p14p22, and 8q22. Our finding of regional gains and losses and breakpoints represents information that may contribute to NPC studies in vitro.     

Carboxymethyl-histaminocarbonylmethylamylose as a mimetic system of chymotrypsin in the catalytic hydrolysis of esters

A new type of polysaccharide host, carboxymethyl-histaminocarbonylmethylamylose ( 2b ), containing carboxylic, imidazolyl and hydroxyl groups in the backbone, was used as a mimetic system for chymotrypsin in the catalytic hydrolysis of 3-acetoxy-N-dodecylpyridinium iodide ( 1 ). The substrate is located in the hydrophobic cavity of the amylose helix. The apparent saturation, the entropy-favored kinetics and the pronounced catalytic efficiency (9 times higher than that of a system consisting of the same concentration of carboxymethylamylose and histamine) show that 2b is a good enzyme model in which the definite binding site, active center and self-organization characteristics are present. Most distinctly, the pH-rate constant profile of the hydrolysis of 1 and 2b is of bell-type and has an optimum at pH 7,98, which is very close to 7,90 for chymotrypsin. In conclusion, the charge relay mechanism is also involved in the catalytic effect of 2b .     

巢蛋白和阶段特异性胚胎抗原-1在大鼠2型星形胶质细胞中的表达

目的 观察1型和2型星形胶质细胞(T1A、T2A)是否表达神经干细胞的标志物、是否具有神经干细胞的特性.方法 取新生大鼠脑皮质,体外培养纯化的O-2A祖细胞、T1A和T2A,应用激光共焦双重免疫荧光标记技术检测巢蛋白和阶段特异性胚胎抗原-1(SSEA-1)的表达;观察O-2A祖细胞、 T1A和T2A在碱性成纤维生长因子(bFGF)和表皮生长因子(EGF)的培养液中生长方式的改变.结果 巢蛋白在O-2A祖细胞和T2A中表达,T1A不表达;SSEA-1仅在T2A中表达.在干细胞培养基中培养10d,T2A形成能增殖和连续传代的细胞球,细胞球巢蛋白标记阳性,贴壁后分化细胞具有神经元、星形胶质细胞和少突胶质细胞样形态;但相同培养条件下的O-2A祖细胞和T1A生长方式无改变.结论 巢蛋白和SSEA-1在两型星形胶质细胞中的表达存在差异,T2A具有神经干细胞的某些生物学特性.     

华南、华北人群HLA-DQB1等位基因多态性

目的从基因水平调查了中国华南、华北地区人群HLA-DQB1等位基因频率，并研究比较两地区人群HLA-DQB1多态性分布。方法采用深圳益生堂生物企业有限公司研制开发的“HLA-DQB1低分辨率分型基因芯片检测试剂盒”，应用聚合酶链反应．序列特异性引物＋序列特异性寡核苷酸探针芯片检测技术，对700名南方地区的中国人和320名北方地区的中国人进行基因分型。结果鉴定了10个HLA-DQB1等位基因，获得了一组准确、科学的统计数据。结论得到了中国华南、华北地区人群HLA-DQB1等位基因频率差异的数据，证明中国人群HLA-DQB1＊02，05，0601，0602，0603的分布南北差异有统计学意义（P〈0．05），为疾病相关性研究、人文科学研究提供了可靠的遗传学数据。     

应用多层螺旋CT对耳硬化症的术前评估价值

目的:评估MDCT在术前耳硬化症诊断中的作用。方法:收集经临床证实为耳硬化症、且CT扫描采用螺旋扫描病例共18例,采集的数据传输到4.1工作站,进行多平面重建。结果:18例共36耳显示异常:单独前庭窗异常18耳,表现为前庭窗扩大或狭小,周围骨质密度降低或镫骨底板板密度增高;前庭窗及蜗窗同时受累共8耳;主要累及耳蜗周围迷路骨质10耳,表现为耳蜗骨迷路边缘不整,呈条片状密度减低或双环征。MPR交互重建充分显示了所有重要解剖结构的位置、形态:其中3耳为颈静脉球高位。结论:MDCT可以正确显示耳硬化症病灶的细微改变,提供详细的术前诊断信息;结合MPR技术可全面观察病变范围,并充分显示颞骨内重要解剖结构的位置和形态。对于手术方案的设计、防止手术并发症和提高疗效等具有重要意义。     

Epithelioid trophoblastic tumor: clinicopathological features with an emphasis on uterine cervical involvement.

We report on the clinical and histological features of five cases of epithelioid trophoblastic tumor, with an emphasis on its involvement of the uterine cervix. All five patients were of reproductive age (median age 38.4 years) and all, except one, presented with vaginal bleeding 3 to 18 years after the most recent pregnancy. One patient presented with amenorrhea. Elevation of serum human chorionic gonadotropin (hCG) was seen in four cases. Pathologically, the tumor involved endocervix in three cases and involved uterine corpus in another two. All five tumors were invasive, nodular lesions consisting of epithelioid intermediate trophoblastic cells that were mononuclear with abundant eosinophilic cytoplasm, along with zones of hyaline material and necrotic debris. In three cases of cervical involvement, the neoplastic cells focally replaced endocervical surface and glandular epithelium, simulating high-grade squamous intraepithelial lesions. Immunohistochemically, all five tumors displayed focal positivity for human placental lactogen and hCG. Positive nuclear staining of p63 was seen in all five cases. All patients received total hysterectomy and various regimes of adjuvant chemotherapy. Three patients survived the tumor with no recurrences or metastases with follow-up periods of 3, 7 and 16 years. One patient is currently alive with lung metastasis 1 month after the surgery. One patient died of tumor metastasis 8 months after the diagnosis. In summary, with its unusual ability to simulate an invasive squamous cell carcinoma and other epithelioid neoplasms, epithelioid trophoblastic tumor frequently poses a diagnostic challenge, especially when involving the uterine cervix. High index of suspicion and an awareness of elevation of serum chorionic gonadotropin are crucial in reaching a correct diagnosis.