Human papillomavirus infection in Egyptian esophageal carcinoma: correlation with p53, p21, mdm2, C-erbB2 and impact on survival

The etiological role of human papillomavirus (HPV) in esophageal carcinoma (EC) in relation to p53, mdm2, p21(waf), c-erbB2 and the overall survival (OS) rate was investigated. Tumor and normal tissues from 50 EC were evaluated by polymerase chain reaction and InnoLiPA for HPV. Single strand conformation polymorphism/sequencing were used to detect p53 gene mutations. Immunohistochemistry was performed to determine p53, mdm2, p21(waf)and c-erbB2 expression. Human papillomavirus was detected in 54% of tumors and in 24% of normal tissues. p53, mdm2 and c-erbB2 overexpression was detected in 68%, 70% and 60% of tumors and in 14%, 16% and 10% of normal samples, whereas loss of p21(waf) was evident in 64% of tumors. p53 mutations were detected in 20% of cases. Exon 8 and 5 showed the highest mutation rate (40% each), followed by exons 6 and 7 (10% each). There was a significant correlation between HPV and p53, mdm2, c-erbB2 overexpression. The OS was significantly associated with overexpression of p53 and loss of p21(waf). Human papillomavirus infection is frequent in Egyptian EC. Both p53-dependent and p53-independent pathways seem to be involved in HPV-associated EC. mdm2 and c-erbB2 are possible targets for HPV in the p53-independent pathway. However, only advanced stage and aberrant expression of p53 and p21(waf) are independent prognostic markers.     

中国汉族雄激素过多症女性21-羟化酶缺陷症携带者基因检测

目的　初步了解中国汉族女性雄激素过多症患者中2 1-羟化酶缺陷症(2 1- hydroxylasedeficiency,2 1- OHD)携带者发生率,探讨促肾上腺皮质激素(adrenocorticotropic hormone,ACTH)兴奋试验结果与基因突变检测结果的相关性。方法　82例汉族女性雄激素过多症患者及14名健康女性进行ACTH兴奋试验,并应用PCR扩增产生限制性酶切位点方法检测已知的9个2 1- OHD常见突变位点。结果　雄激素过多组(n=82 ) F0 显著高于正常对照组(P<0 .0 1) ;17- OHP0 及17- OHP6 0 也显著高于对照组(P<0 .0 1) ,而F6 0 差异没有统计学意义(P>0 .0 5 )。比较17- OHP净增值及17- OHP净增值/ F净增值,雄激素过多组也均显著高于正常对照组(P<0 .0 1)。正常对照组未检测出细胞色素P4 5 0 (cytochrome P4 5 02 1,CYP2 1)基因突变。发现雄激素过多组4例CYP2 1基因突变携带者(4/ 82 ,4 .9% ) ,分别携带V2 81L(2例) ,i2 g及Q318X(各1例) ,携带者的ACTH兴奋试验结果与正常对照及未检出突变的雄激素过多症患者的结果存在一定的交叉。结论　82例汉族雄激素过多症女性中2 1- OHD携带者为4例,占4 .9%。ACTH兴奋试验不能用以发现携带者,应进行基因检测确定。     

荧光定量PCR快速诊断21三体综合征

目的　建立荧光定量PCR技术检测 2 1三体综合征。方法　采用PCR方法同时扩增位于 2 1号染色体上的人肝型磷酸果糖激酶基因 (humanliver typephosphofructokinasegene ,PFKL CH 2 1)和位于 1号染色体上的人肌型磷酸果糖激酶基因 (humanmuscle typephosphofructokinasegene ,PFKM CH1) ,使用SYBRGreenⅠ荧光染料处理产物、琼脂糖电泳后在凝胶成像系统进行分析 ,得出扩增产物的荧光强度对比值。用此方法检测 2 6例 2 1三体综合征患儿及 2 0名正常人。结果　 2 6例 2 1三体综合征患儿PFKL CH2 1/PFKM CH 1扩增产物的荧光强度对比值为 1.5 8± 0 .17,而正常人为 1 0 0± 0 .0 5 ,两者差异有显著性。结论　SYBRGreenⅠ荧光定量PCR技术检测 2 1三体综合征具有准确、快速、安全、实用等特点 ,有较高的临床使用价值。     

人恶性畸胎瘤PA-1细胞染色体特性及其影响因素的探讨

目的:探讨人类恶性畸胎瘤PA-1细胞株染色体特性及其影响因素。方法:采用G带核型分析、DNA碱基序列分析及Western blot(蛋白印迹分析)等方法对经20余年407-445继代培养的PA-1细胞株染色体核型及p 53 基因状态进行了研究。结果:PA-1细胞株80%以上仍然保持近乎二倍体的核型,30代以后的细胞由于第15号染色体与20号染色体间的相互易位形成了M1及M2标识染色体。RT-PCR产物DNA定向序列分析显示具有野生及突变两个带(p53密码子239突变),Western blot 未检测出突变的p53基因蛋白,而p21蛋白的表达水平比正常成纤维细胞低。结论:人卵巢恶性畸胎瘤PA-1细胞株经20年的继代培养后,一个p53 等位基因发生错义突变,另一个仍然是野生型的。仅一个p53 等位基因发生突变,不足以引起细胞的染色体不稳定性。     

Trisomy/tetrasomy 21 mosaicism in CVS: interpretation of cytogenetic discrepancies between placental and fetal chromosome complements

Trisomy/tetrasomy 21 mosaicism was found in chorionic villi (semidirect preparation) obtained from a 40 year old pregnant woman. Since both cell lines were abnormal, the couple elected for pregnancy termination. Placenta and fetal tissue samples were obtained for cytogenetic study. Long term cultured villi showed a non-mosaic trisomy 21 karyotype, while other tissues showed either a normal karyotype or normal/trisomy21 mosaicism. These discrepancies could be explained by a modified "bottle neck" embryogenic model with a trisomic zygote and a non-disjunction event taking place in one of the first divisions. Our case emphasises the need for confirmatory studies in other tissues when mosaicism is encountered in chorionic villi, even if all cell lines are abnormal.     

STAT3 couples with 14-3-3σ to regulate BCR signaling,B-cell differentiation,and IgE production

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Co‐occurring medical conditions in adults with Down syndrome: A systematic review toward the development of health care guidelines. Part II

Adults with Down syndrome (DS) represent a unique population who are in need of clinical guidelines to address their medical care. Many of these conditions are of public health importance with the potential to develop screening recommendations to improve clinical care for this population. Our workgroup previously identified and prioritized co‐occurring medical conditions in adults with DS. In this study, we again performed detailed literature searches on an additional six medical conditions of clinical importance. A series of key questions (KQ) were formulated a priori to guide the literature search strategy. Our KQs focused on disease prevalence, severity, risk‐factors, methodologies for screening/evaluation, impact on morbidity, and potential costs/benefits. The available evidence was extracted, evaluated and graded on quality. The number of participants and the design of clinical studies varied by condition and were often inadequate for answering most of the KQ. Based upon our review, we provide a summary of the findings on hip dysplasia, menopause, acquired cardiac valve disease, type 2 diabetes mellitus, hematologic disorders, and dysphagia. Minimal evidence demonstrates significant gaps in our clinical knowledge that compromises clinical decision‐making and management of these medically complex individuals. The creation of evidence‐based clinical guidance for this population will not be possible until these gaps are addressed.     

21-三体嵌合型母亲二次妊娠21-三体患儿

目的报告1例嵌合型母亲连续2次孕育单纯型21-三体患儿。方法对21-三体患儿、21-三体胎儿和其父母的血标本、父亲精子进行了DNA多态性检测,选择2个SRTR多态性位点,即D21S1412和D21S11,进行荧光定量PCR检测以确定额外21号染色体的起源。对父亲和母亲的外周血染色体和母亲皮肤染色体也进行了分析。结果对2个患儿与双亲的STR结果进行比较,显示2个患儿的额外21号染色体都来自母亲。双亲的STR检测中仅发现有2个微卫星标志物,外周血淋巴细胞染色体也均为正常。但母亲皮肤成纤维细胞检测到21-三体的细胞存在,占4%。结论母亲是21三体细胞/正常细胞的嵌合体,推测母亲生殖细胞中存在21三体细胞与正常细胞的嵌合,这可能是导致连续2次孕育21-三体患儿的原因。     

大鼠单克隆抗体夹心ELISA法检测肝病病人血清中p21^ras蛋白

本文应用抗癌基因ｒａｓ表达产物Ｐ２１ｒａｓ蛋白的大鼠单克隆抗体建立的双抗体夹心ＥＬＩＳＡ法，检测了肝癌及癌病变前病人血清中ｐ２１ｒａｓ蛋白的浓度。所获阳性检出率分别为：慢性乙型肝炎为１３．０％（１２／９２），肝硬化为２７．８％（１０／３６）和肝癌为５０．０％（８／１６）。另外，对试验方法的敏感性、特异性及稳定性，以及检测Ｐ２１ｒａｓ蛋白与ＡＦＰ的关系进行了评价。结果表明，Ｐ２１ｒａｓ蛋白的过高表达发生在肝细胞癌变之前。提示在慢性乙型肝炎及肝硬化病人血清中检出Ｐ２１ｒａｓ蛋白，是预测肝细胞癌变的危险信号。