Immunophenotype and possible origin of nevi with phenotypical heterogeneity

Biphenotypical nevi or nevi with phenotypical heterogeneity consist of phenotypically different cell populations in a pattern other than that observed in classical combined nevi or in various maturation stages of banal nevocellular nevi. Besides several well-known entities such as deep penetrating nevi and plexiform spindle cell nevi, this category of pigment cell lesions also harbors fewer delineated lesions such as nevi with atypical dermal nodules (N-ADN) and nevi with a focal atypical epithelioid cell component (N-FAECC). Their worrisome histology may result in a wrong diagnosis of malignancy. In order to discriminate them from malignant melanoma and to shed light on their histogenesis, we analyzed the immunophenotypical profile of 33 N-FAECC, 6 N-ADN, and 10 giant congenital nevi removed shortly after birth, using antibodies directed to S100 protein, gp100, tyrosinase, NKI-C3, Melan-A and Mib-1. In N-FAECC and N-ADN, the large polygonal cells expressed gp100, S100 protein and Melan-A, and reacted with monoclonal antibody NKI-C3. In addition, there was intense tyrosinase expression but no Mib-1 immunoreactivity. Unexpectedly, we observed similar single or clustered, large epithelioid cells in three out of ten giant congenital nevi; these cells showed a similar phenotype to those observed in N-ADN and N-FAECC. Our histological and immunohistochemical data suggest that N-FAECC and N-ADN may reflect different stages of the same disorder. Moreover, their resemblance to the large polygonal cells in congenital nevi may suggest that the histogenesis of N-ADN and N-FAECC may be related to the persistence and expansion of large epithelioid cells in congenital nevi shortly after birth.     

Paranormal experience and the COMT dopaminergic gene: a preliminary attempt to associate phenotype with genotype using an underlying brain theory

Paranormal belief and suggestibility seem related. Given our recent findings outlining a putative association between suggestibility and a specific dopaminergic genetic polymorphism, we hypothesized that similar exploratory genetic data may offer supplementary insights into a similar correlation with paranormal belief. With more affordable costs and better technology in the aftermath of the human genome project, genotyping is increasingly ubiquitous. Compelling brain theories guide specific research hypotheses as scientists begin to unravel tentative relationships between phenotype and genotype. In line with a dopaminergic brain theory, we tried to correlate a specific phenotype concerning paranormal belief with a dopaminergic gene (COMT) known for its involvement in prefrontal executive cognition and for a polymorphism that is positively correlated with suggestibility. Although our preliminary findings are inconclusive, the research approach we outline should pave the road to a more scientific account of elucidating paranormal belief.     

多囊卵巢综合征患者Ⅰ级亲属异常家族史与其临床表型的相关性

目的探讨多囊卵巢综合征（PCOS）患者Ⅰ级亲属异常家族史与PCOS患者临床表型的相关性。方法选择2004年8月至2006年4月在北京大学第三医院生殖医学中心诊断为PCOS的不孕症患者139例，计算体重指数（BMI）、腰围臀围比值（WHR）并进行多毛评分，测定卵泡刺激素（FSH）、黄体生成素（LH）、泌乳素、睾酮、雄烯二酮（A）、雌二醇水平，进行口服糖耐量试验（OGTT）及胰岛素释放试验等。收集PCOS患者Ⅰ级亲属的异常家族史，并分析其与PCOS患者临床表型的相关性。结果（1）有糖尿病家族史PCOS患者与无糖尿病家族史者相比，WHR（分别为0．99±0．10、0．79±0．08）、多毛评分[分别为（1．9±1．2）、（1．8±1．2）分]、月经稀发周期[分别为（108±10）、（92±19）d]均明显增加，稳态模型胰岛素抵抗指数（HOMA-IR，分别为3．5±2．0、2．7±1．6）、葡萄糖曲线下面积[GLUAUC，分别为（836±245）、（748±139）nmol·L^-1·min^-1]、胰岛素曲线下面积[INSAUC，分别为（9670±458z）、（7330±4311）mIU·L^-1·min^-1]、空腹血糖（FG）水平[分别为（5．0±1．1）、（4．8±0．5）mmol/L]、空腹胰岛素（FINS）水平[分别为（15±8）、（11±8）mIU／L]和A水平[分别为（11±6）、（8±5）nmol／L]均明显升高，胰岛初期分泌功能指数（△I60／△G60，分别为32±22、52±30）、胰岛素敏感指数（ISI，分别为0．019±0．011、0．033±0．014）和葡萄糖处置指数（DI，分别为18±10、30±22）明显降低，以上各指标两者间比较，差异均有统计学意义（P〈0．05）。（2）有月经紊乱家族史PCOS患者与无月经紊乱家族史者相比，WHR（分别为0．99±0．09、0．80±0．10）明显增加，多毛评分[分别为（1．9±1．0）、（1．6±1．1）分]也明显增加，月经稀发周期[分别为（105±28）、（84±31）d]明显延长，HOMA-IR和FINS水平[分别为（3．6±2．4）、（2．5±1．7）和（15±14）、（12±11）mIU／L]明显升高，而胰岛B细胞功能指数（HOMA-β）、ISI和DI（分别为178±134和207±175，0．017±0．019和0．034±0．012，23±18和28±19）明显降低，以上各指标两者间比较，差异均有统计学意义（P〈0．05）。（3）有早秃家族史PCOS患者与无早秃家族史者相比，BMI[分别为（26±4）、（23±5）kg／m^2]和多毛评分[分别为（2．1±1．1）、（1．7±1．3）分]也明显增加，DI（分别为20±11、30±23）明显降低，差异均有统计学意义（P〈0．05）。（4）有高血压家族史PCOS患者与无高血压家族史者相比，△I60／△G60（分别为34±27、50±30）明显降低，FINS水平[分别为（13±10）、（10±9）mIU／L]明显升高，上述指标两者间比较，差异均有统计学意义（P〈0．05）。（5）冠心病家族史则对上述各指标无明显影响（P〉0．05）。结论糖尿病家族史对PCOS患者临床表型影响最大，其次为月经紊乱家族史、早秃家族史、高血压家族史等，冠心病家族史则对PCOS患者临床表型无明显影响。     

人海绵状血管瘤内皮细胞特性的体外研究

目的 研究人海绵状血管瘤内皮细胞在形态、表型和功能方面的改变。方法 从人海绵状血管瘤组织分离、纯化血管内皮细胞,并应用透射电子显微镜、流式细胞术、逆转录聚合酶链反应（RT-PCR）、明胶酶谱法和激光共聚焦显微镜等技术与人正常人肝窦内皮细胞进行比较分析。结果 与正常人肝窦内皮细胞相比,人海绵状血管瘤内皮细胞的超微结构上,具有异常膨大的内质网和空泡样结构;表型上,高表达整合素αvβ3;功能上,体外形成血管样网络结构异常,并可能与其高表达的内源性血管内皮细胞生长因子、血管生成素1以及基质金属蛋白酶2有关。结论 人海绵状血管瘤内皮细胞在形态、表型和功能特性上都不同于正常肝窦内皮细胞。     

E2F"诱骗"策略抑制膀胱出口梗阻后逼尿肌细胞的表型转化

目的利用自建的膀胱出口梗阻（BOO）细胞水平的模型,探讨转录因子E2F“诱骗”（decoy）策略抑制逼尿肌细胞（DSMC）的表型转化作用。方法对培养的DSMC施加周期性张力负荷以建立细胞水平的BOO模型;以Lipofectamine2000介导E2F—decoy脱氧寡核苷酸（ODN）转染DSMC,设立E2F-decoy ODN转染组（Decoy组）,错配E2F-decoy ODN转染组（Mis—decoy组）及空白对照组（非转染组）;四甲基偶氮唑盐比色法（MTT）测定细胞的增殖活性,逆转录．聚合酶链反应（RT-PCR）分析增殖细胞核抗原（PCNA）mRNA表达水平,Western印迹检测PCNA和细胞周期依赖性蛋白激酶cdk2表达。结果Lipofectamine介导转染E2F-decoy ODN后24h可获得表达;Decoy组增殖活性显著低于非转染组和Mis-decoy组（均P〈0．01）;Decoy组PCNA mRNA表达显著低于非转染组（P〈0．01）;Decoy组PCNA和cdk2蛋白表达显著低于非转染组（126±14vs180±10;155±6vs210±22,均P〈0．01）;而Mis—decoy组与非转染组之间以上指标差异均无统计学意义（均P〉0．05）。结论E2F-decoy ODN能够转染DSMC并获得表达;转录因子E2F“诱骗”策略有效抑制了BOO后DSMC的表型转化,显示了从逼尿肌结构的角度改善梗阻后膀胱功能的前景。     

PHEX gene mutations and genotype-phenotype analysis of Korean patients with hypophosphatemic rickets

X-linked hypophosphatemic rickets (XLH) results from mutations in the PHEX gene. Mutational analysis of the PHEX gene in 15 unrelated Korean patients with hypophosphatemic rickets revealed eight mutations, including five novel mutations, in nine patients: two nonsense mutations, two missense mutations, one insertion, and three splicing acceptor/donor site mutations. Of these, c.64G>T, c.1699C>T, c.466_467 insAC, c.1174-1G>A, and c.1768+5G>A were novel mutations. To analyze the correlation between genotype and phenotype, phenotypes were compared between groups with and without a mutation, in terms of mutation location, mutation type, and sex. Skeletal disease tended to be more severe in the group with a mutation in the C-terminal half of the PHEX gene, but no genotype-phenotype correlation was detected in other comparisons. Further extensive studies of the PHEX gene mutations and analyses of the genotype-phenotype relationships are required to understand PHEX function and the pathogenesis of XLH.     

大鼠骨髓间充质干细胞体外分离培养表型鉴定与标记

目的 探讨大鼠骨髓间充质干细胞（MSCs）体外分离培养、表型鉴定和标记的方法，为临床进行细胞移植治疗心、肝、脑等器官急性衰竭提供种子细胞。方法 无菌条件下取大鼠股骨、胫骨和腓骨，用冲洗法冲出骨髓，用直接贴壁法分离纯化MSCs，体外扩增，用免疫细胞化学法及流式细胞仪分别对培养的MSCs进行鉴定，并检测第3代MSCs的细胞周期。结果体外培养的原代MSCs 72h内可见有少量贴壁细胞，7d左右达到汇合。免疫细胞化学示，MSCs CD29、CD44、CD73、CD105、CD166表达阳性，而CD14、CD34、CD45表达阴性。流式细胞仪示，CD14阳性率为0．19％、CD29为64．36％、CD34为0．17％、CT44为86．73％、CD45为0．18％、CD73为90、21％、CD105为74．25％、CD166为54．60％。细胞周期显示，第3代MSCs约有90％的细胞处于G0／G1期。结论 MSCs在体外很容易分离培养和扩增，DAPI标记MSCs敏感性好，标记效率高，可作为标记细胞的一种有效手段，MSCs体外培养成功为细胞移植治疗急危重症器官衰竭提供新的治疗途径。     

Suggestive linkage on chromosome 1 for a quantitative alcohol-related phenotype

BACKGROUND: Alcohol dependence is a clinically and etiologically heterogeneous disorder. Accordingly, a variety of subtypes of alcohol-dependent individuals have been proposed, and multiple operational definitions of alcohol use, abuse, and dependence have been used in linkage analyses directed toward detecting genes involved in alcohol use and problems. Here, we develop quantitative phenotypes that characterize drinking patterns among both alcoholic and nonalcoholic subjects, and use these phenotypes in subsequent linkage analyses. METHODS: More than 9000 individuals from alcoholic and control families were administered a semistructured interview and personality questionnaire as part of the initial stage of the Collaborative Study on the Genetics of Alcoholism (COGA). A principal component analysis was conducted on items that captured many of the dimensions of drinking and related behaviors, including aspects of alcohol use, antisocial behavior and affective disturbance when drinking, and personality. Factor scores were computed for all individuals. Nonparametric linkage analyses were conducted on these factor scores, in the initial COGA sample consisting of 987 individuals from 105 extended families, and in a replication sample consisting of 1295 individuals from 157 extended families. RESULTS: Three factors were identified, accounting for 68% of the total variance. The most promising regions of linkage appeared for factor 2, on which higher scores indicate a later age of onset of regular drinking and higher harm avoidance. Chromosome 1 yielded consistent evidence of linkage in both samples, with a maximum lod score of 3.3 when the samples were combined for analysis. Consistent suggestion of linkage also was found to chromosome 15. CONCLUSIONS: Developing novel phenotypes that more accurately model the effect of influential genes may help efforts to detect genes involved in complex disorders. Applying principal component analysis in the COGA sample provided support for some regions of linkage previously reported in COGA, and identified other new, promising regions of linkage.     

感染表型慢性阻塞性肺疾病

COPD是一种慢性炎症性病变,可累及大小气道、肺实质以及肺血管.引起COPD的危险因素众多,其中下呼吸道感染,尤其是细菌感染是导致COPD发生及急性加重的一个重要原因,以至有学者提出一个全新概念——感染表型COPD.本文拟对感染表型COPD概念提出背景及感染表型COPD的特征作一综述.