应用受体学说模型研究硝基苯类化合物的致毒机理

应用受体学说推出的定量结构活性相关(QSAR)模型研究了硝基苯类化合物的致毒机理,结果表明,硝基苯类化合物的主要致毒机理是化合物亲电中心与受体分子亲核活性中心发生反应．并引入硝基数目和位置指示变量I,分析表明,苯环上硝基的数目和位置的差别引起化合物的最低未占轨道能ELUMO的变化,即化合物亲电结合能的变化,从而影响了化合物的生物活性．     

中国嗅觉实验室建设现状调查及规范制订建议

嗅觉实验室的环境是影响嗅辨实验准确性的关键因素。中国的嗅觉实验室在建设过程中,由于缺乏具体的技术指导,各地区的嗅觉实验室形态差异较大,不能为嗅觉实验提供规范化的实验场所。通过中国嗅觉实验室的现状调查,分析了目前嗅觉实验室存在的问题,提出了嗅觉实验室建设技术规范的制订原则和重点内容。     

基于受体作用理论的类雌激素效应测试方法

以17β雌二醇为标准参考物质,对基于受体作用理论的环境激素分析方法实验条件进行了重构和优化,建立了环境类雌激素分析方法。结果表明:用营养缺陷型培养基30℃恒温振荡66 h培养时间进行重组基因酵母的复苏与增殖,20℃～35℃水浴样品与酵母混合液培养3～6 h暴露,优先选用机溶剂处理法释放β-半乳糖苷酶,35℃恒温水浴进行酶活测试反应,采用反应终止后2.5 h 420 nm波长进行分析测试,同时实际样品的分析,加测不少于一个的稀释水样效应值,可使方法更加科学高效、准确度高,应用于各类实际样品分析。     

Prenatal analysis of insulin receptor autophosphorylation in a family with leprechaunism

We describe a method for the isolation and functional characterization of insulin receptors from chorionic villi and cultured amniotic fluid cells. The functionality of these receptors is assayed by measuring the insulin-induced stimulation of autophosphorylation of the receptor β-chain. The method is expected to allow the prenatal diagnosis of those forms of lep-rechaunism and related diseases which are the result of a decreased stimulation by insulin of receptor autophosphorylation. A pregnancy at risk for leprechaunism was examined and an unaffected child was correctly predicted by study of the functionality of the insulin receptor on cultured amniocytes and by echoscopic examination.     

Blood transferrin receptor expression in chromosomally abnormal fetuses

In a cross-sectional study of 13 chromosomally abnormal fetuses, umbilical venous blood was obtained by cordocentesis at 17–32 weeks' gestation. Fetal blood transferrin receptor (CD71) expression (mean=79·8 per cent, range=60–98 per cent) and nucleated red cell count (mean=10·4 × 10⁹ per 1, range=1·0–25·0 × 10⁹ per 1) were significantly higher than the appropriate normal mean for gestation (z=3·92, P<0·0001 and z=3·69, P<0·001, respectively). These haematological changes in chromosomally abnormal fetuses would facilitate their prenatal diagnosis by analysis of fetal nucleated red blood cells isolated from the maternal circulation on the basis of CD71 expression.     

Prenatal overgrowth and mosaic trisomy 15q25-qter including the IGF1 receptor gene

Overgrowth is rarely associated with chromosomal imbalances. Here, we report on a male foetus presenting with overgrowth and additional material on the short arm of one of the chromosome 15 in 12% of lymphocytes and 50% of amniotic cells. Parents' karyotypes were normal, indicating a de novo origin for this unbalanced rearrangement. Complementary studies using cytogenetic and FISH studies showed that this additional material resulted in a 15q25-qter trisomy and confirmed the presence of three copies of the insulin-like growth factor 1 receptor (IGF1R) gene, included in the trisomic region. Autopsy performed after termination of pregnancy revealed isolated overgrowth and absence of visceral malformations. The possible mechanisms and origins for the formation of this mosaic pure trisomy are complex. The present observation emphasises the hypothesis that the overgrowth phenotype, frequently reported in patients with trisomy including the 15q26 region, might be causally related to a dosage effect of the IGF1R gene, as well as the importance of chromosome analysis in patients with overgrowth. It also confirms that the overgrowth is of prenatal onset in those observations. Copyright © 2004 John Wiley & Sons, Ltd.     

ERα和ERβ介导的有机磷农药雌激素效应差异分析

雌激素受体（Estrogen Receptor,ER）ERα和ERβ能与雌激素特异性结合,它们在结构上的差异性可能影响与类雌激素的相互作用,这进而会影响其功能.因此,针对10种有机磷农药对ERα和ERβ的雌激素效应差异,采用分子对接方法比较分析了它们与ERα、ERβ相互作用的差异并筛选出与ERα和ERβ相互作用的最佳结合模式.结果发现,10种有机磷农药分子与ERα配体结合域（Ligand Binding Domain,LBD）精氨酸（Arg394）、赖氨酸（Lys449）、色氨酸（Trp393）形成氢键;而部分农药分子与ERβLBD精氨酸（Arg346）、亮氨酸（Leu343）、赖氨酸（Lys401）形成氢键.有机磷农药配体与ERαLBDArg394、Lys449、苯丙氨酸（Phe445）、脯氨酸（Pro324）、Leu387、谷氨酸（Glu353）、甘氨酸（Gly390）等存在疏水作用,与ERβLBD氨基酸Arg346、Glu305、Leu343、蛋氨酸（Met336）、组氨酸（His279）、丙氨酸（Ala302）等存在疏水作用.采用量子化学从头算进一步分析了10种有机磷农药分子表面静电势的差异.研究发现,有机磷农药分子与ERα和ERβ受体不同的相互作用是导致雌激素效应差异的重要原因.     

Effects of estrogen exposure in mussels, Mytilus edulis, at different stages of gametogenesis

Mytilus edulis were exposed to 17β-estradiol (E2) and the synthetic estrogens ethinyl estradiol (EE2) and estradiol benzoate (EB) for 10 days. Two exposures were performed to determine their effect on vitellogenin (VTG) and estrogen receptor 2 (ER2) mRNA expression at different stages of the reproductive cycle. Significant natural variation was not observed in VTG mRNA expression, though ER2 mRNA expression displayed significantly lower values during January, February and July compared with other times of the year. A significant increase in VTG and ER2 mRNA expression was observed in mussels exposed to estrogens at the early stage of gametogenesis. In contrast, mature mussels displayed no statistically significant change in the VTG or ER2 mRNA expression. The data presented suggests that the reproductive physiology of molluscs, in terms of VTG and ER2 mRNA expression, may be susceptible to damage by environmental estrogens at certain points in their gametogenesis process.