Kinetics and enzyme involvement in the metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in microsomes of rat lung and nasal mucosa.

The rat lung and nasal cavity are two target organs for carcinogenesis by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). In order to characterize further the enzymes involved in the bioactivation of NNK, detailed kinetic and inhibitory studies were conducted with rat lung and nasal mucosa microsomes, and the results were compared with previous studies. The enzymes in rat lung microsomes catalyzed the alpha-hydroxylation, pyridine N-oxidation and carbonyl reduction of NNK. The apparent Km for the formation of the NNK-derived keto aldehyde, NNK-N-oxide, the NNK-derived keto alcohol and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol were 28.8, 10.4, 7.0 and 178.1 microM respectively. In rat nasal microsomes, alpha-hydroxylation was the predominant pathway and the rate was approximately 200 times higher than that in lung microsomes. The apparent Kms for keto aldehyde and keto alcohol formation in rat nasal microsomes were 9.6 and 10.1 microM respectively. The cytochrome P450 inhibitors metyrapone and carbon monoxide markedly inhibited the metabolism of NNK in both rat lung and nasal microsomes. In rat lung microsomes, alpha-naphthoflavone and monospecific antibodies against P450s 1A2, 2A1 and 2B1 inhibited the formation of keto aldehyde by 39, 46, 64 and 23% respectively. In rat nasal microsomes, alpha-naphthoflavone and antibodies against P450s 1A2, 2A1 and 3A inhibited the metabolism of NNK by 80, 35, 20 and 14% respectively. The results indicate that cytochromes P450 play a major role in the metabolic activation of NNK in rat lung and nasal microsomes, and that there are tissue-related differences in NNK metabolism.     

STUDIES ON NUTRITION AND PRECANCEROUS LESIONS OF THE ESOPHAGUS IN THE ADOLESCENTS

This paper reports the prevalence of chronic esophagitis and nutritional status among 538 young persons aged 15 to 26 years from the high risk area for esophageal cancer. Of these subjects, 166 were from households with history of esophageal cancer and 372 were from households without history of esophageal cancer. The Incidences of chronic esophagltis among male and female adolescents were 37. 6% and 36% respectively, which was significantly higher than those in the low risk area (17%). The frequency of chronic esophagltis in the adolescents in the households with history of esophageal cancer was aiso higher than in those In the households without history of esophageal cancer. The deficiencies of vitamins, especially of riboflavin and ascorbate, are prevalent and severe among these adolescents. Ascorbate deficiency Is correlated with the severity of the chronic esophagltis. These results indicate that chronic esophagltis may be involved in the natural history of esophageal carclnogenesis. Nutrient defic     

慢性乙型肝炎病人血清中游离白细胞介素2受体升高的意义

应用放射免疫分析法测定慢性活动性肝炎(CAH)和慢性迁延性肝炎(CPH)病人及健康人血清中游离白细胞介素2受体(fIL2R)水平,CAH和CPH病人的cpm分别是2326±617及1277±397,健康人仅为343±213。结果发现:CAH和CPH病人血清中fIL2R水平均显著高于健康人(P<0.01);CAH病人血清中fIL2R水平高于CPH病人(P<0.01)。提示,慢性乙型肝炎病人血清中fIL2R水平升高可能与其免疫应答异常及炎症活动性有关。     

地塞米松对哮喘豚鼠肺组织Giα、Gqα的抑制作用

目的　研究糖皮质激素对豚鼠哮喘模型肺组织G蛋白α亚族表达的影响。方法　 18只豚鼠随机分为正常对照组(NS) ,哮喘组 (AS)和地塞米松治疗组 (DEX)。AS组用卵蛋白皮下及腹腔注射致敏 ,卵蛋白重复雾化吸入激发复制豚鼠哮喘模型。DEX组在每次激发前腹腔内注射地塞米松 2mg/kg进行干预。用Westernblot分析法测定豚鼠肺组织G蛋白α亚族的表达水平。结果　三组豚鼠肺组织Giα水平分别为NS组 10 0 % ,AS组 (15 3± 18) % ,DEX组 (113± 18) % ,AS组与NS组比较、DEX组与AS组比较差别显著 (P <0 .0 5 )。三组豚鼠肺组织Gqα水平分别为NS组 10 0 % ,AS组 (15 1± 19) % ,DEX组 (98± 4 ) % ,AS组与NS组比较、DEX组与AS组比较差别显著 (P <0 .0 5 )。在同样的条件下Gsα水平无显著变化 (P >0 .0 5 )。地塞米松能够显著抑制哮喘豚鼠肺组织中Giα、Gqα的高表达。结论　肺组织Giα ,Gqα的高表达变化参与了豚鼠哮喘模型的病理性信号传导 ,抑制哮喘肺组织Giα、Gqα的高表达可能是糖皮质激素治疗哮喘的机制之一。     

备用根大鼠脊髓后角提取液中神经营养活性组分的分离及生物活性测定

制作备用根大鼠脊髓后角提取液，取其分子量大于10kD的组分进行SDS-聚丙烯酰胺凝胶电泳分析，发现手术侧和非手术侧的电泳区带数目大致相同，但手术侧样品的第四条蛋白质区带扫描的吸收峰面积百分比大于非手术侧样品的第四条区带，两者在量上可能有差别。将手术侧样品经交联葡聚精G-75凝胶层析，得到两个洗脱峰．第一峰洗脱液有促进体外培养的背根节神经元存活及其突起生长的作用，其电泳分析显示4条主带，分子量在40～80kD之间．实验结果提示部分去传入纤维支配的脊髓后角组织含有神经营养活性物质，该物质的分子量约在40～78kD之间．     

胰岛素抵抗与心血管产现危险因素聚集性关系研究

The coexistence of multiple cardiovascular risk factors in the same individual is called a clustering of cardiovascular risk factors. Many studies have shown that this phenomenoa is associated with a increased morbility of cardiovascular disease, and insulin resistance may be the common link between the risk factors. This study was designed to link the clustering of cardiovascular risk factors with insulin resistance. Using a new insulin sensitivity index [-log (fasting serum Glu x Ins)] to evaluate the insulin resistance, we investigated the relationship between the insulin sensitivity and cardiovascular risk factors in 106 patients with hypertension or coronary heart disease and 32 normal subjects. The normal group without cardiovascular risk factors was selected as controls. The individual with 2 risk factors were defined as having mild clustering, and those with > or = 3 risk factors as severe clustering. As the number of risk factors increased from 1 to > or = 3, the insulin sensitivity index increased from -1.69 +/- 0.24, -1.95 +/- 0.17 to -2.14 +/- 0.21 respectively. The insulin resistance was positively correlated with serum uric acid in women (P < 0.05), but not in men (P > 0.05). The insulin sensitivity was more decreased in postmenopausal than in pre-menopausal women. The insulin sensitivity index was -2.23 +/- 0.39 vs -1.73 +/- 0.13 (P < 0.05). The insulin resistance is associated with a clustering of risk factors of cardiovascular disease, more cluste-ring, more resistant.     

肝病患者肝组织中丙型肝炎病毒感染的初步研究

采用直接酶标记法对174例慢性肝炎、重症肝炎和肝癌组织中的HCV抗原进行了检测,HCV 抗原的检出率分别为10.71％、8.10％和2.68％。表明在我国慢性和重症肝病中存在HCV的感染。通过对HCV与HBV 感染关系的研究,发现肝内HBV 标志阳性和阴性者HCV抗原的检出率无明显差异,说明HCV感染与HBV感染之间似无明显关系。     

动脉分支处的红细胞流变学研究与小动脉端侧吻合

为了探讨动脉分支处及小动脉端侧吻合处的血液流动方式，采用微循环电视显微镜成像技术，活体观察大鼠肠系膜微动脉分支区域血液流动方式和红细胞流变行为，研究动脉血流方向的改变对血流方式的影响。实验中观察到，在形态各异的大鼠肠系膜微动脉分支区域血液流态为稳定层流；红细胞通过不规则变形能很好地适应血管腔不同的几何形态，以保持血液流态的稳定。结果表明，微小动脉血流方向的改变未能在分支区域导致湍流发生，小动脉端侧吻合只是人为增加了侧支循环，同样不会导致血流紊乱和增加血栓形成的危险     

羊水细胞培养宫内诊断的应用(附120例分析)

报告120例羊膜腔穿刺羊水细胞培养结果:在成功的99例中,发现二例染色体异常,核型为47,xy,+18和46,xx/47,xx,+F,在21例失败中出现一例眼球畸形。培养成功率为82.5%;染色体异常检出率为2.02%。无一例因羊膜腔穿刺而导致流产,但出现一例轻度羊水栓塞合并症。并对羊水细胞培养在产前宫内诊断中应用价值及术后并发症进行了讨论。     

P53、C-erbB-2基因蛋白和EGFR在泌尿系移行细胞癌中的表达及相互关系

应用免疫组化技术研究65例泌尿系移行细胞癌（包括47例膀胱癌和18例肾盂癌）组织中P53、C－erbB－2基因蛋白和表皮生长因子受体（EGFR）的表达及相互关系。结果显示P53在膀胱癌中阳性率为57．5％（27／47），在肾益癌中为50．0％（9／18）；C－erbB－2基因蛋白在膀胱癌和肾盂癌中的表达率分别为40．4％和38．9％；EGFR的表达率分别为42.6％和44．4％。P53、C－erbB－2基因蛋白和EGFR表达均与膀胱癌和肾盂癌的分级和分期有关，P53、C－erbB－2基因蛋白和EGFR有显著相关关系。结果表明P53、C－erbB－2基因蛋白和EGFR对膀胱癌和肾盂癌的恶性程度和预后评估具有重要参考意义。