美国临床遗传学进展

第四讲 不孕症及高风险妊娠 临床遗传学医生的另一项重要职责是通过以下多种措施提供优生优育的建议和指导：①不孕症的病因诊断；②试管婴儿的产前及孕前咨询；③产前筛查及普查；④携带者的检出及产前咨询；⑤超声波的应用及所带来的困惑；⑥产前诊断及手段。     

Pretreatment with Tongxinluo protects porcine myocardium from ischaemia/reperfusion injury through a nitric oxide related mechanism

Background The traditional Chinese medicine Tongxinluo can protect myocardium against ischaemia/reperfusion injury, but the mechanism of its action is not well documented. We examined the involvement of nitric oxide in the protective role of Tongxinluo. Methods Miniswine were randomized to four groups of seven: sham, control, Tongxinluo and Tongxinluo coadministration with a nitric oxide synthase inhibitor Nω-nitro-L-arginine (L-NNA, 10 mg/kg i.v.). Three hours after administration of Tongxinluo, the animals were anaesthetised and the left anterior descending coronary artery ligated and maintained in situ for 90 minutes followed by 3 hours of reperfusion before death. Area of no reflow and necrosis and risk region were determined pathologically by planimetry. The degree of neutrophil accumulation in myocardium was obtained by measuring myeloperoxidase activity and histological analysis. Myocardial endothelial nitric oxide synthase activity and vascular endothelial cadherin content were measured by colorimetric method and immunoblotting analysis respectively.Results Tongxinluo significantly increased the local blood flow and limited the infarct and size of no reflow. Tongxinluo also attenuated myeloperoxidase activity and neutrophil accumulation in histological sections and maintained the level of vascular endothelial cadherin and endothelial nitric oxide synthase activity in the reflow region when compared with control group. The protection of Tongxinluo was counteracted by coadministration with L-NNA. Conclusions Tongxinluo may limit myocardial ischaemia and protect the heart against reperfusion injury. Tongxinluo regulates synthesis of nitric oxide by altering activity of endothelial nitric oxide synthase.     

Autologous peripheral blood stem cell transplantation in the patients with hematologic malignancies and solid tumors

Objective To evaluate the long-term therapeutic effects of autologous peripheral blood st em cell transplantation (auto-PBSCT) on the treatment of hematological and soli d tumors. Methods Fifty-one patients were recruited in this auto-PBSCT study, in which several p otentially important parameters were studied including the optimal time for stem cell co llection, the dose of stem cell reinfusion, the time of hematopoietic reconsti tution, the disease free survival (DFS) and overall survival (OS), complication s related to transplantation, and maintenance chemotherapy after auto-PBSCT. Results After APBSCT, 3-year and 5-year survival rates of NHL were 83.3%; those of AM L were 74.7%; those of MM were 37.9% and 19%; those of ALL were 40% and 0% res pectively. Hematopoietic reconstitution was greatly promoted by granulocyte col ony stimulating factor (G-CSF). The mean time for patients’ neutrophil to reco ver up to >0.5×10(9) /L after APBSCT was 11.14 days in the group of the patien ts receiving G-CSF in contrast to 17.6 days in the group receiving no G-CSF. The most common complications of transplantation were fever, liver dysfunction and hypokalaemia, which were curable. No death was due to transplantation related complications.Conclusion Comparing with conventional chemotherapy, our study suggests that auto-PBSCT i s a very important therapeutic option that can significantly improve the prognos is in the patients with hematological and solid tumors, especially in the patien ts with AML and NHL.     

Interleukin-6 in bronchoalveolar lavage fluid from patients with COPD

目的　本研究通过检测支气管肺灌洗液 (BALF)中及肺泡巨噬细胞 (AM)产生的IL 6 ,揭示IL 6与慢性支气管炎(COPD)肺气肿发生的关系 ,为IL 6提供新的研究领域。方法　检测 6名正常无吸烟人及 2 1名COPD患者BALF中及AM释放的IL 6 ,根据正常人组BALF中IL 6的 95 %正常值可信区限 ,将COPD患者分为二组 ,在正常值可信区限内为第一组 ,在正常值可信区限外为第二组。结果　表明 2组中AM产生的IL 6第二组明显高于第一组 ,且 2组患者肺功能 (Dlco ,FEV1,FEV1/FVC和RV/TLC)有明显差异结论　AM产生的IL 6可能与COPD患者肺功能变化有关 ,在COPD患者肺气肿发生发展过程中发挥重要作用     

Effect of ipratropium bromide on airway and pulmonary muscarinic receptors in a rat model of chronic obstructive pulmonary disease

Objective　To observe the level of muscarinic receptors in airway and lung tissues, and the effect of inhaled ipratropium bromide on these receptors in a rat model of chronic obstructive pulmonary disease (COPD). Methods　This model was developed by exposure of rats to 250 ppm SO2 gas, 5?h/d, 5d/wk, for a period of 7 wk. The COPD rats inhaled 0.025% aerosolized iratropium bromide for 20 min, 2 times daily, in an airtight chamber. Muscarinic receptors in airway and lung tissues of normal rats, ipratropium bromide-treated COPD rats and the recovering COPD rats were measured by the radio-ligand binding assay. Results　Airway/lung pathology and pulmonary function tests showed that chronic SO2 exposure caused pathophysiologic changes similar to those observed in human COPD. The density (0.038±0.011, pmol/mg protein) and affinity (Kd, 23±11 pmol/L) of muscarinic receptors in airway and lung tissues of COPD rats were not changed compared with those of normal control rats (0.030±0.008 and 29±19, respectively, P>0.05). Densities of the muscarinic receptors were not changed after inhalation of ipratropium bromide for 5 days, but increased significantly after inhalation for 30 days, as compared with those of the untreated COPD rats. The muscarinic receptors returned the normal levels at day 6 after cessation of ipratropium bromide treatment. There were no differences among different groups of rats in equilibrium dissociation constants (Kd). Conclusion　A rat model of COPD with pathophysiologic changes similar to the human counterpart was developed using chronic SO2 exposure. There was no significant change in the number and function of muscarinic receptors in airway and lung tissues of the COPD rats, but upregulation of the muscarinic receptors was observed after long-term inhalation of ipratropium bromide.     

医学重复观测数据裂区方差分析的假定条件的检验

目的 重复观测数据存在自相关性常导致一元方差分皙误用,探讨一元方差分析两个假定条件的检验。方法 通过标准正交对比变换克服数据间的自相关性,应用似然比统计量进行假定条件的检验。结果 给出了重复观测数据一元方差分析的假定条件检验方法,并用软件REP得以实现。结论 只有满足假定条件,才可以保证重复观测资料单变量方差分析的有产性。     

内皮素与脑梗死

目的 :检测脑梗死病人的内皮素 - 1(ET - 1)水平 ,研究ET - 1与脑梗死的关系。方法 :检测脑梗死病人ET - 1的水平 ,并与正常对照组比较。结果 :脑梗死病人的ET - 1明显高于正常对照组水平 (U =13.45 ,P<0 0 1) ,还发现ET - 1与高血压、糖尿病、高血脂症有一定的关系。结论 :ET - 1的增高是脑梗死发病的内源性危险因素之一 ,ET - 1的增高不但与脑梗死的发病有关而且与脑梗死的发展有关     

电针对大鼠胃粘膜胃泌素和EGFR表达及AgNOR的影响

目的 观察电针足三里穴对胃粘膜细胞受体表达及核增殖的影响。探讨针灸作用机制。方法 75只SD大鼠随机分段分为5线,在清醒状态下针刺实验,SABC法免疫组化染色观察胃粘膜细胞胃泌素（Gas)、表皮生长因子受体（EGFR）表达程度,AgNOR特染观察胃腺细胞增殖情况。结果 电针足三里穴胃粘膜EGFR阳性表达率73.3%,Gas表达率66.7%;电针三阴交对EGFR表达远景as表达率为46.7%;联合穴位组Gas,EGFR表达均达60.0%,AgNOR特染各组核内嗜银颗粒无明显差异。结论 电针足三里可提高胃粘膜细胞Gas和EGFR表达率。改变细胞分子结构。影响细胞功能,电针对胃粘膜细胞核增殖无影响。     

石蜡切片中BCL-6抗原失活机制及修复

目的　探讨石蜡切片中BCL 6抗原失活机制及修复的最佳方法 .方法　淋巴组织反应性增生 11例石蜡切片分别用二乙胺四乙酸 (EDTA)、柠檬酸、碳酸钠及去离子水 4种与钙离子结合力不同的修复液 ,结合高压、微波和煮沸 3种不同方法修复后 ,比较检出的BCL 6阳性率及强度 .结果　BCL 6阳性率由高至低依次为 :EDTA 0 .73>柠檬酸 0 .45 (P<0 .0 1) >碳酸钠 0 .12 (P <0 .0 1) ,去离子水组无 1例阳性 .高压修复阳性率 0 .5 5 >微波修复 0 .2 8和煮沸修复 0 .12 (P <0 .0 5 ) .不同修复液与高压结合修复检出BCL 6阳性率及强度 :EDTA与柠檬酸阳性率分别为 1,0 .82 (P >0 .0 5 ) ,高于碳酸钠组 (0 .36 )和去离子水组 (0 ) (P <0 .0 1) .EDTA组强阳性占 0 .82 ,显著高于其他各组 (P <0 .0 1) .结论　EDTA结合高压是修复BCL 6抗原的理想方法 ,钙离子的参与可能是甲醛固定后BCL 6抗原失活的原因之一     

槲皮素对NB4细胞株p53及蛋白的影响

目的研究治疗白血病的有效药物。方法将槲皮素作用于培养的NB4细胞株,应用RT-PCR及Westem bolt方法,研究不同浓度槲皮素(30、60、90μmol/L)诱导细胞24、48、72、96、120h后,急性早幼粒细胞白血病NB4细胞株中突变型p53基因及蛋白表达的情况。结果证实其在30～90μmol/L浓度时对突变型p53基因无影响,而对突变型p53蛋白的表达有抑制作用。结论本研究为槲皮素应用于急性早幼粒细胞白血病的研究提供了有效手段。