Microsatellite instability in primary and metastatic lung carcinomas

Fifty-seven primary lung carcinomas and 35 metastatic lung carcinomas were analyzed for microsatellite instability at 11 different chromosomal loci. Although no instability was detected in 37 small cell lung carcinomas (SCLC), it was frequently detected in non-small cell lung carcinomas (NSCLC) (16/55, 29%). In NSCLC, the incidence of replication errors (RERs) in metastatic tumors (12/22, 55%) was significantly higher than that in primary tumors (4/33, 12%) (P = 0.0021). Among 10 pairs of primary tumors and corresponding metastases, there were 4 cases which manifested the identical RER phenotypes in both primary and metastatic tumors. In two cases, RER phenotypes were detected in metastatic but not in primary tumors. Never was an RER phenotype found only in a primary tumor but not in the metastases. RERs were detected more frequently in stage III or IV tumors (3/8, 38%) than stage I or II tumors (1/25, 4%) (P = 0.0359). Tumor cells with allelic losses on chromosome arm 3p or 18q tended to have RER phenotypes (P = 0.0432 and P = 0.0187, respectively). The data suggest that microsatellite instability is common in NSCLC but not in SCLC, and that genomic instability appears late in tumor progression and plays an important role in the acquisition of more malignant phenotypes in NSCLC.     

荧光定量PCR检测活检组织EB病毒感染的临床意义

目的　建立检测EBV感染的新方法并观察EBV与鼻咽癌的关系。方法　鼻咽部活检组织和石蜡包埋标本6 6例 ,采用荧光定量聚合酶链反应 (FQ -PCR)和原位杂交 (ISH)两种方法检测EBV ,其检测结果与病理诊断对照。结果 :FQ-PCR检测EBV -DNA阴性 5 2例 ,其中 5 1例为炎性病变 ,另 1例为腺癌 ;EBV -DNA阳性 14例 ,其中 13例为鳞状细胞癌 ,另 1例虽为炎症。但部分上皮细胞呈不典型增生。ISH检测EBV阳性 4 9例 ,其中 4 7例为炎性病变 2例为癌。EBV阳性 17例 ,其中 12例为癌 ,5例为炎性病变。FQ -PCR和ISH检测EBV结果 ,经卡方检测差异无显著性 (P >0 .0 5 )。结论　EBV感染与鼻咽癌有高度相关性。FQ -PCR检测EBV具有方法简单、快速、定量准确等优点。     

卵巢切除对四氯化碳诱导大鼠肝纤维化形成的影响

为探讨卵巢切除对CCl4 诱导大鼠肝纤维化形成的影响 ,采用CCl4 诱导雌性大鼠肝纤维化动物模型 ,观察卵巢切除及雌激素替代治疗 (苯甲酸雌二醇 1mg kg)对肝脏胶原沉积和I、Ⅲ型胶原蛋白表达的影响 ,并分别检测血清学标志及肝脏组织学等变化。结果显示CCl4 模型组大鼠肝脏发生典型的肝纤维化改变 ,卵巢切除组的肝脏胶原沉积更为明显 ,肝脏表达I、Ⅲ型胶原及血清肝纤维化指标也明显高于CCl4 摸型组 (P <0 0 5 ) ,而雌激素干预及替代治疗则可抑制肝纤维化的形成。表明卵巢切除加速CCl4 诱导大鼠肝纤维化的形成 ,其发生可能与卵巢分泌的雌激素对肝纤维化的抑制作用有关。     

Dosimetric effect of respiration-gated beam on IMRT delivery

Intensity modulated radiation therapy (IMRT) with a dynamic multileaf collimator (DMLC) requires synchronization of DMLC leaf motion with dose delivery. A delay in DMLC communication is known to cause leaf lag and lead to dosimetric errors. The errors may be exacerbated by gated operation. The purpose of this study was to investigate the effect of leaf lag on the accuracy of doses delivered in gated IMRT. We first determined the effective leaf delay time by measuring the dose in a stationary phantom delivered by wedge-shaped fields. The wedge fields were generated by a DMLC at various dose rates. The so determined delay varied from 88.3 to 90.5 ms. The dosimetric effect of this delay on gated IMRT was studied by delivering wedge-shaped and clinical IMRT fields to moving and stationary phantoms at dose rates ranging from 100 to 600 MU/min, with and without gating. Respiratory motion was simulated by a linear sinusoidal motion of the phantom. An ionization chamber and films were employed for absolute dose and 2-D dose distribution measurements. Discrepancies between gated and nongated delivery to the stationary phantom were observed in both absolute dose and 2-D dose distribution measurements. These discrepancies increased monotonically with dose rate and frequency of beam interruptions, and could reach 3.7% of the total dose delivered to a 0.6 cm3 ion chamber. Isodose lines could be shifted by as much as 3 mm. The results are consistent with the explanation that beam hold-offs in gated delivery allowed the lagging leaves to catch up with the delivered monitor units each time that the beam was interrupted. Low dose rates, slow leaf speeds and low frequencies of beam interruptions reduce the effect of this delay-and-catch-up cycle. For gated IMRT it is therefore important to find a good balance between the conflicting requirements of rapid dose delivery and delivery accuracy.     

Local Suppression of Epileptiform Activity by Electrical Stimulation in Rat Hippocampus In Vitro

High frequency electrical stimulation of deep brain structures (DBS) has been effective at controlling abnormal neuronal activity in Parkinson's patients and is now being applied for the treatment of pharmacologically intractable epilepsy. The mechanisms underlying the therapeutic effects of DBS are unknown. In particular, the effect of the electrical stimulation on neuronal firing remains poorly understood. Previous reports have showed that uniform electric fields with both AC (continuous sinusoidal) or DC waveforms could suppress epileptiform activity in vitro . In the present study, we tested the effects of monopolar electrode stimulation and low-duty cycle AC stimulation protocols, which more closely approximate those used clinically, on three in vitro epilepsy models. Continuous sinusoidal stimulation, 50 % duty-cycle sinusoidal stimulation, and low (1.68 %) duty-cycle pulsed stimulation (120 μs, 140 Hz) could completely suppress spontaneous low-Ca²⁺ epileptiform activity with average thresholds of 71.11 ± 26.16 μA, 93.33 ± 12.58 μA and 300 ± 100 μA, respectively. Continuous sinusoidal stimulation could also completely suppress picrotoxin- and high-K⁺-induced epileptiform activity with either uniform or localized fields. The suppression generated by the monopolar electrode was localized to a region surrounding the stimulation electrode. Potassium concentration and transmembrane potential recordings showed that AC stimulation was associated with an increase in extracellular potassium concentration and neuronal depolarization block; AC stimulation efficacy was not orientation-selective. In contrast, DC stimulation blocked activity by membrane hyperpolarization and was orientation-selective, but had a lower threshold for suppression.     

经颅磁刺激对握力影响机理的初步研究

目的:探讨在不同刺激强度和不同手部握力输出的条件下,磁刺激前后对握力大小的改变。方法:10名健康受试者,其右手分别以3个不同的背景力量握住握力计,用圆形磁刺激线圈刺激左侧运动皮层,施加的刺激强度从阈值开始,每次递增10%,记录磁刺激施加前后握力输出的变化。结果:对于同一背景握力,刺激强度越大,握力大小的峰峰值及负峰值也越大;而在刺激强度不变的情况下,握力波形的峰峰值和负峰值也随握力的增大而增大;输出握力波形的正峰值和恢复时间与刺激强度、背景握力大小无明显关系。结论:实验结果提示握力峰峰值及负峰值的变化可能与参与肌肉收缩的运动单位数量及其兴奋性有关。     

应用噬菌体随机肽库技术筛选幽门螺杆菌中性粒细胞激活蛋白的抗原表位

目的 筛选和鉴定幽门螺杆菌(Helicobacter pylori,Hp)中性粒细胞激活蛋白(neutrophil-activating protein,NAP)的有效抗原表位,为Hp疫苗的研制提供基础.方法 以抗NAP的单克隆抗体作为固相筛选分子,经3轮吸附-洗脱-扩增免疫,筛选噬菌体随机7肽库,随机挑选噬菌体克隆,经噬菌体酶联免疫吸附试验(ELISA)、交叉反应试验及竞争抑制试验鉴定阳性克隆,测定阳性克隆所携带DNA序列并进行计算机辅助分析.以制备的阳性噬菌体克隆短肽液免疫小鼠,免疫血清与NAP经Western blot分析,以验证NAP的模拟表位.结果 经3轮免疫筛选后挑选到45个阳性克隆,经ELISA鉴定有12个阳性克隆,测序结果显示5种表位,其中P17噬菌体展示肽FAHLATQ与NAP氨基酸序列(137～143)高度同源,位于NAP高抗原区域(118～140),免疫血清可识别NAP.结论 用噬菌体随机7肽库成功筛选到了NAP的模拟表位,为基于NAP的诊断和疫苗的研制提供了基础.     

NucliSens HIV-1 QT和Amplicor HIV-1 monitor1.5方法测定HIV-1病毒载量的比较研究

目的进行NuchSens HIV-1 QT和Amplicor HIV-1 monitor 1．5检测相同临床样品HIV-1病毒载量值之间的比较研究。方法收集临床样本82份，使用两种方法测定病毒载量，对病毒载量值进行统计分析。结果未测到核酸的和两种方法病毒载量对数值之差小于0．5的占88．9％；用△log10 VL〈0．5的56份样本统计两种方法的相关性，相关系数为0．956。结论NucliSens HIV-1 QT和Amphcor HIV-1 monitor 1．5两种方法测定的HIV病毒载量值有很好的相关性。