三氧化二砷诱导血管内皮细胞凋亡和抑制血管生成的研究

目的：研究三氧化二砷(As2O3)抑制血管内皮细胞(HUVECs)生长、诱导凋亡和抑制血管生成的作用。方法：As2O3与HUVECs共同孵育一定时间后，观察细胞形态学变化，并用MTT方法测定细胞生长曲线图、TUNEL方法检测细胞凋亡；观测As2O3对鸡胚血管生成的影响。结果：在0．75μmol／L～6μmol／L浓度范围内随药物浓度增加或作用时间延长，细胞生长抑制和细胞凋亡效果越显著；As2O3作用鸡胚绒毛尿囊膜后血管生成减少。结论：As2O3抑制HUVECs生长、诱导细胞凋亡，对血管生成有抑制作用。     

三氧化二砷-碘油化疗栓塞对兔肝移植瘤转移及与血管形成关系的研究

目的观察三氧化二砷（ As2O3）-碘油经肝动脉化疗栓塞对兔VX2肝移植瘤生长及转移的影响及与血管形成的关系。方法 48只家兔肝内肿瘤种植后2周，完全随机法分为4组，经肝动脉插管分别给予不同处理，实验设生理盐水灌注组、单纯碘油栓塞组、阿霉素．碘油栓塞组及 As2O3-碘油栓塞组。治疗后1周，免疫组织化学测定肿瘤区的微血管密度（MVD），治疗后3周，测量计算肝移植瘤的体积、坏死面积，观察肝内、双肺及其他器官肿瘤转移的发生率。结果 治疗后1周，各组MVD分别为（21．8±5．3）、（23．4±3．9）、（22．4±4．50）、（14．3±3．4）条／400倍视野（F=11．246，P=0．000）， As2O3-碘油栓塞治疗组与其他组相比差异有统计学意义；肿瘤植入后5周，各处理组肿瘤体积分别为（35．5±7．1）、（21．2±8．3）、（20．7±9．1）、（11．8±3．7）cm^3（F=21．203，P=0．000）。单纯碘油栓塞组、阿霉素一碘油栓塞组及 As2O3-碘油栓塞组与生理盐水灌注组相比差异有统计学意义（q值分别为6．723、6．940、11．119，P〈0．05）， As2O3-碘油栓塞组与单纯碘油栓塞及阿霉素-碘油栓塞组相比差异有统计学意义（g值分别为4．398、4．178，P值均〈0．05）；各组肿瘤坏死面积间差异无统计学意义（F=1．284，P=0．292）； As2O3-碘油栓塞治疗组双肺转移结节数目少于其他组（H=14．983，P=0．002），结节直径小于其他组（F=4．580，P=0．007），差异有统计学意义。腹腔转移淋巴结记分显示 As2O3-碘油栓塞治疗组腹腔淋巴结转移少于其他组（H=9．148，P=0．027）。双肺转移结节的数目、直径及腹腔转移淋巴结与肿瘤的微血管密度呈正相关（P〈0．05）。结论 As2O3-碘油联合经肝动脉栓塞治疗，抑制兔肝移植瘤的生长，抑制肿瘤的肺及腹腔淋巴结转移，其抑制转移的机制可能与抑制肿瘤血管形成有关。     

As2O3治疗急性早幼粒细胞白血病的作用机制

目的：研究三氧化二砷（As2O3）治疗M3型急性早幼粒细胞白血病（APL）的作用机制。方法：将培养的NB4细胞加入不同浓度（0．5μM,1μM,1．5μM,2μM,3μM）的As203作用48h后,采用MTT比色法观察不同浓度As2O3对NB4细胞活力的影响,用流式细胞术及Caspase-3活性检测试剂盒检测As2O3引起NB4细胞凋亡情况,用westernBlot检测As203对Caspase-3蛋白的作用。结果：MTT比色法结果显示,As2O3明显抑制NB4细胞增殖,且呈浓度依赖性,2μMAs2O3孵育48hNB4细胞活力下降约50％;流式细胞术结果显示,2μMAs2O3作用48h后,NB4细胞凋亡率显著增加,且以早期凋亡率增加为主（P〈0．01）;同时As2O3处理后的NB4细胞Caspase-3活性明显增加,为对照组的2．2倍（P〈0.01）;WesternBlot结果显示,As2O3显著增加Caspase-3总蛋白及其激活型cleaved—Caspase-3（p17）蛋白表达量。结论：As2O3可诱导NB4细胞凋亡,此作用与激活依赖Caspase-3的细胞凋亡通路相关,但是具体是通过何种凋亡通路,以及参与其中的信号分子需要进一步验证。     

三氧化二砷诱导急性早幼粒白血病细胞凋亡的机制

目的 探讨线粒体在三氧化二砷(As2O3)诱导急性早幼粒细胞白血病NB4细胞凋亡中的作用并观察线粒体基因组在该过程中的表达变化.方法 采用荧光显微镜、流式细胞仪、细胞生长抑制实验、线粒体膜电位检测、RT-PCR等方法,观察As2O3对NB4细胞的诱导凋亡、生长抑制作用及线粒体基因差异表达变化.结果 荧光显微镜观察显示,NB4细胞经As2O3处理48h后呈现出明显的凋亡形态学改变.As2O3在一定的浓度范围内对NB4细胞具有显著的生长抑制效应.流式细胞仪分析发现,NB4细胞经0.5、1、2、3μmol/L As2O3处理后,其细胞凋亡率分别为5.02%、6.40%、28.40%、33.34%.以0.5、1、2、4、8μmol/LAs2O3分别处理NB4细胞48h后,流式细胞仪检测NB4细胞线粒体膜电位分别下降12.8%、21.6%、66.9%、83.7%、83.8%.对As2O3诱导NB4细胞凋亡过程中的13个线粒体基因组基因进行RT-PCR分析发现,COX2基因表达下调,其余12个基因表达无明显改变.结论 As2O3在体外对NB4细胞具有显著的诱导凋亡及生长抑制效应,其诱导凋亡作用与线粒体膜电位下降密切相关;线粒体相关基因COX2的表达变化参与了As2O3诱导的NB4细胞凋亡过程.     

三氧化二砷诱导血管内皮细胞凋亡和抑制血管生成的实验研究

 目的研究三氧化三砷(As2O3)抑制人脐静脉血管内皮细胞(HUVECs)生长、诱导凋亡和抑制血管生成的作用.方法As2O3与HUVECs共同孵育一定时间后,观察细胞形态学变化,并用MTT方法测定细胞生长抑制率、TUNEL方法检测细胞凋亡;观测As2O3对鸡胚血管生成的影响.结果在0.75～6 μmol/L浓度范围内随药物浓度增加或作用时间延长,细胞生长抑制和细胞凋亡效果越显著;As2O3作用鸡胚绒毛尿囊膜后血管生成减少.结论As2O3抑制HUVECs生长、诱导细胞凋亡,对血管生成有抑制作用.     

三氧化二砷对鼻咽癌离体细胞的放射增敏作用

目的探讨三氧化二砷(As2O3)对鼻咽癌离体肿瘤细胞的放射增敏作用及其机理。方法利用多靶单击数学模型拟合放射剂量一细胞存活曲线，观察As2O3对鼻咽癌细胞株CNE-1的放射增敏作用。流式细胞法观察As2O3对细胞周期分布的影响，末端脱氧核苷酰转移酶法(TUNEL法)检测细胞凋亡，免疫组织化学观察As2O3对p53，bcl-2基因表达的影响。结果As2O3对鼻咽癌细胞株CME-1有明显的放射增敏效应，1．0，1．5μmol／L的As2O3作用48h的放射增敏比分别为1．33和1．57。药物作用后G2／M期细胞比例逐渐增加，S期细胞比例逐渐减少；细胞凋亡指数增加，p53基因表达，bax／bcl-2基因表达上调。结论As2O3对鼻咽癌细胞株CNE-1有明显的放射增敏效应，放射增敏的机理可能与As2O3使细胞周期阻滞在G2／M并使S期细胞减少，以及细胞p53、bax、bcl-2基因表达变化导致凋亡增加有关。     

纤维蛋白(原)对人血管平滑肌细胞增殖和移行的影响

目的　观察纤维蛋白原 (Fg)、纤维蛋白 (Fb)及其降解产物 (FDPs)对体外人血管平滑肌细胞(VSMC)增殖和移行的影响 ,探讨凝血 纤溶系统中的产物在再狭窄过程中的作用。方法　 (1)用凝血酶转化Fg制备Fb ,纤溶酶降解Fb制备FDPs并按不同倍数稀释用于实验 ;(2 )传代VSMC 2～ 3d铺满后 ,饥饿培养 2 4h同步化 ,继而进行干预实验 ,2 4孔板VSMC采用细胞计数法测定 ,96孔板VSMC采用四唑盐(MTT)比色实验、BIO -RAD酶联检测仪在 4 90nm波长处测定吸光度 ;(3)刮伤实验观察细胞移行情况 ,同时应用Transwell装置观察细胞的早期移行情况 ;(4 )实验数据以均数±标准差 ( x±s)表示 ,采用统计软件SPSS11.0进行均数t检验。结果　 (1)分别以 0、0 .2、0 .4、0 .8、1.6和 3.2mg/ml浓度的Fg作用于VSMC(每个计量组 6孔 ) ,培养 4 8h后细胞计数显示 ,各浓度Fg对VSMC无促增殖作用 ,而 0 .8mg/ml以上浓度Fg对VSMC的生长抑制率分别为 38%、5 5 %和 70 % (P <0 .0 5 ) ;同时用MTT法检测各浓度对细胞作用 ,发现较高浓度的细胞抑制率分别为 4 2 %、5 9%和 71% ,显示MTT检测法与细胞计数法有较好的相关性 ;(2 )按以上浓度铺板和凝血酶作用后接种VSMC ,培养 4 8h后细胞计数显示 ,0 .2、0 .8和 3.2mg/ml浓度细胞计数值分别为 (8.33± 0 .5     

活性炭纳米粒子对人胃癌BGC-823细胞作用的体外实验研究

目的：探讨活性炭纳米粒子（activated carbon nanoparticles,ACNP）对人胃癌BGC-823细胞的作用。方法：将ACNP以不同浓度和时间作用于BGC-823细胞,通过MTT试验观察ACNP对细胞增殖的抑制作用;测定培养上清液乳酸脱氢酶（LDH）活性,判断细胞损伤状况;用甲基绿-派洛宁染色法及透射电镜观察细胞凋亡形态;用流式细胞术检测细胞凋亡率和细胞周期。结果：ACNP能明显抑制BGC-823细胞的增殖,呈剂量和时间依赖性,作用24,48,72h后的半数抑制浓度（IC50）分别是1．57,1．18,0．87g／L。低浓度ACNP（0．1,0．2g／L）作用24h后,LDH漏出量与对照组相比没有显著差异。0．1g／L的ACNP作用24h后,细胞出现凋亡特征的形态学改变。0．1,0．2g／L的ACNP作用24h后,细胞凋亡率分别为（5．01±1．16）％、（8．21±1．63）％,与对照组（2．48±0．58）％比较均有显著性差异;ACNP作用组的S期细胞所占比例明显增高。结论：ACNP抑制BGC-823细胞的增殖,可使细胞阻滞于S期。诱导细胞凋亡。     

幼龄兔缺氧缺血性脑损伤的细胞凋亡显像研究

目的探讨99^Tc^m-联肼尼克酰胺．膜联蛋白Ⅴ（HYNIC-Annexin Ⅴ）在幼龄兔缺氧缺血性脑损伤（HIBD）细胞凋亡显像中的价值。方法制作幼龄兔假手术组、HIBD4h组、HIBD40h组模型，对各组动物行注药后60min平面脑显像和脑组织石蜡切片观察，对HIBD 40h组还进行注药后5，30，120min显像；用ROI技术计算各组动物脑患侧与健侧放射性计数比值（T／NT）；假手术组和HIBD4h组还进行MRI、弥散加权成像（DWI）。结果假手术组、HIBD4h组和HIBD40h组注药后60minT／NT分别为0．94±0．14，1．32±0．11，1．81±0．07（F=82．385，P〈0．01）；HIBD40h组不同时间（5，30，60，120min）显像获得的T／NT分别为1．72±0．04，1．77±0．06，1．81±0．07，1．71±0．03（F=3．994，P〉0．01）。切片观察假手术组脑组织未见凋亡细胞，HIBD4h组与HIBD40h组患侧脑见凋亡细胞，后者较明显；HIBD4h组MRI、DWI和表观弥散系数（ADC）图均未见异常。结论99^Tc^m-HYNIC-AnnexinⅤ显像可以早期发现神经细胞凋亡，在新生儿HIBD细胞凋亡的无创性诊断、抑制凋亡疗效评价和预后估计方面有重要的应用前景。     

神经生长因子和脑源性神经营养因子在氧化应激诱导细胞凋亡中的作用

目的 探讨神经生长因子（NGF）和脑源性神经营养因子（BDNF）在氧化应激诱导细胞凋亡的作用。方法 脂质体介导入NGF和BDNF基因转染鼠成纤维细胞NIH3T3,使目的基因在细胞中表达,过氧化氢（H2O2）处理转染细胞,吖啶橙荧光染色法和流式细胞检测细胞凋亡。结果 50μmol/LH2O2能诱导NIH3T3细胞凋亡,处理后24h凋亡率为16．7％,而NIH3T3细胞分别经NGF、BDNF和NGF／BDNF转染表达目的基因后,能对抗H2O2诱导的细胞凋亡,其24h凋亡率分别为8．21％、9．51％和6．26％。结论 氧化应激能诱导细胞凋亡,NGF和BDNF能抑制氧化应激诱导的细胞凋亡,两者具有协同作用。     

Influence of in vivo copper on MR images of the liver in rats

To investigate the effects of in vivo copper on magnetic resonance (MR) images, the authors studied Long-Evans cinnamon rats, which develop hepatitis and hepatocellular carcinoma as a result of abnormal copper metabolism. The livers of the rats were imaged before hepatitis developed; the absence of hepatic disease was confirmed histopathologically. The copper that accumulated in the liver of the rats was thought to exist in the form of divalent ions, which were suspected of reducing the T1 and T2 of neighboring protons. However, the signal intensities of the liver on T1- and T2*-weighted images did not change, suggesting that in vivo copper, even when accumulated abnormally, does not influence the signal intensity of MR images.     

经导管动脉化疗栓塞联合内皮抑素对兔VX2肝移植瘤新生血管生成的影响

目的 探讨兔VX2肝移植瘤经介入治疗联合应用内皮抑素(endostatin,ES)治疗后,残瘤组织微血管密度(micmvagcular density,MVD)和血管内皮生长因子(vascular endothelial growth factor,VEGF)的表达情况及其相关性.方法 建立兔VX2肝移植瘤模型,随机分为对照组(n=10)、经导管动脉化疗栓塞(TACE)组(碘油+阿霉素,n=10)和TACE联合抗血管生成组(碘油+阿霉素+ES,n=10),术后1周取出病理标本,用免疫组织化学染色分别检测残瘤组织VEGF和MVD的表达,3组间的比较采用方差分析.结果 对照组、TACE组和TACE联合抗血管生成组的VEGF平均吸光度值(A)分别为0.130 ±0.038、0.200±0.049和0.120±0.047(F=9.42,P＜0.01),TACE组表达水平最高,与其余两组比较差异有统计学意义(q值分别为4.93、5.63,P＜0.01),TACE联合抗血管生成组VEGF的表达水平低于对照组,但两组之间差异无统计学意义(q=0.70,P＞0.05);各组MVD值分别为(80 ±17)、(84±16)和(57±13)个/高倍镜(F=8.70,P＜0.01),TACE联合抗血管生成组MVD值最低,与其余两组比较均有统计学意义(q值分别为4.63、5.48,P＜0.01),对照组和TACE组之间差异无统计学意义(q=0.85,P＞0.05).结论 TACE联合应用内皮抑素治疗较单纯化疗栓塞可以明显降低肿瘤VEGF的表达,并可显著减少肿瘤微血管的形成,影响肿瘤的预后.     

Automated myocardial edge detection on MR images: Accuracy in consecutive subjects

The authors previously demonstrated the feasibility of graph-searching-based automated edge detection in cardiac magnetic resonance (MR) imaging. To further assess the clinical utility of this method, unselected images from 11 consecutive subjects undergoing clinically indicated (except for one healthy volunteer) short-axis spin-echo MR imaging were analyzed. A total of 142 images from the 11 subjects, encompassing the left ventricle from apex to outflow tract, were analyzed. The computer algorithm correctly identified complete endocardial and epicardial contours in 121 of 142 images (85%). Correlations between observerbraced and computer-derived epicardial areas for all images were good (r = .71 for epicardium, r = .83 for endocardium); they improved for a subset of higherquality images (r = .82 for epicardium, r = .92 for endocardium). The authors conclude that the current data further support the usefulness of computer digital image processing in geometric analysis of cardiac MR image data.     

Nodular sarcoidosis of the liver and spleen: Appearance on MR images

Small nodular lesions in the liver and spleen have been reported as an infrequent manifestation of sarcoidosis. Five patients with this appearance on either dynamic contrast material—enhanced computed tomographic (CT) or ultrasound scans underwent magnetic resonance (MR) imaging with and without dynamic gadolinium enhancement. The lesions were relatively uniform in size, ranging from 0.5 to 1.5 cm. On CT scans, they were hypoattenuating relative to surrounding parenchyma. On MR images, the lesions were hypointense relative to background parenchyma with all sequences. No substantial enhancement was observed in the lesions, although lesion conspicuity decreased over time on serial postcontrast images. Lesion conspicuity was greatest on either T2-weighted fat-suppressed (T2FS) images or early-phase dynamic contrast-enhanced images. Abdominal adenopathy was seen in three of the five patients and was hyperintense relative to liver on T2FS images in two and intermediate in intensity in one patient.     

Identification of aberrant right subclavian artery on MR images of the cervical spine.

Nine cases of aberrant right subclavian artery were identified after review of 674 magnetic resonance (MR) studies of the cervical spine. This common aortic arch anomaly is readily identified on sagittal MR images. All vessels were found in the typical retroesophageal location, abutting the esophagus from the vertebral C-7 to T-3 levels. Arterial flow created signal voids on T1-weighted images and confirmatory increased signal intensity due to flow-related enhancement on gradient-echo images. This anomaly should be recognized and distinguished from pathologic processes in the prevertebral space. The diagnosis may allay patient concern regarding their dysphagia and also have important ramifications in certain clinical settings.     

Pancreatic signal intensity on Tl- weighted fat saturation MR images: Clinical correlation

To determine whether signal intensity (SI) of the pancreas that was less than that of liver on Tl- weighted fat-suppressed (T1FS) magnetic resonance (MR) images could be used to help predict the presence of pancreatic disease, three blinded independent observers graded pancreatic SI relative to liver and/or renal cortex in 89 patients on T1PS images. Results were correlated with patient age and diagnosis. Among the 47 patients with a clinically normal pancreas, pancreatic SI was higher than that of liver in 42 and equal to that of liver in the rest, none of whom had evidence of fatty pancreas. These five patients had a mean age of 71 years, compared with 55 years for patients whose pancreas was more intense than liver (P=.02). Of the 42 patients with a clinically abnormal pancreas, only eight had pancreatic SI higher than that of liver. The positive predictive value for normal pancreas of an SI higher than that of liver was 84% and the positive predictive value for abnormal pancreas of an SI less than or equal to that of liver was 88%, with an overall accuracy of 86%. If normal pancreatic SI is defined as higher than that of liver for patients younger than 60 years and as equal to or higher than that of liver for patients older than 60 years, the positive predictive value of normal SI becomes 76%, the positive predictive value of decreased SI becomes 100%, and the overall accuracy becomes 83%. Pancreatic SI less than that of liver correlates highly with pancreatic disease, especially in younger patients. Mildly decreased pancreatic SI, equal to that of nondiseased liver, is common in older persons without clinically apparent pancreatic disease.     

用钡造影剂模型研究18F-FDG符合线路显像中基于CT的过度衰减校正

目的通过模型实验探讨钡造影剂（简称钡剂）在基于CT衰减校正（AC）技术的^18F-脱氧葡萄糖（FDG）符合线路显像中产生伪影的规律。方法将不同质量浓度（0．05、0．1、0．2、0．3、0．4、0．5、1．0、2．0、3．0kg／L）、相同体积（2．5m1）和相同质量浓度（0．5kg／L）、不同体积（0．5、1．0、1．5、2．0、2．5m1）的钡剂灌人乳胶指套并浸于含^18F—FDG水溶液（3．7kBq／m1）的圆柱体模型中。按常规行符合线路数据采集和重建，观察图像并作定量分析。结果模型中均匀液体部分的AC图像放射性分布均匀，非衰减校正（NAC）图像放射性分布呈中央低周边高的不均匀状态。钡剂部位在NAC图像中低于周围液体计数形成“冷区”，在AC图像中高于周围计数呈“热区”。质量浓度≥0．1kg／L的钡剂以及直径〉10mm（V银剂=0．5ml）的乳胶指套在AC图像上产生了“热区”伪影。结论基于CT的AC技术改善了^18F—FDG符合线路显像的图像质量，但钡剂的存在可能造成衰减的过度校正，形成“热区”伪影。对体内残留钡剂的患者，通过仔细阅读CT图像、AC及NAC图像，能够鉴别放 射性浓聚区是否为伪影。     

Pancreatic masses with inconclusive findings on spiral CT: Is there a role for MRI?

This prospective study evaluates the ability of MRI using T1-weighted fat-suppressed spin-echo (T1FS) and dynamic gadolinium chelate (Gd) enhanced spoiled-gradient echo (SGE) to detect the presence of pancreatic tumor in patients in whom spiral CT findings are inconclusive. Sixteen consecutive patients who underwent spiral CT and had findings that were considered inconclusive for pancreatic tumor underwent MR within 2 weeks of CT. Spiral CT and MR images were interpreted in a prospective fashion by separate individual investigators blinded to the results of the other imaging modality. CT was performed on a spiral CT scanner. MRI was performed on a 1.5-T MR machine. Imaging sequences included T1FS pre-Gd and post-Gd and SGE pre-Gd and immediately post-Gd. Data were analyzed using receiver operating characteristic (ROC) analysis. Confirmation was obtained by pancreatic biopsy (n = 4), surgical resection (n = 1), and clinical imaging (n = 4) or clinical follow-up (n = 7). MRI was superior to spiral CT (P = .027) in this selected patient group at detecting or excluding pancreatic tumor by ROC analysis, with areas under the curve of .982 and .764, respectively, which was significant (P = .041). The greatest advantage of MRI was in patients in whom spiral CT demonstrated enlargement of the pancreatic head without clear definition of tumor, which was significant (P = .033). In 10 patients with this CT appearance, MRI demonstrated a high confidence for presence of tumor in four and a high confidence of absence in six. Association of imaging findings with patient diagnosis was significant for MRI (P = .001) but not significant for CT (P = .148). The results of our study suggest that MRI may add significant diagnostic information in patients in whom spiral CT is inconclusive for the presence of pancreatic tumor. The greatest advantage of MRI was in the evaluation of patients in whom spiral CT findings revealed an indeterminate enlarged pancreatic head.     

Report on a lethal antazoline intoxication

Summary A lethal antazoline intoxication is reported and a method for isolation and determination of this compound and two hydrolysis products in autopsy material is described. Analytical findings in liver tissue, kidney tissue and blood are given. Definite identification of the compounds found was obtained by mass spectrometry.

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Zusammenfassung Ein Fall von tödlicher Vergiftung mit Antazolin und eine Methode zur Isolierung und Bestimmung dieser Verbindung und zweier Hydrolyseprodukte in Leichenmaterial wurden beschrieben. Es wurden die analytischen Ergebnisse aus dem Blut, Leberund Nierengewebe referiert. Die definitive Identifikation der Komponenten wurde mit Hilfe der Massenspektrometrie durchgeführt.

     

Effect of a patellar realignment brace on patellofemoral relationships: Evaluation with kinematic MR imaging

The effect of a newly developed patellar realignment brace was evaluated in 21 patellofemoral joints (19 patients) with patellar subluxation (13 joints with lateral subluxation and eight with medial subluxation) by using active-movement, loaded kinematic magnetic resonance (MR) imaging. Sixteen patellofemoral joints (76%) demonstrated a qualitative correction of or improvement in patellar subluxation (ie, centralization of the patella or a decrease in the displacement of the patella) after application of the brace. Four of the five “failures” occurred in patellofemoral joints that had patella alta and/or dysplastic bone anatomy. These results indicate that the patellar realignment brace was able to counteract patellar subluxation in the majority of patellofemoral joints studied, as shown by active-movement, loaded kinematic MR imaging. This brace appears to be useful for conservative treatment of patients with patellofemoral joint pain secondary to patellar malalignment and maltracking.