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991.
992.
目的 利用三维伪连续动脉自旋标记(3D pcASL)成像技术比较阿尔茨海默病(AD)和帕金森病痴呆(PDD)病人脑灌注的异同,并分析脑灌注改变与认知功能损害的相关性。 方法 前瞻性收集AD病人24例、PDD病人26例、正常对照(NC)36例,均行颅脑常规MRI及3D pcASL灌注MRI检查。采用基于Matlab的SPM12软件对3D pcASL序列扫描获得的脑血流(CBF)图进行预处理,通过单因素协方差分析及独立样本t检验进行组间比较。利用DPABI软件提取AD组与NC组、PDD组与NC组灌注存在差异脑区的相对脑血流量(rCBF)值,采用Pearson相关方法对rCBF值与简易精神状态量表(MMSE)及蒙特利尔认知评估量表(MoCA)评分做相关性分析。 结果 与NC组相比,AD组双侧大脑皮质的广泛区域灌注减低,双侧丘脑、基底节、海马及辅助运动区(SMA)灌注增高;PDD组表现为与AD组基本一致的灌注减低和增高的脑区,但是脑区变化范围缩小。与AD组相比,PDD组双侧壳核、左侧中央前回、右侧SMA灌注减低,右侧顶下小叶灌注增高。AD组左侧额中回及左侧颞中回的灌注值与MMSE评分(分别r=0.64,P<0.001;r=0.50,P=0.01)及MoCA评分(分别r=0.44,P=0.03;r=0.48,P=0.02)均呈正相关,PDD组相关脑区与认知评分未见显著相关性。 结论 3D pcASL成像技术能够直观地反映AD与PDD病人类似的脑血流灌注模式,同时显示两者的灌注差异。AD病人多个脑区灌注值与认知相关评分呈正相关,提示脑血流改变与认知损伤具有相关性。 相似文献
993.
目的:了解疟原虫的多胺代谢与咯萘啶(PND)抗药性的关系。方法:感染伯氏疟原虫ANKA株(PS)和由该株培育的中抗PND品系(PRA)及高抗PND品系(PRB)的昆明株小鼠于腹腔接种(ip)后d7取血,经薄层层析后用荧光分光光度法测定正常RBC、PS、PRA和PRB感染RBC的丁二胺(PTC)、精脒(SPD)和精胺(SPM)量。另有感染PS和PRB的小鼠于ip后d6分别1次灌胃(ig)PND5mg/kg和10mg/kg,d7取血,按上述方法测定给药后感染RBC的多胺量,并与不给药组比较。结果:PS感染RBC的多胺量均明显高于未感染疟原虫的正常RBC,而感染PRA和PRB的RBC多胺量又显著高于PS感染RBC,且多胺量的增高与抗性程度有关。经PND治疗后PS感染RBC的SPD和SPM较未治疗组显著下降,而PRB感染RBC则未见明显变化。结论:伯氏疟原虫对PND的抗药性与其多胺代谢有关。 相似文献
994.
Relation of spontaneous transformation in cell culture to adaptive growth and clonal heterogeneity. 总被引:1,自引:8,他引:1 下载免费PDF全文
A L Rubin A Yao H Rubin 《Proceedings of the National Academy of Sciences of the United States of America》1990,87(1):482-486
Cell transformation in culture is marked by the appearance of morphologically altered cells that continue to multiply to form discrete foci in confluent sheets when the surrounding cells are inhibited. These foci occur spontaneously in early-passage NIH 3T3 cells grown to confluency in 10% calf serum (CS) but are not seen in cultures grown to confluency in 2% CS. However, repeated passage of the cells at low density in 2% CS gives rise to an adapted population that grows to increasingly higher saturation densities and produces large numbers of foci in 2% CS. The increased saturation density of the adapted population in 2% CS is retained upon repeated passage in 10% CS, but the number and size of the foci produced in 2% CS gradually decrease under this regime. Clonal analysis confirms that the focus-forming potential of most if not all of the cells in a population increases in response to a continuously applied growth constraint, although only a small fraction of the population may actually form foci in a given assay. The acquired capacity for focus formation varies widely in clones derived from the adapted population and changes in diverse ways upon further passage of the clones. We propose that the adaptive changes result from progressive selection of successive phenotypic variations in growth capacity that occur spontaneously. The process designated progressive state selection resolves the apparent dichotomy between spontaneous mutation with selection on the one hand and induction on the other, by introducing selection among fluctuating states or metabolic patterns rather than among genetically altered cells. 相似文献
995.
目的:通过序列分析确定抗胃癌抗体重链可变区(VH)的一级结构,并借助同源模建方法模拟其三级结构.方法:从抗人胃癌噬菌体抗体库中筛选出VH基因,并进行序列测定、翻译和分析.利用计算机辅助蛋白质空间模拟技术,采用同源模建、力学优化合理模建VH的三维空间结构.结果:序列比对分析表明获得的VH序列符合鼠抗体可变区特征,通过Kabat分析确定了FR、CDR;合理搭建了抗体重链可变区的空间构象,并通过分子力学优化获得了稳定的三维结构.结论:所测得的VH一级结构和构建的三维空间结构均有较高的可靠性,为进一步的生物学实验奠定了基础. 相似文献
996.
In this study we examined the effect of mitogens and epidermal cells in inducing a Sezary cell morphology in normal peripheral blood lymphocytes. Peripheral blood mononuclear cells from six healthy volunteers were stimulated with the mitogens phytohemaglutinin and concanavalin A, and also cocultivated with human epidermal cell cultures. Incubation times with mitogens and epidermal cells were four days and stimulation of the lymphocytes by mitogens was confirmed by standard 3H-thymidine uptake. Standard transmission electron microscopy showed that in the mitogen-driven system 20% to 60% (33 +/- 15%) and in the epidermal cell-driven system 5% to 15% (8 +/- 4%) of the lymphoid cells exhibited mild to moderate indentation of the nuclei with nuclear contour indices (NCI) of 4.6 to 6.5 but no Sezary cells were observed (cells with NCI greater than 6.5 and up to 19.2). In the mitogen- stimulated preparation 2% to 5% (3 +/- 1%) of the lymphoid cells showed nuclear multilobulation resembling the cells seen in adult T cell lymphoma/leukemia. Incubation of mononuclear cells for longer periods of up to 4 weeks with mitogens and exogenous IL-2 resulted in no further morphologic changes. Using an indirect immunogold technique at the electron microscopic level, the cells showing nuclear indentation or lobulation were shown to bear both T helper (CD4) and T suppressor (CD8) cell phenotypes in a similar ratio to the total numbers of T helper and T suppressor cells present. Mitogens and epidermal cells are thus not able to induce a morphologic change to Sezary cells in normal peripheral blood lymphocytes. 相似文献
997.
Isolation of drug-resistant variants of HIV-1 from patients on long-term zidovudine therapy. Canadian Zidovudine Multi-Centre Study Group 总被引:26,自引:0,他引:26
R Rooke M Tremblay H Soudeyns L DeStephano X J Yao M Fanning J S Montaner M O'Shaughnessy K Gelmon C Tsoukas 《AIDS (London, England)》1989,3(7):411-415
We determined whether drug-resistant variants of HIV-1 could be isolated from the peripheral blood mononuclear cells of 20 individuals with HIV infection (Centers for Disease Control groups II and III) on long-term zidovudine (AZT) therapy. Toward this end, zidovudine (10 microM) has been included in the tissue culture medium used to isolate HIV-1. Under these circumstances, virus with a zidovudine-resistant phenotype was successfully obtained in five out of 20 cases. This property of drug resistance appeared to be stable, and did not disappear upon extended replication of such virus in the absence of drug pressure. Drug-resistant virus could also be isolated from these subjects on subsequent occasions, but was not present in samples obtained prior to therapy. Replication of these zidovudine-resistant isolates in tissue culture was inhibited by each of four other nucleoside analogues. Thus, other drugs may be useful in controlling selective zidovudine-resistant variants of HIV-1. 相似文献
998.
银杏苦内酯B对重症急性胰腺炎大鼠血浆细胞因子的影响 总被引:8,自引:0,他引:8
目的:观察重症急性胰腺炎(SAP)大鼠血浆中TNF-α,血小板活化因子(PAF),IL-10, IL-12,sTNFR的水平变化及其银杏苦内酯B(BN52021)的影响.方法:实验选用Wistar♂大鼠45只,随机分成SAP模型组(SAP,n=15),BN52021治疗组(BN,n=15)和阴性对照组(NC,n=15).前两组以50 g/L牛磺胆酸钠逆行注入主胰管制成SAP模型,NC组开腹后仅翻动十二指肠并触摸胰腺数次关腹.制模15 min后,SAP组经股静脉以5 mL/mg注射生理盐水;BN组以BN52021(5 mg/kg)代替生理盐水静注.制模后分别于1,6,12 h采血,应用ELISA技术测定血浆TNF-α,PAF,IL-10,IL-12和sTNFR水平.结果:SAP组,NC组和BN组大鼠血浆TNF-α和PAF水平相比,具有显著性差异,SAP组(746.2±374.1,82.5±35.4 ng/L)显著高于NC组(385.1±86.3.1.1±1.9 ng/L),BN组(503.7±177.9,39.9±29.9 ng/L)显著低于SAP组(P<0.05).血浆sTNFR水平三组相比存在明显差异,SAP组(488.7±363.8 ng/L)显著高于NC组(50.0±21.0 ng/L),BN组(883.4±552.5 ng/L)显著高于SAP组(488.7±363.8 ng/L)(P<0.05).血浆IL-12三组相比存在明显差异,SAP组(97.1±55.9 ng/L)显著高于NC组(20.4±19.4 ng/L),BN组在1 h时相点(133.5±33.4 ng/L)显著高于SAP组(55.9±14.7 ng/L)(P<0.05).血浆IL-10三组相比不存在明显差异(P>0.05).结论:SAP大鼠促炎细胞因子和抗炎细胞因子均显著升高.BN52021能降低血浆促炎因子含量,提高IL-12和细胞因子拮抗剂sTNFR含量. 相似文献
999.
目的: 在传统基因芯片技术基础上, 应用生物传感器技术, 研制一种能将基因芯片信号原位放大后达肉眼判读灵敏度, 无需专用基因芯片检测仪器就可使用, 易于在基层医疗单位推广的薄膜生物传感器基因芯片诊断系统.方法:在薄膜生物传感器基片基础上, 经过表面化学处理, 使特定的基因捕获探针在传感器表面固定, 形成特定检测目的生物传感器基因芯片. 并以乙肝病毒YMDD区的特异序列设计为例, 通过特定的YMDD区的捕获探针, 以矩阵的形式点样于传感器芯片表面来实现本系统. 同时, 纳米金标记的检测探针取代了传统芯片中的荧光标记探针. 扩增后的目的PCR片段与捕获探针、生物素标记探针、链亲蛋白纳米金探针进行反应, 最后得到探针-生物素-链亲蛋白-纳米金复合物, 并在芯片表面经生物传感器芯片将信号原位放大, 获得肉眼观的芯片信号并进行分析, 完成芯片诊断. 以乙型肝炎病毒YMDD突变为例, 观察该芯片系统对临床诊断标本诊断的可靠性.结果: 基因芯片的检测信号经生物传感器原位放大后能肉眼判读或借助普通数码照像机或计算机扫描, 根据信号出现的特定位置即可确定突变的类型. 且该生物传感器基因芯片系统信噪比高, 在人工合成的寡核苷酸及临床血清的检测中, 均可实现生物芯片阴阳性信号完全的有或无的判读; 临床血清标本检测证实, 使用该传感器芯片系统对前期经过测序确定为YMDD突变的23份临床血清结果与测序结果完全一致. 结论:薄膜生物传感器基因芯片集纳米材料、生物传感器技术及原位放大技术为一体, 实现了信号的肉眼判读, 具有通用性高, 准确可靠, 无需大型设备, 易于在基层医疗单位推广使用. 相似文献
1000.
Cheng X Chen Y Xie JJ Yao R Yu X Liao MY Ding YJ Tang TT Liao YH Cheng Y 《Journal of molecular and cellular cardiology》2008,45(2):168-175
Atherosclerosis is a chronic inflammatory disease, which is positively and negatively regulated by T helper (Th) 1 and Th2 lymphocytes, respectively. Recent findings indicate that suppressive oligodeoxynucleotides (ODNs) expressing TTAGGG motifs selectively reduce Th1 cytokine production and have been proven effective at blocking the development of organ-specific autoimmune diseases. In the current research, we hypothesized that suppressive ODNs may alter the development of atherosclerosis. Eight-week-old homozygous ApoE−/− male mice were injected with 300 μg ODNs A151 (TTAGGG) or nonspecific ODNs 1612. Atherosclerotic lesion sizes were dramatically reduced by ODNs A151, but not by nonspecific ODNs. MCP-1 and VCAM-1, which are the key inflammatory factors in atherogenesis, were significantly attenuated by the suppressive ODNs A151. In the splenic lymphocytes, FACS analysis showed ODNs A151 reduced the percentage of IFN-γ-producing Th1 cells and slightly increased the percentage of IL-4-producing Th2 cells, indicating that suppressive ODNs skewed the Th1/Th2 balance toward Th2 inflammation in vivo. Furthermore, ODNs A151 down-regulated the phosphorylation of STAT1 and STAT4 and suppressed up-regulation of T-bet, a signal modulator for Th1, and didn't impact GATA-3 and STAT6, which are associated with a Th2 phenotype. Consistent with this in vivo observation, ELISA analysis demonstrated that ODNs A151 suppressed Th1 cytokines IFN-γ and TNF-α, and augmented Th2 cytokines IL-4 and IL-10 in vitro. This study provides the first experimental evidence that suppressive ODNs inhibit the development of atherosclerosis through inhibition of the STAT1/4 and T-bet pathways, which further modulate the Th1/Th2 balance in vivo. 相似文献