凝聚态Aβ 25～35可通过JNK/p38 MAPK途径诱导胎鼠皮层神经元Tau蛋白过度磷酸化

目的 探讨JNK/p38 MAPK在β淀粉样蛋白多肽片段25～35(Aβ25～35)诱导的阿尔茨海默病(AD)样胎鼠皮层神经元Tau蛋白过度磷酸化中的作用.方法 应用蛋白免疫印迹和免疫细胞化学染色的方法,观察Tau蛋白磷酸化和JNK/p38丝裂原活化的蛋白激酶(JNK/p38 MAPK)的表达情况.结果 凝聚态Aβ25～35(20μmol/L)作用于皮层神经元12h,Tau蛋白Ser396、Ser199/202、Thr205位点的磷酸化水平明显增高,同时JNK/p38 MAPK的总量及其活性形式-磷酸化JNK/p38 MAPK的蛋白表达水平也增加.结论 Aβ25～35可通过激活JNK/p38 MAPK使Tau蛋白的磷酸化水平增高.     

多囊卵巢综合征患者的生长分化因子9基因的突变分析

目的通过对多囊卵巢综合征（PCOS）妇女的生长分化因子9（GDF-9）基因的突变分析，探索GDF-9基因与PCOS的发病机制的关系。方法对120例PCOS患者釉80例正常对照的GDF-9基因进行聚合酶链反应（PCR）特异扩增，应用单链构象多态性（SSCP）分析和DNA测序方法检测基因突变。结果PCOS患者的GDF-9的所有外显予均未发现错义突变。结论GDF-9因子的DNA变异可能与PCOS的发病没有相关关系。研究PCOS患者的GDF-9的mRNA与蛋白表达水平与其发病的关系可能是今后的研究方向。     

基于曲面拟合法的肝脏超声成像仿真数学建模

目的研究虚拟人体器官三维影像轮廓的计算机仿真建模。方法以肝脏虚拟影像轮廓的三维数学建模为例，以人体肝脏的声阻二维分布为依据，应用曲面拟合的数值方法进行研究。结果计算机仿真证明了该建模方法的正确性和有效性。结论人体器官的虚拟超声成像是医学超声仿真系统的一项关键技术，在医务人员上岗培训中具有重要的意义。该文所提出的数学建模方法对于虚拟器官三维影像轮廓的仿真切实可行。     

人肿瘤细胞与正常细胞内微管的PAP免疫酶细胞化学观察

我们利用兔抗微管蛋白抗体和兔抗辣根过氧化物酶(HRP)抗血清制备的HRP—抗HRP(PAP)复合物,建立了微管的PAP免疫酶细胞化学方法。应用此法观察到人食管癌ECa 109、胃癌SGC 7901,乳腺癌MCF 7和成骨肉瘤OS 732细胞间期胞质微管减少或消失,只有大量弥散分布的微管蛋白棕色反应产物,在微管组织中心(MTOC)附近十分密集,而正常成纤维细胞和胎儿胃粘膜上皮细胞间期,都有发达的胞质微管结构(CMTC)。在分裂期,这些肿瘤细胞都显示纺锤体微管,与正常细胞比较无明显差异。本研究应用PAP方法进一步证明,以前用免疫荧光细胞化学方法观察到的人肿瘤细胞间期胞质微管缺陷的特征。除去低温(4℃)或秋水仙酰胺处理后,解聚的CMTC又可恢复,表明本方法与免疫荧光染色法,同样具有很高的特异性。本工作在细胞固定及免疫反应的某些步骤上有所改进。     

Detection and deletion of motion artifacts in electrogastrogram using feature analysis and neural networks

Electrogastrogram is a surface measurement of gastric myoelectrical activity, and electrogastrography has been an attractive method for physiological and pathophysiological studies of the stomach due to its nonivasive nature. Motion artifacts, however, ruin the electrogastrogram (EGG), and make the analysis very difficult and sometimes even impossible. They must be eliminated from EGG signals before analysis. Up to now, this can only be done by visual inspection, which is not only time-consuming but also subjective. In this study, a method using feature analysis and neural networks has been developed to realize automatic detection and elimination of the motion artifacts in EGG recordings by computer. Experiments were conducted to investigate the characteristics of different motion artifacts. Useful features were extracted, and different combinations of the features used as the input of the neural network were compared to obtain the optimal performance for the detection of motion artifacts using the artificial neural network.     

The effect of neonatal BCG vaccination on atopy and asthma at age 7 to 14 years: an historical cohort study in a community with a very low prevalence of tuberculosis infection and a high prevalence of atopic disease

BACKGROUND: There are conflicting reports on the effect of BCG vaccination on the subsequent development of atopy and asthma. There are no data on the effects of neonatal BCG vaccination on cytokine responses of lymphocytes that are exposed in vitro to allergens. OBJECTIVES: We sought to test the hypothesis that neonatal BCG vaccination or, alternatively, evidence of an immunologic memory of this vaccination is associated with a reduced prevalence of allergic sensitization, asthma, eczema, and hay fever during childhood. METHODS: An historical cohort study was conducted among 7- to 14-year-old children who were born in 2 districts in Sydney, Australia, and whose mothers were born in southeast Asia. One district had routinely administered BCG vaccination to infants born to overseas-born mothers and the other had not. Eligible subjects were identified from birth registers. Consenting subjects completed questionnaires, performed spirometric and airway hyperresponsiveness testing, and had allergen skin prick testing and tuberculin skin testing. Blood was collected to measure total serum IgE levels and for in vitro lymphocyte culture in the presence of an extract of house dust mite, the dominant allergen in this region, and purified protein derivative of Mycobacterium tuberculosis (tuberculin). IL-4, IL-5, IL-10, and IFN-gamma were measured in the culture supernatant. RESULTS: The cohort included 309 BCG-vaccinated subjects and 442 non-BCG-vaccinated subjects. BCG-vaccinated subjects did not have a lower rate of allergic sensitization than nonvaccinated subjects. However, among the subgroup of subjects with a family history of rhinitis or eczema, BCG vaccination was associated with a lower prevalence of current asthma (defined as recent wheezing plus airway hyperresponsiveness; relative risk, 0.46; 95% CI, 0.22-0.95). BCG vaccination was also associated with lower levels of allergen-stimulated IL-10 production in vitro. Among the BCG-vaccinated subjects, the 44 (14.3%) who had tuberculin skin test reaction sizes of 5 mm or greater and the 31 (18.3%) who demonstrated an in vitro IFN-gamma response to purified protein derivative of M tuberculosis did not have lower rates of allergic sensitization and, overall, did not have a lower prevalence of allergic disease than tuberculin skin test or IFN-gamma nonreactors. CONCLUSION: We conclude that neonatal BCG vaccination has an effect on T-cell allergen responsiveness 7 to 14 years after vaccination and that among a subgroup of subjects with an inherited predisposition to allergic disease, this is associated with clinically relevant beneficial effects. The findings of this study encourage the view that external influences on the immune system in the neonatal period have consequences that extend into later childhood and influence the expression of asthma. Genetic factors are likely to modify the effect of those external factors.     

高原红细胞增多症患者血浆组织因子水平

目的:通过测定高原低氧环境中，不同人群血浆组织因子水平，探讨其在高原红细胞增多症病理变化中的作用。 方法:采用固相双抗体夹心酶联免疫吸附法测定高原红细胞增多症患者、高原世居健康人群及不同居住时间的高原移居健康人群血浆组织因子浓度，与世居西宁健康人群对照，进行方差分析和相关分析比较研究。 结果:高原红细胞增多症组血浆组织因子浓度明显高于对照组（P<0.01），并与高原世居及移居各组比较均有显著差异（P<0.01）；高原红细胞增多症组血浆组织因子浓度与血红蛋白水平呈正相关（r=0.608, P<0.01），与血小板计数呈负相关（r=-0.862, P<0.01）。 结论:高原红细胞增多症患者及移居高原健康居民血浆组织因子水平明显升高。     

不同年龄高血压大鼠心肌中MKP-1的表达及对心肌肥厚的影响

目的：研究不同年龄的自发性高血压大鼠（SHR）和Wistar Kyoto大鼠（WKY）心室肌组织中丝裂原活化蛋白激酶（MAPK）及其磷酸酶（MKP-1）的表达以及与心肌肥厚的关系。方法： 用左心室重量与体重的比值作为心肌肥大指数并以此指标反映心肌肥厚；分别用Western blotting方法和RT-PCR法半定量测定心室肌组织中磷酸化细胞外信号调节激酶（p-ERK）的蛋白表达和MKP-1 mRNA的含量。结果： （1）SHR的血压自8周龄起明显高于WKY（P<0.01），心肌肥大指数明显大于WKY（P<0.05），ERK和MKP-1的表达均比WKY高（P<0.05）；（2）SHR的血压随年龄增长而升高（P<0.05），至14周趋于稳定，心肌肥大指数则在24周时出现激增（P<0.01）；（3）p-ERK随年龄增长呈递增趋势，而MKP-1呈递减趋势，且与心肌肥大指数和ERK的表达呈负相关（P<0.01）。结论： MKP-1在高血压大鼠随年龄和血压增加的心肌肥厚过程中起重要作用，其表达逐渐下降可能是导致ERK激活增加，进而引起心肌细胞肥大的重要原因。     

钙离子载体在诱导人外周血单核细胞分化为树突状细胞中的作用

目的研究钙离子载体(CI)能否诱导人外周血单核细胞(PBMC)分化为树突状细胞(DC)，并初步探讨其信号转导途径。方法分离健康献血者的PBMC，在体外用CI(A23187)或人重组粒细胞／巨噬细胞集落刺激因子(rhGM—CSF)和CI培养40h，或rhGM-CSF和白细胞介素4(IL-4)培养7d，部分PBMC预先用W-7或CsA或K35926处理30min后，再加入上述细胞因子或CI。相差显微镜下观察细胞形态，流式细胞仪检测细胞表面CD14、CD80、CD86、CD83等分子的表达，MTT比色法检测其对同种异体混合T淋巴细胞的刺激增殖作用。结果健康献血者的PBMC经CI培养40h，或rhGM—CSF与CI培养40h，或rhGM-CSF与IL-4培养7d，均可获得DC的典型形态和表面分子的表达，包括CD14表达下调、共刺激分子(CD80、CD86)表达上调，以及较强刺激同种异体混合T淋巴细胞增殖的作用；CI诱导的DC其CD14分子的下调及CD83分子的上调更明显，刺激混合T淋巴细胞的增殖能力更强；rhGM-CSF可协同CI诱导PBMC向DC的分化。经rhGM—CSF及CI处理的PBMC，其形态、表面标志物及对T细胞的刺激增殖能力，均受到W-7或CsA或KT5926不同程度的抑制；而rhGM-CSF及IL-4所诱导的PBMC其形态、表面分子的表达以及刺激T细胞增殖的作用却不受上述抑制剂的影响。结论CI可快速诱导PBMC向DC分化，其分化过程可能受控于Ca^2 /钙调蛋白及其下游的多个细胞信号转导途径的调节。