目的：制备乳腺癌患者自体肿瘤特异性细胞毒T淋巴细胞（auto-tumor specificcytotoxicity T lymphocytes，CTLs），观察其对乳腺癌患者骨髓微转移的治疗作用。方法：以CK18、CK19为标志物、应用流式细胞术检测河北医科大学第四医院外一...目的：制备乳腺癌患者自体肿瘤特异性细胞毒T淋巴细胞（auto-tumor specificcytotoxicity T lymphocytes，CTLs），观察其对乳腺癌患者骨髓微转移的治疗作用。方法：以CK18、CK19为标志物、应用流式细胞术检测河北医科大学第四医院外一科2007年3-12月间治疗的82例原发性乳腺癌（Ⅰ～Ⅲ期）术前患者（参加本实验的患者全部知情同意）骨髓微转移状况，将23例术前骨髓微转移阳性的乳腺癌患者随机分为2组：肿瘤特异性CTLs治疗组17例，IL-2治疗对照组6例。术中取治疗组患者腋下淋巴结及外周血体外诱导培养肿瘤特异性CTLs，于术后10—14d回输，观察特异性CTLs对乳腺癌骨髓微转移的治疗效果。结果：本组82例乳腺癌患者中23例（28．05％）骨髓微转移阳性，骨髓微转移的阳性率随临床分期、组织学分级的增加而增高，随ER、PR蛋白表达增强而降低。自乳腺癌患者外周血中成功分离、诱导培养出树突状细胞（dendriticcells，DCs），并经自体肿瘤抗原致敏，与患者腋窝淋巴结来源的淋巴细胞共培养后诱导产生自体肿瘤特异性CTLs。治疗组17例患者经特异性CTLs治疗后，14例转为阴性，转阴率为82．35％；对照组6例中仅1例转为阴性，转阴率为16．67％；肿瘤特异性CTLs的治疗效果显著高于对照治疗（P=0．00028）。结论：成功制备的肿瘤特异性CTLs对乳腺癌骨髓微转移有较好的治疗效果。展开更多
This paper mainly investigates the effect of the lévy jumps on the stochastic HIV infection model with cytotoxic T lymphocytes (CTLs) immune response. First, we prove that there is a unique global positive soluti...This paper mainly investigates the effect of the lévy jumps on the stochastic HIV infection model with cytotoxic T lymphocytes (CTLs) immune response. First, we prove that there is a unique global positive solution in any population dynamics, then we find sufficient conditions for the extinction of the disease. For proofing the persistence in mean, a special Lyapunov function be established, we obtain that if the infected CD4<sup>+</sup> T-cells and virus particles will persistence in mean. Finally, numerical simulations are carried out to illustrate the theoretical results.展开更多
The aim of this study is to find the experimental evidence that the precursor frequency of alloreactive CTLs is proportional to the number of the T-cell epitope specificities. The number of T-cell epitope specificitie...The aim of this study is to find the experimental evidence that the precursor frequency of alloreactive CTLs is proportional to the number of the T-cell epitope specificities. The number of T-cell epitope specificities was manipulated by pulsing different humor of HLA-A2 restricted peptide（s） onto the T2 cells, which acted as stimulating cells to elicit allo-reaction by co-culturing with peripheral blood lymphocytes （PBLs） of HLA-A2 negative individual. Ten HLA-A2 restricted peptides （all were normal cell components ） were synthesized, and cell peptide extract was prepared by frozen and thawed. T2 cells loaded with different number of peptide（s） were co-cultured with PBLs of an HLA-A2 negative individual; the latter were stained with PKH67 in advance. Then the proliferation was monitored with flow cytometry, and the precursor frequency of the effector cells was ＇analyzed by the ModFit Software. After 6 d of culture, no proliferation was observed in the bulk culture of PBL alone, and obvious proliferation took place when PBLs of the HLA-A2 negative were co-cultured with T2 cells loaded with or without loading peptide（ s）. The precursor frequency of the alloreactive CTLs was 0.052 819 for co-culture with T2 cells loaded without peptide; however it was 0. 030 429 for T2 cells with EBV/LMP2A and 0. 030 528 for T2 cells loaded with a single autogeneic peptide, and increased up to 0. 144 942 for T2 cells loaded with 10 autogeneic peptides; the precursor frequency was 0. 203 649 when co-cultured with T2 cells loaded with miscellaneous peptides extracted from the cytoplasm of T2 cells. This study reveals that the precursor frequency of alloreactive CTLs is proportional to the number of T-cell epitope specificities, and independent of the density of the allogeneic HLA Class Ⅰ molecule. Our findings support the hypothesis that the alloreactive T cell populations comprise miscellaneous T cell clones; each is specific to corresponding pMHC. The novel constellation of peptides presented by allogeneic MHC molecules makes thousands of different epitopes, which account for the exceptional high precursor frequency of alloreactive T cells.展开更多
【目的】监测当前湖南省猪圆环病毒2型(Porcine circovirus type 2,PCV2)流行毒株及其衣壳蛋白(capsid protein,Cap)变异情况,并预测Cap蛋白细胞毒性T淋巴细胞(cytotoxic T lymphocyte,CTL)表位,为新型PCV2疫苗研制和病毒净化提供参考...【目的】监测当前湖南省猪圆环病毒2型(Porcine circovirus type 2,PCV2)流行毒株及其衣壳蛋白(capsid protein,Cap)变异情况,并预测Cap蛋白细胞毒性T淋巴细胞(cytotoxic T lymphocyte,CTL)表位,为新型PCV2疫苗研制和病毒净化提供参考依据。【方法】本研究对2019-2021年于湖南省6个地区收集的17份PCV2阳性组织样品进行PCV2全基因组序列扩增及测序分析,绘制系统进化树,利用生物信息学方法分析Cap蛋白氨基酸变异情况,并预测CTL表位。【结果】系统进化树显示,获得的17株PCV2全基因组序列中,1株PCV2a、7株PCV2b和9株PCV2d。Cap蛋白氨基酸序列比对分析发现,共有16个氨基酸残基突变位点位于病毒Cap蛋白表面,且有11个突变位点参与构象型表位的形成。此外,共预测出9个PCV2 Cap蛋白潜在的CTL表位,其中4个表位(16-24、28-36、136-144和179-187位氨基酸)在GenBank的1610株PCV2不同基因型毒株中高度保守。通过TCR-pMHC复合物3D结构对4个保守性表位进一步分析,结果显示,这4个肽段均能与MHCⅠ分子和TCR形成稳定的TCR-pMHC复合物。【结论】本研究结果表明,PCV2b和PCV2d为当前湖南省主要流行的基因型,且表现出高度变异;预测的CTL表位可作为候选抗原表位。展开更多
本文以散射中心的指数衰减和模型(Damped Exponentials,DE)为基础将全极化散射中心的参数提取问题转化为全极化信息融合的约束总体最小二乘(Constrained Total Least Squares,CTLS)算法问题,据此计算出全部散射中心的距离参数和类型参数...本文以散射中心的指数衰减和模型(Damped Exponentials,DE)为基础将全极化散射中心的参数提取问题转化为全极化信息融合的约束总体最小二乘(Constrained Total Least Squares,CTLS)算法问题,据此计算出全部散射中心的距离参数和类型参数,然后利用最小二乘法求解全极化测量方程,得到每个散射中心的复幅度信息,从而获得每个散射中心的散射矩阵,其中散射矩阵与类型参数是密切相关的.然后分析了其中参数估计的精度问题,针对极化通道噪声方差的不同提出了相应的改进算法.最后进行了仿真,并与单极化散射中心估计参数作了对比,结果证实了该方法的有效性,为雷达极化信息与散射中心的有效融合提供了新方法.展开更多
文摘目的：制备乳腺癌患者自体肿瘤特异性细胞毒T淋巴细胞（auto-tumor specificcytotoxicity T lymphocytes，CTLs），观察其对乳腺癌患者骨髓微转移的治疗作用。方法：以CK18、CK19为标志物、应用流式细胞术检测河北医科大学第四医院外一科2007年3-12月间治疗的82例原发性乳腺癌（Ⅰ～Ⅲ期）术前患者（参加本实验的患者全部知情同意）骨髓微转移状况，将23例术前骨髓微转移阳性的乳腺癌患者随机分为2组：肿瘤特异性CTLs治疗组17例，IL-2治疗对照组6例。术中取治疗组患者腋下淋巴结及外周血体外诱导培养肿瘤特异性CTLs，于术后10—14d回输，观察特异性CTLs对乳腺癌骨髓微转移的治疗效果。结果：本组82例乳腺癌患者中23例（28．05％）骨髓微转移阳性，骨髓微转移的阳性率随临床分期、组织学分级的增加而增高，随ER、PR蛋白表达增强而降低。自乳腺癌患者外周血中成功分离、诱导培养出树突状细胞（dendriticcells，DCs），并经自体肿瘤抗原致敏，与患者腋窝淋巴结来源的淋巴细胞共培养后诱导产生自体肿瘤特异性CTLs。治疗组17例患者经特异性CTLs治疗后，14例转为阴性，转阴率为82．35％；对照组6例中仅1例转为阴性，转阴率为16．67％；肿瘤特异性CTLs的治疗效果显著高于对照治疗（P=0．00028）。结论：成功制备的肿瘤特异性CTLs对乳腺癌骨髓微转移有较好的治疗效果。
文摘This paper mainly investigates the effect of the lévy jumps on the stochastic HIV infection model with cytotoxic T lymphocytes (CTLs) immune response. First, we prove that there is a unique global positive solution in any population dynamics, then we find sufficient conditions for the extinction of the disease. For proofing the persistence in mean, a special Lyapunov function be established, we obtain that if the infected CD4<sup>+</sup> T-cells and virus particles will persistence in mean. Finally, numerical simulations are carried out to illustrate the theoretical results.
基金The work was supported by the grants from the National Natural Science Foundation of China(No.30271201)the Major State Basic Research Development Program of China(No.2001C510008).
文摘The aim of this study is to find the experimental evidence that the precursor frequency of alloreactive CTLs is proportional to the number of the T-cell epitope specificities. The number of T-cell epitope specificities was manipulated by pulsing different humor of HLA-A2 restricted peptide（s） onto the T2 cells, which acted as stimulating cells to elicit allo-reaction by co-culturing with peripheral blood lymphocytes （PBLs） of HLA-A2 negative individual. Ten HLA-A2 restricted peptides （all were normal cell components ） were synthesized, and cell peptide extract was prepared by frozen and thawed. T2 cells loaded with different number of peptide（s） were co-cultured with PBLs of an HLA-A2 negative individual; the latter were stained with PKH67 in advance. Then the proliferation was monitored with flow cytometry, and the precursor frequency of the effector cells was ＇analyzed by the ModFit Software. After 6 d of culture, no proliferation was observed in the bulk culture of PBL alone, and obvious proliferation took place when PBLs of the HLA-A2 negative were co-cultured with T2 cells loaded with or without loading peptide（ s）. The precursor frequency of the alloreactive CTLs was 0.052 819 for co-culture with T2 cells loaded without peptide; however it was 0. 030 429 for T2 cells with EBV/LMP2A and 0. 030 528 for T2 cells loaded with a single autogeneic peptide, and increased up to 0. 144 942 for T2 cells loaded with 10 autogeneic peptides; the precursor frequency was 0. 203 649 when co-cultured with T2 cells loaded with miscellaneous peptides extracted from the cytoplasm of T2 cells. This study reveals that the precursor frequency of alloreactive CTLs is proportional to the number of T-cell epitope specificities, and independent of the density of the allogeneic HLA Class Ⅰ molecule. Our findings support the hypothesis that the alloreactive T cell populations comprise miscellaneous T cell clones; each is specific to corresponding pMHC. The novel constellation of peptides presented by allogeneic MHC molecules makes thousands of different epitopes, which account for the exceptional high precursor frequency of alloreactive T cells.
文摘【目的】监测当前湖南省猪圆环病毒2型(Porcine circovirus type 2,PCV2)流行毒株及其衣壳蛋白(capsid protein,Cap)变异情况,并预测Cap蛋白细胞毒性T淋巴细胞(cytotoxic T lymphocyte,CTL)表位,为新型PCV2疫苗研制和病毒净化提供参考依据。【方法】本研究对2019-2021年于湖南省6个地区收集的17份PCV2阳性组织样品进行PCV2全基因组序列扩增及测序分析,绘制系统进化树,利用生物信息学方法分析Cap蛋白氨基酸变异情况,并预测CTL表位。【结果】系统进化树显示,获得的17株PCV2全基因组序列中,1株PCV2a、7株PCV2b和9株PCV2d。Cap蛋白氨基酸序列比对分析发现,共有16个氨基酸残基突变位点位于病毒Cap蛋白表面,且有11个突变位点参与构象型表位的形成。此外,共预测出9个PCV2 Cap蛋白潜在的CTL表位,其中4个表位(16-24、28-36、136-144和179-187位氨基酸)在GenBank的1610株PCV2不同基因型毒株中高度保守。通过TCR-pMHC复合物3D结构对4个保守性表位进一步分析,结果显示,这4个肽段均能与MHCⅠ分子和TCR形成稳定的TCR-pMHC复合物。【结论】本研究结果表明,PCV2b和PCV2d为当前湖南省主要流行的基因型,且表现出高度变异;预测的CTL表位可作为候选抗原表位。
文摘本文以散射中心的指数衰减和模型(Damped Exponentials,DE)为基础将全极化散射中心的参数提取问题转化为全极化信息融合的约束总体最小二乘(Constrained Total Least Squares,CTLS)算法问题,据此计算出全部散射中心的距离参数和类型参数,然后利用最小二乘法求解全极化测量方程,得到每个散射中心的复幅度信息,从而获得每个散射中心的散射矩阵,其中散射矩阵与类型参数是密切相关的.然后分析了其中参数估计的精度问题,针对极化通道噪声方差的不同提出了相应的改进算法.最后进行了仿真,并与单极化散射中心估计参数作了对比,结果证实了该方法的有效性,为雷达极化信息与散射中心的有效融合提供了新方法.
