Mathematical modelling of the spatio-temporal response of cytotoxic T-lymphocytes to a solid tumour.

In this paper a mathematical model describing the growth of a solid tumour in the presence of an immune system response is presented. In particular, attention is focused upon the attack of tumour cells by so-called tumour-infiltrating cytotoxic lymphocytes (TICLs), in a small, multicellular tumour, without necrosis and at some stage prior to (tumour-induced) angiogenesis. At this stage the immune cells and the tumour cells are considered to be in a state of dynamic equilibrium--cancer dormancy--a phenomenon which has been observed in primary tumours, micrometastases and residual disease after ablation of the primary tumour. Nonetheless, the precise biochemical and cellular mechanisms by which TICLs control cancer dormancy are still poorly understood from a biological and immunological point of view. Therefore we focus on the analysis of the spatio-temporal dynamics of tumour cells, immune cells and chemokines in an immunogenic tumour. The lymphocytes are assumed to migrate into the growing solid tumour and interact with the tumour cells in such a way that lymphocyte-tumour cell complexes are formed. These complexes result in either the death of the tumour cells (the normal situation) or the inactivation (sometimes even the death) of the lymphocytes. The migration of the TICLs is determined by a combination of random motility and chemotaxis in response to the presence of chemokines. The resulting system of four nonlinear partial differential equations (TICLs, tumour cells, complexes and chemokines) is analysed and numerical simulations are presented. We consider two different tumour geometries--multi-layered cell growth and multi-cellular spheroid growth. The numerical simulations demonstrate the existence of cell distributions that are quasi-stationary in time and heterogeneous in space. A linear stability analysis of the underlying (spatially homogeneous) ordinary differential equation (ODE) kinetics coupled with a numerical investigation of the ODE system reveals the existence of a stable limit cycle. This is verified further when a subsequent bifurcation analysis is undertaken using a numerical continuation package. These results then explain the complex heterogeneous spatio-temporal dynamics observed in the partial differential equation (PDE) system. Our approach may lead to a deeper understanding of the phenomenon of cancer dormancy and may be helpful in the future development of more effective anti-cancer vaccines.     

大气中不同粒径颗粒物诱导人羊膜FL细胞UDS的研究

本研究以诱导人羊膜细胞ＵＤＳ为指标，对太原市大气不同粒径的颗粒物提取液进行了致突变性检验，结果表明，不同粒径颗粒物的提取液均可产生一定的遗传毒性，尤以３．３μｍ以下的颗粒物的遗传毒性较强。     

哮喘患者CD8+T细胞对单核/巨噬细胞抗原递呈功能的影响

目的：探讨支气管哮喘患者CD8⁺T细胞对单核/巨噬细胞抗原递呈功能的影响。方法：哮喘患者20例，健康对照22例，分别取静脉血5 mL，并分离MΦ、CD8⁺T细胞和B细胞。每份血样分成4组：MΦ递呈抗原组、CD8⁺T细胞参与MΦ递呈抗原组、CD8⁺T细胞体外活化后对MΦ递呈抗原影响组及自然状态下CD8⁺T细胞对MΦ细胞递呈抗原影响组。各组用CTLL₂P抗原刺激18 h后，洗去刺激原，与自体B细胞共同孵育10 d，吸取上清液，测定特异性IgM、IgE、IgG含量。 结果:①哮喘患者MΦ单独递呈抗原，自体B细胞特异性IgM(A490值)（0.034±0.022）明显低于健康人(0.116±0.080)（P<0.05）；CD8⁺T细胞与MΦ共同培养递呈抗原时，产生的特异性IgM(A490值)(0.031±0.021)低于健康人(0.079±0.064)（P<0.05）；②哮喘患者CD8⁺T细胞与MΦ共同培养递呈抗原时，产生的特异性IgG(A490值)(0.102±0.041)明显高于健康人(0.081±0.067)（P<0.05），自然状态下及体外活化后CD8⁺T细胞与递呈抗原MΦ共同培养，产生的特异性IgG(A490值)(0.105±0.066, 0.079±0.059)与健康人(0.066±0.038, 0.069±0.047)无明显差别(P>0.05)；③哮喘患者CD8⁺T细胞与MΦ共同培养递呈抗原产生的特异性IgE(A490值)(0.171±0.154)高于健康人(0.147±0.059)（P<0.05）。 结论:哮喘患者CD8⁺T细胞对MΦ递呈抗原产生免疫球蛋白有调节作用,而且参与哮喘发病。     

Fabricating fixed partial dentures using existing restorations

A technique has been described for utilizing an existing fixed splint in the fabrication of a fixed partial denture to replace splinted teeth that are extracted.     

吗啡及纳洛酮对淋巴细胞体外增殖的作用(英文)

目的:研究吗啡对不同淋巴细胞增殖的作用及纳洛酮的影响.方法:观察吗啡对未成熟的、静止的及活化的脾脏淋巴细胞体外增殖影响及纳洛酮的阻断作用.结果:吗啡(1×10~(-10)—1×10~(-6)mol L~(-1))能增加Con A诱导的T-细胞的增殖,1 μmol L~(-1)还能促进LPS诱导的B-细胞的增殖,同时这些增强作用都能被纳洛酮50μmol L~(-1)阻断,纳洛酮单独亦能促进活化T-细胞的增殖.而吗啡1×10~(-10)—1×10~(-5)mol L~(-1)对静止的脾脏淋巴细胞及Con A活化的胸腺淋巴细胞的增殖都无影响.但是吗啡1mmol L~(-1)能广泛抑制静止的、LPS活化的脾脏细胞及Con A活化的胸腺,脾脏淋巴细胞增殖,且都不能被纳洛酮阻断.结论:吗啡对活化T-和B-细胞的促进作用是由细胞表面的阿片受体介导的,此阿片受体随着淋巴细胞的成熟和活化而变化,而吗啡1 mmol L~(-1)对淋巴细胞增殖的抑制作用却不是由经典的阿片受体介导的.     

单用达那唑治疗慢性再生障碍性贫血19例临床观察

单用达那唑（ＤＮＺ）治疗１９例慢性再生障碍性贫血（ＣＡＡ）病人。结果表明，基本治愈１例，缓解５例，明显进步７例，有效者共１３例，总有效率为６８．４％，初治者５／７例有效，有效率为７１．４％；复治者８／１２例有效，有效率为６６．７％。治疗后与治疗前比较，血红蛋白、白细胞、血小板和网织红细胞均明显升高（Ｐ＜０．００１）；骨髓红系、粒系及巨核细胞明显增高（Ｐ＜０．０５）；Ｔ辅助细胞（ＣＤ４）明显增加、Ｔ抑制细胞（ＣＤ８）明显降低，ＣＤ４／ＣＤ８比值明显升高（Ｐ＜０．０５）。并结合文献对ＤＮＺ的作用原理进行讨论。     

Lymphocyte subclasses and function in patients with optic neuritis in childhood with special reference to multiple sclerosis

Ten patients with childhood optic neuritis (5 with a single attack of ON and 5 with later MS) were studied at various stages of the disease. Lymphocyte count and function were analysed in the peripheral blood of all patients, 3 repeatedly, and in one they were also analysed in the CSF. T-lymphocytes counts were normal in all but 2 MS cases who had high counts. In acute stages the T4/T8 ratio were high in 1/3 determinations, in recovery low in 2/2 determinations, and in stable stages normal in 6/8 determinations. Lymphocyte function, measured by PHA, ConA and PWM stimulation, was normal in all but one. One patient showed significantly higher T-cell percentages and a high number of stimulated lymphocytes in CSF but a lower count of suppressor cells than in the blood. We found no abnormalities specific to MS nor to childhood MS or to disease activity stage. Rather than peripheral blood, it would seem more worthwhile to study CSF to clarify the pathogenesis of ON and MS.     

B细胞杂交瘤技术制备抗同种特异T细胞膜抗原单克隆抗体

目的：为进一步分析ＴＣＶ免疫诱导同种免疫反应低下的机制。方法：采用Ｂ细胞杂交瘤技术获得分泌单克隆抗体的杂交瘤细胞。结果：两次的细胞融合中共得到１２株稳定分泌单抗的杂交瘤细胞，为分析抗体在ＴＣＶ中的作用提供条件。结论：ＴＣＶ免疫可引起抗ＴＣＶ细胞抗体的产生，以同系免疫的方法得到的活化Ｂ细胞用于Ｂ细胞杂交生产单抗是可行的。     

转染可溶性CD40基因的树突状细胞在体外对T淋巴细胞功能的抑制作用

目的探讨转染可溶性CD40(sCD40)基因的树突状细胞(DC)在体外对T淋巴细胞增殖和细胞毒性T淋巴细胞(CTL)的细胞毒活性的影响。方法采用脂质体转染法,将携带鼠CD40胞外区和绿色荧光蛋白的融合基因的质粒pEGFP-N1/sCD40转染小鼠DC细胞株(DC 2.4)。以Balb/c小鼠淋巴细胞为反应细胞,分别以转染组DC、空载体转染组(空载体组)DC和未行转染处理的DC(空白DC)作为刺激细胞,进行单向混合淋巴细胞培养,四唑氮化合物比色法检测细胞增殖情况。用乳酸脱氢酶释放试验和流式细胞术检测转染组DC及其培养上清液对CTL细胞毒活性及其凋亡的影响。结果转染组DC及其培养上清液对同种细胞刺激的淋巴细胞增殖反应有显著的抑制作用(P<0.05),并对特异性CTL的细胞毒活性具有明显的抑制作用(P<0.05);转染组DC可诱导CTL凋亡(P<0.05)。结论稳定表达sCD40-EGFP融合蛋白的DC,在体外对T淋巴细胞的增殖和CTL的细胞毒活性具有明显的抑制作用,并可诱导CTL凋亡。     

自发免疫耐受大鼠移植肝内调节性T细胞的生物学特性

目的研究大鼠肝移植后自发免疫耐受的形成与移植肝内CD4~ CD25~ 调节性T细胞(Tr细胞)的关系。方法按供、受者不同将实验分为3组。急性排斥组:DA大鼠为供者,LEW大鼠为受者;自发耐受组:LEW大鼠为供者,DA大鼠为受者;同基因组:供、受者均为DA大鼠。各组均建立大鼠原位肝移植模型。分别在肝移植术后4、7、14、30和90 d时采用密度梯度离心法分离移植肝内淋巴细胞,免疫磁珠分离(MACS)法分选出CD4~ CD25~ Tr细胞;用流式细胞术(FCM)检测细胞纯度,同时分析CD4~ CD25~ Tr细胞比例的变化;体外细胞增殖试验研究CD4~ CD25~ Tr细胞对CD4~ CD25~-T细胞的免疫抑制作用。结果肝移植早期,急性排斥组和自发耐受组移植肝内CD4~ CD25~ Tr细胞比例均明显增加,其中急性排斥组增加更为明显;移植后4 d左右,两组CD4~ CD25~ Tr细胞比例开始下降,急性排斥组的下降幅度较大;移植后30 d,自发耐受组受者的移植肝内CD4~ CD25~ Tr细胞比例达到第2次高峰,约在移植后90 d时下降至正常生理水平。移植后7 d左右,急性排斥组受者均因发生排斥反应而死亡,而自发耐受组受者均存活。此外,CD4~ CD25~ Tr细胞能有效抑制CD4~ CD25~-T细胞的增殖。结论CD4~ CD25~ Tr细胞是一种具有特异免疫调节功能的T细胞亚群,其主动的免疫抑制功能可能是诱导大鼠肝移植自发免疫耐受的机制之一。