高血压对血管内皮功能的影响

目的:探讨高血压的血管内皮功能变化。方法:应用高分辨率超声仪检测我院门诊及住院的高血压患者的肱动脉对反应性充血(血流介导的内皮依赖性血管扩张)的舒张反应.并与健康人进行对比。结果:基础血管内径:高血压组3.89±0.47 mm.健康组3.84±0.455 mm,P>0.05;反应性充血的肱动脉内径的变化百分率:高血压组为7.4±2.83%.健康组为12.40±3.79%.有非常显著差异.P<0.001;含服硝酸甘油后肱动脉内径的变化百分率:高血压组为14.20±2.90%.健康组为14.22±0.88%(P>0.05)。结论:高血压患者血管内皮功能受损。     

卡维地洛对抗乌头碱诱发的大鼠心律失常作用的研究

评价卡维地洛抗大鼠实验性心律失常的作用 ,探讨其抗心律失常作用的离子通道机理 ,为临床用药提供理论依据。采用乌头碱诱发大鼠心律失常模型 ;采用膜片钳技术 ,观察乌头碱、卡维地洛对急性分离的大鼠心室肌细胞钠通道电流 (INa)的影响。结果 :诱发大鼠出现室性早搏、室性心动过速、心室颤动及心脏停搏时 ,对照组及卡维地洛组所用乌头碱的量 (μg)分别为 :室性早搏 :2 1.75± 3.4 7vs 31.81± 2 .0 4 ;室性心动过速 :2 3.5 2± 4 .13vs 36 .0 6± 3.79;心室颤动 :37.6 3± 7.94vs 6 4 .13± 1.4 0 ;心脏停搏 :6 9.31± 1.85vs 84 .6 5± 5 .2 5。利用膜片钳技术观察到 :对照组INa密度为 :5 8.6 3± 11.6 5 pA/pF ;卡维地洛组加入乌头碱后以及再加入卡维地洛后的INa密度分别为73.35± 12 .80 (pA/pF) ;10 .19± 0 .0 2 (pA/pF) ,与自身加药前相比P <0 .0 5。乌头碱及卡维地洛使INaI V曲线分别向下方及向上方移位。结论 :卡维地洛具有抗乌头碱诱发的大鼠心律失常的作用 ,其抗心律失常作用机制之一可能与Ⅰ类抗心律失常药类似 ,即抑制INa。     

Glucose-responsive insulin-producing cells from stem cells

Recent success with immunosuppression following islet cell transplantation offers hope that a cell transplantation treatment for type 1 (juvenile) diabetes may be possible if sufficient quantities of safe and effective cells can be produced. For the treatment of type 1 diabetes, the two therapeutically essential functions are the ability to monitor blood glucose levels and the production of corresponding and sufficient levels of mature insulin to maintain glycemic control. Stem cells can replicate themselves and produce cells that take on more specialized functions. If a source of stem cells capable of yielding glucose-responsive insulin-producing (GRIP) cells can be identified, then transplantation-based treatment for type 1 diabetes may become widely available. Currently, stem cells from embryonic and adult sources are being investigated for their ability to proliferate and differentiate into cells with GRIP function. Human embryonic pluripotent stem cells, commonly referred to as embryonic stem (ES) cells and embryonic germ (EG) cells, have received significant attention owing to their broad capacity to differentiate and ability to proliferate well in culture. Their application to diabetes research is of particular promise, as it has been demonstrated that mouse ES cells are capable of producing cells able to normalize glucose levels of diabetic mice, and human ES cells can differentiate into cells capable of insulin production. Cells with GRIP function have also been derived from stem cells residing in adult organisms, here referred to as endogenous stem cell sources. Independent of source, stem cells capable of producing cells with GRIP function may provide a widely available cell transplantation treatment for type 1 diabetes.     

Insulin expressing cells from differentiated embryonic stem cells are not beta cells

Aim/hypothesis Embryonic stem (ES) cells have been proposed as a potential source of tissue for transplantation for the treatment of Type 1 diabetes. However, studies showing differentiation of beta cells from ES cells are controversial. The aim of this study was to characterise the insulin-expressing cells differentiated in vitro from ES cells and to assess their suitability for the treatment of diabetes.Methods ES cell-derived insulin-expressing cells were characterised by means of immunocytochemistry, RT-PCR and functional analyses. Activation of the Insulin I promoter during ES-cell differentiation was assessed in ES-cell lines transfected with a reporter gene. ES cell-derived cultures were transplanted into STZ-treated SCID-beige mice and blood glucose concentrations of diabetic mice were monitored for 3 weeks.Results Insulin-stained cells differentiated from ES cells were devoid of typical beta-cell granules, rarely showed immunoreactivity for C-peptide and were mostly apoptotic. The main producers of proinsulin/insulin in these cultures were neurons and neuronal precursors and a reporter gene under the control of the insulin I promoter was activated in cells with a neuronal phenotype. Insulin was released into the incubation medium but the secretion was not glucose-dependent. When the cultures were transplanted in diabetic mice they formed teratomas and did not reverse the hyperglycaemic state.Conclusions/Interpretation Our studies show that insulin-positive cells in vitro-differentiated from ES cells are not beta cells and suggest that alternative protocols, based on enrichment of ES cell-derived cultures with cells of the endodermal lineage, should be developed to generate true beta cells for the treatment of diabetes.Abbreviations ES Embryonic stem - LIF leukemia inhibitory factor - ITSF insulin-transferrin-selenite-fibronectin.Bleackley and Korbutt laboratories contributed equally to this paper     

DC与CIK或LAK联合对结肠癌细胞株SW480杀伤作用的研究

[目的]研究树突状细胞(DC)联合细胞因子诱导或未诱导的杀伤细胞(CIK)或淋巴因子激活的杀伤细胞(LAK)对结肠癌细胞株SW480的杀伤活性.提供DC联合CIK或LAK治疗结肠癌的实验依据.[方法]取人外周血分离出单个核细胞(PBMNC),诱导生成DC、CIK、LAK细胞;流式细胞仪检测DC经SW480肿瘤抗原冲击后的表型变化;以CIK+DC细胞、CIK细胞、LAK+DC细胞及LAK细胞作为效应细胞,SW480为靶细胞,以15∶1、30∶1、45∶1为效靶比,LDH释放法测定细胞杀伤试验活性;ELISA检测杀伤试验中干扰素γ(IFN-γ)、白细胞介素2(IL-2)、IL-12、IL-17的分泌水平.[结果]流式细胞仪检测DC经SW480肿瘤抗原冲击后,其表面分子HLA-DR、CD40、CD80和CD86表达分别平均为90.23％、73.68％、85.96％、57.55％,与未经肿瘤抗原冲击DC比较,DC成熟的表面标志分子表达明显增加(P＜0.01).相同效靶比下,CIK+DC细胞组对SW480的杀伤作用最强,明显高于其他细胞组(P＜0.01);CIK+ DC细胞组在效靶比为45∶1时,杀伤活性最强(P＜0.01);单独CIK细胞组的杀伤活性明显高于LAK+DC细胞组(P＜0.01);LAK+ DC细胞组的杀伤活性明显高于单独LAK细胞组(P＜0.01).效靶比为45∶1时,各杀伤试验细胞组上清液中IFN-γ、IL-2、IL-12、IL-17的分泌量,CIK+DC细胞组的IFN-γ、IL-12的分泌量显著高于其他细胞组(P＜0.05);LAK+DC、单独LAK细胞组IL-2的分泌量明显高于CIK+DC、单独CIK细胞组(P＜0.05);单独CIK细胞组IFN-γ的分泌量明显高于LAK+DC、单独LAK细胞组(P＜0.05).[结论]CIK+DC细胞组对SW480的杀伤活性明显强于单独CIK、LAK+ DC组、单独LAK细胞组.其机制可能是,SW480抗原致敏的DC分泌IFN-γ、IL-12等刺激、诱导CIK细胞的活化和增殖,明显增强CIK细胞杀伤SW480的活性.     

Dendritic cells: specialized antigen presenting cells

Renewing interest in cancer immunotherapy reflects the excellent results that have been obtained in animal models and the promising results in early clinical trails with dendritic cell (DC) based approaches. The central role that DCs play in the initiation of an immune response raises the possibility of using them to trigger specific anti-tumor immunity. In addition, deeper knowledge of DC biology will allow better understanding of the mechanism(s) underlying allergic and autoimmune diseases as well as tolerance phenomena. These crucial issues were critically reviewed during a workshop organized by the Italian Society for Experimental Hematology in Florence, Italy, on March 18th, 1999. The chairmen have prepared this report for the readers of Haematologica.     

树突状细胞联合细胞因子诱导的杀伤细胞对胃癌细胞杀伤作用

目的探讨树突状细胞联合细胞因子诱导的杀伤细胞对胃癌细胞的杀伤作用。方法采用胃癌患者自身血液中单个核细胞(peripheral blood mononuclear cells,PBMC),经体外诱导分别扩增出DC和CIK细胞,二者共同培养后,利用MTT法检测DC细胞联合CIK细胞体外杀伤人胃癌细胞株(MNK-45、MNK-28、SG-7901)的活性。结果DC与CIK细胞共培养后得到的细胞群高表达CD3 CD56 ,平均值达到(56.74±7.63)%。通过彼此相互作用诱导出的细胞群体对胃癌细胞株MNK-45、MNK-28、SG-7901有杀伤作用,且杀伤活性随着效靶比的增加而增强。结论DC与CIK细胞共培养后有很强的增殖能力,对胃癌细胞具有杀伤活性,且其杀伤作用与胃癌细胞类型无相关性。