荷EL4肿瘤小鼠模型的建立及美法仑抑瘤作用免疫机制的探讨

目的:建立荷小鼠淋巴瘤EL4的野生型C57BL/6小鼠及其裸鼠模型,探讨美法仑(melphalan)抑瘤作用的免疫机制。方法:给正常野生型C57BL/6小鼠皮下接种小鼠淋巴瘤EL4细胞,建立荷EL4肿瘤的小鼠模型。于野生型C57BL/6小鼠皮下接种瘤细胞后12d,经腹腔给荷瘤小鼠单次注射不同剂量的美法仑,找出美法仑可发挥最大的抑瘤作用,并能致使肿瘤消退、不再复发的最小使用剂量。然后再给野生型C57BL/6小鼠及其裸鼠(遗传背景相同)皮下同时接种小鼠淋巴瘤EL4细胞建立两种荷瘤小鼠模型。同样于接种瘤细胞后12d,经腹腔给两种荷瘤小鼠模型均注射可使野生型C57BL/6小鼠肿瘤消退、不再复发的最低剂量的美法仑,以正常野生型C57BL/6小鼠为对照,观察在T淋巴细胞缺陷的裸鼠体内美法仑的抑瘤作用。结果:注射7.5mg/kg美法仑治疗后,免疫功能正常的野生型C57BL/6荷瘤小鼠的肿瘤消退;而荷瘤C57BL/6裸鼠的肿瘤仍继续生长。结论:单一剂量的美法仑对荷淋巴瘤EL4小鼠具有明显的治疗作用,其作用的发挥需要T淋巴细胞的参与,可能与T细胞的杀伤作用有关。     

美法仑治愈荷瘤小鼠的过程与TNFα的关系

目的探讨单一剂量的美法仑治愈荷瘤野生型C57BL/6小鼠的过程与肿瘤坏死因子α(TNFα)的关系。方法以3种遗传背景相同、肿瘤坏死因子受体1(TNFR1)基因型不同的TNFR1 / 、TNFR1 /-和TNFR1-/-C57BL/6小鼠为实验动物,皮下接种数量相同的小鼠淋巴瘤EL4细胞。接种瘤细胞后12d,给基因型不同的各组荷瘤小鼠腹腔内单次注射7.5mg/kg的美法仑。以荷瘤野生型C57BL/6小鼠(TNFR1 / )为对照,观察美法仑对荷瘤TNFR1 /-C57BL/6小鼠和荷瘤TNFR1-/-C57BL/6小鼠的治疗效应。结果在美法仑(7.5mg/kg)治疗后的1周内,基因型不同的各组荷瘤小鼠肿瘤消退的速度基本相同。在随后的2月内,荷瘤TNFR1 / 和TNFR1 /-C57BL/6小鼠的肿瘤结节逐渐消退、肿瘤治愈;而多数荷瘤TNFR1-/-C57BL/6小鼠的肿瘤结节缩小后又再次出现并逐渐长大、肿瘤复发。结论TNFα与美法仑治愈肿瘤的过程密切相关,其中美法仑的抗肿瘤作用与荷瘤小鼠TNFR1的表达无关,但在美法仑治疗后,机体预防或避免肿瘤复发方面需要TNFR1在机体细胞的表达,而不是在肿瘤细胞的表达。     

Catheter obstruction during prolonged parenteral alimentation. Are lipids responsible?

Catheter obstruction is a serious incident during prolonged parenteral nutrition (PN). This retrospective study was carried out in order to compare the frequencies of catheter obstruction with nutritive mixtures in bags according to whether or not lipids were mixed with the entire 24 h nutritional supply (Group I, n=33) or infused separately (Group II, n=30). Our results show that obstructions are significantly more frequent in Group I (11 13 ) than in group 2 (3 10 ), appearing within a mean interval of 29 days after inserting the catheter. The global percentages of patients undergoing cyclic PN were the same in both patient groups. In group I, however, the percentage of patients on cyclic PN was significantly higher for the obstructed catheters (100%) than for the unobstructed catheters (59%). In conclusion, the mixture of lipids with the remainder of the nutrients in the conditions of this study is the prime cause of catheter obstruction, although the exact mechanism is not elucidated. The role of cyclic PN appears to be accessory.     

检测Ⅳ型胶原蛋白直接双抗夹心法的建立与评价

目的 :建立血清 型胶原蛋白 (COL - )浓度测定的直接双抗夹心法 ,为临床诊断肝纤维化提供一种新的指标。方法 :采用本科室自制的 COL - 单克隆酶标抗体、多克隆抗体建立的直接双抗夹心法 ,同时采用日本试剂盒测定 6 0份正常和肝脏病人血清 COL- 浓度做对照比较。结果 :两种方法无显著性差异 (P>0 .0 5 ,t=0 .16 6 ) ;两法相关分析 ,γ=0 .834,回归方程为 Y=0 .5 9X+ 70 .874。结论 :直接双抗夹心法测定血清 COL- 操作简便、特异、准确 ,可作为辅助诊断肝纤维化的可靠指标 ,并可在临床推广应用     

Ultrastructural neuropathologic effects of Taxol on neurons of the freshwater snailLymnaea stagnalis

Summary Cerebral ganglia of the freshwater snailLymnaea stagnalis were incubatedin vitro in 10 M Taxol for 8 and 24 h. Cremophor EL (0.1%) was used as a diluant. The tissue was processed for electron microscopy. Various ultrastructural parameters were assessed quantitatively. Cremophor EL appeared to seriously affect the cell somata of the multipeptidergic caudodorsal cells. In the Cremophor-controls the mean area of Golgi zones, the percentage dense material (neuropeptides) in these zones, the number of large electron dense granules (these are involved in neuropeptide processing) and the mean nuclear heterochromatin clump size, were significantly smaller than in the Ringer-controls, whereas the number of lipid droplets was higher. All these parameters, except for the lipid droplets, were not different in the Cremophor-controls and the Taxol-treated specimens. After 24 h treatment, but not after 8 h, Cremophor EL furthermore induced an increase in the number of axonal microtubules. It is argued that the results might signify activation of the neurons by Cremophor EL. Taxol induced a significant increase in the number of microtubules in axons and cell somata. Furthermore an increase in the number of Golgi zones was observed, suggesting activated neuropeptide synthesis. In all groups immunostaining with antibodies to neuropeptides produced by the caudodorsal cells was normal. Release of neuropeptide (exocytosis) from axon endings was elevated after Taxol treatment, and exceptionally high in specimens cotreated with Taxol and Org 2766 (incubation time 22 h). The effect of Org 2766 and Taxol on the number of microtubules was cumulative. It is argued that transport of neuropeptide granules from the cell somata to the axon terminals was not affected by Taxol. It is concluded that Taxol neurotoxicity is probably not due to impeded microtubular axonal transport.     

Comparative patterns of i-antigen expression, F-cell frequency and Hb A2 level in acute myeloid leukemia and in acute lymphoid leukemia

Hb F, Hb A₂ and i-antigen expression were investigated in adulthood acute leukemias. The study of i-antigen expression by immuno-agglutination and immunofluorescence showed that it is preferentially increased among AML patients. A similar result was obtained for F-cell frequency which was often increased in AML, while it was normal in ALL. Hb A₂ level was significantly lower in AML than in ALL. These differences between AML and ALL red cell patterns further suggest that the leukemic clone involves the erythroid lineage in AML but not in ALL.     

Differential modulation of cisplatin accumulation in leukocytes and tumor cell lines by the paclitaxel vehicle Cremophor EL

Background: Several clinical studies have shown that poly-chemotherapy with the taxanes paclitaxel or docetaxel preceded or followed by cisplatin is associated with important schedule-dependent differences in toxicities, such as leukocytopenia. In general, the pharmacokinetics of both drugs during the combined treatment are unaltered, suggesting that a pharmacodynamic interaction might have occurred.Materials and methods: In order to gain insight into this pharmacologic interaction, we performed in vitro drug accumulation studies using peripheral blood leukocytes and a panel of tumor and non-malignant cell lines with paclitaxel and docetaxel, as wel as with their respective formulation vehicles Cremophor EL and Tween 80.Results: Our results show a significant reduction in the intracellular cisplatin concentration in leukocytes of up to 42% in the presence of Cremophor EL and Tween 80 as compared to the control. This pharmacodynamic interaction of these surfactants with cisplatin seems to be specific for haematopoietic cells, and does not occur in solid tumor cells.Conclusion: The present data suggest that the pharmaceutical vehicles Cremophor EL and Tween 80 might contribute to the reduced cisplatin-associated myelotoxicity observed in the clinical combination chemotherapy studies with paclitaxel and docetaxel.     

电针阳陵泉,脾俞穴对重症肌无力模型大鼠神经肌肉接头传递的影响

以乙酰胆碱电位 (Ach P)、小终板电位 (MEPP)及血清抗乙酰胆碱受体抗体 (Ach RAb)滴度为观察指标 ,探讨了电针“阳陵泉”、“脾俞”穴对重症肌无力模型大鼠神经肌肉接头传递过程的影响及其作用机制。结果表明 ,电针“阳陵泉”穴或“脾俞”穴均能使重症肌无力 (MG)大鼠的 Ach P与MEPP振幅升高 ,但对 Ach P时程、MEPP的频率及血清 Ach RAb滴度却没有明显影响 ;同时电针“阳陵泉”、“脾俞”二穴 ,则使 MG大鼠的 Ach P、MEPP振幅升高更加显著 ;电针穴位临近肌肉则没有如此效应。提示 ,电针“阳陵泉”、“脾俞”穴有提高 MG大鼠神经肌肉接头传递的作用。     

三种方法检测乙型肝炎病毒表面抗原阳性结果的分析

目的探讨微粒子化学发光检测技术(MEIA),酶联免疫吸附试验(ELISA)和胶体金免疫层析试验(GICA)检测乙型肝炎病毒表面抗原(HBs Ag)的结果符合率。方法用MEIA、ELISA和GICA三种方法对200份标本进行乙型肝炎病毒表面抗原检测,比较三种方法的阳性率、敏感度和特异度。结果 ELISA法阳性率为43.5%,阴性率为56.5%;GICA法阳性率为41.0%,阴性率为59.0%;MEIA法阳性率为45.5%,阴性率为54.5%。ELISA与MEIA符合度较高,阳性率较高,GICA与MEIA符合度差,阳性率最低。三种方法中以MEIA法的敏感度和特异度最高,其次为ELISA法,GICA法最低。结论 GICA灵敏度较低,只能作为初筛;ELISA较MEIA灵敏度略低,遇到检测样本吸光度值(OD值)在对照样本临界值(cut off值)附近时,需要复检。     

内皮脂肪酶与高密度脂蛋白及动脉粥样硬化的关系

高密度脂蛋白具有一定的抗动脉粥样硬化的作用,而内皮脂肪酶可水解高密度脂蛋白,进而影响动脉粥样硬化的进展,故深入探讨三者关系,可能为动脉粥样硬化相关疾病的防治提供崭新的靶点.