杂多阴离子对SiO_2细胞毒性的拮抗作用

本文采用离体细胞培养法,以细胞存活率、乳酸脱氢酶活性和酸性磷酸酶活性为指标,研究了几种α-Keggin结构的杂多阴离子对石英粉尘细胞毒性的影响。结果表明,与对照组比较,所用杂多阴离子无细胞毒性(P>0.05),石英尘经杂多阴离子作用后,细胞毒性显著降低,与石英尘组比较,上述三项指标差异均有显著意义(P<0.01),由此表明杂多阴离子对石英的细胞毒性有明显的拮抗作用。     

Analysis of Vascular Endothelial Growth Factor (VEGF) and a receptor subtype (KDR/flk-1) in the liver of rats exposed to riddelliine: a potential role in the development of hemangiosarcoma

Riddelliine alters hepatocellular and endothelial cell kinetics and function including stimulating an increase in hepatocytic vascular endothelial growth factor (VEGF) in the absence of increased serological levels of VEGF (Nyska etal. 2002). The objective of this study was to further assess hepatic VEGF and KDR/flk-1 synthesis and expression by hepatic cells under riddelliine treatment conditions. Forty-two male F344/N rats were dosed by gavage with riddelliine (0, 1.0, and 2.5 mg/kg/day) for 6 weeks. Seven animals/group were sacrificed after 8 consecutive daily doses; remaining rats were terminated after 30 daily doses, excluding weekends. Hepatic tissues were evaluated by immunohistochemistry and in situ hybridization. The results showed that VEGF mRNA expression was observed in control and treated animals; however, qualitative differences were noted. Treated animals exhibited VEGF mRNA in clustered, focal hepatocytes and bile duct epithelium, whereas VEGF mRNA in hepatocytes from vehicle control rats was distributed evenly across all hepatocytes. Results evaluating the distribution of the VEGF cognate receptor, KDR/flk-1 showed that randomly distributed, rare sinusoidal endothelium, including those demonstrating karyomegaly and cytomegaly expressed KDR/flk-1. Phosphorylation of KDR/flk-1 at pTyr996 and pTyr1054/1059, but not pTyr951, was also detected, evidence that endothelial cell KDR/flk-1 was activated. These results suggest that both hepatocytes and endothelial cells are targets of riddelliine-induced injury. We speculate that damage to both populations of cells may lead to dysregulated VEGF synthesis by hepatocytes and activation of KDR/flk-1 by endothelium leading to the induction of sustained endothelial cell proliferation, culminating in the development of hepatic hemangiosarcoma.     

Granulysin: A Novel Host Defense Molecule

Granulysin is a novel cationic molecule present in the granules of cytotoxic T lymphocytes and natural killer cells. Cytotoxic T lymphocytes have long been associated with graft destruction in transplant rejection. Recent studies implicate granulysin in cell-mediated cytotoxicity, chemoattraction, immune activation and as a potential diagnostic biomarker for transplant rejection.     

神经胶质瘤患者细胞免疫的近代实验研究

本文检测了40例脑胶质瘤患者淋巴细胞亚群、NK细胞杀伤活性、淋巴细胞增殖率以及免疫抑制活性的变化,与正常对照组(40例)相比较,该四项免疫学指标均有显著性差异(均P<0.001),并阐述了患者细胞免疫功能低下可能与患者血清免疫抑制因子有关。     

Evidence for delayed cytotoxicity effects following exposure of rat hepatoma-derived Fa32 cells: implications for predicting human acute toxicity

The delayed cytotoxicity of the Multicentre Evaluation of In vitro Cytotoxicity (MEIC) reference chemicals was investigated in rat hepatoma-derived Fa32 cells. The cells were treated for 24 h with the test chemicals, and were than further cultured for 5 days in normal culture medium. The cytotoxicity was measured by the neutral red uptake inhibition, and the results were quantified by determining the NI50del. This is the concentration of test compound required to decrease the neutral red uptake with 50% compared with control cells. The results were compared with the acute NI50, the corresponding value measured immediately after 24 h treatment of the cells. On a total of 44 chemicals, nine showed delayed cytotoxicity (NI50del lower than or equal to NI50), 11 a probably delayed, and 24 no delayed cytotoxicity (NI50del more than 1.5×NI50). When the NI50del was compared with human toxicity, a correlation coefficient r²⁼0.761 was obtained. For the same series of 44 chemicals this correlation was clearly higher than that for human hepatoma-derived Hep G2 cells (r²=0.695). The Hep G2 assay was the best acute in vitro assay for the prediction of human toxicity within the MEIC study. Consequently, the delayed cytotoxicity assay on cultured Fa32 cells has the best prediction value so far obtained for the human toxicity.     

A novel strategy for the detection and definition of HLA-specific antibodies in patients awaiting renal transplantation

Abstract Conventional testing for HLA-specific antibodies employs complement-dependent cytotoxicity (CDC) which is labour intensive and dependent on a supply of viable lymphocytes. Our strategy to minimise CDC screening is initially to screen sera by ELISA (Quikscreen) to detect HLA Class I-specific antibodies. Negative sera are then screened by flow cytometry (FCS) using lymphoblastoid cell line pools to detect HLA Class II-specific antibodies. Only Quikscreen-or FCS-positive sera are then tested by CDC and, when indicated, with an ELISA kit (PRA-STAT) for specificity definition. Of 3680 sera, 886 (24.1%) were Quikscreen positive. Of the 2794 Quikscreen-negative sera, 374 (13.4%) were FCS positive. Therefore, only 1265 of the 3680 (34.3%) sera contained HLA-specific antibodies requiring specificity definition. This novel screening strategy has significantly reduced the CDC workload of the laboratory whilst enabling the detection of additional HLA-specific antibodies.     

Decreased antibody-dependent cellular cytotoxicity in minimal change nephrotic syndrome

Secondary IgG response to a tetanus toxoid booster and in vitro measurement of immunoglobulin synthesis, antibody-dependent cellular cytotoxicity (ADCC) and -interferon (IFN-) production were evaluated in 20 healthy controls and in 17 children with minimal change nephrotic syndrome (MCNS), during the acute nephrotic phase and 6 months after remission. Defective responses were observed in all but IFN- production during the acute nephrotic phase; these improved with disease remission. There was a significant correlation between decreases in vitro IgG production and ADCC reaction. These data indicate that defective antibody production is associated with decreased ADCC during the acute nephrotic phase of MCNS.     

Synthesis,Physicochemical Properties,and Cytotoxicity of a Series of 5′-Ester Prodrugs of 5-Iodo-2′-deoxyuridine

Five aliphatic 5-esters of 5-iodo-2deoxyuridine (IDU) were synthesized via an acid chloride alcoholysis reaction. The solubility in pH 7.4 phosphate buffer, lipophilicity as determined by partition experiments in octanol/pH 7.4 buffer, and cytotoxicity of these potential prodrugs were evaluated. The esters showed a 43- to 250-fold increase in lipophilicity and a 1.6- to 14-fold decrease in aqueous solubility relative to IDU. At a concentration of 50 µM, all esters showed reduced cytotoxicity toward uninfected Vero cells relative to IDU.     

Transfected rat islet tumour cells express mouse major histocompatibility complex class I antigens functionally

Summary Rat insulinoma cells clone 5AH-B, were transfected by electroporation with the gene encoding the mouse major histocompatibility complex class I antigen H-2K^b, whereupon stable transfectants were selected and analysed. Data from flow cytometric analyses using three different H-2K^b specific monoclonal antibodies and functional assays using H-2K^b specific alloimmune cytotoxic T cells revealed that the encoded H-2 antigen was expressed in a functional manner. Similar experiments employing the monoclonal antibody OX-18, which recognizes rat major histocompatibility class I molecules, and xenoimmune cytotoxic T cells specific for the endogenously expressed RT1^g antigen showed that functional expression of the RT1^g antigen was maintained. However, a down-regulation of the expression was observed in H-2K^b positive transfectants, whereas normal expression was retained in K^b negative transfectants. The function of the native promoters of both the endogenous and the transfected class I genes was found to be preserved in the transfectants as assessed by the response to stimulation with interferon-. The present study was unable to confirm the reports of RIN specific lysis by T cells from multiple low dose streptozotocin diabetic mice. Even in the presence of the syngeneic restriction element no lysis was observed. We conclude, that rat insulinoma cells clone 5AH-B, are able to integrate a foreign class I antigen gene and express the encoded product functionally. The data also suggest the possibility of creating major histocompatibility antigen positive rat insulinoma cells which are RT1^g negative. Such transfectants will be of great potential value for the dissection of cell mediated B cell destructive processes.