癌基因c-fos、c-jun蛋白在鳞状细胞癌皮损中的表达及意义

目的　探讨癌基因c fos、c jun的表达与皮肤鳞癌发生和发展的关系。　方法　采用免疫组化法对 6 0例皮肤鳞癌的c fos、c jun的表达情况进行检测 ,并与正常皮肤组织进行对照。　结果　c fos、c jun在正常皮肤组织不表达 ,在皮肤鳞癌中的表达阳性率分别为 6 1.7%和 4 8.3% ,其表达水平与癌组织的分化程度有关 (P <0 .0 5 ) ,肿瘤的分化程度越高其表达水平越高。　结论　c fos、c jun的表达水平可作为判定皮肤鳞癌分化的指标。     

Polymorphism p53 codon-72 and invasive cervical cancer: a meta-analysis.

OBJECTIVES: Although some studies have reported that the arginine isoform on codon 72 of p53 increases the susceptibility to invasive cervical cancer, such data remain controversial. The objective of this study was to quantitatively summarize the evidence for such a relationship. METHODS: Our data sources consisted of a MEDLINE search of the literature published before December 2002, bibliography review, and expert consultation. Thirty-seven studies met the inclusion criteria. Information on sample size, study design, Hardy-Weinberg equilibrium, and method of genotype determination was abstracted by two reviewers using a standardized protocol. The overall odds ratio (OR) of the p53 gene on invasive cervical cancer was estimated using the Mantel-Haenzel method. RESULTS: The overall OR (95% confidence interval) for cervical cancer among those with the homozygous mutant (Arg/Arg) was 1.2 (1.1-1.3, P=0.001) compared with those with the heterozygous mutant (Arg/Pro). By a cellular type of cervical cancer, the overall OR among those with Arg/Arg was statistically significant in adenocarcinomas (1.7, 1.1-2.6, P=0.024), but not in squamous cell carcinomas (1.1, 0.9-1.2, P=0.960), compared with Pro/Pro. Compared with Arg/Pro, the OR among those with Arg/Arg was statistically significant in HPV types 16 (1,5, 1.2-2.0, P=0.002). CONCLUSIONS: Overall, the p53 gene was associated with increased risk for invasive cervical cancer. However, the risk varied by country, cellular, and HPV type.     

非小细胞肺癌转移预测指标的研究

目的 :研究非小细胞肺癌 (NSCLC)淋巴结和远处转移的预测指标 ,并建立Logistic回归模型。　 方法 :通过免疫组化、ELISA、酶谱电泳等方法 ,对NSCLC肿瘤病理标本、血清、尿液和骨髓等进行检查 ,并通过Logistic回归分析建立预测概率模型。　结果 :免疫组化指标肿瘤组织内微血管密度 (IMVD)、血管内皮细胞生长因子(VEGF)、碱性成纤维细胞生长因子 (b FGF)、白细胞分化抗原变异型 (CD4 4v6 )、基质金属蛋白酶 2 (MMP 2 )与NSCLC淋巴结转移危险有关 (P <0 .0 5 ) ,组织金属蛋白酶抑制物 (TIMP 2 )、上皮型钙粘素 (E cad)与NSCLC淋巴结转移危险下降有关 (P <0 .0 5 )。血清MMP 2、MMP 9,尿液MMP 2、MMP 9及骨髓上皮膜抗原 (EMA)阳性细胞与NSCLC远处转移危险有关 (P <0 .0 5 )。其中免疫组化指标CD4 4v6、IMVD、E cad及尿液MMP 2、骨髓EMA阳性细胞对NSCLC转移有显著回归效果而分别被选入概率模型 1和 2 ,其预测准确率分别为 81.1%和 72 .7%。　结论 :组织标本中CD4 4v6、IMVD、E cad以及尿液中MMP 2及骨髓EMA阳性细胞检查 ,可预测绝大多数NSCLC的淋巴结转移和远处转移状况 ,为NSCLC转移的早期诊断提供重要信息 ,有助于NSCLC的个体化治疗和改善预后     

高效液相色谱法测定人肝细胞色素P450 3A4转基因细胞中氨氯地平

目的 :研究氨氯地平经人肝细胞色素 P4 5 0 3A4 (CYP3A4 )的代谢 ,建立反相高效液相色谱的测定人肝转基因细胞 CYP3A4酶 S9孵育液中氨氯地平浓度的方法。方法 :与人肝转基因细胞提取的 S9上清液孵育之后的样品 ,用 3倍量的甲醇沉淀后离心 ,取上清液用 0 .4 5μm微孔滤膜滤过后进样。采用 Hypersil C18柱 ,以乙腈 -磷酸盐缓冲液 (4 5∶ 5 5 ,v/ v,p H4 .5 )为流动相 ,普萘洛尔为内标 ,在 2 5 0 nm波长处测定。结果 :氨氯地平浓度在 0 .2～ 30 .0μg/ ml范围内线性关系良好 ,r=0 .9993,方法平均回收率为 (98.2± 2 .4 ) % (n=5 ) ,日内和日间相对标准偏差(RSD)均小于 10 % ,检测限为 2 0 ng/ ml,定量限为 0 .2 μg/ ml(回收率为 10 4 .0 % ,RSD为 11.4 % ,n=5 )。结论 :建立的反相高效液相色谱方法简便、准确 ,可用于研究氨氯地平在人肝 CYP3A4转基因细胞中的代谢。     

Noonan syndrome associated with central giant cell granuloma

We report a case of Noonan syndrome associated with central giant cell granuloma. The patient was a 101/2-year-old boy with the chief complaint of proptosis of the right eye. He also had various malformations such as short stature, webbed neck, pectus excavatum, cubitus valgus, pulmonary valve stenosis and patent foramen ovale, a characteristic face appearance and cryptorchidism and so on. Chromosome analysis showed a 46, XY karyotype. A computed tomographic scan and magnetic resonance imaging showed a mass originated from the lateral wall of the right maxillary sinus. The patient underwent Caldwell-Luc operation. Histological examination of the mass showed the characteristics of central giant cell granuloma. This case report describes a patient with the features of the recently described Noonan-like/multiple giant cell lesion syndrome.     

卵巢癌细胞多种细胞因子基因表达的研究

本文应用RT-PCR方法,检测5例刚分离的晚期上皮性卵巢癌患者肿瘤细胞和3例卵巢痛患者腹水中肿瘤细胞IL-2、IL-2R、TNF-a,IL-6、TGF-p、IL-10等细胞因子基因的表达,用免疫学方法检测卵巢癌细胞上清液中IL-6活性。结果发现:卵巢癌肿瘤细胞表达IL-6mRNA和抑制性细胞因子TGF-p、IL-10。腹水中存在较多量lL-6可能来自肿瘤细胞。     

Preselection Thymocytes Are More Sensitive to T Cell Receptor Stimulation Than Mature T Cells

During T cell development, thymocytes which are tolerant to self-peptides but reactive to foreign peptides are selected. The current model for thymocyte selection proposes that self-peptide–major histocompatibility complex (MHC) complexes that bind the T cell receptor with low affinity will promote positive selection while those with high affinity will result in negative selection. Upon thymocyte maturation, such low affinity self-peptide–MHC ligands no longer provoke a response, but foreign peptides can incidentally be high affinity ligands and can therefore stimulate T cells. For this model to work, thymocytes must be more sensitive to ligand than mature T cells. Contrary to this expectation, several groups have shown that thymocytes are less responsive than mature T cells to anti-T cell receptor for antigen (TCR)/CD3 mAb stimulation. Additionally, the lower TCR levels on thymocytes, compared with T cells, would potentially correlate with decreased thymocyte sensitivity. Here we compared preselection thymocytes and mature T cells for early activation events in response to peptide–MHC ligands. Remarkably, the preselection thymocytes were more responsive than mature T cells when stimulated with low affinity peptide variants, while both populations responded equally well to the antigenic peptide. This directly demonstrates the increased sensitivity of thymocytes compared with T cells for TCR engagement by peptide–MHC complexes.     

Interactions between membrane IgM and the cytoskeleton involve the cytoplasmic domain of the immunoglobulin receptor

Cross-linking induced interactions between the membrane form of immunoglobulin (mIg) and the cytoskeletal matrix have been described by several groups. To date, the function of mIgM association with the cytoskeleton is not yet understood. Delineation of the molecular basis of these interactions will be instrumental in elucidating their function. We have previously shown that the Igα/β heterodimer is not required for ligand-induced mIgM binding to the cytoskeleton. In this study, we have investigated the role of other B cell-specific proteins in mediating these interactions. For this, we expressed mIgM in the non-hematopoietic human cervical carcinoma cell line HeLa S3 and verified the capacity of the surface-expressed IgM to interact with the cytoskeletal matrix upon cross-linking with anti-μ chain antibodies. We show here that only the mIgM molecule itself and no other B cell-specific protein(s) is required in mediating mIgM interactions with actin filaments. In an attempt to determine the cytoskeleton-binding site of mIgM we investigated the role of the cytoplasmic tail of mIgM (KVK) in binding the receptor to actin-based microfilaments. Using mutated forms of mIgM expressed in J558L cells, we show here that KVK plays a role in mediating these interactions. The absence of KVK did not, however, completely abrogate mIgM-cytoskeletal interactions, suggesting that there are additional molecular requirements for the ligand-induced mIgM binding to the cytoskeletal matrix.     

All-trans retinoic acid suppresses liver injury induced by Propionibacterium acnes and lipopolysaccharide in rats

All-trans retinoic acid (ATRA) has been reported to exert major effects on the immune system, including monocytes/macrophages. The present study was designed to determine whether ATRA would modulate macrophage-associated liver injury induced by Propionibacterium acnes and lipopolysaccharide (LPS) in rats. All-trans retinoic acid administration alleviated the liver injury and reduced the incidence of death following hepatic failure. Serum alanine aminotransferase (ALT) levels 5 h after, and survival rates within 12 h after the administration of LPS were significantly lower in the ATRA-treated group (134 ± 119 IU/L and 72.7%) compared with the control group (713 ± 411 IU/L and 18.2%; P < 0.05). Histological findings supported these results. These effects may be due to suppression of tumour necrosis factor-α (TNF-α) and superoxide anions produced by activated macrophages. Serum levels of TNF-α 1 h after LPS administration were significantly lower in the ATRA-treated group (60.5 ± 7.0 ng/mL) as compared with the control group (105.2 ± 39.3 ng/mL; P < 0.05). Formazan deposition that was generated by the perfusion of the liver with nitroblue tetrazolium, also suggested suppression of the release of superoxide anions from hepatic macrophages. These results suggest that ATRA acts as an immunomodulator in liver injury by suppressing the activation of liver macrophages.     

Abortive Proliferation of Rare T Cells Induced by Direct or Indirect Antigen Presentation by Rare B Cells In Vivo

Antigen-specific B cells are implicated as antigen-presenting cells in memory and tolerance responses because they capture antigens efficiently and localize to T cell zones after antigen capture. It has not been possible, however, to visualize the effect of specific B cells on specific CD4⁺ helper T cells under physiological conditions. We demonstrate here that rare T cells are activated in vivo by minute quantities of antigen captured by antigen-specific B cells. Antigen-activated B cells are helped under these conditions, whereas antigen-tolerant B cells are killed. The T cells proliferate and then disappear regardless of whether the B cells are activated or tolerant. We show genetically that T cell activation, proliferation, and disappearance can be mediated either by transfer of antigen from antigen-specific B cells to endogenous antigen-presenting cells or by direct B–T cell interactions. These results identify a novel antigen presentation route, and demonstrate that B cell presentation of antigen has profound effects on T cell fate that could not be predicted from in vitro studies.