氯磷酸二钠表面改性羟基磷灰石血清蛋白吸附行为的改变

目的:观察二磷酸盐药物对羟基磷灰石进行表面改性后对材料表面蛋白吸附的影响。方法:实验于2005-06/08在口腔生物医学工程教育部重点实验室完成。①将羟基磷灰石制成10mm×10mm×2mm大小的块状,共48块,随机分为实验组与对照组,每组24块。②实验组羟基磷灰石与氯磷酸二钠复合制成氯磷酸二钠-羟基磷灰石,对照组不复合氯磷酸二钠,用乙醇和蒸馏水超声波清洁,干燥备用。③将两组标本分别置入100g/L小牛血清(蛋白吸附溶液)和0.2mol/LPBS磷酸缓冲液(对照吸附溶液)中浸泡吸附,每种溶液中12块。④通过X射线光电子能谱分析检测和蛋白质电泳对两组材料表面吸附的蛋白进行对比分析。结果:①X射线光电子能谱分析检测提示吸附小牛血清后,实验组和对照组表面氮元素百分含量分别是(9.83±1.33)%和(10.11±1.67)%,差异无显著性意义(P>0.01)。②十二烷基磺酸钠-聚丙烯酰胺凝胶电泳提示两组材料均可以吸附大量白蛋白,实验组表面吸附的白蛋白要少于对照组。③双向电泳提示两组材料表面吸附的蛋白相对分子质量均大于50000;对照组吸附的酸性蛋白量要多一些,实验组表面吸附的碱性蛋白和中性蛋白要多一些;偏酸性的蛋白中,β球蛋白和玻璃粘连蛋白在实验组表面吸附量较对照组表面多。结论:氯磷酸二钠复合羟基磷灰石对材料表面吸附蛋白的种类有一定影响,但对总量没有明显影响。     

国人全膝关节假体置换胫骨近端截骨面至腘血管距离的测量及意义

目的:测量国人全膝关节假体置换术胫骨近端截骨面后缘至腘窝血管之间的距离,以期为临床全膝关节置换术中避免损伤腘窝血管提供参考数据。方法:选择2006-06/12于解放军第二军医大学长征医院体检的50名正常成人(53膝),男29名(31膝),女21名(22膝)。所有观察对象均知情同意,且得到医院伦理道德委员会批准。对所有膝关节进行MRI扫描,在胫骨外侧平台以下10mm水平横断面上辨认腘动静脉,并测量胫骨近端截骨面后缘至腘窝动静脉的距离。结果:53膝全部进入结果分析,无脱落。①男性胫骨近端截骨面后缘至腘动脉、腘静脉平均距离为(6.7±2.5,7.3±2.3)mm,95%可信区间分别为5.8～7.6mm,6.5～8.1mm。②女性胫骨近端截骨面后缘至腘动脉、腘静脉平均距离为(6.6±1.9,7.1±2.7)mm,95%可信区间分别为:5.8～7.4mm,5.9～8.3mm。③不同性别观察对象胫骨近端截骨面后缘至腘血管的距离差异无显著性意义(P>0.05)。结论:腘窝血管紧邻全膝关节假体置换术胫骨近端截骨面后缘,不同性别间无明显差异。全膝关节假体置换术中进行胫骨近端截骨,特别是后方操作时需特别谨慎,以避免损伤腘窝血管。     

Novel mode of action of c-kit tyrosine kinase inhibitors leading to NK cell-dependent antitumor effects

Mutant isoforms of the KIT or PDGF receptors expressed by gastrointestinal stromal tumors (GISTs) are considered the therapeutic targets for STI571 (imatinib mesylate; Gleevec), a specific inhibitor of these tyrosine kinase receptors. Case reports of clinical efficacy of Gleevec in GISTs lacking the typical receptor mutations prompted a search for an alternate mode of action. Here we show that Gleevec can act on host DCs to promote NK cell activation. DC-mediated NK cell activation was triggered in vitro and in vivo by treatment of DCs with Gleevec as well as by a loss-of-function mutation of KIT. Therefore, tumors that are refractory to the antiproliferative effects of Gleevec in vitro responded to Gleevec in vivo in an NK cell-dependent manner. Longitudinal studies of Gleevec-treated GIST patients revealed a therapy-induced increase in IFN-gamma production by NK cells, correlating with an enhanced antitumor response. These data point to a novel mode of antitumor action for Gleevec.     

A population-based survey of the epidemiology of symptom-defined gastroesophageal reflux disease: the Systematic Investigation of Gastrointestinal Diseases in China

Background

Hepatitis B immune globulins (HBIG) in combination with nucleos(t)ide analogues (NA) are effectively used for the prevention of hepatitis B virus (HBV) recurrence after liver transplantation (LT). However, associated treatment costs for HBIG are exceedingly high.

Methods

Fresh frozen plasma obtained from blood donors with high anti-HBs levels (hyperimmune plasma, HIP) containing at least 4,500 IU anti-HBs was used as alternative treatment for HBV recurrence prophylaxis post-LT.

Results

Twenty-one HBV-related LT recipients received HIP starting at transplantation, followed by long-term combination treatment with NA. Mean follow-up time was 4.5 years (range 0.5-12.6) and each patient received on average 8.2 HIP per year (range 5.8-11.4). Anti-HBs terminal elimination kinetic after HIP administration was 20.6 days (range 13.8-30.9), which is comparable to values reported for commercial HBIG products. All 21 patients remained free of HBV recurrence during follow-up and no transfusion-transmitted infection or other serious complication was observed. Seven patients developed reversible mild transfusion reactions. The cost for one HIP unit was US$140; average yearly HBIG treatment cost was US$1,148 per patient, as compared to US$25,000-100,000 for treatment with commercial HBIG.

Conclusion

The results of this study suggest that the use of HIP may be a useful and economical approach for the prevention of HBV recurrence post-LT if used in combination with NA. Additional prospective controlled studies in larger populations are needed to confirm these results.     

Caspase-9 regulates apoptosis/proliferation balance during metamorphic brain remodeling in Xenopus

During anuran metamorphosis, the tadpole brain is transformed producing the sensorial and motor systems required for the frog's predatory lifestyle. Nervous system remodeling simultaneously implicates apoptosis, cell division, and differentiation. The molecular mechanisms underlying this remodeling have yet to be characterized. Starting from the observation that active caspase-9 and the Bcl-X(L) homologue, XR11 are highly expressed in tadpole brain during metamorphosis, we determined their implication in regulating the balance of apoptosis and proliferation in the developing tadpole brain. In situ hybridization showed caspase-9 mRNA to be expressed mainly in the ventricular area, a site of neuroblast proliferation. To test the functional role of caspase-9 in equilibrating neuroblast production and elimination, we overexpressed a dominant-negative caspase-9 protein, DN9, in the tadpole brain using somatic gene transfer and germinal transgenesis. In both cases, abrogating caspase-9 activity significantly decreased brain apoptosis and increased numbers of actively proliferating cells in the ventricular zone. Moreover, overexpression of XR11 with or without DN9 was also effective in decreasing apoptosis and increasing cell division in the tadpole brain. We conclude that XR11 and caspase-9, two key members of the mitochondrial death pathway, are implicated in controlling the proliferative status of neuroblasts in the metamorphosing Xenopus brain. Modification of their expression during the critical period of metamorphosis alters the outcome of metamorphic neurogenesis, resulting in a modified brain phenotype in juvenile Xenopus.     

Validation of prognostic scores for survival in cancer patients beyond first-line therapy

Background

DNA methylation in the SHOX2 locus was previously used to reliably detect lung cancer in a group of critical controls, including 'cytologically negative' samples with no visible tumor cell content, at a high specificity based on the analysis of bronchial lavage samples. This study aimed to investigate, if the methylation correlates with SHOX2 gene expression and/or copy number alterations. An amplification of the SHOX2 gene locus together with the observed tumor-specific hypermethylation might explain the good performance of this marker in bronchial lavage samples.

Methods

SHOX2 expression, gene copy number and DNA methylation were determined in lung tumor tissues and matched morphologically normal adjacent tissues (NAT) from 55 lung cancer patients. Quantitative HeavyMethyl (HM) real-time PCR was used to detect SHOX2 DNA methylation levels. SHOX2 expression was assayed with quantitative real-time PCR, and copy numbers alterations were measured with conventional real-time PCR and array CGH.

Results

A hypermethylation of the SHOX2 locus in tumor tissue as compared to the matched NAT from the same patient was detected in 96% of tumors from a group of 55 lung cancer patients. This correlated highly significantly with the frequent occurrence of copy number amplification (p < 0.0001), while the expression of the SHOX2 gene showed no difference.

Conclusions

Frequent gene amplification correlated with hypermethylation of the SHOX2 gene locus. This concerted effect qualifies SHOX2 DNA methylation as a biomarker for lung cancer diagnosis, especially when sensitive detection is needed, i.e. in bronchial lavage or blood samples.     

癌症化学预防的分子靶标

乙肝病毒和人乳头状瘤病毒分别是肝细胞癌和子宫颈癌的风险因素,针对这2种病毒感染的疫苗已在临床上成功用于癌症化学预防。分子靶向药物能够预防乳腺癌（雷洛昔芬与他莫昔芬）、大肠腺瘤（塞来昔布）和前列腺癌（非那雄胺）。然而,化学预防广泛应用于临床还不现实。分子靶标的深入研究将扩展化学预防的范围并使其个性化。