TNF alpha and Fas mediate tissue damage and functional outcome after traumatic brain injury in mice.

Tumor necrosis factor-alpha (TNFalpha) and Fas are induced after traumatic brain injury (TBI); however, their functional roles are incompletely understood. Using controlled cortical impact (CCI) and mice deficient in TNFalpha, Fas, or both (TNFalpha/Fas-/-), we hypothesized that TNFalpha and Fas receptor mediate secondary TBI in a redundant manner. Compared with wild type (WT), TNFalpha/Fas-/- mice had improved motor performance from 1 to 4 days (P<0.05), improved spatial memory acquisition at 8 to 14 days (P<0.05), and decreased brain lesion size at 2 and 6 weeks after CCI (P<0.05). Protection in TNFalpha/Fas-/- mice from histopathological and motor deficits was reversed by reconstitution with recombinant TNFalpha before CCI, and TNFalpha-/- mice administered anti-Fas ligand antibodies had improved spatial memory acquisition versus similarly treated WT mice (P<0.05). Tumor necrosis factor-alpha/Fas-/- mice had decreased the numbers of cortical cells with plasmalemma damage at 6 h (P<0.05 versus WT), and reduced matrix metalloproteinase-9 activity in injured brain at 48 and 72 h after CCI. In immature mice subjected to CCI, genetic inhibition of TNFalpha and Fas conferred beneficial effects on histopathology and spatial memory acquisition in adulthood (both P<0.05 versus WT), suggesting that the beneficial effects of TNFalpha/Fas inhibition may be permanent. The data suggest that redundant signaling pathways initiated by TNFalpha and Fas play pivotal roles in the pathogenesis of TBI, and that biochemical mechanisms downstream of TNFalpha/Fas may be novel therapeutic targets to limit neurological sequelae in children and adults with severe TBI.     

抗体阴性重症肌无力发病与凝集素之间关系研究

借助研究抗体阴性重症肌无力（ＭＧ）发病与凝集素之间的关系，以阐明其发病过程是否与凝集素有关。方法观察伴刀豆球蛋白Ａ（ＣｏｎＡ）和麦胚凝集素（Ｔｒｉｔｉｃｕｍ）及其凝集素－糖复合物对ＴＥ６７１细胞表达的乙酰胆碱受体（ＡＣｈＲ）功能的作用，以及对α－ＢｕＴｘ结合试验的影响。结果有两种凝集素对ＡＣｈＲ功能均有抑制作用，抑制率（％）分别为５４±１４（ｎ＝１１）和４７±１６（ｎ＝１０），此作用可被３种糖抑制，抑制率（％）分别为：９５±５（ｎ＝５）和８４±８（ｎ＝５）；６９±６（ｎ＝４）和６５±５（ｎ＝４）；３９±４（ｎ＝５）和５７±６（ｎ＝５）；ＣｏｎＡ抑制α－ＢｕＴｘ结合试验，而Ｔｒｉｔｉｃｕｍ则不能。结论Ｔｒｉｔｉｃｕｍ和抗体阴性ＭＧ患者非ＩｇＧ部分对ＡＣｈＲ功能和α－ＢｕＴｘ结合试验的作用类同或一致，表明抗体阴性ＭＧ患者非ＩｇＧ部分中的内源性Ｔｒｉｔｉｃｕｍ样糖蛋白在其发病过程中起重要作用。     

A case of recrudescent groove pancreatitis, which was in remission by proximal gastrectomy with vagotomy for gastric cancer]

This report describes our experience with a 60 year old male who suffered from a recrudescence of groove pancreatitis. He had been treated by conservative medication therapy by proton pump inhibitor used for therapy of duodenal ulcer, and was in remission. During a follow-up one year later, endoscopy revealed gastric cancer, for which a proximal gastrectomy and vagotomy were performed. The patient continues to remain in remission for the groove pancreatitis. Our experience with the clinical course of this disease, in which treatment for duodenal ulcer was used effectively, offers new insights into the progression and therapy of groove pancreatitis.     

Nucleotide changes around the splicing acceptor of intron 24 in the factor VIII gene and its impact on splicing.

Nucleotide 6724 of the factor VIII gene harbors a polymorphism of low frequency. A report from Taiwan claimed that 97.9% of the 83 alleles examined were of the A nucleotide at this position, which is quite different to the data from Western populations. Furthermore, this nucleotide is the start of exon 25, located in juxtaposition to the splicing acceptor of intron 24. We wonder if the nucleotide change at this location might have any effect on the splicing process of pre-mRNA. Using genomic DNA with direct sequencing of the polymerase chain reaction-amplified intron 24/exon 25 junction site, we found that 59 of the 60 patient samples were of the GTG sequence at nucleotides 6724-6726. The polymorphism is similar between populations in Taiwan and Western countries. The sequence of intron 24 around the splicing acceptor was always TCCAACTCTATTGCCCTCAG (-20 to -1), except for one hemophiliac patient who had a mutation in which the absolute consensus AG doublet of the intron 24 splicing acceptor changed to the AA dinucleotide. Owing to the mutation, exon 24 was erroneously spliced to exon 26, and exon 25 was skipped. This finding further testifies to the importance of the invariant AG dinucleotide in the example of the factor VIII gene.     

奎的平与氯氮平治疗精神分裂症对照研究

目的：探讨奎的平、氯氮平对精神分裂症的疗效及副作用。方法：80例患者随机分为两组，分别应用奎的平或氯氮平治疗6周，采用四级临床疗效评定标准、阳性症状与阴性症状量表(PANSS)、副反应量表(TESS)评定疗效及副反应。结果：奎的平组有效率87．5％，氯氮平组有效率82．5％。治疗第一周末，奎的平组PANSS量表总分较治疗前差异有显著性(P＜0．05)。奎的平组副反应低于氯氮平组。结论：奎的平与氯氮平疗效相似，但奎的平起效较快，副反应较轻。     

对称性颅脑损伤的临床诊断与治疗(附123例报告)

目的提高治疗对称性颅脑损伤临床疗效。方法总结123例对称性颅脑损伤患者的临床资料,对其临床特点和治疗情况进行回顾性分析。结果预后良好64例(52.0%),中残25例(20.3%),重残8例(6.5%),植物生存4例(3.3%),死亡22例(17.9%)。结论对称性颅脑损伤是一种较为危重的特殊损伤类型,重视其临床特点,严密观察病情变化,正确把握治疗适应证,方可提高疗效。     

LPS信号转导分子TLR4表达与小鼠肝损伤的关系

目的：探讨脂多糖(1ipopolysaccharide，LPS)信号转导分子，TLR4(Toil-like receptor 4,TLR4)与肝脏损伤的关系。方法：小鼠腹腔注射LPS后不同时间点取肝脏组织，HE染色观察病理改变，RT-PCR法检测肝组织，TLR4 mRNA的表达。结果：腹腔注射LPS后24h小鼠肝脏出现明显炎性浸润、坏死，肝组织TLR4 mRNA的表达在注射LPS后6，12h明显抑制，24h则基本恢复。结论：LPS致肝损伤呈时间依从性；LPS信号转导分子TLR4在介导LPS肝损伤中起重要作用。。     

经肝动脉灌注三氧化二砷对肝移植瘤血管的作用

目的 :探讨经肝动脉灌注As2 O3 对肝移植瘤血管的作用 .方法 :采用新西兰大白兔建立 5 0只肝脏Vx 2移植瘤动物模型 ,随机平均分成 5组 .移植瘤术后 2wk ,经肝动脉插管灌注不同浓度As2 O3 ,并以顺铂和生理盐水作对照 ,连续 7d ,6wk末切取肝肿瘤组织 ,观察肿瘤组织微血管有无改变 ,检测移植瘤组织血管内皮生长因子 (VEGF)的表达 .结果 :实验组肿瘤组织毛细血管内皮细胞肿胀、细胞核碎裂、细胞坏死及微血栓形成 ,阴性对照组和阳性对照组无类似改变 .实验组VEGF表达低于对照组 ,差异有显著性 (P <0 .0 1 ) ,而实验组间VEGF表达无差异性 (P =1 .0 0 ) .结论 :经肝动脉灌注As2 O3可减少肿瘤组织的血管生成 ;选择性破坏肝移植瘤组织血管 ,并存在一定剂量效应相关性