Bile mediates intestinal pathology in endotoxemia in rats

Intestinal pathology frequently accompanies experimental endotoxic shock and is mediated by proinflammatory cytokines. Our hypotheses are that hepatobiliary factors operating from the luminal side of the gut make a major contribution to this damage and that tumor necrosis factor alpha (TNF-alpha) is involved in the pathology. We treated rats with lipopolysaccharide (LPS) intravenously and found that external drainage of bile totally protected the gastrointestinal tract, macroscopically and microscopically, 4 h after LPS administration and dramatically improved survival of the animals for 48 h after LPS administration. The concentration of TNF-alpha in bile increased markedly after LPS administration and was over 30 times higher in bile than in serum. Tissue damage and the biliary TNF-alpha response were abrogated when animals were pretreated with gadolinium chloride to eliminate Kupffer cells. TNF-alpha infusion into the duodenal lumen caused intestinal damage similar to that elicited by intravenous LPS. In rats treated with LPS, survival was significantly increased during the first 36 h in animals given an infusion of anti-TNF-alpha antibody into the duodenum. These results demonstrate that in endotoxemia, intestinal damage is mediated by factors derived from the bile. The findings indicate that luminally acting TNF-alpha contributes to the intestinal damage.     

The UDP-galactose translocator gene is mapped to band Xp11.23-p11.22 containing the Wiskott-Aldrich syndrome locus

We have cloned a segment of the human gene encoding UDP-galactose translocator by genetic complementation of its defective mutant in mouse FM3A cells. Chromosome mapping using fluorescentin situ hybridization revealed that the cloned gene hybridized to the Xp11.23-11.23 region of the X chromosome. This region is shared by the locus of Wiskott-Aldrich syndrome, an X-linked recessive immunodeficiency disorder, characterized by defective sugar chains on cell surface components. Genetic and phenotypic similarities suggest a possible link between UDP-galactose translocator and the Wiskott-Aldrich syndrome (WAS).     

虚拟咬合运动初步仿真模拟的研究与实现

我们试验了利用VR技术进行虚拟咬合仿真制作的全部过程。首先,采用光学三维测量仪对上下颌石膏模型进行数字化,通过预处理获取有效的三角网格曲面模型;其次,对咬合运动模型进行合理的简化,分解为一系列的平移运动和旋转运动;通过动态刷新完成开闭口运动、侧移运动的计算机运动仿真,可视化地观察咬合运动;然后利用模型碰撞检测算法动态地计算咬合接触位,并详细地分析了咬合接触时的咬合点位置分布和咬合剖切面上的咬合点接触关系;最后讨论了目前虚拟咬合仿真存在的问题和今后研究的方向。     

The kinase haspin is required for mitotic histone H3 Thr 3 phosphorylation and normal metaphase chromosome alignment

Post-translational modifications of conserved N-terminal tail residues in histones regulate many aspects of chromosome activity. Thr 3 of histone H3 is highly conserved, but the significance of its phosphorylation is unclear, and the identity of the corresponding kinase unknown. Immunostaining with phospho-specific antibodies in mammalian cells reveals mitotic phosphorylation of H3 Thr 3 in prophase and its dephosphorylation during anaphase. Furthermore we find that haspin, a member of a distinctive group of protein kinases present in diverse eukaryotes, phosphorylates H3 at Thr 3 in vitro. Importantly, depletion of haspin by RNA interference reveals that this kinase is required for H3 Thr 3 phosphorylation in mitotic cells. In addition to its chromosomal association, haspin is found at the centrosomes and spindle during mitosis. Haspin RNA interference causes misalignment of metaphase chromosomes, and overexpression delays progression through early mitosis. This work reveals a new kinase involved in composing the histone code and adds haspin to the select group of kinases that integrate regulation of chromosome and spindle function during mitosis and meiosis.     

STAT3 couples with 14-3-3σ to regulate BCR signaling,B-cell differentiation,and IgE production

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Mutational analysis of the yeast multidrug resistance ABC transporter Pdr5p with altered drug specificity

Multidrug resistance ABC transporter Pdr5p of Saccharomyces cerevisiae is particularly important due to its ability to export a wide range of unrelated substrates. To clarify its function, we generated Pdr5p mutants by random mutagenesis and screened for mutants with altered drug specificity in vivo by using 5 drug compounds. Nine point mutations that caused significant changes in drug specificity distributed throughout the length of Pdr5p, namely, in the extracellular, transmembrane or cytoplasmic regions of the transporter. We then investigated their effects upon drug resistance, using 36 chemically related or distinct substrates. From this study, overall geometry of the Pdr5p was suggested to contribute in acquiring the enormous range of drug specificity. Based on their ability to inhibit the growth of the mutant strains, the 36 tested drugs were classified into: drugs to which the mutants responded differently (Group 1), drugs to which all the mutants showed sensitivity (Group 2), and drugs to which all the mutants exhibited resistance (Group 3). The ability of the compounds to be partitioned to the plasma membrane seemed an important factor for recognition by Pdr5p.     

Astrocytes give rise to oligodendrogliomas and astrocytomas after gene transfer of polyoma virus middle T antigen in vivo

The cells of origin for oligodendrogliomas and astrocytomas are not known but are presumed to be oligodendrocyte and astrocyte precursors, respectively. In this paper we report the generation of mixed gliomas from in vivo transformation of glial fibrillary acidic protein (GFAP)-positive cells (differentiated astrocytes) with polyoma virus middle T antigen (MTA). MTA is a powerful oncogene that activates a number of signal transduction pathways, including those proposed to be involved in gliomagenesis, and has been shown to induce tumors in many cell types. We have achieved transfer of MTA expression specifically to GFAP(+) cells in vivo using somatic cell gene transfer, and find resultant formation of anaplastic gliomas with mixed astrocytoma and oligodendroglioma morphological features. We conclude that GFAP- expressing astrocytes, with appropriate signaling abnormalities, can serve as the cell of origin for oligodendrogliomas, astrocytomas, or mixed gliomas.     

大白鼠下丘脑促肾上腺皮质激素(ACTH)样免疫反应神经元的分布及功能意义

本文应用免疫细胞化学技术观察大白鼠下丘脑促肾上腺皮质激素样神经元胞体,纤维及串珠样膨体的分布。胞体位于弓状核、下丘脑前核的腹侧、视上背侧连合、室周层的腹侧区及乳头体核腹侧。纤维及串珠样膨体广泛地分布于下丘脑,串珠样膨体在室旁核和室周层密集。串珠样膨体贴室管膜分布,伸至室管膜下神经毯,有的穿行室管膜上皮细胞之间并多与室管膜上皮细胞接触或穿过室管膜上皮细胞之间至第三脑室腔。在第三脑室侧壁的室管膜上皮细胞之间偶见促肾上腺皮质激素反应细胞。室旁核区促肾上腺皮质激素免疫反应串珠样膨体可能作用于催产素和后叶加压素神经元,控制催产素和后叶加压素的分泌和释放。室周层的串珠样膨体直接与脑脊液接触可认为是促肾上腺皮质激素神经元释放分泌产物的另一途径。     

乳腺富糖原透明细胞癌2例报道及文献复习

目的 探讨乳腺富糖原透明细胞癌临床病理特点及鉴别诊断要点。方法 对2例乳腺富糖原透明细胞癌进行临床资料及光镜和免疫组化标记观察。结果 组织学特点：癌细胞为多边形或柱状，胞界清楚，胞质透明，呈实性巢状、片状排列，可有乳头形成。表现为导管内癌和浸润性癌结构。免疫组化染色显示：癌细胞呈上皮性免疫表型，CK(AE1)、CEA强阳性，不表达S-100蛋白、肌动蛋白。PAS染色阳性。结论 富含糖原透明细胞癌是上皮性特殊类型乳腺癌，其诊断主要依靠组织病理学和免疫组化标记。