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.     

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。     

The refined crystal structure of cowpea mosaic virus at 2.8 A resolution

Comoviruses are a group of plant viruses in the picornavirus superfamily. The type member of comoviruses, cowpea mosaic virus (CPMV), was crystallized in the cubic space group I23, a = 317 A and the hexagonal space group P6(1)22, a = 451 A, c = 1038 A. Structures of three closely similar nucleoprotein particles were determined in the cubic form. The roughly 300-A capsid was similar to the picornavirus capsid displaying a pseudo T = 3 (P = 3) surface lattice. The three beta-sandwich domains adopt two orientations, one with the long axis radial and the other two with the long axes tangential in reference to the capsid sphere. T = 3 viruses display one or the other of these two orientations. The CPMV capsid was permeable to cesium ions, leading to a disturbance of the beta-annulus inside a channel-like structure, suggesting an ion channel. The hexagonal crystal form diffracted X rays to 3 A resolution, despite the large unit cell. The large ( approximately 200 A) solvent channels in the lattice allow exchange of CPMV cognate Fab fragments. As an initial step in the structure determination of the CPMV/Fab complex, the P6(1)22 crystal structure was solved by molecular replacement with the CPMV model determined in the cubic cell.     

亮氨酸脑啡肽样和P物质样免疫反应物在大鼠延髓迷走神经背核簇和网状结构内的分布

用PAP法研究亮氨酸脑啡肽样(L—ENK—LI)和P物质样(SP—LI)免疫反应物在大鼠延髓迷走神经背核簇和网状结构内的分布。证明在孤束核、迷走神经背核、外侧网状核外侧部及其外侧的区域内有大量的L-ENK样终末和纤维,在背侧和腹侧网状核之间的移行区内有中等量的分布,其余区内为少量。L-ENK样胞体在孤束核、咀侧腹外侧网状核、巨细胞网状核的腹侧部和α部、外侧旁巨细胞核以及中缝大核内均有许多分布,在迷走神经背核的尾侧部、背侧和腹侧网状核之间的移行区有中等量,其余区内为少量。SP样反应物的分布与L-ENK样物类似,但其终末和纤维的数量较L-ENK者略少,阳性胞体的数量除了在中缝核及外侧旁巨细胞核内侧端中的量较L-ENK样胞体多以外,在其余区内均较少。     

Differential targets of CpG island hypermethylation in primary and metastatic head and neck squamous cell carcinoma (HNSCC)

Head and neck squamous cell carcinomas (HNSCC) often metastasise to the cervical lymph nodes. It is known for HNSCC as well as other cancers that progression from normal tissue to primary tumour and finally to metastatic tumour is characterised by an accumulation of genetic mutations. DNA methylation, an epigenetic modification, can result in loss of gene function in cancer, similar to genetic mutations such as deletions and point mutations. We have investigated the DNA methylation phenotypes of both primary HNSCC and metastatic tumours from 13 patients using restriction landmark genomic scanning (RLGS). With this technique, we were able to assess the methylation status of an average of nearly 1300 CpG islands for each tumour. We observed that the number of CpG islands hypermethylated in metastatic tumours is significantly greater than what is found in the primary tumours overall, but not in every patient. Interestingly, the data also clearly show that many loci methylated in a patient's primary tumour are no longer methylated in the metastatic tumour of the same patient. Thus, even though metastatic HNSCC methylate a greater proportion of CpG islands than do the primary tumours, they do so at different subsets of loci. These data show an unanticipated variability in the methylation state of loci in primary and metastatic HNSCCs within the same patient. We discuss two possible explanations for how different epigenetic events might arise between the primary tumour and the metastatic tumour of a person.     

Differential effect of brain-derived neurotrophic factor on high-threshold mechanosensitivity in a rat neuropathic pain model

We investigated the effect of the systemic infusion of brain derived neurotrophic factor (BDNF) on the behavioral response in a rat neuropathic pain model. One microgram per hour infusion of BDNF significantly attenuated mechanical hyperalgesia tested by the pin-prick test, however, 20 microg/h-BDNF infusion, on the contrary, enhanced the response. Neither 0.5 nor 10 microg/h-BDNF infusion influenced the mechanical hyperalgesia. Mechanical allodynia and thermal hyperalgesia, tested using a von Frey filament (23.0 mN) and the plantar test, were not influenced by BDNF treatment. These data suggest that systemic BDNF treatment can specifically alter high-threshold mechanosensitivity.     

Changes of interleukin expression correlate with Helicobacter pylori infection and lymph node metastases in gastric carcinoma.

Helicobacter pylori (HP) infection induces expression of IL-8 and IL-10 in benign gastric epithelium. This study compared the expression of cytokines in CD4+ and CD8+ lymphocyte subsets of peripheral blood lymphocytes (PBL), benign mucosal lymphocytes (ML), and tumor infiltrative lymphocytes (TIL) as well as in the benign and malignant epithelial cells of the same patient, with respect to the presence of HP infection, lymph node metastases, and tumor histologic type. The mRNA of the cytokines was measured by a semiquantitative RT-PCR method. The levels were ranked and compared using the Wilcoxon sign-ranked test. Compared with CD8+ ML, the CD8+ TIL expresses higher levels of IL-6 and IL-8 but lower level of IL-4 in patients with lymph node metastases. In patients with HP infection, expression of IL-8 and IL-10 was higher in the gastric carcinoma cells than in the benign epithelial cells while expression of IL-6 and IL-8 were higher in CD8+ TIL than CD8+ ML. Overexpression of IL-8 in HP associated gastric carcinomas suggested that they might have arisen from HP-infected epithelial cells.     

生物陶瓷微颗粒引发的细胞和组织损害

为论证生物陶瓷烧结不完全形成的微颗粒（〈5μm）引发细胞和组织损害的假设，对该类颗粒在体内和体外的细胞和组织损害进行了研究：（1）对4种双相生物陶瓷（BCP）进行细胞毒性试验。试验发现所有的浸出液出现细胞毒性，但是浸出液经离心后，毒性消失；（2）对羟基磷灰石（HA）、p磷酸三钙（pTCP）和40％pTCP／60％HA混合物微颗粒进行细胞抑制实验。结果显示随着微颗粒的浓度增加，成纤维细胞活力下降；而当微颗粒浓度达到一万个／细胞时，细胞活力和增殖能力完全消失；（3）HA，pTCP和BCP陶瓷颗粒（500-1500um）被植入到兔子股骨远端，种植12周后β-TCP的降解率为40％，BCP为5％，但是HA接近不降解。新骨形成在β-TCP（21％）和HA（18％）比BCP（12％）更为明显。同时BCP颗粒的周围有很多的微颗粒形成，可见吞噬细胞吞噬微颗粒，形成吞噬体。以上结果提示，微颗粒可能是局部炎症和细胞损害的首要原因，而且有可能影响骨形成。因此，我们必须注意生物陶瓷烧结的重要性，它们的烧结不良就可形成微颗粒，引发细胞和组织的损害。特别是BCP陶瓷含有两种需要不同烧结温度的粉体，它的烧结难度较高，很易形成微颗粒。