HBV基因组转染对小鼠NIH3T3细胞内基质金属蛋白酶组织抑制因子的转录调控作用

ObjectiveTo understand the mechanism of liver cirrhosis after the infection of hepatitis B virus.MethodsMouse fibroblast NIH3T3 cells were transfected with 3.2 kb HBV DND by exposure of the cells to calcium phosphate.The change of the levels of mRNA for tissue inhibitor of metalloproteinase 1and 2(TIMP1,2) was detected in mouse fibroblast NIH3T3 cells and the cells of transfection with HBV Genome by in situ hybridization.ResultsThe levels of mRNA for TIMP1 and TIMP2 were increased significantly.ConclusionHBV infection can induce the expression of the mRNA for TIMP1 and TIMP2.     

Protein phosphatase PP1 is required for normal DNA methylation in Neurospora

Covalent modifications of histones integrate intracellular and extracellular cues to regulate the genome. H3 Lys 9 methylation (H3K9me) can direct heterochromatin formation and DNA methylation, while phosphorylation of H3 Ser 10 (H3S10p) drives gene activation and chromosome condensation. To examine the relationship between H3S10p, H3K9me, and DNA methylation in Neurospora crassa, we built and tested mutants of the putative H3S10 phosphatase, PP1. A PP1-impaired mutant showed increased H3S10p and selective reduction of methylation of H3K9 and DNA. Similarly, amino acid substitutions of H3S10 abolished methylation of H3K9 and DNA. Thus, H3S10 dephosphorylation by PP1 is required for DNA methylation of some loci.     

The dysregulated glomerular cell growth in Denys–Drash syndrome

While diffuse mesangial sclerosis is traditionally described as being the glomerulopathy of Denys–Drash syndrome (DDS), the podocyte proliferative lesions may be overlooked in these DDS cases. In the present study, an evolving process is extrapolated from a selected case of DDS that demonstrated glomerulopathy with conspicuous podocyte proliferation. The observation that podocytes express proliferation markers (Ki67, proliferating-cell nuclear antigen and topoisomerase II) in non-proliferative, mature-looking glomeruli suggests an initial pathogenic act to activate or to keep podocytes from quiescence. The subsequent proliferation of podocytes is in keeping with downregulation of WT1 and cyclin kinase inhibitors of p16 and p21. The emergence of cytokeratin-positive cells in glomeruli that show typical mesangial sclerosis implies elimination of podocytes and replacement with tubular and/or parietal epithelial cells. The final scene of evolving glomerulopathy displays apoptosis and expression of Fas-L and Bax in sclerotic mesangial lesions, which eventually end up with global sclerosis. This novel concept of DDS glomerulopathy implies complex molecular mechanisms involved in glomerular injury.     

人TFPI基因转染对兔移植静脉血栓形成和近期通畅率的影响

目的： 为减少冠状动脉旁路移植术后血栓形成，探讨人组织因子途径抑制因子(TFPI)基因转染对兔移植静脉血栓生成的影响。方法：构建真核表达质粒pCMV-(Kozak)TFPI。采用阳离子脂质体和腔内加压灌注法，转染移植静脉内皮细胞。RT-PCR、Western blotting和免疫组化法检测外源基因在兔移植静脉中的表达。病理标本、扫描电镜观察移植静脉血栓形成情况，血管多普勒观测其通畅率。结果：移植静脉中有人TFPI基因和蛋白表达。静脉移植术后3 d，基因转染组、空载体和空白对照组分别有1条、8条和7条移植静脉发生血栓，术后30 d，以上各组分别有0条、5条和5条移植静脉完全闭塞，前者静脉血栓发生率和闭塞率均低于后两者(P<0.05)。扫描电镜显示两对照组内皮表面有红细胞和血小板黏附、聚集，而转染组基本正常。结论：人TFPI基因干预，减少了兔移植静脉血栓形成，提高了近期通畅率。     

Histone deacetylase activity is necessary for chromosome condensation during meiotic maturation in Xenopus laevis

Chromosome condensation is thought to be an essential step for the faithful transmission of genetic information during cellular division or gamete formation. The folding of DNA into metaphase chromosomes and its partition during the cell cycle remains a fundamental cellular process that, at the molecular level, is poorly understood. Particularly, the role of histone deacetylase (HDAC) activities in establishing and maintaining meiotic metaphase chromosome condensation has been little documented. In order to better understand how metaphase chromosome condensation is achieved during meiosis, we explored, in vivo, the consequences of HDAC activities inhibition in a Xenopus oocyte model. Our results show that deacetylase activity plays a crucial role in chromosome condensation. This activity is necessary for correct chromosome condensation since the earlier stages of meiosis, but dispensable for meiosis progression, meiosis exit and mitosis entry. We show that HDAC activity correlates with chromosome condensation, being higher when chromosomes are fully condensed and lower during interphase, when chromosomes are decondensed. In addition, we show that, unlike histone H4, Xenopus maternal histone H3 is stored in the oocyte as a hypoacetylated form and is rapidly acetylated when the oocyte exits meiosis.     

Prevention of cerebral vasospasm with OKY-046 an imidazole derivative and a thromboxane synthetase inhibitor. A preliminary co-operative clinical study

Summary The prevention of cerebral vasospasm with OKY-046, an imidazole derivative and a thromboxane synthetase inhibitor, was studied co-operatively at ten neurosurgical services. Intravenous administrations of 2, 5 or 10 /kg/minute of OKY-046 were given continuously from the earliest possible day to the 14th SAH-day to 82 pateints with ruptured cerebral aneurysm. Sixty-eight patients (83%) showed moderate to high high-density (SAH) in their initial CTs. Angiographic vasospasms were seen in 58 patients, representing 71% of all cases or 81% of the 72 cases for which angiograms were available; the vasospasms of 45 patients (55 or 63%) were moderate to severe. Symptomatic vasospasm occurred, however, only in 27 patients (33%); in 18 of those cases, moreover, the symptoms were mild or transient. The conditions of the patients at one month after the SAH were classified into 9 grades from 0 (normal) to 8 (deceased). Fifty-two patients (63%) were classified as 0 or 1, and 64 (78%) as better than 3 (possible daily life unaided). The administration of OKY-046 was proven to decrease TXB₂ in the blood.This paper emphasizes the effectiveness of the drug for symptomatic vasospasm, and supports our previous contention that cerebral microthrombosis may play an important role in the pathogenesis of cerebral vasospasm.     

Phenylethylamine-induced stereotypies in the rat: a behavioral test system for assessment of MAO-B inhibitors

Stereotyped sniffing behavior together with forepaw padding — defined as the -phenylethylamine (PEA) syndrome — is induced by MAO-B inhibitors in rats injected with 30 mg/kg IP PEA. The comparison of the abilities of the MAO-B inhibitors to induce the syndrome and to inhibit MAO-B in rat brain homogenates indicated that at least 75% of MAO-B activity in rat brain had to be inhibited to induce the PEA syndrome. A good correlation was found between the abilities of MAO-B inhibitors to induce the behavioral syndrome and to increase levels of PEA in rat brain. Specific MAO-A inhibitors potentiated the behavioral effect of the MAO-B inhibitor deprenyl, while they did not induce the syndrome themselves or only at very high doses. Inhibitors of the reuptake of 5-HT or noradrenaline were inactive under the described experimental conditions. This behavioral test system seems to be useful in vivo screening test in rats for detecting compounds with strong MAO-B inhibiting activity.