桥小脑角区脑膜瘤显微外科手术17例分析

目的:探讨桥小脑角脑膜瘤的临床表现及相应的手术治疗方案,提高显微外科手术治疗效果.方法:回顾分析我院近5年来收治的17例桥小脑角脑膜瘤患者,均采用枕下乙状窦后手术入路.结果:本组肿瘤全切率为88.3%面神经和位听神经功能大部分保留,无死亡病例.结论:术前详细的检查和完善的手术方案制订对桥小脑角区脑膜瘤的手术治疗至关重要,显微外科手术是治疗桥小脑角区脑膜瘤安全有效的方法     

PTEN和EGFR在胃癌中的表达及相关性研究

目的:检测第10号染色体缺失的磷酸酶和张力蛋白同源物基因PTEN及表皮生长因子受体EGFR在胃癌组织中的表达,探讨两者与胃癌肿瘤行为的关系及意义。方法:采用免疫组织化学染色法(S-P法)检测105例胃癌组织及癌旁正常胃组织中EGFR和PTEN蛋白的表达水平,并将检测结果与临床病理参数进行综合分析。结果:胃癌组织PTEN的表达56.19%明显低于正常组织中的表达的表达92.3%,而胃癌组织EGFR的表达46.67%明显高于正常组织7.62%,(P<0.01)。二者的表达与性别和年龄无相关性(P>0.05),与胃癌的分化程度、浸润深度、淋巴结转移及临床分期有相关性(P<0.05)。结论:PTEN在胃癌组织中呈低表达,EGFR在胃癌组织中存在高表达,与胃癌的发生、发展有一定关系,并与胃癌的分化程度、浸润深度、淋巴结转移及临床分期密切相关,二者呈负相关。     

Investigations of a prion infectivity assay to evaluate methods of decontamination

Prions are unique infectious agents which have been shown to be transmitted iatrogenically through contaminated surfaces. Surface contamination is a concern on reusable medical devices and various industrial surfaces, but there is currently no standard, accepted model to evaluate surface prion decontamination. In this report, a set of both in vitro and in vivo methods were investigated based on the contamination of surface through artificial exposure to infected brain. An in vitro surface contamination protocol was developed with subsequent biochemical detection of the prion protein (PrPres). In parallel, the in vivo investigations included the contamination of different types of surface materials (stainless steel or plastic wires) with different prion strains (scrapie strain adapted to hamsters 263K or bovine spongiform encephalopathy strain adapted to mouse 6PB1). The in vivo models with various prion strains and brain homogenate dilutions reproducibly transmitted the disease and a relationship was established between the infectivity titre, the transmission rate and the incubation period. Moreover, the in vivo models were studied for their ability to demonstrate the efficacy of heat and chemical-based decontamination methods, with similar results. The in vivo scrapie method described is proposed as a standard to evaluate existing and developing prion decontamination technologies.     

Evidence for a quantitative trait locus affecting low levels of apolipoprotein B and low density lipoprotein on chromosome 10 in Caucasian families

High plasma apolipoprotein B (apoB) and LDL cholesterol levels increase cardiovascular disease risk. These highly correlated measures may be partially controlled by common genetic polymorphisms. To identify chromosomal regions that contain genes causing low plasma levels of one or both parameters in Caucasian families ascertained for familial hypobetalipoproteinemia (FHBL), we conducted a whole-genome scan using 443 microsatellite markers typed in nine multigenerational families with at least two members with FHBL. Both variance components and regression-based linkage methods were used to identify regions of interest. Common linkage regions were identified for both measures on chromosomes 10q25.1-10q26.11 [maximum log of the odds (LOD) = 4.2 for LDL and 3.5 for apoB] and 6q24.3 (maximum LOD = 1.46 for LDL and 1.84 for apoB). There was also evidence for linkage to apoB on chromosome 13q13.2 (LOD = 1.97) and to LDL on chromosome 3p14.1 at 94 centimorgan (LOD = 1.52). Bivariate linkage analysis provided further evidence for loci contributing to both traits (6q24.3, LOD = 1.43; 10q25.1, LOD = 1.74). We evaluated single nucleotide polymorphisms (SNPs) in genes within our linkage regions to identify variants associated with apoB or LDL levels. The most significant finding was for rs2277205 in the 5' untranslated region of acyl-coenzyme A dehydrogenase short/branched chain and LDL (P = 10(-7)). Three additional SNPs were associated with apoB and/or LDL (P < 0.01). Although only the linkage signal on chromosome 10 reached genome-wide statistical significance, there are likely multiple chromosomal regions with variants that contribute to low levels of apoB and LDL and that may protect against coronary heart disease.     

Activation of a dimeric metabotropic glutamate receptor by intersubunit rearrangement

Although many G protein-coupled receptors (GPCRs) can form dimers, a possible role of this phenomenon in their activation remains elusive. A recent and exciting proposal is that a dynamic intersubunit interplay may contribute to GPCR activation. Here, we examined this possibility using dimeric metabotropic glutamate receptors (mGluRs). We first developed a system to perfectly control their subunit composition and show that mGluR dimers do not form larger oligomers. We then examined an mGluR dimer containing one subunit in which the extracellular agonist-binding domain was uncoupled from the G protein-activating transmembrane domain. Despite this uncoupling in one protomer, agonist stimulation resulted in symmetric activation of either transmembrane domain in the dimer with the same efficiency. This, plus other data, can only be explained by an intersubunit rearrangement as the activation mechanism. Although well established for other types of receptors such as tyrosine kinase and guanylate cyclase receptors, this is the first clear demonstration that such a mechanism may also apply to GPCRs.     

Cutting Edge: IFN-gamma-producing CD4 T lymphocytes mediate spore-induced immunity to capsulated Bacillus anthracis

Virulent strains of Bacillus anthracis produce immunomodulating toxins and an antiphagocytic capsule. The toxin component-protective Ag is a key target of the antianthrax immune response that induces production of toxin-neutralizing Abs. Coimmunization with spores enhances the antitoxin vaccine, and inactivated spores alone confer measurable protection. We aimed to identify the mechanisms of protection induced in inactivated-spore immunized mice that function independently of the toxin/antitoxin vaccine system. This goal was addressed with humoral and CD4 T lymphocyte transfer, in vivo depletion of CD4 T lymphocytes and IFN-gamma, and Ab-deficient (muMT(-/-)) or IFN-gamma-insensitive (IFN-gammaR(-/-)) mice. We found that humoral immunity did not protect from nontoxinogenic capsulated bacteria, whereas a cellular immune response by IFN-gamma-producing CD4 T lymphocytes protected mice. These results are the first evidence of protective cellular immunity against capsulated B. anthracis and suggest that future antianthrax vaccines should strive to augment cellular adaptive immunity.     

HP1alpha guides neuronal fate by timing E2F-targeted genes silencing during terminal differentiation

A critical step of neuronal terminal differentiation is the permanent withdrawal from the cell cycle that requires the silencing of genes that drive mitosis. Here, we describe that the alpha isoform of the heterochromatin protein 1 (HP1) protein family exerts such silencing on several E2F-targeted genes. Among the different isoforms, HP1alpha levels progressively increase throughout differentiation and take over HP1gamma binding on E2F sites in mature neurons. When overexpressed, only HP1alpha is able to ensure a timed repression of E2F genes. Specific inhibition of HP1alpha expression drives neuronal progenitors either towards death or cell cycle progression, yet preventing the expression of the neuronal marker microtubule-associated protein 2. Furthermore, we provide evidence that this mechanism occurs in cerebellar granule neurons in vivo, during the postnatal development of the cerebellum. Finally, our results suggest that E2F-targeted genes are packaged into higher-order chromatin structures in mature neurons relative to neuroblasts, likely reflecting a transition from a 'repressed' versus 'silenced' status of these genes. Together, these data present new epigenetic regulations orchestrated by HP1 isoforms, critical for permanent cell cycle exit during neuronal differentiation.     

Impending disaster or sliver of hope for Southeast Asian forests? The devil may lie in the details

Here, I report on how forest area in Southeast Asia has changed for different types of forest and across different countries between the periods of 1990–2000 and 2000–2005. The loss of old growth forests has accelerated in Indonesia, Cambodia and Vietnam but have ceased in Thailand, Malaysia, Laos and the Philippines. Secondary forests continue to be lost in Malaysia, Cambodia, Laos, Myanmar, Indonesia, Thailand and the Philippines. Plantation forests have increased in area by 25.0% from 1990 to 2005 but still comprise only 6.2% of the total forest area in Southeast Asia. Overall, the loss of native forests (old growth and secondary forests) has slowed down in Thailand, the Philippines and Brunei but has worsened in Laos, Myanmar, Indonesia, Malaysia and Cambodia.