Magnetic resonance elastography of the lung: technical feasibility.

Magnetic resonance elastography (MRE) is a phase-contrast technique that can spatially map shear stiffness within tissue-like materials. To date, however, MRE of the lung has been too technically challenging-primarily because of signal-to-noise ratio (SNR) limitations and phase instability. We describe an approach in which shear wave propagation is not encoded into the phase of the MR signal of a material, but rather from the signal arising from a polarized noble gas encapsulated within. To determine the feasibility of the approach, three experiments were performed. First, to establish whether shear wave propagation within lung parenchyma can be visualized with phase-contrast MR techniques, MRE was performed on excised porcine lungs inflated with room air. Second, a phantom consisting of open-cell foam filled with thermally polarized (3)He gas was imaged with MRE to determine whether shear wave propagation can be encoded by the gas. Third, preliminary evidence of the feasibility of MRE in vivo was obtained by using a longitudinal driver on the chest of a normal volunteer to generate shear waves in the lung. The results suggest that MRE in combination with hyperpolarized noble gases is potentially useful for noninvasively assessing the regional elastic properties of lung parenchyma, and merits further investigation.     

Gln与rhGh对肝硬化病人肠黏膜屏障的影响

目的观察Gln与rhGh各单独应用及联合应用对肝硬化病人小肠黏膜屏障形态学和功能学的影响。方法20个肝硬化病人随机分成四组,给予等氮等热量营养支持7d,Gln+rhGh组口服Gln[0.3g/(Kg·d)]和皮下注射rhGh(10U/d);Gln组口服Gln;rhGh组应用皮下注射rhGh;CONT对照组应用相应安慰剂。观察治疗前后患者小肠黏膜通透性和十二指肠黏膜绒毛高度和隐窝深度的变化,分别比较。结果Gln+rhGh组治疗后小肠黏膜通透性有显著性的降低(P<0.05),且显著低于其他三组(P<0.05);十二指肠黏膜绒毛高度和隐窝深度有显著性的增高(P<0.05),且显著高于其他三组(P<0.05)。结论Gln与rhGh联合应用能减低肠道黏膜的通透性和维持其形态学的完整。     

NF-κB在肝细胞癌组织中的表达及意义

目的：探讨NF-κB基因在肝细胞癌组织中的表达及生物学意义。方法：采用逆转录聚合酶链反应(RT-PCR)、Western-blot免疫组织化学技术检测32例肝癌组织及癌旁肝组织中的NF-κB基因的mRNA和蛋白表达水平及蛋白定位。结果：NF-κB基因在肝癌组织中的表达较癌旁肝组织显著性增高(P<0.05)。免疫组化结果显示，NF-κB蛋白在肝癌细胞胞浆和胞核中均有表达，而在癌旁肝细胞中仅在胞浆中有表达。结论：NF-κB基因在肝癌组织中呈显著高表达，提示其可能参与了肝癌的发生发展。NF-κB表达定位在癌细胞和癌旁肝细胞中的差异，提示NF-κB活化后，进入胞核，通过调节下游基因的转录，促进肝癌的发生。     

原发性肝癌患者外周血GPC-3mRNA的表达与微转移的关系

目的探讨原发性肝细胞癌（HCC）患者外周血的Glypican-3（GPC-3）mRNA检测用于诊断HCC早期微转移的可行性。方法采用巢式逆转录聚合酶链反应（RT-PCR）技术检测39例原发性肝细胞癌（HCC）、19例肝炎和肝硬化、10例转移性肝癌、10例肝血管瘤患者、19例健康献血员外周血GPC-3mRNA水平。结果HCC患者外周血中，GPC-3mRNA的检出率为62％（24／39），GPC-3mRNA的检出率与肿瘤直径77％（17／22）、癌结节数目67％（19／24）、临床TNM分期76％（19／25）、门静脉癌栓90％（9／10）、远处转移100％（6／6）等临床参数密切相关。GPC-3mRNA在转移性肝癌、肝炎和肝硬化、肝血管瘤患者及健康献血员外周血中均未检出。结论巢式RT—PCR检测HCC患者外周血单核细胞GPC-3mRNA是一种早期发现原发性肝细胞癌血道播散的可靠而又敏感的实验方法。     

口服抗原对巨噬细胞共刺激分子CD80/CD86表达的影响

目的探讨口服抗原对巨噬细胞(M)共刺激分子CD80/CD86表达的影响及其在诱导妊娠免疫耐受中的作用。方法自然流产小鼠(CBA/J×DBA/2)分为免疫组和未免疫组,免疫组分别口服滋养细胞膜抗原(TMA2)和卵清蛋白(OVA),以正常妊娠小鼠(CBA/J×BALB/c)作为对照组。采用双标记流式细胞分析技术,分别检测各组小鼠脾脏及肠系膜淋巴结(MLN)CD80 M和CD86 M的表达。结果MLN内,未免疫组CD80 M表达明显高于对照组(P<0.05),而CD86 M含量明显低于对照组(P<0.001);TMA2免疫组CD80 M含量明显低于未免疫组(P<0.05);OVA免疫组CD86 M含量明显高于未免疫组(P<0.001)。脾脏内,CD80 M表达在各组间比较无显著差异;CD86M表达,未免疫组明显低于对照组(P<0.05),TMA2免疫组显著低于未免疫组(P<0.05),OVA免疫组则显著高于未免疫组(P<0.001)。结论流产的发生与M表面共刺激信号CD80/CD86异常有关;口服适当抗原可改变CD80/CD86 M表达模式,诱导妊娠免疫耐受的形成。     

Cognitive profiles of individual patients with Parkinson's disease and dementia: comparison with dementia with lewy bodies and Alzheimer's disease.

We describe the pattern of cognitive profiles within a community-based sample of patients with Parkinson's disease (PD) and dementia (PDD) using cluster analyses, and compare the results with data from patients with Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). Fifty patients with PDD and 39 with AD from Stavanger, Norway, and 62 patients with DLB from San Diego, CA, USA were diagnosed by either standardized clinical procedures or criteria (all PDD and all AD cases) or necropsy (all DLB cases). Four subgroups were identified: two subgroups with a subcortical cognitive profile (one with mild and one with moderate dementia severity), one subgroup with global impairment and severe dementia, and one subgroup with a cortical cognitive profile and moderate dementia. Of the patients with PDD and with DLB, 56% and 55%, respectively, had a subcortical cognitive profile, compared with only 33% of the AD patients. Conversely, 30% of the patients with PDD and 26% of those with DLB had a cortical cognitive profile, compared with 67% of the patients with AD. These findings suggest that in some patients with PDD, frontosubcortical changes are the main contributing factor to dementia, whereas in other patients, cortical and hippocampal changes are more important.     

Arsenic trioxide exposure to ovarian carcinoma cells leads to decreased level of topoisomerase II and cytotoxicity

The objective of this study was to investigate the effect of arsenic trioxide (As(2)O(3)) on topoisomerase II levels using western blotting method on MDAH 2774 ovarian carcinoma cell culture. Experimental designs were established to determine the cytotoxic effects of As(2)O(3) on MDAH 2774 cells and the IC50 (fatal dose for the 50% of cells) value. Cytotoxicity experiments were carried out using various concentrations of As(2)O(3). The 2,3-bis[2-methyloxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide (XTT) and trypan blue dye-exclusion tests were used to evaluate cytotoxicity. Topoisomerase II expressions were investigated using western blotting method with various concentrations of As(2)O(3). Densitometric analysis of topoisomerase 2 bands was carried out using Quantity One 1-D analysis software (Bio-Rad USA, Life Science Research, Hercules, CA). IC50 value of As(2)O(3) was found to be 5 x 10(-6) M for MDAH 2774 cells. When the bands were evaluated, it was observed that there was a decrease in topoisomerase II levels in MDAH 2774 cells with increasing concentrations of As(2)O(3). It was also observed by the densitometric analysis that topoisomerase II expression ratios of MDAH 2774 cells were decreased by approximately 50% at this concentration. Topoisomerase II levels were significantly decreased with the increasing concentrations of As(2)O(3). Inhibition of topoisomerase II enzyme was one of the antiproliferative influence mechanisms of As(2)O(3).     

Effects of antisense mediated inhibition of cathepsin K on human osteoclasts obtained from peripheral blood.

Cathepsin K is a cystein protease that displays a proteolytic activity against Type I collagen and is abundantly and selectively expressed in osteoclasts where it plays a critical role in bone degradation. Its direct role in bone tissue has been defined by knock-out mice studies and inhibiting strategies in animals models. However, direct proof of cathepsin K function in human osteoclast model in vitro is lacking. The aim of this study is to analyze cathepsin K expression and localization in human osteoclasts obtained from peripheral blood and to examine cathepsin K function in these cells by antisense oligodeoxynucleotide (AS-ODN) strategy. AS-ODN was added to the culture of osteoclast precursors induced to differentiate by RANKL and M-CSF. AS-ODN treatment produced a significant down-regulation of cathepsin K mRNA (>80%) and protein expression, as verified respectively by Real-time PCR and by immunocytochemistry or Western blot. The cathepsin K inhibition caused an impairment of resorption activity as evaluated by a pit formation assay ( p = 0.045) and by electron microscopy, while the acidification process was unaffected. We demonstrated that antisense strategies against cathepsin K are selectively effective to inhibit resorption activity in human osteoclasts, like in animal models.     

Chemokine receptor CCR6 as a prognostic factor after hepatic resection for hepatocellular carcinoma

Background and Aims: Chemokines and their receptors have recently been shown to have major roles in cancer metastasis. The aim of this study was to determine whether the interaction between chemokine receptor 6 (CCR6) and its ligand, macrophage inflammatory protein‐3 alpha (MIP‐3α), correlates with metastasis of hepatocellular carcinoma (HCC). Methods: To observe the reaction of CCR6 expressed cancer cells to MIP‐3α stimulation, chemotactic and actin polymerization assays for both CCR6 high cells (HepG2) and CCR6 low cells (MCF‐7) were performed. CCR6 mRNA levels in tumor specimens from 30 HCC patients were quantified by real‐time polymerase chain reaction. Patients were classified into two groups, high (≥ 20 copies; n = 10) CCR6 and low (<20 copies; n = 20) CCR6 on the basis of CCR6 expression, and the groups were compared with respect to clinicopathological features. Results: When HepG2 cells (CCR6 high) were stimulated with MIP‐3α, they migrated in a dose‐dependent manner, and formation of pseudopodia was observed. These phenomena were not observed in the CCR6 low cells. The incidence of intrahepatic metastasis was higher in the high CCR6 expression group than in the low CCR6 expression group (P < 0.05). Disease‐free survival was significantly poorer in the high CCR6 expression group than in the low CCR6 expression group (P < 0.05). Conclusions: It was indicated that CCR6 might be associated with intrahepatic metastasis of HCC and might be able to become one of the prognostic factor after hepatic resection for HCC.