• 【欧洲男性和非洲女性对非裔美国人基因组的贡献增加。】 复制标题 收藏 收藏
    DOI:10.1007/s00439-006-0261-7 复制DOI
    作者列表:Lind JM,Hutcheson-Dilks HB,Williams SM,Moore JH,Essex M,Ruiz-Pesini E,Wallace DC,Tishkoff SA,O'Brien SJ,Smith MW
    BACKGROUND & AIMS: :The differential relative contribution of males and females from Africa and Europe to individual African American genomes is relevant to mapping genes utilizing admixture analysis. The assessment of ancestral population contributions to the four types of genomic DNA (autosomes, X and Y chromosomes, and mitochondrial) with their differing modes of inheritance is most easily addressed in males. A thorough evaluation of 93 African American males for 2,018 autosomal single nucleotide polymorphic (SNP) markers, 121 X chromosome SNPs, 10 Y chromosome haplogroups specified by SNPs, and six haplogroup defining mtDNA SNPs is presented. A distinct lack of correlation observed between the X chromosome and the autosomal admixture fractions supports separate treatment of these chromosomes in admixture-based gene mapping applications. The European genetic contributions were highest (and African lowest) for the Y chromosome (28.46%), followed by the autosomes (19.99%), then the X chromosome (12.11%), and the mtDNA (8.51%). The relative order of admixture fractions in the genomic compartments validates previous studies that suggested sex-biased gene flow with elevated European male and African female contributions. There is a threefold higher European male contribution compared with European females (Y chromosome vs. mtDNA) to the genomes of African American individuals meaning that admixture-based gene discovery will have the most power for the autosomes and will be more limited for X chromosome analysis.
    背景与目标: : 非洲和欧洲的男性和女性对非裔美国人单个基因组的不同相对贡献与利用混合分析定位基因有关。在男性中,最容易解决祖先种群对四种类型的基因组DNA (常染色体,X和Y染色体以及线粒体) 及其不同遗传方式的贡献的评估。提出了对93名非洲裔美国男性的2,018个常染色体单核苷酸多态性 (SNP) 标记,121个X染色体SNP,10个由SNP指定的Y染色体单倍群以及6个定义mtDNA SNP的单倍群的全面评估。在X染色体和常染色体混合组分之间观察到的明显缺乏相关性支持在基于混合的基因作图应用中对这些染色体进行单独处理。欧洲对Y染色体的遗传贡献最高 (非洲最低) (28.46%),其次是常染色体 (19.99%),然后是X染色体 (12.11%) 和mtDNA (8.51%)。基因组区室中混合组分的相对顺序验证了先前的研究,这些研究表明,性别偏向的基因流具有较高的欧洲男性和非洲女性贡献。与欧洲女性相比,欧洲男性对非裔美国人个体基因组的贡献高出三倍 (Y染色体与mtDNA),这意味着基于混合物的基因发现将对常染色体具有最大的力量,并且对X染色体分析。
  • 【听力下降的听众的语音掩蔽释放: 掩蔽率对识别分数和语音特征接收的影响。】 复制标题 收藏 收藏
    DOI:10.1080/14992020600753213 复制DOI
    作者列表:Lorenzi C,Husson M,Ardoint M,Debruille X
    BACKGROUND & AIMS: :Consonant identification was measured for a stationary and amplitude-modulated noise masker in four listeners with flat cochlear hearing loss, and four age-matched normal-hearing listeners. The masker modulation rate was systematically varied between 2 and 128 Hz. Masking release (MR), that is better identification performance in fluctuating, than in stationary noise, was highest in a masker fluctuating at 8-16 Hz in all normal-hearing listeners. In comparison, MR was only observed in two out of the four impaired listeners. In these listeners, MR was poorer than normal, and peaked at lower rates, that is 2 or 8 Hz. MR corresponded to increased reception of information for voicing, place, and manner between 2 and 64 Hz in all normal-hearing listeners. In impaired listeners, increased reception of information was mainly observed for manner, and mainly reduced for place, but these differences were not significant. For all phonetic features, MR was observed at lower masker fluctuation rates (< or =32 Hz) than in normal-hearing listeners. This study therefore shows that cochlear damage affects MR, both quantitatively and qualitatively.
    背景与目标: : 在四个患有扁平耳蜗听力损失的听众和四个年龄匹配的正常听力听众中,测量了固定和幅度调制的噪声masker的辅音识别。掩蔽器调制速率在2和128Hz之间系统地变化。在所有正常听力的听众中,掩蔽释放 (MR) 在波动中比在固定噪声中更好的识别性能,在8-16Hz波动的掩蔽器中最高。相比之下,仅在四个受损听众中的两个中观察到MR。在这些听众中,MR比正常人差,并且以较低的速率 (即2或8Hz) 达到峰值。MR对应于所有正常听力的听众在2到64Hz之间的发声,位置和方式的信息接收增加。在受损的听众中,主要观察到方式的信息接收增加,而地点的信息接收则主要减少,但这些差异并不显着。对于所有语音特征,与正常听力的听众相比,以较低的掩蔽率 (<或 = 32Hz) 观察到MR。因此,这项研究表明,耳蜗损伤在定量和定性上都会影响MR。
  • 【数学与语言处于同一侧吗?右半球失语症和数学能力。】 复制标题 收藏 收藏
    DOI:10.1016/j.neulet.2006.07.063 复制DOI
    作者列表:Semenza C,Delazer M,Bertella L,Granà A,Mori I,Conti FM,Pignatti R,Bartha L,Domahs F,Benke T,Mauro A
    BACKGROUND & AIMS: :The main purpose of the present study was to learn how mathematical abilities are located and develop in the brain with respect to language. Mathematical abilities were assessed in six right-handed patients affected by aphasia following a lesion to their non-dominant hemisphere (crossed aphasia) and in two left-handed aphasics with a right-sided lesion. Acalculia, although in different degrees, was found in all cases. The type of acalculia depended on the type of aphasia, following patterns that have been previously observed in the most common aphasias resulting from left hemisphere lesions. No sign of right hemisphere or spatial acalculia (acalculia in left lateralised right-handed subjects) was detected. These results suggest that, as a rule, language and calculation share the same hemisphere. A primitive computational mechanism capable of recursion may be the precursor of both functions.
    背景与目标: : 本研究的主要目的是了解语言在大脑中如何定位和发展数学能力。在六名非优势半球病变 (交叉失语症) 后受失语症影响的右手患者和两名右侧病变的左手失语症患者中评估了数学能力。尽管在不同程度上,但在所有情况下都发现了Acalculia。Aalculia的类型取决于失语症的类型,遵循先前在左半球病变引起的最常见失语症中观察到的模式。未检测到右半球或空间无alculia (左侧右手受试者中的无alculia) 的迹象。这些结果表明,通常,语言和计算具有相同的半球。能够递归的原始计算机制可能是这两个功能的前身。
  • 【数字和空间的共享空间表示: SNARC和Simon效应的逆转。】 复制标题 收藏 收藏
    DOI:10.1037/0096-1523.32.5.1197 复制DOI
    作者列表:Notebaert W,Gevers W,Verguts T,Fias W
    BACKGROUND & AIMS: :In 4 experiments, the authors investigated the reversal of spatial congruency effects when participants concurrently practiced incompatible mapping rules (J. G. Marble & R. W. Proctor, 2000). The authors observed an effect of an explicit spatially incompatible mapping rule on the way numerical information was associated with spatial responses. The authors also observed an effect of an incompatible numerical mapping rule (if smaller than 5, press right; if larger than 5, press left) on the Simon effect. This effect was observed only when both tasks used the same effectors. The results point to a shared spatial representation for explicit spatial information (locations) and implicit spatial information (numbers).
    背景与目标: : 在4个实验中,作者研究了参与者同时实践不兼容映射规则时空间一致性效应的逆转 (J. G. Marble & R. W. Proctor,2000)。作者观察到明确的空间不兼容映射规则对数字信息与空间响应相关联的方式的影响。作者还观察到不兼容的数值映射规则 (如果小于5,则按右; 如果大于5,则按左) 对Simon效果的影响。仅当两个任务使用相同的效应器时才观察到这种效果。结果指向显式空间信息 (位置) 和隐式空间信息 (数字) 的共享空间表示。
  • 【使用部分重建与完全重建的高分辨率肺CT对运动伪影和图像噪声的影响。】 复制标题 收藏 收藏
    DOI:10.2214/AJR.05.0852 复制DOI
    作者列表:Ha HI,Goo HW,Seo JB,Song JW,Lee JS
    BACKGROUND & AIMS: OBJECTIVE:The purpose of our study was to evaluate the effects of 0.3-second high-resolution CT (HRCT) of the lung using partial reconstruction on cardiac motion artifacts and image noise. SUBJECTS AND METHODS:Thirty-seven pairs of 0.3-second (partial reconstruction) and 0.75-second (full reconstruction) HRCT images were obtained for the lower lung zone during full-inspiration breath-holding. Imaging parameters other than temporal resolution were identical for each patient. Two radiologists visually graded motion artifacts of the cardiac border, bronchi, pulmonary vessels, and fissure in the left lung on a 4-point scale (with 4 indicating no artifacts). The maximum width of motion along the left cardiac border and the area percentage of motion artifacts in the left lung were calculated. Image noise in the air and lung was also determined. Cardiac motion artifacts and image noises were compared between the two sets of CT images. RESULTS:Visual grades for the cardiac border (4 +/- 0), bronchi (3.8 +/- 0.7), pulmonary vessels (3.6 +/- 0.8), and fissure (3.9 +/- 0.5) were higher for 0.3-second images than for 0.75-second images (1.7 +/- 0.7, 2.0 +/- 1.0, 1.6 +/- 0.7, and 2.4 +/- 0.9, respectively) (p < 0.001). The maximum width of motion along the left cardiac border (0.1 +/- 0.5 mm) and the area percentage of motion artifacts in the left lung (6.7% +/- 18.4%) were smaller for 0.3-second images than for 0.75-second images (4.5 +/- 1.7 mm and 36.2% +/- 20.9%, respectively) (p < 0.001). Image noises in the air (38.0 +/- 9.2) and the lung (86.0 +/- 23.1) were greater for 0.3-second images than for 0.75-second images (35.6 +/- 9.6 and 76.0 +/- 20.3, respectively) (p < 0.01). CONCLUSION:Compared with 0.75-second HRCT using full reconstruction, 0.3-second HRCT using partial reconstruction substantially reduces cardiac motion artifacts in the lung at the expense of increasing image noise.
    背景与目标:
  • 【雌性大鼠母体行为期间表达Fos的纹状体终末神经元的内侧视前区和腹床核的投影位点。】 复制标题 收藏 收藏
    DOI:10.1046/j.1365-2826.1997.t01-1-00597.x 复制DOI
    作者列表:Numan M,Numan MJ
    BACKGROUND & AIMS: :Medial preoptic area (MPOA) and ventral bed nucleus of the stria terminalis (VBST) neurons are involved in maternal behavior, but the neural sites to which the maternally relevant neurons project have not been determined. Since MPOA and VBST neurons express Fos during maternal behavior, we used a double-labeling immunocytochemical procedure to detect both Fos and a retrograde tracer, wheat germ agglutinin (WGA), in order to determine where these Fos neurons project. On Day 4 postpartum, fully maternal females were separated from their litters. On Day 5, WGA was iontophoretically injected into one of the following regions known to receive MPOA and/or VBST input: Lateral septum, medial hypothalamus at the level of the ventromedial nucleus, lateral habenula, ventral tegmental area, retrorubral field, or periaqueductal gray. On Day 7, females received a 2-h test with either pups or candy, after which they were perfused and their brains were processed for the detection of Fos and WGA. As expected, females tested with pups had more Fos-containing neurons in the MPOA and VBST than did females tested with candy. After WGA injections into several brain sites, the number of double-labeled cells observed in the MPOA and VBST was greater for the maternal females when compared to the non-maternal females. Therefore, these results pinpointed neural circuits that were activated during maternal behavior. For the maternal females, Fos-containing neurons in the MPOA projected most strongly to the medial hypothalamus at the level of the ventromedial nucleus and to the lateral septum, while Fos-containing neurons in the VBST projected most strongly to the retrorubral field, ventral tegmental area, and medial hypothalamus. Although relatively few MPOA and VBST neurons which expressed Fos during maternal behavior projected to the periaqueductal gray, these Fos-expressing neurons made up a relatively large proportion of the MPOA and VBST projection to the periaqueductal gray. This study suggests that MPOA and VBST efferents project to a variety of regions to promote full maternal responsiveness.
    背景与目标: : 视前区 (MPOA) 和纹状体 (VBST) 神经元的腹床核参与母体行为,但尚未确定与母系相关的神经元投射到的神经部位。由于MPOA和VBST神经元在母体行为中表达Fos,因此我们使用双标记免疫细胞化学程序来检测Fos和逆行示踪剂小麦胚芽凝集素 (WGA),以确定这些Fos神经元的投射位置。产后第4天,将完全的产妇与产仔分开。在第5天,将WGA离子电渗注射到以下已知接受MPOA和/或VBST输入的区域之一: 外侧隔膜,腹内侧核水平的下丘脑内侧,外侧habenula,腹侧被盖区,脑后野,或导水管周围灰色。在第7天,雌性接受了2小时的幼崽或糖果测试,然后对其进行灌注,并对其大脑进行处理以检测Fos和WGA。正如预期的那样,与用糖果测试的雌性相比,用幼崽测试的雌性在MPOA和VBST中具有更多的含Fos的神经元。在将WGA注射到多个大脑部位后,与非母体女性相比,在MPOA和VBST中观察到的双标记细胞数量更多。因此,这些结果确定了在母体行为期间激活的神经回路。对于母体女性,MPOA中含Fos的神经元最强烈地投射到腹内侧核水平的下丘脑内侧和外侧隔,而VBST中含Fos的神经元最强烈地投射到脑后野,腹侧被盖区和下丘脑内侧。尽管在投射到导水管周围灰色的母体行为中表达Fos的MPOA和VBST神经元相对较少,但这些表达Fos的神经元在MPOA和VBST投射到导水管周围灰色的比例相对较大。这项研究表明,MPOA和VBST传出剂投射到各个地区,以促进孕产妇的全面反应。
  • 【居住在西西里岛东部卡塔尼亚的哥伦比亚和多米尼加女性性工作者中艾滋病毒和其他性传播疾病的流行。】 复制标题 收藏 收藏
    DOI:10.1007/s10903-006-9002-1 复制DOI
    作者列表:Nigro L,Larocca L,Celesia BM,Montineri A,Sjoberg J,Caltabiano E,Fatuzzo F,Unit Operators Group.
    BACKGROUND & AIMS: INTRODUCTION:STDs are a significant cause of illness throughout the world. Female sex workers (FSWs) are commonly perceived as belonging to a social group which may engage in high-risk behaviour for acquiring or transmitting HIV and other STDs. The number of immigrant women engaged in sex work has increased in Catania, Sicily, over the last 10 years. This study aims to estimate the prevalence of HIV, HBV, HCV and syphilis among Colombian and Dominican FSWs. METHODS:In total 118 (63.78%) of the FSWs contacted in the course of the project agreed to participate in the study. All women enrolled were counselled on STDs/HIV, safer sex practices and the use of condoms. Blood samples were taken and tested for HIV, HBV, HCV and syphilis. RESULTS:Of the 118 FSWs enrolled, all were negative for both HIV and HCV infection. Two women (1.6%) were positive for hepatitis B (HbsAg). Syphilis testing by VDRL showed three positive results (2.5%), which was confirmed by TPHA. DISCUSSION:This study showed that HIV, HBV, HCV and syphilis seroprevalence among Colombian and Dominican FSWs remains low or very rare. It also indicates that these women were healthy when they arrived in Italy and that condom use with clients is high.
    背景与目标:
  • 【吸收氢化酶的调节和氢利用对沼泽红假单胞菌基因表达的影响。】 复制标题 收藏 收藏
    DOI:10.1128/JB.00381-06 复制DOI
    作者列表:Rey FE,Oda Y,Harwood CS
    BACKGROUND & AIMS: :Rhodopseudomonas palustris is a purple, facultatively phototrophic bacterium that uses hydrogen gas as an electron donor for carbon dioxide fixation during photoautotrophic growth or for ammonia synthesis during nitrogen fixation. It also uses hydrogen as an electron supplement to enable the complete assimilation of oxidized carbon compounds, such as malate, into cell material during photoheterotrophic growth. The R. palustris genome predicts a membrane-bound nickel-iron uptake hydrogenase and several regulatory proteins to control hydrogenase synthesis. There is also a novel sensor kinase gene (RPA0981) directly adjacent to the hydrogenase gene cluster. Here we show that the R. palustris regulatory sensor hydrogenase HupUV acts in conjunction with the sensor kinase-response regulator protein pair HoxJ-HoxA to activate hydrogenase expression in response to hydrogen gas. Transcriptome analysis indicated that the HupUV-HoxJA regulatory system also controls the expression of genes encoding a predicted dicarboxylic acid transport system, a putative formate transporter, and a glutamine synthetase. RPA0981 had a small effect in repressing hydrogenase synthesis. We also determined that the two-component system RegS-RegR repressed expression of the uptake hydrogenase, probably in response to changes in intracellular redox status. Transcriptome analysis indicated that about 30 genes were differentially expressed in R. palustris cells that utilized hydrogen when growing photoheterotrophically on malate under nitrogen-fixing conditions compared to a mutant strain that lacked uptake hydrogenase. From this it appears that the recycling of reductant in the form of hydrogen does not have extensive nonspecific effects on gene expression in R. palustris.
    背景与目标: : 红假单胞菌 (Rhodopseudomonas palustris) 是一种紫色的兼性光养细菌,在光自养生长过程中使用氢气作为电子供体进行二氧化碳固定或在固氮过程中进行氨合成。它还使用氢作为电子补充剂,以使氧化的碳化合物 (例如苹果酸盐) 在光异养生长过程中完全同化为细胞材料。R. palustris基因组预测了膜结合的镍铁吸收氢化酶和几种控制氢化酶合成的调节蛋白。还有一个新的传感器激酶基因 (RPA0981) 直接与氢化酶基因簇相邻。在这里,我们显示了R. palustris调节传感器氢化酶HupUV与传感器激酶响应调节蛋白对HoxJ-HoxA共同作用,以响应氢气激活氢化酶表达。转录组分析表明,HupUV-HoxJA调节系统还控制编码预测的二羧酸转运系统,推定的甲酸转运蛋白和谷氨酰胺合成酶的基因的表达。RPA0981在抑制氢化酶合成方面的作用很小。我们还确定,两组分系统RegS-RegR抑制了摄取氢化酶的表达,可能是对细胞内氧化还原状态变化的响应。转录组分析表明,与缺乏摄取氢化酶的突变菌株相比,在固氮条件下在苹果酸上光异养生长时利用氢的R. palustris细胞中约30个基因差异表达。由此看来,以氢形式回收还原剂对R. palustris的基因表达没有广泛的非特异性影响。
  • 【大剂量辛伐他汀对SD大鼠前额叶皮层和纹状体多巴胺水平及其再摄取的影响。】 复制标题 收藏 收藏
    DOI:10.1016/j.neulet.2006.09.009 复制DOI
    作者列表:Wang Q,Tang XN,Wang L,Yenari MA,Ying W,Goh BC,Lee HS,Wilder-Smith EP,Wong PT
    BACKGROUND & AIMS: :Statins are increasingly being used for the treatment of a variety of conditions beyond their original indication for cholesterol lowering. We previously reported that simvastatin increased dopamine receptors in the rat prefrontal cortex [Q. Wang, W.L. Ting, H. Yang, P.T. Wong, High doses of simvastatin upregulate dopamine D(1) and D(2) receptor expression in the rat prefrontal cortex: possible involvement of endothelial nitric oxide synthase, Br. J. Pharmacol. 144 (2005) 933-939] and restored its downregulation in a model of Parkinson's disease (PD) [Q. Wang, P.H. Wang, C. McLachlan, P.T. Wong, Simvastatin reverses the downregulation of dopamine D1 and D2 receptor expression in the prefrontal cortex of 6-hydroxydopamine-induced Parkinsonian rats, Brain Res. 1045 (2005) 229-233]. Here we explore the effects of simvastatin treatment on tissue dopamine content and reuptake. Sprague-Dawley rats were given simvastatin (1 and 10 mg kg(-1)day(-1), p.o.) for 4 weeks. Brain tissue from prefrontal cortex and striatum were taken out for dopamine content and its reuptake. Using high-performance liquid chromatographic-mass spectrometer (HPLC-MS), simvastatin (10 mg kg(-1)day(-1)) was found to increase dopamine content by 110% in the striatum but decreased by 76% in the prefrontal cortex compared with the saline treated group. Dopamine (DA) reuptake was unchanged in both brain regions. These results suggest that chronic treatment with high dose of simvastatin may affect DA tissue level in prefrontal cortex and striatum without changing on DA reuptake. This may have important clinical implications in psychiatric and striatal dopaminergic disorders.
    背景与目标: : 他汀类药物越来越多地用于治疗各种疾病,超出了其降低胆固醇的原始适应症。我们先前报道辛伐他汀增加了大鼠前额叶皮层的多巴胺受体 [Q. Wang,W.L. Ting,H. Yang,P.T. Wong,高剂量辛伐他汀上调了大鼠前额叶皮层的多巴胺D(1) 和D(2) 受体表达: 可能参与内皮型一氧化氮合酶,br.J. Pharmacol. 144 (2005) 933-939] 并在帕金森氏病 (PD) 模型中恢复了其下调 [Q. Wang,P.H. Wang,C. McLachlan,P.T. Wong,辛伐他汀可逆转6-羟基多巴胺诱导的帕金森病大鼠前额叶皮层多巴胺D1和D2受体表达的下调,脑Res. 1045 (2005) 229-233]。在这里,我们探讨辛伐他汀治疗对组织多巴胺含量和再摄取的影响。Sprague-Dawley大鼠给予辛伐他汀 (1和10 mg kg(-1) 天 (-1),p.o.) 4周。取出前额叶皮层和纹状体的脑组织以获取多巴胺含量及其再摄取。使用高效液相色谱-质谱仪 (hplc-ms),发现辛伐他汀 (10 mg kg(-1) 天 (-1)) 在纹状体中110% 增加多巴胺含量,但在前额叶皮层中减少76% 与生理盐水治疗组相比。两个大脑区域的多巴胺 (DA) 再摄取均未改变。这些结果表明,高剂量辛伐他汀的慢性治疗可能会影响前额叶皮层和纹状体的DA组织水平,而不会改变DA的再摄取。这可能对精神病和纹状体多巴胺能疾病具有重要的临床意义。
  • 【热休克蛋白-90 (HSP90) 在多发性骨髓瘤中的表达及HSP90抑制剂 (17-AAG) 的作用分析。】 复制标题 收藏 收藏
    DOI:10.1080/10428190500472123 复制DOI
    作者列表:Duus J,Bahar HI,Venkataraman G,Ozpuyan F,Izban KF,Al-Masri H,Maududi T,Toor A,Alkan S
    BACKGROUND & AIMS: :Heat shock protein 90 (HSP90) is required for structural folding and maintenance of conformational integrity of various proteins, including several associated with cellular signaling. Recent studies utilizing 17-allylamino-17-demethoxygeldanamycin (17-AAG), an inhibitor of HSP90, demonstrated an antitumor effect in solid tumors. To test whether HSP90 could be targeted in multiple myeloma (MM) patients, we first investigated expression of HSP90 by immunofluorescence and flow cytometric analysis in a myeloma cell line (U266) and primary myeloma cells. Following demonstration of HSP90 expression in myeloma cells, archival samples of 32 MM patients were analysed by immunoperoxidase staining. Myeloma cells in all patients showed strong cytoplasmic expression of HSP90 in all samples and 55% also demonstrated concurrent nuclear immunopositivity. Treatment of U266 and primary MM cells with 17AAG resulted in significantly increased apoptosis compared to untreated control cells. Analysis of anti-apoptotic BCL2 family proteins and akt in MM cells incubated with 17-AAG revealed down-regulation of BCL-2, BCL-XL, MCL-1 and akt. Furthermore, although a low concentration of bortezomib resulted in no cell death, a combination of 17AAG and bortezomib treatment revealed a synergistic apoptotic effect on the U266 cell line. These data suggest that targeted inhibition of HSP90 may prove to be a valid and innovative strategy for the development of future therapeutic options for MM patients.
    背景与目标: : 热休克蛋白90 (HSP90) 是各种蛋白质的结构折叠和构象完整性维持所必需的,包括与细胞信号传导相关的几种。利用HSP90抑制剂17-allylamino-17-demethoxygeldanamycin (17-AAG) 的最新研究表明,在实体瘤中具有抗肿瘤作用。为了测试HSP90是否可以靶向多发性骨髓瘤 (MM) 患者,我们首先通过免疫荧光和流式细胞仪分析研究了HSP90在骨髓瘤细胞系 (U266) 和原发性骨髓瘤细胞中的表达。在证明骨髓瘤细胞中HSP90表达后,通过免疫过氧化物酶染色分析了32 MM患者的档案样本。所有患者的骨髓瘤细胞在所有样品中均显示出HSP90的强细胞质表达,并且55% 还显示出同时的核免疫阳性。与未处理的对照细胞相比,用17AAG处理U266和原代MM细胞可显着增加细胞凋亡。对与17-aag孵育的MM细胞中抗凋亡BCL2家族蛋白和akt的分析表明,BCL-2,BCL-XL,MCL-1和akt下调。此外,尽管低浓度的硼替佐米不会导致细胞死亡,但17AAG和硼替佐米的组合治疗显示出对U266细胞系的协同凋亡作用。这些数据表明,靶向抑制HSP90可能被证明是开发MM患者未来治疗选择的有效且创新的策略。
  • 【B细胞慢性淋巴细胞白血病患者T细胞中的信号分子和细胞因子产生: 氟达拉滨和阿仑单抗治疗的长期影响。】 复制标题 收藏 收藏
    DOI:10.1080/10428190600565503 复制DOI
    作者列表:Kiaii S,Choudhury A,Mozaffari F,Rezvany R,Lundin J,Mellstedt H,Osterborg A
    BACKGROUND & AIMS: :Fludarabine and alemtuzumab are routinely used for treatment of B-cell chronic lymphocytic leukemia (B-CLL). The present study aimed to compare the expression of signaling molecules and cytokine production by T cells of B-CLL patients in long-term unmaintained remission/plateau phase following fludarabine or alemtuzumab treatment with that of indolent/untreated B-CLL patients and healthy donors. The frequency and intensity of TCR-CD3zeta chain, p56lck, p59fyn, ZAP-70, PI3-kinase and interferon (IFN)-gamma/interleukin (IL)-4 production in CD4 and CD8 T cells was examined by flow cytometry. T-cell function was assessed by stimulation with purified protein derivative (PPD) and phytohemagglutinin (PHA). Despite a reduction in number, the expression of IFN-gamma/IL-4 in T-cells in patients was significantly higher than in healthy donors. The intensity of most signaling molecules in treated patients was relatively unaffected vs. healthy donors but lower than untreated-indolent patients. However, the total number of T cells which expressed each of the signaling molecules was decreased in patients, with no difference between fludarabine- and alemtuzumab-treated patients. The T-cell response to PHA but not PPD was reduced in treated patients. The results suggest that, despite some alterations in signaling molecules and a reduction in T-cell number, overall T-cell functions may be relatively well preserved long-term after treatment with fludarabine and alemtuzumab.
    背景与目标: : 氟达拉滨和阿仑单抗通常用于治疗b细胞慢性淋巴细胞白血病 (b-cll)。本研究旨在比较在氟达拉滨或阿仑单抗治疗后长期未维持缓解/平台期的b-cll患者的T细胞与惰性/未治疗的b-cll患者和健康的T细胞的信号分子表达和细胞因子产生供体。通过流式细胞术检查CD4和CD8 T细胞中TCR-CD3zeta链,p56lck,p59fyn,ZAP-70,PI3-kinase和干扰素 (IFN)-γ/白细胞介素 (IL)-4产生的频率和强度。通过纯化蛋白衍生物 (PPD) 和植物血凝素 (PHA) 刺激来评估T细胞功能。尽管数量减少,但患者T细胞中IFN-γ/IL-4的表达显着高于健康供体。与健康供体相比,接受治疗的患者中大多数信号分子的强度相对不受影响,但低于未经治疗的惰性患者。然而,在患者中表达每种信号分子的T细胞总数减少,而氟达拉滨和阿仑单抗治疗的患者之间没有差异。在治疗的患者中,T细胞对PHA的反应降低,但对PPD的反应降低。结果表明,尽管信号分子发生了一些变化,T细胞数量减少,但在用氟达拉滨和阿仑单抗治疗后,总体T细胞功能可能长期保持良好。
  • 【ERCP透皮三硝酸甘油的前瞻性,随机,安慰剂对照试验: 对技术成功和ERCP后胰腺炎的影响。】 复制标题 收藏 收藏
    DOI:10.1016/j.gie.2005.11.060 复制DOI
    作者列表:Kaffes AJ,Bourke MJ,Ding S,Alrubaie A,Kwan V,Williams SJ
    BACKGROUND & AIMS: BACKGROUND:Despite the recent improvement in techniques and patient selection, post-ERCP pancreatitis remains the most frequent and dreaded complication of ERCP. Recent studies suggest that pretreatment with glyceryl trinitrate (GTN) may prevent post-ERCP pancreatitis and improve cannulation success. OBJECTIVE:To evaluate the effect of transdermal GTN on ERCP cannulation success and post-ERCP pancreatitis. DESIGN:Prospective, double-blind, placebo-controlled trial. SETTING:Tertiary referral university hospital. PATIENTS:A total of 318 patients (mean age 62 years, 61% women) were randomized to either active (n = 155) or placebo (n = 163) arms. INTERVENTIONS:Active patch (GTN) versus placebo patch. MAIN OUTCOME MEASUREMENTS:Cannulation time and success. Post-ERCP pancreatitis rates. RESULTS:There was no significant difference between the active or placebo arms for the following: successful initial cannulation (96.8% vs 98.8%), deep cannulation (96.1% vs 98.8%), time to successful cannulation, use of guidewire (27% vs 25%) or needle knife (13% vs 13%), and post-ERCP pancreatitis (7.4% of placebo patients and 7.7% active patients). Multivariate analysis identified women, younger patients, pancreatogram, number of attempts on papilla, and poor pancreatic-duct emptying after opacification as risk factors for post-ERCP pancreatitis. Transdermal GTN did not reduce post-ERCP pancreatitis in any of the identified high-risk groups. CONCLUSIONS:Transdermal GTN did not improve the rate of success in ERCP cannulation or prevent post-ERCP pancreatitis in either average or high-risk patient groups.
    背景与目标:
  • 【阿片肽对 μ 受体选择性的直接作用: 豚鼠室旁和视上核的细胞内记录。】 复制标题 收藏 收藏
    DOI:10.1016/0306-4522(90)90426-5 复制DOI
    作者列表:Wuarin JP,Dudek FE
    BACKGROUND & AIMS: :Responses to [D-Ala2, MePhe4, Gly-ol5]enkephalin, a selective agonist for mu-receptors, were recorded intracellularly from 26 neurons in slices of guinea-pig hypothalamus. Of eight cells tested in the supraoptic nucleus, all of which had electrical properties characteristic of magnocellular neuroendocrine cells, four were sensitive to the agonist applied in the perfusion bath or with microdrops. The main effect was a decrease or suppression of spontaneous firing. In the paraventricular nucleus, seven of 18 cells tested also had electrophysiological characteristics similar to magnocellular neurons: two of them were sensitive to the mu-agonist and the effect was similar to that observed in the supraoptic nucleus. The remaining paraventricular neurons displayed low-threshold Ca2+ spikes, and thus had electrophysiological characteristics different from putative magnocellular neurons. Ten of 11 cells with low-threshold Ca2+ spikes were hyperpolarized by more than 10 mV by the mu-agonist, and showed a 33 +/- 1.9% (S.E.M.) decrease in input resistance. In both types of cells, when synaptic transmission was blocked with tetrodotoxin, the mu-agonist could still induce a hyperpolarization, suggesting that the effect was in part direct. Hyperpolarization was also obtained when the Cl- reversal potential was shifted to more positive values by using KCl electrodes, thus excluding a Cl- conductance mechanism. These results provide evidence that opioid peptides can directly inhibit hypothalamic neurons, that the mechanism is an increase in K+ conductance, and that two types of hypothalamic neurons appear to have different sensitivities to a mu-agonist.
    背景与目标: : 从豚鼠下丘脑切片中的26个神经元在细胞内记录了对 [D-Ala2,MePhe4,Gly-ol5] 脑啡肽 (mu受体的选择性激动剂) 的反应。在视上核中测试的八个细胞中,所有这些细胞均具有大细胞神经内分泌细胞的电特性,其中四个对灌注浴或微滴中使用的激动剂敏感。主要效果是减少或抑制自发发射。在室旁核中,测试的18个细胞中有7个具有类似于大细胞神经元的电生理特征: 其中两个对mu激动剂敏感,其作用类似于在视上核中观察到的作用。其余的室旁神经元显示出低阈值的Ca2尖峰,因此具有与假定的大细胞神经元不同的电生理特征。具有低阈值Ca2尖峰的11个细胞中的10个被mu激动剂超极化超过10 mV,并显示输入阻力降低了33/- 1.9% (s.e.M.)。在两种类型的细胞中,当河豚毒素阻断突触传递时,mu激动剂仍可诱导超极化,这表明该作用部分是直接的。当使用KCl电极将Cl反转电位移至更多正值时,也获得了超极化,从而排除了Cl电导机制。这些结果提供了证据,表明阿片肽可以直接抑制下丘脑神经元,其机制是K电导的增加,并且两种类型的下丘脑神经元似乎对mu激动剂具有不同的敏感性。
  • 【在台湾,替加环素与其他抗菌剂对肺炎链球菌,流感嗜血杆菌和卡他莫拉菌的体外活性比较。】 复制标题 收藏 收藏
    DOI:10.1089/mdr.2006.12.130 复制DOI
    作者列表:Lau YJ,Hsueh PR,Liu YC,Shyr JM,Huang WK,Teng LJ,Liu CY,Luh KT
    BACKGROUND & AIMS: :We compared the in vitro activities of tigecycline to those of other agents against 300 nonduplicate isolates of Streptococcus pneumoniae (194 isolates), Haemophilus influenzae (60 isolates), and Moraxella catarrhalis (46 isolates) recovered from patients treated in three major hospitals in Taiwan from August through December, 2003. All of these isolates were inhibited at 0.5 mg/L of tigecycline. For S. pneumoniae isolates, 72% were not susceptible to penicillin (69% intermediate and 3% resistant) and 96% were not susceptible to azithromycin. Among the 178 isolates resistant to azithromycin, 53 isolates (30%) had the M phenotype and 70% had the cMLSB phenotype. The rate of nonsusceptibility to ertapenem, telithromycin, moxifloxacin, and quinupristindalfopristin in S. pneumoniae was 3%, 2%, 1%, and 57%, respectively. For H. influenzae, 36 (60%) were not susceptible to ampicillin, among which 31 possessed beta-lactamase. A high rate (8.3%) of H. influenzae isolates with beta-lactamase-negative and ampicillin-resistant phenotype was found. All H. influenzae isolates were susceptible to azithromycin, but 40% of them were not susceptible to clarithromycin. Ninety-eight percent (44 isolates) of M. catarrhalis possessed beta-lactamase. All three fluoroquinolones tested were highly active (MIC90 < or =0.12 mg/L) against H. influenzae and M. catarrhalis.
    背景与目标: : 我们比较了替加环素与其他药物对300种非重复肺炎链球菌分离株 (194株),流感嗜血杆菌 (60株) 和卡他莫拉菌 (46株) 的体外活性,这些分离株是从8月到2003年12月在台湾的三家主要医院中康复的。在0.5 mg/L替加环素的浓度下,所有这些分离株均被抑制。对于肺炎链球菌分离株,72% 对青霉素不敏感 (69% 中间体和3% 耐药),96% 对阿奇霉素不敏感。在对阿奇霉素耐药的178株中,53株 (30% 株) 具有M表型,70% 株具有cMLSB表型。肺炎链球菌对厄他培南,泰利霉素,莫西沙星和奎奴普汀的不敏感性分别为3%,2%,1% 和57%。对于流感嗜血杆菌,36 (60%) 对氨苄青霉素不敏感,其中31具有 β-内酰胺酶。发现具有 β-内酰胺酶阴性和氨苄青霉素抗性表型的流感嗜血杆菌分离株率高 (8.3%)。所有流感嗜血杆菌分离株对阿奇霉素敏感,但其中40% 对克拉霉素不敏感。卡他氏杆菌的百分之九十八 (44个分离株) 具有 β-内酰胺酶。测试的所有三种氟喹诺酮类药物对流感嗜血杆菌和卡他氏杆菌具有高度活性 (MIC90 <或 = 0.12 mg/L)。
  • 【压力限制通气期间持续气管气吹入对急性肺损伤家兔肺表面活性物质的影响。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Zhu GF,Zhang W,Zong H,Liang Y
    BACKGROUND & AIMS: BACKGROUND:Pulmonary surfactant dysfunction may contribute to the development of ventilator induced lung injury (VILI). Tracheal gas insufflation (TGI) is a technique in which fresh gas is introduced into the trachea and augment ventilation by reducing the dead space of ventilatory system, reducing ventilatory pressures and tidal volume (V(T)) while maintaining constant partial arterial CO2 pressure (PaCO(2)). We hypothesised that TGI limited peak inspiratory pressure (PIP) and V(T) and would minimize conventional mechanical ventilation (CMV) induced pulmonary surfactant dysfunction and thereby attenuate VILI in rabbits with acute lung injury (ALI). METHODS:ALI was induced by intratracheal administration of lipopolysaccharide in anaesthetized, ventilated healthy adult rabbits randomly assigned to continuous TGI at 0.5 L/min (TGI group) or CMV group (n = 8 for each group), and subsequently ventilated with limited PIP and V(T) to maintain PaCO(2) within 35 to 45 mmHg for 4 hours. Physiological dead space to V(T) ratio (V(D)/V(T)), dynamic respiratory compliance (Cdyn) and partial arterial O(2) pressure (PaO(2)) were monitored. After ventilation, lungs were analysed for total phospholipids (TPL), total proteins (TP), pulmonary surfactant small to large aggregates ratio (SA/LA) in bronchoalveolar lavage fluid (BALF) and for determination of alveolar volume density (V(V)), myeloperoxidase and interleukin (IL)-8. RESULTS:TGI resulted in significant (P < 0.05 or P < 0.01) decrease in PIP [(22.4 +/- 1.8) cmH2O vs (29.5 +/- 1.1) cmH2O], V(T) [(6.9 +/- 1.3) ml/kg vs (9.8 +/- 1.11) ml/kg], V(D)/V(T) [(32 +/- 5)% vs (46 +/- 2)%], TP [(109 +/- 22) mg/kg vs (187 +/- 25) mg/kg], SA/LA (2.5 +/- 0.4 vs 5.4 +/- 0.7), myeloperoxidase [(6.2 +/- 0.5) U/g tissue vs (12.3 +/- 0.8) U/g tissue] and IL-8 [(987 +/- 106) ng/g tissue vs (24 +/- 3) mN/m] of BALF, and significant (P < 0.05) increase in Cdyn [(0.47 +/- 0.02) ml.cmH2O(-1).kg(-1) vs (0.31 +/- 0.02) ml.cmH2O(-1).kg(-1)], PaO(2) [(175 +/- 24) mmHg vs (135 +/- 26) mmHg], TPL/TP (52 +/- 8 vs 33 +/- 11) and Vv (0.65 +/- 0.05 vs 0.44 +/- 0.07) as compared with CMV. CONCLUSIONS:In this animal model of ALI, TGI decreased ventilatory requirements (PIP, V(T) and V(D)/V(T)), resulted in more favourable alveolar pulmonary surfactant composition and function and less severity of lung injury than CMV. TGI in combination with pressure limited ventilation may be a lung protective strategy for ALI.
    背景与目标:

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