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21.
Determination of phospholipidosis potential based on gene expression analysis in HepG2 cells. 总被引:1,自引:0,他引:1
Franck Atienzar Helga Gerets Simon Dufrane Karen Tilmant Miranda Cornet Stephane Dhalluin Bernard Ruty Geoffrey Rose Michael Canning 《Toxicological sciences》2007,96(1):101-114
Phospholipidosis (PLD) is characterized by an intracellular accumulation of phospholipids in lysosomes and the concurrent development of concentric lamellar bodies. Recently, H. Sawada et al. (2005, Toxicol. Sci. 83, 282-292) identified 17 genes as potential biomarkers of PLD in HepG2 cells. The present study was undertaken to determine if this set of genes measured by quantitative PCR could be validated in the same cell line. The objective was also to investigate the dose-response relationship to further validate the assay and to select the concentrations to use for screening activities. In a first experiment (one concentration tested), out of the 17 genes, the best gene biomarkers of PLD (i.e., 11 genes) were selected for practical screening reasons. Based on these genes, 91.6% (i.e., 11 of 12) of the compounds known to induce PLD were identified as positive and all the negative compounds (i.e., five of five) were also confirmed. When the data obtained in the first experiment were compared to the data by Sawada et al., (2005) the coefficient of correlation calculated was slightly higher than 75%. In the second experiment (26 compounds [all 17 compounds from the first experiment plus 9 other compounds] tested at a minimum of three concentrations), 93.3% (14/15) of the compounds known to induce PLD were identified as such and all the negative controls (six compounds) were also confirmed. Three compounds likely to induce PLD were identified as positive in our assay. Finally, two compounds for which no data are available were also tested. When both experiments 1 and 2 were compared, the coefficient of correlation for 16 compounds tested at the same concentrations reached 87.7%. In conclusion, the present study further confirms the utility of gene expression in HepG2 cells to identify a potential to induce PLD. Finally, based on the data presented, researchers are encouraged to use a range of minimum three concentrations (e.g., 12.5, 25, and 50 microM) to screen for PLD in the human HepG2 cell line. 相似文献
22.
提出了文题的计算模型,它采用非线性弹塑性蠕变有限元法,计算构件危险点在高温及周期保载的交变载荷谱作用下的应力应变响应,以应变范围区分法累积损伤,从而求出构件的疲劳寿命,并以带孔矩形薄板为例作了计算与验证,结果吻合较好,可供工程应用。 相似文献
23.
Ramona A. Cole Anita Bansal Debra M. Moriarity William A. Haber William N. Setzer 《Journal of natural medicines》2007,61(4):414-417
The leaf essential oil of Eugenia zuchowskiae from Monteverde, Costa Rica, has been obtained by hydrodistillation and analyzed by GC–MS. The principal constituents of
E. zuchowskiae leaf oil were α-pinene (28.3%), β-caryophyllene (13.2%), α-humulene (13.1%), and α-copaene (8.1%). The leaf essential oil
of E. zuchowskiae showed pronounced in-vitro cytotoxic activity against MCF-7, MDA-MB-468, and UACC-257 human tumor cell lines. The major components
showed cytotoxic activities comparable to doxorubicin (LC50 14–70 μg/ml). 相似文献
24.
This study demonstrates that ZnSO4 induced chemical trauma results in an in situ regeneration of the olfactory epithelium which, when maintained in vitro, provides an enriched population of olfactory neurons. Therefore, the ability of the olfactory epithelium to respond to chemical trauma with increased mitotic activity can be used to increase growth of neurons in culture. Tissue obtained from normal or vehicle-treated adult mice produced few olfactory neurons, when maintained in culture, compared to cultures established from tissue following an in situ ZnSO4 trauma. Maximal neuronal yields were obtained in cultures established from tissue that was removed 4–6 days following chemical trauma. The morphological appearance and the presence of cell specific intermediate filament proteins were used to classify the cell types in these olfactory epithelial cultures. Single cells and aggregates of cells which were immunopositive for keratin, but immunonegative for neurofilament protein and GFAP, were identified as epithelioid. Flattened polygonal cells immunopositive for GFAP were identified as glia. A small population of flattened cells was immunonegative for all of the antibodies used in this study. Cells that had processes were immunonegative for GFAP and keratin. Some were immunopositive for 200 kDa and 160 kDa neurofilament proteins but immunonegative for the 68 kDa neurofilament protein. A few of these cells showed positive immunoreactivity with the olfactory marker protein (OMP) antibody and most likely represented the most mature olfactory neurons in the cultures. This trauma-induced culture model using olfactory tissue from adult mice can serve as a source of CNS neurons for comparison with cultured embryonic neurons. 相似文献
25.
化工行业职业性机械伤害危险因素的病例-交叉方法研究 总被引:6,自引:0,他引:6
目的 研究化工行业机械伤害的有关诱发因素,估计其作用强度。方法 采用病例-交叉设计的方法。以操作和检修时受伤的化工工人为研究对象,每个对象在受伤后2d内完成调查,收集他们受伤前10min、上一工作日同一段时间和受伤前1周内有关诱发因素暴露的信息,用配对时间段方法和一般频数法进行分析,评估各种诱发因素的危险度。结果 一般频数法分析的结构表明,操作方法异常、设备工具缺陷、工作紧迫、注意力不集中、不使用防护用品、精神状况较差、与同事配合不协调、工作环境发生变化等瞬时危害因素的RR值及95%可信限的下限均大于1。配对时间段方法分析的结果与其相拟,但95%可信限较宽。结论 化工行业职业性机械伤害的发生存在着诸多诱发因素。病例-交叉研究中的一般频数法与配对时间段方法相比,前者所得结果较为可靠,研究的相对效率较高。建议进一步使用多个时间段方法进行研究,以减小混杂因素的影响。 相似文献
26.
27.
Primary cultures enriched in neurons dissociated from embryonic rat cerebra were used to demonstrate that platelet activating factor and the structurally related ether glycerolipid, dodecylglycerol, are readily taken up in small amounts by neurons and that they stimulate the differentiation of neurons. The stimulation of neuronal differentiation was observed as a precocious development of axon-like extensions which correlated with a concentration-dependent increase in neuronal-specific enzyme activities. This stimulation of morphological and neurochemical factors by either platelet activating factor or dodecylglycerol was almost completely abolished by triazolam, a known inhibitor of platelet activating factor function. Neither platelet activating factor nor dodecylglycerol at the concentrations used to achieve stimulation of neuronal differentiation compromised the plasma membrane, as indicated by the lack of leakage of cytoplasmic lactic acid dehydrogenase. 相似文献
28.
29.
Stanley A. Klein 《Brain topography》1993,6(1):79-82
Summary There are some occasions when it is better to use the Laplacian of the scalp voltages (e.g., for topographic displays and dipole source localization) and other occasions when it is better to use the original voltages (e.g., for comparison to non-Laplacian topography maps). This paper presents a simple algorithm for going between these two representations of the data. The inverse Laplacian involves iterative feedback. An Excel spreadsheet implementation of the algorithm is presented.This research was supported by grant AFOSR 89-0238 from the Air Force Office of Sponsored Research. 相似文献
30.
以S.minnesota R595菌为免疫原,通过细胞融合获得8株分泌抗核心糖脂单抗的杂交瘤细胞系。对其中的两株代表性单抗2D6E7和3H4 2F7的血清学反应性以及在小鼠Hb/Mu腹腔感染模型中的保护作用进行了初步研究。菌体吸收试验和间接免疫荧光试验(ⅡF)表明,单抗能与多种革兰氏阴性杆菌(GNB)产生交叉反应,并且光滑型GNB的煮沸菌体荧光染色呈阳性,活菌染色呈阴性。保护性试验结果表明,3H4 2F7单抗能显著提高S.minnesota(野生菌株),鼠伤寒杆菌和E.Coli等光滑型GNB攻击的小鼠存活率(P<0.05),显示出抗核心糖脂单抗的良好交叉保护作用。若攻击前、后2h或攻击同时输入单抗3H4 2F7,对光滑型GNB的感染均有明显保护效果(P<0.05);2D6 E7单抗未表现有保护活性。 相似文献