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排序方式: 共有146条查询结果,搜索用时 46 毫秒
81.
K W Brown J C Williams N J Maitland M G Mott 《American journal of human genetics》1990,46(5):1000-1001
82.
Tony Taldone Victoria Gillan Weilin Sun Anna Rodina Pallav Patel Kirsty Maitland Kerry O'Neill Gabriela Chiosis Eileen Devaney 《PLoS neglected tropical diseases》2010,4(6)
The chemotherapy of lymphatic filariasis relies upon drugs such as diethylcarbamazine and ivermectin that largely target the microfilarial stages of the parasite, necessitating continued treatment over the long reproductive life span of the adult worm. The identification of compounds that target adult worms has been a long-term goal of WHO. Here we describe a fluorescence polarization assay for the identification of compounds that target Hsp90 in adult filarial worms. The assay was originally developed to identify inhibitors of Hsp90 in tumor cells, and relies upon the ability of small molecules to inhibit the binding of fluorescently labelled geldanamycin to Hsp90. We demonstrate that the assay works well with soluble extracts of Brugia, while extracts of the free-living nematode C. elegans fail to bind the probe, in agreement with data from other experiments. The assay was validated using known inhibitors of Hsp90 that compete with geldanamycin for binding to Hsp90, including members of the synthetic purine-scaffold series of compounds. The efficacy of some of these compounds against adult worms was confirmed in vitro. Moreover, the assay is sufficiently sensitive to differentiate between binding of purine-scaffold compounds to human and Brugia Hsp90. The assay is suitable for high-throughput screening and provides the first example of a format with the potential to identify novel inhibitors of Hsp90 in filarial worms and in other parasitic species where Hsp90 may be a target. 相似文献
83.
Lang SH Smith J Hyde C Macintosh C Stower M Maitland NJ 《In vitro cellular & developmental biology. Animal》2006,42(8-9):273-280
Summary Three-dimensional epithelial culture models are widely used to emulate a more physiologically relevant microenvironment for
the study of genes and signaling pathways. Prostate epithelial cells can grow into solid cell masses or acinus-like spheroids
in Matrigel. To test if the ability to form acinus-like spheroids in Matrigel is dependent on how undifferentiated a cell
is or whether it is tumor or nontumor, we established six novel epithelial cell lines. Primary prostate epithelial cells were
immortalized using HPV16 E6 gene transduction and were named Shmac 2, 3, and 6 (nontumor); Shmac 4, Shmac 5, and P4E6 (tumor).
All cell lines were phenotyped in monolayer culture, and their ability to form acinus-like spheroids in Matrigel investigated.
The cell lines exhibited a wide range of population doubling times and all showed an intermediate phenotype in nonolayer culture
(luminalCK+/basalCK+/CD44+/PSA+/AR−). Only Shmac 5 cells formed acinus-like spheroids when cultured in Matrigel. Co-culture of the spheroids with fibroblasts
advanced differentiation by inducing androgen receptor expression and epithelial polarization. Our findings indicate that
tumor cells can form acinus-like spheroids in Matrigel. 相似文献
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Lamprey‐induced scarring of the nationally rare Coregonus lavaretus, a known host of a freshwater‐resident population of European river lamprey Lampetra fluviatilis, was found to have declined precipitously since the establishment of several non‐native fishes in Loch Lomond. Evidence presented in this study points to the possibility that L. fluviatilis in this lake may have altered its trophic ecology in response to the negative impact that non‐native species, in particular ruffe Gymnocephalus cernuus, have had on their favoured host. 相似文献
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Hydrobiologia - Reservoir construction and the introduction of nonnative species are major anthropogenic drivers of biotic change in freshwater ecosystems. To understand the influence of these... 相似文献
89.
The design and application of soft nanocomposite injectable hydrogels containing entrapped microgels for small-molecule drug delivery is demonstrated. Copolymer microgels based on N-isopropylacrylamide and acrylic acid were synthesized that exhibited both ionic and hydrophobic affinity for binding to bupivacaine, a cationic local anesthetic used as a model drug. Microgels were subsequently immobilized within an in situ-gelling hydrogel network cross-linked via hydrazide-aldehyde chemistry to generate hydrogel-microgel soft nanocomposites. Drug release could be sustained for up to 60 days from these nanocomposite hydrogels, significantly longer than that achievable using the constituent hydrogel or microgels alone (<1 week). Drug release kinetics could be readily tuned by varying the affinity of the microgel and hydrogel phases for drug-polymer interactions and the network density of the hydrogel phase. 相似文献
90.
Hwang W Volk BL Akberali F Singhal P Criscione JC Maitland DJ 《Biomechanics and modeling in mechanobiology》2012,11(5):715-729
In this study, compliant latex thin-walled aneurysm models are fabricated to investigate the effects of expansion of shape memory polymer foam. A simplified cylindrical model is selected for the in-vitro aneurysm, which is a simplification of a real, saccular aneurysm. The studies are performed by crimping shape memory polymer foams, originally 6 and 8 mm in diameter, and monitoring the resulting deformation when deployed into 4-mm-diameter thin-walled latex tubes. The deformations of the latex tubes are used as inputs to physical, analytical, and computational models to estimate the circumferential stresses. Using the results of the stress analysis in the latex aneurysm model, a computational model of the human aneurysm is developed by changing the geometry and material properties. The model is then used to predict the stresses that would develop in a human aneurysm. The experimental, simulation, and analytical results suggest that shape memory polymer foams have potential of being a safe treatment for intracranial saccular aneurysms. In particular, this work suggests oversized shape memory foams may be used to better fill the entire aneurysm cavity while generating stresses below the aneurysm wall breaking stresses. 相似文献