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71.
Simon J. Mantell Karl R. Gibson Simon A. Osborne Graham N. Maw Huw Rees Peter G. Dodd Ben Greener Gareth W. Harbottle William A. Million Cedric Poinsard Steven England Pauline Carnell Alison M. Betts Russell Monhemius Rebecca L. Prime 《Bioorganic & medicinal chemistry letters》2009,19(8):2190-2194
The SAR of a series of novel pyrido[3,4-d]pyramid-4-ylamine mGluR1 antagonists is described. The multiple of the unbound Ki in cerebrospinal fluid necessary to give morphine like analgesic effects in an electromyograph pinch model in rodents is determined and the effect of structure on CNS penetration examined. 相似文献
72.
73.
J. Luker I. J. Crane C. Scully S. S. Prime 《Virchows Archiv. B, Cell pathology including molecular pathology》1989,57(1):19-26
This study examined the effect of 3T3 fibroblasts on the expression of anchorage independence and the degree of cornification in early cultures of three carcinoma-derived epithelial cell lines (R59, R63a, R63b) and in one cell line derived from non-malignant dysplastic epithelium where there was no evidence of invasion (R66a). The epithelial cell lines originated from the palatal (R63a, R66a) and the lingual (R59, R63b) mucosa of rats that had been painted with the carcinogen 4-nitroquinoline N-oxide. In the absence of 3T3 fibroblasts, progressive culture resulted in an increase in the colony forming efficiency (CFE) of R63a, R63b and R59 and a decrease in the percentage of cornified cells in all cell lines. 3T3 fibroblasts caused a decrease in the CFE and the degree of cornification in the 3T3-dependent cell line (R63a), particularly at the lower passages, but these parameters remained essentially unchanged by 3T3 fibroblasts in the 3T3-independent cell lines (R59, R63b). 3T3 fibroblasts did not influence the cornification of R66a and this cell line remained anchorage dependent throughout the study. The results suggest that in malignant cell lines characterised by being independent of 3T3 fibroblasts (R63b, R59) the CFE was inversely correlated to the degree of cornification. However, in the malignant cell line showing a greater dependence on support (R63a) the relationship between CFE and cornification was unclear because these parameters may have been modulated by the presence of 3T3 fibroblasts. The cell line from dysplastic non-invasive tissue (R66a) differed from its malignant counterparts in the fact that CFE and cornification were unaffected by 3T3 fibroblasts despite previous studies showing a dependence on mesenchymal support. 相似文献
74.
75.
A hyaluronic acid‐based compound inhibits fibroblast senescence induced by oxidative stress in vitro and prevents oral mucositis in vivo
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76.
Sheikh AA Vimalachandran D Thompson CC Jenkins RE Nedjadi T Shekouh A Campbell F Dodson A Prime W Crnogorac-Jurcevic T Lemoine NR Costello E 《Proteomics》2007,7(11):1929-1940
The cross-talk between tumour cells and the surrounding supporting host cells (stroma) is a key regulator of cancer growth and progression. By undertaking 2-DE analysis of laser capture microdissected malignant and stromal components of pancreatic tumours and benign ductal elements, we have identified high levels of S100A8 and S100A9 in tumour-associated stroma but not in benign or malignant epithelia. Immunohistochemical analysis (n = 71 patients) revealed strong expression of both proteins in stromal myeloid cells, subsequently identified as CD14(+)/CD68(- )monocytes/macrophages. Co-immunofluorescence revealed that S100A8 was expressed in a subset of S100A9-positive cells. Correlation of the expression of S100A8 and S100A9 to patient parameters revealed that the microenvironments of tumours which lacked expression of the tumour suppressor protein, Smad4, had significantly reduced numbers of S100A8-immunoreactive (p = 0.023) but not S100A9-immunoreactive (p = 0.21) cells. The ratio of S100A8- to S100A9-positive cells within individual tumours was significantly lower in Smad4-negative tumours than in Smad4-positive tumours (p<0.003). Pancreatitic specimens also contained S100A8- and S100A9-expressing cells, although this was not observed in regions displaying extensive fibrosis. In conclusion, our study provides an extensive analysis of S100A8 and S100A9 in pancreatic disease and highlights a potentially important relationship between pancreatic cancer cells and their surrounding microenvironment. 相似文献
77.
78.
Replication process of the parvovirus H-1. VIII. Partial denaturation mapping and localization of the replication origin of H-1 replicative-form DNA with electron microscopy. 总被引:7,自引:5,他引:2
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Partial denaturation mapping, restriction endonuclease digestion, and electron microscopy were used to determine which end of the linear duplex replicative-form (RF) DNA molecule contains the origin of RF replication for the parvovirus H-1. This origin was localized within approximately 300 base pairs of the arbitrarily designated right end of the RF DNA, in the EcoRI or HaeII-A fragment. Based on denaturation behavior in formamide, the right end was also found to have a relatively high guanine plus cytosine content, whereas the region adjacent to the left terminus of the RF DNA molecule was adenine plus thymine rich. 相似文献
79.
A nursing mother was given haloperidol 5 mg twice daily for puerperal psychosis and continued to breast feed under hospital supervision. Despite considerable amounts of haloperidol being secreted in the breast milk (up to 23.5 micrograms/l), the infant was apparently not sedated, fed well, and continued to thrive. The findings suggest that maternal ingestion of haloperidol for short periods has no deleterious effect on the infant''s development. 相似文献
80.
Santoni V Rouquié D Doumas P Mansion M Boutry M Degand H Dupree P Packman L Sherrier J Prime T Bauw G Posada E Rouzé P Dehais P Sahnoun I Barlier I Rossignol M 《The Plant journal : for cell and molecular biology》1998,16(5):633-641
A plasma membrane (PM) fraction was purified from Arabidopsis thaliana using a standard procedure and analyzed by two-dimensional (2D) gel electrophoresis. The proteins were classified according to their relative abundance in PM or cell membrane supernatant fractions. Eighty-two of the 700 spots detected on the PM 2D gels were microsequenced. More than half showed sequence similarity to proteins of known function. Of these, all the spots in the PM-specific and PM-enriched fractions, together with half of the spots with similar abundance in PM fraction and supernatant, have previously been found at the PM, supporting the validity of this approach. Extrapolation from this analysis indicates that (i) approximately 550 polypeptides found at the PM could be resolved on 2D gels; (ii) that numerous proteins with multiple locations are found at the PM; and (iii) that approximately 80% of PM-specific spots correspond to proteins with unknown function. Among the later, half are represented by ESTs or cDNAs in databases. In this way, several unknown gene products were potentially localized to the PM. These data are discussed with respect to the efficiency of organelle proteome approaches to link systematically genomic data to genome expression. It is concluded that generalized proteomes can constitute a powerful resource, with future completion of Arabidopsis genome sequencing, for genome-wide exploration of plant function. 相似文献