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Arora J Bordeleau M Dube L Jarvie K Mazzocco L Peragine J Tehim A Egle I 《Bioorganic & medicinal chemistry letters》2005,15(23):5253-5256
A series of N-[(3S)-1-benzylpyrrolidin-3-yl]-(2-thienyl)benzamides 8 has been prepared and found to bind with high affinity to the human D(4) (hD(4)) and 5-HT(2A) receptors. Several compounds displayed selectivity for these receptors versus hD(2) and alpha(1) adrenergic receptors of over 500-fold. 相似文献
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Morandi F Scaruffi P Gallo F Stigliani S Moretti S Bonassi S Gambini C Mazzocco K Fardin P Haupt R Arcamone G;Italian Cooperative Group for Neuroblastoma Pistoia V Tonini GP Corrias MV 《PloS one》2012,7(1):e29922
Metastases in the bone marrow (BM) are grim prognostic factors in patients with neuroblastoma (NB). In spite of extensive analysis of primary tumor cells from high- and low-risk NB patients, a characterization of freshly isolated BM-infiltrating metastatic NB cells is still lacking. Our aim was to identify proteins specifically expressed by metastatic NB cells, that may be relevant for prognostic and therapeutic purposes. Sixty-six Italian children over 18 months of age, diagnosed with stage 4 NB, were included in the study. Metastatic NB cells were freshly isolated from patients' BM by positive immunomagnetic bead manipulation using anti-GD2 monoclonal antibody. Gene expression profiles were compared with those obtained from archived NB primary tumors from patients with 5 y-follow-up. After validation by RT-qPCR, expression/secretion of the proteins encoded by the up-regulated genes in the BM-infiltrating NB cells was evaluated by flow cytometry and ELISA. Compared to primary tumor cells, BM-infiltrating NB cells down-modulated the expression of CX3CL1, AGT, ATP1A2 mRNAs, whereas they up-regulated several genes commonly expressed by various lineages of BM resident cells. BM-infiltrating NB cells expressed indeed the proteins encoded by the top-ranked genes, S100A8 and A9 (calprotectin), CD177 and CD3, and secreted the CXCL7 chemokine. BM-infiltrating NB cells also expressed CD271 and HLA-G. We have identified proteins specifically expressed by BM-infiltrating NB cells. Among them, calprotectin, a potent inflammatory protein, and HLA-G, endowed with tolerogenic properties facilitating tumor escape from host immune response, may represent novel biomarkers and/or targets for therapeutic intervention in high-risk NB patients. 相似文献
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A membrane protein that specifically binds the insect neuropeptide proctolin was purified using standard chromatography from cockroach foregut membranes. Proctolin-binding sites were efficiently solubilized with either the nonionic detergent digitonin or the zwitterionic detergent Chaps, as indicated by the specific binding of 3H-proctolin to solubilized samples. A solubilized sample obtained from 1600 foregut membranes was subjected to a five-step chromatographic purification including chromatofocusing, anion-exchange and size-exclusion chromatographies. The final size-exclusion separation resulted in the isolation of approximately 100 pmol of purified proctolin-binding proteins, eluting as a single peak at approximately 74 kDa. Analysis of the purified sample using SDS/PAGE and silver staining showed two bands at 80 kDa and 76 kDa. Densitometric analysis of the gel indicated that each band contained approximately 7-8 microg of protein, suggesting that one band corresponds to the proctolin-binding activity. Proctolin-binding proteins were thus purified 1800-fold using standard chromatography. 相似文献
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R. P. Johnson B. Holtslander A. Mazzocco S. Roche J. L. Thomas F. Pollari K. D. M. Pintar 《Applied and environmental microbiology》2014,80(7):2166-2175
Verotoxin-producing Escherichia coli (VTEC) strains are the cause of food-borne and waterborne illnesses around the world. Traditionally, surveillance of the human population as well as the environment has focused on the detection of E. coli O157:H7. Recently, increasing recognition of non-O157 VTEC strains as human pathogens and the German O104:H4 food-borne outbreak have illustrated the importance of considering the broader group of VTEC organisms from a public health perspective. This study presents the results of a comparison of three methods for the detection of VTEC in surface water, highlighting the efficacy of a direct VT immunoblotting method without broth enrichment for detection and isolation of O157 and non-O157 VTEC strains. The direct immunoblot method eliminates the need for an enrichment step or the use of immunomagnetic separation. This method was developed after 4 years of detecting low frequencies (1%) of E. coli O157:H7 in surface water in a Canadian watershed, situated within one of the FoodNet Canada integrated surveillance sites. By the direct immunoblot method, VTEC prevalence estimates ranged from 11 to 35% for this watershed, and E. coli O157:H7 prevalence increased to 4% (due to improved method sensitivity). This direct testing method provides an efficient means to enhance our understanding of the prevalence and types of VTEC in the environment. This study employed a rapid evidence assessment (REA) approach to frame the watershed findings with watershed E. coli O157:H7 prevalences reported in the literature since 1990 and the knowledge gap with respect to VTEC detection in surface waters. 相似文献
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Meng CQ Rakhit S Lee DK Kamboj R McCallum KL Mazzocco L Dyne K Slassi A 《Bioorganic & medicinal chemistry letters》2000,10(9):903-905
A series of 5-(2- or 3-thienyl)tryptamine derivatives (9) has been synthesized and shown to be potent and selective 5-HT1D versus 5-HT1B receptor agonists and, therefore, potential treatments for migraine. 相似文献
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K. Mazzocco P. Scaruffi C. Gambini F. Negri G. P. Tonini 《Apoptosis : an international journal on programmed cell death》1996,1(1):63-68
We studied apoptosis in 36 neuroblastomas by DNA ladder assay. Expression of bcl2- and mRNA isoforms and protein were detected by RT-PCR and by immunohistochemistry, respectively. Internucleosomal DNA fragmentation was found in 20/36 (56%) tumor tissues collected both at onset and relapse of disease. Bcl-2 and mRNAs and protein were found in almost all examined tumors irrespective of DNA ladder, thus showing lack of correlation with the clinical stage. BCL-2 protein was observed to be expressed at various levels in undifferentiated and in more differentiated neuroblasts, while the stroma and the fibrovascular tissue were negative. Our results show that apoptosis is present in neuroblastoma at all stages and that bcl-2 gene is widely expressed in tumor tissue. In our series of neuroblastomas, bcl-2 expression is not correlated with unfavorable prognosis. 相似文献