排序方式: 共有26条查询结果,搜索用时 31 毫秒
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Ha-Soon Choi Paul V. Rucker Zhicheng Wang Yi Fan Pamela Albaugh Greg Chopiuk Francois Gessier Fangxian Sun Francisco Adrian Guoxun Liu Tami Hood Nanxin Li Yong Jia Jianwei Che Susan McCormack Allen Li Jie Li Auzon Steffy AnneMarie Culazzo Celine Tompkins Van Phung Andreas Kreusch Min Lu Bin Hu Apurva Chaudhary Mahavir Prashad Tove Tuntland Bo Liu Jennifer Harris H. Martin Seidel Jon Loren Valentina Molteni 《ACS medicinal chemistry letters》2015,6(5):562-567
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Kati WM Montgomery D Carrick R Gubareva L Maring C McDaniel K Steffy K Molla A Hayden F Kempf D Kohlbrenner W 《Antimicrobial agents and chemotherapy》2002,46(4):1014-1021
A-315675 is a novel, pyrrolidine-based compound that was evaluated in this study for its ability to inhibit A and B strain influenza virus neuraminidases in enzyme assays and influenza virus replication in cell culture. A-315675 effectively inhibited influenza A N1, N2, and N9 and B strain neuraminidases with inhibitor constant (K(i)) values between 0.024 and 0.31 nM. These values were comparable to or lower than the K(i) values measured for oseltamivir carboxylate (GS4071), zanamivir, and BCX-1812, except for the N1 enzymes that were found to be the most sensitive to BCX-1812. The time-dependent inhibition of neuraminidase catalytic activity observed with A-315675 is likely due to its very low rate of dissociation from the active site of neuraminidase. The half times for dissociation of A-315675 from B/Memphis/3/89 and A/Tokyo/3/67 (H3N2) influenza virus neuraminidases of 10 to 12 h are significantly slower than the half times measured for oseltamivir carboxylate (33 to 60 min). A-315675 inhibited the replication of several laboratory strains of influenza virus in cell culture with potencies that were comparable or superior to those for oseltamivir carboxylate and BCX-1812, except for the A/H1N1 viruses that were found to be two- to fourfold more susceptible to BCX-1812. A-315675 and oseltamivir carboxylate exhibited comparable potencies against a panel of A/H1N1 and A/H3N2 influenza virus clinical isolates, but A-315675 was found to be significantly more potent than oseltamivir carboxylate against the B strain isolates. The favorable in vitro results relative to other clinically effective agents provide strong support for the further investigation of A-315675 as a potential therapy for influenza virus infections. 相似文献
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Abimbola A. Akintola Annette van den Berg Irmhild Altmann-Schneider Steffy W. Jansen Mark A. van Buchem P. Eline Slagboom Rudi G. Westendorp Diana van Heemst Jeroen van der Grond 《Age (Dordrecht, Netherlands)》2015,37(4)
Given the concurrent, escalating epidemic of diabetes mellitus and neurodegenerative diseases, two age-related disorders, we aimed to understand the relation between parameters of glucose metabolism and indices of pathology in the aging brain. From the Leiden Longevity Study, 132 participants (mean age 66 years) underwent a 2-h oral glucose tolerance test to assess glucose tolerance (fasted and area under the curve (AUC) glucose), insulin sensitivity (fasted and AUC insulin and homeostatic model assessment of insulin sensitivity (HOMA-IS)) and insulin secretion (insulinogenic index). 3-T brain MRI was used to detect macro-structural damage (atrophy, white matter hyper-intensities, infarcts and/or micro-bleeds) and magnetization transfer imaging (MTI) to detect loss of micro-structural homogeneity that remains otherwise invisible on conventional MRI. Macro-structurally, higher fasted glucose was significantly associated with white matter atrophy (P = 0.028). Micro-structurally, decreased magnetization transfer ratio (MTR) peak height in gray matter was associated with higher fasted insulin (P = 0.010), AUCinsulin (P = 0.001), insulinogenic index (P = 0.008) and lower HOMA-IS index (P < 0.001). Similar significant associations were found for white matter. Thus, while higher glucose was associated with macro-structural damage, impaired insulin action was associated more strongly with reduced micro-structural brain parenchymal homogeneity. These findings offer some insight into the association between different parameters of glucose metabolism (impairment of which is characteristic of diabetes mellitus) and brain aging. 相似文献
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Liu J Johnson K Li J Piamonte V Steffy BM Hsieh MH Ng N Zhang J Walker JR Ding S Muneoka K Wu X Glynne R Schultz PG 《Proceedings of the National Academy of Sciences of the United States of America》2011,108(35):14560-14565
Regeneration of peripheral differentiated tissue in mammals is rare, and regulators of this process are largely unknown. We carried out a forward genetic screen in mice using N-ethyl-N-nitrosourea mutagenesis to identify genetic mutations that affect regenerative healing in vivo. More than 400 pedigrees were screened for closure of a through-and-through punch wound in the mouse ear. This led to the identification of a single pedigree with a heritable, fast, and regenerative wound-healing phenotype. Within 5 wk after ear-punch, a threefold decrease in the diameter of the wound was observed in the mutant mice compared with the wild-type mice. At 22 wk, new cartilage, hair follicles, and sebaceous glands were observed in the newly generated tissue. This trait was mapped to a point mutation in a receptor for TGF-β, TGFBR1. Mouse embryonic fibroblasts from the affected mice had increased expression of a subset of TGF-β target genes, suggesting that the mutation caused partial activation of the receptor. Further, bone marrow stromal cells from the mutant mice more readily differentiated to chondrogenic precursors, providing a plausible explanation for the enhanced development of cartilage islands in the regenerated ears. This mutant mouse strain provides a unique model to further explore regeneration in mammals and, in particular, the role of TGFBR1 in chondrogenesis and regenerative wound healing. 相似文献
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V. Anil Kumar Katherin Steffy Maitrayee Chatterjee Madhan Sugumar Kavitha R. Dinesh Anand Manoharan Shamsul Karim Raja Biswas 《Journal of clinical microbiology》2013,51(1):318-319
Reports of oxacillin-susceptible mecA-positive Staphylococcus aureus strains are on the rise. Because of their susceptibility to oxacillin and cefoxitin, it is very difficult to detect them by using routine phenotypic methods. We describe two such isolates that were detected by chromogenic medium and confirmed by characterization of the mecA gene element. 相似文献
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Iriart X Delarche N Auzon P Denard M Estrade G 《Annales de cardiologie et d'angeiologie》2005,54(5):257-262
The treatment of acute myocardial infarction is in evolution. Several strategies are utilized ranging from thrombolysis to percutaneous angioplasty (PCI), and the combination of both treatments; the latter providing an interesting compromise between treatment delay and efficiency of early myocardial reperfusion. We reviewed the early treatment strategies of acute myocardial infarctions undertaken by Samu in region 6 (south west of France) in 2002. Of a cohort of 115 patients, 83 patients (72.1%) had a revascularisation strategy: 56 (48.7%) had a primary PCI, and 27 (23.4%) had thrombolysis (92.6% being performed in the prehospital treatment). In those undergoing thrombolysis, 13 patients (48%) had ongoing features of ischaemia; excluding 4 patients who died during transport, all had a PCI at the admission in hospital. For the 14 patients with successful thrombolysis, 5 had facilitated PCI at the admission, 8 had a delayed angioplasty and 1 patient did not have angiography. Although the number of patients receiving thrombolysis in this study was small, this treatment was begun 62 minutes before primary PCI. There are important intra and extra hospital delays to the commencement of PCI. The easy utility of thrombolysis together with the potential to PCI argue in favour for a strategy of prehospital thrombolysis associated with a facilitated angioplasty. 相似文献
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Ovenden SP Sberna G Tait RM Wildman HG Patel R Li B Steffy K Nguyen N Meurer-Grimes BM 《Journal of natural products》2004,67(12):2093-2095
The new diketopiperazine dimer 1, as well as the known compounds TMC-256A1 (2), TMC-256C1 (3), and demethylkotanin (4), were isolated from a culture of Aspergillus niger. The gross structure of 1 was determined by 2D NMR studies and comparison with literature data, and the absolute stereochemistry was elucidated by chiral HPLC analysis of the hydrolysis products. 相似文献
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