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101.
Dallemagne P Khanh LP Alsaïdi A Varlet I Collot V Paillet M Bureau R Rault S 《Bioorganic & medicinal chemistry》2003,11(7):1161-1167
A series of 10 derivatives 2-6 issued from the fusion of various five-membered heterocycles to cyclopenta[c]thiophene were evaluated for potential anticancer activity in the NCI's in vitro human disease-oriented tumor cell line screening panel that consisted of 60 human tumor cell lines arranged in nine subpanels, representing diverse histologies. Among these tested compounds, four were found to be cytotoxic allowing us to point out some structure-activity relationships. The oxazolidinone derivatives 2a-c displayed further in vivo antitumor activity in the hollow fiber assay and standard xenograft testing developed at the NCI. 相似文献
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105.
Belinda J. Gabbe Pam M. Simpson Ronan A. Lyons Shanthi Ameratunga James E. Harrison Sarah Derrett Suzanne Polinder Gabrielle Davie Frederick P. Rivara 《PloS one》2014,9(12)
Objective
To determine associations between the number of injuries sustained and three measures of disability 12-months post-injury for hospitalised patients.Methods
Data from 27,840 adult (18+ years) participants, hospitalised for injury, were extracted for analysis from the Validating and Improving injury Burden Estimates (Injury-VIBES) Study. Modified Poisson and linear regression analyses were used to estimate relative risks and mean differences, respectively, for a range of outcomes (Glasgow Outcome Scale-Extended, GOS-E; EQ-5D and 12-item Short Form health survey physical and mental component summary scores, PCS-12 and MCS-12) according to the number of injuries sustained, adjusted for age, sex and contributing study.Findings
More than half (54%) of patients had an injury to more than one ICD-10 body region and 62% had sustained more than one Global Burden of Disease injury type. The adjusted relative risk of a poor functional recovery (GOS-E<7) and of reporting problems on each of the items of the EQ-5D increased by 5–10% for each additional injury type, or body region, injured. Adjusted mean PCS-12 and MCS-12 scores worsened with each additional injury type, or body region, injured by 1.3–1.5 points and 0.5 points, respectively.Conclusions
Consistent and strong relationships exist between the number of injury types and body regions injured and 12-month functional and health status outcomes. Existing composite measures of anatomical injury severity such as the NISS or ISS, which use up to three diagnoses only, may be insufficient for characterising or accounting for multiple injuries in disability studies. Future studies should consider the impact of multiple injuries to avoid under-estimation of injury burden. 相似文献106.
Diane Rebourcet Peter J. O’Shaughnessy Ana Monteiro Laura Milne Lyndsey Cruickshanks Nathan Jeffrey Florian Guillou Tom C. Freeman Rod T. Mitchell Lee B. Smith 《PloS one》2014,9(8)
The Sertoli cells are critical regulators of testis differentiation and development. In the adult, however, their known function is restricted largely to maintenance of spermatogenesis. To determine whether the Sertoli cells regulate other aspects of adult testis biology we have used a novel transgenic mouse model in which Amh-Cre induces expression of the receptor for Diphtheria toxin (iDTR) specifically within Sertoli cells. This causes controlled, cell-specific and acute ablation of the Sertoli cell population in the adult animal following Diphtheria toxin injection. Results show that Sertoli cell ablation leads to rapid loss of all germ cell populations. In addition, adult Leydig cell numbers decline by 75% with the remaining cells concentrated around the rete and in the sub-capsular region. In the absence of Sertoli cells, peritubular myoid cell activity is reduced but the cells retain an ability to exclude immune cells from the seminiferous tubules. These data demonstrate that, in addition to support of spermatogenesis, Sertoli cells are required in the adult testis both for retention of the normal adult Leydig cell population and for support of normal peritubular myoid cell function. This has implications for our understanding of male reproductive disorders and wider androgen-related conditions affecting male health. 相似文献
107.
Three proteins secreted by Listeria monocytogenes facilitate escape from macrophage vacuoles: the cholesterol-dependent cytolysin listeriolysin O (LLO), a phosphoinositide-specific phospholipase C (PI-PLC) and a broad-range phospholipase C (PC-PLC). LLO and PI-PLC can activate several members of the protein kinase C (PKC) family during infection. PKCepsilon is a novel PKC that contributes to macrophage activation, defence against bacterial infection, and phagocytosis; however, a role for PKCepsilon in Lm infections has not been described. To study PKCepsilon dynamics, PKCepsilon-YFP chimeras were visualized in macrophages during Lm infection. PKCepsilon-YFP was recruited to forming vacuoles during macrophage phagocytosis of Lm and again later to fully formed Lm vacuoles. The PKCepsilon-YFP localization to the fully formed Lm vacuole was LLO-dependent but independent of PI-PLC or PC-PLC. PKCepsilon-YFP recruitment often followed LLO perforation of the membrane, as indicated by localization of PKCepsilon-YFP to Lm vacuoles after they released small fluorescent dyes into the cytoplasm. PKCepsilon-YFP recruitment to vesicles also followed phagocytosis of LLO-containing liposomes or osmotic lysis of endocytic vesicles, indicating that vacuole perforation by LLO was the chief cause of the PKCepsilon response. These studies implicate PKCepsilon in a cellular mechanism for recognizing damaged membranous organelles, including the disrupted vacuoles created when Lm escapes into cytoplasm. 相似文献
108.
Characterization of inhibition of M2 ion channel activity by BL-1743, an inhibitor of influenza A virus.
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Q Tu L H Pinto G Luo M A Shaughnessy D Mullaney S Kurtz M Krystal R A Lamb 《Journal of virology》1996,70(7):4246-4252
The influenza A virus M2 integral membrane protein has ion channel activity that can be inhibited by the antiviral drug amantadine. Recently, a spirene-containing compound, BL-1743 (2-[3-azaspiro (5,5)undecanol]-2-imidazoline), that inhibits influenza virus growth was identified (S. Kurtz, G. Lao, K. M. Hahnenberger, C. Brooks, O. Gecha, K. Ingalls, K.-I. Numata, and M. Krystal, Antimicrob. Agents Chemother. 39:2204-2209, 1995). We have examined the ability of BL-1743 to inhibit the M2 ion channel when expressed in oocytes of Xenopus laevis. BL-1743 inhibition is complete as far as can be measured by electrophysiological methods and is reversible, with a reverse reaction rate constant of 4.0 x 10(-3) s(-1). In contrast, amantadine inhibition is irreversible within the time frame of the experiment. However, BL-1743 inhibition and amantadine inhibition have similar properties. The majority of isolated influenza viruses resistant to BL-1743 are also amantadine resistant. In addition, all known amino acid changes which result in amantadine resistance also confer BL-1743 resistance. However, one BL-1743-resistant virus isolated, designated M2-I35T, contained the change Ile-35-->Thr. This virus is >70-fold more resistant to BL-1743 and only 10-fold more resistant to amantadine than the wild-type virus. When the ion channel activity of M2-I35T was examined in oocytes, it was found that M2-I35T is BL-1743 resistant but is reversibly inhibited by amantadine. These findings suggest that these two drugs interact differently with the M2 protein transmembrane pore region. 相似文献
109.
Brownridge P Holman SW Gaskell SJ Grant CM Harman VM Hubbard SJ Lanthaler K Lawless C O'Cualain R Sims P Watkins R Beynon RJ 《Proteomics》2011,11(15):2957-2970
In this paper, we discuss the challenge of large-scale quantification of a proteome, referring to our programme that aims to define the absolute quantity, in copies per cell, of at least 4000 proteins in the yeast Saccharomyces cerevisiae. We have based our strategy on the well-established method of stable isotope dilution, generating isotopically labelled peptides using QconCAT technology, in which artificial genes, encoding concatenations of tryptic fragments as surrogate quantification standards, are designed, synthesised de novo and expressed in bacteria using stable isotopically enriched media. A known quantity of QconCAT is then co-digested with analyte proteins and the heavy:light isotopologues are analysed by mass spectrometry to yield absolute quantification. This workflow brings issues of optimal selection of quantotypic peptides, their assembly into QconCATs, expression, purification and deployment. 相似文献
110.
Ronan M Conroy 《BMJ (Clinical research ed.)》1993,307(6910):1004-1005