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The binding and processing of monoclonal human IgG1 by cells of a human macrophage-like cell line (U937) 总被引:2,自引:0,他引:2
The goal of these experiments was to assess the relationship between the binding and processing of IgG by Fc-receptor-bearing cells. Cells of the U937 human macrophage-like cell line were incubated with 125I- labeled monomers, dimers, oligomers (composed of 2-4 IgG1 subunits), and HP (heavy polymers composed of 5 or more subunits per polymer) of monoclonal human IgG1 in vitro. Binding was assessed by spinning cells through a layer of phthalate oils. Internalization of IgG1 was assessed by quantitating residual binding to cells after surface-bound IgG was removed by a brief treatment with a solution containing 0.25 M acetic acid and 0.5 M sodium chloride. Catabolism was assessed by measuring the release of radioactive fragments of IgG1, which were not precipitated by 10% trichloroacetic acid. Unstimulated U937 bound about 10,000 molecules per cell of IgG1 monomer, with an equilibrium binding constant (Ka) of 5 X 10(8) M-1. After stimulation with a conditioned medium in vitro, binding per cell was increased 3-7--fold, and the Ka was decreased 2-4--fold. Both unstimulated and stimulated cells internalized and catabolized labeled IgG1 HP, but stimulated cells internalized and digested much more IgG1 HP per cell than unstimulated cells. Both monomers and dimers of IgG1 were internalized and degraded very slowly by stimulated cells, even though both preparations readily bound to cells. In contrast, oligomers and (to an even greater extent) IgG1 HP were internalized and degraded much more rapidly. Internalization of IgG1 HP was markedly inhibited by incubation at 4 degrees C, but not by incubation with a variety of metabolic inhibitors. Catabolism was inhibited by chloroquine and monensin (inhibitors of lysosomal acidification) and by cytochalasin (an inhibitor of microfilament polymerization). Binding to the surface of cells was not markedly inhibited by any agent tested. The capacity of cells to bind labeled IgG1 was markedly reduced by prior incubation in the presence of unlabeled IgG1. This reduction was in part due to the steric blockade of receptors caused by the avid, but reversible, binding of IgG1. In addition, IgG1 oligomers or HP (but not IgG1 monomers or dimers) also caused an irreversible reduction in the number of Fc receptors by a process analogous to receptor down-regulation, as observed in other receptor--ligand systems. 相似文献
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Australian occupational health was shaped by various social, political and economic forces during the latter half of the last century. An overall downturn in manufacturing and increased wage restraint during the early 1970s, encouraged trade unions to turn their attention to broader social issues, such as workplace health. Mainstream Australian society was also being influenced by wider community sentiment during this time, including anti-war protests, environmental lobby groups and the women's movement. Interest in occupational health subsequently flourished, with formalised education commencing in the 1970s, and the number of tertiary courses rapidly increasing throughout the 1980s. Occupational health and worker's compensation legislation similarly evolved throughout the latter stages of the twentieth century. Australian workplace health and safety is now based on a theory of self-regulation and managed in a tri-partite model, consisting of employers, trade unions and government departments. In Part 1 of our occupational health review, we outlined the historical development of Australian occupational health between 1788 and 1970. In the current paper, Part 2, we describe the historical development of Australian occupational health between 1970 and 2000. 相似文献
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We investigated the prevalence and distribution of Needlestick and Sharps Injuries (NSI) among a group of Australian medical undergraduates from 4 consecutive grades. Data was obtained by means of an anonymous, self-reporting survey. A total of 254 questionnaires were obtained (response rate 97.3%). Among them, 35 students (13.8%) had suffered a total of 41 NSI incidents. By gender, 71.4% of the NSI reporters were female and 28.6% were male. NSI prevalence varied significantly with respect to students' year of study (P for Trend=0.0106), ranging from 7.3% in the 1st year to 26.8% in the 3rd year. Of the 41 NSI incidents, 29.2% were caused by a glass item, 24.4% by a hollow bore needle, 24.4% by another device and 22.0% by a surgical device. The distribution by causative device also varied from year to year. Overall, this study has shown that NSI represent an important hazard for Australian medical students. As such, the importance of intervention strategies to reduce NSI exposures must remain an essential facet of medical education, worldwide. Future preventive measures will also need to consider the unique situation of medical students in Australia, as elsewhere. 相似文献
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