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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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Droperidol-fentanyl sedation for cardiac catheterization was evaluated in 106 consecutive children ≥ two years of age. The dose of 0.025 c.c. per kilogram of body weight (maximum 1 c.c.) produced adequate sedation in all but two patients without producing significant hypoventilation or heart rate changes. In patients without left heart volume overload or myocardial disease, left ventricular volume studies and pressurevelocity indices of contractile state were normal. Side effects were rarely encountered and easily controlled or reversed with diphenhydramine. Although we recommend this combination for cardiac catheterization sedation, we would not recommend exceeding our dosage schedule. 相似文献
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Abstract We report a case of a patient who sustained superior vena cava perforation just proximal to the innominate-caval confluence during pacemaker implantation. Because this complication was recognized early and the dilator was left in place, the patient remained hemodynamically stable and successfully underwent a videoscopically assisted repair of the superior vena caval perforation through a limited thoracotomy incision. 相似文献