Cellular fibronectin (Fn) bearing an alternatively spliced extra type III structural repeat (ED1) is normally present at low concentrations in blood plasma. The source of this material remains uncertain. In this study, primary cultures of human umbilical vein endothelial cells (HUVEC) labeled with 35S-methionine were observed to synthesize Fn monomers both with and without this segment. Monomers isolated from cell lysates with antibodies to the ED1 sequence comigrated in nonreduced sodium dodecyl sulfate polyacrylamide gel electrophoresis with the slower (designated M1), but not the faster (designated M2), of two major monomeric populations that were recognized by antibodies raised to plasma-derived Fn. The differences between M1 and M2 were not due to glycosylation, since they were also observed between species of Fn monomer purified from cells grown in the presence of tunicamycin. M1 and M2 were both observed to incorporate with a similar rate into dimeric Fn, indicating that Fn monomers with and without the ED1 site can dimerize with similar efficiency. Analysis of reduced samples of Fn isolated from cells with anti-ED1 antibodies indicated the presence of both M1-M1 and M1-M2 dimers. In addition to being incorporated into extracellular matrix, ED1 + Fn was observed to be secreted in soluble form into the medium, potentially reflecting intravascular release of this protein by endothelial cells in vivo.
Sulfoxone was administered to 14 patients and the leveIs of dapsone (DOS) and monoacetyldapsone (MADDS) in plasma and urine were determined by spectro photofluorometric techniques. Peak plasma leveIs of DOS were approximately 600 ng/ml 5-8 h after treatment with 330 mg sulfoxone. The urinary excretion pattern of DOS and MADDS after this drug was similar to that found after DOS treatment, but total DOS excretion was lower. The results indicate that regular sulfoxone therapy provides plasma leveIs of DOS that would be expected to be therapeutically effective and to protect patients from the development of DDS-resistant le prosy. A recently developed high pressure liquid chromatogra phic f1uorome tric procedure was used to determine plasma leveIs of DOS, MADDS and parent drug in six patients receiving solasulfone. After a single SOO-rng intramuscular injection, plasma leveIs of DOS were only slightly above the minimal inhibitory concentration of DOS for My cobacterium leprae, but the concentration increased 4-fold after six 500-mg twice-weekly doses. The rate of disappearance of solasulfone was rapid, but concurrent DOS and MADDS c1earance times were longer than after DOS treatment. Direct relationships were found between 24-h DOS and solasulfone leveIs and among the disappearance rates of DOS, MADDS and solasulfone. Low leveIs of DOS after a single dose of solasulfone, as may be encountered in in terrupted therapy, could be accompanied by an unusually high risk of the emergence ar the selection of DDS-resistant My co. leprae in certain patients.
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