The histogenesis of hamster pancreatic cancer induced by N-nitroso-bis(2-hydroxypropyl)amine.
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Biomedical subjects
Publications and source records attributed to K Miyazaki.
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Fursosemide kinetics were studied in 25 patients with congestive heart failure. The elimination half-life (t1/2) was longer and the elimination rate constant and the plasma clearance smaller in patients with advanced (n = 15) than in those with moderate (n = 10) failure. Furosemide kinetics with and without hydralazine were compared in eight patients with advanced heart failure. Furosemide t1/2 patients receiving both drugs fell from 96 +/- 16 to 81 +/- 15 min (P less than 0.02), elimination rate constant increased from 0.0186 +/- 0.0056 to 0.0214 +/- 0.0068 min -1 (P less than 0.05), and plasma clearance rose from 72.6 +/- 18.5 to 88.1 +/- 26.9 ml/min (P less than 0.01). Renal clearance rose from 45.4 +/- 12.0 to 60.9 +/- 19.0 ml/min (P less than 0.01) and creatinine clearance was unchanged. We conclude that hydralazine affects furosemide kinetics.
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Competitive inhibitory behavior among zwitterionic beta-lactam antibiotics in the rat intestinal absorption process was examined. Intestinal absorption of cephradine and cephalexin was significantly inhibited by cyclacillin. The mutual inhibition between these amino-cephalosporins was also observed. On the other hand, in the pretreatment experiments with cyclacillin, it was found that absorption of cephradine was significantly inhibited, but the inhibitory effect of cyclacillin was not observed for cephalexin. These results showed that cephradine had a common carrier-mediated transport mechanism with cyclacillin which is not present in the absorption process of cephalexin. It was postulated that the mutual inhibition between cephradine and cephalexin is based on the competitive inhibition in the accumulation or uptake by the intestinal mucosa.
The binding characteristics of zwitterionic and monobasic beta-lactam antibiotics to the components in the intestinal mucosa of rat was investigated. From the binding experiments using the brush border membrane preparation and the insoluble cellular fractions, there was no correlation between the binding behavior and the absorption characteristics. However, there was a highly significant correlation between the affinity to the soluble F1 fraction and the absorption characteristics of these antibiotics. It was also found that the binding of these antibiotics to the other soluble protein fractions were significantly smaller than that to F1 fraction. It was postulated that the binding properties of these antibiotics to soluble F1 fraction play an important role in the absorption process.
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Unlike those experiments described in the previous several reports, a carcinogen was given to pregnant rats in our experiment to induce a tumor similar to yolk sac tumor which often occurs in human cases, aiming at contribution to establishment of an experimental model. Using Wister rat on the 10th day of gestation, ater removal of the fetus, the yolk sac was extracted out of the uterus, and a carcinogen was administered to it. Induced tumor was examined morphologically. By the 16th week after experiment, tumor was induced in 70% out of rats treated. The tumor volume was varied from a bean to a thumb tippize. Histologically, most of them were considered to be teratoma. But in 30% of them, human pure-type yolk sac tumor or the tumor similar to it were observed. Reticular and endodermal sinus or polyvesicular vitelline patterns were also clearly observed. Presence of hyaline body by PAS-staining and AFP by fluorescent antibody method were confirmed.
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When nuclei from various tissues of rats were incubated at 25 degrees with ATP[gamma-32P], the amounts of 32P incorporated in histone and non-histone protein per mg DNA reached maxima at 1 hr (maximum phosphorylation level). H1 histone and over 30 species of non-histone protein were phosphorylated as detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Only some of those species of non-histone protein, which were so low in content as to be indetectable by conventional protein staining, were prominently phosphorylated; their apparent molecular weights were 106K, 82K, 71K, 62K, 39K, 38K and 28K with brain, 39K, 38K, 32K, 31K and 22K with kidney and liver, 17.5K and 11.5K with thymus, and 11.5K with Rhodamine sarcoma (tissue-specific). In phosphorylation with liver nuclei, the tissue specificity changed neither with partial hepatectomy nor upon transplanting Rhodamine sarcoma. However, the maximum phosphorylation levels of the five species of non-histone protein increased with operation and decreased with tumor-bearing, to similar extents. On the other hand, the amounts of all the species of histone per mg DNA changed neither with operation nor with tumor-bearing, whereas the maximum phosphorylation level of H1 histone increased with operation, but not with tumor-bearing.
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