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Biomedical subjects

S Haga

Publications and source records attributed to S Haga.

At least 181 records · Page 10Linked to original sources

Studies on the synthesis of chemotherapeutics. 10. Synthesis and antitumor activity of N-acyl- and N-(alkoxycarbonyl)-5-fluorouracil derivatives.

A number of N-acyl and N-(alkoxycarbonyl)-5-fluorouracil derivatives possessing, for example, benzoyl, o-toluyl, acetyl, propionyl, heptanoyl, ethoxycarbonyl, phenoxycarbonyl, and benzyloxycarbonyl groups as N1 and/or N3 substituents were synthesized, and their antitumor activities were evaluated. The synthesis was achieved by a direct and two-step acylation of 5-fluorouracil and by selective N1-deacetylation of N1-acetyl-N3-substituted-5-fluorouracil under appropriate reaction conditions. Several N3-benzoyl- and N3-o-toluyl-5-fluorouracil derivates and showed significant activity against experimental tumor, and N1-acetyl-N3-o-toluyl-5-fluorouracil was found to be most promising among them. Further investigation revealed 12 to retain higher activity toward various tumors, with lower toxicity and good blood level, than either 1 or FT-207, even for oral administration.

Animals↗

Partial purification of guinea pig MIF by affinity column chromatography using macrophages.

First we have confirmed the previous observation that the macrophage migration inhibitory factor (MIF) was adsorbed on normal peritoneal macrophages when they were incubated at 4 C for 60 min. It was found that macrophages fixed with 2% glutaraldehyde gave more reproducible results than viable cells in terms of "adsorption" of guinea pig MIF. The adsorption was achieved more completely at 37 C than at 4 C, indicating that this reaction is a temperature-dependent phenomenon. Using these glutaraldehyde-fixed macrophages, a kind of cell-affinity column was successfully developed. The guinea pig MIF preparation lost its activity when it was passed through this affinity column, and MIF adsorbed on the column was recovered by elution with 0.1 M (L)-fucose of 0.1 M (D)-glucose. Such MIF active eluate was found to be at least 30--40 fold more pure than the original MIF preparation which had been previously fractionated according to its molecular weight. Therefore, this type of macrophage-affinity column may be useful for the purification of MIF.

Adsorption↗

Immunofluorescence studies on localization of actin-like protein in the mouse brain.

Localization of actin-like protein in the mouse brain was studied by the immunofluorescence method using FITC-labeled antiactin antibody. Antibody against actin was prepared according to Lazarides (1974). The problem of poor antigenicity and the presence of contaminants in the antigen preparation was circumvented by way of denaturation of the protein with sodium dodecyl sulfate (SDS) and subsequent purification of the antigen by SDS polyacrylamide gel electrophoresis (Lazarides, 1974). Intense specific fluorescence against actin was noted in the cytoplasma of the epithelial cells of the choroid plexus, of the ependymal cells of the ventricles, and a little less one in arachnoidea and in leptomeninges, as well as in the muscle layers, endothelial linings, and adventitia of the arteries. Diffuse but weak fluorescence was noted also in the neuropil of the grey matter of the brain. Among the latter, fluorescence in the granular layer of Ammon's horn and of the cerebellum appeared clearer than the diffuse one in the rest of the grey matter. Functional significance of the presence of actin-like protein in the above tissues was discussed.

Actins↗

The statistical distribution of macrophage migration distance and its application to MIF test.

The measurement of the distance of macrophage migration is very simple and reasonable as a technique in MIF assay. By the use of this technique, a large scale model experiment was performed and its data were analysed statistically. As the result of analysis, Student's t-test for significance of the difference between control and test readings of migration distance at low activity level in the MIF test was justified, and it was proved that it is applicable to the routine MIF test. In addition to this, the measurement of migration distance was compared with that of migration area.

Animals↗