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Biomedical subjects

S Kitano

Publications and source records attributed to S Kitano.

At least 415 records · Page 23Linked to original sources
PubMed1980

Effect of coadministration of thymine or thymidine on the antitumor activity of 1-(2-tetrahydrofuryl)-5-fluorouracil and 5-fluorouracil.

The antitumor activity of 1-(2-tetrahydrofuryl)-5-fluorouracil (FT-207) on sarcoma was enhanced by oral coadministration of uracil, thymine, or thymidine. The activity was enhanced equally by thymine and by uracil than by thymidine, but thymine caused loss in body weight. The antitumor activity of 5-fluorouracil (5-FU) was also enhanced by thymine or uracil, but both caused loss in body weight. Degradation of 5-FU in vitro was inhibited more by thymine than by uracil. Phosphorylation of 5-FU, however, was not inhibited by uracil, thymine, or thymidine, even at 100 times the concentration of 5-FU. These results suggest that the mechanism of enhancement of the antitumor activity of FT-207 by thymine or thymidine was similar to that by uracil, and that uracil had more effect than thymine or thymidine in enhancing antitumor effect of these drugs to FT-207 without toxicity.

Administration, Oral↗
PubMed1979

Effect of coadministration of uracil or cytosine on the anti-tumor activity of clinical doses of 1-(2-tetrahydrofuryl)-5-fluorouracil and level of 5-fluorouracil in rodents.

Concentration of 5-fluorouracil (5-FU) in the tumor, blood, and various organs of AH130-bearing rats after administration of clinical doses of 1-(2-tetrahydrofuryl)-5-fluorouracil (FT-207) and uracil was examined. The concentration of 5-FU in blood was less than 0.02 microgram/ml with all combinations of FT-207 and uracil except high molar ratios of uracil to FT-207 (ratio, 5 and 10), whereas high concentrations of up to a maximum of 0.200 microgram/g on administration of uracil plus 5 or 7.5 mg/kg of FT-207 (ratio, 4), was found in the tumor. On oral administration of FT-207 plus uracil in various combinations, the highest T/B (ratio of concentration of 5-FU in the tumor to that in blood) value was obtained at a ratio of uracil to FT-207 of 4. With this combination, 5-FU concentration in the tumor, muscle, and spleen was higher than that after administration of FT-207 alone (5 mg/kg). These results suggest that at the clinical doses the optimum molar ratio of uracil to FT-207 is 4. Coadministration of cytosine enhanced the antitumor activity of FT-207 on sarcoma-180 in mice. However, cytosine enhanced the antitumor activity of FT-207 less than uracil and its coadministration resulted in a lower concentration of 5-FU in the tumor than coadministration of uracil.

Administration, Oral↗
PubMed1979

Effect of uracil on metabolism of 5-fluorouracil in vitro.

The effect of uracil on the metabolism of 5-fluorouracil (5-FU) in vitro was studied. 5-FU was mainly phosphorylated in intact Yoshida sarcoma cells, whereas it was mainly degraded in liver slices. Uracil inhibited degradation of 5-FU much more than its phosphorylation; incubation of 2,500 microM of uracil with 2.5 microM of 5-FU (molar ratio, 1,000:1) inhibited the degradation of 5-FU by 70%, but did not affect its phosphorylation. With homogenates of Yoshida sarcoma or liver uracil inhibited degradation of 5-FU greatly, phosphorylation of 5-FU by alpha-D-ribose 1-phosphate (RiblP) and ATP to some extent, and phosphorylation by 5-phospho-alpha-D-ribosyl diphosphate (PPRibP) very little. The activities of the enzymes involved in the metabolism of 5-FU in various tissues were also determined. Degradation of 5-FU was much faster in liver than in other tissues and was very slow in tumor tissue. Phosphorylation of 5-FU with RiblP and ATP was rapid in Yoshida sarcoma and bone marrow. Phosphoribosyltransferase activity was high in Yoshida sarcoma and thymus, but low in bone marrow.

Animals↗
PubMed1978

"Chemical aminoacylation" of tRNA's.

Incubation of abbreviated tRNA's (tRNA-C-COH's) with (chemically) preaminoacylated P1, P2-di(adenosine 5'-)diphosphates in the presence of purified RNA ligase effected transfer of an aminoacyladenylate moiety to the 3'-terminus of the abbreviated tRNA's in good yield. Aminoacylated (or misacylated) tRNA's may thus be prepared from fractionated or unfractionated tRNA-C-COH's; each of the five aminoacylated dinucleoside diphosphates tested was utilized as a substrate by RNA ligase. That the resulting "chemically aminoacylated" tRNA's were identical with those prepared by enzymatic aminoacylation was judged by comparison of 1) chromatographic properties on benzolated diethylaminoethyl-cellulose, 2) rates of chemical deacylation, and 3) affinities for elongation factor Tu, as well as 4) the ability of misacylated tRNA's so derived to be deacylated chemically and then reactivated enzymatically with their cognate amino acids.

Adenine Nucleotides↗
PubMed1978

Interaction of "aza" and "deaza" analogs of adenosine cyclic 3', 5'-phosphate with some enzymes of adenosine cyclic 3', 5'-phosphate metabolism: evidence that the lone pair electrons of N-3 are involved in the binding of adenosine cyclic 3', 5'-phosphate to type II adenosine cyclic 3', 5'-phosphate-dependent protein kinase.

Five hetercyclic analogs of adenosine cyclic 3',5'-phosphate (cyclic AMP) were examined for their ability (1) to stimulate type II cyclic AMP-dependent kinases from bovine brain, bovine heart, and rat liver; (2) to serve as substrates for "high Km" (Km for cyclic AMP = 0.13-0.43 mM) cyclic nucleotide phosphodiesterases from bovine heart, rabbit kidney, and rat liver; and (3) to inhibit the hydrolysis of cyclic AMP catalyzed by "low Km" (Km for cAMP = 0.32-1.5 muM) cyclic nucleotide phosphodiesterases from bovine brain, bovine heart, dog heart, rabbit liver, rat brain and rat liver. The analogs all had a purine ring system which had been modified by replacement of a ring carbon with nitrogen or vice versa to yield 2-aza-cAMP (7-amino-4-beta-D-ribofuranosylimidazo [4,5-d] -v-triazine cyclic 3',5'-phosphate); 8-aza-cAMP (7-amino-3-beta-D-ribofuranosyl-v-triazolo-[4,5-d]-pyrimidine cyclic 3',5'-phosphate); 1 deaza-cAMP (7-amino-3-beta-D-ribofuranosylimidazo [4,5-b[pyridine cyclic 3',5'-phosphate); 3-deaza-cAMP (4-amino-1-beta-D-ribofuranosylimidazo[4,5-c]pyridine cyclic 3',5'-phosphate) and 7-deaza-cAMP (7-amino-4-beta-D-ribofuranosylpyrrolo[2,3-d]pyrimidine cyclic 3',5'-phosphate).

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1977

[The cialit-conserved trachea homograft (author's transl)].

After all techniques for reconstruction of tracheal segments with trachea-homografts, known from the literature, have failed to show satisfactory functional results, we have carried out further experiments concerning this subject. Our main interest was focused on the following topics: 1. the regeneration pattern of the respiratory epithelium in the trachea, 2. possibilities of the conservation of trachea-transplants, 3. the behaviour of the receptor area against trachea homografts. We found, that in correspondence with clinical observations, even large circumferencial defected epithelial areas in the mucous layer of the trachea have been regenerated in a form of new mucous membrane which showed no morphological difference from normal structure. Segments of trachea can be preserved in Cialit solution. Prefixation in formaldehydsaline fixative improves the preservation of the tissue structure. Homografts obtained in the above described technique could almost always be made to heal, either directly in the trachea or in the subcutaneous tissue of the recipient-animals. The behaviour of the cartilage and the epithelium is demonstrated by histological methods as well as by scanning electronmicroscopy.

Animals↗