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Biomedical subjects

A Matsuda

Publications and source records attributed to A Matsuda.

At least 487 records · Page 27Linked to original sources
PubMed1980

Kinetics of the reaction of bleomycin-Fe(II)-O2 complex with DNA.

The kinetics of the reaction of BLM-Fe(II)-O2 with DNA in the absence or presence of 2-mercaptoethanol (2-ME) were studied. The total number of bases released by BLM-Fe(II)-O2 in the presence of 2-ME increased about 6.5 times more than that in the absence of 2-ME in the reaction of 6 hours at 37 degrees C. The molar ratios of the released bases ware little affected by the reaction time, temperature or 2-ME. Among the four bases, thymine was preferentially released. On the basis of a reaction scheme of BLM-Fe(II)-O2 with DNA, the equations were derived by the steady-state method. In the absence of 2-ME, the release of bases from DNA was dependent on the concentration of BLM-Fe(II)-O2, but independent of the concentration of DNA. In the presence of 2-ME, a biphasic reaction was observed; the first one is due to BLM-Fe(II) which originally existed and the second one is due to BLM-Fe(II) produced by the reduction of BLM-Fe(III) with 2-ME. In the second reaction, the rate of the release of bases from DNA was proportional to the concentration of BLM-Fe(II) and 2-ME, but inversely proportional to the concentration of DNA. The rate-determining step in the reaction of BLM-Fe(II)-O2 with DNA in the presence of 2-ME was found to be the reduction of BLM-Fe(III) to BLM-Fe(II). By these kinetic studies, the reaction of BLM-Fe(II)-O2 with DNA in the presence of 2-ME was elucidated to proceed in a catalytic fashion. Furthermore, the maximum number of bases released by BLM from DNA was one base per twelve to thirteen bases.

Base Composition↗
PubMed1980

Use of alpha-secondary isotope effects in nucleophile-promoted reactions of pyrimidine derivatives; evidence for transient 5,6-dihydropyrimidine intermediates.

alpha-Secondary isotope effect provides a useful tool for detection of transient 5,6-dihydropyrimidine intermediates which have been indirectly implicated in a number of chemical and enzymic conversions of pyrimidine heterocycles. The method involves the use of kinetic secondary alpha-hydrogen isotope effects which are expected to accompany sp2 to sp3 rehybridization of C-6 of the pyrimidine ring if they occur prior to or at the rate determining step. Thus, using 6-tritiated pyrimidines, and measurement of the isotopic ratio of reactant and products, kT/kH values of 1.15 or greater would be indicative of rehybridization. Using this method, we have studied the inhibition of thymidylate synthetase by 5-fluorodeoxyuridylate and 5-nitro-deoxyuridylate as well as the chemical and enzymic dehalogenation of 5-bromodeoxyuridine and 5-bromodeoxyuridylate. Large secondary isotope effects observed in all of these reactions provided strong evidence for the formation of 5,6-dihydropyrimidine intermediates.

Bromodeoxyuridine↗
PubMed1979

A quantitative analysis of orbital soft tissue in Graves' disease based on B-mode ultrasonography.

Using B-mode ultrasonography, an attempt was made to measure the volume of extraocular muscles and retrobulbar fat in 31 patients (62 orbits) with Graves' disease. None of the patients had exophthalmometric measurements greater than 21 mm or had eye symptoms. The mean value of muscle volume of Graves' patients was significantly larger than that of normal controls (6.48 +/- 2.70 cm3 and 3.25 +/- 1.30 cm3, respectively, p less than 0.001). All of the patients had extraocular muscle swelling, although 2 of them had no extraocular muscle change for their unilateral eye. The extraocular muscle volume increased as the degree of the proptosis increased. The fat volume tended to increase in parallel with the degree of the proptosis. In the Graves' group with obvious proptosis (Hertel reading: 19--21 mm), the fat volume increased more significantly than in any other group. The ratio of extraocular muscle volume to retrobulbar fat volume was significantly higher in Graves' disease, but it did not increase as the degree of the proptosis increased. A significant correlation between proptosis and muscle volume plus fat volume was observed. No significant difference of the extraocular muscle volume was observed between the patients untreated and treated with antithyroid drugs. The data show a uniform enlargement of the extraocular muscles in Graves' disease and also suggest an involvement of increased retrobulbar fat volume in a group of obvious exophthalmos. The degree of the proptosis is in aclose proportion ot the quantitative change of the orbital soft tissue.

Adipose Tissue↗
PubMed1979

Radioimmunoassay of glibenclamide.

A specific, sensitive, and simple radioimmunoassay was developed for the oral hypoglycemic drug glibenclamide, N-4-[2-(5-chloro-2-methoxy-benzamide)-ethyl]-benzenesulfonyl-N'-cyclohexylurea. Antiserum against glibenclamide was obtained from rabbits immunized with an antigen prepared by conjugating the diazonium salt of N(p-amino-benzamidoethyl)-benzenesulfonyl-N'-cyclohexylurea to bovine serum albumin through the diazocoupling. [3H]glibenclamide was used as a tracer. Dextran-coated charcoal was used to separate bound and free [3H]glibenclamide in the reaction mixture. The radioimmunoassay is able to determine as little as 25 pg of glibenclamide directly in plasma without the need for extraction. The antiserum used for the assay was highly specific for glibenclamide, and did not cross-react with two known major metabolites of glibenclamide. Comparable values of glibenclamide in dog plasma were obtained by radioimmunoassay and liquid chromatography. Plasma concentrations of glibenclamide in diabetic patients on glibenclamide treatment can be determined by radioimmunoassay, and the method has been applied to the routine assay of clinical samples. This radioimmunoassay seems to be useful for monitoring plasma glibenclamide concentrations.

Animals↗
PubMed1979

Biological studies on the degradation products of 3-[(S)-1'-phenylethylamino]propylaminobleomycin: a novel analog (pepleomycin).

Pepleomycin (PEP), 3-[(S)-1'-phenylethylamino]propylaminobleomycin has potent activity and is less pulmonary toxic than bleomycin (BLM). Biological activity and toxicity of the following degradation products of PEP have been studied in detail: the product of carbamoyl migration (ISO), the product of decarbamylation (DC), the product of ring closure of the side chain on the pyrimidine moiety (RC), the depyruvamide product (DP) and the product of an enzymatic inactivation (DA). These degradation products showed much lower activity than PEP in vitro: antimicrobial and anti-HeLa activities, inhibition of DNA synthesis in AH66 cells and the DNA strand cleavage. Acute toxicity and pulmonary toxicity were tested in mice. Results indicated much lower acute toxicity corresponding to the decreased in vitro activity when compared to PEP. DP and RC did not cause lung fibrosis in mice, while ISO and DC showed 1/2.6 and 1/5.7 degree of pulmonary toxicity, respectively, in comparison with PEP.

Animals↗
PubMed1979

[Toxicological studies on pepleomycin sulfate (NK631). VI. Chronic toxicity of pepleomycin in dogs (author's transl)].

Chronic toxicity and its recovery of pepleomycin sulfate was studied in both sexes of beagle dogs. At dose levels of 0.3, 0.15 and 0.075 mg/kg, pepleomycin was administered intramuscularly to dogs for 180 successive days. Two dogs of the 0.15 mg/kg dose group were used for recovery test for 35 days. As general findings, the decrease of food intake, the loss of body weight, ulceration of foot pad, nail root necrosis and onychoptosis, ulcer of tongue and labia, and alopecia, dermatitis and necrosis at friction sites were observed more severely in the 0.3 mg/kg dose group of both sexes, especially in male, than those in bleomycin were. In the dose groups of 0.15 and 0.075 mg/kg, their findings were observed as slightly as those in bleomycin were. The death occurred in the 0.3 mg/kg dose group of both sexes. The lesions of liver and kidney were recognized in the 0.3 mg/kg dose group of both sexes, severely in male, on histopathological findings. Additionally severe fibrosis of lung was observed in one of the 0.3 mg/kg dose group of female. In general chronic toxicity of pepleomycin was revealed more severely in the 0.3 mg/kg dose group than that of bleomycin was, but in the dose groups of 0.15 and 0.075 mg/kg difference between their toxicities was not significant. In addition, chronic toxicity of pepleomycin in dogs showed more severely in male and its recovery was hardly recognized during its period. The maximum safety dose in this studies was estimated to be between 0.075 and 0.15 mg/kg in dogs.

Animals↗
PubMed1978

[Toxicological studies on pepleomycin sulfate (NK 631). I. Acute toxicity of pepleomycin in mice, rats and dogs (author's transl)].

Studies on acute toxicities of pepleomycin sulfate were carried out in both sexes of mice and rats, comparing with bleomycin, and male dogs. Pepleomycin was administered subcutaneously, intravenously and intraperitoneally in both sexes of mice and rats, and intravenously in male dogs respectively. Mice and rats, and intravenously in male dogs respectively. Mice and rats were observed respectively for 10 and 14 days after the administration. LD50 values were calculated by the method of Litchifield & Wilcoxon. LD50 values of pepleomycin were 4 approximately 6 times smaller than those of bleomycin in all routes of mice, but difference between them was not significant in all routes of rats. Additionally sex-difference of LD50 values was scacely recognized in all routes of both species. Toxicological findings observed in common to all routes of both species were ataxia, depression, tremor and epiphora, and only in all routes of mice, head-twitch, running-round and rolling were especially recognized as toxic behavior, which were not observed in bleomycin. Hepatic and renal lesions were recognized in biochemically and histopathologically in the survived rats. The dogs treated with pepleomycin 50 and 30 mg/kg had the decrease in food intake and the loss of body weight. They became moribund in 9 approximately 36 days after administration. In these dogs the lesions of liver and kidney were severely recognized in biochemical and histopathological findings. One of them which received 50 mg/kg recovered biochemically and histopathologically in 209 days after administration by the supplemental nutrition in early stage.

Animals↗