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Biomedical subjects

M Komori

Publications and source records attributed to M Komori.

At least 109 records · Page 6Linked to original sources
PubMed1988

Cytochrome P-450 in human liver microsomes: high-performance liquid chromatographic isolation of three forms and their characterization.

Three forms of cytochrome P-450, designated as P-450-HM1, P-450-HM2, and P-450-HM3, were isolated from human liver microsomes using high-performance liquid chromatography (HPLC) techniques. Each purified preparation showed a single protein band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). From the results of SDS-PAGE, the molecular weights of P-450-HM1, P-450-HM2, and P-450-HM3 were estimated to be 51,000, 54,000, and 52,000, respectively. The oxidized absolute spectra of these three forms of cytochrome P-450 showed Soret absorption peaks at around 417 nm, indicating that these forms were in the low spin state. In a reconstituted system, P-450-HM1 showed the highest catalytic activities of nifedipine and (S)- or (R)-nilvadipine oxidases. The same form showed higher activities of testosterone 6 beta-hydroxylase and progesterone 6 beta- and 16 alpha-hydroxylases. P-450-HM2 showed high N-demethylase activities for benz-phetamine and aminopyrine, and also showed the highest activity of testosterone 16 beta-hydroxylase among the three forms, while it did not show detectable activities of testosterone 6 beta-hydroxylase and progesterone 6 beta- and 16 alpha-hydroxylases. Anti-P-450-HM1 immunoglobulin G (IgG), but not anti-P-450-HM2 IgG, inhibited the activities of testosterone 6 beta-hydroxylase and nifedipine and nilvadipine oxidases in human liver microsomes. Anti-P-450-HM1 IgG was also inhibitory against progesterone 6 beta- and 16 alpha-hydroxylases.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1988

Effects of muroctasin on the activities of drug metabolizing enzymes in liver microsomes of rats.

1. Effects of repeated administration of N2-[(N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine (MDP-Lys (L18), muroctasin) to female rats on the activities of drug metabolizing enzymes in liver microsomes were examined. The in vitro effects of the compound on the activities of drug metabolizing enzymes in liver microsomes from male rats were also investigated. 2. The subcutaneous administration of MDP-Lys (L18) at a dose of 1 mg/kg (high dose) caused slight but significant decrease in the contents of cytochrome P-450 and cytochrome b5. The daily subcutaneous injection at a dose of 0.1 mg/kg (middle dose) resulted in the induction of aminopyrine N-demethylase, aniline hydroxylase and 7-ethoxycoumarin O-deethylase. Such induction of the enzymes was seen only when calculated on the basis of microsomal protein but not wet weight of livers. The changes were relatively small as compared with those caused by phenobarbital. 3. At one week after the last injection of the high dose of MDP-Lys (L18), slightly higher levels of the contents of cytochrome P-450 and cytochrome b5 and the activity of NADPH-cytochrome c reductase were noted. The cessation of the administration tended to increase the activities of drug metabolizing enzymes in rats treated with the high dose of the drug. These changes were seen only when the activities were calculated on the basis of mg of microsomal protein. 4. MDP-Lys (L18) inhibited drug metabolizing enzymes in vitro to various extents depending on the substrate used.(ABSTRACT TRUNCATED AT 250 WORDS)

7-Alkoxycoumarin O-Dealkylase↗
PubMed1985

Cardiodynamic effects of experimental right bundle branch block in canine hearts with normal and hypertrophied right ventricles.

Cardiodynamic effects of acute experimental right bundle branch block (RBBB) were studied in canine hearts: group A included 15 normal hearts; group B-1 had seven hearts with mild right ventricular hypertrophy (RVH), and group B-2 had 11 hearts with marked RVH. The main sequential changes following RBBB were marked prolongation of the Q upstroke interval of the right ventricle and striking shortening of right ventricular systolic time that affected right and left ventricular interaction, particularly in the hearts with RVH. Hemodynamic changes were: the right ventricular end-diastolic pressure was elevated markedly (4.4 +/- 2.2----9.8 +/- 2.6 mm Hg, p less than 0.001) in group B-2, moderately (p less than 0.01) in group B-1, and not at all in group A. The right ventricular positive peak dp/dt decreased remarkably (1036 +/- 151----827 +/- 152 mm Hg/sec, p less than 0.001) in group B-2 and negligibly in the other groups. A significant correlation existed between the percentage of decrease in right ventricular peak dp/dt and the QRS duration of RBBB in each group (p less than 0.01). The left ventricular peak negative dp/dt decreased distinctly (2570 +/- 326----+/- 2055 +/- 362 mm Hg/sec, p less than 0.01) in group B-2 and not at all in the other groups. The stroke volume showed 12% decrease in group B-2 (p less than 0.001), 8% decrease in group B-1 (NS), and no decrease in group A. In the presence of RVH, acute RBBB causes significant impairment of right and left ventricular function. The magnitude of the impairment invariably depends upon both the prior degree of RVH and the width of the QRS complex.

Animals↗
PubMed1985

[Clinical studies on TMS-19-Q.O tablet in respiratory tract infection].

A new macrolide antibiotic preparation, TMS-19-Q.O tablet, was used to investigate the efficacy in the treatment of patients with respiratory tract infection, and the results obtained were as follows: Three hundred and seven cases were included in this report, and overall efficacy rate was 76.2%. Especially high clinical effect (86.0%) was observed in the treatment of patients with pneumonia including mycoplasmal pneumonia. Bacteriological effect was 87.5% in 51 cases identified as single infection of Gram-positive cocci and was 48.0% in 34 cases Gram-negative rods infection. Side effects were observed in 11 cases (3.50%): gastrointestinal disorder in 8, eruption in 2 and other in 1. Abnormality in laboratory tests was observed in 23 cases, hepatic disorder in 13, renal disorder in 3 and other laboratory tests in 7. It was considered from the results of clinical and bacteriological efficacy in different dose study that dose of TMS-19-Q should be 600 mg.

Adolescent↗
PubMed1984

Purification and characterization of cytochrome P-450 with high affinity for 7-alkoxycoumarins.

A unique form of cytochrome P-450 (called P-450(2] with high affinity for 7-alkoxycoumarins was purified from liver microsomes of phenobarbital-treated rabbits with an overall yield of about 0.6%. The purified preparation had a specific cytochrome P-450 content of 15-16 nmol per mg of protein and was homogenous on sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis. The apparent molecular weight estimated for P-450(2) was 50,500. In the oxidized state its absorption spectrum was characteristic of low-spin cytochrome P-450. The activity of purified P-450(2) to catalyze O-dealkylation of several 7-alkoxycoumarins in the reconstituted system was compared with those of P-450(1), the major phenobarbital-inducible form in rabbit liver microsomes, and rat P-448(2), purified from liver microsomes of beta-naphthoflavone-treated rats. With 7-ethoxycoumarin as substrate, the pH optimum for P-450(2) was 6.5, whereas those for P-450(1) and rat P-448(2) were 7.5-8.0. P-450(2) showed Km values of 0.38 to 1.4 microM for the five alkoxycoumarins tested, whereas the corresponding Km values determined for P-450(1) and rat P-448(2) were 40- to 700-fold higher. The Km values of P-450(2) and P-450(1) were relatively unaffected by the length of the alkyl chain in the alkoxycoumarins, whereas those of rat P-448(2), decreased markedly as the length of the alkyl chain increased. For all the three forms of cytochrome P-450, the highest Vmax values were observed with 7-ethoxycoumarin, and Vmax values tended to decrease with increase in the alkyl chain length in the substrate. Only P-450(2) catalyzed 7-hydroxylation of coumarin, though at a low rate. Progressive and irreversible inactivation of P-450(2), but not P-450(1) and rat P-448(2), was observed during the catalysis of 7-methoxycoumarin O-demethylation, and this inactivation was considerably prevented by inclusion of cytochrome b5 in the reconstituted system.

7-Alkoxycoumarin O-Dealkylase↗