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Biomedical subjects

T Komiyama

Publications and source records attributed to T Komiyama.

124 records · Page 7Linked to original sources

Reduction of cinerulose in aclacinomycin-A by soluble and microsomal cinerulose reductases.

The in vitro metabolism of the antitumor anthracycline antibiotic, aclacinomycin-A, was studied using rat liver homogenate. In the presence of NADH or NADPH, aclacinomycin-A was converted to aclacinomycin-A analogs, MA144 M1 and MA144 N1, which were stereospecifically reduced at the keto group of the C-4''' position of L-cinerulose in aclacinomycin-A. Subcellular fractionation indicated that the production of MA144 M1, which was reduced to L-amicetose, was catalyzed by NADPH-dependent soluble cinerulose reductase I, and the production of MA144 N1, which was reduced to L-rhodinose, was catalyzed by NADPH-dependent soluble cinerulose reductase II and NADH-dependent microsomal cinerulose reductase. The properties of these three enzymes were studied. Soluble cinerulose reductase I which produces MA144 M1 showed a optimum pH at 6.3, Km values of 3.3 x 10(-4) M for aclacinomycin-A and 3.2 x 10(-5) M for NADPH. Soluble cinerulose reductase II which produces MA144 N1 showed a pH optimum at 6.3 and Km values of 2.0 x 10(-3) M for aclacinomycin-A and 4.0 x 10(-5) M for NADPH. All thesse reductases were sensitive to sulfhydryl reagents and were inhibited by vitamin K3. Microsomal cinerulose reductase showed sensitivity to diconmarol and ferrous ion. The main nondegradative pathways of aclacinomycin-A were discussed from these results.

Animals↗

Reduction of anthracycline glycoside by NADPH--cytochrome P-450 reductase.

The in vitro degradation of the new antitumor anthracycline antibiotic, aclacinomycin-A, was studied using rat liver homogenate. In the presence of NADH or NADPH, the glycosidic bond at C-7 position of aclacinomycin-A was reductively cleaved to produce 7-deoxyaklavinone and 7-deoxyaklavinone dimer, MA144 E1. Subcellular fractionation indicated that most of the enzyme activity was present in the microsomal fraction and required anaerobic condition and NADPH. The purified enzyme reduced the glycosidic metabolites, MA144 M1 and MA144 N1, as well as aclacinomycin-A. The optimum pH for the anthracycline glycoside reductase reaction using aclacinomycin-A as substrate was 7.4. The enzyme was sigmoidally saturated with aclacinomycin-A and showed the concentration of 1.2 x 10(-4) M required for half maximal activity, and Km value of 7.7 x 10(-5) M for NADPH. The degradative pathway of aclacinomycin-A and its glycosidic metabolites was discussed.

Anaerobiosis↗

The influence of temperature and urea on intrinsic fluorescence of Streptomyces subtilisin inhibitor. A study by fluorescence polarization and quenching.

Intrinsic fluorescence of new microbial protease inhibitor, Streptomyces subtilisin inhibitor was studied by observing fluorescence polarization degree and lifetime in the temperature range 25-81 degrees C. Striking thermal changes in these fluorescence properties of tryptophan residues were observed. The apparent molecular volumes for tryptophan and tyrosine residues in the native form were determined to be 89 and 75 A3, respectively. The fluorescence quenching by Br- or Cs+ was investigated to obtain a microenvironmental information around tryptophan residues both in the native and denatured form. Cs+ quenches the fluorescence slightly stronger than Br-, implying that there is not any distinctive electrostatic interaction between tryptophan residues and their neighborhood.

Bacterial Proteins↗

Linkage disequilibrium and association with methamphetamine dependence/psychosis of mu-opioid receptor gene polymorphisms.

Several studies indicate that the mu-opioid receptor plays a role in addiction not only to opiate drugs but also to alcohol and non-opiate addictive drugs. Our studies aim to reveal the associations between gene polymorphisms and methamphetamine (MAP) dependence/psychosis. We newly identified several polymorphisms and four substantial linkage disequilibrium (LD) blocks in the mu-opioid receptor (OPRM1) gene. We found significant differences in both genotype and allele frequencies of the single-nucleotide polymorphism (SNP) IVS2+G691C between control (n=232) and MAP-dependent/psychotic patients (n=128). There was also a significant association between IVS2+G691C and patients with transient psychosis. These results suggest that the OPRM1 gene variations may be a factor in development and prognosis of MAP psychosis.

Adult↗

Clear demonstration of carcinoma of the ampulla of Vater with ultrasonography.

We present a non-icteric case, in which an ampullary polypoid lesion was clearly demonstrated by ultrasonography, suggesting carcinoma of the ampulla of Vater. The lesion was a 3 cm in diameter, spherical tumor with a polypoid surface, and internal hyperechogenicity. The patient underwent a curative pylorus-preserving pancreaticoduodenectomy.

Adenocarcinoma, Papillary↗