Biomedical subjects
Osamu Ueda
Publications and source records attributed to Osamu Ueda.
Involvement of molybdenum hydroxylases in reductive metabolism of nitro polycyclic aromatic hydrocarbons in mammalian skin.
Molybdenum hydroxylases, aldehyde oxidase and xanthine oxidoreductase, were shown to be involved in the nitroreduction of 2-nitrofluorene (NF), 1-nitropyrene, and 4-nitrobiphenyl, environmental pollutants, in the skin of various mammalian species. NF was reduced to 2-aminofluorene by hamster skin cytosol in the presence of 2-hydroxypyrimidine, 4-hydroxypyrimidine, N(1)-methylnicotinamide, or benzaldehyde, but not hypoxanthine or xanthine. Inhibitors of aldehyde oxidase markedly inhibited these nitroreductase activities, but oxypurinol, an inhibitor of xanthine oxidoreductase, had little effect. In DEAE column chromatography of hamster skin cytosol, the major fraction exhibiting nitroreductase activity also showed aldehyde oxidase activity. 2-Hydroxypyrimidine-linked nitroreductase activities of skin cytosol from rabbits and guinea pigs were also inhibited by an inhibitor of aldehyde oxidase. In contrast, nitroreductase activities of skin cytosols of rats and mice were markedly inhibited by oxypurinol. When aldehyde oxidase activity was estimated in skin cytosol of various mammals using benzaldehyde oxidase activity as a marker, considerable variability of the activity was found. The highest activity was observed with hamsters, and the lowest activity with rats. On the other hand, the highest xanthine oxidoreductase activity was observed with rats, and the lowest activity with rabbits. These skin cytosols of various mammals also exhibited significant 2-hydroxypyrimidine-linked nitroreductase activities toward 1-nitropyrene and 4-nitrobiphenyl catalyzed by aldehyde oxidase and xanthine oxidoreductase. Thus, NF was mainly reduced by aldehyde oxidase and xanthine oxidoreductase in skins of animals. However, the contributions of these two molybdenum hydroxylases were considerably different among animal species.
Mutations in human urate transporter 1 gene in presecretory reabsorption defect type of familial renal hypouricemia.
To date, 11 loss of function mutations in the human urate transporter 1 (hURAT1) gene have been identified in subjects with idiopathic renal hypouricemia. In the present studies we investigated the clinical features and the mutations in the hURAT1 gene in seven families with presecretory reabsorption defect-type renal hypouricemia and in one family with the postsecretory reabsorption defect type. Twelve affected subjects and 26 family members were investigated. Mutations were analyzed by PCR and the direct sequencing method. Urate-transporting activities of wild-type and mutant hURAT1 were determined by [14C]urate uptake in Xenopus oocytes. Mutational analysis revealed three previously reported mutations (G774A, A1145T, and 1639-1643 del-GTCCT) and a novel mutation (T1253G) in families with the presecretory reabsorption defect type. Neither mutations in the coding region of hURAT1 gene nor significant segregation patterns of the hURAT1 locus were detected in the postsecretory reabsorption defect type. All hURAT1 mutants had significantly reduced urate-transporting activities compared with wild type (P < 0.05; n = 12), suggesting that T1253G is a loss of function mutation, and hURAT1 is responsible for the presecretory reabsorption defect-type familial renal hypouricemia. Future studies are needed to identify a responsible gene for the postsecretory reabsorption defect-type familial renal hypouricemia.
Acute mitral regurgitation due to total rupture in the anterior papillary muscle after acute myocardial infarction successfully treated by emergency surgery.
A 68-year-old female was admitted for sudden onset of chest pain. She received a successful percutaneus coronary intervension for total occlusion in the diagonal artery, but continued to develop progressive heart failure. A chest X-ray showed right pulmonary edema without cardiomegaly, and an echocardiogram revealed massive mitral regurgitation with prolapse in the anterior mitral leaflet due to a rupture in the papillary muscle. An emergency operation was conducted using routine cardiopulmonary bypass. There was complete rupture in the anterior papillary muscle. Mitral valve replacement with posterior mitral leaflet preservation was performed using a size 25 mm Carbomedics prosthetic valve. The postoperative course was uneventful, and she was discharged on postoperative day 29 in New York Heart Association class I. Postoperative pathological findings showed necrosis in the papillary muscle with inflammatory changes. Early diagnosis, prompt medical stabilization, and aggressive surgical intervention are essential to save such a group of patient.
Xanthine oxidase-catalyzed metabolism of 2-nitrofluorene, a carcinogenic air pollutant, in rat skin.
The reductive metabolism of 2-nitrofluorene, a carcinogenic air pollutant, in rat skin microsomes and cytosol was investigated. 2-Nitrofluorene was reduced to the corresponding amine by the microsomes with NADPH and by the cytosol with 2-hydroxypyrimidine or 4-hydroxypyrimidine under anaerobic conditions. The cytosolic activity was much higher than that of skin microsomes. The 2- or 4-hydroxypyrimidine-linked nitroreductase activity was inhibited by oxypurinol and (+/-)-8-(3-methoxy-4-phenylsulfinylphenyl) pyrazolo[1,5-a]-1,3,5-triazine-4(1H)-one (BOF-4272), inhibitors of xanthine oxidase, but not by menadione, chlorpromazine and isovanillin, inhibitors of aldehyde oxidase. When skin cytosol was applied to a DEAE-cellulose column, the fractions containing xanthine oxidase exhibited a marked 2-hydroxypyrimidine-linked nitroreductase activity. In contrast, the aldehyde oxidase fraction showed little activity. Nitroreductase fractions obtained by ion exchange chromatography showed a band in Western blotting analysis using anti-rat xanthine oxidase. Moreover, the xanthine oxidase fraction exhibited a significant nitroreductase activity in the presence of 2-hydroxypyrimidine, 4-hydroxypyrimidine or hypoxanthine, and these activities were inhibited by inhibitors of xanthine oxidase. These results indicated that reduction of 2-nitrofluorene in the skin was mainly catalyzed by xanthine oxidase.
A successful management of concomitant renovascular hypertension and symptomatic subclavian steal syndrome due to Takayasu's arteritis using balloon angioplasty and axillo-axillary bypass grafting.
We present a case of Takayasu's arteritis with severe renovascular hypertension and symptomatic subclavian steal syndrome. A 60-year-old woman underwent successful percutaneous balloon renal angioplasty and axillo-axillary bypass grafting. The role of hybrid therapy, angioplasty and extra-anatomical bypass grafting for revascularization of symptomatic ischemia in this disease is reviewed. (Ann Thorac Cardiovasc Surg 2003: 9; 334-6)
Deacylation of N-arylformamides and N-arylacetamides by formamidase in rat liver.
The in vitro deacylation of N-arylformamides and N-arylacetamides to arylamines was examined in rat liver preparations. When 2-acetylaminofluorene or 2-formylaminofluorene was incubated with rat liver microsomes or cytosol, the deacylated metabolite, 2-aminofluorene, was formed. The deacylating activity of liver microsomes was inhibited by bis(4-nitrophenyl)phosphate and phenylmethanesulfonyl fluoride, inhibitors of carboxylesterase. In contrast, the activity of liver cytosol was inhibited by diisopropyl fluorophosphate, an inhibitor of formamidase. Deacylation of these compounds appear to be mainly catalyzed by carboxylesterase in liver microsomes and formamidase in liver cytosol. 2-Formylaminofluorene, 2-acetylaminofluorene, 1-formylaminopyrene, 4-formylaminobiphenyl, 2-formylaminonaphthalene, 1-formylaminonaphthalene, and 2-acetylaminofluorene were deacylated by formamidase purified from rat liver cytosol. Formamidase catalyzed both N-formylation of arylamines, and deacylation of N-arylformamides and N-arylacetamides.