The step of carbon monoxide liberation in the sequence of heme degradation catalyzed by the reconstituted microsomal heme oxygenase system.
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Biomedical subjects
Publications and source records attributed to M Noguchi.
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The secretin injection test has been proved to be useful in the diagnosis of gastrinoma in vivo. Fresh gastrinoma cells were cultured for a short time in vitro and then stimulated with secretin. A rise in the gastrin concentration in the culture medium was observed within 10 min after the addition of secretin. This fact may be evidence that gastrinoma cells have receptors which bind with secretin resulting in the release of gastrin.
Biliverdins formed from heme by a microsomal preparation and a reconstituted heme oxygenase system were each converted to their dimethyl esters and analyzed for isomeric composition by reversed-phase high-performance liquid chromatography, using a column of mu Bondapak C18 (Waters Associates); on this column, the dimethyl esters of four biliverdin IX isomers, that is IX alpha, IX beta, IX gamma, and IX delta, have been shown to be eluted separately in the order IX alpha, IX beta, IX delta, and IX gamma, when developed with methanol/water. The analysis indicated that the enzymatically formed biliverdins were exclusively IX alpha; the elution profile exhibited no other significant elution peak due to other biliverdin isomers. It was concluded that the heme oxygenase system cleaves the heme ring specifically at the alpha-methene bridge to yield biliverdin IX alpha.
The extent of the binding of beta-lactam antibiotics to 100,000 X g supernatant fluid of rabbit liver homogenates was investigated. Urinary excretion tended to decrease as the extent of the binding to 100,000 X g supernatant fluid increased. Predicting urinary excretion was achieved using the binding to 100,000 X g supernatant fluid and other physicochemical factors. A good coincidence resulted from multiple regression analysis. [14C]Benzylpenicillin binding proteins in rabbit liver were investigated and revealed that the affinity of cefoperazone was much stronger than that of cefazolin.
To characterize the effect of the binding of antibiotics to tissue protein on urinary excretion, we examined the extent of the binding of 9 penicillins and 9 cephems to 100,000 X g supernatant fluid of human liver homogenates. The correlation analysis revealed a significant simple correlation between the binding to 100,000 X g supernatant fluid of liver homogenates and urinary excretion. Drugs with lesser binding were mainly excreted in the urine, conversely, urinary excretion of highly bound drugs exhibited lower values. The prediction with regard to urinary excretion of healthy subjects was done by multiple regression analysis using the binding to 100,000 X g supernatant fluid and other physicochemical factors. The values predicted for urinary excretion coincided well with the observed values.
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The pharmacokinetics of piperacillin (PIPC) after intravenous injection of 4 g and 8 g was studied on healthy volunteers, and the following results were obtained. 1. Serum concentrations of PIPC were measured, and simulation curves were obtained by using 2-compartment model. PIPC has been found to produce higher serum level soon after intravenous administration and it was rapidly eliminated. 2. In the view of pharmacokinetic parameter and peripheral compartment level of PIPC, it was estimated that distribution of PIPC of various tissues was prompt after administration. 3. PIPC was excreted rapidly, and approximately 100% excretion was observed up to 8 hours after instillation of 8 g PIPC for 2 hours. No accumulation of PIPC was noted.
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The heptacosapeptide amide corresponding to the entire amino acid sequence of chicken gastrin-releasing peptide (cGRP) was synthesized similarly to the synthesis of porcine GRP by assembling six peptide fragments followed by deprotection with 1 M trifluoromethanesulfonic acid-thioanisole in TFA. A new carboxyl-activating reagent, thiazolidine-2-thione, was preferentially adopted for preparation of necessary fragments. The synthetic cGRP, purified by ion-exchange chromatography, followed by partition chromatography, was active as the synthetic porcine GRP, when plasma immunoreactive gastrin level was examined in rats. No obvious difference was observed when synthetic and natural cGRP preparations were compared by HPLC, immunochemical property and biological activity in dogs.
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The distribution of T-1982, a new semisynthetic cephamycin antibiotic, was studied with whole body autoradiography in normal male mice, pregnant mice and experimental pyelonephritic mice following a single intravenous administration of 80 mg/kg of 14C-T-1982. 1. In normal male mice, the radioactivity was distributed at high concentration in the liver, kidney, lung, gastrointestinal tracts, skin, salivary gland, tongue and muscle, but was hardly observed in the central nervous system that composed of the brain and spinal cord. 2. In pregnant mice, the radioactivity was hardly observed in the fetuses. 3. In experimental pyelonephritic mice, considerable radioactivity was concentrated on the acute inflammatory area.