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Biomedical subjects

B S Masters

Publications and source records attributed to B S Masters.

At least 109 records · Page 6Linked to original sources
PubMed1982

Monooxygenase activities of human liver, lung, and kidney microsomes - a study of 42 post mortem cases.

The cytochrome P-450-dependent monooxygenase system was examined in microsomal fractions prepared from 42 post mortem human livers and 9 lungs and kidneys. Electron microscopy studies indicated that the human liver samples were relatively free of mitochondrial and plasma membrane contamination, but samples of kidney and lung were less pure. The microsomal fractions from all organs were judged to be relatively free of haemoglobin and methaemoglobin. The specific enzyme activities for several drug substrates for the monooxygenase, NADPH-cytochrome c reductase activity and the content of the microsomal cytochromes were measured. The values of the biochemical parameters studied were found to be quite variable and the values for the human liver were appreciably lower than those obtained with liver microsomes from laboratory rodents. The enzyme activities of the human kidney and lung microsomal fractions were 1-10% of those seen for human liver samples, except for NADPH-cytochrome c(P-450) reductase activity. In order to evaluate any post mortem changes in human liver, correlations between drug metabolism activities and either cytochrome P-450 or NADPH-cytochrome c (P-450) reductase content were examined. Strong correlations (r greater than 0.91) were seen only between aminopyrine or ethylmorphine demethylase activity and cytochrome P-450 content in samples obtained within 4 hours of death. Longer post mortem times gave poorer correlation between activity and cytochrome content. These studies document several conditions required in order to obtain human microsomal fractions representative of the activities in fresh, viable tissue.

Adult↗
PubMed1982

Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin and phenobarbital on the occurrence and distribution of four cytochrome P-450 isozymes in rabbit kidney, lung, and liver.

The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and of phenobarbital (PB) on the distribution and occurrence of four cytochrome P-450 isozymes, Forms 2, 3, 4, and 6, in the kidney, lung, and liver of adult male rabbits was investigated using immunofluorescence. In the kidney, Forms 2 and 3 were localized in the proximal tubules of both untreated and PB-treated animals, while antibodies to Forms 4 and 6 showed weak to negative staining. In TCDD-pretreated animals, Forms 4 and 6 appeared in the renal endothelium, in addition to staining the proximal tubular epithelium intensely. Form 2 was the only isoenzyme of those studied found to be present in the lungs of normal and PB-pretreated rabbits; it was also present in lungs of TCDD-pretreated rabbits. Form 3 was not detected in any of the rabbit lungs examined. Forms 4 and 6, while not apparent in the lungs of normal or PB-treated animals, were found in the lungs of TCDD-treated animals and also appeared in the endothelium of the pulmonary arteries and veins. All forms tested were present in control liver. The staining for Form 2 was intense in the livers of PB-pretreated animals, as was the staining for Forms 4 and 6 in the livers of TCDD-pretreated animals. Our results indicate that, while PB altered the intensity of staining for Form 2 in the liver and kidney, TCDD altered both the staining intensity and distribution of the isozymes in kidney, lung, and liver, producing, for example, a localization of Forms 4 and 6 in the endothelium of both the kidney and lung which was not seen in either untreated or PB-pretreated rabbits.

Animals↗
PubMed1981

Identification of 25,26-dihydroxyvitamin D3 as a rat renal 25-hydroxyvitamin D3 metabolite.

25,26-Dihydroxyvitamin D3 [25,26-(OH)2D3] was unequivocally identified as a major renal microsomal metabolite of 25-hydroxyvitamin D3 in rats fed a vitamin D sufficient diet. The structural assignment was based on a comparison of the high-performance liquid chromatograms of synthetic and in vitro generated 25,26-(OH)2D3 through four different systems, the ultraviolet absorbance and mass spectral characteristics of biological 25,26-(OH)2D3, and the chromatographic and mass spectral characteristics of the sodium metaperiodate cleavage product of the metabolite. The enzymic synthesis of 25,26-(OH)2D3 was inhibited 60--80% by a semipurified goat anti-rat NADPH--cytochrome P-450 reductase. This implicates cytochrome P-450 as the probable terminal oxidase of the 25-hydroxyvitamin D3-26-hydroxylase system. The methodology used to assay rat renal 25-OH-D3-hydroxylases is also discussed.

Animals↗
PubMed1981

Quantitative evaluation of plasma-opsonizing activity from the lag period of phagocytosis-connected oxygen consumption by leukocytes in whole blood.

The lag period preceding the burst of oxygen consumption by phagocytes was measured with an oxygen electrode after the addition of unopsonized zymosan in CO-treated and diluted whole blood. The duration of the lag period correlated with the phagocytic index (r = 0.98, p < 0.001). The phagocytic index was defined as the mean number of zymosan particles per phagocyte. The lag period was termed opsonizing time and used for evaluation of plasma opsonizing activity. The opsonizing time was found to be inversely related to the plasma concentration used (< 15%) and was independent of phagocyte concentration. Magnesium ions were required throughout the opsonizing time, but calcium ions were essential only during the initial phase, indicating that the alternative complement pathway plays a major role in the observed opsonizing time. The mean opsonizing times in blood from normal adults and newborn infants were 5.6 +/- 0.7 min (n = 7) and 9.1 +/- 0.7 (n = 4), respectively. The opsonizing time, expressed as its reciprocal value, correlated significantly with phagocytic index, CH50 activity, and immunochemically assayed C3, but not C4, concentration in plasma.

Adult↗
PubMed1980

Immunofluorescence of NADPH-cytochrome c (P-450) reductase in rat and minipig tissues injected with phenobarbital.

The enzyme NADPH-cytochrome c (P-450) reductase was identified by indirect immunofluorescence in hepatocytes, bronchioles, and proximal tubules of liver, lung, and kidney, respectively, of rats and minipigs that had been injected with phenobarbital or saline. The distribution of this component of the cytochrome P-450-mediated microsomal system may be relevant to sites of drug toxicity and carcinogenesis.

Animals↗
PubMed1979

The role of NADH-NADPH oxidase activity in the leukocyte function of burned patients.

Irreversible sepsis, in spite of advancements in topical therapy and antimicrobial agents, remains the leading cause of death in major thermal injury. A defect in intracellular bactericidal capacity in leukocytes from severely burned patients appears to correspond with increases in bacterial wound colonization and ultimate sepsis. This leukocyte defect has been demonstrated by abnormally low nitroblue tetrazolium reduction (NBT) and oxygen consumption of white cells in patients with major thermal injury. The subcellular mechanisms responsible for decreased bactericidal capacity were therefore investigated. Nicotinamide-adenine dinucleotide (NADH) and nicotinamide-adenine phosphodinucleotide (NADPH) oxidase activity was measured in patients with major burns, controls (normals), and in patients with nonburn stress or infection. NADH and NADPH oxidase levels in leukocytes from burn patients were not significantly different from those of normal nonchallenged controls but were significantly lower than the leukocyte values found in the patients with nonburn infections or stress. This NADH and NADPH defect in the subcellular leukocyte fraction suggests that it may be a significant factor in the reduced bactericidal function of the intact leukocyte in thermally injured patients.

Burns↗