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Biomedical subjects

M Mackinnon

Publications and source records attributed to M Mackinnon.

45 records · Page 3Linked to original sources
PubMed1980

Effect of cycloheximide on bile flow adaptive response in selective biliary obstruction.

The adaptive increase in bile flow was studied up to 24 h after selective biliary obstruction (SBO) in the rat. Between 6 and 12 h after SBO bile flow increased significantly, such that 12 and 24 h after SBO bile flow did not differ significantly from control. The prior administration of cycloheximide (300 micrograms/100 g) resulted in a significant impairment of the increase in bile flow normally occurring between 6 and 12 h after SBO. These data indicate that the adaptive response in bile flow is dependent on de novo protein synthesis and suggest that the protein composition of the plasma membrane may determine the adaptive increase in bile flow that occurs after SBO in the rat.

Animals↗
PubMed1979

The aspirin-ibuprofen interaction in rheumatoid arthritis.

1 This was a double-blind crossover trial of ibuprofen and soluble aspirin against each drug alone and against placebo in patients with rheumatoid arthritis. Two dosage regimes were tested. 2 A weak clinical additive effect was demonstrated between soluble aspirin and ibuprofen in patients with rheumatoid arthritis using moderate (1600 mg ibuprofen and 3.6 g aspirin daily) but not low (800 mg ibuprofen and 2.4 g aspirin daily) dosages of both drugs. 3 A significant correlation between clinical efficacy and serum ibuprofen but not salicylate level was found in the single drug periods of the trial. 4 No consistent effect of ibuprofen administration on serum salicylate levels was found. 5 Concurrent salicylate administration produced significant lowering of serum ibuprofen levels without affecting elimination half-lives of the drug.

Adult↗
PubMed1977

Effects of ethinyl estradiol on hepatic microsomal proteins and the turnover of cytochrome P-450.

The effect of ethinyl estradiol, a steroid commonly used in birth control pills and possibly associated with impaired drug metabolism in humans, on the activity of and turnover of components of the hepatic microsomal mixed-function oxidase system was studied in male rats. After 5 days of ethinyl estradiol, 5 mg/kg/day, there was a significant decrease in the activity of ethylmorphine-N-demethylase and in cytochrome P-450, cytochrome b2, and NADPH cytochrome c reductase. Cytochrome P-450 apoproteins were identified within an SDS-polyacrylamide gel system, and the rate of turnover of cytochrome P-450 apoproteins was studied by double-isotope labeling techniques. After 5 days of ethinyl estradiol administration, the rate of degradation of cytochrome P-450 apoprotein was reduced (half-life of 50 hr compared to 24 hr in control), and their relative rate of synthesis was likewise reduced, indicating that a new steady state of protein turnover associated with reduced synthesis rate had been reached. This was confirmed by studies of the effect of ethinyl estradiol on the level of microsomal cytochrome P-450 over a 10-day period.

Animals↗
PubMedDate not supplied

Plasma clearance of intravenous chenodeoxycholic acid in rabbits with varying severity of hepatocellular necrosis.

The plasma clearance of an i.v. bolus of chenodeoxycholic acid (10 micrometer per kg) was determined in rabbits with graded degrees of hepatocellular necrosis produced by i.p. injection of carbon tetrachloride. Plasma chenodeoxycholic acid levels were determined by radioimmunoassay, and the volume fraction of necrosis was quantitated by a computerized (Quantimet 720) system. Impaired plasma clearance was observed only when necrosis was extensive, and the volume fraction of necrosis greater than 34%. In contrast, measurement of fasting plasma chenodeoxycholic acid concentration was more sensitive, and elevated levels were associated with a mean volume fraction of necrosis of 12.5%. This study reinforces the conclusion based on clinical studies that measurement of fasting bile acid concentration is a more sensitive discriminant of hepatic dysfunction than is measurement of the plasma clearance of an i.v. bolus of bile acid.

Animals↗
PubMedDate not supplied

High density lipoprotein subpopulations in chronic liver disease.

Severe liver disease may be associated with a reduction in plasma concentration of high density lipoprotein and an impairment of plasma cholesterol esterification. These changes were confirmed in two patients with severe acute on chronic alcoholic liver disease. In five additional patients with biopsy-proven clinically compensated cirrhosis, there was minimal reduction in concentration of plasma cholesteryl esters; there was, however a reduction of the plasma high density lipoprotein concentration to only 48 to 66% of normal. The particle size distribution of high density lipoprotein in these five patients was determined by gradient gel electrophoresis. The high density lipoprotein2 subfraction was preserved. The high density lipoprotein3 subfraction, however, was markedly changed with a reduction in the normal particles of radius 4.3 m and an accentuation of smaller particles of radius 3.9 m; in two patients, these smaller particles were the major high density lipoprotein subpopulation. Further investigations of this finding of a distinctive distribution of high density lipoprotein subpopulations in patient with chronic liver disease may provide new insights into high density lipoprotein metabolism.

Adult↗
PubMedDate not supplied

The effect of mixed selected and unselected samples on the power of QTL mapping.

It is known from previous work that selection by truncation can lead to substantial loss of power to detect linkage with a QTL We examine the effect of mixed selected and unselected samples. We show that even if a modest proportion of the sample originates from an unselected population, this loss of power is quite effectively neutralized. Moreover, we reach the unexpected conclusion that if the selection intensity in the selected subpopulation is high, the power to detect QTL may actually increase.

Animals↗