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P Meijer

Publications and source records attributed to P Meijer.

13 recordsLinked to original sources

Heterogeneity of rat liver parenchyma in cholesterol 7 alpha-hydroxylase and bile acid synthesis.

Periportal and perivenous hepatocytes were isolated from rat liver by digitonin/collagenase perfusion for investigating the acinar distribution of bile acid synthesis. The specific activity of cholesterol 7 alpha-hydroxylase (EC 1.14.13.17) was 7.9-fold higher in perivenous cells than in periportal hepatocytes. Mass production of bile acids differed 4.4-fold between cultured perivenous and periportal hepatocytes. In contrast, the levels of free cholesterol in homogenates and microsomes derived from both subfractions were similar. Feeding of rats with the bile-acid-sequestering anion-exchange resin colestid resulted in a pronounced stimulation of cholesterol 7 alpha-hydroxylase activity and bile acid mass production, but decreased the perivenous/periportal ratio of both parameters. These results demonstrate that bile acid mass production, but decreased the perivenous hepatocytes, possibly owing to feedback suppression by bile acids from the enterohepatic circulation. Furthermore, the opposite acinar localization of cholesterol and bile acid biosynthesis provides an interesting alternative to current views of the regulation of their metabolic pathways.

Animals

Cyclosporin A blocks bile acid synthesis in cultured hepatocytes by specific inhibition of chenodeoxycholic acid synthesis.

Bile acid synthesis, determined by conversion of [4-14C]cholesterol into bile acids in rat and human hepatocytes and by measurement of mass production of bile acids in rat hepatocytes, was dose-dependently decreased by cyclosporin A, with 52% (rat) and 45% (human) inhibition of 10 microM. The decreased bile acid production in rat hepatocytes was due only to a fall in the synthesis of beta-muricholic and chenodeoxycholic acids (-64% at 10 microM-cyclosporin A), with no change in the formation of cholic acid. In isolated rat liver mitochondria, 26-hydroxylation of cholesterol was potently inhibited by the drug (concn. giving half-maximal inhibition = 4 microM). These results suggest that cyclosporin A blocks the alternative pathway in bile acid synthesis, which leads preferentially to the formation of chenodeoxycholic acid.

Animals

[Canine scabies in man].

Parasitic prurigo caused by scabies mites from recently acquired puppies is described in two patients and their family members. Because Sarcoptes scabiei var. canis (dog) occasionally survives in man, patients with persisting complaints despite treatment of their dogs should be treated with the topical scabicide lindane for one night.

Adult

Maintenance of bile acid synthesis and cholesterol 7 alpha-hydroxylase activity in cultured rat hepatocytes.

Addition of foetal-bovine serum to rat hepatocytes cultured in Williams E medium resulted in improved maintenance of bile-acid-synthetic capacity and cholesterol 7 alpha-hydroxylase activity as compared with cultures supplemented with rat or newborn-bovine serum or cultures in a hormonally defined serum-free medium. Minimally, 5% (v/v) foetal-bovine serum was necessary to maintain these liver-specific functions. Serum factor(s) responsible for these effects were not dialysable or associated with lipoproteins, but were removed by charcoal extraction.

Animals

[Contact allergy for Alstrumeria (inca lily)].

We report 6 patients with occupational contact allergy to Alstroemeria cultivars. Four of them presented with the clinical picture of 'tulip fingers'. They all reacted to parts of fresh plants and to tuliposide A. The literature on Alstroemeria allergy is reviewed.

Adolescent

Dexamethasone regulates bile acid synthesis in monolayer cultures of rat hepatocytes by induction of cholesterol 7 alpha-hydroxylase.

To study the effect of steroid hormones on bile acid synthesis by cultured rat hepatocytes, cells were incubated with various amounts of these compounds during 72 h and conversion of [4-14C]cholesterol into bile acids was measured. Bile acid synthesis was stimulated in a dose-dependent way by glucocorticoids, but not by sex steroid hormones, pregnenolone or the mineralocorticoid aldosterone in concentrations up to 10 microM. Dexamethasone proved to be the most efficacious inducer, giving 3-fold and 7-fold increases in bile acid synthesis during the second and third 24 h incubation periods respectively, at a concentration of 50 nM. Mass production of bile acids as measured by g.l.c. during the second day of culture (28-52 h) was 2.2-fold enhanced by 1 microM-dexamethasone. No change in the ratio of bile acids produced was observed during this period in the presence of dexamethasone. Conversion of [4-14C]7 alpha-hydroxycholesterol, an intermediate of the bile acid pathway, to bile acids was not affected by dexamethasone. Measurement of cholesterol 7 alpha-hydroxylase activity in homogenates of hepatocytes, incubated with 1 microM-dexamethasone, showed 10-fold and 90-fold increases after 48 and 72 h respectively, as compared with control cells. As with bile acid synthesis from [14C]cholesterol, no change in enzyme activity was found in hepatocytes cultured in the presence of 10 microM steroid hormones other than glucocorticoids. Addition of inhibitors of protein and mRNA synthesis lowered bile acid production and cholesterol 7 alpha-hydroxylase activity and prevented the rise of both parameters with dexamethasone, suggesting regulation at the mRNA level. We conclude that glucocorticoids regulate bile acid synthesis in rat hepatocytes by induction of enzyme activity of cholesterol 7 alpha-hydroxylase.

Animals

Comparison of taurocholate accumulation in cultured hepatocytes of pig, rat and man.

Intracellular accumulation at 37 degrees C of 50 microM [14C]taurocholic acid by hepatocytes of pig and rat, cultured for 24 hours, and by human hepatocytes, cultured for 12 hours, reached equilibrium after an incubation time of 1 to 2 hours. Maximum capacity to accumulate taurocholate intracellularly was assessed in 3-hour incubations with increasing extracellular taurocholate concentrations. Accumulation capacity of pig and rat hepatocytes was saturated at 100 microM, while uptake by human hepatocytes slightly increased even further above this concentration. At extracellular concentrations of 100 to 500 microM, hepatocytes of these three species concentrated taurocholic acid intracellularly to between 13 and 17 nmol per mg cell protein, corresponding to an intracellular concentration which was 10-70 times higher than the added extracellular concentration. With proceeding culture age, accumulation capacity of rat and human hepatocytes declined steeply (-80% and -60%, respectively between the first and second culture day). In contrast, in cultured pig hepatocytes, this capacity was only 40% lower on the third day compared to the first day of culture. It is concluded that in cultured pig hepatocytes, the capacity to accumulate bile acids is retained for a longer time than in cultured rat and human hepatocytes.

Animals

[Inflammation of the tail in swine. Slaughter-house findings during 1972, 1973, and 1974 (author's transl)].

In the Public Salughter-House of Utrecht, a percentage increase in the number of pigs with inflammation of the tail, which had or had not healed, was observed during the period from 1972 to 1974 inclusive. The most common secondary symptoms of inflammation consisted in embolic pneumonia, osteomyelitis of the vertebrae and abscess formation in other parts of the body, particularly the semimebranosus muscles. Osteomyelitis was found to be the most common complication in pigs in which the inflammation of the tail had healed, whereas this usually consisted in embolic pneumonia in those cases in which the inflammation of the tail had not healed. The bacteriological examination carried out in accordance with the Meat Inspection Regulations was positive in 21.7 per cent, 13.5 per cent of the cases respectively in 1972, 1973 and 1974. Micro-organisms were isolated much more frequently from the kidney than they were from the spleen and meat. There was no relationship between the presence of inflammation of the tail and climatological conditions during the fattening period. The losses at slaughter from inflammation of the tail in the Netherlands are estimated at 3-4 million guilders per annum.

Animals