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R Bean

Publications and source records attributed to R Bean.

7 recordsLinked to original sources
PubMed2001

cyp7b1 catalyses the 7alpha-hydroxylation of dehydroepiandrosterone and 25-hydroxycholesterol in rat prostate.

Dehydroepiandrosterone (DHEA) is the most prominent circulating steroid in humans, and it is a precursor for sex-steroid synthesis in peripheral tissues, including the prostate. Recently, enzyme-mediated pre-receptor metabolism has been recognized as a key step in determining steroid action in vivo. Hydroxylation of 3beta-steroids at the 7alpha-position has been reported in rat and human prostate to be a major inhibitory pathway to sex-steroid synthesis/action. However, the molecular identity of the enzyme responsible is so far unknown. We recently described a novel cytochrome P450 enzyme, cyp7b1, strongly expressed in the hippocampus of rodent brain, which catalyses the metabolism of DHEA, pregnenolone and 25-hydroxycholesterol to 7alpha-hydroxy products. In the light of this new enzyme, we have examined its possible role in 7alpha-hydroxylation conversion in rat prostate. NADPH-dependent 7alpha-hydroxylation was confirmed for 3beta-hydroxysteroids including DHEA and androstenediol, as well as 25-hydroxycholesterol. Kinetic analysis yielded an apparent K(m) of 14+/-1 microM for 7alpha-hydroxylation of DHEA in the prostate gland, a value similar to that recorded for recombinant cyp7b1 enzyme [13.6 microM; Rose, Stapleton, Dott, Kieny, Best, Schwarz, Russell, Bjoorkheim, Seckl and Lathe (1997) Proc. Natl. Acad. Sci. U.S.A. 94, 4925-4930]. The V(max) value of the prostate was 46+/-2 pmol/min per mg, and this activity was inhibited by clotrimazole, a P450-enzyme blocker. Moreover, RNA analysis (reverse-transcription PCR, Northern blotting and in situ hybridization) revealed a high expression of cyp7b1 mRNA in the rat prostate, restricted to the epithelium, suggesting that cyp7b1 catalyses oxysterol 7alpha-hydroxylation in the prostate gland.

Animals↗
PubMed2001

Ontogeny of the neurosteroid enzyme Cyp7b in the mouse.

The function of the major adrenal steroid dehydroepiandrosterone (DHEA) is not known. It has been reported to improve learning and memory in mice and can exert neuroprotective and trophic effects, particularly in the hippocampus. We recently described a cytochrome P450 (Cyp7b), that catalyses the 7alpha-hydroxylation of DHEA and related steroids and sterols. In this paper, we have used mRNA in situ hybridisation to map the ontogeny of cyp7b in the foetal and adult mouse. Cyp7b mRNA is highly expressed throughout from embryonal (E) day 12.5 (the earliest day studied). There is also expression throughout the body, including the spine, thymus, developing kidneys, lungs and urogenital region. Widespread expression becomes more restricted towards birth: in newborn mice expression is largely limited to the hippocampus, with some expression being detected in kidney. The overall decline in mRNA, and increasing restriction to the hippocampus, is reflected in the DHEA hydroxylation activity of brain homogenates. This pattern of cyp7b mRNA expression in specific organs could be consistent with a protective role in foetal development, with highest expression seen when the foetus is most vulnerable to steroid excess (i.e.) early gestation.

Animals↗
PubMed2000

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Health Insurance Portability and Accountability Ac↗
PubMedDate not supplied

Statistical analysis of environmental monitoring data: does a worst case time for monitoring clean rooms exist?

To determine the relationship between the sampling time of the environmental monitoring, i.e., viable counts, in aseptic filling areas and the microbial count and frequency of alerts for air, surface and personnel microbial monitoring, statistical analyses were conducted on 1) the frequency of alerts versus the time of day for routine environmental sampling conducted in calendar year 1994, and 2) environmental monitoring data collected at 30-minute intervals during routine aseptic filling operations over two separate days in four different clean rooms with multiple shifts and equipment set-ups at a parenteral manufacturing facility. Statistical analyses showed, except for one floor location that had significantly higher number of counts but no alert or action level samplings in the first two hours of operation, there was no relationship between the number of counts and the time of sampling. Further studies over a 30-day period at the floor location showed no relationship between time of sampling and microbial counts. The conclusion reached in the study was that there is no worst case time for environmental monitoring at that facility and that sampling any time during the aseptic filling operation will give a satisfactory measure of the microbial cleanliness in the clean room during the set-up and aseptic filling operation.

Drug Industry↗