Biomedical subjects
C J Potter
Publications and source records attributed to C J Potter.
Discoordinate hormonal and ontogenetic regulation of four rat serpin genes.
To understand the roles of four highly homologous rat hepatic serine protease inhibitor genes (Spi 2.1, Spi 2.2, Spi 2.3, and alpha 1-antitrypsin), we measured the hepatic content of their specific mRNAs under several physiological conditions. Spi 2.1 and 2.3 mRNAs, which are regulated by growth hormone, paralleled serum growth hormone levels developmentally. Only Spi 2.1 mRNA decreased with starvation, while Spi 2.2, 2.3, and alpha 1-antitrypsin mRNAs did not change. Despite the close homology of the Spi genes to mouse contrapsin, which is regulated by testosterone, none of the serine protease inhibitor mRNAs examined here was dependent on androgens for expression. Spi 2.2 mRNA displayed a unique ontogenetic regulation, with a rise in hepatic content at day 19 to levels five times that of any other age group. These studies confirm the importance of growth hormone in the regulation of Spi 2.1 and 2.3 mRNAs and suggest that Spi 2.2 mRNA may be regulated by metabolic alterations occurring in the weaning period.
Developmental regulation of the hepatic acute phase response.
For evaluation of the ontogenetic regulation of the acute phase response, inflammation was induced in Fischer rat litters at different postnatal ages. Four homologous rat hepatic serine protease inhibitor (Spi 2.1, Spi 2.2, Spi 2.3, and alpha 1-antitrypsin) mRNAs were measured in livers 24 h after injection. Animals mounted both positive and negative acute phase responses at all ages, but responses were blunted in young animals, reaching adult levels by days 7-19. alpha 1-Antitrypsin mRNA had no response, and Spi 2.2 mRNA had 50% the rise seen in adults on days 3 and 7. Spi 2.1 and 2.3 mRNAs, negative acute phase reactants, showed attenuation of adult response to inflammation in infant animals of 33% (Spi 2.1) and 40% (Spi 2.3). In hypophysectomized animals, the responses of Spi 2.2, 2.3, and alpha 1-antitrypsin mRNAs after turpentine stimulation were similar to that of normal animals, whereas Spi 2.1 mRNA did not change. In conclusion, infant animals mount a blunted response to tissue injury; multiple factors may be involved in the development of the full adult response. Immaturity of the pituitary may play a role in the suppression of Spi 2.1 mRNA's response during inflammation in infant animals. These highly evolutionary related genes will be helpful in identifying specific factors regulating gene expression in inflammation and development.
Use of an in vitro haemolysis test to predict tissue irritancy in an intramuscular formulation.
As part of a drug development program, an in vitro haemolysis test has been used to predict the in vivo muscle tissue irritancy of intramuscular (i.m.) formulations of a new drug entity. Solutions of lactic acid, polyvinylpyrrolidone (PVP) 12PF and two commercial injections were also included in the study. The results indicated that the test was able to differentiate formulations in terms of haemolytic potential and the correlation between the haemolysis test results and in vivo intramuscular irritancy studies indicated that the test may be used to screen formulations for potential tissue irritancy prior to in vivo evaluation.