Although erythropoietin (Epo) is produced primarily by the kidneys in response to hypoxia, the precise cell type(s) and mechanisms by which these cells regulate production are poorly understood. In the experiments we report, the kinetics of renal Epo production in response to acute hypoxia and the intrarenal localization of cellular Epo synthesis were studied at the level of Epo mRNA. Erythropoietin mRNA expression was determined by Northern blot analysis of rat kidney RNAs using a probe derived from the mouse Epo gene. Renal Epo mRNA content increased as early as 1 hour after initiation of hypoxia and continued to accumulate during 4 hours of stimulation. Discontinuation of the hypoxic stimulus resulted in rapid decay of mRNA levels. Kidney and plasma Epo levels measured by radioimmunoassay paralleled, with respective lag times, the changes in renal Epo mRNA content, suggesting that Epo production in response to acute hypoxia represents de novo synthesis and is regulated by changes in Epo mRNA. Northern blot analysis of RNAs extracted from separated glomerular and tubular tissue fractions revealed Epo mRNA in the tubular fraction, whereas glomerular tissue did not contain Epo mRNA. Thus, the site of cellular Epo synthesis is located in the renal tubule or its interstitium and not in the glomerular tuft.
Subcutaneous administration of octreotide 500 microg thrice daily is not of additional benefit as adjuvant therapy to high dose corticosteroids in severe ulcerative colitis.
This study suggests that less than 20% of patients identified with Barrett's oesophagus at routine endoscopy would benefit from endoscopic cancer surveillance. Prospective surveillance programmes should be limited to patients with an increased cancer risk and a good health profile.
SummaryIn liver disease low prekallikrein levels may be found which has been suggested to be due to diminished synthesis. However, it may also be due to endotoxemia accompanying liver disease. To study the last possibility prekallikrein, endotoxins and Normotest were determined in 18 cirrhosis patients. The relation between the prekallikrein concentration (after 15 min activation) and the Normotest was significant (r = +0.72, P <0.001). Endotoxemia was only found in the more severe forms of liver disease (Normotest below 60%). During endotoxemia the prekallikrein levels were significantly lower than when no endotoxins were present in the blood of the same patients. The Normotest did not differ significantly in these patients in relation to the presence or absence of endotoxins. The activation of prekallikrein was slower in the more severe forms of liver disease. This might be due to reduced levels of factor XII and high molecular weight kininogen.
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