[Comparison of prothrombin activity and concentration in various liver conditions].
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Rat liver contains an ATP-stimulated translocation promoter (ASTP), which is not a receptor and which enhances nuclear binding of activated receptor-glucocorticoid complex in the presence of ATP. Studies were made on changes in ASTP activity under various conditions to elucidate its physiological role in the action of glucocorticoid hormone. ASTP activity in the cytosol fraction increased markedly after adrenalectomy. Conversely, 30 min after a single injection of dexamethasone it decreased and then gradually increased. The increase in ASTP activity after adrenalectomy was inhibited by actinomycin D or cycloheximide. With decrease in ASTP activity in the cytosol fraction after the administration of glucocorticoids, activity appeared in the nuclear fraction 30 min after injection and then decreased. Thus, after the dexamethasone injection, the changes in ASTP activity in the cytosol and nuclei were similar to but not coincident with those in the glucocorticoid receptor. These results suggest, but do not prove, that ASTP is translocated or binds to nuclei with activated receptor-glucocorticoid complexes. From these results, we consider that ASTP may be an integral part of the regulatory mechanism for the action of steroid hormones and may influence specific gene expression by increasing nuclear binding of the activated complex.
The secretion rates of triglycerides from liver into plasma of obese animals and controls, as well as in obese animals 4 weeks from feeding a fat-deprived diet were determined. In the dynamic phase of obesity (9-week-old animals receiving fat-rich food for 4 weeks) an increase in secretion rate over the control was determined, which persisted to the same extent after having fed a fat-deprived diet for 4 weeks. In the static phase of obesity (24-week-old animals given a fat-rich diet for 9 weeks) the control animals showed the same secretion rate as the control animals in the dynamic phase. In contrast to the dynamic phase, obese animals revealed no changes of the secretion rate also in these animals. Since the present knowledge about the regulation of triglyceride release from the liver into the plasma via the VLDL is scarce, various food-, hormone-, and enzyme effects have been discussed in more detail, and the changes observed were correlated, on the basis of own experiments, in particular with hyperinsulinemia present in the obese animals and with the increased supply of free fatty acids to the liver in the dynamic phase of obesity. The changes in secretion rate following the shift to fat-deprived food cannot at present be satisfactorily explained.
Activities of enzymes relating to the acyl dihydroxyacetone phosphate (acyl DHAP) pathway were determined in rat liver under conditions known to elevate the peroxisomal beta-oxidation activity. In fasted and streptozotocin-induced diabetic rats, DHAP acyltransferase activity showed a small but significant increase, though the activities of glycerol-3-phosphate (GP) acyltransferase and alkyl DHAP synthase were not changed. After 2 weeks, feeding of 20% partially hydrogenated marine oil, the activity of DHAP acyltransferase also increased to 140% of the control. The feeding of 0.25% clofibrate and 2% di(2-ethylhexyl)phthalate (DEHP) increased the activities of both DHAP and GP acyltransferases by 2- to 3-fold, whereas alkyl DHAP synthase activity decreased under the same conditions. A fractionation study showed that the increases in the activities of DHAP acyltransferase and acyl/alkyl DHAP reductase in the liver of rats treated with DEHP occurred mainly in peroxisomes and microsomes, respectively. The phospholipid contents per mg protein of the isolated hepatic peroxisomes from rats were as follows (percent of the control): fasting, 62%; diabetic, 69%; high fat-diet, 89%; clofibrate-treated, 126%; DEHP-treated, 119%. These results suggest that glycerophospholipid metabolism might also be controlled by peroxisomal enzymes under physiological and pathological conditions.
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Urinary copper excretion was found to be increased in patients with cholestasis, hepatitis and cirrhosis, but the penicillamine-induced increment was normal. Wilson's disease patients had increased copper excretion before and after penicillamine, especially in untreated cases. Hepatic copper concentrations correlated with urinary copper excretion in cholestasis and treated Wilson's disease, but not in hepatitis or cirrhosis. In treated Wilson's disease, measurement of urinary copper excretion should be valuable in estimating the degree of removal of copper from the body during therapy. Urinary copper clearances were raised in various liver conditions, maximally in untreated Wilson's disease. It is suggested that only part of the serum non-caeruloplasmin copper is available for excretion into urine.
An ultrasonic analytical method has been developed which is capable of remote, in vivo differentiation between various types of soft tissue on the basis of differences in their gross histological structure. The method is analogous to that employed in X-ray crystallography and is referred to as ultrasonic diffraction analysis. A clinical trial of this method in the investigation of liver disease in 70 patients is reported, in which a total of 416 ultrasonic diffraction patterns associated with various liver conditions have been analysed and related to independent follow-up information. The existance of a malignant condition of the liver has been identified in 95% of the cases involving focal metastatic deposits and in all of the 11 cases studied where the livers had diffuse malignant involvement. Cirrhosis and secondary involvement of the liver due to Hodgkin's disease have also been shown to exhibit specific tissue signatures which enable them to be differentiated from other hepatic disorders.
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Serum glutathione reductase activity was measured in various conditions including acute hepatitis, chronic hepatitis, liver cirrhosis, malignant neoplastic diseases, and obstructive jaundice. A statistically significant elevation of the enzyme activity was found in all of these clinical conditions above normal value, especially in patients with acute hepatitis, some liver cancer, and malignant biliary obstruction. Comparison with other liver function tests showed the existence of statistically significant correlations of serum glutathione reductase with SGOT, SGPT and alkaline phosphatase in acute hepatitis, and with alkaline phosphatase in cirrhosis. In parenchymatous liver disease, serial determination was found to be important. High values in obstructive jaundice suggest the malignant obstruction.
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The rate of liver protein synthesis in vivo and hepatic messenger ribonucleic acid (mRNA) levels were measured to examine the mechanisms regulating liver protein synthesis in chicks under various nutritional conditions. Fractional synthesis rate (FSR) of liver protein was measured by using a large dose injection of L-[4-3H]phenylalanine. Poly(A)+RNA was extracted as mRNA from total RNA using poly(U)-Sepharose 4B affinity chromatography. The influence of varying dietary protein levels (0-60%) on protein synthesis and mRNA concentration in the liver of chicks was examined. Both FSR (%/d) and absolute synthesis rate (ASR, mg/d) of liver protein increased with increasing dietary protein levels from 0 to 20% (the dietary protein requirement), whereas when dietary protein increased from 20 to 40%, both rates decreased significantly. This change was accounted for by changes in RNA concentration (RNA:protein ratio) and hepatic mRNA content. Second, the time course of changes in liver protein synthesis and hepatic mRNA content were measured in force-fed chicks that had been deprived of food for 2 d. Liver protein synthesis (FSR) was significantly greater 30 min after refeeding compared with that of unfed chicks. Liver protein synthesis (FSR) correlated with the activity of RNA to synthesize protein (r = 0.61, P < 0.001), and ASR was correlated with hepatic mRNA content (r = 0.37, P = 0.030). Third, experimental diets containing individual nutrients were force-fed to chicks after 2 d of food deprivation. When chicks were refed carbohydrate and protein diets, liver protein synthesis (FSR) tended to be greater by 24% (P = 0.063) and 22% (P - 0.075) at 30 min after refeeding compared with that of unfed chicks, respectively. These findings indicate that changes in the rate of liver protein synthesis in vivo due to the alteration in nutritional conditions are, at least partially, accounted for by not only RNA concentration and the activity of RNA synthesizing protein but also hepatic mRNA levels.