Biomedical subjects
D H Russell
Publications and source records attributed to D H Russell.
Activation of 3':5'-cyclic AMP-dependent protein kinase and induction of ornithine decarboxylase as early events in induction of mixed-function oxygenases.
The parenteral administration of a single dose of 3-methylcholanthrene to rats caused an increase in the liver of the concentration of 3', 5'-cAMP and of the activity of cAMP-dependent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37). These events were followed by an increased activity of ornithine decarboxylase (L-ornithine carboxy-lase, EC 4.1.1.17), the enzyme that controls the biosynthesis of polyamines. Finally, the activity of benzo[a]pyrene hydroxylase, as well as the amount of cytochrome P-448, was increased. Similarly, after the administration of phenobarbital, there was first an increase in the cAMP concentration and in the activity of cAMP-dependent protein kinase, then the induction of ornithine decarboxylase, and finally, an enhanced activity of ethylmorphine N-demethylase and an increased content of cytochrome P-450. These data suggest that the drug-induced processes in liver that increase the activities of the oxidative, and presumably other, drug-metabolizing enzymes include the following sequence of events: (1) increase in cAMP concentration and/or activation of cAMP-dependent protein kinase; (2) induction of ornithine decarboxylase; and, (3) induction of drug-metabolizing enzymes.
Polyamine synthesis in liver and kidney of flounder in response to methylmercury.
The effect of methylmercury administration on polyamine synthesis was studied in the liver and kidney of the winter flounder (Pseudopleuronectes americanus). A single injection of methylmercury resulted in five- and sevenfold elevations of ornithine decarboxylase activity in the liver and kidney within 15 and 45 h, respectively. There were elevations of both putrescine- and spermidine-stimulated S-adenosylmethionine decarboxylase activities (approximately 1.5-fold) in both tissues. Evaluation of the polyamine accumulation patterns in these tissues indicated that in the liver all three polyamines increased in concentration until 48 h and then decline. In the kidney, the concentration of putrescine increased steadily until it was 200% of control at 72 h and then declined. Spermidine concentration decreased throughout the time studied and was 17% of control at 1 wk. There was no significant change in the concentration of spermine throughout the period studied. The changes in the polyamine pools and in the activities of the polyamine biosynthetic enzymes after methylmercury administration are consistent with an involvement of the polyamines in the recovery phase to a toxic dose of methylmercury.
Changes in serum putrescine and spermidine levels following local radiation to hepatoma 3924A of the rat.
Local irradiation of tumors of rats bearing 3924A hepatomas resulted in more than a doubling of the putrescine levvel and nearly a doubling of spermidine concentration in the serum within 12 hr. Within 24 hr, the putrescine concentration had increased four-fold in the serum, along with a continued increase in the spermidine concentration. The decrease in the spermidine concentration of the tumor paralleled increased levels of spermidine in the serum, whereas the concentrations of polyamines in the liver were unchanged. These changes are similar to previously reported changes in the spermidine concentration in sera and in tumors following the administration of a single dose of 5-fluorouracil to rats with 3924A hepatomas. Since local irradiation was confined to the tumor, we conclude that the increases in putrescine and spermidine detected in the serum are derived from the tumor tissue with no involvement of the host tissues.
Adenosine cyclic 3',5'-monophosphate-dependent protein kinase and ornithine decarboxylase involvement in the induction of cytochrome P-450 and hepatic hypertrophy.
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Ornithine decarboxylase: transsynaptic induction in the adrenal medulla.
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Relationship of ornithine decarboxylase to RNA polymerase i activity.
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Polyamines as predictors of success and failure in cancer chemotherapy.
Polyamines appear to have clinical utility for monitoring cancer therapy. Investigations on the patterns of urinary excretion of polyamines in patients receiving cancer chemotherapy and studies of the tritiated-thymidine labelling index of tumour cells in a subgroup of these patients form the basis for a hypothesis that spermidine can serve as a marker of tumour-cell kill, whereas putrescine appears to reflect the proliferative behaviour or "growth fraction" of the tumour. Although tests of this hypothesis are necessary to establish the predictive value of polyamines for monitoring cancer therapy, it is clear that polyamines may provide important new information on tumour cytokinetic parameters.
Estimation of urinary diamines and polyamines by thin-layer chromatography.
The dansylated derivatives of ammonia, 1,3-diaminopropane, 1,4-diaminobutane, 1,5-diaminopentane, spermidine, histamine, and spermine were separated by one ascending development in chloroform-triethylamine (5:1) on a 250-mum silica gel 60 plate. Putrescine, cadaverine, spermidine, and spermine in human urine were quantitated by a direct scan of the fluorescent intensity of the spots corresponding to these compounds. Higher amounts of spermidine and spermine were found in the urines of cancer patients compared to the values of these substances in normal urine.
In vivo activation of cAMP-dependent protein kinase by aminophylline and 1-methyl, 3-isobutylxanthine.
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Ornithine decarboxylase activity: control by cyclic nucleotides.
Both exposure to cold and administration of aminophylline result in rapid increases in cyclic adenosine monophosphate (cyclic AMP) in the adrenal medulla and adrenal cortex. These increases are followed by dramatic increases in ornithine decarboxylase activity is due to new enzyme systhesis. The data suggest that the decarboxylase activity is regulated by an increase in cyclic AMP.
Alterations in the accumulation patterns of polyamines in brains of myelin-deficient mice.
Quaking mutants and jimpy mutants of mice have known deficiencies of myelination of the central nervous system, as well as lesser involvement of the peripheral nervous system. Both mutants also have altered polyamine synthesis and accumulation, particularly in the hindbrain and spinal column. The ratio of spermidine/spermine, which generally is higher in tissues with high rates of biosynthetic activity, was significantly lower in the mutants as compared to their normal siblings. In quaking mutants, 5 months of age, the spermidine concentration of hindbrain and spinal column was 60% that of controls. In contrast, the decreased spermidine/spermine ratio in jimpy mutants resulted from a marked increase in the spermine concentration in both forebrain and hindbrain. Alterations in the spermidine/spermine ratio could lead to reductions in the biosynthetic potential of the brain during development.
Changes in polyamine metabolism in WI38 cells stimulated to proliferate.
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Cell cycle specific fluctuations in adenosine 3':5'-cyclic monophosphate and polyamines of Chinese hamster cells.
Chinese hamster V79 cells were synchronized by mitotic selection, which resulted in approximately 95% synchrony. The adenosine 3':5'-cyclic monophosphate level was elevated within 3 hr (G1 phase) and reached a level 2-fold higher than in early G1 within 6 hr (early S phase). An increase in ornithine decarboxylase activity (6-ornithine carboxy-lyase, EC 4.1.1.17), the initial enzyme in the polyamine biosynthetic pathway, was detected within 4 hr and was maximal at 8 hr. Since about 20% of the cells were labeled with [3-H]thymidine at 4 hr, ornithine decarboxylase exhibits cell-cycle specific activity starting in late G1 and continuing through middle S phase. The activity of S-adenosylmethionine decarboxylase (S-adenosyl-L-methionine carboxylase, EC 4.1.1.50) increased within 5 hr, i.e., early S phase. It is suggested on the basis of these data and other studies discussed herein that the increase in ornithine decarboxylase activity, which parallels closely the elevation in cyclic AMP, is an example of adenosine 3':5'-cyclic monophosphate-mediated protein synthesis.
Relative usefulness of measuring polyamines in serum, plasma, and urine as biochemical markers of cancer.
Serial samples of plasma and serum were collected in the morning and afternoon from cancer patients, along with 24-h urine specimens. Values for serum and plasma samples taken at the same time from the same patient differed little, suggesting that either procedure is acceptable for polyamine analysis. Increases in concentrations of putrescine and spermidine in serum and plasma correlate well with such increases in 24-h urine samples. Spermidine concentrations in sera were consistently about 10-fold lower than corresponding urine values. Putrescine concentrations were 10- to 100-fold different. The variation in putrescine values may be due to its more active metabolism by diamine oxidase, an enzyme known to be present in serum. Concentrations of polyamines in serum and urine increased in response to effective chemotherapy.
Vincent van Gogh--genius in a mental hospital.
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Effects of methyl xanthine derivatives on cyclic AMP levels and ornithine decarboxylase activity of rat tissues.
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Comparative properties of rat liver and sea urchin eggs S-adenosyl-L-methionine decarboxylase.
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