Synthesis of 2-amino-2-deoxyarabinose hydrochloride.
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Biomedical subjects
Publications and source records attributed to S Otani.
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Mouse interferon (alpha + beta) given to mice by intraperitoneal injection suppressed both the accumulation of putrescine and stimulation of DNA synthesis in liver caused by partial hepatectomy. The suppression of DNA synthesis was completely reversed by exogenous putrescine. The same results were obtained when core 2',5'-oligoadenylate instead of interferon was given to partially hepatectomized mice. These results suggest that interferon inhibits putrescine formation through elevating the 2',5'-oligoadenylate level and thus inhibits DNA synthesis in the regenerating liver.
The activity of ornithine decarboxylase and the intracellular concentrations of putrescine and spermidine in the non-ligated lobes of the liver increased after portal branch ligation. These changes were followed by increased [3H]thymidine uptake into the acid-insoluble fraction of the liver. The induction of ornithine decarboxylase and changes in intracellular polyamines are important biochemical events in liver regeneration, so our results suggest that portal branch ligation causes formation of some stimuli that trigger liver regeneration. Changes were less with ligation than with partial hepatectomy.
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The effect of splenectomy on hepatic ornithine decarboxylase (ODC) induction, DNA synthesis, and mitosis of hepatocytes was studied in rat liver after partial hepatectomy. ODC activity markedly increased in the early stages of liver regeneration, and the increase in the activity was significantly enhanced in splenectomized rats. Splenectomy specifically induced ODC since tyrosine aminotransferase and general protein synthesis were not affected. Splenectomy also enhanced increase in hepatic polyamines, DNA synthesis, and mitosis in regenerating liver. The results suggest that splenectomy affects liver regeneration after partial hepatectomy by enhancing induction of ODC activity, which is an important biochemical event in the early stage of liver regeneration.
Retinoic acid potentiated the increases in ornithine decarboxylase (L-ornithine carboxy-lyase [EC 4.1.1.17]) activity, [3H]difluoromethylornithine binding to ornithine decarboxylase, intracellular levels of polyamines and DNA synthesis in guinea pig lymphocytes stimulated with phytohemagglutinin. The stimulatory effect on the ornithine decarboxylase induction was dependent on the dose of retinoic acid and on the time of addition of the drug. Retinoic acid has to be added not later than 2 h after phytohemagglutinin to elicit the potentiation. Retinyl acetate also potentiated ornithine decarboxylase induction caused by phytohemagglutinin. Both of these retinoids augmented ornithine decarboxylase induction caused by phorbol 12-myristate 13-acetate. The half-life of ornithine decarboxylase activity estimated after addition of actinomycin D was longer in cells treated with phytohemagglutinin or phorbol 12-myristate 13-acetate together with retinoic acid than in cells treated with the mitogen alone. The half-life after addition of cycloheximide was not affected by retinoic acid. These results suggest that the retinoids are stimulators rather than inhibitors of ornithine decarboxylase induction caused by phytohemagglutinin or phorbol 12-myristate 13-acetate in guinea pig lymphocytes and that retinoic acid potentiates the enzyme activity at the transcriptional or posttranscriptional, but not at the post-translational stage.
The human promyelocytic leukemia cell line, HL-60, differentiated into macrophage/monocytes in the presence of 1 alpha,25-dihydroxycholecalciferol [1 alpha,25(OH)2D3], as assessed by the percentage of morphologically mature cells and their ability to reduce nitroblue tetrazolium. In this study of the mechanism involved, the activities of ornithine decarboxylase and spermidine/spermine-N1-acetyltransferase (SAT), the rate-limiting enzymes of polyamine metabolism, as well as the cellular levels of polyamine were measured. ODC activity reached a peak 24 h after the addition of 1 alpha,25(OH)2D3 and then decreased, while SAT activity gradually increased as differentiation commenced. An increase in putrescine and decreases in spermidine and spermine were also observed. Addition of alpha-difluoromethylornithine, an irreversible inhibitor of ODC, with or without methylglyoxalbis(guanylhydrazone), an inhibitor of S-adenosylmethionine decarboxylase, caused no effect on 1 alpha,25(OH)2D3-induced cell differentiation, although the cellular levels of putrescine and spermidine decreased markedly. Addition of alpha-difluoromethylornithine markedly suppressed cell proliferation; this effect was reversed by the addition of exogenous putrescine. Addition of exogenous spermidine or spermine to overcome activation of SAT also had no effect on 1 alpha,25(OH)2D3-induced cell differentiation. These results suggest both that polyamine metabolism is not important in 1 alpha,25(OH)2D3-induced differentiation of HL-60 cells, but that it is intimately involved in the proliferation of these cells.
We measured ubiquinone (UQ)-9 and UQ-10 content in various foods using high performance liquid chromatography. UQ-9 was detected in cereals, some vegetables and their products. Corn oil and wheat germ had large amounts of UQ-9 in particular. UQ-10 was detected in meats, fishes, pulses, nuts, dairy products and various vegetables. Migratory fishes, rapeseed oil and soybean oil had considerably large amounts of UQ-10.
The divalent cation ionophore A23187 increased the activity in bovine lymphocytes of spermidine/spermine N1-acetyltransferase, a rate-limiting enzyme in polyamine biodegradation. The enzyme was induced in a dose- and time-dependent manner. Induction was suppressed by indomethacin, but not by trifluoperazine (TFP), N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) or palmitoylcarnitine. These results suggest that the activation of phospholipase A2 involves the induction of spermidine/spermine N1-acetyltransferase. Ornithine decarboxylase, a rate-limiting enzyme in polyamine biosynthesis, was not suppressed by indomethacin but was by TFP and W-7. The molecular mechanism of the induction of spermidine/spermine N1-acetyltransferase and ornithine decarboxylase may be different.
When guinea pig lymphocytes were cultured with 1-oleoyl-2-acetyl-glycerol (OAG), A23187, and cholera toxin, ornithine decarboxylase activity was induced synergistically, peaking at 6 h. Addition of 12-O-tetradecanoyl-phorbol 13-acetate (TPA), A23187, and dibutyryl cAMP caused the same kind of induction. Cholera toxin potentiated the ability of A23187 to induce ornithine decarboxylase, but not that of OAG. Dibutyryl cAMP augmented the induction caused by A23187 but not by TPA. These results suggest that both the activation of Ca++-sensitive, phospholipid-dependent protein kinase (protein kinase C) and the increase in intracellular levels of Ca++ and cAMP are necessary for this induction. cAMP may potentiate the induction by modulating a Ca++ messenger system other than that for protein kinase C activation.
Calmodulin antagonists, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), N-(6-aminohexyl)-1-naphthalenesulfonamide (W-5) and trifluoperazine inhibited ornithine decarboxylase induction in lymphocytes activated with phytohemagglutinin or inophore A23187. W-7, a more potent calmodulin antagonist than W-5, suppressed ornithine decarboxylase induction in a higher extent than did W-5. These results suggest that calmodulin may play an important role in ornithine decarboxylase induction in the activated lymphocytes. However, the extent of ornithine decarboxylase induction was greater in cells pretreated with Clostridium phospholipase C and then incubated with ionophore A23187 than in cells incubated with ionophore A23187 without the pretreatment. Moreover, combined treatment of cells with ionophore A23187 and tumor promotor, phorbol 12-myristate 13-acetate, caused synergistic induction of ornithine decarboxylase activity. These results, taken together, suggest that both activations of Ca2+-activated phospholipid-dependent protein kinase by diacylglycerol and of calmodulin-dependent function resulted from an elevation of cytosolic Ca2+ concentration may operate in the induction of ornithine decarboxylase in the activated lymphocytes.
We report two cases of a membranous stenosis of the hepatic portion of the inferior vena cava. Membranotomy was performed with a specially designed instrument similar to a Tubbs' dilator following balloon membranotomy. During the procedures, ultrasonographic observations were made and this technique was confirmed to be effective for proper placing of a balloon and a dilator in the stenotic portion. Follow-up evaluation of the procedures was also feasible with this ultrasonic aid.
Parathyroid hormone (PTH) increased the activity of spermidine/spermine N1-acetyltransferase, a rate-limiting enzyme of polyamine biodegradation, in rabbit costal chondrocytes in culture. The enzyme activity increased in a dose-dependent manner after addition of PTH to the culture, reaching a maximum at 8 h. The increase in the enzyme activity was abolished by cycloheximide or actinomycin D. Dibutyryl cyclic AMP also induced the acetyltransferase to some extent. These results suggest that the induction of spermidine/spermine N1-acetyltransferase by PTH may play some significant role in the expression of the differentiated phenotype of chondrocytes.
Phorbol 12-myristate-13-acetate (PMA) inhibited an increase in [3H]thymidine incorporation induced by phytohemagglutinin (PHA) in cultured bovine lymphocytes. Cellular levels of putrescine increased in the presence of PHA and PMA but the levels of spermidine and spermine had decreased to the control levels by 40 h. In cells treated with PHA and PMA, the activity of spermidine/spermine N1-acetyltransferase, a rate-limiting enzyme in polyamine biodegradation, was stimulated synergistically. Phorbol esters with tumor-promoting ability also stimulated the enzyme activity and a reciprocal correlation between the enzyme activity and DNA synthesis was observed. Addition of spermine reversed the PHA- and PMA-induced inhibition of DNA synthesis but putrescine and spermidine failed to restore it. These results suggest that the enhancement of spermidine/spermine N1-acetyltransferase activity results in the depletion of intracellular spermine and a concomitant decrease in DNA synthesis.
In order to evaluate cardiac contractile reserve, echocardiographic studies were performed on 59 patients with acquired valvular heart disease and 13 patients with atrial septal defect. After epinephrine loading, the 59 patients were classified into three groups. In group I, echocardiographically-obtained left ventricular posterior wall excursion (PWE) remained below 10 mm after the administration of 2 microgram/min epinephrine. This group included patients with PWE below 10 mm after 1 microgram/min epinephrine loading but who could not endure the 2 microgram/min infusion because of significant adverse effects. In group II, PWE was less than 10 mm before the loading, but exceeded 10 mm after the administration of 1 or 2 microgram/min epinephrine loading. In group III, PWE exceeded 10 mm without stress. The conclusions derived from our data are as follows: The PWE and mean left ventricular posterior wall velocity (mPWV) obtained by echocardiography reflect the stroke volume derived from the thermodilution technique. It is possible to estimate the cardiac contractile force in patients who have a paradoxical motion of the interventricular septum, in the preoperative and even in the early postoperative periods. Patients whose PWE and mPWV are less than 10 mm and 35 mm/sec, respectively, after 2 microgram/min loading of epinephrine (group I), are likely to have severe cardiac failure after surgery. Inotropic stimulation is considered to be a very useful indicator for prediction of cardiac contractile reserve. Patients having decreased PWE, mPWV, mVcf and EF before surgery may have arrested recovery in both short- or long-term follow-up. However, surgical treatment is recommended for these patients with low cardiac function, because some improvement can be expected after surgery.
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