Biomedical subjects

S Morisawa

Publications and source records attributed to S Morisawa.

At least 91 records · Page 5Linked to original sources

PubMed1989

Effect of 1 alpha,25-dihydroxyvitamin D3 on polyamine metabolism in human monocyte cell line-U937.

1. Pretreatment with 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] caused an increase in ornithine decarboxylase (EC 4.1.1.17) (ODC) activity in lipopolysaccharide (LPS)-stimulated human monocyte cell line, U937. 2. The increase in ODC activity was dose-dependent and preincubation-time dependent. 3. 26,26,26,27,27,27-Hexafluoro-1,25-dihydroxyvitamin D3 was ca 7 times more potent than 1,25-(OH)2D3 in increasing ODC activity. 4. Pretreatment with 1,25-(OH)2D3 also potentiated the activity of spermidine/spermine-N1-acetyltransferase in LPS-stimulated U937 cells. 5. Putrescine levels in cells pretreated with 1,25-(OH)2D3 increased ca 2-fold 4-8 hr after LPS addition. 6. However, pretreatment with 1,25-(OH)2D3 did not cause any increase in ODC mRNA level, suggesting that 1,25-(OH)2D3 may modulate polyamine metabolism at the posttranscriptional level rather than the transcriptional step.

Acetyltransferases↗

PubMed1989

Release of leukotriene B4 from rat Kupffer cells.

In order to examine the production of leukotriene B4 (LTB4) from Kupffer cells, Kupffer cells isolated from the normal rat liver were incubated with calcium ionophore A23187, opsonized zymosan, or platelet activating factor (PAF), and the amount of LTB4 in the culture supernatant was determined by the combined technique of reverse-phase high-performance liquid chromatography and radioimmunoassay. As a result, when activated in vitro with calcium ionophore A23187, Kupffer cells generated LTB4. When Kupffer cells were stimulated with calcium ionophore after 10-min preincubation with AA861, a selective 5-lipoxygenase inhibitor, the release of LTB4 from Kupffer cells was markedly suppressed. PAF, which is a phospholipid mediator having a wide spectrum of biological activities, significantly enhanced the release of LTB4 from Kupffer cells stimulated with calcium ionophore or opsonized zymosan. Even when the Kupffer cell were not stimulated with calcium ionophore or opsonized zymosan, LTB4 production was significantly increased by PAF. Thus, our studies indicate that Kupffer cells could generate LTB4 as well as polymorphonuclear leukocytes and macrophages. In addition, it is suggested that Kupffer cells may be able to modify inflammatory and immunological events in the liver tissue by the release of LTB4.

Animals↗

PubMed1989

[Effects of the cholestatic factor and the prostaglandin E1 derivative on the level of cAMP in isolated hepatocytes of rats].

It has been reported that cAMP in hepatocytes plays an important role in bile discharge. Therefore, in order to examine the action mechanism of the cholestatic factor, we studied the effect of the cholestatic factor and prostaglandin E1 derivative which inhibits the activity of the cholestatic factor on the cAMP level in hepatocytes. As a result, the cAMP level in hepatocytes was decreased by treatment with the cholestatic factor, but was increased by the prostaglandin E1 derivative. Furthermore, the cAMP level which was decreased by the cholestatic factor returned to the original level by treatment with the prostaglandin E1 derivative. Because the increase in the cAMP level in hepatocytes promotes the bile acid independent bile discharge, it is suggested that the cholestatic factor reduces the bile flow by the decrease in the cAMP level in hepatocytes, and that the prostaglandin E1 derivative competes with the action of the cholestatic factor through the increase in the cAMP level in hepatocytes.

Alprostadil↗

PubMed1989

Effects of ursodeoxycholic acid on intrahepatic cholestasis.

Ursodeoxycholic acid (UDCA) was administered to 16 intrahepatic cholestasis patients with severe jaundice, and its clinical effects were studied. As a result, it was remarkably effective in 6 patients, significantly effective in 5 patients, slightly effective in 2 patients and unchanged in 3 patients. As for the dose, when 600 mg/day was administered, it was effective in all patients, but even when only 150 mg/day was administered, it was effective in one patient (50%). Duration of treatment was 15 to 177 days with a mean of 55.3 days. These results suggested that while there is no adequate treatment for intrahepatic cholestasis with severe jaundice, UDCA should be considered as a possible method of treatment.

Adult↗

PubMed1989

Choleretic effects of ursodeoxycholic acid on experimentally-induced intrahepatic cholestasis.

When a lymphokine, the cholestatic factor, is intravenously injected into rats through a mesenteric vein, remarkable reductions in bile flow and bile acid excretion are observed. Using this experimentally-induced intrahepatic cholestasis model, the choleretic effects of ursodeoxycholic acid (UDCA) were studied. When UDCA was injected with the cholestatic factor, the reductions in bile flow and bile acid excretion were significantly suppressed. Remarkable choleretic effects were also noted, when UDCA was administered to normal rats. These results suggested that UDCA may be effective in the treatment of intrahepatic cholestasis.

Animals↗

PubMed1989

Estradiol receptors in the cytosol of peripheral blood mononuclear cells in hepatitis virus carriers.

Sex hormones are known to affect the immune system. Asymptomatic hepatitis B virus (HBV) carriers are thought to be immunologically tolerant to HBV, but in some HBV carriers, the immune response to HBV is induced, especially in females during their sexually-mature periods. This may be caused by the effects of estrogen on the immune system. In this study, we found that the level of estradiol receptors in the cytosol of peripheral blood mononuclear cells was significantly lower in asymptomatic HBV carriers and patients with chronic hepatitis (B type and non A non B type) compared to healthy controls. This suggests that one cause of the deficiency in virus elimination in hepatitis virus carriers may be the unresponsiveness of the immune system to sex hormones, as a result of the low level of cytosol estradiol receptors.

Carrier State↗

PubMed1989

Serotonin and tryptamine metabolism in the acute hepatic failure model: changes in tryptophan and its metabolites in the liver, brain and kidney.

When heat-killed Propionibacterium acnes, a gram-positive anaerobe, is intravenously injected into mice followed by an intravenous injection of gram-negative lipopolysaccharide (LPS) 7 days later, most of the mice die of massive hepatic cell necrosis within 24 hours of LPS injection. Using this experimental model, acute hepatic failure was induced in mice, and the tryptophan metabolism in the liver, brain and kidney was studied. As a result, the tryptophan level was remarkably high in all three organs, and the metabolism of both the tryptamine pathway and serotonin pathway was induced. However, in the brain, the tryptamine metabolism was more induced compared to the serotonin, suggesting that the metabolites of tryptamine, may be involved in hepatic encephalopathy.

Acute Disease↗

PubMed1989

Effect of acylated derivatives of ascorbate on ornithine decarboxylase induction in Ehrlich ascites tumor cells.

We studied the effects of 6-0-acylated derivatives of ascorbate on ornithine decarboxylase (ODC, E.C.4.1.1.17) activity and the ODC-mRNA level in Ehrlich ascites cells. These derivatives are known to inhibit cell growth. When cells grown to the stationary phase were diluted and stimulated with fresh medium containing 10% dialyzed fetal calf serum, the ODC activity increased rapidly and transiently with a peak at 4 hr. Ascorbate or 2,6-dipalmitoyl ascorbate had little or no effect on the induction of ODC, but 6-0-palmitoyl ascorbate (6P) suppressed the enzyme activity in a time- and dose-dependent way. 6-0-Stearoyl ascorbate had a similar effect. The amount of ODC-mRNA formed after growth stimulation was not affected by 6P. These results indicate that the treatment of Ehrlich ascites tumor cells with 6P caused dose-dependent suppression of ODC induction post-transcriptionally.

Acetylation↗

PubMed1989

[Changes in production of platelet activating factor by adherent hepatocytes of mice with experimental liver failure].

It is thought that the platelet activating factor (PAF) enhances the immune response and inflammatory reaction. We studied the production of PAF from liver adherent cells. As a result, liver adherent cells produced PAF, when they were stimulated with calcium ionophore. In addition, when mice were treated with heat-killed Propionibacterium acnes and the mononuclear cells were infiltrated into the liver, a significantly larger amount of PAF was produced compared to normal mice.

Acute Disease↗

PubMed1988

Altered production of the active oxygen species is involved in enhanced cytotoxic action of acylated derivatives of ascorbate to tumor cells.

Our previous study shows that 6-O-acyl derivatives of L-ascorbic acid inhibits more markedly cell growth of mouse Ehrlich carcinoma than ascorbic acid. The present study shows that 6-O-palmitoyl ascorbic acid but not ascorbic acid prolongs the lifespan of mice into which tumors such as Meth A fibrosarcoma, MM46 mammary carcinoma, Ehrlich carcinoma and sarcoma 180 are implanted. The potentiated cytotoxicity of 6-O-palmitoyl ascorbic acid is not due to an increase in duration time of the cytotoxic action, because 6-O-palmitoyl ascorbic acid is gradually inactivated during contact with tumor cells and exhibits a similar action time curve to that of ascorbic acid as shown by clonal growth assay. Cytotoxicity of 6-O-palmitoyl ascorbic acid is markedly diminished by combined addition of catalase and superoxide dismutase (SOD), as shown by dye exclusion assay, whereas the cytotoxicity was slightly reduced by either enzyme alone but not by the specifically inactivated or heat-denatured enzymes. In contrast, cytotoxicity of ascorbic acid is abolished by catalyse but not SOD. Autooxidation of 6-O-palmitoyl ascorbic acid was not inhibited by catalase plus SOD. The results indicate that cytotoxicity of 6-O-palmitoyl ascorbic acid is attributed at least partly to both hydrogen peroxide (H2O2) and superoxide (O2-.) generated at the early stage. Cytotoxicity of 6-O-palmitoyl ascorbic acid is also appreciably attenuated by singlet oxygen (1O2) scavengers such as hydroquinone, 1,4-diazobicyclo-2,2,2-octane or sodium azide, but not by hydroxyl radical scavengers including butylated hydroxytoluene, D-mannitol, benzoic acid and ethanol. Thus, in contrast to cytotoxicity of ascorbic acid mediated entirely by H2O2 initially generated, acylated ascorbic acid produces a diversity of active oxygen species including H2O2, O2-. and other species secondarily generated via disproportion, which may be additively involved in the enhanced cytotoxic action.

Animals↗

PubMed1988

Release of peptide leukotrienes from rat Kupffer cells.

Kupffer cells isolated from the normal rat liver were incubated with calcium ionophore A23187, and the levels of peptide leukotrienes (LTC4, LTD4, and LTE4) contained in the culture supernatant were determined by the combined technique of reverse-phase high-performance liquid chromatography and radioimmunoassay. In response to A23187, Kupffer cells released LTC4, LTD4, and LTE4. After 10 min-preincubation of Kupffer cells with AA861, a 5-lipoxygenase inhibitor, the generation of LTC4, LTD4, and LTE4 from A23187-stimulated Kupffer cells was significantly suppressed. Platelet activating factor (PAF), a phospholipid mediator, significantly enhanced the release of LTC4, LTD4, and LTE4 from Kupffer cells stimulated with A23187. These results suggested that Kupffer cells may participate in inflammatory and immunologic events in the liver tissue by the release of peptide leukotrienes.

Animals↗

PubMed1988

Effects of an anti-tumor polysaccharide, schizophyllan, on interferon-gamma and interleukin 2 production by peripheral blood mononuclear cells.

We examined the effect of schizophyllan, a neutral glucan isolated from the culture filtrate of Schizophyllum commune Fries, on the production of interferon-gamma (IFN-gamma) and interleukin 2 (IL 2) from the mitogen-stimulated human peripheral blood mononuclear cells (PBMC). When the levels of IFN-gamma and IL 2 in the culture medium of phytohemagglutin (PHA)- or concanavalin A (Con A)-stimulated PBMC were measured by radioimmunoassay and enzyme-linked immunosorbent assay (ELISA) respectively, a significant increase in the production of both cytokines by schizophyllan was demonstrated. These results suggest that the increased production of IFN-gamma and IL 2 may be responsible for the anti-tumor activity of this glucan.

Concanavalin A↗

PubMed1988

Inhibition of ornithine decarboxylase induction of interferon (alpha + beta) and its reversal by dibutyryl adenosine 3',5'-monophosphate.

Interferon (alpha + beta) given to C3H/HeN mice intraperitoneally inhibited increases in the activities of adenylate cyclase and ornithine decarboxylase after partial hepatectomy. The inhibition of ornithine decarboxylase was prevented by administration of dibutyryl cAMP. Core (2'-5')oligo(adenylate), i.e. A2'p5'A2'p5'A or (A2'p)2A, as well as interferon inhibited the increases in these two enzymes caused by partial hepatectomy. The inhibition by (A2'p)2A of ornithine decarboxylase activity was reversed by dibutyryl cAMP. These results suggested that the activity of interferon was similar to that of (A2'p)2A and that the inhibition of ornithine decarboxylase induction caused by these agents resulted from the inhibition of adenylate cyclase activity.

Animals↗

PubMed1988

Synergistic stimulation of S-adenosylmethionine decarboxylase activity by Ca2+ ionophore A23187, cholera toxin and 1-oleoyl-2-acetylglycerol.

The Ca2+ ionophore A23187 induced S-adenosylmethionine decarboxylase in guinea-pig lymphocytes, and cholera toxin stimulated the induction synergistically. The activator of protein kinase C, 1-oleoyl-2-acetylglycerol, did not induce S-adenosylmethionine decarboxylase activity but potentiated the enzyme activity induced by A23187 or by A23187 and cholera toxin. The addition of both A23187 and cholera toxin induced S-adenosylmethionine decarboxylase, but the further addition of 1-oleoyl-2-acetylglycerol or 12-O-tetradecanoylphorbol 13-acetate did not potentiate the enzyme induction in protein kinase-C-down-regulated cells that had been treated with 12-O-tetradecanoylphorbol 13-acetate for 18 h. These results suggest that a Ca2+-dependent pathway, other than that for protein kinase C, is essential for the induction of S-adenosylmethionine decarboxylase and that a cAMP-dependent pathway and also protein kinase C are involved in the potentiation of the induction.

Adenosylmethionine Decarboxylase↗

PubMed1988

Pericardium of rodents: pores connect the pericardial and pleural cavities.

Numerous circular fenestrations or pores were present in the pericardium of the rat, golden hamster, and mouse. The pericardial pores were most numerous in the mouse. They were usually less than 50 micron in diameter and situated in a meshwork formed by thick, wavy bundles of collagen fibers and thin, straight, elastic fibers. These pores directly connected the pericardial and pleural cavities and indirectly connected the right and left pleural cavities; i.e., the pericardial cavity in the rodents is not independent from but intercommunicates with the adjacent pleural cavities. There were many aggregates of free cells or milky spots in the pericardium. They principally consisted of lymphocytes, macrophages, and mast cells and were directly exposed to the pericardial cavity.

Animals↗

PubMed1988

Protective effects of a leukotriene inhibitor in an experimental massive hepatic cell necrosis model.

When heat-killed Propionibacterium acnes was intravenously injected into mice and seven days later, a small amount of gram-negative lipopolysaccharide was also intravenously injected, most of them died of massive hepatic cell necrosis. However, when azelastine hydrochloride, a leukotriene antagonist chemically known as 1(2H)-phthalazinone, 4-[(4-chlorophenyl)methyl]-2-(hexahydro-1-methyl-1H-azepine-4-yl)-, monohydrochloride, or AA861, 2-(12-hydroxydodeca-5, 10-diynyl)-3,5,6-trimethyl-1, 4-benzoquinone, a specific inhibitor of 5-lipoxygenase, was administered during this experimental induction of massive hepatic cell necrosis, the survival rate of the mice increased and the histological changes of the liver improved remarkably. These results suggested that leukotriene may be important for the induction of massive hepatic cell necrosis in our experimental model.

Animals↗

PubMed1988

Effect of interleukin 1 and interleukin 2 on antibody production in asymptomatic hepatitis B virus (HBV) carriers.

Peripheral blood mononuclear cells from asymptomatic hepatitis B virus (HBV) carriers and healthy controls were incubated with recombinant interleukin 1 (r-IL1) or recombinant interleukin 2 (r-IL2) at 37 degrees C for 24 hours and with pokeweed mitogen (PWM) and estradiol for 72 hours. The number of antibody-producing cells was counted by hemolytic plaque assay. When the mononuclear cells were not pretreated with r-IL1 or r-IL2, the number of antibody-producing cells was not increased by estradiol in asymptomatic HBV carriers. However, when the mononuclear cells were pretreated with r-IL1 or r-IL2, the number of antibody-producing cells was increased. As we have reported before, this may be have been due to the increase in the estradiol-binding capacity of the mononuclear cells by treatment with IL1 and IL2. In asymptomatic HBv carriers, IL1 and IL2 production of the mononuclear cells or the response of the mononuclear cells to IL1 and IL2 is reduced. Consequently, the estradiol binding capacity is decreased, and antibody production is not increased by estradiol.

Antibody Formation↗

PubMed1988

Tryptophan metabolism in D-galactosamine-induced liver injury.

We have reported that in rats with D-galactosamine-induced liver injury, the serum level of indoleacetic acid (IAA), a metabolite of tryptophan (TRP), increases before the increase in serum transaminase activity. To determine whether this IAA is derived from hepatocytes, isolated hepatocytes were treated with D-galactosamine and loaded with TRP, and the changes in TRP and IAA levels in the culture supernatant of the isolated hepatocytes were measured at various time intervals. As a result, IAA level in the culture supernatant of hepatocytes treated with D-galactosamine and loaded with TRP significantly increased in a time-dependent manner. This indicates that in D-galactosamine-induced liver injury, a metabolic pathway which produces IAA from TRP through tryptamine is present in hepatocytes.

Animals↗