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Biomedical subjects

M Suda

Publications and source records attributed to M Suda.

At least 91 records · Page 5Linked to original sources
PubMed1995

Ethanol as a xanthine dehydrogenase inhibitor.

In the present study, we investigated whether ethanol inhibits the activity of xanthine dehydrogenase. Ethanol and/or inosine were administered to normal subjects, and plasma concentration and urinary excretion of purine bases were measured together with blood concentrations of lactic acid and pyruvic acid. In addition, ethanol and pyrazinamide were administered to these subjects, and plasma concentration and urinary excretion of pyrazinamide and its major metabolites were measured. Increases in plasma concentration and urinary excretion of xanthine induced by a combination of ethanol and inosine were greater than the sums of increases induced separately by ethanol and inosine, although increases in plasma concentration and urinary excretion of uric acid induced by the combination of ethanol and inosine were not different from the sums of increases induced separately by ethanol and inosine. Ethanol increased the ratio of blood lactic acid to blood pyruvic acid and decreased plasma concentration and urinary excretion of 5-hydroxypyrazinamide and 5-hydroxypyrazinoic acid. These results suggest that ethanol inhibits xanthine dehydrogenase presumably by an ethanol-induced increase in the cytosolic concentration of NADH in the liver.

Acetates↗
PubMed1995

Inhibitory effects of bisbenzylisoquinoline alkaloids on induction of proinflammatory cytokines, interleukin-1 and tumor necrosis factor-alpha.

Bisbenzylisoquinoline alkaloids are known to affect immune responses as well as inflammatory responses, and have been used for the treatment of inflammatory symptoms in China. This study is aimed at elucidating the inhibitory effects of two alkaloids, fangchinoline and isotetrandrine, on the induction of the proinflammatory cytokines, interleukin-1 (IL-1), and tumor necrosis factor-alpha (TNF-alpha), by Staphylococcus aureus Cowan 1 (SAC)-stimulated human peripheral blood mononuclear cells. These two alkaloids inhibited cytokine production in a dose-dependent manner, and they inhibited it by more than 90% at 10 micrograms/ml at every time point examined. Of note was that these two alkaloids appeared to inhibit IL-1 beta production more effectively than IL-1 alpha production. When the levels of cytokine mRNA were measured by semiquantitative RT-PCR, these alkaloids reduced the levels of the mRNAs of IL-1 beta and TNF-alpha, but not that of beta 2-microglobulin, suggesting that these alkaloids may suppress cytokine transcription selectively.

Alkaloids↗
PubMed1995

Function of RNH-1/14-3-3 beta gene in cellular differentiation and proliferation.

It has recently been reported that the members of 14-3-3 protein family participate in cell cycle control and associate with Raf, Bcr, Bcr-Abl, and polyomavirus middle tumor antigen (MT) as modulators of signal transduction. During cDNA cloning for the 17-kDa neuronal differentiation factor (K2 factor) secreted from rat hepatoma Kagura-2 (K2) cells from a K2 cDNA library using rat prepronerve growth factor (prepro NGF) cDNA as a probe, we obtained RNH-1 (rat NGF homologue) clone, which was identified as 14-3-3 beta cDNA, but not K2 factor, although no significant homology is present between 14-3-3 beta and prepro NGF cDNAs. RNH-1/14-3-3 beta gene was markedly expressed as a 2.9-kb mRNA in K2 cells and in newborn rat brain tissue. In PC12 cells the expression of this gene was down-regulated during the neuronal differentiation primed by NGF. The enforced expression of RNH-1/14-3-3 beta in PC12 and K2 cells conferred on them a higher sensitivity to NGF for neuronal differentiation and an intense growth ability in low serum medium, respectively. These results provide additional evidence that RNH-1/14-3-3 beta protein participates in cellular differentiation, proliferation and transformation through the signal transduction pathways of various growth factors.

14-3-3 Proteins↗
PubMed1995

Accumulation and massive cell death of polymorphonuclear neutrophils in the developing bone marrow of the mouse: a histological study.

Accumulation and cell death of neutrophils were studied by light and electron microscopy in neonatal mouse bone marrow. At the beginning of bone marrow hematopoiesis, the marrow cavity contained a large number of polymorphonuclear leukocytes. Polymorphs comprised approximately 75% of the total nucleated cells in the hematopoietic compartment of the newborn marrow, the majority being neutrophils. Mature neutrophils were sometimes crossing the endothelium of the marrow blood sinus. Neutrophils in neonatal marrow show features typical of apoptosis, e.g. formation of nuclear pockets and blebs, margination of compact nuclear chromatin to form sharply circumscribed masses, condensation of cytoplasm, and convolution of cell outlines. Dying neutrophils were devoured and digested by phagocytes. The occurrence of large-scale neutrophil death and removal of neutrophils by phagocytes in neonatal bone marrow are discussed in relation to programmed cell death in development of the fetal hematopoietic system.

Animals↗
PubMed1995

Effect of glucose infusion on the renal transport of purine bases and oxypurinol.

The effect of glucose infusion on renal handling of purine bases and oxypurinol was examined in 6 normal subjects. Five hundred milliliters of 1.1 M glucose solution were administered intravenously in 1 h. Fractional clearances of uric acid, xanthine and oxypurinol were significantly increased during glucose infusion, but that of hypoxanthine was not changed, while a 1-hour infusion of 500 ml of 1.1 M mannitol had no effect on the fractional clearances of purine bases and oxypurinol. These data indicate that the effect of glucose infusion on the renal clearances of uric acid, xanthine and oxypurinol was not related to osmotic diuresis but induced by glycosuria and/or hyperglycemia. Accordingly, the glycosuria- and/or hyperglycemia-induced decrease in the biological half-life of oxypurinol must be considered in the administration of allopurinol to gouty patients with uncontrolled diabetes mellitus.

Adult↗
PubMed1995

Inactivation of (1-->3)-beta-D-glucan in mice.

Intraperitoneally or intravenously administered (1-->3)-beta-D-glucan remained in the liver and spleen, for a long time without major structural changes, but the priming activity to lipopolysaccharide (LPS)-triggered tumor necrosis factor-alpha (TNF-alpha) production was reduced more quickly. The relationship between the deposited glucan contents and the antitumor activity was examined by comparing kinetics of the activity using solid form Sarcoma 180 tumor in ICR mice. We used three kinds of soluble glucans, sonifilan (SPG), grifolan (GRN), and SSG, and a particulate glucan, zymosan (ZYM). These were administered 5 weeks before (-5W) the tumor inoculation and the tumor weight was compared 5 weeks after the inoculation. Compared with the activity of those administered at the optimum timing, all of the glucans reduced the activity about 5 fold, although significant activity still remained, especially in the case of SPG. Five weeks after intraperitoneal (SPG, GRN, SSG) or intravenous (ZYM) administration of the glucans, all were found in the liver and spleen in significant quantities. These facts strongly suggested that the activity of the glucan was reduced not only because of chemical/physical degradation but also a certain physiological inactivation mechanism.

Animals↗
PubMed1995

Modulation of the antitumor effect and tissue distribution of highly branched (1-->3)-beta-D-glucan, SSG, by carrageenan.

The action of carrageenan (CAR), a representative blocking reagent for phagocytes, on the antitumor effect and tissue distribution of highly branched (1-->3-beta-D-glucan, SSG, was examined. CAR inhibited the antitumor effect of intraperitoneally administered SSG only when applied before inoculation of the tumor, and had little effect when applied after tumor inoculation. A similar result was observed when SSG was administered intralesionally. In contrast, CAR had considerable effect on tissue distribution of i.p. SSG. The differences with respect to the results in normal mice were: 1) the distribution of SSG from the peritoneal cavity to the rest of the body was inhibited, 2) large numbers of peritoneal exudate cells (PEC) were produced and a relatively high concentration of 3H-SSG was found in the PEC fraction 48h after administration of 3H-SSG, 3) one week after administration, 3H-SSG was distributed to throughout the body but the amount of 3H-SSG distributed was lower than in normal mice, 4) a significant amount of 3H-SSG was recovered from ligaments (containing omental milky spots, peritoneum, mesentery and associated fat) in which negligible amounts were found in normal mice. The results suggest that the inhibition of the antitumor effect of SSG by CAR probably results from the prevention of the natural resistance of mice which is related to phagocytic function, and that the distribution of SSG to throughout the body is significantly modulated by CAR.

Animals↗
PubMed1995

Metabolic 13C-labeling of an antitumor (1-->3)-beta-D-glucan, SSG, from Sclerotinia sclerotiorum IFO 9395.

A (1-->3)-beta-D-glucan, SSG, from Sclerotinia sclerotiorum IFO 9395 was metabolically labeled using [1-13C] and [2-13C]glucose, and the fate of the 13C-label was examined by 13C-NMR spectroscopy. 13C-NMR spectra of metabolically labeled SSG (13C-SSG) showed that most of the 13C-label in glucose residues of 13C-SSG were recovered from the originally labeled sites of carbon in glucose residue, and suggested little rearrangement during take-up from the medium. In the case of poor SSG producing culture conditions (reduced shaking rate), 13C-glucose incorporation in SSG molecule was similar to that in the case of high SSG-producing culture conditions. In addition, significant amounts of 13C-labeled trehalose were found in 13C-NMR spectra of the mycelium cultured in both poor and high SSG-producing conditions. These results suggested that different culture conditions affected SSG production, but not the metabolism of glucose and the biosynthetic pathway of SSG.

Antineoplastic Agents↗
PubMed1995

The ultrastructure of intravascular and coelomic scavenger macrophages of the mouse embryo.

The aim of this study was to establish whether or not mononuclear cells which appear in both the vitelline vessels and embryonic coelom in mice prior to liver hemopoiesis are specialized scavengers. Before the initiation of liver hemopoiesis, the majority of the embryonic blood cells were primitive erythroblasts derived from yolk sac hemopoietic foci. In addition, the peripheral blood contained a few free phagocytes as early as 10 days of gestation. The phagocytes devoured various cell elements such as degenerating erythroblasts and cell fragments. Ultrastructurally, they had long filamentous cytoplasmic projections on their cell surface, clear subsurface vacuoles or vesicles, lipid droplets, a few lysosomal granules, large heterogeneous phagolysosomes and residual bodies. Mononuclear phagocytes with ultrastructural features similar to those of the intravascular phagocytes also could be observed in the intraembryonic peritoneal cavities at 10 days of gestation; they sometimes engulfed possible mesothelial cells undergoing degeneration. Based on fine structural criteria, these intravascular and coelomic phagocytes were considered to be specialized scavenger macrophages with the function of clearing the blood and tissue fluid of whatever has been ingested. In so doing, they serve as the most primitive discriminating filter set in embryonic circulation.

Animals↗
PubMed1995

Xylitol-induced increase in the concentration of oxypurines and its mechanism.

We investigated the effect of xylitol on the plasma concentration and the urinary excretion of purine bases, 5-hydroxypyrazinamide and 5-hydroxypyrazinoic acid in subjects who had ingested pyrazinamide (60 mg/kg weight). One liter of 10% xylitol was infused intravenously over 2 hours to 5 subjects to whom pyrazinamide had been administered 10 hours before. Xylitol increased the plasma concentration of uric acid, hypoxanthine and xanthine, the urinary excretion of hypoxanthine and a ratio of lactic acid/pyruvic acid in blood, while it decreased the plasma concentration and the urinary excretion of inorganic phosphate, 5-hydroxypyrazinamide and 5-hydroxypyrazinoic acid. These results suggested that in addition to an increase in purine degradation by xylitol, xylitol-induced increase in the cytosolic NADH inhibited xanthine dehydrogenase activity in the liver and the small intestine.

Administration, Oral↗
PubMed1994

Preparation and properties of metabolically 3H- or 13C-labeled (1-->3)-beta-D-glucan, SSG, from Sclerotinia sclerotiorum IFO 9395.

Metabolically labeled (1-->3)-beta-D-glucan (SSG) obtained from the culture filtrate of Sclerotinia sclerotiorum IFO 9395, with the radio (3H) or the stable isotope (13C) was prepared. The specific radioactivity of 3H-SSG was increased in accordance with the amount of D-[3H]glucose added, and was 15-20 kBq/mg SSG when 222 kBq/mL of D-[3H]glucose was added. Physicochemical analyses of 3H-SSG suggested a structural similarity between SSG and 3H-SSG. 13C NMR spectra of 13C-labeled SSG (13C-SSG) revealed that a strong signal of the 13C-nucleus was observed at the C-1 or C-2 position when D-[1-13C]glucose or D-[2-13C]glucose was used, respectively, suggesting that most of the glucose residues in SSG were directly taken up from the medium. In addition, part of the 13C-nucleus was incorporated into the SSG molecule at all carbon atoms after metabolic degradation and reconstruction of the glucose molecule. Analyses of the culture filtrate and the mycelium of the fungus suggested that part of the glucose was also metabolized to trehalose and mannitol.

Ascomycota↗
PubMed1994

Purification and characterization of a cell growth factor from a human leukemia cell line: immunological identity with ferritin.

We have succeeded in long-term cultivation of a human erythroleukemia cell line, K-562-T1 (T. Okabe, M. Fujisawa, and F. Takaku, Proc. Natl. Acad. Sci. USA, 81: 453-455, 1984). The cells grown in a protein-free chemically defined medium have been shown to produce cell growth factors (A. Mihara et al., In Vitro Cell. Dev. Biol., 23: 317-322, 1987). In this study, we have purified a cell growth factor from the conditioned medium that stimulates the proliferation of human leukemia cells, HL-60. In the purified factor, two major protein bands of 24 kDa and 22 kDa were identified on a sodium dodecyl sulfate-polyacrylamide gel. The 22 kDa protein was stained with a monoclonal antibody to the light chain of ferritin. The growth-promoting activity of the purified factor was coprecipitated with a monoclonal antibody to the light chain or heavy chain of human ferritin. These results suggest that K-562-T1 cells produce a cell growth factor that is related to ferritin.

Culture Media, Conditioned↗
PubMed1994

Acute promyelocytic leukaemia in a patient treated with etoposide for Langerhans cell histiocytosis.

We report a child with acute promyelocytic leukaemia (APL) who was treated with etoposide (VP16) for Langerhans cell histiocytosis (LCH). A 3-year-old Japanese girl was diagnosed as having LCH. She was treated with combination chemotherapy using VP16 and prednisolone. 56 months after beginning the chemotherapy she developed APL. Her bone marrow was occupied with atypical promyelocytes including giant granules and multiple Auer bodies. A cytogenetic analysis of the leukaemic cells showed 46,XX,11p-,14q+,t(15,17). The cumulative dose of the administered VP16 was 12,120 mg/m2, which suggested that VP16 may be responsible for the development of APL. The risk of developing secondary leukaemia after the administration of VP16 should therefore be considered when managing patients with LCH.

Child↗
PubMed1994

Acute heart failure and acute renal failure in Kawasaki disease.

Acute renal failure and acute heart failure are rare in Kawasaki disease. We experienced two patients with Kawasaki disease who presented acute renal failure and acute heart failure. These two patients gave us an important insight into the understanding of water balance and fluid therapy in Kawasaki disease. One patients showed acute prerenal failure due to fluid exudation from the intravascular to the extravascular space, and subsequent acute heart failure. The other patient showed acute heart failure caused by fluid infusion for the treatment of dehydration. It is suggested that acute renal failure could be caused by a fluid shift from the intravascular to the extravascular space in Kawasaki disease. It is also demonstrated that the reserve of cardiac function could be decreased in patients with Kawasaki disease due to myocarditis even with normal echocardiography and chest X-rays.

Acute Disease↗
PubMed1994

Relationship between the tissue distribution and antitumor activity of highly branched (1-->3)-beta-D-glucan, SSG.

Distribution of 3H-labeled (1-->3)-beta-D-glucan([3H]SSG) obtained from the culture filtrate of Sclerotinia sclerotiorum IFO 9395, in various tissues in tumor-bearing mice was examined. [3H]SSG administered intra-peritoneally was mainly detected in liver, spleen, kidney and tumor masses. In contrast to i.p. administration, intra-lesionally administered [3H]SSG was not released from the tumor. Similarly, in a double grafted tumor system, [3H]SSG was located in the administered tumor and not distributed in the distant site tumor, in spite of the fact that significant antitumor effect was shown in both tumor sites in this system. Winn assay confirmed the activation of the systemic antitumor immunity. These results suggested that the distribution of glucans would be one important factor in determining their antitumor effects. However, this would not always be necessary if systemic immunity could be induced.

Animals↗
PubMed1993

Effect of BOF-4272 on the oxidation of allopurinol and pyrazinamide in vivo. Is xanthine dehydrogenase or aldehyde oxidase more important in oxidizing both allopurinol and pyrazinamide?

Allopurinol or pyrazinamide was administered to rats treated with BOF-4272 (a potent xanthine oxidase inhibitor) to investigate to what degree xanthine dehydrogenase participates in the oxidation of these agents. BOF-4272 markedly decreased the plasma concentration and the urinary excretion of both oxypurinol and 5-hydroxypyrazinamide. It also decreased the sum of the urinary excretion of allopurinol and oxypurinol and that of pyrazinamide and its metabolites, although it did not affect the sum of the plasma concentrations of allopurinol and oxypurinol at 105 min after administration of allopurinol or the plasma concentration of pyrazinamide during the period after the administration of pyrazinamide. These results suggested that BOF-4272 almost completely inhibited the oxidation of allopurinol and pyrazinamide and had some effect on the excretion and/or the tissue incorporation of these two compounds. Since the in vitro study demonstrated that BOF-4272 did not inhibit the activity of aldehyde oxidase, which oxidized both allopurinol to oxypurinol and pyrazinamide to 5-hydroxypyrazinamide, the results suggested that xanthine dehydrogenase was the more important enzyme in converting allopurinol to oxypurinol and pyrazinamide to 5-hydroxypyrazinamide.

Aldehyde Oxidase↗