Biomedical subjects

S Tanuma

Publications and source records attributed to S Tanuma.

104 records · Page 6Linked to original sources

PubMed1981

ATP requirement for the processes of DNA replication in isolated HeLa cell nuclei.

The ATP requirement for two steps of DNA replication, the synthesis and subsequent joining of Okazaki fragments, was investigated by using isolated HeLa cell nuclei. Among adenine nucleotides tested, high levels of dATP and ADP stimulated DNA synthesis. In the presence of high levels of ATP, the addition of high levels of dATP or ADP resulted in about 70% inhibition of DNa synthesis. The optimal concentration of ATP for the stimulation of DNA synthesis varied depending on the magnesium ion concentration. When the molar ratio of magnesium ion to ATP was approximately 1, maximal stimulation was attained. Product analysis by sedimentation in an alkaline sucrose gradient revealed that both Okazaki fragments and high molecular weight DNA were synthesized in the presence of high levels of ATP, whereas in the case of dATP and ADP, little high molecular weight DNA was synthesized. The ability to synthesize high molecular weight DNA was restored to nuclei by adding low levels of ATP in the presence of high levels of ADP but not of dATP.

Adenine Nucleotides↗

PubMed1979

Effect of thymidine on poly(ADP-ribosyl)ation in vivo.

The addition of thymidine as well as nicotinamide to isolated nuclei resulted in a strong inhibition of poly(ADP-ribosyl)ation, whereas that of hydroxyurea and amethopterin has essentially no effect. The nuclei isolated from the cells immediately after release from thymidine synchronization exhibited a significantly increased activity of poly(ADP-ribosyl)ation. Thereafter, the fluctuation pattern of the activity of poly(ADP-ribosyl)ation in isolated nuclei during the cell cycle was essentially the same as in the case of hydroxyurea synchronization. The activity of poly(ADP-ribosyl)ation in isolated nuclei after treatment with thymidine in vivo increased with the treatment time. The time-dependent increase was also evident in the case of nicotinamide treatment. Little increase in the activity was observed in hydroxyurea and amethopterin treatment. When poly(ADP-ribose) polymerase was extracted from the nuclei isolated from the cells which were pretreated with each of the four compounds, there was no significant difference in the amount among these compounds. The reason for the increase in the poly(ADP-ribosyl)ation in vitro by the in vivo treatment with thymidine is discussed.

Cell Nucleus↗

PubMedDate not supplied

Inhibition of herpes simplex virus infection by tannins and related compounds.

Several chemically defined plant extracts were investigated for their antiviral action on herpes simplex virus (HSV-1, HSV-2)-infected African green monkey kidney cells and human adenocarcinoma cells, using a plaque formation assay. Among them, the monomeric hydrolyzable tannins, oligomeric ellagitannins and condensed tannins, having galloyl groups or hexahydroxydiphenoyl groups, had the most potent anti-HSV activity. Their 50% effective doses (0.03-0.1 microgram/ml) were by two-three orders of magnitude lower than their 50% cytotoxic doses (greater than 10 micrograms/ml). On the other hand, gallic acid, neutral polysaccharides, chemically modified (N,N-dimethylaminoethyl-, carboxymethyl-, and sulfated-) glucans, sialic acid-rich glycoproteins, and uronic acid-rich pine cone polysaccharide showed little or no activity. Using radiolabeled virus particles, we demonstrated that the anti-HSV effect of the tannins is due to inhibition of virus adsorption to the cells.

Adsorption↗

PubMedDate not supplied

Synergistic down-regulation of telomerase activity and hTERT mRNA expression by combination of retinoic acid and GM-CSF in human myeloblastic leukemia ML-1 cells.

Telomerase, the enzyme that synthesizes telomeric DNA, is repressed in normal human somatic cells but is activated with in vitro immortalization or during tumorigenesis. In this study, we investigated telomerase activity and expression of genes involved in telomerase activity in human myeloblastic leukemia ML-1 cells, differentiated synergistically by treatment with all-trans retinoic acid (ATRA) and granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF alone was not effective in changing telomerase activity whilst ATRA alone slightly decreased the activity. A combination of ATRA and GM-CSF remarkably reduced telomerase activity. We also detected remarkable suppression of hTERT mRNA expression in ML-1 cells treated with ATRA and GM-CSF. These results indicate that a synergistic down-regulation of telomerase activity and hTERT mRNA expression is induced by treatment with ATRA and GM-CSF in ML-1 cells.

Antineoplastic Agents↗

PubMedDate not supplied

Stimulation of monocyte iodination and IL-1 production by tannins and related compounds.

Various tannins and related compounds were compared for their ability to stimulate the iodination (incorporation of radioactive iodine into an acid-insoluble fraction) of human peripheral blood monocytes. The stimulating activity of most of the monomeric and dimeric hydrolyzable tannins was generally higher than that of the trimeric and tetrameric compounds. Compounds that had dehydrohexahydroxydiphenoyl or chebuloyl groups had considerably less activity than those that had other functional groups (hexahydroxydiphenoyl, valoneoyl, dehydrodigalloyl, isodehydrodigalloyl, lactonized valoneoyl, hellinoyl, euphorbinoyl, dehydroeuphorbinoyl or woodfordinoyl group). The methylated derivative, nonacosa-O-methylcoriariin A, was essentially inactive, suggesting the requirement of a phenolic hydroxyl group. Three condensed tannins ((-)-epicatechin 3-O-gallate (ECG)-dimer, ECG-trimer and ECG-tetramer) significantly stimulated both monocyte iodination and their interleukin-1-like factor production. The results suggest the dependence of stimulation of monocyte iodination by tannins and related polyphenols on molecular weight.

Animals↗

PubMedDate not supplied

Antitumor, antiviral and immunopotentiating activities of pine cone extracts: potential medicinal efficacy of natural and synthetic lignin-related materials (review).

Several antitumor substances that effectively inhibited the growth of ascites and solid tumor cells transplanted in mice were isolated from pine cone NaOH extract by acid- and ethanol-precipitation. These antitumor substances were also potent antiviral agents against human immunodeficiency virus, herpes simplex virus and influenza virus; they induced antimicrobial activity against Staphylococcal aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Candida albicans, and induced antiparasite activity against Hymenolepis nana in mice. Chemical analysis of these substances by IR, UV, NMR, ESR and partition chromatography on cellulose-TLC plate disclosed that they had lignin-related structures complexed with sugars or polysaccharides. Chlorinated decomposition of the lignin portion significantly reduced their antiviral activity. In agreement with this, the antiviral activity of synthesized lignins prepared by polymerization of phenylpropanoid precursors was comparable to that of the undecomposed counterparts of the pine cone extract. Acid hydrolysis of the polysaccharide portion significantly reduced the ability of the substances to induce antitumor and antimicrobial activities in mice. With an appropriate eliciting agent, intravenous administration of natural lignified substances transiently induced endogenous production of a cytotoxic factor (possibly tumor necrosis factor) in normal mice. Their priming activity was significantly higher than that of their component units or degradation products. These data suggest the importance of conjugating lignins with polysaccharides for in vivo expression of various kinds of immunopotentiating activity. As possible explanations for their induction of a variety of immunopotentiating activities, these natural and synthetic lignins stimulated macrophage NBT-reducing activity, polymorphonuclear cell (PMN) iodination and splenocyte DNA synthesis and inhibited poly (ADP-ribose) glycohydrolase, RNA-dependent DNA polymerase (reverse transcriptase) and RNA-dependent RNA polymerase activities.

Adjuvants, Immunologic↗

PubMedDate not supplied

Induction of tumor degeneration by sodium benzylideneascorbate.

Intravenous administration of sodium benzylideneascorbate (SBA) rapidly necrotized inoperable human lung cancer, and induced degeneration of 3'-methyl-4-dimethylaminoazobenzene-induced rat hepatocellular carcinoma (vacuolar, eosinophilic degeneration, nuclear debris) without affecting the serum glutamic oxaloacetic transaminase, gamma-glutamyl transpeptidase and total protein levels. Cultured normal human lung and skin fibroblasts, and human glioma and glioblastoma cell lines were relatively resistant to SBA, when compared to human myelogenous leukemic cell lines. SBA had no apparent host immunopotentiation activity such as stimulation of cytokine action or production; activation of monocyte or polymorphonuclear cells; or modulation of poly (ADP-ribose) glycohydrolase activity. The data suggest that the antitumor activity of SBA might be produced by direct action of authentic SBA or its metabolized form(s), rather than by immunopotentiation of the hosts.

Animals↗

PubMedDate not supplied

Induction of immunopotentiation activity by a protein-bound polysaccharide, PSK (review).

A protein-bound polysaccharide, PSK, extracted from the mycelium of Coriolus versicolor (Fr.) Quel, has been recognized for its host-mediated induction of antitumor and antimicrobial activities in mice. Intravenous administration of PSK, in association with OK-432 (Picibanil), transiently induced endogenous production of a cytotoxic factor (CF) (possibly tumor necrosis factor, TNF) in normal mice. The ability to produce CF depended greatly on both dose and interval between administration of the PSK and OK-432. Although PSK has been reported to contain several active ingredients, unfractionated PSK has been used in almost all experiments performed so far. We recently reported that, of the four subfractions separated by successive filtration through membrane filters, only the highest molecular weight fraction F4 (MW greater than 200 kD) induced significant antimicrobial activity in mice. PSK stimulated the NBT-reducing activity of mouse peritoneal macrophages and the iodination (incorporation of radioactive iodine into an acid-insoluble fraction) of human peripheral blood polymorphonuclear cells (PMN). Among the subfractions of PSK, the highest molecular weight fraction F4, and the fraction precipitated at pH 4.0-4.5 (Fr. 4), stimulated macrophage NBT-reducing activity and PMN iodination most. In contrast, natural and chemically modified glucans had little or no stimulating activity. PSK, F4 or Fr. 4 additively or synergistically stimulated TNF-induced cytotoxicity against L-929 cells, differentiation of human myelogenous leukemia cell lines toward monocytes/macrophages, and iodination of human peripheral blood PMN. The active PSK subfractions significantly reduced the down regulation of specific 125I-TNF or 125I-IFN-gamma binding to cellular receptors. These data suggest that (i) immunopotentiation activity of PSK might be ascribed, at least in part, to stimulation of cytokine action and production, and (ii) PSK might have some unique structural features.

Adjuvants, Immunologic↗

PubMedDate not supplied

Induction of cytotoxic factor in mice by lignified materials combined with OK-432 (Picibanil).

Intravenous administration of pine cone lignin-related substance (Fr. VI) significantly stimulated OK-432-elicited cytotoxic factor (CF) production in ICR mouse serum. The level of CF elicited after OK-432 administration peaked after 2 h and declined to basal level within 6 h. The CF productibility depended greatly on both dose and the interval between the administration of the Fr. VI and OK-432. Most natural and synthetic lignins, their degradation products, and polysaccharides, including pine cone hemicellulose fractions, had much weaker CF-inducing (priming) activity. When Fr. VI was treated with NaCl02 to decompose the lignin portion, the priming activity was significantly reduced. The data suggest that the potent priming activity of Fr. VI might de a result of some conjugation between the lignin portion and other components including polysaccharides.

Animals↗

PubMedDate not supplied

Stimulation of interferon-gamma-induced human myelogenous leukemic cell differentiation by high molecular weight PSK subfraction.

PSK, a protein-bound polysaccharide extracted from the mycelia of Coriolus versicolor (Fr.) Quel, stimulated tumor necrosis factor-induced cytotoxicity against mouse L-929 fibroblast. PSK also stimulated interferon-gamma-induced differentiation of human myelogenous leukemic U-937 and THP-1 cells. The differentiated cells had higher proportions of cells that expressed NBT-reducing activity and alpha-naphthyl acetate esterase activity. Among four PSK subfractions, the highest molecular weight fraction (MW greater than 200 kD) had the most potent stimulating activity. This is the first report regarding direct PSK modulation of cytokine action.

Animals↗

PubMedDate not supplied

Antimicrobial spectrum of lignin-related pine cone extracts of Pinus parviflora Sieb. et Zucc.

Pine cones of Pinus parviflora Sieb., et Zucc, were extracted successively with 5% NaHCO3, 3% NH4OH, 1% NaOH and 4% NaOH, and the extracts were tested for ability to induce antimicrobial activity in mice infected with Staphylococcal aureus. Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Candida albicans, or Salmonella enteritidis. These alkaline extracts were potent against the first 5 of these strains of microorganisms, and the activity was recovered mostly from their acid-precipitates at pH 5. After further fractionation on a Sephadex LH-60 column, the highest molecular weight fraction was most potent. Chemical structures in these bioactive fractions were assumed to be lignin-related structures, based on spectral data from UV, NMR and IR spectroscopy.

Anti-Bacterial Agents↗

PubMedDate not supplied

Stimulation of granulocytic cell iodination by tannins and related compounds.

Tannic acid stimulated the iodination (incorporation of radioactive iodine into an acid-insoluble fraction) of human peripheral blood polymorphonuclear cells (PMN) and human promyelocytic leukemic HL-60 cells, without affecting the iodination of 9 other cultured cell lines. The stimulation of both PMN and HL-60 cells depended on incubation time and temperature, and was significantly suppressed by myeloperoxidase inhibitors. Among chemically defined natural polyphenols, condensed tannins (epicatechin gallate oligomers) and monomeric and oligomeric hydrolyzable tannins potently stimulated PMN iodination, whereas polyphenols of lower molecular weight (gallic acid, alkyl gallates, epicatechin, epicatechin gallate, epigallocatechin, caffeic acid derivatives and licorice flavonoids) had much less activity. Various synthetic polyphenolic compounds structurally unrelated to tannins also stimulated PMN iodination depending upon their molecular weight, but to a slightly lesser extent. The results suggest that the stimulation activity of tannins and related polyphenols might depend more on their molecular weights than the number of hydroxyl groups on each benzene ring in the molecule, or the presence of sugars or hexahydroxydiphenoyl groups.

Animals↗

PubMedDate not supplied

Antioxidative activity of benzylideneascorbate and its effect on adriamycin-induced cardiotoxicity.

The in vitro antioxidative activity of benzylideneascorbate (SBA) and the in vivo effect on adriamycin (ADR)-induced cardiotoxicity in a mouse model were investigated. The radical-scavenging activity of SBA was assayed in terms of reduction of chemiluminescence induced by O2-, generated in xanthine/xanthine oxidase and macrophage/phorbol myristate acetate reaction systems. SBA showed a strong antioxidative activity (IC50 = 3 to 4 microM) in both assay systems, though its activity was weaker than that of ascorbic acid (Asc). In the assay of the antioxidative activity against auto-oxidation of linolenic acid, SBA was stable and retained its potency for a long period of time in comparison with Asc, 6-palmitoylascorbic acid (6-P-Asc) and cysteamine (CysNH2). Electron spin resonance examination indicated that SBA strongly scavenged both superoxide anion and hydroxy radical. The in vivo protective effect of SBA against ADR-induced cardiotoxicity, in which active oxygen radicals play a role, was examined. The serum creatine phosphokinase activity, a parameter of cardiotoxicity, was remarkably increased from the 3rd day until the 4th day after ADR treatment. This elevation was significantly suppressed by SBA treatment, whereas Asc, 6-P-Asc and CysNH2 were ineffective. SBA could have clinical potential for the treatment of diabetes and other disorders in which active oxygen species play a pathogenic role.

Animals↗

PubMedDate not supplied

Induction of DNA fragmentation in human myelogenous leukemic cell lines by sodium 5,6-benzylidene-L-ascorbate and its related compounds.

High-performance liquid chromatography revealed that sodium 5,6-benzylidene-L-ascorbate (SBA), dissolved in distilled water, was gradually decomposed into ascorbic acid and benzaldehyde. Among these three compounds, ascorbic acid showed the most potent cytotoxic activity. The cytotoxic activity of each compound was significantly reduced during degradation in culture medium. Agarose gel electrophoresis and fluorometric determination of DNA revealed that ascorbic acid, as well as SBA, induced DNA fragmentation into nucleosomal oligomers in human myelogenous leukemic cell lines, but not in freshly isolated human peripheral blood cells. The results suggest that antitumor activity of SBA might be at least in part mediated by the action of ascorbic acid, a degradation product of SBA.

Animals↗