Biomedical subjects

M Suganuma

Publications and source records attributed to M Suganuma.

At least 91 records · Page 5Linked to original sources

PubMed1991

Differential effects of cryptoporic acids D and E, inhibitors of superoxide anion radical release, on tumor promotion of okadaic acid in mouse skin.

Cryptoporic acids D and E, isolated from the fungus Cryptoporus volvatus, are inhibitors of superoxide anion radical release. Cryptoporic acid E inhibited tumor promotion of okadaic acid in two-stage carcinogenesis experiments on mouse skin, initiated with 7,12-dimethylbenz[a]anthracene. Treatment with cryptoporic acid E using two different doses per application, 1 (1.2 mumol) and 5 mg (5.9 mumol), reduced the percentage of tumor-bearing mice from 73.3 to 53.3% and 20.0%, and the average number of tumors per mouse from 4.2 to 2.3 and 0.5 respectively in week 20 of tumor promotion. However, cryptoporic acid D slightly enhanced tumor promotion rather than inhibition of okadaic acid. Cryptoporic acid D was expected to have additional biochemical activities, such as activation of protein kinases. Cryptoporic acid D at concentrations of up to 100 microM activated protein kinase C and stimulated other protein kinase activity in vitro, whereas cryptoporic acid E did not. These two compounds provided differential effects on tumor promotion of okadaic acid on mouse skin.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1991

Platelet aggregation induced by strains of various species of coagulase-negative staphylococci.

Major species of coagulase-negative staphylococci (CNS) were tested for their ability to induce platelet aggregation in rabbit platelet-rich plasma (PRP). Among 11 species of CNS tested, a majority of the strains of 10 species of CNS (S. epidermidis, S. simulans, S. capitis, S. hyicus, S. sciuri, S. cohnii, S. xylosus, S. hominis, S. haemolyticus, S. warneri) caused induction of the platelet aggregation and serotonin release, while S. saprophyticus did not show such activity. The addition of aspirin (10 mM) or quinacrine (1 mM) to PRP resulted in no remarkable effect on the platelet aggregation induced by these strains and it was shown that the platelet aggregation did not require arachidonate pathways. Complement system components were shown to be one of the plasma factors required for platelet aggregation by ten strains of each species of CNS. The bacterial substance participating in the platelet aggregation by ten species of CNS tested was indicated to be heat-stable and trypsin-resistant, while the activity of a strain of S. epidermidis was susceptible to trypsin.

Animals↗

PubMed1991

Platelet aggregation by strains of enterococci.

The platelet aggregation capability of whole cells of Enterococcus faecalis, E. faecium and E. avium was tested. The optimum ratios of bacteria to platelets in E. faecalis (strain SMU-37), E. faecium (strain SMU-138) and E. avium (strain SMU-197) were 1.0, 1.2 and 2.0, respectively. During the platelet aggregation induced by the three strains of enterococci, 65-69% of total serotonin was released. The aggregation was totally inhibited by ethylenediaminetetraacetate (10 mM) and apyrase (1 mg/ml), while no effect was shown by aspirin (10 mM), indomethacin (10 mM) and quinacrine (1 mM). By pretreatment of platelet-poor plasma with heat (56 C, 30 min) or zymosan, the reactivities with platelets of each strain of species were markedly diminished. These results suggest that enterococci-induced platelet aggregation was an ion-dependent, cyclooxygenase-insensitive event, and plasma component(s) was (were) required for the reaction.

Animals↗

PubMed1991

Inhibitory effect of sarcophytol A on development of spontaneous hepatomas in mice.

The inhibitory effect of sarcophytol A, a cembrane-type diterpene isolated from a marine soft coral, Sarcophyton glaucum, on development of spontaneous hepatomas was investigated in C3H/HeNCrj mice. A total of 80 mice were divided equally into two groups. The experimental and control groups were given basal diets with and without 0.01% sarcophytol A, respectively. At week 65 of the experiment, mice were examined for hepatomas. The percentages of hepatoma-bearing mice of the subgroup with three or more tumors and the tumor diameters of the group treated with sarcophytol A were smaller than those of the control group. Ridit analysis revealed that these differences were statistically significant. The body weight gain, and the food intake were not significantly different between these two groups. Analysis of blood serum revealed that feeding the diet containing 0.01% sarcophytol A for 65 weeks did not show any adverse effects. These results suggest that sarcophytol A inhibits the development of spontaneous hepatomas without toxicity, and should be considered as a possible cancer chemopreventive agent for hepatomas in humans.

Alanine Transaminase↗

PubMed1991

Structure-function relationships of microcystins, liver tumor promoters, in interaction with protein phosphatase.

Microcystins, isolated from toxic blue-green algae, are potent inhibitors of protein phosphatases 1 and 2A. Recently, we have reported that microcystin LR has a potent tumor-promoting activity on rat liver initiated with diethylnitrosamine. The structure of microcystins is unique in having an unusual amino acid, 3-amino-9-methoxy-10-phenyl-2,6,8-trimethyl-deca-4(E),6(E)-dienoic acid (Adda), which is thought to be significant for the activity. Geometrical isomers at C-7 in the Adda portion of microcystins, 6(Z)-Adda microcystins LR and RR, have been isolated from cyanobacteria. To estimate their tumor-promoting activities and to understand the importance of the Adda portion for activity, the maternal microcystins LR and RR and their isomers were subjected to examination of their interaction with protein phosphatases 1 and 2A and the release of glutamic pyruvic transaminase from rat liver. 6(Z)-Adda microcystins LR and RR bound to protein phosphatases 1 and 2A, inhibited their activities and released glutamic pyruvic transaminase from rat liver into serum, ten to one hundred times more weakly than the maternal microcystins LR and RR. These results indicated that the conjugated diene with 4(E),6(E) geometry in the Adda portion is important in the interaction with protein phosphatases.

Alanine Transaminase↗

PubMed1991

Pendolmycin, a new tumor promoter of the teleocidin A class on skin of CD-1 mice.

Pendolmycin, isolated from Nocardiopsis, is a compound structurally similar to teleocidin A, one of the 12-O-tetradecanoylphorbol-13-acetate (TPA)-type tumor promoters. Pendolmycin has a C5 dimethyl allyl group attached to C-7 of (-)-indolactam-V, whereas teleocidin A has a C10 linalyl group attached to the molecule. The structure-activity relationships of a hydrophobic moiety attached to (-)-indolactam-V were studied in four compounds, (-)-indolactam-V, pendolmycin, teleocidin A and newly synthesized 7-(nerolidyl)-(-)-indolactam-V in tests on inhibition of the specific [3H]TPA binding to a particulate fraction of mouse skin, activation of protein kinase C and induction of both adhesion of HL-60 cells and ornithine decarboxylase in mouse skin. The potencies of the compounds for these activities increased mainly depending on the length of the hydrophobic group. Pendolmycin had a tumor-promoting activity on mouse skin initiated with a single application of 7,12-dimethyl-benz[a]anthracene, and its potency was just between those of (-)-indolactam-V and teleocidin A. The role of the hydrophobic moiety is discussed with particular emphasis on the results obtained with 7-(nerolidyl)-(-)-indolactam-V.

Alkaloids↗

PubMed1991

Relation of human serum antibody against Staphylococcus epidermidis cell surface polysaccharide detected by enzyme-linked immunosorbent assay to passive protection in the mouse.

A specific and rapid enzyme-linked immunosorbent assay (ELISA) has been applied for the detection of immunoglobulins to Staphylococcus epidermidis cell surface polysaccharides in human serum. Positive IgG, IgM and IgA titres of more than 1: 6400, 1: 1600 and 1: 400 were observed with this assay against passive protective human serum. However, IgG, IgM and IgA titres of less than 1: 400, 1: 100 and 1: 50 were shown in non-protective serum. When the cross-reactivity of passive protective human serum to homologous and heterologous cell surface polysaccharides was examined by inhibition test with ELISA, remarkable inhibition was shown with homologous cell surface polysaccharide, whereas no inhibition was observed with heterologous substances. According to these results, the quantitation of human serum antibody by the ELISA method against Staph. epidermidis cell surface polysaccharide was found to be significant for the demonstration of passive protective activities against Staph. epidermidis.

Animals↗

PubMed1991

Conversion of biological and immunological properties during a process of decapsulation in a strain of Staphylococcus hyicus.

Repeated subculture at 42 degrees C of Staphylococcus hyicus strain ST67P, which exhibits streaming-type growth in a soft-agar medium, yielded three variants, ST67L, ST67S and ST67C, which had different colonial morphologies; small compact colonies possessing long and short tails and perfect compact colonies. The parent strain and ST67L respectively gave strong and weak positive intensity when stained by rabbit antisera prepared by capsular type I and II strains of Staph. epidermidis conjugated with fluorescein isothiocyanate. Variant ST67L gave a positive result with antiserum prepared by capsular type I strain and no staining was observed with variants ST67S and ST67C against these antisera preparations. Strain ST67C had the lowest virulence although no remarkable difference was shown between the parent strain and variants ST67L and ST67S. The cell volume index of the parent strain was 1.35, 2.43 and 3.71 times larger than those of ST67L, ST67S and ST67C, respectively. The converting activity of rabbit anti-ST67P strain serum absorbed by strain ST67C required four times more of the organisms than strain ST67P, changing the colonial morphology of the strain from diffuse to compact type by the addition of antiserum to soft agar medium. Positive coagulase and false positive clumping factor reaction were shown in variants ST67C, but no remarkable alteration was observed with 19 biochemical properties determined by a conventional identification kit. In ulta-thin sections of the parent strain labelled with rabbit anti-strain ST67P serum conjugated with ferritin, large capsule surrounded by ferritin granules were demonstrated by electron microscopy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Monoclonal IgM antibody protection in mice against infection with an encapsulated strain of Staphylococcus epidermidis.

Passive protective activities of three different classes of monoclonal antibodies in mice against challenge with strain ATCC 31432 (capsular type I) of Staphylococcus epidermidis were examined. Monoclonal IgM antibody passively protected mice against challenge with the homologous strain, whereas monoclonal IgG1 and IgG2b antibodies did not. The protective activity of IgM was absorbed by the cell surface antigen extracted from the homologous strain but not by the antigen from heterologous strains. Rapid reduction of viable cells took place in the peritoneal cavity of mice immunized with monoclonal IgM as early as 6 h after the challenge with the homologous strain. An enzyme-linked immunosorbent inhibition assay showed there was remarkable inhibition with the homologous cell surface antigen but not with heterologous preparations from other strains. Results suggest that in the mouse the major passive protection against the S. epidermidis strain is provided by the IgM antibody to the cell surface antigen.

Animals↗

PubMed1991

Mechanisms of action of okadaic acid class tumor promoters on mouse skin.

Okadaic acid, dinophysistoxin-1 (35-methylokadaic acid), and calyculin A are the okadaic acid class of non-12-O-tetradecanoylphorbol-13-acetate (TPA)-type tumor promoters, which do not bind to the phorbol ester receptors in cell membranes or activate protein kinase C in vitro. They have potent tumor-promoting activities on mouse skin, as strong as TPA-type tumor promoters, such as TPA, teleocidin, and aplysiatoxin. DNA samples isolated from tumors induced by dimethylbenz[alpha]anthracene and each of the okadaic acid class tumor promoters had the same mutation at the second nucleotide of codon 61 (CAA to CTA) in the c-H-ras gene. Okadaic acid receptors, protein phosphatases 1 and 2A, are present in the particulate as well as cytosolic fractions of various mouse tissues. The apparent "activation" of protein kinases by the okadaic acid class tumor promoters, after their incubation with 32P-ATP, protein kinases, and protein phosphatases, was observed. This activation was caused by inhibition of protein phosphatases 1 and 2A by the okadaic acid class tumor promoters. Treatment of primary human fibroblasts and human keratinocytes with the okadaic acid class tumor promoters induced the hyperphosphorylation of a 60-kDa protein in nuclear and cytosolic fractions, due to the inhibition of protein phosphatases. The 60-kDa protein is a proteolytic fragment of nucleolin, a major nonhistone protein and is designated as "N-60." The mechanisms of action of the okadaic acid class tumor promoters are discussed with emphasis on the inhibition of protein phosphatase activity.

Animals↗

PubMed1990

Photoaffinity labeling of protein phosphatase 2A, the receptor for a tumor promoter okadaic acid, by [27-3H]methyl 7-O-(4-azidobenzoyl)okadaate.

The interaction of okadaic acid and a protein phosphatase, which is the receptor for a tumor promoter, okadaic acid, was studied. [27-3H]Methyl 7-O-(4-azidobenzoyl)okadaate was synthesized and protein phosphatase 2A, which consists of two regulatory subunits of 65 kDa and 42 kDa and a catalytic subunit of 37 kDa, was purified from bovine brain. After UV irradiation of the reaction mixture, [3H]methyl 7-O-(4-azidobenzoyl)okadaate covalently bound to the catalytic subunit, but not to the two regulatory subunits. These results strongly suggest that okadaic acid, a potent inhibitor of protein phosphatases, binds specifically to the catalytic subunit rather than to the other regulatory subunits.

Affinity Labels↗

PubMed1990

Tumor-promoting activity of staurosporine, a protein kinase inhibitor on mouse skin.

Staurosporine, which is a potent inhibitor of protein kinases, such as protein kinase C, inhibited both inductions of adhesion of human promyelocytic leukemia cells (50% effective dose = 9.0 nM) and Epstein-Barr virus early antigen in Raji cells (50% effective dose = 3.4 nM) by teleocidin. However, staurosporine induced irritation on mouse ear and histidine decarboxylase activity in mouse skin. It did not induce ornithine decarboxylase activity in mouse epidermis. The two-stage carcinogenesis experiments of staurosporine were carried out at two different doses. Experiment 1 revealed that the group treatment with a single application of 100 micrograms of 7,12-dimethylbenz(a)anthracene, followed by repeated applications of 50 micrograms of staurosporine, resulted in 85.7% of tumor-bearing mice at Wk 30, whereas group treatment with staurosporine alone or 7,12-dimethylbenz(a)anthracene alone gave 6.7% and 0%, respectively. Experiment 2 showed that group treatment with 7,12-dimethylbenz(a)anthracene followed by applications of 10 micrograms of staurosporine resulted in 33% of tumor-bearing mice at Wk 30. In addition, staurosporine treatment reduced the percentages of tumor-bearing mice treated with teleocidin from 100% to 67% in Wk 15. These results demonstrated that staurosporine is a weak tumor promoter of mouse skin compared with teleocidin, but staurosporine has some potency to inhibit tumor promotion by teleocidin.

Alkaloids↗

PubMed1990

Calyculin A, an inhibitor of protein phosphatases, a potent tumor promoter on CD-1 mouse skin.

Calyculin A, isolated from a marine sponge, has a novel spiro ketal skeleton. Structurally unrelated to okadaic acid, calyculin A bound to the okadaic acid receptors in particulate and soluble fractions of mouse skin. The biochemical and tumor-promoting activities of calyculin A were studied with those of okadaic acid. Calyculin A inhibited the activity of protein phosphatases, which serve as the okadaic acid receptors. The effective dose of calyculin A for 50% inhibition was 0.3 nM, similar to that of okadaic acid. Like okadaic acid, calyculin A induced ornithine decarboxylase in mouse skin and hyperphosphorylation of a Mr 60,000 protein in human papilloma virus type 16-transformed human keratinocytes. A two-stage carcinogenesis experiment on mouse skin, initiated by 100 micrograms (390 nmol) of 7,12-dimethylbenz(a)anthracene and followed by 1 microgram (1.0 nmol) of calyculin A, revealed that calyculin A is an additional member of the okadaic acid class of tumor promoters. The percentages of tumor-bearing mice in the groups treated with DMBA plus calyculin A, and with DMBA followed by 1 microgram (1.2 nmol) of okadaic acid were 86.7 and 80.0%, respectively, in week 30. The mechanisms of action of calyculin A and okadaic acid, in addition to dinophysistoxin-1 (35-methylokadaic acid), are discussed. Calyculin A is the first tumor promoter to be screened by the okadaic acid receptor binding test.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1990

Inhibition of platelet aggregation by a whole cell extract from strains of group B streptococcus.

A whole cell extract (HCl-Ext) from strains of group B streptococci (GBS) possessing fibrinogen binding activity prevented the platelet aggregation induced with adenosine 5'-diphosphate (ADP), collagen and thrombin, while aggregation by epinephrine and ristocetin was slightly inhibited and arachidonic acid-induced platelet aggregation was not affected whatsoever. When the HCl-Ext was added after commencement of the aggregation, deaggregation was observed in cases induced by ADP, collagen, and thrombin. By precoating the washed platelets with HCl-Ext, both of ADP- and collagen-induced platelet aggregation were suppressed. The active factor in the HCl-Ext seemed to be undialyzable, trypsin-susceptible, and proteinaceous substance, unlike GBS polysaccharide type antigen.

Fibrinogen↗

PubMed1990

New antitumor promoters: (-)-epigallocatechin gallate and sarcophytols A and B.

EGCG, the main constituent of green tea, and sarcophytols A and B, isolated from a soft coral, inhibited tumor promotion by teleocidin in a two-stage carcinogenesis experiment on mouse skin. EGCG and sarcophytols showed inhibition of tumor development by chemical carcinogenesis. A possibility of developing these compounds as cancer chemopreventives for human beings is discussed.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1990

Immunochemical characterization and biological properties of a cell surface antigen extracted from encapsulated Staphylococcus epidermidis strain SE-10.

Protection inducing antigen (PIA) was mechanically extracted from Staphylococcus epidermidis (encapsulated strain SE-10) and purified by DEAE-Sephadex A 25 (C1- form) ion exchange chromatography. Major carbohydrate constituents of PIA were galactose, glucose, and N-acetylglucosamine at the molar ratio 1.00:0.96:0.78. Antigenic activity was considerably reduced after sodium metaperiodate oxidation, however, pronase digestion was not effective. N-acetylglucosamine residues were shown to be closely related to the antigenic determinant. No cross reactivity to PIAs from other encapsulated strains of S. epidermidis was found which indicates type specificity. Protection of mice after immunization and enhancement of human granulocyte function suggests that PIA might be considered to be a biological response modifying substance.

Antigens, Bacterial↗

PubMed1990

Structure-activity relationship within a series of okadaic acid derivatives.

Okadaic acid (OA) is a potent non-12-O-tetradecanoyl-phorbol-13-acetate (non-TPA) type tumor promoter on mouse skin. OA acts on cells through inhibiting the activity of protein phosphatases and results in the increase of phosphorylation of proteins. Seventeen OA derivatives were evaluated as possible tumor promoters by means of three biochemical tests: inhibition of specific [3H]OA binding to a particulate fraction of mouse skin containing protein phosphatases, inhibition of protein phosphatase activity, and induction of ornithine decarboxylase in mouse skin. Potency in each of these biochemical tests correlated well for each of these derivatives. We present results indicating that the carboxyl group as well as the four hydroxyl groups at C-2, C-7, C-24 and C-27 of OA are important for activity. Acanthifolicin, which gave positive responses in these three biochemical tests as strong as those of OA and dinophysistoxin-1, is predicted to be an additional member of the OA class of tumor promoters.

Animals↗

PubMed1990

Isolation of a serologically different compact-colony-forming active substance from strains of Staphylococcus aureus.

To observe the possible serological heterogeneity of compact-colony-forming active substance (CCFAS), heat-killed vaccines were prepared by two strains of Staphylococcus aureus, strains SMU 1-46 and SMU 7931, cultured in 0.03 M trishydrochloride-buffered brain heart infusion, pH 8.4. After immunization with the vaccine in rabbits, antibody responses were observed during a period of six weeks after the immunization either by homologous and heterologous organisms using alkaline serum-soft agar technique. The results showed that remarkable antibody production was shown only against homologous strain, but not against heterologous strain. The antibodies were absorbed out only with highly purified preparation of CCFAS extracted from homologous strain and not with heterologous CCFAS. Differences of the major chemical composition of the substances showed that highly purified CCFAS extracted from strain SMU 7931 contained 2.84 and 2.04 times higher amounts of galactose and 2-amino-2-deoxy-D-galacturonic acid than those of CCFAS obtained from strain SMU 1-46.

Agar↗