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T Ebina

Publications and source records attributed to T Ebina.

At least 109 records · Page 6Linked to original sources

Activated macrophages are responsible for the tumor-inhibitory effect in mice receiving intravenous injection of OK-432.

Mouse spleen cells, either pretreated in vitro with 100 U/ml of OK-432-induced IFN gamma for 18 h or obtained from mice 24 or 48 h after i.v. injection of OK-432(100 micrograms/mouse), were examined for their anti-tumor effect by Winn's neutralization assay against Meth-A tumor cells in BALB/c mice. Spleen cells treated in vitro or obtained in vivo 24 h after i.v. injection clearly neutralized the growth of admixed Meth-A cells. Two booster injections of 200 U of IFN gamma near the tumor site accelerated this neutralizating effect. In order to determine the effector subpopulation, inhibitory spleen cells were treated with either anti-Thy-1 monoclonal antibody plus complement, anti-asialo GM1 serum plus complement or with adherence on plastic plates followed by Sephadex G-10 column treatment. The effector cell activity in Winn assay was lost only after the removal of macrophages through plastic plate adherence and Sephadex G-10 column treatment, but not after anti-Thy-1 or anti-asialo GM1 treatment, with either in vitro- or in vivo-treated spleen-cell populations. The growth of Meth-A cells was inhibited not only by these activated macrophages in Winn's assay, but also by adoptive transfer of OK-432-induced cytotoxic macrophages intralesionally 4 days after the implantation of 1 X 10(6) Meth-A cells. Our evidence suggests that the systemic action of OK-432 can be explained by the effect of induced IFNgamma, through the activation of macrophages.

Animals↗

Hemagglutination by human rotavirus strains.

Human rotavirus isolates, KUN , MO, and Wa strains were found to agglutinate erythrocytes of the day-old chicken and adult goose, optimally at pH 6.6. Only those fractions containing double-shelled rotavirus particles isolated by isopycnic centrifugation in cesium chloride had hemagglutinating activity. Trypsin treatment decreased the hemagglutination titer of human rotavirus strains and conversely increased their infectivity. Hemagglutination inhibition tests with antisera against type-specific antigens demonstrable by neutralization showed no type specificity.

Animals↗

Further observations on the morphogenesis of human rotavirus in MA 104 cells.

Human rotavirus "KUN" strain was cultivated in a fetal rhesus monkey kidney cell line, MA 104 cells. Four types of virus particles in cells infected with KUN strain were clearly identified: nucleoid cores, single-shelled particles, double-shelled particles, and membrane band, "enveloped" particles. "Enveloped" particles were found only in the thin sections of infected cells. When first visible, the virus precursors appeared at the ribosome free membrane of rough endoplasmic reticulum (RER), increasing in size while simultaneously being coated with nucleocapsid, inner shell. Single-shelled particles were also synthesized within bundles of filaments of viroplasm in the cytoplasma. During subsequent virus maturation two types of "budding" processes were observed. Double-shelled particles arising at the RER membrane entered the cisternae of the RER through an exocytosis-like process. In contrast, the "enveloped" particles developed in the cisternae by being completely enclosed with RER membrane, and later during cytolysis released the single-shelled particles. These "enveloped" virus particles appeared to be the result of inefficient virus maturation at the last stage of outer capsid formation.

Animals↗

Treatment of multiple sclerosis with anti-measles cow colostrum.

Previous virological and immunological studies have suggested that multiple sclerosis (MS) is an auto-immune disease triggered by a virus infection. In order to inhibit the growth of measles virus in the patient's jejunum, we obtained an IgA-rich cow colostrum containing anti-measles lactoglobulin resistant to proteases. This colostrum was orally administered to patients with MS to investigate its effect on the course of the disease. Measles-positive antibody colostrum was orally administered every morning to 15 patients with MS at a daily dosage of 100 ml for 30 days. Similarly, measles-negative antibody (less than 8) control colostrum was orally administered to 5 patients. As a clinical assessment, disability scores developed by the International Federation of Multiple Sclerosis Societies were used. As a result, of 7 high NT titre (512-5120) anti-measles colostrum recipients 5 patients improved and 2 remained unchanged. Among 8 low NT titre (8-32) anti-measles colostrum recipients 5 patients improved and 3 remained unchanged. However, of 5 negative NT titre (less than 8) colostrum recipients 2 patients remained unchanged and 3 worsened. No side-effects were observed in colostrum recipients. These findings suggest the efficacy of orally administered anti-measles colostrum in improving the condition of MS patients (P less than 0.05).

Adolescent↗

Induction by butylated hydroxyanisole of specific molecular forms of glutathione S-transferase and UDP-glucuronyltransferase and inhibition of development of gamma-glutamyl transpeptidase-positive foci in rat liver.

Effects of an antioxidant, butylated (3-tert-butyl-4-) hydroxyanisole (BHA) on the induction of specific molecular forms of glutathione S-transferase (GST), UDP-glucuronyltransferase (UDP-GT) and other glutathione-related enzymes in rat liver were investigated. The development of gamma-glutamyl transpeptidase (gamma-GTP)-positive foci and hyperplastic nodules induced by diethylnitrosamine, 200 mg/kg i.p., followed by 0.02% N-2-fluorenylacetamide (FAA) in diet plus partial hepatectomy was inhibited by the administration of 0.75% BHA in the FAA-containing diet. Inhibition was reflected in decreased area of gamma-GTP-positive foci which correlated with a decrease in gamma-GTP activity measured biochemically. Under the present experimental conditions, total activities of GSTs, especially that of GST-A form, and of UDP-GTs, especially that of the late fetal form (o-GT), were markedly increased, together with glutathione levels in the whole liver, within one week after BHA administration. Without BHA administration the activities of GST-A and o-GT, as well as glutathione levels, were also increased by FAA treatment, primarily localized within gamma-GTP-positive foci. These results suggest that the induction of specific molecular forms of detoxicating enzymes either in enzyme-altered foci or in the whole liver may play an important role in determining the extent of development of preneoplastic nodules from initiated foci under the short term induction conditions used.

Animals↗

Immune interferon production by TH69, a lyophilized preparation of Streptococcus faecalis, in murine spleen cell cultures.

In mouse spleen cell cultures, TH69, a live Streptococcus faecalis (ATCC 31663) preparation, at a concentration of 20 micrograms/ml induced immune interferon (IFN gamma) with molecular weight ranging from 20,000 to 40,000 daltons together with a small amount of IFN alpha/beta. By using nonsensitized mouse spleen cells, the fact that both T-cells and macrophages are required for this IFN production was established. When these spleen cells were obtained from mice sensitized 12 days earlier with 4 mg of TH69, twice as much IFN was produced than in cells obtained from nonsensitized mice. This increase was explained by the presence of both sensitized macrophages and T-cells in a reconstitution experiment.

Animals↗

Participation of macrophages in enhanced in vitro immune interferon (IFN gamma) production with mouse spleen cells.

IFN gamma production in cultures of spleen cells obtained from mice sensitized with TH69, a live Streptococcus faecalis preparation, was examined to determine how macrophages participate. It was demonstrated that sensitized spleen macrophages participated in enhanced IFN gamma production by T cells at an early stage (0-6 hr) of incubation, and that this production is mainly dependent on Ia-bearing macrophages In the reconstitution experiments where different combinations of spleen macrophages and T cells obtained from mice sensitized with TH69, OK-432, and BCG were used, T cells required that the identity between the sensitizing organisms in vivo and the stimulating organisms in vitro be the same for enhanced IFN gamma production while macrophages did not. Macrophage-mediated production of IFN gamma appears to be genetically restricted because IFN gamma was only produced in cultures where the H-2 region of macrophages and T cells matched. Further examination revealed that for macrophages to participate in enhanced IFN gamma production, first contact between cycloheximide-treated macrophages and T cells was required. Second, enhanced IFN gamma production occurred when culture supernatants of macrophages obtained from sensitized spleen cells were added to T cells. However, the addition of culture supernatant obtained from sensitized peritoneal macrophages resulted in inhibition of IFN gamma production. These results clearly showed the crucial role of macrophages in enhanced IFN gamma production by spleen T cells in vitro.

Animals↗

[Effects of krestin and p-aminobenzoic-N-xyloside sodium salt on activities of drug-metabolizing enzymes and glutathione-related enzymes in rat liver].

Effects of krestin (PSK) and p-aminobenzoic-N-xyloside sodium salt (K-247) (both products of Kreha Chemical Co., Japan) on activities of drug-metabolizing enzymes and glutathione (GSH)-related enzymes were investigated in rat liver. When PSK was administered at a dose of 100 mg/kg body weight, ip every day for 7 or 14 days, the action of UDP-glucuronyltransferase (UDP-GT) on o-aminophenol (o-GT) and those of GSH S-transferase (GST) on both 1, 2-dichloro-4-nitrobenzene ( DCNB ) and 1-chloro-2, 4-dinitrobenzene (CDNB) slightly increased together with increased activities of GSH-peroxidase on both H2O2 and cumene hydroperoxide, were as GSH levels were decreased. When PSK or K-247 was administered at 1% in diet for 4 or 8 weeks, o-GT activity and GST activities with both substrates increased on K-247 feeding, while GST activity for CDNB decreased on PSK and K-247 feedings. These changes were statistically significant but very small. The content of P-450 and the activity of gamma-glutamyl transpeptidase changed little in any administration schedules mentioned above.

4-Aminobenzoic Acid↗

[Antitumor effect of interferons].

Recent reports on the antitumor activity of interferon-gamma were reviewed and compared to a study on interferon-alpha beta. Secondly our results on the antitumor effects of murine IFN-gamma on Meth-A sarcoma in syngeneic BALB/c mice were described in detail. Topical injection of IFN-gamma to the tumor site, Winn neutralization test of IFN-gamma activated spleen cells and adoptive transfer of IFN-gamma activated cells to the tumor site all resulted in positive antitumor effects. Finally, data on clinical trials of natural and recombinant IFNs presented at the 13th International Congress of Chemotherapy were summarized and the development of future IFN research was discussed.

Animals↗

In vitro production of immune interferon (IFN gamma) by murine spleen cells when different sensitizing antigens are used in vivo and in vitro.

OK-432, a killed preparation of Streptococcus pyogenes, as well as bacillus Calmette-Guérin (BCG) and Corynebacterium parvum are all known to induce immune interferon (IFN gamma) in mice. To examine the mechanisms of IFN gamma induction by OK-432, DDI mice were sensitized with various doses of OK-432, either by a single injection of a 1-mg dose or repeated injections of 0.1-mg doses given intraperitoneally. Spleen cells removed from the mice 7-9 days after the last injection produced high-titered IFN gamma (600-800 IU/ml) in vitro in the presence of 5 micrograms/ml of OK-432. In the absence of OK-432, however, in vitro IFN gamma production of sensitized spleen cells was quite limited. Moreover, when inducers of different antigenic entities such as serologically unrelated Streptococcus faecalis, Listeria monocytogenes, or Con A were added in vitro, instead of OK-432, to the OK-432-sensitized spleen cells, high-titered IFN gamma production also occurred. This may indicate that the signal required by T cells to produce IFN gamma in vitro need not necessarily be the same as that required to sensitize mouse macrophage in vivo. Once sensitized with OK-432, mice spleen cells continued to produce high-titered IFN gamma for more than 3 but less than 5 weeks.

Animals↗

Molecular forms of glutathione S-transferase and UDP-glucuronyltransferase as hepatic preneoplastic marker enzymes.

Changes in molecular forms of glutathione S-transferase (GST) and UDP-glucuronyltransferase (UDP-GT) as hepatic detoxicating enzymes were investigated during chemical hepatocarcinogenesis in the rat. The activity and the protein amount (formula; see text) itself of the GST-A form, which has fetal characteristics and is separable from other forms by CM-Sephadex column chromatography and by immunologic techniques, was much increased in gamma-glutamyl transpeptidase (gamma-GTP)-positive foci or hyperplastic nodules (HNs) induced by diethylnitrosamine and 2-fluorenylacetamide or 3'-methyl-4-dimethylaminoazobenzene. The activity of enzyme 1 (late fetal form) of UDP-GT assayed with o-aminophenol (o-GT) also increased with increased number of the foci or HNs, while the activity of enzyme 2 (neonatal form) assayed with phenolphthalein (p-GT) changed but little. The foci and HNs were stained more strongly than the nonnodular areas immunohistochemically using the antibody against purified GST-A or o-GT. The two activities were also increased in well-differentiated hepatomas, but they were decreased in moderately and poorly differentiated hepatomas, and activating enzymes such as cytochrome P-450 were markedly decreased from HN. GST-A and o-GT differ from fetal enzymes such as those of carbohydrate metabolism in that they are inducible in the short-term by drugs, including carcinogens, and they show the highest activities in HNs, and so they may be considered as hepatic preneoplastic (PN) antigens.

Animals↗

[Anticancer effects of OK-432 (2). Anticancer actions of M phi activated by OK-432].

Mouse spleen cells (DDI, BALB/c, 10 weeks old), either pretreated in vitro with 100 u/ml of OK-432-induced IFN gamma for 18 hr or obtained from mice 24 or 48 hr after iv injection of OK-432 (100 micrograms/mouse), were examined for their antitumor effect by Winn assay against Meth-A tumor cells in BALB/c mice. Both of these spleen cells preparations clearly inhibited the growth of admixed Meth-A cells. In order to determine the effector subpopulation, these spleen cells were treated with either anti-Thy-1 monoclonal antibody plus complement, anti-asialo GM1 serum plus complement or in combination of adherence on plastic plates followed by Sephadex G-10 column treatment. As a result, the effector activity in Winn assay was lost only after the removal of macrophages through plastic plate adherence and Sephadex G-10 column treatment, but not after anti-Thy-1 or anti-asialo GM1 treatment, with either spleen cell populations. Moreover, after anti-Thy-1 treatment, the effector activity of spleen cells increased, suggesting the presence of suppressor T cells in these spleen cell populations. The growth of Meth-A cells was not only inhibited by these activated macrophages in Winn assay but also by adoptive transfer of OK-432-induced cytotoxic spleen macrophages, intralegionally 4 days after the implantation of 1 X 10(6) Meth-A cells. In conclusion, the effector cells which appeared in mouse spleens after iv injection of OK-432 were found to be cytotoxic macrophages, which inhibited the growth of Meth-A cells, both in vitro and in vivo. IFN gamma induced by OK-432 in mouse spleen cell cultures produced the same cytotoxic macrophages when added to the spleen cell cultures, at a dose as low as 100 u/ml. All of our evidence suggests that the systemic action of OK-432 can be explained by the effect of IFN gamma induction.

Animals↗