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Biomedical subjects

J C Cyong

Publications and source records attributed to J C Cyong.

At least 19 recordsLinked to original sources

[New BRM from kampo-herbal medicine].

The action mechanisms of Toki-shakuyakusan (TSS), one of Kampo-herbal medicine, on the clearance of immune complexes and macrophage function were investigated. In the in vivo study, oral administration of TSS enhanced the immune complexes clearance from the circulation in MRL Mp-lpr/lpr mice and C3H/He mice, but no effect was observed in the carbon clearance assay. In the in vitro study, TSS increased the binding of immune complexes to macrophages or Kupffer cells, and the digestion of immune complexes by Kupffer cells. By flow cytometric analysis, the expressions of Fc gamma 11/111 receptors and complement receptor 3 (CR3) on macrophages were increased by the treatment with TSS. Besides, it was also reported that the appearance of the activity was owe to the combination of Angelicae Radix and Atractylodis Lanceae Rhizoma, two of six ingredients of TSS. Both outer and inner dialysate of the extract of Angelicae Radix and Atractylodis Lanceae Rhizoma potentiated the binding of immune complexes to macrophages. Low molecular fraction was further fractionated by using colomn chromatography, and the active components were concentrated in fraction 5-C (named LMW5-C). In conclusion, one of the mechanism of enhancement of immune complexes clearance was thought to due to increase the immune complexes binding to macrophage though augment of Fc gamma 11/111 receptors and CR3 expression. And it was revealed that the active components were not only high moleculer substances but low molecular ones.

Animals

Effects of lycopene, a carotenoid, on intrathymic T cell differentiation and peripheral CD4/CD8 ratio in a high mammary tumor strain of SHN retired mice.

We previously reported that lycopene, one of the carotenoids, significantly suppressed the development of spontaneous mammary tumors of mice and the contribution of lycopene to the maintenance of physical homeostasis was suggested. In this study, we investigated the effects of lycopene on the intrathymic and peripheral T cell subpopulation as immunoregulatory parameters. In tumorous control mice, inactivation of intrathymic T cell differentiation, an increase of the percentage of CD4+ CD8+ cells and a decrease of CD4+CD8+ cells were observed. On the other hand, in the lycopene-treated mice, the abnormal intrathymic T cell differentiation was recovered and brought to non-tumorous levels. The peripheral CD4/CD8 ratio was partially augmented by lycopene treatment which resulted from an increased CD4+ subpopulation. These observations suggest that one of the immunomodulating roles of lycopene is to normalize the change of intrathymic T cell differentiation caused by tumorigenesis.

Animals

Preventive effect of taraxasteryl acetate from Inula britannica subsp. japonica on experimental hepatitis in vivo.

The survival rate for acute hepatic failure induced by Propionibacterium acnes and lipopolysaccharide (LPS) was increased when a hot water extract from the flowers of Inula britannica L. subsp. japonica Kitam. was injected into the experimental hepatitis mice, and anti-hepatitis substances could be extracted with CHCl3. The CHCl3 extract from I.britannica was fractionated and anti-hepatitis fractions IB-3-2 and IB-3-3 were obtained. IB-3-3 had the most potent anti-hepatitis activity among the fractions but further purification of the active compound was not achieved because of the low yield. IB-3-2 contained only one substance which was identified to be taraxasteryl acetate by 1H- and 13C-NMR and MS. Taraxasteryl acetate showed potent preventive activity against acute hepatic failure induced by P.acnes and LPS in a dose-dependent manner, however deacetylation and modification of the olefinic bonds significantly decreased the anti-hepatitis activity of taraxasteryl acetate. Taraxasteryl acetate also inhibited the increment of plasma transaminase on acute hepatic failure induced by carbon tetrachloride (CCl4) or D-galactosamine. From a histological study it appeared that degeneration and necrosis, which were observed in the liver from CCl4 mice, were not found in the liver cells from taraxasteryl acetate treated mice. These results indicates that taraxasteryl acetate shows preventive effects on experimental hepatitis caused by either immunologically induced injuries or hepatotoxic chemicals.

Animals

[Effects of azithromycin on fecal flora of healthy adult volunteers].

New macrolide antibiotic, azithromycin (AZM), was administered to six healthy male volunteers and its effects on their intestinal microflora were investigated. Each volunteer was given 500 mg of AZM orally, once a day for 3 consecutive days. Stool samples were obtained from them prior to the medication and 1, 7, 14 and 28 days after the third day the medication. A slight decrease in the total aerobic bacterial count was observed. Also, several species of anaerobic bacteria showed slight decreases through the 14th day post medication. Individual variances were observed, however. A marked decrease in the number of Bifidobacterium was found for each of the volunteers. Clostridium difficile was detected from one of the volunteers on the 28th day post medication without diarrhea related symptoms.

Adult

Effects of Kampo medicines on the clearance of circulating immune complexes in mice.

Toki-Shakuyaku-san (TSS), a Japanese (Kampo) formulation which consists of six herbs, was administered orally to MRL Mp-lpr/lpr mice for 6 weeks. Clearance was measured by in vivo enzymatic immune complex clearance (EIC) assay. Glucose oxidase-anti-glucose-oxidase complexes (GAG), as a model of immune complexes (ICs), was injected into mouse tail veins and at intervals thereafter the enzyme activity of the GAG remaining in the circulation were estimated. The half life (T1/2) of GAG from the circulation was significantly shortened in the TSS-treated group. Furthermore, the amount of circulating immune complexes, measured by anti-mouse C3 ELISA, tended to decrease in the TSS-treated group. We also evaluated three other Kampo formulas, but no significant effect was observed for these formulations. We then examined the activity of the individual herbs in TSS and in formulations excluding one component herb. No significant changes were observed with individual herbs. On the other hand, the activity observed in the TSS-treated group disappeared in the TSS minus Angelicae Radix formulation and the TSS minus Atractylodis Lanceae Rhizoma formulation. These observations indicate that TSS is a potent formula and its enhancing activity on ICs clearance is strengthened by both Angelicae Radix and Atractylodis Lanceae Rhizoma.

Administration, Oral

The pectic polysaccharide from Bupleurum falcatum L. enhances immune-complexes binding to peritoneal macrophages through Fc receptor expression.

Binding of glucose oxidase-anti-glucose oxidase complexes (GAG), a model of immune complexes, to macrophages was enhanced by treatment with an acidic pectic polysaccharide, bupleuran 2IIb, from Bupleurum falcatum L. GAG binding to macrophages by bupleuran 2IIb increased in a dose-dependent fashion, and was abolished when the Pronase-treated macrophages were incubated with bupleuran 2IIb. The GAG binding enhancing activity of bupleuran 2IIb was reduced by periodate oxidation but not Pronase digestion of bupleuran 2IIb. When bupleuran 2IIb was digested with endo-polygalacturonase, the resulting enzyme resistant carbohydrate portion showed potent activity. Scatchard analysis indicated enhanced expression of the Fc receptor (FcR) on the surface by the action of bupleuran 2IIb. The enhancement of GAG binding by bupleuran 2IIb was inhibited by the presence of actinomycin D or cycloheximide. Bupleuran-2IIb-stimulated cells showed enhanced expression of both FcRI and FcRII mRNA, which were measured as PCR products. These results suggested that the endo-polygalacturonase resistant carbohydrate portion of bupleuran 2IIb is important for the expression of the activity, and that the activity of bupleuran 2IIb on GAG binding was mediated by receptors for polysaccharide on the cells. The up-regulation of the Fc receptor by bupleuran 2IIb was also suggested to mediate by de novo synthesis of the receptor protein.

Animals

Mitogenic and complement activating activities of the herbal components of juzen-taiho-to.

The Kampo (Japanese herbal) medicine "Juzen-Taiho-To" (TJ-48), which was prepared by decocting a concoction (formula), contains ten kinds of herbs and has several immunostimulating activities. In order to determine the contribution of each herbal component, the complement-activating and mitogenic activities of the hot water extract as well as the polysaccharide fraction from each herb were tested. Hot water extracts of Glycyrrhizae radix, Astragali radix, and Atractylodes lanceae rhizoma showed significant mitogenic activity whereas that of Cinnamomi cortex showed potent complement-activating activity. However, the exclusion of any single component herb whether active or not on its own did not result in a loss or an increase of the overall activity of TJ-48. The polysaccharide fraction from Glycyrrhizae radix showed the most potent of both activities among the same fractions from the other nine herbs, and reduced both activities after periodate oxidation, thus indicating that the carbohydrate moiety may contribute to both activities.

Animals

Stimulatory effects of ingenols from Euphorbia kansui on the expression of macrophage Fc receptor.

Immune complex binding to macrophages was enhanced by treatment with an E. kansui extract. Systematic fractionation of the extract led to the characterization of 3-O-(2'E,4'Z-decadienoyl)- and 3-O-(2,3-dimethylbutyryl)-13- O-n-dodecanoyl-13-hydroxyingenol as the active principles. Immune complex binding to macrophages by the action of these compounds increased in a dose-dependent manner. When each ingenol (10 nM) was added to the separated culture medium, the immune complex binding ability of macrophages increased up to 2-fold, respectively. Scatchard analysis showed the enhanced expression of the Fc-receptor for gamma-globulin by the action of each ingenol to macrophages. This Fc-receptor upregulation was dependent on RNA synthesis, suggesting a possible de novo synthesis.

Animals

Evidence for an essential role of long chain acyl-CoA synthetase in animal cell proliferation. Inhibition of long chain acyl-CoA synthetase by triacsins caused inhibition of Raji cell proliferation.

Triacsins A, B, C, and D are new inhibitors of long chain acyl-CoA synthetase (EC 6.2.1.3) and possess different inhibitory potencies against the enzyme (Tomoda, H., Igarashi, K., and Omura, S. (1987) Biochim. Biophys. Acta 921, 595-598). Acyl-CoA synthetase activity in the membrane fraction of Raji cells was also inhibited by triacsins. The same hierarchy of inhibitory potency as that against the enzyme from other sources, triacsin C greater than triacsin A much greater than triacsin D greater than or equal to triacsin B, was observed. When Raji cells were cultivated in the presence of triacsins, cell proliferation was inhibited in a dose-dependent fashion. The drug concentrations required for 50% inhibition of cell growth at day 2 were calculated to be 1.8 microM for triacsin A, much greater than 20 microM for triacsin B, 1.0 microM for triacsin C, and much greater than 15 microM for triacsin D, demonstrating a hierarchy for inhibitory potency of triacsins similar to that against the acyl-CoA synthetase activity. To understand the role of long chain acyl-CoA synthetase in animal cells, the effect of triacsins on the lipid metabolism of Raji cells was studied. When intact Raji cells were incubated with [14C]oleate in the presence of individual triacsins, the incorporation of [14C]oleate into each of the lipid fractions such as phosphatidylcholine, phosphatidylethanolamine, and triacylglycerol was inhibited to an analogous extent. A common hierarchy, triacsin C greater than triacsin A much greater than triacsin D greater than triacsin B, was shown for the inhibition in each synthesis of the three lipids, which was identical with that for acyl-CoA synthetase. These findings indicate that the inhibition of acyl-CoA synthetase is well correlated with the inhibition of lipid synthesis. Taken together, the data strongly suggest that the inhibition of acyl-CoA synthetase by triacsins leads to the inhibition of lipid synthesis and eventually to the inhibition of proliferation of Raji cells.

Cell Division

Chemical properties and anti-complementary activities of heteroglycans from the leaves of Panax ginseng.

Four anti-complementary neutral (GL-NIa and GL-NIb) and acidic (GL-AIa and GL-AIb) polysaccharides were purified from the leaves of Panax ginseng C. A. Meyer. Only GL-NIa and GL-AIa exhibited potent anti-complementary activities at low concentrations probably through the alternative complement pathway. Glycosyl linkage analysis demonstrated that GL-NIa mainly consisted of arabinogalactan moieties, whereas GL-NIb contained large amounts of (1----4)-linked glucosyl residues. Beta-Elimination indicated that GL-AIa and GL-AIb were pectic polysaccharides consisting of a rhamnogalacturonan core with neutral side chains. GL-AIa reacted strongly with beta-glucosyl-Yariv antigen, GL-NIa reacted weakly, whereas GL-NIb and GL-AIb showed no reaction with the antigen.

Carbohydrate Sequence

Mode of complement activation by acidic heteroglycans from the leaves of Artemisia princeps PAMP.

The mode of action of the anti-complementary acidic heteroglycans, AAF-IIb-2 and IIb-3 which consisted of rhamnogalacturonan core and arabinogalactan moieties, purified from the leaves of Artemisia princeps PAMP (Japanese name = Gaiyo) were investigated. The anti-complementary activities of AAF-IIb-2 and IIb-3 were reduced partially in the absence of Ca2+ ions. A marked consumption of C4 was observed to have occurred when serum was incubated with both polysaccharides in the presence of Ca2+ ions. AAF-IIb-2 showed more potent C4 consumption than IIb-3. After the incubation of the serum with AAF-IIb-2 in the absence of Ca2+ ions, a cleavage of C3 in the serum was detected by immunoelectrophoresis. AAF-IIb-2 showed more significant consumption of the complement than IIb-3 when rabbit erythrocytes were used in the assay system in the absence of Ca2+ ions. These results indicate that AAF-IIb-2 activates the complement via both the alternative and classical pathways, whereas IIb-3 mainly activates the complement via the classical pathway. The absorption of serum with Protein A-Sepharose results in a decrease of the activity of AAF-IIb-2 and IIb-3. However, the decrease of the activity was restored by the replacement of the immunoglobulin G (IgG) fraction after its recovery from the Protein A-Sepharose. These results suggest that IgG dependent mechanisms are both involved in the anti-complementary activity of AAF-IIb-2 and IIb-3.

Complement Inactivator Proteins

A new enzymatic assay for evaluating the clearance of immune complexes from the circulation of mice.

A new photometric in vivo enzymatic immune complex clearance (EIC) assay was developed in a homologous system using glucose oxidase-anti-glucose oxidase complexes (GAG) as a model of immune complexes. Chromatographically purified GAG was injected into mouse tail veins and at intervals thereafter the enzyme activities of GAG remaining in the circulation were estimated. The GAG were cleared in a size dependent manner and were stable, being eluted as the same discrete peaks on HPLC size-exclusion chromatography both before and after injection into mice. The complement consuming activity of the GAG was weak, and depletion of complement components with cobra-venom factor did not alter clearance of the GAG from the circulation, whereas pretreatment of aggregated mouse gamma globulin suppressed the clearance rate. These results suggested that most of the GAG were not cleared via complement receptors but via FcR. Normal clearance rates were significantly changed by administration of immunomodulators such as carrageenan or LPS. Intravenous administration of GAG at a dose 50 times higher than normal caused no deaths suggesting that the complexes were of low toxicity. The enzymatic method presented should be of value for measuring the function of the mononuclear phagocytic system with respect to immune complex clearance. It provides a rapid and sensitive alternative assay which avoids using radioisotopes.

Adult

A new photometric microassay for the quantitation of macrophage Fc receptor function. In vitro enzyme-containing immune complexes clearance (EIC) assay.

A new photometric microassay for immune complex (IC) binding to macrophages was developed in a homologous system using glucose oxidase-anti-glucose oxidase complexes (GOAGO) as a model for IC clearance in vitro. Thioglycollate-elicited murine peritoneal cells were incubated with GOAGO solution and then cell-associated glucose oxidase activity was measured after the washing and solubilization of the cell membrane in a microtitre plate. GOAGO binding to macrophages was inhibited in the presence of either IgG or its Fc fragments in a dose-dependent manner, while yeast mannan or IgG Fab fragments had no effect. These results indicated that this binding occurred solely via the Fc receptors on the macrophages. The Fc receptors for GOAGO were eliminated by trypsin digestion of the cells. When the macrophages were cultured with LPS or TPA, GOAGO binding was enhanced compared to that of control, whereas carrageenan treatment suppressed GOAGO binding. The present results suggest that this assay may be of value in the measurement of IC clearance and for studying the expression of Fc receptors on macrophages.

Animals

Structural characterization and antitumor activity of a pectic polysaccharide from the roots of Angelica acutiloba.

The polysaccharide fraction from the root of Angelica acutiloba Kitagawa showed a potent antitumor activity against ascitic form of Sarcoma-180, IMC carcinoma, and Meth A fibrosarcoma as well as the solid form of MM-46 tumor. An active polysaccharide, AR-4E-2, was purified by precipitation with cetyl-trimethylammonium bromide, anion-exchange chromatography on DEAE-Sepharose, and gel filtration on Sepharose CL-4B from the polysaccharide fraction. An active polysaccharide fraction showed a weak anti-complementary activity. AR-4E-2 was composed of arabinose, galactose, and rhamnose in the molar ratios of 3.3:1.0:0.7, and also contained 14.5% galacturonic acid and 3.2% protein. Methylation analysis and base-catalysed beta-elimination studies suggested that AR-4E-2 contained a rhamnogalacturonan moiety in which 2,4-di-substituted rhamnose residues were attached to 4-substituted galacturonic acid through position 2 of rhamnose. AR-4E-2 also contained highly branched 3,5-arabinan and (1----4)-galactan.

Animals

Fractionation and characterization of mitogenic and anti-complementary active fractions from kampo (Japanese Herbal) medicine "juzen-taiho-to".

"Juzen-Taiho-To" (TJ-48), which is a kampo (Japanese herbal) medicine prepared by decocting a prescription of ten kinds of herbs, has several immunostimulating activities. In order to characterize the active substances for anti-complementary and mitogenic activities, TJ-48 was fractionated. Anti-complementary activity was observed in the water- and methanol-insoluble fraction (F-2) and the crude polysaccharide fraction (F-5), whereas mitogenic activity was only found in F-5. However, other low molecular mass fractions did not show both activities. Methylation analysis indicated that F-2 mainly contained amylopectin-like polysaccharides. Both Pronase digestion and periodate oxidation decreased the anti-complementary activity of F-2, and the beta-amylase-resistant fraction of F-2 still retained the potent anti-complementary activity. When F-5, which has the most potent of both activities, was further fractionated, only the major acidic polysaccharide fraction, F-5-2, showed potent mitogenic activity. Endo-alpha-(1----4)-polygalacturonase digestion showed that F-5-2 mainly contained pectic polysaccharides, and the endo-polygalacturonase treatment of F-5-2 reduced the mitogenic activity but not the anti-complementary activity. F-2 and F-5 each activated the complement system by a different mode of action.

Animals

Relationship between structure and activity of an anti-complementary arabinogalactan from the roots of Angelica acutiloba Kitagawa.

An anti-complementary arabinogalactan (AGIIb-1), isolated from the roots of Angelica acutiloba Kitagawa, comprised one neutral (N-I) and two acidic arabinogalactan (A-I and A-II) units and one neutral arabinan unit (N-II). N-I showed the most potent anti-complementary activity. AGIIb-1, A-I, and A-II had similar moderate activities, but N-II had weak activity. The product (AF-AGIIb-1) of digestion of AGIIb-1 with exo-alpha-L-arabinofuranosidase had markedly increased anti-complementary activity, as did that (AF-N-I) of N-I. Degradation of the rhamnogalacturonan core in AGIIb-1 slightly decreased the anti-complementary activity, whereas the high-molecular-weight neutral arabinogalactan and galacto-oligosaccharide side-chains in A-I and A-II showed potent activities. When AF-AGIIb-1 was digested with endo-arabinanase, the activity decreased slightly. Partial elimination of the (1--6)-beta-D-galactosyl side-chains from AF-N-I by digestion with exo-beta-D-galactosidase did not affect the activity. AGIIb-1 reacted weakly with the beta-D-glucosyl-Yariv antigen, but AF-AGIIb-1 and AF-N-1 had increased reactivity with the antigen. The anti-complementary activity of AGIIb-1 was expressed mainly through the classical pathway, whereas AF-AGIIb-1 and AF-N-I had markedly increased activity through the alterative pathway.

Animals

Relationship between structure and activity of the "ramified" region in anti-complementary pectic polysaccharides from Angelica acutiloba Kitagawa.

One of the anti-complementary pectic polysaccharides (AR-2IIa) isolated from the root of Angelica acutiloba Kitagawa gives the "ramified" region (PG-1a,rhamnogalacturonan with neutral side-chains) in addition to oligogalacturonides on digestion with endo-alpha-D-(1--4)-polygalacturonase. When the neutral side-chains in PG-1a were digested with both exo-alpha-L-arabinofuranosidase and exo-beta-D-galactosidase, approximately 70% of the arabinosyl chains and approximately 30% of the galactosyl chains were released. The resistant product E-PG-1a had the same anti-complementary activity as PG-1a. E-PG-1a gave long (d.p. greater than or equal to 5) and short (d.p. less than or equal to 4) neutral galactosyl chains after degradation of the GalA moiety by base-catalysed beta-elimination in the presence of sodium borodeuteride followed with lithium-mediated degradation. Methylation analysis showed that the long galactosyl chains consisted mainly of terminal, 6-linked and 3,6-disubstituted Gal, and that the short chains were rich in 6-linked Gal. Degradation of the GalA moieties in PG-1a markedly decreased the anti-complementary activity, but the long and short galactosyl chains still expressed approximately 50 and approximately 20%, respectively, of the anti-complementary activity of E-PG-1a.

Animals