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Biomedical subjects

S Pyo

Publications and source records attributed to S Pyo.

At least 19 recordsLinked to original sources
PubMed2001

Inhibition of gamma-irradiation induced adhesion molecules and NO production by alginate in human endothelial cells.

Inflammation is a frequent radiation-induced reaction following therapeutic irradiation. Treatment of human umbilical endothelial cells (HUVEC) with gamma-irradiation (gammaIR) induces the expression of adhesion proteins such as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. Since the upregulation of these proteins on endothelial cell surface has been known to be associated with inflammation, interfering with the expression of adhesion molecules is an important therapeutic target. In the present study, we demonstrate that high mannuronic acid-containing alginate (HMA) inhibits gammaIR induced expression of ICAM-1, VCAM-1, and E-selectin on HUVEC in a dose dependent manner. HMA also inhibited gammaIR induced production of Nitric oxide (NO). These data suggest that HMA has therapeutic potential for the treatment of various inflammatory disorder associated with an increase of endothelial leukocyte adhesion molecules.

Alginates↗
PubMed2001

Stimulation of various functions in murine peritoneal macrophages by high mannuronic acid-containing alginate (HMA) exposure in vivo.

High mannuronic acid-containing alginate (HMA) was tested to affect murine peritoneal macrophages. In the present study, we measured various functions of murine peritoneal macrophages that were isolated 20 h after intraperitoneal injection with HMA (25 and 100 mg/kg). HMA increased the number of peritoneal macrophages and phagocytosis. Macrophages from HMA-treated mice significantly inhibited growth of tumor cells compared to macrophages from control mice. In addition, supernatants from macrophages of HMA-treated mice contained nitric oxide (NO), hydrogen peroxide (H2O2) and TNF-alpha. The increased production of these cytotoxic molecules induced by HMA is consistent with tumoricidal activity of activated macrophages. Furthermore, HMA-induced tumoricidal activity was partially abrogated by anti-TNF-alpha, inhibitors of NO and the scavenger of reactive oxygen. Thus, the tumoricidal activity induced by HMA appeared to be mediated by the production of TNF-alpha, NO and H2O2. Taken together, these results suggest that HMA has the immunostimulating effect on macrophages after in vivo exposure of it.

Adjuvants, Immunologic↗
PubMed2001

Structure-borne noise reduction for an infinite, elastic cylindrical shell.

A theoretical model was developed to evaluate the reduction of structure-borne noise generated by an axially symmetric ring force which is applied on the interior of the cylindrical shell. The vibrating cylindrical shell is coated with a microvoided elastomer that is acoustically soft material designed for the reduction of the generated noise. The analytical model is a two-layer shell structure comprised of a cylindrical shell and an outer layer (coating) that is perfectly bonded to the cylindrical shell. The outer and inner surfaces of the coated shell are in contact with water and air, respectively. The analysis for this problem is based on the theory of elasticity, acoustic wave equations, and pertinent boundary conditions. Effects of various parameters such as coating thickness and material properties on the noise reductions are presented.

Journal Article↗
PubMed2001

Peroral immunization with Helicobacter pylori adhesin protein genetically linked to cholera toxin A2B subunits.

Helicobacter pylori is a major cause of gastric-associated diseases. To evaluate the efficacy of a possible vaccine antigen against H. pylori infection, the chimaeric construct adhesin--CTXA2B, derived from H. pylori adhesin genetically coupled to cholera toxin (CTX) subunits A2 and B (CTXA2B), was expressed in Escherichia coli as an insoluble recombinant chimaeric protein. The protein was then purified by denaturation, renaturation and size-exclusion chromatography. The composition of purified adhesin--CTXA2B was verified by SDS/PAGE and Western blotting with antibodies to antigenic components of adhesin and CTXB, and confirmed as a chimaeric protein with G(M1)-ganglioside binding activity and adhesin epitopes by a G(M1)-ELISA developed using antibodies to adhesin. Oral immunization of mice with adhesin--CTXA2B induced higher levels of mucosal IgA and serum IgG antibodies to H. pylori adhesin and to CTXB than in mice immunized with adhesin or CTXA2B alone. Adhesin--CTXA2B was also demonstrated to be a potential protective antigen in a mouse model of H. pylori infection. The immunization of mice with adhesin--CTXA2B protected 62.5% of mice infected with H. pylori SS1 strain, whereas adhesin immunization was not able to confer protection to mice. This protection may be correlated with high levels of mucosal IgA and serum IgG antibodies against H. pylori adhesin. Taken together, the results indicate that the genetically linked CTXA2B acts as a useful mucosal adjuvant, and that the adhesin-CTXA2B chimaeric protein could be a potential component in future H. pylori vaccine development.

Adhesins, Bacterial↗
PubMed2000

Alteration of kinase-mediated signalings in murine peritoneal macrophages by aflatoxin B(1).

Aflatoxin B(1) (AFB(1)) is a potent hepatocarcinogen which is thought to exhibit an impairment of specific and non-specific immunity. Macrophages are responsible for non-specific immunity in host defense against tumors and microorganisms, and release a number of cytotoxic compounds, including nitric oxide (NO). We investigate whether the effect of AFB(1) on signal transduction is related to the decrease of NO production in murine peritoneal macrophages. When macrophages were stimulated with lipopolysaccharide (LPS) after AFB(1)-pretreatment, AFB1 decreased the NO production. The percentage of NO production in AFB(1)-pretreated macrophages was inversely increased by the addition of cholera toxin, phorbol 12-myrisate 13-acetate (PMA) and ionomycin. This suggests that AFB(1) affects the function of signaling constituents, including guanine nucleotide-binding protein (G protein), protein kinase C (PKC) and the calcium ion. AFB(1)-pretreatment significantly decreased PKC activity and tyrosine phosphorylation after LPS-stimulation. Taken together, these data propose that the inhibition of LPS-stimulated NO production by AFB(1) is related to the suppression of kinase-mediated intracellular signal transduction in murine peritoneal macrophages.

Aflatoxin B1↗
PubMed2000

Aflatoxin B(1) inhibits CD14-mediated nitric oxide production in murine peritoneal macrophages.

Aflatoxin B(1) (AFB(1)), a potent hepatocarcinogen, has been known to impair non-specific and specific immunity. Macrophages play an important role in host defense against tumors and microorganisms and a number of compounds are implicated in macrophage cytotoxicity. Since activated by the reaction of LPS with CD14, macrophages produce nitric oxide (NO) that is a cytotoxic effector molecule in cell killing. In the present study, we investigated whether the alteration of CD14 level on macrophages by AFB(1) affects NO production in murine peritoneal macrophages. When macrophages were stimulated with LPS after AFB(1)-pretreatment, or they were co-treated with LPS and AFB(1), the NO production decreased in a dose-dependent manner. In contrast, when macrophages were post-treated with AFB(1) after LPS-stimulation, NO production was unchanged. DNA, RNA, and protein synthesis were reduced by AFB(1)-pretreatment of macrophages. The addition of anti-CD14 antibodies to the cultures decreased NO production further. FACS analysis showed that the binding of anti-CD14 antibodies to the macrophages was suppressed by AFB(1)-pretreatment followed by LPS-stimulation. However, AFB(1) does not alter the binding anti-CD14 antibodies to the macrophages without LPS-stimulation. In contrast, AFB(1) pretreatment increased an amount of CD14 released in culture medium. Taken together, these data indicate that the reduced NO production in murine peritoneal macrophages by AFB(1)-pretreatment is related to the suppressed expression of CD14 on macrophage membrane and to the increased secretion of it to culture medium after LPS-stimulation.

Aflatoxin B1↗
PubMed2000

Activation of murine peritoneal macrophages by Streptococcus pneumoniae type II capsular polysaccharide: involvement of CD14-dependent pathway.

In this study we examined the ability of capsular polysaccharide type 2 (PS) from Streptococcus pnemoniae to induce secretory and cellular responses in peritoneal macrophages. Tumour cytotoxicity induced by preincubation with PS was demonstrated to be concentration-dependent. PS-induced tumouricidal activity was partially abrogated by anti-tumour necrosis factor (TNF)-alpha and inhibitor of nitric oxide, whereas anti-interferon (IFN)-alpha/beta antibody and the scavengers of reactive oxygen intermediates had no effect. In addition, supernatants from macrophages treated with PS contained TNF-alpha, and their iNOS-enzymatic activity was significantly increased. Thus, the tumouricidal activity induced by PS appeared to be mediated by the production of TNF-alpha and nitrite. Treatment of macrophages with PS increased the expression of CD14, the receptor for lipolysaccharide (LPS)/LPS-binding protein. Moreover, blocking antibody to CD14 abrogated partially TNF-alpha and nitrite induction by PS, suggesting that the PS-induced CD14 upregulation was correlated with secretion of TNF-alpha and nitrite. Taken together, these results demonstrate that PS may induce macrophage-secretory and cellular activities, in part, possibly via CD14-dependent pathway.

Animals↗
PubMed1999

Antitumor activity of 4-phenyl-1-arylsulfonylimidazolidinone, DW2143.

We examined the ability of sulfonylurea derivative, DW2143 (4-phenyl-1-[1-(4-aminobenzoyl)-indoline-5-sulfonyl]-4,5-dihydro-2-imida zolone hydrochloride), to inhibit the growth of tumor cells in vitro and in vivo. When its anti-proliferative activities were tested on five murine tumor (B 16, Colon26, E1-4, 3LL and P388) and nine human tumor (BxPC-3, HepG2, Lovo, MCF-7, NCI-H69, SW480, WiDR, KB and KBV20C) cells of diverse tissue origins, the in vitro antitumor activities of DW2143 were comparable to those of doxorubicin against all tumor cell lines. In addition, the anti-proliferative activities of DW2143 against KBV20C, a vincristine-resistant cell line, are similar or superior to those of doxorubicin. When the in vivo antitumor activities using three murine tumor cells were tested after oral administration of DW2143, a wide range of tumor growth inhibition was observed. Tumor growth inhibition against 3LL at doses of 50 and 100 mg/kg DW2143 was 84.3% and 47.2%, respectively, which was comparable or superior to those of doxorubicin (5 mg/kg). Tumor growth inhibition of B16 at a dose of 100 mg/kg in the DW2143-treated group was 42% as compared to 54% for doxorubicin (5 mg/kg). When mice implanted with Colon26 were tested, tumor growth inhibition at a dose of 80 mg/kg DW2143 was 36% as compared with 37% for doxorubicin (5 mg/kg). Taken together, these results indicate that the novel sulfonylurea derivative, DW2143, is an attractive candidate for further development as a useful oral anticancer drug.

Animals↗
PubMed1999

In vitro suppressive effect of aflatoxin B1 on murine peritoneal macrophage functions.

We examined the immunosuppressive effects of aflatoxin B1 (AFB1), a toxic compound produced by the Aspergillus flavus, on murine peritoneal macrophages after in vitro pre-exposure. When thioglycollate-elicited macrophages pre-exposed to AFB1 were stimulated with lipopolysaccharide (LPS), antitumor activity induced by LPS was suppressed by 10 and 50 microM AFB1. In addition, the production of reactive intermediates including nitric oxide (NO), superoxide anion and hydrogen peroxide which have been known to be implicated in macrophage-mediated cytotoxicity, was decreased by AFB1 pretreatment in a dose-dependent manner. We also determined whether the macrophage-mediated cytokine production was altered by AFB1 in vitro pretreatment. AFB1 markedly inhibited TNF-alpha interleukin-1 (IL-1) and IL-6 production by LPS-stimulated macrophages. Taken together, these data indicate that AFB1 inhibits the killing ability of murine macrophages, decreases various secretory molecules in those cells and the macrophages would be one of many systems affected by AFB1.

Aflatoxin B1↗
PubMed1999

Involvement of NO, H2O2 and TNF-alpha in the reduced antitumor activity of murine peritoneal macrophages by aflatoxin B1.

Aflatoxin B, (AFB1), a potent hepatocarcinogen, has been known to impair non-specific and specific immune responses. Nitric oxide (NO), hydrogen peroxide (H2O2), superoxide anion (O2-) and tumor necrosis factor-alpha (TNF-alpha) produced by macrophages play an important role in host defense against tumors and microorganisms. In the present studies, we investigated the involvement of those products in the reduced antitumor activities by AFB1. When macrophages are stimulated with LPS after AFB1-pretreatment, the cytolytic activities decrease in a dose-dependent manner. The addition of N(G)-monomethyl arginine (NMMA), anti-TNF-alpha antibodies, catalase and peroxidase decreases antitumor activities further. In contrast, superoxide dismutase (SOD) does not change the antitumor activities. NO and TNF-alpha production was reduced by the addition of NMMA and anti-TNF-alpha antibodies, respectively. Taken together, these data indicate that the reduced antitumor activities in murine peritoneal macrophages are mediated by the suppressed production of NO, TNF-alpha and H2O2 by AFB1 pretreatment, suggesting that the inhibitory effect of AFB1 on those materials may provide the tumors with readily growing condition in vivo.

Aflatoxin B1↗
PubMed1999

Enhanced macrophage antitumor effects of protein A in combination with IFN-gamma.

In this study we examined the potential for the synergistic augmentation of the antitumor activity of inflammatory mouse peritoneal macrophages by stimulation with protein A combined with IFN-gamma. The moderate augmentative effect induced by preincubation with protein A was demonstrated to be concentration-dependent, whereas IFN-gamma had a very low activating effect. Following preincubation with both protein A and IFN-gamma, a marked enhancement of macrophage activity was noted. In addition, based on the utilization of neutralizing antibody to TNF-alpha or the inhibition of NO production, TNF-alpha and NO were proven to be involved as mediators during the activation of tumoricidal macrophages by protein A in combination with IFN-gamma. We also demonstrated that supernatants from macrophages treated with protein A plus IFN-gamma contained both TNF-alpha and NO at markedly increased levels. Thus, tumor cell lysis in the combined system was mediated via TNF-alpha or NO. These results demonstrate the synergistic effects on mouse peritoneal macrophage function of protein A in combination with IFN-gamma and suggest that combinations of such agents may serve as the basis for future in vivo immunotherapy.

Animals↗
PubMed1999

Inhibition of various functions in murine peritoneal macrophages by aflatoxin B1 exposure in vivo.

Aflatoxin B1 (AFB1) has been known to impair specific and nonspecific immunity. In the present study, we tested various functions of murine peritoneal macrophages that were isolated and stimulated with LPS after AFB1 (400 microg/5 ml/kg) was administered every other day for 2 weeks. AFB1 decreased phagocytosis and the production of superoxide anion (O2-) and hydrogen peroxide (H2O2), compared to those of corn oil-treated control group. In addition, the production of NO and TNF-alpha was decreased in macrophages of AFB1-treated mice. In vitro antitumor activity of in vivo AFB1-treated macrophages was reduced against target cell, L929. Taken together, these results suggested that AFBI might have the immunosuppressive effect on macrophages after in vivo exposure, which was related to the antitumor activity reduction.

Aflatoxin B1↗
PubMed1998

Aflatoxin B1-induced suppression of nitric oxide production in murine peritoneal macrophages.

Aflatoxin B1 (AFB1), a potent hepatocarcinogen, is known to impair specific and non-specific immune responses. AFB1 mainly decreases lymphocyte functions and may also affect macrophages assisting lymphocyte functions. Macrophages play an important role in a host defense against tumors and bacteria. Furthermore, some macrophage products, including nitric oxide (NO), may be involved in cytotoxicity. The effect of aflatoxin B1 (AFB1) was investigated on NO production from murine peritoneal macrophages. Macrophages were pretreated with AFB1 for 24 h and then stimulated with lipopolysaccharide (LPS) for 24 h. AFB1 at 10 or 50 microM reduced the production of NO. Compared to vehicle control, there was a greater reduction of NO production with increased AFB1 pretreatment and LPS stimulation. AFB1 at 10 or 50 microM decreased inducible nitric oxide synthase (iNOS) activity about 24% and 28%, respectively, after stimulation with 1 microg/ml LPS and about 12% and 24%, respectively, after stimulation with 10 microg/ml LPS. AFB1 pretreatment also decreased the synthesis of iNOS protein and the mRNA of macrophages. Taken together, these results suggest that AFB1 pretreatment reduces NO production from murine peritoneal macrophages stimulated by LPS, which is mediated by the reduction of iNOS activity, mRNA, and protein.

Aflatoxin B1↗
PubMed1998

Immunomodulating activity of DW-116, a new quinolone antibiotic.

DW-116, (1-(5-fluoro-2-pyridyl)-6-fluoro-7-(4-methyl-1-piperazinyl)-1, 4-dihydro-4-oxoquinoline-3-carboxylic acid hydrochloride), is a new quinolone antibiotic with a broad antibacterial spectrum against G(+) and G(-) bacteria. DW-116 was evaluated for the immunomodulating activities, which is one of the efforts to investigate the mechanism of action related to the good in vivo antibacterial efficacy. The results of in vitro studies revealed there was no statistically significant increase in B and T lymphocyte proliferation. But the results of in vivo studies showed that the number of plaque forming cells (PFC), the amount of polyclonal antibodies and delayed-type hypersensitivity (DTH) were significantly increased after the repeat administration with 12 and 60 mg/kg of DW-116. Taken together, these results proposed that immunostimulating effect of DW-116 could be one of the action mechanisms for demonstrating in vivo antibacterial activities under these experimental conditions.

Adjuvants, Immunologic↗
PubMed1995

Protease footprinting reveals a surface on transcription factor TFIIB that serves as an interface for activators and coactivators.

Transcriptional stimulation by the model activator GAL4-VP16 (a chimeric protein consisting of the DNA-binding domain of the yeast activator GAL4 and the acidic activation domain of the herpes simplex virus protein VP16) involves a series of poorly understood protein-protein interactions between the VP16 activation domain and components of the RNA polymerase II general transcription machinery. One of these interactions is the VP16-mediated binding and recruitment of transcription factor TFIIB. However, TATA box-binding protein (TBP)-associated factors (TAFs), or coactivators, are required for this interaction to culminate in productive transcription complex assembly, and one such TAF, Drosophila TAF40, reportedly forms a ternary complex with VP16 and TFIIB. Due to TFIIB's central role in gene activation, we sought to directly visualize the surfaces of this protein that mediate formation of the ternary complex. We developed an approach called protease footprinting in which the broad-specificity proteases chymotrypsin and alkaline protease were used to probe binding of 32P-end-labeled TFIIB to GAL4-VP16 or TAF40. Analysis of the cleavage products revealed two regions of TFIIB protected by VP16 from protease attack, one of which overlapped with a region protected by TAF40. The close proximity of the VP16 and TAF40 binding sites on the surface of TFIIB suggests that this region could act as a regulatory interface mediating the effects of activators and coactivators on transcription complex assembly.

Amino Acid Sequence↗
PubMed1994

The mechanism of poly I:C-induced antiviral activity in peritoneal macrophage.

Macrophages play an important role in defense against virus infection by intrinsic resistance and by extrinsic resistance. Since interferon-induced enzymes which are 2'-5' oligoadenylate synthetase and P1/eIF-2 protein kinase have been shown to be involved in the inhibition of viral replication, I examined the mechanism by which poly I:C, an interferon inducer, exerts its antiviral effects in inflammatory macrophages infected with herpes simplex virus type 1 (HSV-1). The data presented here demonstrate that poly I:C-induced antiviral activity is partially due to the activation of 2'-5' oligoadenylate synthetase. The activation of 2'-5' oligoadenylate A synthetase by poly I:C is also at least partly mediated via the production of interferon-beta. Taken together, these data indicate that interferon-beta produced in response to poly I:C acts in an autocrine manner to activate the 2'-5' oligoadenylate synthetase and to induce resistance to HSV-1.

2',5'-Oligoadenylate Synthetase↗
PubMed1994

Levels of viral glycoprotein reflect enhanced effectiveness of combined drug treatments.

A chemosensitivity assay with small replicate Mm5mt/cl C3H mammary tumor cell cultures was developed to determine whether changes in viral antigen expression and release into culture fluids could be utilized as an in vitro measure of single and combined drug effect. The measurement of drug concentrations required for identical 50% reductions in viral antigen levels (ED50s) allowed the dosage-dependence of the same drug to be compared alone and in combination drug treatments. The 52,000 MW viral envelope glycoprotein (gp52) of the mouse mammary tumor virus (MMTV) was measured in culture fluids of control and drug-treated cultures while cell density was simultaneously determined by cell staining and OD 664 mu determination. While extracellular gp52 levels and cell density increased over 72 hours in control cultures, dose-dependent declines in both parameters provided dual measures of effect for combination CAF treatment [cyclophosphamide: doxorubicin (Adriamycin): 5-fluorouracil], combination CMF treatment [cyclophosphamide: methotrexate: 5-fluorouracil] and single component treatments of these combinations. Comparison of ED50s for gp52 reduction revealed that each drug's ED50 concentration was lower in combination treatment than it was in single treatment. In combined drug treatments, the ED50 of doxorubicin was lowered from 5.17 microM to 0.36 microM, that of 5-fluorouracil was lowered from 0.69 microM to 0.22 microM and that of methotrexate was lowered from 15 nM to 1.65 nM. Reductions of ED50 in combined drug treatments argued for drug synergisms in these combinations. When drug concentrations, rather than gp52 reductions, were fixed at identical levels in single and combined treatments, additional declines in gp52 levels reflected the enhanced effects of CAF and CMF combinations over single drug treatments. When the anti-estrogen, tamoxifen, was added to CAF and CMF treatments, further declines in gp52 levels (below CAF and CMF levels) reflected the fact that these hormone-augmented treatments were more effective than either hormone or combination chemotherapy alone. These results indicate that decreases in extracellular levels of MMTV gp52 can be utilized in this in vitro assay as an alternative measure of chemotherapeutic effect for evaluating the synergistic or antagonistic nature of drug or hormone interactions and as a tool for in vitro optimization of combined drug effect.

Adenocarcinoma↗