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Biomedical subjects

M Toyoda

Publications and source records attributed to M Toyoda.

At least 91 records · Page 5Linked to original sources
PubMed2000

The emetic and anti-emetic effects of the capsaicin analogue resiniferatoxin in Suncus murinus, the house musk shrew.

1. In SUNCUS: murinus the ultrapotent capsaicin analogue resiniferatoxin (RTX) induced an emetic response in the dose range 1 - 1000 microg kg(-1), s.c. The latency was inversely related to dose and ranged from 41.2+/-4.4 min. (1 microg kg(-1), s.c.) to 2.7+/-0.6 min. (1000 microg kg(-1), s.c.). 2. The emetic response to RTX (10 or 100 microg kg(-1), s.c.) was blocked or markedly reduced by pre-treatment with RTX (100 microg kg(-1), s.c.), 8-OH-DPAT (100 microg kg(-1), s.c.), morphine (2 mg kg(-1), s.c.), neonatal capsaicin (100 mg kg(-1), s.c.) and the NK(1) receptor antagonist CP-99,994 (10 - 20 mg kg(-1), s.c.) but not by the 5-HT(3) receptor antagonist tropisetron (200 microg kg(-1), s.c.). 3. RTX (100 microg kg(-1), s.c.) induced c-fos-like immunoreactivity in the area postrema and parts of the nucleus tractus solitarius. This pattern is consistent with the proposal that the emetic effect is mediated via one or both of these structures and an involvement of substance P is discussed. 4. RTX (10 and 100 microg kg(-1), s.c.) had broad-spectrum antiemetic effects in Suncus as indicated by its ability to block or markedly reduce the emetic response to motion (1 Hz, 4 cm lateral, 10 min.), cisplatin (20 mg kg(-1), i.p.), intragastric copper sulphate (40 mg kg(-1), p.o.), nicotine (10 mg kg(-1), s.c.) and RTX (100 microg kg(-1), s.c.) itself. 5. It is proposed that the site of the anti-emetic effect is in the nucleus tractus solitarius and mechanisms involving the modulation of substance P release are discussed. 6. The general utility of SUNCUS: for investigations of vanilloid receptors is reviewed in the light of the exquisite sensitivity of the emetic reflex in this species to resiniferatoxin.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2000

Asymmetry of masticatory muscle activity during the closing phase of mastication.

The purpose of this study was to investigate the asymmetry of masticatory muscle activity between working and nonworking sides in the closing phase during mastication. Fifty adult subjects displaying normal oral function and occlusion participated in this study. Electromyographic (EMG) activity of the anterior temporalis and the superficial masseter muscle were recorded during mastication, simultaneously with motion data of the mandible. EMG activities of elevator muscles and their Asymmetry Index (AI) were analyzed depending on the vertical deviation of the lower incisal point with a two mm gap from the intercuspal position (ICP). EMG activities of both the anterior temporalis and the masseter on the working side were significantly greater than those on the nonworking side. Masseter muscles tended to show greater AI than the anterior temporalis muscles. Thus, asymmetry of the elevator muscles during mastication was a common finding in normal subjects. The normal range of variability of EMG activity and AI was confirmed in each section.

Adult↗
PubMed2000

Prognostic significance of p27(kip1) protein expression and spontaneous apoptosis in patients with colorectal adenocarcinomas.

Tumor cell apoptosis, proliferation and p27 expression using an in situ apoptosis detection kit, anti-Ki67 antibody and anti-p27 antibody were investigated in 171 colorectal adenocarcinoma specimens, together with the assessment of mutated p53 expression. No apparent association was observed among p27 expression, mutated p53 accumulation, the Ki67 labeling index and the apoptotic index (AI). In the multivariate analysis using the median values as the cut-off points (46.8% for p27 expression and 0.89% for AI), p27 expression was identified as an independent and significant predictor for overall survival. When the present series of patients were dichotomized by these cut-off points to categorize the cases into 4 subgroups, the patients in the group with low p27 expression and a low AI had the poorest prognosis. The assessment of p27 expression and AI therefore may prove valuable in identifying patients with colorectal adenocarcinoma who may have a poor prognosis.

Adenocarcinoma↗
PubMed2000

Antiallergic effect of apple polyphenols on the allergic model mouse.

We studied here the antiallergic effect of apple condensed tannins (ACT) administered orally to a type I allergy model mouse transplanted with an IgEL a2 hybridoma secreting anti-2,4,6-trinitrophenyl (TNP) immunoglobulin E (IgE). The oral administration of ACT significantly inhibited the ear swelling responses at 1 h after antigen-stimulation with picryl chloride. The response was dose dependent within 0.1 to 10 mg/mouse. The inhibition of the ear swelling response reached the maximal level (90% inhibition) when ACT was administered 2 h before the antigen challenge. These findings suggest that ACT has an antiallergic effect on type I allergic symptoms.

Animals↗
PubMed2000

Capability for identification of gamma-irradiated bovine liver by new high sensitivity comet assay.

DNA in food will sustain damage by gamma radiation. The detection capability of the high sensitivity comet assay was studied using fluorescence-microscopy. Beef liver was irradiated at a range of 1 Gy to 8 kGy. Single cells were obtained from the irradiated liver, then analyzed by agaros-gel electrophoresis. The pH of the buffer for electrophoresis was pH 13, which is generally utilized for sensitive detection of DNA damage. The pattern formed by DNA was visualized by staining with ethidium bromide. The resulting comets were evaluated with a scale we developed, and Influence Scores were calculated based on the Tice method. It is possible to detect irradiation damage to beef liver at 10 Gy. Together with Influence Score, histogram of comet type is used for detection of irradiation. We elucidated those histograms were useful for distinguishing damage caused by irradiation from that of others. DNA damage can be caused not only by irradiation, but also by the other treatments. Therefore, the respective influences of freezing, preservation, irradiating temperature, atmosphere of irradiation, cooking, and homogenizing devices were also examined. This new comet assay will be a useful method of detecting DNA damage to identify irradiated foods.

Animals↗
PubMed2000

Differential expression of the chemokine receptors by the Th1- and Th2-type effector populations within circulating CD4+ T cells.

The in vitro studies have proposed that human Th1 cells favor expression of CXCR3 or CCR5, whereas Th2 cells favor CCR3 and CCR4. In this study, the in vivo relevance of expression of these chemokine receptors on Th cells was investigated in patients with atopic dermatitis (AD) as the Th2-dominated disorder and nonatopic normal individuals. Flow-cytometric analysis using monoclonal antibodies against CXCR3, CCR5, CCR3, and CCR4 disclosed that a substantial proportion of memory (CD45RO+) CD4+ T cells in the blood of AD and normal patients expressed CXCR3, CCR5, or CCR4, but expression of CCR3 on these cells was negligible. Stimulation studies combined with intracellular cytokine staining revealed that the cells capable of producing Th2 cytokines, such as interleukin-4 (IL-4), IL-5, and IL-13, were restricted to the CCR4-expressing population within memory CD4+ T cells. Concerning Th1 cytokine production, interferon-gamma (IFN-gamma)-producing cells resided exclusively in CXCR3-expressing memory CD4+ T cells, although IFN-gamma production was found in both memory CD4+ T cells with and without CCR5 expression. We observed that CCR4-expressing memory CD4+ T cells in the blood were more increased in AD patients as compared with normal patients, whereas CXCR3-expressing memory CD4+ T cells were present in a lower frequency in AD than seen in normal patients. These results suggest that CXCR3 and CCR4, but not CCR5 or CCR3, appear to serve as the useful markers for identification of circulating Th1 and Th2 effector populations.

Adult↗
PubMed1999

Immunological characterization of anti-endothelial cell antibodies induced by cytomegalovirus infection.

BACKGROUND: We have previously shown that the levels of anti-endothelial cell antibodies (AECA) determined by an enzyme immunoassay are elevated during cytomegalovirus (CMV) infection in cardiac and renal transplant recipients. In a separate study, high levels of AECA are associated with higher frequency of humoral allograft rejection (AR), chronic AR and lower 2 year allograft survival in cardiac transplant recipients. These results suggests that high levels of AECA produced during CMV infection may have a pathogenic role or be a risk factor for humoral AR, chronic AR and decreased allograft survival. Here we examined the reactivity of AECA against endothelial cells and other tissues to further characterize AECA induced by CMV infection. METHODS: Sodium dodecyl sulfate-polyacrylamide gel electrophoresis/Western blot analysis was performed. RESULTS: The number and intensity of bands reactive with human umbilical vein ECs (HUVECs) increased during and after CMV infection. AECA(+) plasma reacted with multiple antigens expressed not only on endothelial cells but also on human fibroblasts, keratinocytes, platelets (PLs), peripheral blood mononuclear cells (PBMCs), Raji cells and THP-1 cells. Each individual's AECA(+) plasma showed different patterns of reactivity against these cells, whereas each plasma showed similar patterns of reactivity against ECs, PLs or peripheral blood mononuclear cells obtained from different individuals. AECA(+) plasma also showed a similar pattern of reactivity against HUVECs pretreated with/without interferon-gamma/tumor necrosis factor-alpha. The reactivity of preabsorbed sera with PLs significantly decreased against most reactive antigens expressed on PLs and other cell types. CONCLUSIONS: (1) Antibodies induced by CMV infection are not specific to endothelial cells and appear to react with multiple cell types, (2) AECA (+) plasma react with multiple antigens expressed on various cell types that are primarily constitutively expressed on these cells and are not individual specific, (3) CMV-induced antibodies in AECA (+) plasma are primarily autoantibodies. These results suggest that the elevated AECA levels seen in CMV-infected transplant recipients may represent a polyclonal activation of humoral immune responses induced by CMV, which is of uncertain pathogenic significance.

Autoantibodies↗
PubMed1999

Prolongation of skin allograft survival is associated with reduced Th1 cytokine responses in the WKY-->F344 rat model.

BACKGROUND: We have reported previously that F344 rats develop a spontaneous tolerance to WKY lung allografts and show long-term retention of donor-specific skin grafts placed 35 days after lung transplantation. In this study, we investigated the immunologic mechanisms that may be responsible for the prolonged skin graft survival in animals tolerized with lung allografts. METHODS: In the rejection group, WKY skin grafts were placed on normal F344 rats, whereas, in the tolerance group, the skin grafts were placed on F344 rats that had received a WKY lung transplant 35 days before skin grafting. Th1 (interleukin [IL]-2 and interferon-gamma [IFN-gamma]) and Th2 (IL-4 and IL-10) cytokine as well as transforming growth factor-beta1 mRNA expression in skin grafts and in draining lymph nodes were determined by reverse transcription-polymerase chain reaction. Macrophage and lymphocyte infiltration in skin grafts and the number of Langerhans cells in epidermal sheets of the grafts were examined by immunohistochemistry. RESULTS: IL-2 and IFN-gamma mRNA expression was significantly decreased in both the skin grafts and the draining lymph nodes of the tolerance group, compared to the rejection group, whereas IL-10 and transforming growth factor-beta1 mRNA expression was similar in both groups and IL-4 mRNA was rarely detected. Decreased and delayed CD8+, macrophage, and natural killer cell infiltration in the skin grafts from the tolerance group was also detected. Similar reduction in the number of Langerhans cells in the epidermis of the grafts from both groups was seen on day 1 after skin grafting, and thereafter the number remained stable in both groups. CONCLUSIONS: Reduced expression of Th1 cytokines and decreased infiltration of CD8+ cells, macrophages, and natural killer cells in the skin grafts may be responsible for prolongation of skin graft survival in the tolerance group.

Animals↗
PubMed1999

Impact of the expression of cyclin-dependent kinase inhibitor p27Kip1 and apoptosis in tumor cells on the overall survival of patients with non-early stage gastric carcinoma.

BACKGROUND: The expression of p27Kip1 and apoptosis have been implicated in tumor aggressiveness and proved to be prognostic predictors for several human malignancies. In this study, the authors sought to investigate the expression of p27Kip1 and apoptosis and their potential significance in determining the prognosis of patients with non-early stage gastric carcinoma. METHODS: Primary gastric tumor specimens from 225 patients were investigated by immunohistochemistry with anti-p27Kip1 and anti-Ki-67 antibodies, and their apoptotic indices were determined with the use of an Apop-Tag in situ detection kit. RESULTS: The median p27Kip1 labeling index (LI) was 48.4%. There was a significant association between the p27 LIs and the apoptotic indices (Als). However, there was no association between the p27 LIs and the Ki-67 LIs. p27 LI was demonstrated to be one of the most significant and independent prognostic factors in multivariate analysis. Although AI was found to be prognostically significant in univariate analysis, it failed to retain an independent and significant value regarding overall survival in multivariate analysis. CONCLUSIONS: Decreased expression of p27Kip1 and reduction of apoptotic potential were two of the most important factors in predicting a poor prognosis for patients with non-early stage gastric carcinoma. These findings support the hypothesis that decreased p27Kip1 expression, which may reflect a decreased rate of apoptosis, is closely related to the aggressiveness of gastric carcinoma. Therefore, the assessment of p27Kip1 expression and apoptotic potential may prove valuable in identifying patients with gastric carcinoma who are at high risk for recurrence and would benefit from adjuvant therapy.

Adenocarcinoma↗
PubMed1999

Expression of interleukin-2 receptor alpha and CD45RO antigen on T lymphocytes cultured with rubella virus antigen, compared with humoral immunity in rubella vaccinees.

We studied the expression of interleukin-2 receptor alpha (CD25)+ CD45RO+ CD4+ T lymphocytes (T-cell activation) in response to the rubella virus (RV) antigen (Matsuura strain, Biken, Osaka, Japan) using three-color-staining flow cytometry. The subjects were 48 healthy children (3-14 years old, 31 boys and 17 girls), who had received either monovalent vaccine (n = 5; mean age, 13.2 years) or measles-mumps-rubella (MMR) vaccine (n = 21; mean age, 10.5 years), had been naturally infected (n = 5; mean age, 11.4 years), or had been neither vaccinated nor naturally infected (n = 17; mean age, 10.0 years) and 62 healthy adolescents and adults (15-37 years old; 19 males and 43 females), who had received monovalent vaccine (n = 26, mean age, 27.4 years), had been naturally infected (n = 8; mean age, 24.0 years), or had been neither vaccinated nor naturally infected (n = 8; mean age, 16.5 years). Ninety-four of 110 subjects had HI titers > or = 1:16. T-cell activation in these subjects was significantly higher than that in 6 seronegative (HI titers < 1:8) subjects (p < 0.05). T-cell activation did not differ significantly with the history of exposure to RV. HI antibody titers > or = 1:16 and T-cell activation persisted in vaccinated subjects for > or = 20 years and was similar to those in naturally infected subjects. Our results suggest that cell-mediated immunity and humoral immunity persist for at least 20 years after vaccination.

Adolescent↗
PubMed1999

Expression of interleukin-2 (IL-2) receptor alpha and CD45RO antigen on T-lymphocytes cultured with measles virus antigens, compared with humoral immunity in measles vaccinees.

In response to two types of measles virus (MV) antigens, a vaccine strain CAM and a wild strain isolated in 1994, the expression of IL-2 receptor alpha (CD25)(+)CD45RO(+)CD4(+) T-lymphocytes (T-cell activation) was analyzed by flow cytometry. In 75 healthy subjects with measles hemagglutination inhibition tests > or =1:16, the percentage of T-cell activation was significantly increased compared with that in seronegative individuals (p) < 0.05). Moreover, the T-cell expression was not significantly different among the vaccinated (n = 38), the naturally infected (n = 28) and the subclinically infected (exposed with wild type without history of measles infection and HI titers > or =1:16) (n = 10) groups. T-cell activation stimulated with MV antigens and HI antibody titers persisted for almost 30 years in the vaccinated group. These results suggest that cell-mediated immunity persists for long periods after vaccination and does not be influenced by antigenic drift.

Adolescent↗
PubMed1999

Antithrombin III treatment improves parameters of acute inflammation in a highly histoincompatible model of rat lung allograft rejection.

BACKGROUND: Antithrombin III (AT-III) is an antithrombotic agent with known anti-inflammatory properties that is also known to attenuate acute inflammation, prevent ischemia-reperfusion injury, and disseminated intravascular coagulation (DIC) associated with sepsis and endotoxemia. Here, we examined the ability of AT-III to modify parameters of acute inflammation in a highly histoincompatible model of rat lung allograft rejection (AR). METHODS: After left single lung transplantations (BN-->Lew), recipient animals were treated i.v. with 50 U/kg of human AT-III (low dose group), 500 U/kg of human AT-III (high dose group), or normal saline (control group) on days 2 and 4 posttransplant. All animals were sacrificed on day 6, and several pathological categories of acute inflammation related to AR were scored (0-4). The effect of AT-III on concanavalin A (Con A)-stimulated rat spleen cell proliferation was also examined. RESULTS: The stage of AR, and the degrees of edema, hemorrhage, and necrosis were significantly reduced in the high dose group compared with the control group. AT-III significantly inhibited rat spleen cell proliferation in response to Con A, in a dose-dependent manner. Maximal inhibition was seen at 15 U/ml in culture. Identical inhibition of Con-A-stimulated cultures occurred in both serum free and serum-containing media, indicating that AT-III inhibition of Con-A-stimulated rat spleen cell proliferation is independent of its actions on thrombin. CONCLUSIONS: 1) AT-III treatment significantly improves parameters of acute inflammation seen in a highly histoincompatible model of rat lung AR. 2) AT-III inhibits in vitro T cell proliferation to the potent mitogen Con A, suggesting that protease inhibition may inhibit T cell activation in vitro. 3). The beneficial effects of AT-III on parameters of lung AR relate to the anti-coagulant, anti-inflammatory, and possibly immunoregulatory actions of AT-III.

Acute Disease↗
PubMed1999

The clinical significance of antibodies to human vascular endothelial cells after cardiac transplantation.

BACKGROUND: Vascular endothelial cells are primary targets for injury during both cellular and humoral allograft rejection (AR). In cardiac transplantation, the role of humoral immunity in mediating AR has not been extensively characterized. METHODS: Antibodies against human vascular endothelial cells (AECA) were measured using a cellular ELISA developed from human umbilical vein endothelial cells in 80 consecutive patients after cardiac transplantation. The aim was to determine the incidence of AECA formation after transplantation and their association with different types of AR, graft survival, and development of cardiac allograft vasculopathy (CAV). At least eight serum samples obtained from each patient were examined for AECA and an endomyocardial biopsy was performed at regular intervals during the first year after transplantation. RESULTS: Of the 80 patients examined, 31 were AECA (+) and 49 patients were AECA (-). There were no significant differences between the AECA (+) and (-) groups when examined for age, sex, and pretransplantation ischemia time. A significant correlation was found between the presence of AECA and humoral AR (P<0.015). AECA positivity did not correlate with the presence of cellular AR or the number of rejection episodes. In addition, allograft survival at 2 years after transplantation was significantly better in the AECA (-) group compared with that in the AECA (+) group (89.8% vs. 71.0%, P<0.0004). The persistence of AECA positivity during the first year after transplantation was also associated with a significantly greater incidence of CAV when compared with the patients who were AECA (-) (25.8% vs. 14.3%, P<0.004). CONCLUSIONS: AECA may be important in the mediation of humoral AR, may decrease allograft survival, and may identify a high-risk group for CAV.

Adolescent↗
PubMed1999

Mechanistic studies of catechins as antioxidants against radical oxidation.

The antioxidative mechanisms of catechins were studied by investigating products generated at the first stages by 2, 2'-azobis(2-aminopropane)hydrochloride (AAPH)-induced radical oxidation, without any isolation, using LC/MS, spectrophotometry, and PM3 semiempirical molecular orbital (MO) calculations. Catechins were quite effective in scavenging peroxyl radicals in a liposomal system and in an aqueous system except for (-)-epigallocatechin (EGC). EGC was the least effective among four catechins tested. From the results of LC/MS and spectroscopic studies, (-)-epicatechin (EC) would be gently converted to an anthocyanin-like compound. According to the mechanisms, the compound produced from EC by radical oxidation can also function as an antioxidant. As a result, EC has a longer inhibition period (tinh = 9360 s). On the other hand, EGC decreased shortly after oxidation (tinh = 3420 s) and was transformed to a quinone-like compound. The addition of superoxide dismutase (SOD) reduced the chemiluminescence from EGC during oxidation. Active oxygen including superoxide anion radicals (O-2) may be produced in the case of EGC, but not in the case of EC. However, EGC has a more rapid scavenging effect on peroxyl radicals (kinh/kp = 232) than EC (kinh/kp = 41). The calculated C-H bond dissociation enthalpies (BDEs) for catechins at the C-2 position were unexpectedly low (65 kcal/mol) compared to O-H BDEs at phenolic sites (70 kcal/mol), suggesting that hydrogen at the C-2 position may be abstracted by free radicals. The authors propose the tentative antioxidative mechanisms of catechins depending on the experimental results and theoretical calculations.

Amidines↗
PubMed1999

Involvement of VEGF and its receptors in ascites tumor formation.

Vascular endothelial growth factor (VEGF) has potent endothelial cell mitotic and vascular permeability activity. Several reports have suggested that VEGF may be one of the major factors regulating ascites formation, although no quantitative and systematic analyses have been carried out. To determine the role of VEGF in ascites formation, we examined the expression of VEGF in 13 mouse ascites tumors (5 sarcomas, 3 carcinomas, and 5 hematopoietic malignancies). We found that significant amounts (6-850 ng/mL) of biologically active VEGF accumulated in the ascites fluid of all 13 tumors, particularly in tumors of sarcoma and carcinoma origin (430 +/- 234 ng/mL). The microvessel densities in the peritoneal walls of tumor-bearing mice, which are significantly higher than those in healthy mice, basically correlated with but did not parallel VEGF concentrations, suggesting the existence of an additional modulator(s) of the angiogenic process. Administration of anti-mouse VEGF-neutralizing antibody to mice bearing the carcinoma-derived ascites tumor MM2 suppressed ascites accumulation, tumor growth, and tendency to bleed. These results directly demonstrate the crucial role of VEGF in carcinoma-derived ascites tumor formation in vivo.

Animals↗
PubMed1999

Increased activity and expression of MAP kinase in HCC model rats induced by 3'-methyl-4-dimethylamino-azobenzene.

BACKGROUND/AIMS: The ras-mitogen-activated protein kinase (MAPK) cascade plays an important role not only in the mitogenic signal transduction pathway but also in the development of cancer, and it is believed to be one of the important regulators in normal hepatocytes and hepatocellular carcinoma. The aim of this study was to determine the role of insulin receptor substrate-1 and the MAPK cascade in rats with hepatocellular carcinoma induced by 3'-methyl-4-dimethylamino-azobenzene (3'-MeDAB). METHODS: Liver cancer was induced in rats by feeding 3'-MeDAB, and the changes in expression of IRS-1 and MAPK were analyzed in tumorous, non-tumorous and control liver. RESULTS: Expression of insulin receptor substrate-1 (IRS-1) showed a 1.4-fold increase at protein level in the tumors (p<0.01), but the tyrosine phosphorylation of IRS-1 did not differ between the tumor and control liver. Expression of MAPK and its activity were elevated 4.5-7.5-fold (p<0.01) and 4.6-fold (p<0.01) in the tumor compared with control liver. In non-tumorous lesions from rats fed with 3'-MeDAB, expression of MAPK, but not IRS-1, increased significantly (p<0.01). Between tumorous and adjacent non-tumorous lesions, there was a significant difference in MAPK expression (p<0.05) and activities (p<0.05). CONCLUSIONS: The increased expression of MAPK may play an important role in the progression or initiation of HCC in this rat model.

Animals↗