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Biomedical subjects

H Takada

Publications and source records attributed to H Takada.

At least 19 recordsLinked to original sources

Micrococcus luteus cells and cell walls induce anaphylactoid reactions accompanied by early death and serum cytokines in mice primed with muramyl dipeptide.

Micrococcus luteus strains at a dose of 500 microg of whole cells caused anaphylactoid reactions leading to death in some instances within 1 h in C3H/HeN mice primed with muramyl dipeptide (MDP, 100 microg). Tumor necrosis factor (TNF) and interleukin-6 (IL-6) were induced in the serum of half and of all the surviving mice, respectively. Cell wall specimens of M. luteus so far examined also caused anaphylactoid reactions accompanied by early death and one strain induced high levels of TNF and IL-6. Cytoplasmic membranes also induced IL-6. Essentially similar results were obtained with representative M. luteus cells and a cell wall specimen in MDP-primed C3H/HeJ mice. These results indicate that M. luteus has virulence activities that are associated with the induction of septic shock and systemic inflammatory diseases.

Acetylmuramyl-Alanyl-Isoglutamine

Theiler's murine encephalomyelitis virus subgroup strain-specific infection in a murine macrophage-like cell line.

We compared infection of a murine macrophage-like cell line, J774-1, with two Theiler's murine encephalomyelitis virus subgroup strains. The GDVII strain, which is highly virulent and produces acute polioencephalomyelitis in mice, did not actively replicate in J774-1 cells, although there was a significant inhibition in cellular protein synthesis. In contrast, the DA strain, which is less virulent and causes demyelination with a persistent virus infection, productively infected J774-1 cells; however, there was less virus produced than in BHK-21 cells, and there was little if any cellular protein shutoff. These in vitro data may provide some explanation for the biological activities that are observed between both subgroup strains.

Actins

Captopril suppresses interstitial fibrin deposition in coxsackievirus B3 myocarditis.

The effects of captopril on murine coxsackievirus B3 (CB3) myocarditis were investigated, with focus on interstitial fibrin deposition and changes in the connective tissue matrix. Captopril was administered intraperitoneally at a dose of 0.1 mg/g to CB3-infected mice daily on days 10-30 in experiment I (inflammatory phase) and on days 30-60 in experiment II (fibrotic phase). In experiment I, mouse survival was higher in the captopril-treated group than in the untreated group. Histological improvement, including prevention of extravasated fibrin deposition, maintenance of connective tissue architecture, suppression of myocyte hypertrophy, and prevention of myosin isoform shift from alpha to beta, was observed in captopril-treated mice in experiment I, but not in experiment II; in experiment II, captopril administration suppressed thickening of the interstitial reticulin fibers. Captopril inhibited inflammatory fibrin deposition, postmyocarditic myocyte hypertrophy, and ventricular remodeling during the inflammatory phase, but not during the fibrotic phase, of CB3 myocarditis in mice.

Animals

Nitric oxide and murine coxsackievirus B3 myocarditis: aggravation of myocarditis by inhibition of nitric oxide synthase.

OBJECTIVES: This study sought to investigate the effects of nitric oxide inhibition in a murine model of coxsackievirus B3 myocarditis. BACKGROUND: Little is known about the contribution of nitric oxide to the pathophysiology of myocarditis. METHODS: Antiviral activity was tested in vitro using nitric oxide inhibition by treatment with activated macrophages of NG-nitro-L-arginine methyl ester. In the in vivo experiments, NG-nitro-L-arginine methyl ester and NG-nitro-D-arginine methyl ester (both at 100 micrograms/ml) were administered to C3H/He mice early (days 0 to 14) and late (days 14 to 35) after infection with coxsackievirus B3. RESULTS: In the in vitro experiments with interferon-gamma- and lipopolysaccharide-induced activated murine macrophages, treatment with the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester, but not its inactive enantiomer NG-nitro-D-arginine methyl ester, restored coxsackievirus B3 titers. In the in vivo experiments in the early treatment group, myocardial virus titers were higher in NG-nitro-L-arginine methyl ester-treated than infected untreated animals, and both inflammatory cell infiltration and necrosis were more severe. In the late treatment group, more severe necrosis and more dense myocardial and perivascular fibrosis were observed in NG-nitro-L-arginine methyl ester-treated than in infected untreated animals. NG-Nitro-D-arginine methyl ester administration was ineffective. CONCLUSIONS: Nitric oxide inhibition increases myocardial virus titers, resulting in the aggravation of cardiac pathology in the early stage of coxsackievirus B3 myocarditis. In the late stage, it induces more severe cardiomyopathic lesions. Nitric oxide plays a defensive role in the pathogenesis of coxsackievirus B3 myocarditis.

Animals

Assessment of posterior aortic wall motion using echocardiogram in patients with atrial fibrillation.

BACKGROUND AND HYPOTHESIS: Noninvasive evaluation of left ventricular (LV) diastolic function was performed on 12 patients with atrial fibrillation (AF) using posterior aortic wall echocardiogram and a parameter for determining the optimal heart rate in patients with chronic atrial fibrillation was considered. METHODS: Subjects were divided into two groups; one with no underlying cardiac disease (AF only group; n = 7) and the other with dilated cardiomyopathy (DCM group; n = 5). Left atrial emptying index (LAEI) obtained from the posterior aortic wall echocardiogram was used as the parameter of LV diastolic function, and R-R interval-LAEI relation and minimum R-R interval showing LAEI = 1.0 were investigated and compared between the two groups. RESULTS: There was a good correlation between R-R interval and LAEI until LAEI of 1.0 was obtained in all patients. Slope of the regression line was significantly steeper in the AF only group than in the DCM group, and minimum R-R interval showing LAEI = 1.0 was significantly shorter in the AF only group. CONCLUSION: Assessment of R-R interval-LAEI relation was useful for the noninvasive evaluation of LV diastolic function, and this parameter could be used for clinical application to determine the optimal heart rate in atrial fibrillation.

Aorta

Lipopolysaccharides from Porphyromonas gingivalis, Prevotella intermedia and Actinobacillus actinomycetemcomitans promote osteoclastic differentiation in vitro.

Bacterial lipopolysaccharides possess bone-resorbing activity. Here, lipopolysaccharides from three putative periodontopathic bacteria were examined for effects on osteoclast-like cell formation of bone marrow cells from lipopolysaccharide-responsive C3H-HeN and non-responsive C3H/HeJ mice. The bone marrow cells were cultured with or without various doses of lipopolysaccharide in the presence of 1,25-dihydroxyvitamin D3 and dexamethasone. These lipopolysaccharide preparations significantly increased the number of osteoclast-like cells formed in the culture of C3H/HeN marrow cells; the same as lipopolysaccharides from Escherichia coli and a synthetic lipid A with E. coli-type structure (LA-15-PP), at doses from 0.1 to 1 microgram/ml. This stimulating effect of each lipopolysaccharides was uniformly abrogated by the addition of polymyxin B at 5 micrograms/ml. All the lipopolysaccharide and the synthetic lipid A had no effect on osteoclast formation of the C3H/HeJ marrow cells, whereas lipopolysaccharide from Porphyromonas gingivalis and Prevotella intermedia showed significant mitogenic activity on C3H/HeJ spleen cells. It seems likely that the activity of lipopolysaccharides to augment osteoclast-like cell formation in the bone marrow cell cultures is derived from a common structure of the lipid A portion.

Acid Phosphatase

Inheritance of acetohexamide reductase activities in liver microsomes and cytosol of rats.

The inheritance patterns of acetohexamide reductase activities in liver microsomes and cytosol of rats were determined by using the inbred Wistar-Imamichi and Fischer-344 strains as a model of low and high metabolizers, respectively. A simple Mendelian genetic analysis for the frequency distribution of acetohexamide reductase activity in liver microsomes of male rats led us to conclude that the phenotype is genetically regulated by an autosomal co-dominant fashion. Female rats, unlike male rats, did not exhibit microsomal enzyme activity in parental, first filial (F1) and second filial (F2) generations, indicating that the inheritance of the microsomal enzyme activity is sex-limited. On the other hand, the frequency distribution of acetohexamide reductase activities in liver cytosol of male and female rats was unimodal in all generations and there was no significant difference among these cytosolic enzyme activities.

Alcohol Oxidoreductases

Interleukin-8 gene expression by human dental pulp fibroblast in cultures stimulated with Prevotella intermedia lipopolysaccharide.

Interleukin (IL)-8 mRNA expression was investigated in human dental pulp fibroblast cultures after stimulation with lipopolysaccharide (LPS) prepared from Prevotella intermedia and inflammatory cytokines. The expression of IL-8 mRNA and the release of IL-8 induced by P. intermedia LPS in pulpal fibroblast cultures were detected by Northern blot analysis and ELISA, respectively. The sufficient concentration of P. intermedia LPS on the IL-8 mRNA expression was 0.1 microgram/ml in pulpal fibroblast cultures. IL-8 mRNA levels began to increase after 2 h of exposure, reached a maximum at 4 to 8 h, and declined after 48 h, reaching the unstimulated level by 60 h. IL-8 production by the pulpal fibroblasts began to increase after 8 h of exposure upon stimulation with 10 microgram/ml of P. intermedia LPS. By contrast Salmonella LPS and synthetic lipid A did not increase IL-8 mRNA concentrations in pulpal fibroblast cultures. Recombinant human IL-1 alpha, beta, and tumor necrosis factor-alpha were capable of stimulating these cells to express IL-8 mRNA but natural human interferon-beta, gamma, and recombinant human IL-6 were incapable in our assay. These results suggest that pulpal fibroblasts are immunoresponsive cells and can elaborate IL-8 upon stimulation with P. intermedia LPS.

Adolescent

Cytokine-induced neutrophil chemoattractant release from hepatocytes is modulated by Kupffer cells.

To clarify the role of intercellular communication in the liver during accumulation of neutrophils, the release of cytokine-induced neutrophil chemoattractant (CINC) (interleukin-8 [IL-8] related protein in rodents) by hepatocytes was investigated in the presence of Kupffer cell-conditioned medium in vitro. Kupffer cells were prepared by perfusion of rat liver with collagenase followed by centrifugation on a metrizamide gradient and were cultured in the presence or absence of lipopolysacharide (LPS). The conditioned medium was collected after 24 hours, and rat hepatocytes were cultured in the presence or absence of Kupffer cell-conditioned medium. An amount of CINC in the culture supernatant was measured by western blotting analysis and enzyme-linked immunosorbent assay (ELISA), and expression of its messenger RNA (mRNA) was assessed by the polymerase chain reaction. LPS-stimulated Kupffer cell-conditioned medium enhanced an expression of CINC mRNA in hepatocytes and increased the production of CINC by hepatocytes. Enhanced production of CINC was not shown when the Kupffer cell-conditioned medium was pretreated with heat (56 degrees C, 30 minutes). The production of CINC by hepatocytes in the presence of the LPS-stimulated Kupffer cell-conditioned medium was reduced by an antibody against interleukin 1 beta (IL-1 beta), but not by antibodies against tumor necrosis factor alpha (TNF-alpha) or LPS. These results suggest that production of CINC by hepatocytes could be regulated by IL-1 beta released from Kupffer cells, leading to neutrophil accumulation during liver injury, because this protein is a strong chemoattractant for neutrophils.

Animals

Functional difference between Thy-1-positive and Thy-1-negative gamma delta T cells induced by Escherichia coli infection in mice.

There is an increase in number of gamma delta T cells in the peritoneal cavity after intraperitoneal (i.p.) inoculation with Escherichia coli. The E. coli-induced gamma delta T cells in C3H/He mice contain a large amount of Thy-1-negative population in addition to the Thy-1-positive population. We investigated the difference between the Thy-1-positive and the Thy-1-negative gamma delta T cells. Although it was found that only up to 4% of the gamma delta T cells on day 5 after infection were in cycling phase, and that the gamma delta T cells did not proliferate by immobilized anti-T-cell receptor (TCR) gamma delta monoclonal antibody stimulation, the gamma delta T cells proliferated in the presence of interleukin-2 (IL-2) and IL-7. The Thy-1-negative gamma delta T cells showed higher proliferative response compared with the Thy-1-positive gamma delta T cells. Furthermore, the Thy-1-negative gamma delta T cells showed lower IFN-gamma mRNA expression than the Thy-1-positive gamma delta T cells. On the other hand, both the Thy-1-positive and Thy-1-negative gamma delta T cells predominantly expressed V gamma 1, V gamma 4, V gamma 5, V gamma 6 and V delta 1, and no difference of V region usage was detected between them. These results suggest that functions of Thy-1-positive gamma delta T cells differ from Thy-1-negative gamma delta T cells although Thy-1-positive and Thy-1-negative gamma delta T cells may have similar V region repertoire and, possibly, similar antigen specificity.

Animals

Structural characteristics of peptidoglycan fragments required to prime mice for induction of anaphylactoid reactions by lipopolysaccharides.

Structural characteristics of peptidoglycan fragments required to prime mice for the induction of anaphylactoid reactions by Salmonella abortusequi lipopolysaccharide were examined in endotoxin-resistant C3H/HeJ mice, with special focus on the disaccharide-pentapeptide [N-acetylglucosaminyl-beta(1-4)-N-acetylmuramyl-L-alanyl-D -isoglutaminyl-meso-2,6-diaminopimelyl (DAP)-D-alanyl-D -alanine] and its smaller partial derivatives. The bacterial and synthetic muramyl tripeptides (DAP- and lysine [Lys]-type, respectively) and synthetic muramyl dipeptide primed mice for induction of anaphylactoid reactions accompanied by death within 1 h. The disaccharide-tripeptide exhibited weaker activity, and the disaccharide-tetrapeptide and muramyl tetrapeptide exhibited marginal activity. In contrast, intact peptidoglycans of various bacteria and the disaccharide-pentapeptide lacked the priming activity, although they showed adjuvant activity similar to that of the above components.

Anaphylaxis

Lipoteichoic acid and interleukin 1 stimulate synergistically production of hepatocyte growth factor (scatter factor) in human gingival fibroblasts in culture.

Lipoteichoic acids (LTA) from various gram-positive bacteria, including oral streptococci such as Streptococcus sanguis, enhanced the production of hepatocyte growth factor (HGF) (scatter factor) by human gingival fibroblasts in culture, whereas lipopolysaccharides (LPS) from various gram-negative bacteria did not. In contrast, LPS induced interleukin 1 activity in human gingival epithelial cells in culture, while LTA had little effect. LTA and recombinant human interleukin 1 alpha enhanced synergistically the production of HGF/SF in human gingival fibroblast cultures. Recombinant human HGF, in turn, enhanced the proliferation of human gingival epithelial cells in culture.

Cells, Cultured

Plasma endothelin-1 levels during asphyxia in the fetal goat.

The changes in fetal carotid arterial plasma levels of endothelin-1, catecholamines, PO2, PCO2 and pH were measured after intermittent repetitive umbilical cord occlusion in late gestation pregnant goats (n = 9). Endothelin-1 levels increased to 3.58 +/- 0.28 pg/ml immediately after the onset of fetal hypoxia, a level significantly higher than the respective values in the control period (p < 0.05). The elevation of fetal plasma endothelin-1 levels correlated inversely with carotid arterial PO2 (r = -0.41, p < 0.05) and pH (r = - 0.43, p < 0.05). The results suggest that increased endothelin-1 levels may contribute to the maintenance of the fetal circulation during fetal asphyxia.

Animals

Induction of lymphocytes cytotoxic to oral epithelial cells by Streptococcus mitis superantigen.

The preparation of a superantigenic fraction F-2 from the culture supernatant of Streptococcus mitis 108, a fresh isolate from human tooth surfaces, was reported previously. Now, to determine the possible pathogenic role of the superantigen in oral mucosal diseases, we examined the cytotoxic effects of human peripheral blood T-cells activated with F-2 on human oral epithelial cells. T-cells activated with F-2 were cytotoxic to the human squamous carcinoma HO-1-N-1 cells derived from the oral mucosa, similar to those activated with Staphylococcus aureus enterotoxin B (SEB). This cytotoxic effect was increased in a dose-dependent manner by the addition of the respective stimulant, F-2 or SEB, to the cytotoxic assay system. F-2 endowed mainly CD8+ T-cells with cytotoxic activity. Pretreatment with human interferon gamma increased the sensitivity of the HO-1-N-1 cells to the cytotoxic effects of F-2-activated T-cells. The F-2-activated T-cells were also cytotoxic to human keratinocytes derived from gingiva. There was no correlation between the degree of cytotoxicity and the levels of tumor necrosis factor alpha in co-cultures of F-2-activated T-cells and HO-1-N-1 cells. A double-chamber plate experiment revealed no cytotoxic effects when the F-2-activated T-cells were separated from the HO-1-N-1 cells. Supernatants of the co-cultures of target and effector cells were not cytotoxic to HO-1-N-1 cells. These findings suggest that the cytotoxic effects of the F-2-activated T-cells on HO-1-N-1 cells were mediated not by soluble factors but by the direct interaction between the activated T-cells and the target cells. The cytotoxicity of the F-2-activated T-cells against HO-1-N-1 cells was markedly inhibited by monoclonal antibodies (MAbs) against CD11a and CD54, but was only slightly inhibited by MAbs against human leukocyte antigen (HLA)-DR and CD2. Thus, the interaction between lymphocyte-function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) was crucial for the F-2-dependent T-cell-mediated cytotoxicity against oral epithelial cells, while HLA-DR and CD2 molecules are not necessarily involved in the cytotoxicity observed.

Antigens, Bacterial

Central conduction in somatosensory evoked potentials: comparison of ulnar and median data and evaluation of onset versus peak methods.

To compare central conduction in ulnar and median nerve somatosensory evoked potentials (SEPs), we recorded SEPs from the neck and scalp elicited by median and ulnar nerve stimulation in 46 normal young adults. We determined the central conduction time (CCT) in each subject from peak-to-peak and onset-to-onset measurements. The mean value of the onset CCT for the ulnar nerve SEP was 6.2 +/- 0.3 msec, and for the median nerve SEP, 5.9 +/- 0.3 msec. Onset CCT was significantly longer for the ulnar nerve SEP, and there was a significant correlation between onset CCT in both median and ulnar nerve SEPs and subject height. In contrast, the mean value of the "conventional" peak CCT for the ulnar nerve SEP was 5.6 +/- 0.6 msec, and for the median nerve SEP, 5.8 +/- 0.5 msec, with no significant difference between them. In addition, the peak CCT was not correlated with subject height in the ulnar or median nerve SEPs. Our findings suggest that onset CCT measurement is superior to the conventional peak CCT measurement for ulnar as well as median nerve SEPs, and confirm that the central conduction pathway for the ulnar nerve SEP is slightly longer than that for the median nerve SEP.

Adolescent

Microstructure of etched "IPS Empress" heat-pressed ceramics observed by SEM.

A valuable characteristic of the "IPS Empress" used for producing all ceramic dental restorations is that it is a prefired ceramic ingot. The ingot is heated, softened and press-injected into the cavity, and ceramic restorations are fabricated by the lost wax casting method. The leucite crystal present in the ingot are scattered and distributed into the glassy phase in a more homogeneous manner through this pressing procedure, and the resulting ceramics are of higher flexural strength than conventional ones. The present study was carried out to clarify the microstructure of Empress ceramics by etching, and to observe the etched surface by scanning electron microscopy, in comparison with several other conventional ceramics. It was shown that the form and distribution of the leucite crystals in Empress ceramics are quite different before and after pressing, and that the staining and layering ceramics are also different from conventional ceramics. The method of surface treatment of ceramics prior to etching, such as fracturing or grinding, the kind of etching material used, the concentration and the etching time are important factors for revealing, observing and evaluating the microstructure of ceramics containing leucite crystals.

Aluminum Oxide

Acetohexamide reductase activities in liver microsomes and cytosol of cisplatin-treated male rats: cisplatin indirectly modulates the microsomal enzyme activity.

Treatment with cisplatin, at a dose of 7.2 mg/kg body weight, caused a significant decrease of acetohexamide reductase activity in liver microsomes of male rats at 4 and 7 days after its treatment; this dose of cisplatin has been reported to decrease testosterone levels in serum of male rats. However, the treatment with cisplatin could not decrease acetohexamide reductase activity in liver cytosol of male rats at the days tested. Although acetohexamide reductase activity in liver microsomes of male rats, as described above, was decreased by the treatment with cisplatin, the decreased microsomal enzyme activity was nearly restored when testosterone propionate was given once daily for 7 days after cisplatin treatment. Based on these results, it is reasonable to postulate that cisplatin indirectly decreases the microsomal enzyme activity which is regulated by androgens, by causing a significant decrease of the testosterone level in serum of male rats.

Alcohol Oxidoreductases

Therapy with immunoglobulin suppresses myocarditis in a murine coxsackievirus B3 model. Antiviral and anti-inflammatory effects.

BACKGROUND: The treatment of some inflammatory diseases (eg, Kawasaki disease) with immunoglobulin has been demonstrated to be effective. Accordingly, to elucidate the mechanism underlying such actions of immunoglobulin, we examined its effects on murine coxsackievirus B3 (CB3) myocarditis. METHODS AND RESULTS: An in vitro study showed dose-dependent suppression of CB3 by immunoglobulin. Immunoglobulin 1 g.kg-1.d-1 IP was administered to CB3-infected C3H/He mice daily for 2 weeks, beginning simultaneously with virus inoculation in experiment 1 and on day 14 after virus inoculation in experiment 2. In both experiments, survival was higher in treated than in control mice; at the time of death, inflammatory also were reduced. Notably, in experiment 1, immunoglobulin administration completely suppressed the development of myocarditis. Serum-neutralizing antibody titers in the treated mice were significantly higher than those in untreated mice in experiment 1 but not in experiment 2. The circulating antibodies of the treated mice were primarily of exogenous origin in experiment 1 and of exogenous and endogenous origins in experiment 2. The analysis of splenic lymphocyte subsets revealed a marked decrease of the B cell population in the treated mice. CONCLUSIONS: Immunoglobulin therapy completely suppressed acute CB3 myocarditis by transferring the neutralizing antibody into the host in the acute viremic stage and induced an anti-inflammatory effect in the subsequent aviremic stage; the reduction of the splenic B-cell population may be closely associated with an anti-inflammatory effect.

Animals