Biomedical subjects

T Hisada

Publications and source records attributed to T Hisada.

At least 19 recordsLinked to original sources

PubMed2006

Transversely isotropic properties of porcine liver tissue: experiments and constitutive modelling.

Knowledge of the biomechanical properties of soft tissue, such as liver, is important in modelling computer aided surgical procedures. Liver tissue does not bear mechanical loads, and, in numerical simulation research, is typically assumed to be isotropic. Nevertheless, a typical biological soft tissue is anisotropic. In vitro uniaxial tension and compression experiments were conducted on porcine cylindrical and cubical liver tissue samples respectively assuming a simplistic architecture of liver tissue with its constituent lobule and connective tissues components. With the primary axis perpendicular to the cross sectional surface of samples, the tissue is stiffer with tensile or compressive force in the axial direction compared to that of the transverse direction. At 20% strain, about twice as much force is required to elongate a longitudinal tissue sample than that of a transverse sample. Results of the study suggest that liver tissue is transversely isotropic. A combined strain energy based constitutive equation for transversely isotropic material is proposed. The improved capability of this equation to model the experimental data compared to its previously disclosed isotropic version suggests that the assumption on the fourth invariant in the constitutive equation is probably correct and that anisotropy properties of liver tissue should be considered in surgical simulation.

Animals↗

PubMed2004

Combined compression and elongation experiments and non-linear modelling of liver tissue for surgical simulation.

Uniaxial stress-strain data were obtained from in vitro experiments on 20 porcine livers for compressions, elongations and cycles of compression and then elongation. There were about 70 cylindrical samples, with diameter 7mm and varying height (4-11 mm). The combined compression and elongation test provide a unified framework for both compression and elongation for applications such as computer-aided surgical simulation. It enable the zero stress state of the experimental liver sample to be precisely determined. A new equation that combined both logarithmic and polynomial strain energy forms was proposed in modelling these experimental data. The assumption of incompressibility was justified from a preliminary Poisson's ratio for elongation and compression at 0.43+/-0.16 and 0.47+/-0.15, respectively. This equation provided a good fit for the observed mechanical properties of liver during compression-elongation cycles and for separate compressions or elongations. The root mean square errors were 91.92+/-17.43 Pa, 57.55+/-13.23 Pa and 29.78+/-17.67 Pa, respectively. In comparison with existing strain energy functions, this combined model was the better constitutive equation. Application of this theoretical model to small liver samples and other tissues demonstrated its suitability as the material model of choice for soft tissue.

Animals↗

PubMed2001

Atrial natriuretic peptide inhibits tumor necrosis factor-alpha production by interferon-gamma-activated macrophages via suppression of p38 mitogen-activated protein kinase and nuclear factor-kappa B activation.

We investigated whether the atrial natriuretic peptide (ANP) might have an inhibitory effect on inflammatory cells. Treatment of RAW264.7 macrophages with interferon-gamma (IFN- gamma) caused a significant increase in tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) production. Activation of p38 mitogen-activated protein (MAP) kinase was observed 30 to 120 min after IFN-gamma, and transcription factor nuclear factor-kappa B (NF-kappaB) was activated about 7 to 9 times of the basal activity. Human ANP(99-126) and a specific p38 MAP kinase inhibitor SB203580 inhibited the IFN-gamma-induced TNF-alpha production in a dose-dependent manner without affecting NO production. ANP inhibited the IFN-gamma-induced p38 MAP kinase activation, and ANP and SB203580 inhibited NF-kappaB activation. To study the involvement of oxidative stress in this system, the effects of allopurinol and acetovanillone, inhibitors of xanthine oxidase and NADPH oxidase, respectively, were studied. Allopurinol or acetovanillone did not inhibit the IFN-gamma-induced production of TNF-alpha or NO, suggesting little involvement of oxidative stress in this system. This is the first evidence in vitro that ANP has an anti-inflammatory activity on IFN-gamma-activated macrophages by suppressing signal transduction pathway leading to p38 MAP kinase and NF-kappaB activation.

Animals↗

PubMed2001

[Mycotic infection].

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗

PubMed2000

Involvement of haemoxygenase-1 in ozone-induced airway inflammation and hyperresponsiveness.

Haemoxygenase catalyses the degradation of haem to bilirubin, and the inducible form of haemoxygenase, haemoxygenase-1, is highly induced in response to oxidative stress in vitro. The effect of haemoxygenase-1 in oxidant stress in vivo is not known. We determined the effect of exposure to ozone on haemoxygenase-1 expression, and the modulation of haemoxygenase-1 expression on ozone-induced lung neutrophilia and bronchial hyperresponsiveness in rats. Ozone caused a significant induction of lung haemoxygenase-1. Pretreatment of rats with haemoglobin, a potent inducer of haemoxygenase-1, resulted in a large induction of haemoxygenase-1 expression, and inhibited ozone-induced neutrophilia and bronchial hyperresponsiveness. Tin protoporphyrin, a competitive inhibitor of haemoxygenase, reduced the expression of haemoxygenase-1 induced by haemoglobin. It enhanced ozone-induced neutrophilia, but not the bronchial hyperresponsiveness, and reduced the protective effect of haemoglobin. Overall, there was an association between bronchial hyperresponsiveness and the neutrophilic response. These data indicate that haemoxygenase-1 plays an important role in modulating the effects of an oxidant, such as ozone in the lungs.

Acetylcholine↗

PubMed2000

Evidence of oxidative stress in asthma and COPD: potential inhibitory effect of theophylline.

To evaluate the potential inhibitory effect of theophylline on the pulmonary oxidative stress in asthma and chronic obstructive pulmonary disease (COPD), we concomitantly measured the blood levels of theophylline, a non-selective phosphodiesterase (PDE) inhibitor and lipid peroxides as an index of oxidative stress. The plasma levels of lipid peroxides were significantly elevated in patients with asthma (3.48 +/- 0.11 nmol ml(-1); mean +/- SEM; n=21, P<0.01), non- or ex-smoking patients with COPD (3.55 +/- 0.11 nmol ml(-1); n = 20, P<0.01), and current-smoking patients with COPD (3.53 +/- 0.15 nmol ml(-1); n = 15, P<0.01), respectively, as compared to those of non-smoking controls (3.02 +/- 0.08 nmol ml(-1); n = 19). There was a significant negative correlation between the plasma level of lipid peroxides and the forced expiratory volume in 1 sec (FEV1)% of forced vital capacity in these subjects (r = -0.304; n = 75, P < 0.01). In asthmatics, there was a significant negative correlation between the plasma level of lipid peroxides and the serum level of theophylline (r = -0.495; n = 18, P<0.05). These results suggest that there may be increased oxidative stress in patients with asthma and COPD, and indicate that oxidative stress could possibly attribute to the pathophysiology of asthma and COPD in leading to airflow obstruction and that theophylline could potentially inhibit oxidative stress in the process of bronchopulmonary inflammation in asthmatics.

Aged↗

PubMed2000

Contribution of upregulated airway endothelin-1 expression to airway smooth muscle and epithelial cell DNA synthesis after repeated allergen exposure of sensitized Brown-Norway rats.

Endothelin-1 is a potent bronchoconstrictor peptide with pro-inflammatory and growth-promoting properties. After exposure of sensitized Brown-Norway rats to six repeated ovalbumin exposures, there was an increase in pro-endothelin (ET)-1 messenger RNA compared with saline-exposed control rats 24 h after the final exposure (P < 0.01). ET-1 immunoreactivity was increased sixfold in the bronchial epithelium of the larger conducting airways in the repeated allergen-exposed rats (P < 0.001). After repeated allergen exposure, there were increased rates of DNA synthesis in the airway smooth muscle (ASM) cells (P < 0.001) and epithelial cells (P < 0. 001) compared with saline-exposed controls, as measured by bromodeoxyuridine incorporation. Treatment with a dual endothelin A and B (ET(A+B)) receptor antagonist caused a significant attenuation in both ASM (P < 0.001) and epithelial cell (P < 0.001) bromodeoxyuridine incorporation compared with the allergen-challenged and vehicle-treated group. The dual ET(A+B) antagonist attenuated eosinophil recruitment into the airways (P < 0. 05) but had no significant effect on increased bronchial reactivity to acetylcholine in allergen-exposed rats. Increased levels of ET-1 in the airways may contribute to inflammation and ASM and epithelial cell DNA synthesis after repeated allergen exposure. Such processes may underlie increased proliferation of resident cells leading to airway wall remodeling in asthmatics.

Allergens↗

PubMed2000

Plasma levels and redox status of ascorbic acid and levels of lipid peroxidation products in active and passive smokers.

Both active and passive smoking are regarded as risk factors for various diseases. To clarify the effects of active and passive smoking on plasma vitamin C levels and lipid peroxidation status, we examined the plasma levels of ascorbic acid (AA), its redox status [ratio of dehydroascorbate (DHAA) to total AA], the levels of thiobarbiturate reactive substance (TBARS), and the levels of lipid peroxides (LPO) in smokers, nonsmokers, and nonsmokers regularly exposed to environmental cigarette smoke (passive smokers). The study population consisted of 149 healthy males: 75 active smokers (consumption of > 15 cigarettes/day for more than 5 years), 36 passive smokers (more than 10 hr/week exposure to environmental cigarette smoke), and 38 nonsmokers (no cigarette smoke exposure). There were no significant differences in plasma TBARS and LPO levels among the three groups. Plasma levels of AA, the reduced form of vitamin C, were significantly lower in active smokers than in the combined nonsmoking groups (7.2 +/- 3.5 and 8.4 +/- 3.4 microg/mL, respectively; p < 0.05). Although no significant differences were found in plasma DHAA levels among the three groups, the ratios of DHAA to total AA were significantly higher in active and passive smokers than nonexposed nonsmokers (11.2, 10.3, and 7.1%, respectively; p < 0.05). These results indicate that passive smoking, as well as direct inhalation of cigarette smoke, affects the redox status of plasma AA. In passive smokers, the altered redox status of plasma AA suggests an oxidative stress.

Adult↗

PubMed2000

Effect of alcohol intake on the levels of plasma homocysteine in healthy males.

Hyperhomocysteinemia in chronic alcoholics has been reported, but it remains unclear whether relatively low alcohol intake compared with the previous reports affects the plasma homocysteine level. To investigate this issue, we performed two studies, a population-based study and an alcohol withdrawal study. An analysis of plasma homocysteine levels in a population of 236 healthy males showed no significant association between alcohol consumption and other tested parameters. In the withdrawal study, the subjects with a history of daily alcohol consumption (81.8 +/- 33.0 g/d, mean +/- SD, 40-150g/d, range) abstained from alcohol for 4 wk. After withdrawal, the levels of serum gamma-glutamyl transpeptidase, aspartate aminotransferase, triglycerides, and high-density lipoprotein cholesterol significantly decreased, but the plasma homocysteine level did not change. These results suggest that alcohol intake, at least as far as the amount of beverages our study subjects consumed, has no effect on the plasma homocysteine level in healthy males.

Adult↗

PubMed1999

Inhibitory effect of tea flavonoids on the ability of cells to oxidize low density lipoprotein.

Dietary flavonoid intake has been reported to be inversely related to mortality from coronary heart disease, and the anti-atherosclerotic effect of flavonoids is considered to be due probably to their antioxidant properties. Oxidation of low density lipoprotein (LDL) has been reported to be induced by the constituent cells of the arterial wall. Accordingly, we examined the effect of pretreatment with tea flavonoids, such as theaflavin digallate, on the ability of cells to oxidize LDL. Theaflavin digallate pretreatment of macrophages or endothelial cells reduced cell-mediated LDL oxidation in a concentration- (0-400 microM) and time- (0-4 hr) dependent manner. This inhibitory effect of flavonoids on cell-mediated LDL oxidation was in the order of theaflavin digallate > theaflavin > or = epigallocatechin gallate > epigallocatechin > gallic acid. Further, we investigated the mechanisms by which flavonoids inhibited cell-mediated LDL oxidation using macrophages and theaflavin digallate. Theaflavin digallate pretreatment decreased superoxide production of macrophages and chelated iron ions significantly. These results suggest that tea flavonoids attenuate the ability of the cell to oxidize LDL, probably by reducing superoxide production in cells and chelating iron ions.

Animals↗

PubMed1999

Inhibition of ozone-induced lung neutrophilia and nuclear factor-kappaB binding activity by vitamin A in rat.

Vitamin A binds to retinoic acid receptors, which in turn may interact with other transcription factors. We determined its effect (2500 and 5000 IU/kg) on nuclear factor-kappaB binding activity in the lung, airway inflammation and bronchial hyperresponsiveness in rats exposed to ozone. Ozone (3 ppm, 3 h) caused neutrophil influx into bronchoalveolar lavage fluid (16.2+/-0.8 x 10(5) cells/ml, p < 0.01) and bronchial hyperresponsiveness (-logPC200ACh = 2.54+/-0.19, p < 0.05, compared to control animals, respectively). Vitamin A inhibited this neutrophilia dose-dependently together with the increased DNA-binding activity of nuclear factor-KB in lung extracts. Vitamin A did not affect bronchial hyperresponsiveness at both doses. Vitamin A inhibits ozone-induced neutrophilic inflammation through a reduction in nuclear factor-kappaB DNA binding activity.

Acetylcholine↗

PubMed1999

Regulation by interleukin-1beta of gene expression of bradykinin B1 receptor in MH-S murine alveolar macrophage cell line.

The effects of recombinant murine interleukin (IL)-1beta on gene expression of murine bradykinin B1 receptor (BDKRB1) in MH-S murine alveolar macrophage cell line were evaluated. BDKRB1 mRNA expression in MH-S cells was increased by IL-1beta (1, 3, and 10 ng/ml) in a time-dependent manner, peaking at 3-4 h by 100-1000 fold. IL-1beta (5 ng/ml, 24h) also induced significant binding to [3H]-des-Arg10-kallidin with a dissociation constant (Kd) of 2.95 nM and a maximal binding density (Bmax) of 670 sites/cell. Des-Arg10-kallidin (10 microM), a BDKRB1 agonist, increased intracellular calcium ion ([Ca2+]i) in IL-1beta (5 ng/ml, 24 h)-exposed cells, an increase not observed in the cells not exposed to IL-1beta. A significant increase of tumor necrosis factor (TNF)-alpha secretion occurred in the IL-1beta (5 ng/ml, 24 h)-exposed cells following addition of des-Arg10-kallidin (the IL-1beta-exposed group: 57. 8 +/- 13.7 vs. the vehicle-exposed group: 16.7 +/- 4.3 pg/ml, p < 0.05 after a 100 nM des-Arg10-kallidin for 8 h), with an optimal effect at 3-100 nM. These data suggest that IL-1beta may up-regulate BDKRB1-mediated functions of alveolar macrophages via an induction of BDKRB1 gene expression.

Animals↗

PubMed1999

Activation of cyclin D1-related kinase in human lung adenocarcinoma.

Cyclin D1 gene amplification is an important event in many cancers, but it is rarely found in non-small-cell lung cancer (NSCLC). This study was conducted in an attempt to clarify any other mechanisms related to cyclin D1 involvement in the malignant transformation of NSCLC, and we clearly showed for the first time that cyclin D1-related kinases are activated in NSCLC, especially in adenocarcinoma but not in squamous cell carcinoma. The results of this study strongly suggest that enhanced cyclin D1-related kinase activity could contribute to a progression of adenocarcinoma in NSCLC.

Adenocarcinoma↗

PubMed1999

Cysteinyl-leukotrienes partly mediate eotaxin-induced bronchial hyperresponsiveness and eosinophilia in IL-5 transgenic mice.

Eotaxin, a selective chemoattractant for eosinophils, induces lung eosinophilia and bronchial hyperresponsiveness (BHR) when administered intratracheally to interleukin-5 (IL-5) transgenic mice. We determined whether these effects of eotaxin were mediated through the production of cysteinyl-leukotrienes. IL-5 transgenic mice were administered eotaxin (5 micrograms) intratracheally after pretreatment with either diluent or a selective 5-lipoxygenase inhibitor SB210661 or a cysteinyl-leukotriene receptor antagonist, pranlukast. Twenty-four hours later, bronchial responsiveness to acetylcholine was measured and the degree of eosinophil influx was determined in bronchoalveolar lavage fluid (BALF) or in lung tissue. Both pranlukast and SB210661 significantly attenuated BHR induced by eotaxin with logPC(50), which is the concentration of acetylcholine needed to increase baseline insufflation pressure by 50%, from -0.43 +/- 0.16 to 0.39 +/- 0.10 and from -0.22 +/- 0.10 to 0.53 +/- 0.10, respectively (p < 0.05). There was also a significant attenuation of the eosinophil counts in BALF and in airways. BALF levels of leukotriene C(4) (LTC(4)) showed a significant increase after eotaxin from 23.9 +/- 6.7 to 165.0 +/- 35.0 pg/ml (p < 0.05) but were partially suppressed by both SB210661 (71.2 +/- 21.0) and pranlukast (62.7 +/- 11.5). Concentrations of LTB(4) were not significantly changed. We conclude that eotaxin-induced effects in the airways of IL-5 transgenic mice are partly mediated by the activation of 5-lipoxygenase enzyme leading to the generation of cysteinyl-leukotrienes.

Acetylcholine↗

PubMed1999

alpha4 integrin-dependent eotaxin induction of bronchial hyperresponsiveness and eosinophil migration in interleukin-5 transgenic mice.

We investigated the roles of eosinophil infiltration and activation induced by the eosinophil-selective chemokine eotaxin, and of the expression of eosinophil alpha4 and beta2 integrins in causing bronchial hyperresponsiveness (BHR) in interleukin (IL)-5 CBA/Ca transgenic mice. These mice did not show BHR, despite the presence of some eosinophils in the lungs. Intratracheal mouse recombinant eotaxin (3 micrograms) did not induce BHR in wild-type mice. In IL-5 transgenic mice, eotaxin (3 and 5 micrograms) increased responsiveness at 24 h and increased eosinophils in bronchoalveolar lavage (BAL) fluid by 9.4- and 14-fold by 24 h, respectively, together with augmentation of eosinophil peroxidase activity and eosinophil infiltration in the airway submucosa. Using flow cytometry, the expression of alpha4, CD11b, and CD18 was upregulated in BAL, but not in blood, eosinophils. A rat anti-alpha4 antibody inhibited eotaxin-induced BHR and eosinophil migration and activation, but an anti-CD11b antibody had no significant effects on BHR. A combination of both antibodies was more effective. IL-5 and eotaxin synergize in the induction of BHR and airway eosinophilia, effects that are dependent on the induction of eosinophil alpha4 integrin. Expression of BHR depends on the recruitment and activation of eosinophils.

Animals↗

PubMed1999

Stable human calcitonin analogues with high potency on bone together with reduced anorectic and renal actions.

Various derivatives of human calcitonin have been synthesized and their biological characteristics compared with those of existing calcitonins. The acute effects of these analogues in reducing serum calcium levels and suppressing appetite were assessed in rats. A calcitonin analogue, PO-1 (CGNLSTCMLGKLSQELHKLQTYPQTAIGVGAP-NH2), having both the N- and C-terminal ten amino acid sequences those of human calcitonin, and the 12 amino acid central region that of salmon calcitonin, was found to have equal effectiveness with salmon calcitonin and elcatonin for reducing serum calcium levels. Strong hypocalcemic activity was also exhibited by PO-23 ([cyclo-Asp1, Lys7]-[des-Gly2]-[Leu8]-PO-1) and PO-29 ([Asp15, Asn17 , Phe19, His20]-PO-23). PO-23 was prepared by replacing the N-terminal Cys-Cys S-S bond of PO-1 with a ring structure composed of an Asp-Lys peptide bond to enhance physicochemical stability. PO-29 was prepared by modifying the central area of the PO-23 molecule to more closely mimic human calcitonin. When tested in vitro, human calcitonin analogues with a [cyclo-Asp1, Lys7] structure showed biological activities on osteoclast-like cells comparable to those of existing calcitonins (salmon calcitonin and elcatonin) in keeping with their relative potencies for in vivo hypocalcemic action. Acute anorectic activity in rats was strong with salmon calcitonin and elcatonin but relatively reduced with human calcitonin analogues having a [cyclo-Asp1, Lys7] structure. The activities of these analogues on kidney cells were also weaker than that of salmon calcitonin or elcatonin. These results suggest that stable human calcitonin analogues with a [cyclo-Asp1, Lys7] structure suppress bone resorption to a degree similar to that of salmon calcitonin or elcatonin with weaker activities on non-osseous tissues which might be related to adverse reaction.

Amino Acid Sequence↗

PubMed1998

Effect of supplementation with vitamin E on LDL oxidizability and prevention of atherosclerosis.

Supplementation of LDL with vitamin E is thought to protect LDL from oxidative modification and prevent the development of atherosclerosis. Large epidemiological studies have revealed that vitamin E levels in plasma are inversely correlated to the incidence of coronary heart disease. Double-blind placebo-controlled trials have reported that supplementation with vitamin E decreases the incidence of coronary events in coronary heart disease (CHD) patients. However, it is not clear how high a dose of vitamin E is needed to prevent formation of atherosclerosis. In animal studies, a diet containing 0.125% vitamin E increased its levels in plasma two-fold and prevented formation of early atherosclerotic lesions in the thoracic aorta of hypercholesterolemic rabbits. Dose-response studies in humans have reported that 400 IU/day vitamin E increased its levels in plasma two-fold and prolonged the lag time before LDL oxidation. It has been reported that oxidizability of LDL was correlated to the atherosclerotic score of coronary angiography in CHD patients. About 400 IU/day vitamin E, which increases its levels two-fold and prolongs sufficiently the lag time before LDL oxidation, might be beneficial in decreasing the individual risk of CHD.

Animals↗

PubMed1998

A possible involvement of oxidative lung injury in endotoxin-induced bronchial hyperresponsiveness to substance P in guinea pigs.

Reactive oxygen-derived free radical species have been implicated in the pathogenesis and pathophysiology of inflammatory lung diseases. In a guinea pig model of aerosolized endotoxin-induced bronchial hyperresponsiveness to substance P, a possible involvement of oxidative lung injury was assessed by measuring the changes in membrane-bound neutral endopeptidase activity in the airway tissues and the level of lipid peroxides in the plasma. Vehicle-treated animals developed a neutrophilic airway inflammation, bronchial hyperresponsiveness to substance P associated with neutral endopeptidase hypoactivity, and elevation of lipid peroxides at 18 to 24 h after an exposure to endotoxin (75 microgram/ml, 40 min). A nonselective phosphodiesterase inhibitor, aminophylline, and selective phosphodiesterase isoenzyme inhibitors, SDZ-ISQ-844 (type III/IV) and SDZ-MKS-492 (type III), attenuated the neutrophilic airway inflammation induced by endotoxin. Aminophylline, SDZ-MKS-492, and a superoxide anion-generating NADPH-oxidase inhibitor apocynin inhibited bronchial hyperresponsiveness to substance P with attenuation of neutral endopeptidase inactivation induced by endotoxin. SDZ-ISQ-844, SDZ-MKS-492, and apocynin attenuated the elevation of lipid peroxides. The generation of hypochlorite (OCl-) from whole blood leukocytes was attenuated by aminophylline, SDZ-ISQ-844, SDZ-MKS-492, and apocynin at 1 to 2 h after exposure. These results suggest that reactive oxygen-derived free radical species-mediated oxidative lung injury may play an important role in endotoxin-induced bronchial hyperresponsiveness to substance P, and that phosphodiesterase isoenzyme inhibitors may be potentially useful as anti-inflammatory drugs.

Acetophenones↗