Information processing of a complex system: Response behaviors specified by the Weierstrass function.
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Biomedical subjects
Publications and source records attributed to T Obata.
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We applied in vivo microdialysis techniques in examining the relation between norepinephrine and free radical generation on myocardial ischemic injury. We designed the microdialysis probe holding system, which includes loose fixation of the tube and synchronization of the movement of the heart and the probe. The heart was subjected to myocardiac ischemia for 15 min by occlusion of rat left anterior descending coronary artery. We confirmed typical changes in the electrocardiogram. The hydroxyl free radical (.OH) reacts with salicylate and generates 2, 3- and 2,5-dihydroxybenzoic acid (DHBA), which can be measured electrochemically in picomole quantity by a high-performance liquid chromatographic-electrochemical procedure. After probe implantation, the norepinephrine concentration of dialysate decreased over the first 120 min and then reached an almost steady-state level of 0.15 +/- 0.02 nmol/ml. However, when the heart was reperfused, the levels of norepinephrine and 2,3- and 2,5-DHBA were elevated. In vivo microdialysis techniques permit monitoring of norepinephrine levels and free radical generation in myocardial ischemic injury.
The role of lipoxygenase metabolites in the pathogenesis of endotoxin (LPS)-induced lung injury remains to be clarified. We investigated the contribution of peptide leukotrienes to LPS-induced acute lung injury using a potent antagonist, ONO-1078 (ONO). Experimental groups consisted of a saline group (n = 10), an LPS group (n = 9) injected intravenously with 2 mg E. coli LPS, an ONO group (n = 8) receiving 30 mg/kg of intraperitoneal ONO, and an LPS+ONO group (n = 6) receiving 30 mg/kg of ONO intraperitoneally 10 min before the LPS injection. The [125I]albumin lung plasma ratio, which is a parameter of acute lung injury, was significantly increased (p < 0.01) in the LPS group compared with the saline, ONO, and LPS+ONO groups. The [125I]albumin BAL fluid plasma ratio was also increased (p < 0.01) in the LPS group compared with the other groups. ONO pretreatment attenuated the LPS-induced increases in neutrophil counts in the BAL fluid. In vitro studies showed that ONO suppresses the neutrophil chemotaxis induced by LTB4, zymosan-activated serum, and FMLP. We conclude that (1) ONO-1078 attenuates LPS-induced acute lung injury; and (2) this effect appears mainly a result of its potent antagonistic actions against peptide leukotrienes and also, in part, the suppression of neutrophil chemotaxis.
Effects of some stresses on monoamine oxidase (MAO) activity in rat liver were investigated. Cold stress decreased MAO-A activity. Immobilization stress (IMMO) significantly decreased both MAO-A and MAO-B activities. The MAO-A/MAO-B ratio of the cold stress was significantly decreased, but IMMO was not significantly decreased. These results suggest that cold stress, but not IMMO may change the proportions of the multiple forms of MAO activity.
The differences in values, accuracy, reproducibility and interdevice variability of three models of portable peak flowmeters (standard and low range of Assess, mini-Wright, Pulmo-Graph) before use and after they had been used 1000 times. A computerized standard flow generator was used to evaluate. Standard range; The three models showed differences in values before and after 100 uses of less than 3 percent at flow rates below 480 L/min. However, the used flowmeters, especially the Assess, showed higher values compared with the new ones at higher flow ranges. There was no significant difference in accuracy between the new and used mini-Wright and Pulmo-Graph models. The used Assess, howevers, showed higher values at higher ranges, thus demonstrating improved accuracy over the new ones. The reproducibilities of the three models deteriorated at high flow rates. The interdevice variability of the used Pulmo-Graph flowmeter was better than that the new one. No significant changes were observed in the mini-Wright, while the Assess showed deteriorated interdevice variability. Low range; The three models showed no significant differences in values, accuracy, reproducibility or interdevice variability before and after use.
The accuracy, reproducibility and interdevice variability of three models of portable peak flowmeters (standard and low range) were evaluated by using a computerized standard flow generator. Standard range; The mini-Wright peak flow meter generally overestimated peak flow from 120 L/min to 540 L/min and the Assess peak flowmeter underestimated peak flow at full range. The Pulmo-Graph peak flowmeter showed a similar pattern to the mini-Wright but with more accuracy. The Assess showed the best linearity. The reproducibilities of the three models deteriorated over 20 L/min at high flow rates. The interdevice variability of the mini-Wright was better than those of the Assess or the Pulmo-Graph. Low range: The accuracy and interdevice variability of the Pulmo-Graph were better than those of the Assess or the mini-Wright. The reproducibility of Assess seemed to be inferior to the other's. The measured flow from the low ranges was not the same as that of the standard ranges. The three peak flowmeter models have different spring mechanisms for their readings, and the measured flows by one model should not be compared with other models.
We studied the responses to ultrasonically nebulized distilled water (UNDW) challenge, exercise challenge and methacholine challenge in asthmatic children. Fifty-four asthmatic and fourteen nonasthmatic control children participated in this study. The UNDW inhalation test was by the methodology described by Anderson. The average output of water was approximately 3.0 mL/min (SD = .1) and inhalation times were 30 seconds, one minute, two minutes and four minutes. Some subjects performed exercise challenge on a bicycle ergometer and methacholine challenge by an Astrograph technique. Twenty-three of 54 asthmatic patients (42.6%) and none of the controls showed a fall in FEV1 greater than 20% with UNDW challenge. The fall in FEV1 with UNDW correlated with that induced by exercise challenge (r = .89) and Log Dmin, which may reflect bronchial sensitivity (r = .70). Our method is not sensitive enough for detecting bronchial hyperresponsiveness in all asthmatic children. Bronchoconstriction induced by UNDW has a similar mechanism of action as exercise and methacholine.
Peptide leukotrienes have been suggested to play an important role in bronchial asthma. As antigen-induced bronchoconstrictions, airway hyperreactivity, and pulmonary eosinophil accumulation are characteristics of the pathology of asthma, we investigated the effect of a peptide leukotriene receptor antagonist, ONO-1078, on these responses using guinea-pig models of asthma. Oral administration of ONO-1078 (3 mg/kg) significantly inhibited slow-reacting substance of anaphylaxis-mediated bronchoconstriction induced by i.v. administered ovalbumin. ONO-1078 (30-100 mg/kg), when administered orally both 1 h before and 4 h after ovalbumin challenge, significantly reduced immediate- and late-phase asthmatic responses, with peak responses occurring immediately and 5-11 h after challenge with inhaled ovalbumin. Oral administration of ONO-1078 significantly reduced the airway hyperreactivity (10-30 mg/kg) and the pulmonary eosinophil accumulation (30-100 mg/kg) observed 4 and 24 h after ovalbumin challenge, respectively. These results suggest that ONO-1078 may be of therapeutic use for bronchial asthma.
The effect of a peptide leukotriene receptor antagonist ONO-1078 on the production of thromboxane (Tx) B2 induced by leukotriene (LT) D4 and antigen challenge was examined in guinea pig lungs. LTD4 (1-1,000 nM) induced a concentration-dependent production of TxB2 in non-sensitized guinea pig lungs and ovalbumin challenge (0.01-100 micrograms/ml) produced TxB2 and peptide leukotrienes in a concentration-dependent manner in ovalbumin-sensitized guinea pig lungs. ONO-1078 inhibited LTD4 (100 nM)-induced TxB2 production with the IC50 value of 0.24 microM. Furthermore, ONO-1078 inhibited antigen (10 micrograms/ml)-induced TxB2 production with the IC50 value of 0.14 microM without effect on the production of peptide leukotrienes. These results suggest that ONO-1078 may prevent the antigen-induced production of TxB2 through the blockade of the activation of receptors by endogenously generated peptide leukotrienes.
1. We applied in vivo microdialysis technique to examine the effect of Fe2+, Fe3+, Cu2+ and Zn2+ on free radical-generation of rat liver. The hydroxyl free radical (.OH) reacts with salicylate and generates 2,3- and 2,5-dihydroxybenzoic acid (DHBA) which can be measured electrochemically in picomole quantity by HPLC-EC procedure. 2. The relative rates of recovery of 2,3- and 2,5-DHBA at 1 microliter/min in vitro were an average of 10.1 +/- 0.8% and 10.5 +/- 9%, respectively. 3. When the metal ion infused through the dialysis probe, Fe2+ but not Fe3+, Cu2+ and Zn2+ caused an increase in the formation of DHBA of rat liver. 4. After the Ringer solution containing 10 mumole/kg was injected into the penile vein, the levels of 2,3- and 2,5-DHBA were increased about 60% and 40%, respectively. 5. These results indicate that non-enzymatic oxidation in the extracellular fluid may play a key role in Fe2+ generation of -OH in liver. Free radical formation processes may contribute to in vivo free radical formation induced by Fe2+.
1. We examined in vivo monitoring of norepinephrine and hydroxyl radical generation in rat myocardium with a microdialysis technique. For this purpose, we designed the microdialysis probe holding system which includes loose fixation of the tube and synchronization of the movement of the heart and the probe. 2. The hydroxyl free radical (.OH) reacts with salicylate and generates 2,3- and 2,5-dihydroxybenzoic acid (DHBA) which can be measured electrochemically in picomole quantity by high performance liquid chromatography (HPLC). 3. After probe implantation, norepinephrine concentration of dialysate decreased over the first 150 min and then reached an almost steady level. A positive linear correlation between the ferrous iron and .OH formation trapped as 2,3-DHBA (R2 = 0.960) and 2,5-DHBA (R2 = 0.982) was observed using the microdialysis technique. 4. The present results indicate that non-enzymatic oxidation in the extracellular fluid may play a key role in hydroxyl radical generation by ferrous iron.
The incidence of latex-induced allergy has been reported to be increasing in Europe and the US but not in Japan. We thus measured latex-specific IgE antibodies and latex-specific IgG antibodies in sera from 196 atopic children with low serum IgE levels (under 1,000 U/ml; group 1), 108 atopic children with high serum IgE levels (over 1,000 U/ml; group 2) and 601 hospital employees (group 3). Atopic children were diagnosed as having asthma, atopic dermatitis and/or food intolerance. One out of group 1 (0.5%) and 11 out of group 2 (10.2%) were found to have latex-specific IgE by radioallergosorbent assay (RAST), and 7 were further found to be positive for latex antigen by skin test. Fifty-five percent of group 1, 65% of group 2 and 9.7% of group 3 were found to have latex-specific IgG over 100 units/ml by enzyme linked immunosorbent assay (ELISA). Prior to our diagnosis most of the children and employees did not realize they were allergic to latex. These data suggest that caution should be taken regarding latex allergy when atopic children have to be operated upon as atopic children tend to be sensitized to the latex antigen after even minimal contact with latex products.
Many cases of latex-induced intraoperatived anaphylaxis have been reported in Europe and the U.S. but not in Japan. We measured latex-specific IgE antibody in sera from the 108 atopic children with high serum IgE levels (over 1,000 U/ml). All of them were diagnosed to have asthma, atopic dermatitis and/or food intolerance. Eleven (10.2%) out of 108 patients were found to have latex-specific IgE by RAST, and 6 of them were positive for latex antigen by skin test. Most of the children did not realize that they were allergic to latex until we discovered it. This data suggest that we should be cautious about latex allergy when atopic children have to be operated upon.
We evaluated the preventive effect and duration of action of disodium cromoglycate (DSCG) and procaterol nebulizer solutions on exercise-induced asthma (EIA) in 14 asthmatic patients. Disodium cromoglycate solution prevented EIA one hour after inhalation in 11 out of 14 (78.6%), and in some patients after four (36.5%) and eight hours (15.4%). The preventive effect and duration of action of DSCG depended on the severity of EIA in each subject. Procaterol solution had a greater effect than DSCG at any time point in the study. With both drugs, however, the effect decreased four and eight hours after inhaling and was related to the severity of the EIA.
Rarobacter faecitabidus protease I (RPI) is a serine protease exhibiting lytic activity toward living yeast cells. RPI is similar to elastase in its substrate specificity and has a lectin-like affinity for mannose. The gene encoding RPI was cloned to elucidate its structure and function. And its nucleotide sequence revealed that it contains an open reading frame encoding a 525-amino acid protein. Homology comparison indicated that pre-pro-RPI consists of three domains: (1) an NH2-terminal prepro domain not found in the mature form of RPI, (2) a protease domain homologous to the trypsin family of serine proteases, and (3) a COOH-terminal domain homologous to the COOH-terminal part of Oerskovia xanthineolytica beta-1,3-glucanase and the NH2-terminal part of the ricin B chain, a lectin isolated from the part of the ricin B chain, a lectin isolated from the castor bean. The RPI gene and its mutant were subsequently expressed in Escherichia coli under its beta-galactosidase promoter to investigate the function of the COOH-terminal domain. The mutant RPI, whose COOH-terminal domain was truncated by site-directed mutagenesis, lost both its mannose-binding and yeast-lytic activity, although the protease activity was not affected. These findings suggest that the COOH-terminal domain actually participates in the mannose-binding activity and is required for yeast-lytic activity.
To understand the regulation by thyroid hormone, 3,3',5-triiodo-L-thyronine (T3), of the synthesis of a cytosolic thyroid hormone binding protein (p58-M2) during liver regeneration, the synthesis of p58-M2 was evaluated. The synthesis of p58-M2 was measured by metabolic labeling of primary cultures derived from the regenerating liver of euthyroid, hypo- or hyperthyroid rats. During regeneration, the increase in the liver/body weight ratio is approximately 25% higher in hyper- than in hypothyroid rats. However, T3 has no effect on the rate of overall liver regeneration observed in four days. In mature liver, T3 increased the synthesis of p58-M2 by approximately 2.5-fold. During regeneration, however, the change in the synthesis of p58-M2 varied with the thyroid status. In euthyroid rats, the synthesis of p58-M2 continued to increase up to 2-fold during liver regeneration. In hyperthyroid rats, after an initial increase by 1.5-fold on day 1, the synthesis of p58-M2 subsequently declined during regeneration. In hypothyroid rats, the synthesis of p58-M2 remained virtually unchanged during regeneration. These results indicate that T3 regulates the synthesis of p58-M2 in mature and regenerating liver.
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Increased formation of hydroxyl free radicals (.OH) reflected by .OH adduct of salicylate in brain dialysate was demonstrated during the sustained (more than 2 hours) dopamine overflow elicited by 75 nmol of 1-methyl-4-phenyldihydropyridine (MPDP+) and 1-methyl-4-phenylpyridinium (MPP+) in the rat striatum. Owing to its weak dopamine releasing action, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) did not significantly increase the .OH formation. This data suggests that sustained elevation of dopamine in the extracellular fluid elicited by MPTP analogues can be auto-oxidized, which in turn leads (possibly by indirect mechanisms) to the formation of cytotoxic .OH free radicals near the nigrostriatal terminals.