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Biomedical subjects

T Satake

Publications and source records attributed to T Satake.

At least 19 recordsLinked to original sources

Implication of oxygen radicals on airway hyperresponsiveness after ovalbumin challenge in guinea pigs.

We elucidated the implication of oxygen radicals on airway hyperresponsiveness after ovalbumin (OA) challenge in guinea pigs. Ten days OA exposure increased airway responsiveness, i.e., a significant decrease in log [acetylcholine (Ach) PC200] (2.445 +/- 0.227) was observed compared with the control group (3.398 +/- 0.269). After OA exposure, the number of beta-adrenoceptors decreased by 38%, and adenylate cyclase activity decreased by 36% (isoproterenol stimulated) and 28% (basal). Significant increases in xanthine oxidase activities in lung tissue, bronchoalveolar lavage fluid (BALF), and serum were observed after the tenth OA exposure (49.1 +/- 11.7 mU/g tissue, 12.6 +/- 3.16 mU/ml, and 11.5 +/- 2.66 mU/ml, respectively) compared with those in the control group (7.35 +/- 6.48 mU/g tissue, 2.85 +/- 1.17 mU/ml, and 3.51 +/- 1.15 mU/ml, respectively). Administration of long-acting superoxide dismutase (SOD) (5,000 U/kg twice a day intraperitoneally) or gamma-glutamylcysteine ethyl ester (gamma-GCE) (10 mg/kg, twice a day, intraperitoneally), a prodrug of glutathione, maintained log [Ach PC200] (3.248 +/- 0.415 and 3.298 +/- 0.246, respectively) in spite of 10 days OA exposure. Decreases in the number of beta-adrenoceptors and adenylate cyclase activity were prevented by long-acting SOD or gamma-GCE. In contrast, long-acting SOD or gamma-GCE inhibited significantly, but not completely, the elevation of xanthine oxidase activities. These results support suggestions that oxygen radicals might be involved in the underlying mechanism of airway hyperresponsiveness after OA challenge in guinea pigs.

Adenylyl Cyclases

Age-related decrease in respiratory muscle mitochondrial function in rats.

The purpose of this study was to elucidate the effects of aging on diaphragmatic mitochondrial function. Diaphragm mitochondria were prepared from specific pathogen-free rats aged 7 wk (n = 7), 35 wk (n = 7), and 55 wk (n = 7). The activities of various portions of the mitochondrial electron transport chain, i.e., complexes I, II, III, and IV, were measured enzymatically. The specific activities of complex I decreased significantly (P less than 0.01) in 35-wk-old rats (726 +/- 90 nmol/min/mg protein) compared with 7-wk-old rats (1,018 +/- 121), and the decrease was more remarkable in 35-wk-old rats (565 +/- 64; P less than 0.01 versus 35-wk-old). The activities of complex IV also decreased significantly (P less than 0.01) in 55-wk-old rats (1,222 +/- 191) compared with 7-wk-old rats (1,797 +/- 208); however, no significant changes in complex IV activities between 7-wk-old rat and 35-wk-old rats were observed. In contrast, the activities of complex II and III were not affected by aging. Limb muscle, heart, and liver mitochondria were also prepared from the same rats. The same tendency was observed in limb muscle mitochondria; however, in heart and liver mitochondria, activities of all four complexes were not changed in rats of all age groups. These results indicate that vulnerability of mitochondrial electron transport chain to aging differs from organ to organ and that it also differs from portion to portion in the electron transport chain and the most vulnerable site was complex I.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging

7S collagen in bronchoalveolar lavage fluid of patients with adult respiratory distress syndrome.

To evaluate the disruption of the basement membrane in the pathogenesis of adult respiratory distress syndrome (ARDS), we measured the level of 7S collagen in the bronchoalveolar lavage (BAL) fluid of patients with ARDS and normal control subjects by using a radioimmunoassay method. Twelve of 14 patients with ARDS had evidence of 7S collagen in the BAL fluid, but no 7S collagen was detected in the BAL fluid of the controls. The mean 7S collagen concentration of the BAL fluid in patients with ARDS was 19.6 +/- 9.4 ng/ml. In patients with ARDS, the BAL levels of 7S collagen correlated strongly with neutrophil counts (r = 0.813; p less than 0.01) and with elastase-complex (r = 0.914; p less than 0.01). We conclude that 7S collagen may be an index of leukocyte-mediated lung injury in patients with ARDS, and detection of 7S collagen in BAL fluid is useful for evaluating the disruption of basement membrane.

Adult

New technique using intraductal ultrasonography for the diagnosis of diseases of the pancreatobiliary system.

Intraductal ultrasonography (IDUS), a new technique for visualizing arterial structures, operates at an ultrasound frequency of 30 MHz to produce high resolution, cross-sectional images in real time. The purpose of this study was to provide a basis for interpreting IDUS images in vitro. We also attempted to determine the clinical usefulness of the IDUS system in diagnosing pancreatobiliary diseases in vivo. IDUS echograms of both the bile duct (BD) and main pancreatic duct (MPD) from autopsy specimens of 15 patients demonstrated three distinct layers with a fine reticular pattern in the pancreas in vitro. In clinical cases, the MPD and BD of four patients could be scanned by inserting the IDUS catheter via the major papilla without requiring endoscopic sphincterotomy. We hope that IDUS will become routine in scanning the BD and MPD to achieve early and accurate diagnoses of pancreatobiliary diseases.

Adenoma, Bile Duct

[An autopsy case of massive pulmonary hemorrhage in systemic lupus erythematosus].

A 60-year-old female was admitted to our hospital because of respiratory failure. She was diagnosed as having systemic lupus erythematosus (SLE) in 1971 and had been treated with low-dose oral corticosteroids for 13 years. She developed cough, fever and anemia several days after oral corticosteroids were tapered. Initially, she had no complications such as congestive heart failure, renal failure or bleeding tendency. Respiratory failure progressed without any response to antibiotic therapy. Chest roentgenogram showed bilateral diffuse infiltrates and air bronchograms. There was no improvement even with steroid pulse therapy, and she died of multiple organ failure. Autopsy revealed massive intra-alveolar hemorrhage and interstitial pneumonitis. Deposition of immunoglobulins in the lung was not seen. To our knowledge, this is the 11th reported case of SLE associated with pulmonary hemorrhage in Japan.

Female

[A clinical study of combined therapy of aspoxicillin and ceftazidime on intractable respiratory infections].

Both aspoxicillin (ASPC) and ceftazidime (CAZ) were administered together to 55 patients with intractable respiratory tract infections. ASPC and CAZ were administered at daily doses of 4 g and 2 to 4 g, respectively. Clinical effects were excellent in 11 cases, good in 33, fair in 7 and poor in 4, thus the efficacy rate was 80.0%. Bacteriologically, identified organisms were eradicated in 14 cases out of 21, decreased in 3, exchanged in 2 and unchanged in 2. The eradication rate was 76.2%. As a side effect, diarrhea was found in only one case, and abnormal laboratory test values were observed in 4 cases. However, these adverse reactions were not severe, therefore it was possible to continue the chemotherapy. These results indicate that the combination antimicrobial chemotherapy of ASPC and CAZ is effective against intractable respiratory tract infections.

Adult

Altered myocardial acetylcholine and norepinephrine concentrations in right ventricular hypertrophy and failure.

The progression of cardiac hypertrophy and failure is associated with marked changes in cardiac autonomic innervation, and there are sympathetic-parasympathetic interactions in the regulation of cardiac function. Although the indexes of sympathetic innervation have been found to be depressed with the development of heart failure, those of parasympathetic innervation have not yet been fully investigated. In order to better understand changes in markers of autonomic innervation associated with cardiac hypertrophy and failure, we measured the myocardial acetylcholine (ACh) store as a parasympathetic marker and the norepinephrine (NE) store as a sympathetic marker in pressure-overloaded right ventricular hypertrophy in rats. Two weeks after the injection of monocrotaline, significant right ventricular hypertrophy occurred. Three weeks after, severe right ventricular hypertrophy with no sign of heart failure occurred, and 4 weeks after, overt heart failure developed. In the right heart of monocrotaline rats, NE concentrations tended to increase at 1 week, returned to baseline at 2 weeks, decreased to one-half of the control values at 3 weeks, and then fell to 14% of the controls at 4 weeks. ACh concentrations in the right heart tended to increase at 1 week and exhibited a significant increase (136% and 129% of the controls in the right atrium and ventricle, respectively) at 2 weeks. As with NE, ACh concentrations in the right atrium and ventricle decreased to 76% and 54% of the controls at 3 weeks, and continued to decrease to 22% and 24% of the controls at 4 weeks after monocrotaline.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine

Age-dependent increase in deleted mitochondrial DNA in the human heart: possible contributory factor to presbycardia.

Cardiac function deteriorates with age, and endogenous damage to mitochondrial DNA (mt DNA) is believed to be a major contributory factor to aging. Mitochondria occupy a pivotal position in energy metabolism, and mitochondria have their own DNA, which encodes 13 subunits of the mitochondrial energy transducing system. Other subunits are encoded by nuclear DNA. DNA has been shown to have a high mutation rate, and genetic mutation might primarily be ascribed to mtDNA mutation in the energy transducing system. Recent advances in gene technology, especially in polymerase chain reactions (PCR), permit us to analyze mtDNA mutations in a small quantity of tissue. We devised rapid and accurate methods to detect mitochondrial mutations--the primer shift PCR method, PCR-Southern method, the modified primer shift PCR method, and the asymmetric PCR method. With these methods, we analyzed myocardia mtDNA in human cadavers of various ages (from 3 years old to 97 years old, mean 57 years old). The 7.4 kb deletion of mtDNA was commonly detected in elderly subjects, and the proportion of deleted mtDNA to normal mtDNA increased with age. Deleted mtDNA was observed in all subjects that were over 70 years old. The mutation was based on the directly repeated sequence: 5'-CATCAA-CAACCG-3', which exists in both the adenosine triphosphatase 6 gene and the displacement loop (D-loop) region. Replication impairment occurred at that directly repeated sequence, which caused the elimination of genomes between the adenosine triphosphatase 6 gene and the D-loop region and resulted in a 7.4 kb deletion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Quantitative estimation of infarct size by simultaneous dual radionuclide single photon emission computed tomography: comparison with peak serum creatine kinase activity.

To test the hypothesis that simultaneous dual energy single photon emission computed tomography (SPECT) with technetium-99m (99mTc) pyrophosphate and thallium-201 (201TI) can provide an accurate estimate of the size of myocardial infarction and to assess the correlation between infarct size and peak serum creatine kinase activity, 165 patients with acute myocardial infarction underwent SPECT 3.2 +/- 1.3 (SD) days after the onset of acute myocardial infarction. In the present study, the difference in the intensity of 99mTc-pyrophosphate accumulation was assumed to be attributable to difference in the volume of infarcted myocardium, and the infarct volume was corrected by the ratio of the myocardial activity to the osseous activity to quantify the intensity of 99mTc-pyrophosphate accumulation. The correlation of measured infarct volume with peak serum creatine kinase activity was significant (r = 0.60, p less than 0.01). There was also a significant linear correlation between the corrected infarct volume and peak serum creatine kinase activity (r = 0.71, p less than 0.01). Subgroup analysis showed a high correlation between corrected volume and peak creatine kinase activity in patients with anterior infarctions (r = 0.75, p less than 0.01) but a poor correlation in patients with inferior or posterior infarctions (r = 0.50, p less than 0.01). In both the early reperfusion and the no reperfusion groups, a good correlation was found between corrected infarct volume and peak serum creatine kinase activity (r = 0.76 and r = 0.76, respectively; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Enzyme Tests

Prostaglandin H2 as an endothelium-derived contracting factor and its interaction with endothelium-derived nitric oxide.

The possibility that prostaglandin H2 is an endothelium-derived contracting factor (EDCF) was evaluated in rings of thoracic aorta of spontaneously hypertensive rats (SHR). When the aortic rings were contracted with norepinephrine (10(-7) mol/l) and treated with acetylcholine (10(-5) mol/l), a relaxant response with a peak after approximately 1 min and a contractile response with a peak after approximately 7 min were observed. When these rings were pretreated with a thromboxane A2/prostaglandin H2 receptor antagonist (ONO-3708), the later contractile response was clearly inhibited and only a sustained relaxant response was observed. This relaxant response was completely inhibited by pretreatment with an inhibitor of nitric oxide production (N-nitroarginine methylester; NNM). When aortic rings in the basal condition were treated with NNM and then with acetylcholine, a contractile response with a peak after 7 min was observed, but this reaction was completely inhibited by pretreatment with ONO-3708. The rate of 6-keto-prostaglandin F1 alpha production showed a peak of 1.4 x 10(-6) mol/l per min per tissue, 2-4 min after administration of acetylcholine. With exogenous prostaglandin H2 (5 x 10(-7) mol/l), a peak contraction was observed after approximately 4 min, the degree and pattern of which were similar to that induced by acetylcholine. Endogenous prostaglandin H2 is considered to be produced by the aortic rings in an amount sufficient to induce vascular contraction within 30 s, and the pattern of this contraction induced by acetylcholine resembles that induced by exogenous prostaglandin H2. These findings most strongly suggest that prostaglandin H2 is an EDCF.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha

Inhibition of cyclic GMP phosphodiesterase by xanthine derivatives relaxes guinea-pig trachealis smooth muscle.

1. For the purpose of clarifying the mechanism of the airways smooth muscle relaxant action of xanthines, cyclic guanosine monophosphate (GMP) phosphodiesterase (PDE) from guinea-pig trachealis muscle was purified with diethylaminoethyl ether (DEAE) cellulose column chromatography. 2. Five 3-alkylxanthines (3-methylxanthine, 3-ethylxanthine, 3-n-propylxanthine (enprofylline), 3-n-butylxanthine, and 3-iso-butylxanthine), and five 1-methyl-3-alkylxanthines (1-methyl-3-methyl-xanthine (theophylline), 1-methyl-3-ethylxanthine, 1-methyl-3-n-propylxanthine, 1-methyl-3-n-butylxanthine, and 1-methyl-3-iso-butylxanthine (IBMX] were compared in terms of purified cyclic GMP PDE inhibition. The relationship between the structure and inhibition of cyclic GMP PDE was studied. 3. The -log EC50 values for relaxation of spontaneous tone of isolated guinea-pig trachealis preparations by the 3-alkylxanthines and 1-methyl-3-alkylxanthines were determined. 4. The five 1-methyl-3-alkylxanthines were each more potent in relaxing isolated trachealis smooth muscle than the corresponding 3-alkylxanthines. The 1-methyl-3-alkylxanthines were also more potent than the corresponding 3-alkylxanthines in their cyclic GMP PDE inhibitory effect. There was a strong positive correlation between the concentration of inhibitor which inhibited hydrolysis by 50% (IC50) values for cyclic GMP PDE inhibition by the xanthine derivatives and their EC50 values for trachealis muscle relaxation. 5. It is suggested that the mechanism by which xanthine derivatives relax trachealis smooth muscle involves inhibition of cyclic GMP PDE in addition to inhibition of cyclic adenosine monophosphate PDE.

3',5'-Cyclic-GMP Phosphodiesterases

Endocrine cells in a normal breast and non-cancerous breast lesion.

The authors confirmed the presence of endocrine cells for the first time in a normal breast as well as in a non-cancerous lesion of the breast. One hundred and eighty-eight blocks of normal breast tissues in 44 cases and 74 blocks of non-cancerous lesions in 35 cases were examined. Argyrophil cells were found in one block from a normal breast and in one block from a phyllodes tumor. Argyrophil cells in the normal breast showed positive reaction to anti-endocrine granule constituent (EGC) antibody with immunohistochemical method. Argyrophil cells found in the phyllodes tumor gave positive reaction to both anti-EGC and anti-serotonin antibodies. The present study is thought to be the first report in the literature of serotonin-positive cells in a non-cancerous breast lesion, a phyllodes tumor.

Adult

Erythromycin reduces the severity of bronchial hyperresponsiveness in asthma.

It has been demonstrated that bronchial hyperresponsiveness is a characteristic feature of bronchial asthma, and airway inflammation plays an important role in bronchial hyperresponsiveness. Erythromycin is an antibiotic extensively used worldwide which is also reported to have anti-inflammatory action. This study was designed to clarify whether erythromycin could favorably alter bronchial responsiveness in patients with bronchial asthma. To estimate bronchial responsiveness, histamine challenge was performed in 23 patients with bronchial asthma (atopic type, 11; nonatopic type, 12). All patients were treated for ten weeks with erythromycin, 200 mg three times daily, orally. After ten weeks' treatment, PC20, an index of bronchial sensitivity, was increased significantly. There was no difference between atopic and nonatopic patients in the improvement of PC20. It was concluded that erythromycin reduces the severity of bronchial responsiveness in patients with bronchial asthma.

Adult

Recovery time course of airway hyperresponsiveness to acetylcholine after ovalbumin challenge in guinea pigs.

Sequential changes in airway and adrenergic responsiveness after ovalbumin (OA) challenge were studied in guinea pigs. Airway responsiveness, alpha 1- and beta-adrenoceptor numbers and adenylate cyclase activity was determined after increasing doses of acetylcholine aerosol were administered before, 0, 3, 7, and 14 days after exposure to 2 percent OA or physiologic saline solution for 10 consecutive days. The antiasthmatic agent, azelastine (1 mg/kg/day, intraperitoneal), was administered for 14 days after the tenth exposure to OA in some animals. Airway responsiveness increased significantly after OA exposure, beta-adrenoceptor numbers decreased by 35 percent, and adenylate cyclase activity decreased by 54 percent (p less than 0.01). Values remained significantly different than control animals for 7 days and required 14 days to normalize completely. Azelastine decreased the recovery period to seven days. Azelastine may affect airway responsiveness, at least in part, by increasing beta-adrenergic responsiveness.

Acetylcholine

Effect of erythromycin on bronchial hyperresponsiveness in patients with bronchial asthma.

The effects of erythromycin (erythromycin stearate, Erythromycin; CAS 643-22-1) on the bronchial hyperresponsiveness and the functions of lymphocytes and neutrophils were evaluated. Administration of erythromycin to asthmatic patients in a dosage of 600 mg/d for 10 weeks reduced the bronchial hyperresponsiveness measured by histamine inhalation test. Furthermore, incubation with erythromycin for 96 h inhibited the mixed lymphocyte reaction at the concentration of more than 10 mumol/l in a dose-dependent manner, and the value of IC50 was about 30 mumol/l. 2-h incubation with erythromycin showed a weak inhibition to n-formyl-methionyl-leucyl-phenylalanine (FMLP)-induced superoxide production of polymorphonuclear neutrophils (PMNs) at the concentration of more than 30 mumol/l in a dose-dependent manner. 1-h incubation with 1 mumol/l and 100 mumol/l of erythromycin inhibited FMLP-induced chemotaxis of PMNs. The rates of inhibition at the concentration of 1 mumol/l and 100 mumol/l were 29.7% and 41.7%, respectively. Erythromycin thus showed a beneficial effect on bronchial hyperresponsiveness. This effect might be due to the regulation of the inflammatory cells.

Adult