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Biomedical subjects

T Horie

Publications and source records attributed to T Horie.

At least 433 records · Page 24Linked to original sources

[Bronchoconstriction in isocapnic hyperventilation-induced asthma].

It is well known that some asthmatic patients develop bronchoconstriction after exercise challenge (exercise-induced asthma, EIA). Recently, it has been pointed out that isocapnic hyperventilation also induces similar bronchoconstriction (hyperventilation-induced asthma, HIA) in the same asthmatic subjects. However, the mechanism of HIA has not yet been determined. In the present study, we performed exercise and hyperventilation challenge in the same patients and pulmonary function data and neutrophil chemotactic factor (NCF) in peripheral blood were examined before and after both challenges. Twelve asthmatic patients with normal pulmonary function data on testing days were subjected to exercise test on a bicycle ergometer and then isocapnic hyperventilation tests in subsequent days. Subjects breathed dry air from the cylinder. Isocapnic hyperventilation was performed by monitoring minute ventilation and each patient followed the same minute ventilation exercise. The reduction of FEV1.0 and time course of airway obstruction were almost the same after exercise and hyperventilation testing. All patients who developed EIA also developed HIA and other patients did not develop both EIA and HIA. Changes of Rrs, V50 and V25 and their time course after each test were also similar in EIA(+) and HIA(+), and in EIA(-) and HIA(-). NCF increased significantly after both challenges in EIA(+) and HIA(+) patient, although increment of NCF was much less these the increases of HIA(+). These data may suggest that the development of bronchoconstriction was compatible after exercise and hyperventilation in each asthmatic patient, however, the mechanism of HIA may differ from EIA, although NCF slightly but significantly increased in HIA, suggesting the possible role of a chemical mediator.

Adolescent↗

[Indication and limitation of inhalation therapy].

In recent years, the clinical application of aerosol inhalation therapy has increased rapidly, however, many problems are not yet fully dissolved. In this symposium, most adequate condition and procedure for the inhalation therapy in terms of lesional localization and the recognition of therapeutic limitation were mainly discussed.

Administration, Inhalation↗

[Corticosteroid--effects of beclomethasone dipropionate 800 micrograms/day].

The effects of beclomethasone dipropionate (BD) 800 micrograms on steroid-dependent adult asthmatics were examined. The study consisted of two groups; 20 patients on 800 micrograms and another 20 patients on 400 micrograms. In addition, 800 micrograms was administered to an additional 12 patients receiving 400 micrograms with insufficient effects. After two weeks of observation period, BD was administered for 12 weeks, and its effects adverse reactions were analyzed on the basis of asthma patients' diary etc. As the results, effects appeared earlier in the 800 micrograms group than in the 400 micrograms group and marked efficacy was seen. The 800 micrograms group was much better than the 400 micrograms group in the achievement of weaning from or of dose reduction of systemic steroid. A significant increase of serum cortisol levels which was considered to be due to the decrease of the systemic steroid usage was noted. Considerable efficacy was also observed in patients whose dosage had been increased from 400 micrograms to 800 micrograms. High dose administration usually increases topical side effects such as hoarseness and stomatitis, however the use of spacers was effective in the prophylaxis and treatment of those symptoms.

Administration, Inhalation↗

[Relationship between pulmonary functions and sleep respiratory abnormalities in obstructive sleep apnea syndrome].

Pulmonary function tests were performed in 18 cases of obstructive sleep apnea in supine and sitting positions and the relationship between pulmonary function and polysomnographic data was analyzed. %FRC and PaO2 were reduced in the supine position compared with those in the sitting position. It was suggested that the reduction of PaO2 was mainly caused by the elevation of CC/FRC ratio in supine position. The relationship between pulmonary function data and polysomnographic data were analyzed, and an inverse relationship between %FRC in sitting position and desaturation was observed and also a positive relationship between PaO2 in the supine position mean-nadir SO2 was found. Saw-tooth sign and VE50/VI50 greater than 1 on flow-volume curves were not related to the apnea index and desaturation index. These results indicate that the F-V curve is not useful for the diagnosis of OSA.

Humans↗

Induction and immunohistochemical localization of cytochrome P-450 PCN by non-steroidal compound, in rat liver microsomes.

Induction of cytochrome P-450 PCN (P-450 PCN) by non-steroidal compound, M79193 (cyclohexane spiro-2,6-chloro-1'-(3-dimethyl-aminopropyl) spiro(chroman-4,4'-imidazolidine)-2',5'-dione], was investigated in both sexes of rats. The immunohistochemical localization of P-450 PCN was also studied in liver lobules of untreated and M79193-treated male rats. Immunoblot analysis of rat liver microsomes with anti-P-450 PCN indicated that the amount of P-450 PCN increased 5- to 7-fold by the treatment with M79193, but no increase was observed in P-450 PB-1 (P450IIB1) or P-450 MC-1 (P-450IA1). P-450 PCN was uniformly distributed in liver lobule of untreated rats, and was significantly increased by the treatment with M79193 in both the periportal and pericentral regions of the lobules.

Animals↗

Vitamin A protects the small intestine from methotrexate-induced damage in rats.

A protective effect of vitamin A (VA) against cytotoxic antitumor drug-induced damage of rat small intestine was found. Oral administration of methotrexate (MTX) for the small intestinal mucosa of rats resulted in a severe histological change, whereas rats coadministered VA with MTX showed a histological status similar to that of control rats. The p.o. administration of MTX led to a decrease in the amounts of membrane proteins and lipids in rat small intestine and its brush border membrane. When administered p.o. with VA, this decrease failed to occur. The brush border membrane of MTX plus VA-treated rats, when monitored by the fluorescence of cationic safranin O and anionic 8-anilino-1-naphthalenesulfonic acid, was found to resemble that from control rats rather than that from MTX-treated rats. The in vitro permeation of MTX in the small intestine of MTX plus VA-treated rats was enhanced, in contrast with the decrease noted for MTX-treated rats. However, that of untreated rats was not affected by the presence of VA. Thus, VA is unlikely to affect the transport process of MTX directly. When administered p.o. with VA, MTX was absorbed effectively to the same or a slightly greater extent than when administered by itself. Consequently, it has been shown histologically, biochemically, physicochemically and physiologically that VA protects the small intestine from the damage induced by MTX.

Administration, Oral↗

Liver resection using a water jet.

The water-jet method has been used during hepatic resection. The instrument cuts the hepatic tissue with the high pressure of the fine water flow, while the exposed elastic intrahepatic vessels are spared injury. A comparative study on the water-jet method with the previously employed conventional methods was undertaken. Hepatic resections were performed on 35 patients using the water-jet method. Cirrhosis of the liver was associated with 10 of the 24 patients with hepatocellular carcinoma. An ordinary saline solution was used as the jet, which was projected at a pressure of between 12 kg/cm2 and 20 kg/cm2 through a 0.15/mm-diameter nozzle. A higher jet pressure was needed to cut the fibrotic hepatic parenchyma. In the case of normal liver, the intrahepatic vessels of more than 0.2 mm were well preserved. In most of the cases, the loss of blood when cutting the hepatic parenchyma can be easily reduced with a jet pressure of 15-16 kg/cm2, thus preserving the fine vessels more than 0.2 mm in diameter without injury. When the same pressure was applied in the cutting of a cirrhotic liver, it took much longer time compared to that of a non-cirrhotic normal liver parenchyma. The cut surface was smooth compared to that after using CUSA, although its disadvantages lie in the formation of air bubbles, which obscure the operative field. The controlled projection of a jet of water under optimal pressure may ensure a safe hepatic resection of both normal and cirrhotic livers. Furthermore, because of its uncomplicated form, a wide range of applications can be expected, while the lower cost will also expedite its large-scale use for economic reasons.

Adolescent↗

Time dependent changes occurring in rat liver microsomes upon lipid peroxidation.

Steady-state fluorescence anisotropy of diphenylhexatriene and n-(9-anthroyloxy)stearic acids (n = 2,12) in rat liver microsomes showed a marked increase in the early stages of enzymatically or non-enzymatically induced lipid peroxidation. The changes in fluorescence anisotropy occurred in parallel with the formation of thiobarbituric acid-reactive substances (TBA-RS). Parallel to these changes, the fluorescence emitted from peroxidized microsomes increased markedly in the early stages of lipid peroxidation. In contrast to the changes in the fluorescence anisotropy and in the formation of TBA-RS, the fluorescence showed a continuing increase over the three hr period of lipid peroxidation. Glucose-6-phosphatase was inactivated in the early stages of lipid peroxidation, whereas NADH-cytochrome b5 reductase underwent a slow deactivation over three hr. The apparently slow deactivation of the peripheral protein may be explained by the formation of fluorescent substances.

Animals↗

Protection of liver microsomal membranes from lipid peroxidation by garlic extract.

Garlic extract, the ethanol-soluble fraction of garlic, prevented formation of thiobarbituric-acid-reactive substances and fluorescent substances during lipid peroxidation of rat liver microsomes. Lipid peroxidation increased the fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene labelled to the microsomes while this increase was prevented by the garlic extract. It thus seems probable that the garlic extract serves to maintain membrane fluidity. These effects were dependent on its concentration and particularly prominent on exceeding a certain concentration of garlic extract. These results suggest its possible role of protecting the membranes from lipid peroxidation.

Animals↗

Change in small intestinal brush border membranes of rats following methotrexate administration.

Change in small intestinal brush border membranes of rats following methotrexate administration was monitored by the fluorescence spectra and polarization of the cationic fluorescent probe, safranin 0. Total protein content of brush border membranes of treated rats was less than that of control rats, whereas no significant difference in total sialic acid content of brush border membranes was observed between them. Thus, an apparent increase in the electronegative charge of brush border membrane vesicles per unit of membrane protein following methotrexate administration may possibly cause the change in fluorescence spectra and polarization of safranin 0.

Animals↗

A flavonoid inhibitor of 5-lipoxygenase inhibits leukotriene production following ischemia in gerbil brain.

Leukotrienes C4 and D4 are arachidonic acid metabolites that constrict blood vessels and enhance vascular permeability; their biosynthesis is initiated by the reaction of arachidonic acid with 5-lipoxygenase enzyme. After bilateral carotid artery occlusion for 15 minutes and reperfusion of the gerbil brain for 15 minutes, we determined the brain tissue concentrations of leukotrienes C4 and D4 by radioimmunoassay; they had increased from a baseline concentration of less than 1 to a mean +/- SEM concentration of 12.8 +/- 3.9 pmol/g brain. We also studied the effect of a flavonoid 5-lipoxygenase inhibitor on leukotriene production in the reperfused gerbil brain. A water-soluble flavonoid (5-hexyloxy-3',4'-dihydroxy-6,7-dimethoxyflavone 4'-disodium phosphate) was administered intravenously at a dose of 200 mg/kg body wt; 15 minutes later, both carotid arteries were occluded. The enhanced production of leukotrienes C4 and D4 in the reperfused brain was reduced by approximately 80% (from a mean +/- SEM of 12.8 +/- 3.9 to 2.2 +/- 1.3 pmol/g brain) in the presence of the 5-lipoxygenase inhibitor. The flavonoid did not affect the production of prostaglandin D2, the concentration of which also increased in the reperfused ischemic brain.

Animals↗

Induction of cytochrome P-450 isozymes by chromanamine derivatives in rat liver.

1. Pretreatment of rats with 6-(3-picolyl)amino-2,2,5,8-tetramethylchromane (PATC) for 7 days resulted in a significant increase in the activities of benzphetamine N-demethylase, p-nitroanisole O-demethylase and aniline hydroxylase in liver microsomes prepared 24 h after the last treatment. 2. Analysis by Western blot showed that PATC induces cytochrome P-450 b, P-450 c and P-450 d, which are the major forms of cytochrome P-450 in liver microsomes of rats when pretreated with phenobarbital and 3-methylcholanthrene. 3. Exposure of liver sections to the antibodies to cytochrome P-450 b and P-450 c resulted in intense immunostaining within the centrilobular regions, but produced staining of considerably weaker intensity in the perilobular region. Semiquantitative immunochemical analysis, by image analyser, of cytochrome P-450 b and P-450 c showed that centrilobular hepatocytes were stained more intensively than perilobular hepatocytes. 4. These results indicate that PATC induces cytochromes P-450 b and P-450 c, in the centrilobular hepatocytes to a greater degree than those in the perilobular hepatocytes. 5. Co-administration of PATC with pentobarbital caused a significant increase in pentobarbital sleeping time. Furthermore, PATC was found to cause a decrease in the activity of benzphetamine N-demethylase in liver microsomes prepared 30 min after treatment with the drug.

Animals↗

[Role of plasma histamine and neutrophil chemotactic factor in exercise-induced asthma].

The mechanism of exercise-induced asthma (EIA) is still controversial, although the role of chemical mediator is strongly suspected. In the present study, 50 asthmatic patients were observed after exercise on bicycle ergometer during dry air breathing, and changes of plasma histamine and neutrophil chemotactic factor (NCF) were measured and effect of anti-allergic drugs was examined. 31 patients developed postexertional bronchoconstriction and their % reduction of FEV1 after exercise correlated significantly with the degree of airway hyperresponsiveness to inhaled methacholine determined by Astograph. Plasma histamine levels were examined in 20 EIA positive cases and 13 EIA negative cases, but no significant changes were observed between pre- and post-histamine levels in either group. On the other hand, NCF was elevated significantly after exercise in both EIA positive and negative cases, but postexertional NCF levels were significantly higher in EIA positive than in EIA negative cases. The relationship between % increase of NCF and the % reduction of FEV1 after exercise was significant (r = 0.472, p less than 0.05). DSCG and Azelastine protected the development of EIA in 14 out on 19 cases and 7 out of 12 cases, respectively. Pretreatment with DSCG significantly reduced the increase of NCF after exercise. These results indicates that one of the chemical mediator, NCF, may play an important role in producing postexertional bronchoconstriction in asthmatic patients.

Adolescent↗

Strain differences of rat liver carboxylesterase activities related to the phenotype difference of esterase-3 (egasyn).

It was demonstrated that the inbred strain EHBR had the C phenotype of esterase-3 judging from the absence of liver microsomal beta-glucuronidase and the pattern of esterase activities of liver homogenates after analytical isoelectric focusing. In addition, in the strain EHBR, liver microsomal hydrolase activities of acetanilide and isocarboxazid which are hydrolyzed well by esterase-3 were lower than in outbred Sprague-Dawley rat and inbred LEW rat having the D phenotype of esterase-3. These results suggest that the phenotype difference of esterase-3 is possible to cause the strain differences of liver microsomal carboxylesterase activities.

Animals↗

[Liver resection by water jet].

Major problem in resecting liver parenchyma is how to control the bleeding. Recently, resection of the liver by water jet has been reported. So, experimental and clinical studies were performed to investigate the usefulness of the water jet equipment. Ten pigs weighing around 17kg were used. The optimal pressure to resect the porcine liver was 7 to 15kg/cm2. By 4 weeks the cut surface was covered with fibrous capsule. Portal angiography showed no abnormality in the resected area. The water jet was also used in 30 human operations. The optimal pressure was 12 to 18kg/cm2 for non cirrhotic liver and 15 to 20kg/cm2 for cirrhotic liver. The surface immediately after jet cutting was more smooth than that of CUSA and histologically there was slight bleeding and necrosis. The volume of blood loss during dissection was not different between water jet group and CUSA group. No significant changes were found in the laboratory data. These results suggest that water jet is as useful as CUSA for cutting the liver parenchyma.

Adult↗

Effect of aztreonam on immunohistochemical localizations of cytochrome P-450 (M-1) in male rats.

The localization of sex-specific cytochrome P-450, P-450 (M-1), was investigated immunohistochemically in the liver of untreated- and Aztreonam-treated male rats. P-450 (M-1) was uniformly distributed in the liver lobule of untreated rats. By treatment with Aztreonam, P-450 (M-1) was decreased more in the periportal region rather than the pericentral region of the lobule. In addition, oxidation of testosterone and 1 alpha-hydroxycholecalciferol catalyzed by P-450 (M-1) was also decreased by Aztreonam administration.

Animals↗

Dog liver glutathione S-transferase and its strong immunoreactivity with rat transferase-P(7-7).

Dog liver cytosolic glutathione S-transferases (GSTs) were investigated to characterize their properties in comparison with rat liver transferases. Dog liver GSTs after the glutathione affinity column chromatography showed three subunit bands on SDS-polyacrylamide gel electrophoresis. These three subunits, designated as Yd1 (mol.wt 26,000), Yd2 (mol.wt 27,000) and Yd3 (mol.wt 28,000), were distinctly different from rat liver GST subunits, i.e. Ya(1) (mol.wt 26,500), Yb1(3)/Yb2(4) (mol.wt 27,500) and Yc(2) (mol.wt 28,500). Western blot analysis revealed that Yd1, Yd2 and Yd3 were immunoreacted with anti-rat GST 7-7, 1-1 and 3-3 antibodies, respectively. Four transferase activity fractions, I (pH greater than 7.63), II (pH 6.92), III (pH 5.80) and IV (pH 5.65), were obtained from affinity purified GSTs by chromatofocusing. Each fraction exhibited a characteristic substrate specificity. GST-II, III and IV were all strongly immunoreacted with anti-rat GST 7-7 antibody by immunoblotting, thus suggesting the occurrence of the heterogeneity of transferases immunologically related to rat GST subunit 7 in dog liver. Immunohistochemical examination showed that transferases immunoreacted with anti-GST 7-7 antibody have diffusely distributed throughout the lobule, while enzymes related to subunit 3 have been localized in a narrow range of cells around the central vein. These data suggest that GSTs immunologically associated with rat transferase subunit 7 may be major forms in dog liver.

Animals↗