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Biomedical subjects

T Horie

Publications and source records attributed to T Horie.

At least 217 records · Page 12Linked to original sources
PubMed1997

[The effect of prophylactic intravenous diltiazem drip infusion on myocardial ischemia during noncardiac surgery].

We evaluated the effect of intravenous diltiazem infusion in 105 noncardiac surgical patients. Subjects were elective surgical patients with coronary artery disease and coronary risk factors which were hypertension (WHO standards), diabetes mellitus, hyperlipemia (total cholesterol > or = 220 mg.dl-1), obesity (body mass index : male > or = 26 kg.m-2, female > or = 25) and old age (70 years old or above). The prophylactic intravenous diltiazem infusion (1.0 micrograms.kg-1.min-1) was started immediately after induction of general anesthesia or epidural analgesia and continued until the end of operation. All patients were monitored by ST trend graph during anesthesia, and ischemia pattern was defined as > or = 1 mm ST changes and lasting over 1 min. Ischemic ST-T changes were noted in 4 cases in the operating room. ST depression was noted in 2 cases before starting anesthesia and these 2 cases showed improvement with diltiazem infusion lasting until the end of operation. ST-T changes were noted in 2 cases during surgery and these 2 cases showed improvement with diltiazem isosorbide dinitrate. We conclude that prophylactic intravenous diltiazem infusion may prevent ischemia during noncardiac surgery.

Aged↗
PubMed1997

Kinetic analysis of the primary active transport of conjugated metabolites across the bile canalicular membrane: comparative study of S-(2,4-dinitrophenyl)-glutathione and 6-hydroxy-5,7-dimethyl-2-methylamino-4-(3-pyridylmethyl)benzothiazole glucuronide.

UNLABELLED: Eisai hyperbilirubinemic rat (EHBR) is a mutant strain with a hereditary defect in canalicular multispecific organic anion transporter (cMOAT). We examined the uptake and mutual inhibition of S-(2,4-dinitrophenyl)-glutathione (DNP-SG), which is a typical substrate for cMOAT, and 6-hydroxy-5,7-dimethyl-2-methylamino-4-(3-pyridylmethyl) benzothiazole (E3040) glucuronide (E-glu) with canalicular membrane vesicles (CMV) prepared from Sprague-Dawley (SD) and EHBR rats to investigate the multiplicity of the organic anion transporter. The ATP-dependent uptake by CMV from SD rats had an apparent Km of 17.6 microM for DNP-SG and 5.7 microM for E-glu, whereas the corresponding uptake by CMV from EHBR had an apparent Km of 44.6 microM for E-glu. The effects of E-glu, 4-methylumbelliferone glucuronide (4 MUG), E3040 sulfate (E-sul) and 4-methylumbelliferone sulfate (4 MUS) on the uptake of [3H]DNP-SG were also examined. The uptake of [3H]DNP-SG was inhibited by glucuronides (E-glu and 4 MUG) in a concentration-dependent manner, although it was enhanced by the sulfate conjugates (E-sul and 4 MUS). This enhancement was shown to be caused by an increased DNP-SG affinity for the transporter. In CMV from SD rats, although ATP-dependent uptake of [3H]DNP-SG was almost completely inhibited by E-glu, that of [14C]E-glu was only reduced to about 30% of controls by DNP-SG. On the other hand, in CMV from EHBR, the ATP-dependent uptake of [14C]E-glu was not inhibited at all by DNP-SG. Kinetic analysis indicated that E-glu inhibited DNP-SG uptake competitively. IN CONCLUSION: 1) cMOAT recognizes both DNP-SG and E-glu, and another transporter present in SD rats is also involved in E-glu transport along with cMOAT; 2) the latter transporter is kinetically similar to the E-glu transporter present in EHBR; 3) E-sul enhances the uptake of DNP-SG by increasing the affinity of glucuronide for the transporter.

Adenosine Triphosphate↗
PubMed1997

[Effects of eicosapentaenoic acid in patients with bronchial asthma].

Eicosapentaenoic acid (EPA) is composed of 20 unsaturated fatty acids and is similar to arachidonic acid. Epadel, the drug made from EPA, is reported not only to reduce levels of serum lipids, but also to have antiinflammatory and antiallergic effects. EPA may exert these effects via control of the production of prostanoids and leukotrienes. We studied the effects of EPA in patients with bronchial asthma who had hyperlipidemia. The patents were given EPA at 1800 mg/day and they recorded signs and symptoms in an asthma diary during a 2-week observation period and the 8 weeks during which they took the drug. Peak flow, leukotriene B4 concentration in urine, Leukotriene E4 concentration in urine, IgE level, total cholesterol level, and triglyceride level were measured before and after the 8 weeks of medication. Administration of EPA was associated with improvements in symptom score, therapeutic score, asthma score, and peak flow. EPA may be useful in patients with asthma complicated by hyperlipidemia.

Adult↗
PubMed1997

[Successful treatment with intermittent administration of etoposide for an adult case with recurrent hemophagocytic syndrome, developed in association with chronic EB virus infection related lymphoid hyperplasia in the small intestine].

A 28-year-old man complaining of melena accompanied by high grade fever was previously operated on for two small ulcerative, infiltrative lesions of the small bowel at another hospital in April, 1992. In the resected small intestines an immunohistochemical study was positive for EBV encoded RNA (EBER). It is assumed that Epstein-Barr (EB) virus infection has contributed to the small bowel lesions. In March, 1993, he was diagnosed as having chronic EB virus infection. In October, 1993, he was transferred to our hospital for further examination of high grade fever, rapidly worsening thrombocytemia and severe liver disfunction. Mature histiocytes with hemophagocytosis were detected in the bone marrow and he was diagnosed as having hemophagocytic syndrome (HPS) due to reactivation of chronic EB virus infection. Although treatment by corticosteroids, acyclovir and gamma globulin was not effective administration of etoposide induced remission of the disease. In December, 1993 and January, 1994 HPS recurred, but etoposide was again effective in alleviating the disease. To prevent recurrence of HPS after we discharge the patient, intermittent administration of small doses of etoposide was started. Since then HPS has not recurred, and the drug was eventually discontinued in November, 1995. Our case suggested that Etoposide could change the fulminant course of EB virus-associated HPS and that it is effective to sustained remission.

Adult↗
PubMed1997

Selective deficiency of debrisoquine 4-hydroxylase activity in mouse liver microsomes.

Cytochrome P450 enzymes belonging to the CYP2D subfamily have been shown to be one of determinants of the polymorphic drug oxidations in the human and the rat. Debrisoquine 4-hydroxylation is a typical reaction catalyzed by these enzymes. However, various strains of mice were observed to have much lower debrisoquine 4-hydroxylase activity than Wistar rats, whereas other monooxygenase activities in mice toward bunitrolol, propranolol, imipramine and amitriptyline, which are mediated by the CYP2D enzymes in the rat, were comparable to those of the rats. Immunoblot analysis of mouse liver microsomes with an antibody raised against a rat CYP2D enzyme indicated that the mouse liver contained a P450 enzyme(s) immunochemically related to the rat CYP2D enzyme. The antibody inhibited propranolol ring-hydroxylase and imipramine 2-hydroxylase activities, as well as testosterone 16alpha-hydroxylase activity, a typical reaction of mouse CYP2D9, but not debrisoquine 4-hydroxylase activity in mouse liver microsomes. We partially purified a P450 enzyme (designated P450 ML2d) from livers of male ddY mice by monitoring the cross-reactivity with the antibody. The partially purified enzyme was indicated to belong to the CYP2D subfamily from its N-terminal amino acid sequence, but the homology of the sequence to other CYP2D enzymes of the mouse (CYP2D9-11) was 62%, suggesting that P450 ML2d is a novel P450 enzyme. P450 ML2d had the oxidation activities for the rat CYP2D-substrates, such as propranolol 4-hydroxylation and imipramine 2-hydroxylation, in higher rates than those of the microsomes, but did not exhibit debrisoquine 4-hydroxylase activity. Our result is the first finding that a mouse CYP2D enzyme also metabolizes substrates for the rat CYP2D enzyme, in addition to steroids, but the enzyme had a limited specificity for the substrates of the CYP2D enzymes of the rat and the human.

Amino Acid Sequence↗
PubMed1997

[Necrotizing sarcoid granulomatosis diagnosed by video thoracoscopic lung biopsy].

A 28-year-old woman was admitted to our hospital because of chest pain. A chest roentgenogram and a chest computed tomogram revealed many nodular shadows on both sides. Examinations of specimens obtained by and by transbronchial lung biopsy during fiberoptic bronchoscopy were not diagnostic, and therefore video thoracoscopic lung biopsy was done. The lung lesion was characterized by aggregates of epithelioid cell granulomas, along with granulomatous and necrotizing angitis. We therefore diagnosed necrotizing sarcoid granulomatosis, and began to administer prednisolone. The nodular shadows disappeared within four weeks. In this case video thoracoscopic lung biopsy was useful in the diagnosis of necrotizing sarcoid granulomatosis in the lung.

Adult↗
PubMed1997

Lansoprazole elevates the ratio of serum pepsinogen I v.s. pepsinogen II.

In order to investigate the mechanism by which proton pump inhibitor increases serum pepsinogen levels, we evaluated the effects of ulcer location and IgG antibody against Helicobacter pylori on lansoprazole-induced elevations. Patients with endoscopically proven peptic ulcer received lansoprazole 30 mg/day for 6 or 8 weeks; pepsinogen I and II levels, along with antibody to H. pylori, were measured in fasting blood samples. We found that whether or not antibody to H. pylori was present, pepsinogen I and II levels and the I/II ratio rose significantly in lansoprazole-treated patients. Patients with stomach-body ulcers showed smaller increases in both pepsinogens than did those with ulcers in the gastric angle/antrum or in the duodenum. In conclusion, lansoprazole increases serum levels of both pepsinogens I and II, although a larger increase in pepsinogen I elevates the pepsinogen I/II ratio. The relatively small increases seen in patients with stomach-body ulcers suggest atrophic changes in the gastric mucosa in patients with stomach-body ulcer.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1997

[Estimation of respiratory muscle endurance using an inspiratory threshold loading device in patients with chronic pulmonary emphysema and in elderly subjects].

We studied respiratory muscle endurance with an inspiratory threshold loading (ITL) device using Martyn's method (2-min incremental loading test) in 9 patients with chronic pulmonary emphysema (CPE patients) and in 9 elderly subjects with no lung disease (NE subjects), and their endurance was compared with that of 9 normal young subjects (NY subjects). In 11 cases (8 CPE patients and 3 NE subjects) a treadmill exercise test was performed and cardiopulmonary parameters obtained from the ITL and treadmill tests were compared. The maximum weight tolerated for 2 minutes (Wmax) and the mean peak inspiratory mouth pressure/maximum inspiratory mouth pressure ratio at the maximum load (Ppk/MIP at Max Load) were used as indices of respiratory muscle endurance. CPE patients had significantly decreased Wmax compared with those of NE and NY subjects. Wmax in all cases positively correlated with Ppk/MIP at Max Load, and endurance time of both the ITL and treadmill tests. During both tests, SaO2 significantly decreased, and heart rate and mean blood pressure significantly increased. There was less change in SaO2 and heart rate during the ITL test than during the treadmill test, and neither arrhythmias nor ST changes on ECG were observed during the ITL test. These results indicate that the ITL test can be easily and safely employed in CPE patients and elderly subjects to estimate respiratory muscle endurance.

Adult↗
PubMed1997

[A case of primary acute pulmonary cavitation in sarcoidosis complicated by multiple nodular lesions in the central nervous system].

A 20-year-old man visited our hospital complaining of headache and a dry cough. Chest X-ray and chest CT showed bilateral hilar and mediastinal lymphadenopathy, multiple cavitations with thin, smooth walls, and diffuse granular shadows. A transbronchial biopsy specimen revealed sarcoid granuloma. Primary acute pulmonary cavitation of sarcoidosis was diagnosed, since there was no evidence of infection, emphysematous change, fibrotic or cystic bronchiectatic change on chest X-ray. EEG, contrast enhancement of brain CT scans and MRI were performed because the patient complained of headache. EEG showed a high voltage paroxysmal slow wave and giant build-up, whereas brain CT showed no abnormalities. T1-weighted MRI with gadolinium enhancement showed multiple high intensity nodules in the convexity, brain stem, and spinal cord. Corticosteroid therapy (60 mg/day) was started. After 1 week of treatment, the headache ceased. After 2 weeks of treatment, both the cavities in the lung field's and the nodules in the central nervous system disappeared. Therefore, the dose of corticosteroids was gradually reduced to a maintenance dose of 5 mg/day, and no relapse was noted. We report a very rare case of primary acute pulmonary cavitation in sarcoidosis complicated by multiple nodular lesions in the central nervous system.

Adult↗
PubMed1996

Fatty acids selectively inhibit eukaryotic DNA polymerase activities in vitro.

The in vitro relationship between eukaryotic DNA polymerases and fatty acids was investigated. Some fatty acids strongly inhibited the activities of DNA polymerase alpha and/or beta in vitro. The kinetics of inhibition by linoleic acid showed that DNA polymerase alpha was non-competitively inhibited with respect to the DNA template and substrate (dTTP), while DNA polymerase beta was inhibited competitively with both DNA and substrate.

Animals↗
PubMed1996

Cytochrome P450 enzymes involved in the enhancement of propranolol N-desisopropylation after repeated administration of propranolol in rats.

Repeated oral administration of propranolol (PL, 100 mg/kg daily, for 5, 10 and 15 days) to male Wistar rats increased PL N-desisopropylase and decreased PL 4-,5- and 7-hydroxylase activities in liver microsomes. The increase was highest at the 10 day time point whereas the decrease was relatively constant over the 15 day treatment period. There were no significant changes in the total content of cytochromes P450 (P450) or cytochrome b5 or in NADPH-cytochrome c reductase activity during the PI, treatment. The enhanced N-desisopropylase activities were markedly inhibited by alpha-naphthoflavone (a P450-1A1/2 inhibitor), and moderately by triacetyloleandomycin (a P450-3A1/2 inhibitor) and diethyldithiocarbamate (a P450-2E1 inhibitor). Phenacetin O-deethylase activity, an index of P450-1A2, was significantly increased on day 5, 10 and 15 of the treatment, whereas p-nitrophenol hydroxylase activity was elevated on day 10 only. The PL N-desisopropylation showed a strong and significant correlation with phenacetin O-deethylation, and a weaker but significant correlation with p-nitrophenol hydroxylation. Immunoblot analysis revealed that a protein band corresponding to P450-1A2 was increased by PL pretreatment, and protein band corresponding to P450-3A tended to be increased slightly, but other protein band corresponding to the subfamily of P450-2B, -2C, or -2E was not changed. Pretreatment of rats with P450 inducers (beta-naphthoflavone, phenobarbital, acetone and dexamethasone) increased PL N-dealkylase activity in liver microsomes. Furthermore, antibodies raised against P450-1A and -3A enzymes suppressed PL N-desisopropylation in a concentration-dependent manner, but P450-2E antibody did not. Reconstitution studies showed that P450-1A1, -1A2, -2E1 and -3A2 exhibited catalytic activities for PL N-dealkylation. These results suggest that P450-1A2 is a major PL N-desisopropylase in the PL-treated rats, and P450-3A related enzyme(s) and P450-2E1 as a moderate or minor enzyme are also involved in PL N-dealkylation in native and PL-treated rats.

Administration, Oral↗
PubMed1996

Retinoic acid regulates differentially the expression of IL-1 beta and IL-1 receptor antagonist (IL-1ra) in PMA-activated human monocytes.

Retinoic acid (RA) is a well-known immunological modulator. Although it has been shown that RA stimulates IL-1 expression in monocytes, it is of interest for understanding of the regulatory role of RA in inflammation to examine whether RA also modulates the expression of the IL-1 receptor antagonist (IL-1ra), which is reported to reduce IL-1 beta-mediated inflammation. In this study, we examined the effect of RA on expression of IL-1 beta and IL-ra in phorbol-myristate-acetate (PMA)-activated human monocytes. RA enhanced gene expression and production of IL-1 beta in PMA-activated monocytes. However, interestingly, gene expression and production of IL-1ra in the cells were markedly inhibited by RA. These results show that RA differentially regulates IL-1 beta and IL-ra expression in PMA-activated human monocytes and suggest that RA may promote IL-1-mediated inflammation.

Blotting, Northern↗
PubMed1996

cDNA cloning of the hepatocyte canalicular isoform of the multidrug resistance protein, cMrp, reveals a novel conjugate export pump deficient in hyperbilirubinemic mutant rats.

ATP-dependent transport of glutathione and glucuronate conjugates from hepatocytes into bile is mediated by a distinct member of the ATP-binding cassette superfamily. We have cloned and sequenced the canalicular isoform of the multidrug resistance protein from rat liver, and termed it cMrp. This membrane glycoprotein is composed of 1541 amino acids with an identity of 47.8% with the human multidrug resistance protein (MRP) and of 41.9% with the yeast cadmium factor (YCF1). The carboxyl-terminal 130 amino acids of the human hepatocyte canalicular isoform of MRP (cMRP) were 80.2% identical with rat cMrp. cMrp was not expressed in the liver of two mutant rat strains, the Eisai hyperbilirubinemic rat and the GY/TR- mutant, which are deficient in the ATP-dependent transport of conjugates across the canalicular membrane. Immunoblotting using an antibody raised against the carboxyl terminus of cMrp detected the glycoprotein of about 190 kDa only in the canalicular membrane from normal liver. Double immunofluorescence and confocal laser scanning microscopy localized cMrp exclusively to the canalicular membrane domain of hepatocytes and demonstrated its loss in the hyperbilirubinemic mutant rat. The results identify cMrp as a canalicular transport protein with a novel sequence and with a function similar to the one of the MRP.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Characterization of the oxidation reactions catalyzed by CYP2D enzyme in rat renal microsomes.

Monooxygenase activities in rat renal microsomes were determined with the substrates of hepatic CYP2D enzymes. Seven kinds of CYP2D-mediated monooxygenase activities and immunochemically determined CYP2D contents in kidneys corresponded to approximately 3% of those in livers. Debrisoquine 4-hydroxylase and bunitrolol 4-hydroxylase in renal microsomes were inhibited almost completely by the antibody against a CYP2D enzyme purified from rat liver. A marked strain difference (Wistar > Dark Agouti) in these activities was observed in kidney like in liver. The two hydroxylases were inhibited stereoselectively by quinine and quinidine both in renal and hepatic microsomes. Substrate stereoselectivity in (+)- and (-)-bunitrolol 4-hydroxylase activities in kidneys was also consistent with that in livers. These results suggested that the CYP2D enzyme(s) was expressed in the kidney at levels much less than in the liver but had similar functions to those in the liver.

Animals↗
PubMed1996

Detection of different quasispecies of hepatitis C virus core region in cancerous and noncancerous lesions.

The quasispecies of hepatitis C virus (HCV) core region in non-cancerous and cancerous hepatocellular carcinoma (HCC) lesions, respectively, of 7 patients with hepatocellular carcinoma were studied. Multiple fluorescence based-polymerase chain reaction (PCR)-single strand conformation polymorphism exhibited a different set and a larger number of quasispecies in cancerous portions than those in non-cancerous portions. DNA sequencing of PCR-amplified core region substantiated an accumulation of nucleotide substitutions, and a greater number of quasispecies in cancerous portions than those in non-cancerous portions. The deduced amino acid sequences disclosed that at the peptide position 45, Ser is dominant in non-cancerous lesions, and Gly in cancerous lesions, respectively. Thus, HCV in hepatocellular carcinoma includes a large number of specific quasispecies presumably due to their vigorous proliferation. A different set of quasispecies with the amino acid change is presumed to be related to the hepatocarcinogenesis.

Aged↗
PubMed1996

Alterations in glutathione homeostasis in mutant Eisai hyperbilirubinemic rats.

Eisai hyperbilirubinemic rats (EHBR) are mutant Sprague-Dawley rats that exhibit impaired biliary organic anion and reduced glutathione (GSH) secretion. In addition, liver GSH levels are twice that of age-matched controls. The mechanisms for the defect in biliary GSH secretion and the increase in cell GSH are not fully understood. We previously showed that canalicular membrane-enriched vesicles isolated from EHBR livers exhibited normal GSH transport. In the present study, we examined the steady-state rat canalicular reduced glutathione transporter (RcGshT) messenger RNA (mRNA) and protein levels, as well as the mechanisms for the increase in cell GSH. Both Northern and Western blot analyses of EHBR livers showed nearly identical RcGshT mRNA and polypeptide levels, respectively, as compared with controls. Treatment with phenobarbital, which increased steady-state RcGshT mRNA by five- to sixfold, RcGshT polypeptide, and biliary GSH secretion by onefold in controls, had a smaller effect on steady-state RcGshT-mRNA level in EHBR (by 1.5-fold) and did not increase RcGshT polypeptide or biliary GSH secretion. In examining possible mechanisms for increased liver GSH, both cysteine level and gamma-glutamylcysteine synthetase (GCS) activity were significantly higher than controls, while the activity of GSH synthetase was unchanged. Northern and Western blot analyses also showed increased steady-state GCS heavy subunit (GCS-HS) mRNA and polypeptide levels, respectively. In addition to liver, GSH levels in kidney, duodenal, jejunal, and ileal mucosa of EHBR were 200% to 300% of age-matched control rats. GCS activity was also increased in kidney cytosol of EHBR. Thus, the defect in biliary GSH secretion in EHBR most likely is either at the posttranslational level of RcGshT or in the inhibition exerted by retained endogenous organic anions. In addition, there is a widespread up-regulation of GSH synthesis capacity in the tissues of EHBR.

Analysis of Variance↗
PubMed1996

Patient with both lupus anticoagulant and acute disseminated encephalomyelitis.

We present the unusual case of 16-year-old girl who developed intractable convulsions five days after the onset of a cold. Meningeal signs, lymphopenia, proteinuria, and lupus anticoagulant were also present. Treatment with anticonvulsants, antituberculous agents, and adenine arabinoside were ineffective. The initiation of methylprednisolone pulse therapy immediately resolved convulsions and fever. The diagnosis, suggested by the clinical course and the marked improvement of the meningoencephalitis by pulse therapy, was an encephalitic form of acute disseminated encephalomyelitis. Clinical and laboratory findings indicated that an immune disorder may have triggered an abnormal response to a viral infection leading to this patient's neurologic disorder.

Acute Disease↗