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Biomedical subjects

T Horie

Publications and source records attributed to T Horie.

At least 235 records · Page 13Linked to original sources
PubMed1996

Biliary excretion of glycyrrhizin in rats: kinetic basis for multiplicity in bile canalicular transport of organic anions.

PURPOSE: To examine the presence of multiplicity for the biliary excretion of xenobiotic conjugates, we studied the disposition of glycyrrhizin (GR), which has glucuronide within its molecular structure and has the ability to inhibit the biliary excretion of liquiritigenin (LG) glucuronides. METHODS: GR was administered intravenously as a bolus to Sprague-Dawley (SD) rats which received an i.v. infusion of inhibitors (dibromosulfophthalein (DBSP) and indocyanine green (ICG)) at their transport maximum rates. Biliary excretion of GR was also examined in Eisai hyperbilirubinemic rats (EHBR), which have a hereditary defect in the canalicular transport system of several organic anions. RESULTS: Infusion of ICG did not affect the biliary excretion of GR, whereas infusion of DBSP reduced it significantly. The plasma concentration of GR was increased by DBSP but not by ICG. In EHBR, the biliary excretion of GR was severely impaired, resulting in an increase in the plasma concentration of GR. CONCLUSIONS: These findings suggest (1) that the biliary excretion of GR is mediated by the system which is shared by DBSP and LG glucuronides but not by ICG and (2) that this system is hereditarily defective in EHBR. Together with our previous findings, the multiplicity for the biliary excretion of organic anions is shown.

Animals↗
PubMed1996

Elevation of plasma-soluble tumour necrosis factor receptors (TNF-R) in sarcoidosis.

Two types of receptor for tumour necrosis factor-alpha (TNF-R), the 55-kD receptor (TNF-RI) and the 75-kD receptor (TNF-RII), have been identified. Soluble TNF-RI (sTNF-RI) and soluble TNF-RII (sTNF-RII) can be measured in culture supernatants and biological fluids, and the role of sTNF-R has been suggested. In the present study, we measured plasma sTNF-RI and sTNF-RII levels in 19 patients with active sarcoidosis by ELISA in order to assess the state of both types of receptors in this disease. Both plasma sTNF-RI and sTNF-RII levels in patients with active sarcoidosis were significantly higher than those in normal control subjects. A longitudinal evaluation of plasma sTNF-RI and sTNF-RII levels showed that the magnitude of changes in sTNF-RII was closely related with the clinical course of sarcoidosis. These results suggest that plasma sTNF-RII levels may be useful parameters for monitoring the clinical course of sarcoidosis as well as markers for identifying disease activity.

Adult↗
PubMed1996

Elevation of serum soluble tumour necrosis factor (TNF) receptor and IL-1 receptor antagonist levels in bronchial asthma.

The specific inhibitor for TNF-alpha activity, soluble form of the 55-kD TNF receptor (sTNF-RI) and soluble form of the 75-kD receptor (sTNF-RII), and the specific inhibitor for IL-1 activity, IL-1 receptor antagonist (IL-1Ra), have been identified. It has been shown that the levels of these inhibitors are elevated in plasma/serum and biological fluids in several diseases, and the protective and inhibitory effect of these inhibitors exist in several inflammatory diseases. In the present study, we measured serum levels of sTNF-RI, STNF-RII and IL-1Ra by ELISA in 36 patients with bronchial asthma (16 atopic and 20 non-atopic) during asthma attacks and in stable conditions in order to assess the state of these inhibitors in allergic inflammation. The levels of sTNF-RI, sTNF-RII and IL-1Ra in sera obtained during bronchial asthma attacks were higher than those in sera obtained in stable conditions. These findings were obtained regardless of atopic status. These results suggest that higher levels of serum sTNF-RI, sTNF-RII and IL-1Ra may reflect up-regulation of TNF-R expression and IL-1Ra production in allergic inflammation, and sTNF-RI, sTNF-RII and IL-1Ra may contribute to regulating TNF-alpha- and IL-1-mediated production and development of allergic inflammation.

Adult↗
PubMed1996

A phase III randomized trial of cisplatin plus vindesine versus cisplatin plus vindesine plus mitomycin C versus cisplatin plus vindesine plus ifosfamide for advanced non-small-cell lung cancer.

A randomized trial of chemotherapy in 105 patients with advanced and metastatic non-small-cell lung cancer (NCSLC) was conducted in order to compare the effect of the additional drug mitomycin C (PVM) or ifosfamide (PVI), to the combination of cisplatin plus vindesine (PV). An objective response rate was observed in 42.8% of the patients treated with PVM, 42.4% with PVI and 28.6% with PV and these response rates were not statistically significant (P > 0.20). No patient achieved the complete response with either of the three regimens. Comparison of the median response durations among the three regimens showed an advantage of PVI over PVM (P < 0.02) and PV (P < 0.05). The median survival times (MST) were similar for all three regimens (PVM, 33.5; PVI, 40.0 and PV, 36.5 weeks); moreover, the difference in survival time between the three regimens of responders was not statistically significant. The univariate analysis showed that significant predictors of survival were performance status (PS) zero (P = 0.0002), limited disease (P = 0.004), no previous weight loss (P = 0.01) and normal serum albumin (P = 0.016), and in multivariate analysis by a stepwise Cox proportional hazard model, these were PS zero (a hazard ratio of 2.3, P = 0.0001) and limited disease (a hazard ratio of 1.9, P = 0.048). Toxicity did not differ among the three treatment regimens.

Aged↗
PubMed1996

Regioselectivity and substrate concentration-dependency of involvement of the CYP2D subfamily in oxidative metabolism of amitriptyline and nortriptyline in rat liver microsomes.

Kinetic analysis of the metabolism of amitriptyline and nortriptyline using liver microsomes from Wister rats showed that more than one enzyme was involved in each reaction except for monophasic amitriptyline N-demethylation. The Vmax values particularly in the high-affinity sites for E-10-hydroxylation of both drugs were larger than those for Z-10-hydroxylations. Their E- and E-10-hydroxylase activities in Dark-Agouti rats, which are deficient for CYP2D1, were significantly lower than those in Wistar rats at a lower substrate concentration (5 microM). The strain difference was reduced at a higher substrate concentration (500 microM). A similar but a smaller strain difference was also observed in nortriptyline N-demethylase activity, and a pronounced sex difference (male > female) was observed in N-demethylation of both drugs in Wistar and Dark-Agouti rats. The reactions with the strain difference were inhibited concentration-dependently by sparteine, a substrate of the CYP2D subfamily, and an antibody against a CYP2D isoenzyme. The profiles of these decreased metabolic activities corresponded to that of the lower metabolic activities in Dark-Agouti rats. These results indicated that a cytochrome P450 isozyme in the CYP2D subfamily was involved in E- and Z-10-hydroxylations of amitriptyline and nortriptyline in rat liver microsomes as a major isozyme in a low substrate concentration range. It seems likely that the CYP2D enzyme contributes to nortriptyline N-demethylation.

Amitriptyline↗
PubMed1996

Localization of a novel non-peptide angiotensin II type 1 receptor antagonist, E4177, in rat adrenal glomerulosa.

We investigated the distribution of a novel angiotensin II type 1 (AT1) receptor antagonist, E4177 (4'-[2-cyclopropyl-7-methyl-3H-imidazo[5,4-b]pyridine-3-yl]methyl-2- biphenylcarboxylic acid), in rat adrenal glomerulosa. In a binding assay of adrenal capsular tissue (mainly glomerulosa), E4177 exhibited a maximum displacement of approximately 80% of total 125I-labeled angiotensin II (125I-[Sal1, Ile8] Ang II) binding, and its IC50 value was 6.9 +/- 0.5 nM. This IC50 value indicated a slightly higher in vitro potency than that of losartan (21.0 +/- 0.6 nM). Also, in a receptor autoradiographic study, E4177 (10000 nM) displaced approximately 80% of radiolabeled 125I-[Sal1, Ile8] Ang II in rat adrenal glomerulosa and caused only slight displacement in rat adrenal medulla. Further, light and electron microscopic autoradiography of adrenal glomerulosa for 15 min after the intravenous administration of 1 mg/kg [14C]E4177, indicated the localization of 14C, possibly in the adrenal zona glomerulosa cell plasma membrane. It was strongly suggested that E4177 is a potent and selective antagonist of the AT1 receptor, and that it specifically binds to AT1 receptors in the adrenal zona glomerulosa.

Angiotensin Receptor Antagonists↗
PubMed1996

Stereoselectivity in bunitrolol 4-hydroxylation in liver microsomes from marmosets and Japanese monkeys.

The stereoselectivity in 4-hydroxylation of bunitrolol (BTL), a beta-adrenoreceptor blocking agent, was examined in liver microsomes from monkeys (marmosets and Japanese monkeys) and compared with the results of human liver microsomes. The formation of (+)-4-OH-BTL from (+)-BTL from (+)-BTL was significantly higher than that of (-)-4-OH-BTL from (-)-BTL in the liver microsomal fractions from the two kinds of monkeys. The 4-OH-BTL-forming activity from racemic BTL was significantly lower than from enantiomeric BTL, indicating a possible metabolic interaction between BTL enantiomers. The in vitro profiles observed in the monkeys were very similar to those in humans, but the stereoselectivity in BTL metabolism [(+)-BTL > (-)-BTL] in the primates was found to be reverse to that in rats [S. Narimatsu et al., Anal. Biochem., 222, 256-261 (1994)]. The 4-OH-BTL-forming activity from BTL enantiomers was significantly suppressed by quinidine and quinine, while the former was more potent than the latter, and also by alpha-naphthoflavone. Furthermore, the activity was also suppressed by antisera against rat cytochromes P450-2D2 and -1A2 in concentration-dependent manners. However, kinetics showed that enantiomeric BTL 4-hydroxylation was monophasic in liver microsomes from marmosets of both genders and from male Japanese monkeys. These results suggest that cytochrome P450-2D and -1A enzymes with similar Km values are involved in BTL 4-hydroxylation in monkey liver microsomes.

Adrenergic beta-Antagonists↗
PubMed1996

Abnormal Q wave, ST-segment elevation, T-wave inversion, and widespread focal myocytolysis associated with subarachnoid hemorrhage.

A 74-year-old Japanese woman with subarachnoid hemorrhage was admitted to our hospital. During her hospitalization, serial electrocardiograms showed the combination of abnormal Q waves, ST-segment elevation, and T-wave inversion, which strongly suggested acute myocardial infarction. However, postmortem examination revealed widespread focal myocytolysis of the myocardium which was unrelated to vascular distribution.

Aged↗
PubMed1996

Isolation and characterization of the heat-responsive genes in Escherichia coli.

The ompC gene expression is induced by increasing temperature as well as osmotic pressure. In this study, a mutant (TD2) defective in this thermoresponse was isolated with transposon Tn10; the mutation was complemented by pMAN55 or pMAN56 containing micF and mapped at 48 min on Escherichia coli K-12. Furthermore, a new gene (hrsA) that suppressed the mutation was cloned. Its nucleotide sequence was analyzed and it was located close to the suc operon at 16.7 min corresponding to #18F11 (Kohara bank) on E. coli genome. In TD2 containing the hrsA on a multicopy plasmid, the ompC expression was induced and dependent on OmpR with increased temperature. The HrsA was found to have Enzyme IIA, IIB, and IIC domains that are homologous to Enzyme II, involved in the fructose-specific PTS (phosphotransferase system). The putative phosphorylation sites (His87 and Cys192) were also conserved in HrsA.

Amino Acid Sequence↗
PubMed1996

Restriction fragment length polymorphism analysis in the HLA class III genes of patients with diffuse panbronchiolitis.

Although diffuse panbronchiolitis (DPB) is known to be positively associated with certain major histocompatibility complex (MHC) class I antigens, e.g., HLA-B54 in Japanese patients, it is not clear whether the MHC genes predispose to the disease or are markers for other disease susceptibility gene(s). Because the HLA class III genes such as tumor necrosis factor (TNF) or the fourth component of complement (C4) are localized in the proximity of the HLA-B locus, one or more of these genes might be responsible for susceptibility to DPB. To analyze the role of HLA class III genes in DPB patients, we first evaluated the HLA-B54 association in 32 patients with DPB, and subsequently, studied the restriction fragment length polymorphism (RFLP) of the TNF-alpha and -beta (TNF-alpha/beta) genes as well as the C4A and B (C4A/B) genes in DPB patients and normal individuals. The HLA-B54 antigen was significantly more frequent in DPB patients than in normal individuals (40.3% vs 13.0%, p < 0.001), however, we did not detect a significant association between DPB and gene polymorphisms of either TNF-alpha/beta or C4A/B. Furthermore, there was no evidence of C4A gene deletion in patients with DPB. These results suggest that the HLA-B54 antigen itself might be directly involved in the pathogenesis of DPB.

Bronchiolitis↗
PubMed1996

[A case of acquired immunodeficiency syndrome associated with cryptococcemia and cryptococcal meningitis].

A case of acquired immunodeficiency syndrome (AIDS) developed cryptococcosis which was successfully treated with amphotericin B (AMPH) and fluconazole (FLCZ) is reported. A 52-year-old man was admitted because of pyrexia and oral candidiasis. He had a history of multiple sexual exposures to persons at risk for AIDS in Thailand. On admission, serologic tests for human immunodeficiency virus (HIV)-1 were positive on both EIA and Western blot analysis for anti-HIV-1 antibody. Furthermore, test for cryptococcal antigen and fungal cultures from blood and cerebrospinal fluid revealed that he was suffering from cryptococcemia and cryptococcal meningitis. In spite of identification of Cryptococcus neoformans in his blood and cerebrospinal fluid, the finding of cerebrospinal fluid had a minimal inflammatory response with mild elevation of protein. He was initially treated with intravenous AMPH, 10 to 30 mg a day, for 7 weeks, and then was given oral FLCZ, 400 mg a day, for the suppressive therapy. His fever subsided three weeks after the start of AMPH therapy. He was eventually discharged 9 weeks after the start of therapy without any symptoms, and continued to receive oral FLCZ as an out-patient. Thus, attention should be paid to diagnosis and treatment for cryptococcal meningitis in AIDS patients.

AIDS-Related Opportunistic Infections↗
PubMed1996

[A study of the significance of serum beta 2-microglobulin levels in patients with multiple myeloma--analyzes as a marker of renal dysfunction and as a marker of tumor cell mass].

Renal involvement known as a myeloma kidney is often observed in patients with multiple myeloma (MM). This complication has been recognized as one of the most important prognostic factors in this disease. Serum beta 2-microglobulin (S beta 2-m) has been also recognized one of the prognostic factor that reflects both a glomerular infiltration rate and a volume of neoplastic cells, because beta 2-m usually can be produced by the neoplastic lymphoid cells. To clarify the significance of the S beta 2-m in MM, we compared S beta 2-m levels and the clinical stage, with another clinical parameters for renal function such as 24 hr creatinine clearance (24 hr Ccr), N-acetyl-beta-glucosaminidase (NAG) levels in urine and serum alpha 1-microglobulin (S alpha 1-m) levels. The elevated S beta 2-m levels were commonly observed not only in patients with stage IIIB, but also in stage IA, IIA and IIIA (76%) who have normal renal function judged by the serum nitrogen or creatine levels. S beta 2-m levels correlated with 24 hr Ccr the most, then correlated with S alpha 1-m levels and less correlated with NAG levels in urine. Although a single elevation of S beta 2-m levels with other normal findings of renal parameters was found only in three out of 30 MM patients, the S beta 2-m levels in these patients did not change after the chemotherapy which had led to the diminution of serum M-protein. Together with these results, it was suggested that the S beta 2-m levels mainly reflect the renal dysfunction even if it stays in the subclinical stage, and reflect less the number of neoplastic cells in MM patients.

Biomarkers↗
PubMed1996

[Swyer-James syndrome with bronchial asthma and recurrent spontaneous pneumothorax].

An 18-year-old woman was admitted to our hospital for treatment of the fifth episode of spontaneous pneumothorax. She had a history of repeated pneumonia in childhood and mycoplasma pneumonia at 12 years of age. A chest X-ray film revealed a left-sided pneumothorax, atelectasis of the left upper lobe, and hyperlucency of the left lung. A bronchogram showed poor filling of the peripheral bronchi by contrast medium and mild cylindrical bronchiectasis in the proximal bronchi. Pulmonary arteriography showed small left pulmonary arteries. From these findings, Swyer-James syndrome was diagnosed. This case was complicated by bronchial asthma, with eosinophilia, a high level of IgE, and airway hyperresponsiveness. Atelectasis, multiple bullae, and bronchial asthma had been caused by mycoplasma pneumonia in childhood. Recurrent pneumothorax had been caused by emphysematous changes in the bronchioli and by underdeveloped pulmonary arteries. Surgery to treat the recurrent spontaneous pneumothorax was considered, but was not done because of the risk of relapse and the ventilation-perfusion imbalance due to the Swyer-James syndrome.

Adolescent↗
PubMed1996

[Hypertonic saline induced bronchoconstriction in sensitized rabbits].

Hypertonic saline is a potent stimulus to airway narrowing in most asthmatic patients. However, the mechanism of airway narrowing induced by a change in osmolarity is not clearly understood. In ovalbumin-sensitized rabbits, we found that bronchoconstriction occurred after inhalation of hypertonic saline, and then studied the mechanisms responsible for this bronchoconstriction. Eighteen anesthetized, paralyzed, mechanically ventilated (40 breath/min, TV 7 ml/kg) ovalbumin-sensitized rabbits were exposed to aerosols of hypertonic saline (ultrasonic nebulizer, 0.5 ml/min, 1 min). Total lung resistance (RL) and dynamic compliance (Cdyr) of the lung were measured before and after the exposure. The concentration of NaCl was increased from 0.9% to 7.2% in 0.9% steps. RL increased and Cdyr decreased as the dose of NaCl rose and they reached plateaus at doses of 6.3% and 7.2%, respectively. These responses were markedly inhibited by treatment with atropine (5 mg/kg i.v., p < 0.05 vs. control group), but treatment with chlorpheniramine (1 mg/kg iv.) suppressed the responses only at low concentrations of NaCl. In contrast, treatment with indomethacin, did not significantly change the responses. We conclude that inhalation of hypertonic saline can cause bronchoconstriction in sensitized rabbits, and that vagal stimulation plays a major role in this bronchoconstriction.

Animals↗
PubMed1996

[Clinical evaluation of fiberoptic bronchoscopy for the diagnosis of solitary pulmonary nodules 2 cm or less in diameter of chest roentgenogram].

The value of fiberoptic bronchoscopy in the diagnosis of solitary pulmonary nodules was studied. The subjects were 59 patients with chest-roentgenographic evidence of a solitary pulmonary nodule 2 cm or less in diameter. Definitive diagnoses were made in 34 patients (57.6%). Primary lung care was diagnosed 21 of 32 patients (65.6%), pulmonary tuberculosis in 7 of 12 (58.3%), metastatic lung cancer in 3 of 5 (60%), old lesions in 3 of 5 (60%), and pulmonary filariasis in 0 of 1 (0%). The diagnostic sensitivity of transbronchial biopsy was superior to that of curettage, and combining the two techniques further improved the diagnostic yield. Bronchial lavage was not effective for diagnosis of lung cancer, but was effective for diagnosis of pulmonary tuberculosis. Diagnostic yield was less for nodules in upper lobes than for those in other lobes, and most malignant tumors that were not diagnosed from the results of fiberoptic bronchoscopy were in upper lobes. We conclude that combining various fiberoptic bronchoscopic procedures can improve the diagnostic yield in patients with small pulmonary nodules. CT-guided needle biopsy and video-assisted thoracoscopic biopsy are two such procedures. Early diagnosis of small pulmonary nodules requires a skilled bronchoscopist who can choose the most appropriate method for biopsy.

Bronchoscopy↗
PubMed1996

Lower serum concentrations of cytokines in elderly patients with pneumonia and the impaired production of cytokines by peripheral blood monocytes in the elderly.

It has been well documented that the immune function declines with age; however, little is known about the monocyte/macrophage function of age. In the present study, we measured the concentrations of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-1 beta, tumour necrosis factor-alpha (TNF-alpha), IL-8 and monocyte inflammatory protein-1 alpha (MIP-1 alpha) in sera from 15 elderly patients and 22 young patients with pneumonia, in the acute phase and after recovery, by ELISA. In addition, we measured the concentrations of these cytokines in culture supernatants from lipopolysaccharide (LPS)-stimulated peripheral blood monocytes from normal healthy elderly subjects and young subjects in order to clarify the ability of the elderly to produce these cytokines. The concentrations of these cytokines in sera from old patients and in those from young patients obtained in the acute phase were higher than those in sera obtained after recovery phase. However, the concentrations of these cytokines in the acute phase were lower in elderly patients compared with those in young patients. Serum concentrations of cytokines did not appear to be associated with clinical outcome. In the production of these cytokines by monocytes, LPS-stimulated monocytes from healthy normal elderly subjects produced smaller amounts of G-CSF, GM-CSF, IL-1 beta, TNF-alpha, IL-8 and MIP-1 alpha than those from healthy normal young subjects. These results with the impaired production of these cytokines in the elderly may prove, at least in part, the characteristic features of host defence mechanisms of the elderly.

Adult↗