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Y Sugiyama

Publications and source records attributed to Y Sugiyama.

At least 73 records · Page 4Linked to original sources
PubMed2001

Chemical characterization of organic carbon dissolved in natural waters using inorganic adsorbents.

Dissolved organic carbon (DOC) in water samples from Lake Biwa was chemically characterized by two inorganic adsorbents with completely different surface characteristics. The two adsorbents were HIO (hydrous iron oxide) and SG (silica gel). Solutions of reference standard materials were analyzed concerning their adsorption behavior to HIO and SG for bovine serum albumin (BSA), fulvic acid extracted from the bottom sediments of Lake Biwa, phthalic acid, and starch. The adsorption of DOC to HIO was mainly controlled by ligand exchange and electrostatic interaction; that of SG was by electrostatic interaction. It was found that in a weak acid solution of around pH 5, BSA adsorbs to both HIO and SG, but that fulvic acid, phthalic acid and starch only show adsorption to HIO. Using these characteristics, DOC samples in natural water samples were characterized into pro-DOC, which adsorbs to both HIO and SG at pH 5, and car-DOC, which only adsorbs to HIO at pH 5. The DOC samples in Lake Biwa on October 7, 1997, at sampling sites Nb-2 and Nb-5 (south basin of Lake Biwa, the depths were about 2 and 4 m), and Ie-1 (north basin of Lake Biwa, the depth was about 75 m) were characterized. The pro-DOC has different values, depending on their sampling sites and depths, and had the maximum value of 0.42 mg C l(-1) at the surface water of Ie-1, and had the lowest values at middle to deeper water depths (0.18-0.27 mg C l(-1)). The car-DOC showed a relatively stable value at Ie-1 regardless of the depth (0.63-0.83 mg C l(-1)), and the maximum value was observed in Nb-2 and Nb-5 (1.2 and 1.3 mg C l(-1)). The ratios between car-DOC and pro-DOC concentrations were 0.2-0.5, and had different values for different sampling sites and depths. The ratios were significantly different for surface water samples where the biological activities are high and for bottom water samples where decomposition predominates.

Absorption↗
PubMed2001

A comparison of the effects of 3-hydroxy-3-methylglutaryl-coenzyme a (HMG-CoA) reductase inhibitors on the CYP3A4-dependent oxidation of mexazolam in vitro.

HMG-CoA reductase inhibitors can be divided into two groups: those administered as the prodrug, i.e., the lactone form (e.g., simvastatin and lovastatin), and those administered in the active form, i.e., the acid form (e.g., pravastatin, fluvastatin, atorvastatin, and cerivastatin). In this study, the influence of the lactone and acid forms of various HMG-CoA reductase inhibitors on metabolism by CYP3A4, a major cytochrome P450 isoform in human liver, was investigated by determining the in vitro inhibition constant (K(i) value) using an antianxiety agent, mexazolam, as a probe substrate. In human liver microsomes, all the lactone forms tested inhibited the oxidative metabolism of mexazolam more strongly than did the acid forms, which have lower partition coefficient (logD(7.0)) values. In addition, the degree of inhibition of mexazolam metabolism tended to increase with an increasing logD(7.0) value of the HMG-CoA reductase inhibitors among the lactone and acid forms. In particular, pravastatin (acid form), which has the lowest logD(7.0) value, failed to inhibit CYP3A4 activity. Taking account of the lipophilicity of the inhibitors, in conjunction with the CYP3A4-inhibitory activity, could be very useful in predicting drug interactions between substrates of CYP3A4 and HMG-CoA reductase inhibitors.

Acids↗
PubMed2001

[Induction chemotherapy (cisplatin + vinorelbine) is found to be markedly effective for squamous cell lung carcinoma with sarcoidosis--a case report].

A sixty-one-year-old man was admitted to our hospital because of a right lung tumor shadow. He had been diagnosed as having sarcoidosis at the age of fifty-seven. He was newly diagnosed as having squamous cell carcinoma by trans bronchial biopsy. He was treated with an induction chemotherapy (cisplatin 80 mg/m2 + vinorelbine 20 mg/m2) followed by right middle and lower lobectomy with a mediastinal nodal dissection, because the stage of his carcinoma was cT2N2M0. Resected lung tissue showed the disappearance of cancer cells. Dissected mediastinal and hilar lymph nodes showed many sarcoid granulomas. Cisplatin combined with vinorelbine might be an effective chemotherapy for non-small cell lung carcinoma.

Antineoplastic Agents↗
PubMed2001

[Case report of a malfunctioning SJM 19 A aortic valve prosthesis requiring reoperation].

The patient was a 56-year-old female diagnosed with poor lung function who had undergone an aortic valve replacement 10 years ago, receiving an SJM 19 A prosthetic valve. She suffered from dyspnea and chest pain with postural change. Her anticoagulation level was maintained therapeutic. A cinefluoroscopy showed that one of the leaflets in the prosthetic valve was not moving. The aortic peak pressure gradient was calculated to be 68 mmHg using Doppler echocardiography. The patient's clinical condition improved after thrombolytic therapy with urokinase, but a complete normalization of her prosthetic discs was not obtained, so the patient was treated surgically. After an aortotomy, a pannus formation covering the entire SJM 19 A valve was observed. The aortic annulus was estimated to be 16 mm in diameter after the excision of the SJM 19 A valve and required before a larger prosthesis could be inserted. A SJM 19 HP valve was then anchored to the enlarged annulus. Her postoperative course was uneventful. We report a case requiring reoperation after a small aortic mechanical valve prosthesis implanted 10 years previously was damaged by thrombosis and pannus. Pannus formation on small aortic prosthesis easily caused hemodynamic obstructions and mechanical failure. Intensive evaluation with Doppler echocardiography and cinefluoroscopy is required for such patients.

Aortic Valve↗
PubMed2001

Carrier-mediated hepatobiliary transport of a novel antifolate, N-[4-[(2,4-dianninopteridine-6-yl)methyl]-3,4-dihydro-2H-1,4-benzothiazin-7-yl]carbonyl-L-homoglutamic acid, in rats.

The hepatic uptake and biliary excretion of a novel methotrexate derivative, N-[4-[(2,4-diamminopteridine-6-yl)methyl]-3,4-dihydro-2H-1,4-benzothiazin-7-yl]carbonyl-L-homoglutamic acid (MX-68), were examined in rats in vitro using isolated hepatocytes and bile canalicular membrane vesicles (CMVs), respectively. The uptake of MX-68 by isolated rat hepatocytes showed a saturable component (Km = 2.15 microM and Vmax = 2.34 pmol/min/mg of protein) and was inhibited by ATP-depletors and anionic compounds such as taurocholate and probenecid. [3H]MX-68 uptake was also inhibited by folate analogs such as methotrexate and 5CH3-tetrahydrofolate, but the effect of these compounds was slightly less than that of unlabeled MX-68. On replacing Na+ with choline, MX-68 uptake remained unchanged, whereas the methotrexate uptake was reduced. Uptake of MX-68 increased as the extracellular pH fell from 7.5 to 5.5. These results suggest that MX-68 is taken up via active transport systems. The uptake of MX-68 by CMVs prepared from normal rats exhibited clear ATP dependence, whereas ATP had only a minimal effect on the uptake by CMVs from Eisai-hyperbilirubinemic rats with a hereditary deficiency in canalicular multispecific organic anion transporter (cMOAT). The initial uptake rate of ATP-dependent MX-68 transport showed saturation with kinetic parameters similar to those of methotrexate. MX-68 inhibited the ATP-dependent transport of 2,4-dinitrophenyl-S-glutathione, a typical substrate for cMOAT, the inhibition constant (162 microM) being comparable with the Km of ATP-dependent MX-68 transport. These results suggest that the biliary excretion of MX-68 via the bile canalicular membrane is mediated mainly by cMOAT. In conclusion, active transport systems are involved in membrane penetration of MX-68 both at sinusoidal and canalicular sides in the liver, the latter being mainly involved with methotrexate (MTX) whereas the former differs partially from that for MTX.

2-Aminoadipic Acid↗
PubMed2001

Inhibition of biliary excretion of methotrexate by probenecid in rats: quantitative prediction of interaction from in vitro data.

This study was designed to establish a strategy to predict drug interactions involving biliary excretion. The interaction between methotrexate and probenecid was examined as an interaction model since this interaction has already been clinically reported. Coadministration of probenecid reduced the biliary clearance of methotrexate in a dose-dependent manner in rats. This inhibition by probenecid was confirmed in vivo both in the uptake and excretion processes of methotrexate across sinusoidal and canalicular membranes, respectively. That is, both hepatic uptake clearance, assessed in integration plot analysis, and steady-state biliary clearance defined with respect to hepatic unbound methotrexate, were reduced in the presence of probenecid. Probenecid inhibited the active transport of methotrexate both in isolated hepatocytes and canalicular membrane vesicles, confirming the interaction at those two membranes. The degree of inhibition of the uptake and excretion processes found in vivo was comparable with the predicted values using the inhibition constant assessed in isolated hepatocytes and canalicular membranes, respectively. This suggests that the interaction at each membrane transport process can be quantitatively estimated from in vitro data. We have also proposed the method to predict the degree of inhibition of the net excretion from circulating plasma into the bile, the predicted values being also comparable with the inhibition actually found in vivo. The present analysis demonstrates a strategic rationale for predicting drug interactions involving biliary excretion using in vitro systems to avoid any false negative predictions.

Animals↗
PubMed2001

Drug interaction between simvastatin and itraconazole in male and female rats.

Taking into account the species and sex differences in drug interactions based on the inhibition of cytochrome P450 (P450)-mediated drug metabolism, we examined whether the interaction between simvastatin and itraconazole observed in humans could also occur in rats, the most commonly used animal species for pharmacokinetic studies. Itraconazole inhibited the in vitro metabolism of simvastatin in female rat liver microsomes, but not in male rat liver microsomes. Using anti-P450 antisera, the main P450 isozyme responsible for the metabolism of simvastatin was identified as CYP3A in female rats and CYP2C11 in male rats. Therefore, the sex difference in the inhibition of simvastatin metabolism by itraconazole seems to be caused by a difference in the P450 isozymes responsible for the metabolism of simvastatin in male and female rats and the different ability of itraconazole to inhibit CYP3A and CYP2C11. In addition, the effect of itraconazole on the pharmacokinetics of simvastatin in rats was also investigated. The area under the curve value of simvastatin was increased approximately 1.6-fold by the concomitant use of itraconazole (50 mg/kg) in female rats, whereas in male rats, itraconazole had no effect. In conclusion, it was found that the results obtained in male rats did not reflect the results in humans as far as the inhibition of simvastatin metabolism by itraconazole was concerned. The P450 isozymes involved in the metabolism of drugs should be taken into consideration when rats are used as a model animal for humans in the investigation of drug interactions.

Animals↗
PubMed2001

Characterization of the efflux transport of 17beta-estradiol-D-17beta-glucuronide from the brain across the blood-brain barrier.

The contribution of organic anion transporters to the total efflux of 17beta-estradiol-D-17beta-glucuronide (E(2)17betaG) through the blood-brain barrier (BBB) was investigated using the Brain Efflux Index method by examining the inhibitory effects of probenecid, taurocholate (TCA), p-aminohippurate (PAH), and digoxin. E(2)17betaG was eliminated through the BBB with a rate constant of 0.037 min(-1) after the microinjection into the brain. Probenecid and TCA inhibited this elimination with an IC50 value of 34 and 1.8 nmol/0.5 microl of injectate, respectively, whereas PAH and digoxin reduced the total efflux to about 80 and 60% of the control value, respectively. The selectivity of these inhibitors was confirmed by examining their inhibitory effects on the transport via organic anion transporting polypeptide 1 (Oatp1), Oatp2, organic anion transporter 1 (Oat1), and Oat3 transfectants using LLC-PK1 cells as hosts. Digoxin specifically inhibited the transport via Oatp2 (K(i) = 0.037 microM). The K(i) values of TCA for Oatp1 and Oatp2 (11 and 39 microM, respectively) were about 20 times lower than those for Oat1 and Oat3 (2.8 and 0.8 mM, respectively). PAH did not affect the transport via the Oatp family, but had a similar affinity for Oat1 and Oat3 (85 and 300 microM, respectively). Probenecid had a similar affinity for these transporters (Oatp1, Oatp2, Oat1, and Oat3) examined in this study. Taking the selectivity of these inhibitors into consideration, the maximum contribution made by the Oatp2 and Oat family to the total efflux of E(2)17betaG from the brain appears to be about 40 and 20%, respectively.

Animals↗
PubMed2001

Human dendritic cells pulsed with autologous Epstein-Barr virus transformed B-cell lymphoblastoid cell (BCL) lysate elicit a BCL specific MHC-class II restricted T-cell response.

Epstein Barr Virus (EBV) associated lymphoproliferative disorders (LPD) express EBV latent antigens that are also expressed on normal B-cells transformed with EBV. This could potentially be exploited to develop immunotherapeutic strategies for LPD and other EBV associated malignancies. To this end we investigated the capacity of human monocyte derived dendritic cells (DC) pulsed with lysate from autologous EBV transformed B-cell lymphoblastoid cell (BCL) lysate to elicit an in vitro antitumor response. BCL lysate pulsed DC generate BCL specific cytotoxic lymphocytes, as lymphocytes primed with such DCs induce cytolysis of autologous (>60%) but not allogeneic BCL (<5%). In addition, lymphocytes primed with BCL lysate pulsed DC secrete gamma-IFN (3176 pg/ml). Whereas gamma-IFN production was markedly reduced (>99%) when BCL specific T-cells were stimulated by BCL lysate pulsed DC in the presence of blocking antibodies to HLA-DR, DP and DQ, use of antibodies to MHC class-I resulted in only a minimal reduction in gamma-IFN production (17%). These studies demonstrate that BCL lysate pulsed DC elicit a predominantly BCL specific, MHC class-Il restricted T cell response. This suggests that vaccination with autologous BCL lysate pulsed DC may represent a viable immunotherapeutic approach for the treatment of LPD.

B-Lymphocytes↗
PubMed2001

Functional characterization of rat organic anion transporter 2 in LLC-PK1 cells.

Rat organic anion transporter 2 (rOat2) is abundantly expressed in the liver and localized to the basolateral membrane. A previous study using the Xenopus laevis oocyte expression system has shown that rOat2 transports organic anions such as salicylate () and, in the present study, rOat2 was characterized using a mammalian expression system. In addition to the substrates previously shown to be transported by rOat2, three substrates, indomethacin [IDM, Michaelis-Menten constant (K(m)) of 0.37 microM] and nucleoside derivatives such as 3'-azido-3'-deoxythymidine (AZT, K(m) of 26 microM) and 2',3'-dideoxycytidine (ddC, K(m) of 3.08 mM), were also identified for the first time The rank order of rOat2-mediated transport of these substrates was IDM > salicylate > prostaglandin E(2) > AZT > ddC > p-aminohippurate (PAH). Ketoprofen, indocyanine green and glibenclamide are potent inhibitors of the uptake of [(14)C]salicylate via rOat2 (K(i) of approximately 12 microM), while diclofenac, benzoate, verapamil, ibuprofen, and tolbutamide are moderate inhibitors (K(i) of approximately 150 microM). The affinity of PAH, a common substrate for the OAT family, for rOat2 is low (K(i) > 1 mM) compared with the other members of the OAT family (rOat1 and rOat3). Salicylate and IDM are also substrates for rOat1, but their affinity for rOat2 was higher than that for rOat1. The present study shows that rOat2 is a multispecific transporter and suggests that it may be involved at least partly, in the hepatic uptake of IDM, salicylate and nucleoside derivatives.

Algorithms↗
PubMed2001

[Clinical analysis of intrapulmonary lymph nodes].

We encountered 12 cases (9 men, 3 women) of intrapulmonary lymph nodes, discovered by chest radiography or chest CT and identified by thoracoscopic lung biopsy (in 10 cases), open lung biopsy (1 case) or lobectomy (1 case). We also studied the literature related to intrapulmonary lymph nodes in Japanese. Many intrapulmonary lymph nodes were found in the lower lung field, few in the upper lung field. All intrapulmonary lymph nodes were spherical and were located under the pleura, but we were not able in some cases to differentiate them from malignancies by the CT scanfindings. We could not diagnose them or rule out malignancy before surgery. Pathological findings revealed that all of them showed anthracosis. Silicotic changes were found in three cases. We consider that thoracoscopy is useful in making a definite diagnosis if peripheral pulmonary lesions cannot be diagnosed. We emphasize that intrapulmonary lymph nodes should be taken into consideration in differential diagnoses of small nodular lesions in the lung.

Aged↗
PubMed2001

[Cytokine production by peripheral blood mononuclear cells in bronchial asthma treated with suplatast tosilate].

Supratast tosilate is a newly developed 'anti-allergic' drug and it has been shown to suppress cytokine production by type-2 helper T cells (Th2) in vitro. However, it is unclear whether a similar inhibitory effect on Th2 cytokines production is produced iv vivo. To elucidate the actions of the in vivo mechanisms of this drug, we isolated peripheral blood mononuclear cells (PBMCs) from 10 atopic asthmatics treated with supratast tosilate and investigated the capacity for cytokine production ex vivo. Interleukin (IL)-5 production by PBMCs stimulated with the combination of phorbol myristate acetate and ionomycin were reduced significantly 6 or 12 weeks after the treatment with supratast tosilate. In contrast, no significant reduction was seen in IL-4 or Interferon (IFN)-gamma production. The peripheral blood eosinophil count and weeks, but no significant difference was sees in total IgE levels. Both morning and evening peak expiratory flow were significantly elevated after 6 weeks. These results suggest that supratast tosilate improves the disease status of bronchial asthma through its ability to inhibit the production Th2 cytokines, at least IL-5, in vivo.

Adult↗
PubMed2001

Prediction of human hepatic clearance from in vivo animal experiments and in vitro metabolic studies with liver microsomes from animals and humans.

We investigated the quantitative prediction of human hepatic metabolic clearance from in vitro experiments focusing on cytochrome P450 metabolism with eight model compounds, FK1052, FK480, zolpidem, omeprazole, nicardipine, nilvadipine, diazepam, and diltiazem. For the compounds, in vivo human hepatic extraction ratios ranged widely from 0.03 to 0.87. In vitro and in vivo hepatic intrinsic clearance (CL(int)) values for each compound were measured and calculated in rats and/or dogs and humans. CL(int,in vitro) was determined from a substrate disappearance rate at 1 microM in hepatic microsomes, which was a useful method. CL(int,in vivo) was calculated from in vivo pharmacokinetic data using three frequent mathematical models (the well stirred, parallel-tube, and dispersion models). The human scaling factor values (CL(int,in vivo)/CL(int,in vitro)) showed marked difference among the model compounds (0.3-26.6-fold). On the other hand, most of the animal scaling factors were within 2-fold of the values in humans, suggesting that scaling factor values were similar in the different animal species. When human CL(int,in vitro) values were compared with the actual CL(int,in vivo), correlation was not necessarily good. By contrast, using human CL(int,in vitro) corrected with the rat and/or dog scaling factors yielded better predictions of CL(int,in vivo) that were mostly within 2-fold of the actual values. Furthermore, successful predictions of human CL(oral) and hepatic extraction ratio (E(H)) were obtained by use of the human CL(int,in vitro) corrected with animal scaling factors. The new variant method is a simple one, incorporating additional information from animal studies and providing a more reliable prediction of human hepatic clearance.

Animals↗
PubMed2001

Elevated soluble CD26 levels in patients with tuberculous pleurisy.

SETTING: Several reports have shown that tuberculous infection elicits a Th1-like immune response with increased levels of IFN-gamma. Recently, expression of CD26 on CD4+ lymphocytes has been shown to correlate with the production of Th1-like cytokines. We therefore hypothesized that CD26 expression might increase in tuberculous pleural effusion, and might thus be a possible marker for detecting tuberculous pleurisy. OBJECTIVE AND DESIGN: To test this hypothesis, we measured soluble CD26 levels in the serum and pleural fluid of patients with tuberculous pleurisy (TB; n = 13), carcinomatous pleurisy (CA, n = 17), empyema (EM, n = 6), and congestive heart failure (HF, n = 10). RESULTS: The pleural CD26 levels, but not the serum CD26 levels, in patients with tuberculous pleurisy were significantly higher than those in other groups, and were correlated with levels of adenosine deaminase and interferon-gamma in the tuberculous pleural effusion. Furthermore, when the cut-off value for p-CD26 was set at 544.5 ng/ml, the positive rate for the TB group was significantly higher than that for the CA, EM and HF groups (P < 0.05). CONCLUSION: These results suggest that elevation of soluble CD26 in pleural fluid is implicated in Th1-like immune response, and may be a useful marker for tuberculous pleurisy.

Adenosine Deaminase↗