[Estimation of insulin sensitivity in vivo using glucose clamp and minimal model].
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Blood Glucose↗
Biomedical subjects
K Ueda
Publications and source records attributed to K Ueda.
[A surgical case of quadricuspid aortic valve associated aortic regurgitation and severe mitral regurgitation due to infective endocarditis].
We report a case of rare anomaly of quadricuspid aortic valve associated aortic regurgitation and severe mitral regurgitation due to infective endocarditis. A 50-year-old man was admitted to our hospital for fever and dyspnea. The transesophageal echocardiography showed severe aortic regurgitation due to four equal aortic cusps and severe mitral regurgitation due to infective endocarditis. At the operation, aortic valve and mitral valve were replaced with 23 mm and 29 mm SJM valves. His postoperative course was uneventful.
Aortic Valve↗
Lung volume reduction surgery for pulmonary emphysema using dynamic Xenon-133 and Tc-99m-MAA SPECT images.
The usefulness of Xe-133 and Tc-99m-MAA single photon emission computed tomography (SPECT) in identifying areas to be resected during video-assisted thoracoscopic lung reduction surgery for emphysema was examined. Twenty-nine patients with advanced emphysema were examined using Xe-133 and Tc-99m-MAA SPECT prior to and following surgery. For the Xe-133 dynamic SPECT, patients inhaled Xe-133 gas for 6 minutes. Equilibrium and subsequent washout SPECT images were acquired every 30 seconds for 6 to 7 minutes during spontaneous breathing. Ventilation was quantified by Xe-133 clearance time (T1/2) in addition to visual assessment. The patients underwent unilateral thoracoscopic volume reduction in the regions with abnormal Xe-133 retention and Tc-99m-MAA defect. All patients demonstrated marked, heterogeneous Xe-133 retention and Tc-99m-MAA defects preoperatively. The worst functioning areas were identified as nonventilated and noflow areas, or areas with air trapping and low perfusion. These changes were found even in patients with diffuse and symmetrical impairments on chest CT. After surgery, most of these "target areas" disappeared and pulmonary function tests demonstrated significant improvement. T1/2 correlated closely with the percent predicted FEV1 (%FEV) and 6-minute walk distance before and after surgery (p<0.0001). Xe-133 and Tc-99m-MAA SPECT imaging was useful in identifying "target areas" in the emphysematous lung. Directed unilateral thoracoscopic volume reduction based on these SPECT images is an effective treatment for emphysema.
Aged↗
[Non-real-time computed tomography-guided percutaneous ethanol injection therapy for hepatocellular carcinoma undetectable by ultrasonography].
The purpose of this study was to evaluate the feasibility of non-real-time CT-guided percutaneous ethanol injection therapy (PEIT) for hepatocellular carcinoma (HCC, 37 lesions) untreatable by ultrasonography-guided (US)-PEIT. The HCC lesion was localized on the lipiodol CT image with a graduated grid system. We advanced a 21 G or 22 G needle in a stepwise fashion with intermittent localization scans using a tandem method to position the tip of the needle in the lesion. Ethanol containing contrast medium was injected with monitoring scans obtained after incremental volumes of injection, until perfusion of the lesion was judged to be complete. A total of 44 CT-PEIT procedures were performed. The average number of needle passes from the skin to the liver in each CT-PEIT procedure was 2.3, the average amount of ethanol injected was 14.4 ml, and the average time required was 49.3 minutes. Complete perfusion of the lesion by ethanol on monitoring CT images was achieved in all lesions with only a single or double CT-PEIT procedure without severe complication. Local recurrence was detected only in 5 lesions. At present, it is more time-consuming to perform CT-PEIT than US-PEIT because conventional CT guidance is not real-time imaging. However, it is expected that this limitation of CT-PEIT will be overcome in the near future with the introduction of CT fluoroscopy. In conclusion, CT-PEIT should prove to be a feasible, acceptable treatment for challenging cases of HCC undetectable by US.
Aged↗
Prediction of pharmacokinetic alterations caused by drug-drug interactions: metabolic interaction in the liver.
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Animals↗
[Combination care of a patient with Joseph's disease local community].
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Activities of Daily Living↗
[Effect of clarithromycin treatment of natural killer cell activity in patients with advanced non-small cell lung cancer].
The treatment of a 14-membered ring macrolide, clarithromycin (CAM), prolongs the survival time of patients with unresectable nonsmall cell lung cancer, and improves the host factor. As we previously reported, one of the underlying mechanisms is that the treatment of CAM increases the bioactivity of interleukin-12 (IL-12). In the present study, we administered CAM to murine lung cancer treatment models with Lewis lung carcinoma and to 18 patients with unresectable non-small lung cancer whose anticancer treatment had been terminated. The timing of CAM administration was examined and the time course of NK activity was measured. In the murine lung cancer treatment models, administration of CAM 7 days after anticancer chemotherapy more strongly inhibited the tumor growth and more rapidly and significantly increased NK activity, compared to the concomitant use of CAM with an anticancer chemotherapy. In humans, the NK activity which had decreased after anticancer treatment, tended to be increased after one month of treatment with CAM (p = 0.06). One month of treatment with CAM significantly increased the NK activity (p < 0.05) of the following subjects: patients with stage III in the clinical stages, patients with squamous cell carcinoma, patients who had received radiotherapy alone as pretreatment therapy, and patients whose pretreatment therapy effect was partial response (PR). We conjectured that increasing NK activity was one of the underlying mechanisms of the macrobiotic effect of CAM. CAM was especially effective for patients in the early clinical stages and patients who responded well to pretreatment therapy. Murine lung cancer models showed that non-concomitant use of CAM with anticancer chemotherapy was more effective.
Aged↗
Circadian rhythms in plasma cortisone and cortisol and the cortisone/cortisol ratio.
We evaluated the circadian rhythms in the plasma concentrations of cortisol, cortisone and their free forms, and in the cortisone/cortisol ratios by means of reversed-phase high performance liquid chromatography in normal adult subjects. Plasma concentrations of cortisone, as well as cortisol, exhibited a circadian rhythm. The ratios of cortisone/cortisol remained almost constant during the waking hours of normal subjects. Changes in the cortisone/cortisol ratios previously reported in patients with various diseases exceeded the diurnal changes detected in the present study. Thus, the determination of the cortisone/cortisol ratio provides information that is useful in assessing the adrenal function of patients with various diseases.
Adrenocorticotropic Hormone↗
MgADP antagonism to Mg2+-independent ATP binding of the sulfonylurea receptor SUR1.
Pancreatic beta-cell ATP-sensitive potassium (KATP) channels play an important role in the regulation of glucose-induced insulin secretion. The beta-cell KATP channel comprises two subunits, the sulfonylurea receptor SUR1, a member of the ATP-binding cassette (ABC) superfamily, and Kir6.2, a member of the inward rectifier K+ channel family. The activity of the KATP channel is under complex regulation by the intracellular ATP and ADP. To understand the roles of the two nucleotide-binding folds (NBFs) of SUR1 in the regulation of KATP channel activity, we introduced point mutations into the core consensus sequence of the Walker A or B motif of each NBF of SUR1 and characterized ATP binding and ADP or MgADP antagonism to it. SUR1 was efficiently photolabeled with 8-azido-[alpha-32P]ATP and 8-azido-[gamma-32P]ATP in the presence or absence of Mg2+ or vanadate. NBF1 mutations impaired ATP binding, but NBF2 mutations did not. MgADP strongly antagonized ATP binding, and the NBF2 mutation reduced MgADP antagonism. These results show that SUR1, unlike other ABC proteins, strongly binds ATP at NBF1 even in the absence of Mg2+ and that MgADP, through binding at NBF2, antagonizes the Mg2+-independent high affinity ATP binding at NBF1.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Amino acid substitutions in the first transmembrane domain (TM1) of P-glycoprotein that alter substrate specificity.
Recently, we showed that the amino acid at position 61 in TM1 of human P-glycoprotein is important in deciding the substrate specificity of this protein. In this work, we investigated whether the amino acids other than His61 in TM1 of P-glycoprotein are also essential in the function of this protein. Nine amino acids residues, from Ala57 to Leu65 in TM1, were independently substituted to Arg, and analyzed the drug resistance of cells stably expressing each of these mutant P-glycoproteins. The mutant P-glycoproteins Ile60 --> Arg, His61 --> Arg, Ala63 --> Arg, Gly64 --> Arg, and Leu65 --> Arg were normally processed and expressed in the plasma membrane. Substrate specificities of mutant P-glycoproteins Gly64 --> Arg and Leu65 --> Arg were quite different from that of the wild type, and similar to that of the His61 --> Arg mutant, while the Ile60 --> Arg and Ala63 --> Arg mutant P-glycoproteins showed similar substrate specificities to that of the wild-type P-glycoprotein, suggesting that not only the amino acid residue at position 61 but also those at position 64 and 65 are also important in deciding the substrate specificity of P-glycoprotein. These three amino acids His61, Gly64, and Leu65 would form a compact region on an alpha-helix arrangement of TM1. These results suggest that a region consisting of His61, Gly64, and Leu65 in TM1 would participate in the formation of the recognition site for substrates of P-glycoprotein.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Alteration of substrate specificity by mutations at the His61 position in predicted transmembrane domain 1 of human MDR1/P-glycoprotein.
In CFTR, a member of the ABC superfamily and a chloride channel, amino acid substitutions in its transmembrane domains 1 and 6 (TM1, TM6) have been reported to modulate the anion selectivity or ion conductance of the ion channel. In P-glycoprotein, no amino acid substitution in TM1, but some in TM6, have been reported to modify the substrate specificity of this protein. In this work, we demonstrated the involvement of His61, which is in the middle of the predicted TM1, in the function of P-glycoprotein. His61 was replaced by all other amino acid residues, and each of the mutant cDNAs was introduced into drug-sensitive human carcinoma cells, KB3-1. The drug-resistance profile of cells stably expressing each mutated P-glycoprotein was investigated by comparing their relative resistance to vinblastine, colchicine, VP16, and adriamycin. The resistance to vinblastine was increased by replacing His61 by amino acids with smaller side chains, while it was lowered by replacing by amino acids with bulkier side chains. The reverse effect was observed for resistance to colchicine and VP16. The resistance to adriamycin was increased by replacing by amino acids with bulkier side chains except Lys or Arg, which have a basic side chain. We also showed that the replacement of His61 by Phe and Lys greatly impaired the efflux of calcein AM, while the replacement had no effect on the efflux of rhodamine 123. These results suggest that an amino acid residue at position 61 in TM1 is important in deciding the substrate specificity of P-glycoprotein.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Application of the variable region in 16S rDNA to create an index for rapid species identification in the genus Streptomyces.
Partial nucleotide sequences (120 bp) of the 16S rRNA gene (rDNA) containing a variable alpha region were compared in 89 strains of the genus Streptomyces belonging to eight major clusters of category I in Bergey's Manual of Systematic Bacteriology. Fifty-seven kinds of partial 16S rDNA sequences were observed among the 89 strains. Forty-three of the strains were grouped into 11 'identity groups', based on the fact that the strains in each group shared an identical sequence in the 120-bp region. The results of a phylogenetic analysis based on the 16S rDNA 120-bp sequences revealed that 60 of the 89 strains could be categorized into seven clusters, each consisting of four or more strains. Based on these observations it was concluded that short nucleotide sequences bearing the variable alpha region are useful for Streptomyces species identification.
DNA, Ribosomal↗
Usefulness of directional coronary atherectomy in patients with acute anterior myocardial infarction.
To assess the usefulness of directional coronary atherectomy (DCA) in acute myocardial infarction (AMI), 139 consecutive patients with anterior wall AMI undergoing successful catheter intervention were studied. The reocclusion rate was significantly lower in the last 70 patients who underwent DCA as aggressively as possible compared with the first 69 patients treated with coronary balloon angioplasty (12.1% vs 3.0%, p <0.05).
Aged↗
Protein kinase C-independent correlation between P-glycoprotein expression and volume sensitivity of Cl- channel.
The possible correlation between P-glycoprotein (PGP) and volume-sensitive Cl- channel was examined in a pair of cell lines: a subline of the human epidermoid KB cell (KB-3-1) and the corresponding MDR1-transfected cell line (KB-G2). Western blot analysis and indirect immunofluorescence studies indicated that KB-G2, but not KB-3-1, exhibits the PGP expression. Patch-clamp whole-cell recordings showed that osmotic swelling activates Cl- currents not only in PGP-expressing but also in PGP-lacking cells. The amplitude of the maximal current was indistinguishable between both cells. Activation of protein kinase C (PKC) or loading with a PKC inhibitor failed to affect the swelling-induced activation of the Cl- currents in both cells. The relation between whole-cell Cl- currents and cell size measured simultaneously showed that volume sensitivity of the Cl- channel was augmented by the PGP expression irrespective of the activity of PKC on the plasma membrane. A similar increase in volume sensitivity of the Cl- channel was also induced by the expression of the ATP hydrolysis-deficient PGP mutant, K433M. We conclude that P-glycoprotein does not represent the volume-sensitive Cl- channel but that its expression modulates volume sensitivity of the Cl- channel in a manner independent of its ATPase activity or of the protein kinase C activity.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Usefulness of transesophageal echocardiography in detecting changes in flow dynamics responsible for malperfusion phenomena observed during surgery of aortic dissection.
Intraoperative transesophageal echocardiography (TEE) was performed in order to study the flow dynamics in the descending aorta during surgery of aortic dissection Stanford A. TEE was seen to be a sensitive and accurate method to promptly detect severe decrease in retrograde pump flow and to clarify some of the mechanisms that can result in malperfusion during cardiopulmonary bypass.
Adult↗
Relationship between expression level of P-glycoprotein and daunorubicin transport in LLC-PK1 cells transfected with human MDR1 gene.
P-Glycoprotein-mediated transcellular transport and intracellular accumulation of [3H]daunorubicin were examined in cell monolayers with different levels of P-glycoprotein. The porcine kidney epithelial cell line LLC-PK1 was transfected with MDR1 cDNA, and four sublines, LLC-GA5, LLC-GA5-VLB4, LLC-GA5-COL10, and LLC-GA5-COL150, were obtained by culturing the cells in the absence or in the presence of 4 ng/mL vinblastine, 10 ng/mL colchicine, and 150 ng/mL colchicine, respectively. Western blot analysis showed a large difference in P-glycoprotein expression within these sublines. The degree of drug resistance was dependent on the expression level of P-glycoprotein. The amount of the unidirectional transport of [3H]daunorubicin by P-glycoprotein corresponded to the expression level of P-glycoprotein, which was followed by the decrease in intracellular accumulation of the agent. The concentration of cyclosporin A required for the inhibition of P-glycoprotein-mediated transport of [3H]daunorubicin was higher in cells with a high expression of P-glycoprotein. These findings suggest that the transport of daunorubicin by P-glycoprotein and its inhibition by cyclosporin A correspond to the expression level of P-glycoprotein.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Chlorpromazine reduces toxicity and Ca2+ uptake induced by amyloid beta protein (25-35) in vitro.
Amyloid beta protein (A beta), has been reported to be toxic to neurons in vitro. However, the molecular mechanism leading to neuronal death remains unknown. Here we report protective effects of phenothiazines, a class of neuroleptic agent, against A beta toxicity in primary cultures of rat cortical neurons and PC12 cells. beta(25-35), an active sequence of A beta, showed dose-dependent reduction of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide dye (MTT) reductivity, and chlorpromazine (CPZ), promethazine or trifluoperazine restored it at micromolar concentration. The significant increase in Ca2+ uptake by chronic treatment of beta(25-35) was reduced not only by nimodipine but also by CPZ. These results suggest that phenothiazines attenuate beta(25-35) toxicity possibly by reducing of Ca2+ influx through L-type Ca2+ channels.
Amyloid beta-Peptides↗
Effects of dithiocarbamates on toxicity of cadmium in rat primary hepatocyte cultures.
The protective effects of N-benzyl-D-glucamine dithiocarbamate (BGD) and N-p-hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD) on the toxicity of Cd in the rat primary hepatocyte cultures were studied. Cytotoxicity was assessed by measuring cell viability, extra cellular lactic dehydrogenase (LDH) activity, and intracellular lipid peroxidation and active oxygen species. Primary hepatocyte cultures were treated with 109CdCl2 (5, 10 or 50 microM Cd and 1.7 KBq of 109Cd/well) for 30 min or 4 h. BGD or HBGD was added to the culture medium to make the final concentration of 100 microM and incubated for 4.5 h in 30 min Cd exposure or 1 h in 4 h Cd exposure. Decreases in the hepatocyte viability caused by all Cd exposure concentrations were significantly prevented by treatment with BGD or HBGD. The treatment with the chelating agents for 4.5 h after Cd exposure for 30 min significantly prevented increases in extracellular LDH activity. Increases in the lipid peroxidation in hepatocytes exposed to Cd for 30 min or 4 h were prevented significantly by treatment with BGD or HBGD for 4.5 h or 1 h, respectively. Moreover, the increases in the level of active oxygen species caused by Cd exposure for 30 min were significantly prevented by treatment with the chelating agents for 1.5 h. These findings suggest that BGD and HBGD protect against the cytotoxicity of Cd in rat primary hepatocyte cultures and that the protective effects of chelating agents presumably result from a decrease in the Cd level, the effective sequestration of the reactive Cd ion, and the direct preventive effect on the active oxygen species in the hepatocytes.
Animals↗