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Biomedical subjects

K Inui

Publications and source records attributed to K Inui.

At least 91 records · Page 5Linked to original sources
PubMed2000

Functional expression of novel peptide transporter in renal basolateral membranes.

We examined the peptide transport activity in renal basolateral membranes. [(14)C]glycylsarcosine (Gly-Sar) uptake in rat renal cortical slices was saturable and inhibited by excess dipeptide and aminocephalosporin cefadroxil. When several renal cell lines were screened for the basolateral peptide transport activity, Madin-Darby canine kidney (MDCK) cells were demonstrated to have the greatest transport activity. [(14)C]Gly-Sar uptake across the basolateral membranes of MDCK cells was inhibited by di- and tripeptide and decreased with decreases in extracellular pH from 7.4 to 5.0. The Michaelis-Menten constant value of [(14)C]Gly-Sar uptake across the basolateral membranes of MDCK cells was 71 microM. The basolateral peptide transporter in MDCK cells showed several different [(14)C]Gly-Sar transport characteristics in growth dependence, pH profile, substrate affinity, and sensitivities to chemical modifiers from those of the apical H(+)-peptide cotransporter of MDCK cells. The findings of the present investigation indicated that the peptide transporter was expressed in the renal basolateral membranes. In addition, from the functional characteristics, the renal basolateral peptide transporter was suggested to be distinguishable from known peptide transporters, i.e., H(+)-peptide cotransporters (PEPT1 and PEPT2) and the intestinal basolateral peptide transporter.

4-Chloromercuribenzenesulfonate↗
PubMed2000

[Effect of itraconazole on digoxin clearance in patients with congestive heart failure].

We showed a digoxin-itraconazole interaction in three patients in whom digoxin serum concentrations were increased. Their electrocardiograms revealed arrhythmias such as ventricular premature contraction, atrioventricular block, and ST depression. The elimination half-life of digoxin in case 3 patient who continued itraconazole therapy was 8.4 days, which was estimated by nonlinear least squares method from the serum concentrations of digoxin versus time curve. In order to evaluate the influence of itraconazole on pharmacokinetic parameters of digoxin, we estimated digoxin clearance by the Bayesian method using the population pharmacokinetic parameters in Japanese patients. During the concomitant use of itraconazole and digoxin, the digoxin clearance in all patients decreased to 50.5 +/- 8.8% (mean +/- S.D.) of the clearance without itraconazole. When digoxin and itraconazole are used concomitantly, careful monitoring of digoxin serum concentrations is necessary. Based on our results of digoxin clearance evaluation, the dose of digoxin should be reduced to 50% of original dose after itraconazole is started, and digoxin serum concentration might be controlled at the same level before the concomitant use.

Aged↗
PubMed2000

Low-intensity pulsed ultrasound accelerates bone maturation in distraction osteogenesis in rabbits.

We investigated the effects of low-intensity pulsed ultrasound on distraction osteogenesis in a rabbit model. Callotasis of the right tibia was performed in 70 male Japanese white rabbits using mini-external fixators. In the first part of the study in 64 animals using normal distraction (waiting period seven days; distraction rate 0.5 mm/12 hours; distraction period ten days), we evaluated the distraction site by radiography, measurement of the bone mineral density (BMD), mechanical testing, and histology. In the second part in six rabbits using fast distraction (waiting period 0 days; distraction rate 1.5 mm/12 hours; distraction period seven days) the site was evaluated radiologically. Half of the animals (35) had received ultrasound to their right leg (30 mW/cm2) for 20 minutes daily after ceasing distraction (ultrasound group), while rigid fixation only was maintained in the other half (control group). With normal distraction, the hard callus area, as shown by radiography, the BMD, and the findings on mechanical testing, were significantly greater in those receiving ultrasound than in the control group. Histological analysis showed no tissue damage attributable to exposure to ultrasound. With fast distraction, immature bone regeneration was observed radiologically in the control group, while bone maturation was achieved in the ultrasound group. We conclude that ultrasound can accelerate bone maturation in distraction osteogenesis in rabbits, even in states of poor callotasis.

Animals↗
PubMed2000

[Studies of gastric acid secretion and gastric mucosal change after Helicobacter pylori eradication--the short and long-term observation].

We studied the gastric acid secretion and the histological findings of gastric mucosa in 48 patients with peptic ulcer before and after successful Helicobacter pylori (H. pylori) eradication. The pH of fasting gastric juice significantly decreased from 2.46 to 1.65 four weeks after eradication (p < 0.001). The factors such as disease, atrophic border, inflammatory cell involvement and histological atrophy were analyzed by logistic regression. Only the atrophic border was a significant and independent factor to convert the acidity after eradication, and the pH of gastric juice prominently decreased in the patients with widespread atrophic mucosal area. In the 24-hour intragastric pH monitoring, the pH3 holding time overnight remarkably decreased from 54.1% to 22.3% after eradication (p < 0.005). In the long follow-up of 17 patients (the mean follow-up period was 15.2 months), the pH of gastric juice kept a lower titer of 1.66. The mean atrophic scores in the upper body reduced from 1.5 to 0.9 (p < 0.05). In addition to the functional recovery of parietal cells after eradication, it was considered that the histological improvement of atrophy in oxyntic mucosa was associated with the recovery of pH.

Adult↗
PubMed2000

[Evaluation of chemotherapy for gastric cancer by endoscopic ultrasonography].

We judged the efficacy of chemotherapy using endoscopic ultrasonography (EUS) in 26 cases of gastric cancer. Treatment efficacy was evaluated according to the General Rules for the Gastric Cancer Study, based on the reduction of the largest cross-sectional area of the tumor. A reduction of over 50% was rated as U-PR and a reduction of -25-50% was rated as U-NC. Our findings showed U-PR in 11 cases and U-NC in 15 cases. Three cases initially considered to be NC according to the rules were judged to be U-PR based on EUS findings. Marked therapeutic efficacy in these 3 cases was demonstrated clinically and this was confirmed by EUS findings. Generalized Wilcoxon test showed a significant difference in the cumulative survival rate between U-PR and U-NC cases (p < 0.05). EUS provides an objective means of evaluating the efficacy of chemotherapy in gastric cancer patients, including those with lesions that cannot be evaluated by the General Rules for the Gastric Cancer Study.

Adult↗
PubMed2000

[A case of spinal muscular atrophy with marked calf hypertrophy and adolescent onset].

We report on a 41-year-old male patient with spinal muscular atrophy (SMA). He had slowly progressive muscular weakness and hypertrophic calves since 14 years of age. The upper arms were slightly, and the thighs moderately atrophic, but the calves were remarkably hypertrophic. There was muscle weakness of both the upper and lower limbs, being more proximal in distribution. He had a positive Gowers' sign and his gait was slightly waddling. Serum creatine kinase level was elevated (518IU/l). Electromyogram revealed a neurogenic pattern. Muscle biopsy of the left biceps brachii showed chronic neurogenic changes. Immunohistochemical examination and Western blot analysis using anti-dystrophin antibodies showed no abnormality. DNA analysis with multiplex PCR proved no deletion in the dystrophin gene, while deletions of exons 7 and 8 of the telomeric copy of survival motor neuron gene were detected. In 1978, Pearn et al. described a new variant syndrome of SMA, characterized by adolescent onset, gross hypertrophy of calves, and a slowly progressive clinical course. The present case is compatible with this syndrome. Therefore, it is suggested that this syndrome, mimicking Becker muscular dystrophy, is not an independent clinical entity, although the phenotype of this syndrome is different from that of typical SMA.

Adolescent↗
PubMed2000

Trans-stimulation effects of folic acid derivatives on methotrexate transport by rat renal organic anion transporter, OAT-K1.

We examined the pharmacological role of the renal organic anion transporter OAT-K1, which localizes predominantly in the brush-border membranes of proximal straight tubules, in the urinary excretion of methotrexate and the possibility of its contribution to "folinic acid rescue." With Madin-Darby canine kidney (MDCK) cells stably transfected with OAT-K1 cDNA, OAT-K1-mediated methotrexate accumulation was inhibited in the presence of various folic acid derivatives. These derivatives included aminopterin, 5-methyltetrahydrofolic acid, unlabeled methotrexate, folinic acid (citrovorum factor, leucovorin), and folic acid with apparent inhibition constant values of 0.5, 1.2, 1.8, 8.2, and 14.1 microM, respectively. In contrast, 10 microM taurocholic acid and sulfobromophthalein did not inhibit OAT-K1-mediated methotrexate accumulation. In addition, methotrexate efflux was stimulated in the presence of inwardly directed gradients of aminopterin, 5-methyltetrahydrofolic acid, unlabeled methotrexate, folinic acid, and folic acid, but not of uric acid, taurocholic acid, and glutathione, indicating that OAT-K1-mediated methotrexate efflux is stimulated by a folic acid derivatives exchange. In conclusion, OAT-K1 was suggested to enhance the apical efflux of highly accumulated methotrexate in tubular epithelial cells and contribute at least in part to folinic acid rescue by exchanging intracellular methotrexate for extracellular folinic acid.

Aminopterin↗
PubMed2000

Sequence analysis of E2 glycoprotein genes of classical swine fever viruses: identification of a novel genogroup in Thailand.

Thirty classical swine fever viruses (CSFV) isolated in Thailand between 1988 and 1996 were characterised by genetic sequence analysis of a part of their E2 coding regions, comparing the new data with that for representative reference viruses from other countries and continents. Thai isolates were divided into three distinct genogroups, indicating multiple origins for the outbreaks. Eighteen isolates from 1988-1995 form a new genogroup not previously described from any other geographical region. Eleven isolates from 1988-1995 are in the same genogroup as old US and European strains represented by reference strains Alfort 187 and Brescia. The viruses of this group seem to have died out in Europe but still persist in Thailand. One recent isolate from 1996 represents another previously described genogroup being closely related to Italian viruses isolated in the same year.

Animals↗
PubMed1999

Gender differences in expression of organic cation transporter OCT2 in rat kidney.

The organic cation transporter (OCT) mediates translocation of various cationic molecules including drugs, toxins and endogenous substances. We examined gender differences in the expression of rat (r) OCT2 in the kidney. Slices and basolateral membrane vesicles of male rat kidney showed a higher transport activity for tetraethylammonium than those of female rat kidney. The expression levels of rOCT2 mRNA and protein in the kidney of males were much higher than those in females. There was no gender difference in mRNA expression of rOCT1 and rOCT3. These findings suggest that rOCT2 is responsible for the gender differences in renal basolateral membrane organic cation transport activity.

Animals↗
PubMed1999

Functional analysis of rat renal organic anion transporter OAT-K1: bidirectional methotrexate transport in apical membrane.

Renal organic anion transporter OAT-K1 was stably transfected in MDCK cells and examined for its transport characteristics and membrane localization. OAT-K1 mediated both uptake and efflux of methotrexate in the apical membranes. Immunoblotting showed that the apparent molecular mass of the expressed OAT-K1 was 50 kDa, which was comparable to that found in the rat renal brush-border membranes. The OAT-K1-mediated methotrexate transport was significantly inhibited in the presence of several organic anions such as folate and sulfobromophthalein. These findings suggest that OAT-K1 mediates bidirectional methotrexate transport across the apical membranes, and may be involved in the renal handling of methotrexate.

Animals↗
PubMed1999

Inhibitory effect of KW-3902, an adenosine A(1) receptor antagonist, on p-aminohippurate transport in OK cells.

KW-3902 (8-(noradamantan-3-yl)-1,3-dipropylxanthine) is a novel potent and selective adenosine A(1) receptor antagonist. We examined the effect of KW-3902 on p-aminohippurate (PAH) transport in opossum kidney (OK) epithelial cells. Pretreatment for 3 h with KW-3902 inhibited the transcellular transport of PAH across OK cell monolayers from the basal to the apical side. The uptake of PAH across the basolateral membrane of OK cells was inhibited by KW-3902 pretreatment in a time- and concentration-dependent manner. A kinetic analysis revealed that the inhibitory effect of KW-3902 on the basolateral PAH uptake was due to an increase in the Michaelis constant (K(m)) as well as a decrease in the maximum uptake rate (V(max)), showing that the inhibition was a mixed type. Pretreatment with adenosine deaminase or 8-cyclopentyl-1,3-dipropylxanthine, another selective adenosine A(1) receptor antagonist, also decreased the basolateral PAH uptake. KW-3902 pretreatment had no effect on the concentration of intracellular alpha-ketoglutarate which exchanges for PAH across the basolateral membrane of OK cells. These results suggest that KW-3902 has an inhibitory effect on PAH transport in OK epithelial cells.

Adenosine Deaminase↗
PubMed1999

Cisplatin-induced toxicity in LLC-PK1 kidney epithelial cells: role of basolateral membrane transport.

Cytotoxicity of cisplatin was evaluated after apical and/or basolateral treatment of LLC-PK1 cell monolayers grown on porous membrane filters with 300 microM cisplatin. When LLC-PK1 cells were exposed from basolateral side for 0.5-4 h, lactate dehydrogenase (LDH) release into culture medium was markedly stimulated. However, apical treatment of the cells with cisplatin for 0.5 h did not stimulate LDH release. gamma-Glutamyltransferase activity and amount of protein in the cell homogenate were markedly decreased by basolateral treatment with cisplatin. However, in the apical treatment with cisplatin, these changes were relatively small, suggesting that degrees of the toxicities were different between basolateral and apical treatment with cisplatin. Cellular platinum level after basolateral treatment with cisplatin was higher compared to that following apical treatment. Furthermore, both accumulation and toxicity of cisplatin in LLC-PK1 cells were decreased by treatment with cisplatin at 4 degrees C. These results suggested that there were specific mechanisms mediating cisplatin uptake at the basolateral membranes of LLC-PK1 cells.

Animals↗
PubMed1999

Enzymatic inactivation of major circulating forms of atrial and brain natriuretic peptides.

We compared the enzymatic inactivation of major circulating forms of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). Both ANP and BNP induced a significant increase in cyclic GMP (cGMP) formation in cultured epithelial cell line derived from porcine kidney, LLC-PK1. The cGMP formation stimulated by ANP in LLC-PK1 cells was significantly decreased by pre-treatment of the peptide with rat renal brush-border membranes, and the inactivation of ANP was inhibited by neutral endopeptidase inhibitors, phosphoramidon and S-thiorphan. BNP exhibited greater resistance to enzymatic inactivation than did ANP. In addition, phosphoramidon potentiated the natriuresis with a low dose (7.5 pmol min(-1) kg(-1)) of ANP but not of BNP in rats. These results suggest that enzymatic degradation of natriuretic peptides is highly dependent on peptide structure, and that the affinity of BNP to neutral endopeptidase is less than that of ANP.

Animals↗
PubMed1999

Molecular mechanisms of organic cation transport in OCT2-expressing Xenopus oocytes.

The molecular mechanisms of organic cation transport by rat OCT2 was examined in the Xenopus oocyte expression system. When extracellular Na+ ions were replaced with K+ ions, uptake of tetraethylammonium (TEA) by OCT2-expressing oocytes was decreased, suggesting that TEA uptake by OCT2 is dependent on membrane potential. Kinetic analysis revealed that the decreased TEA uptake by ion substitution was caused at least in part by decreased substrate affinity. Acidification of extracellular buffer resulted in decreased uptake of TEA, whereas TEA efflux from OCT1- and OCT2-expressing oocytes was not stimulated by inward proton gradient, in consistent with basolateral organic cation transport in the kidney. Inhibition of TEA uptake by various organic cations revealed that apparent substrate spectrum of OCT2 was similar with that of OCT1. However, the affinity of procainamide to OCT1 was higher than that to OCT2. Uptake of 1-methyl-4-phenylpyridinium was stimulated by OCT2 as well as OCT1, but uptake of levofloxacin, a zwitterion, was not stimulated by both OCTs. These results suggest that OCT2 is a multispecific organic cation transporter with the characteristics comparable to those of the basolateral organic cation transporter in the kidney.

1-Methyl-4-phenylpyridinium↗
PubMed1999

Mutation analysis of a Japanese patient with fucosidosis.

Fucosidosis is a rare autosomal recessive disorder resulting from a deficiency of alpha-L-fucosidase. Recently, various mutations have been reported in this disease, but it is difficult to elucidate the phenotype from the genetic mutations. We report a patient with chronic infantile type fucosidosis, with a compound heterozygote of a nonsense mutation (W148X, Trp at codon 148 to stop codon) and a large deletion, including all exons. This is the first report of a large deletion demonstrated in fucosidosis. It is interesting that this patient has a relatively mild clinical course despite the absence of the mRNA. This case also indicates the difficulty in determining the phenotype from the genotype in fucosidosis.

Adolescent↗