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Biomedical subjects

K Inui

Publications and source records attributed to K Inui.

At least 505 records · Page 28Linked to original sources
PubMed1985

H+ gradient-dependent transport of aminocephalosporins in rat renal brush border membrane vesicles: role of H+/organic cation antiport system.

The transport of aminocephalosporin antibiotics such as cephalexin, zwitterion, by rat renal brush border membrane vesicles has been studied in relation to the transport system of organic cation. Cephalexin uptake was inhibited by organic cations such as tetraethylammonium, 1N-methylnicotinamide and choline, whereas cefazolin uptake was not. Tetraethylammonium uptake was inhibited by aminocephalosporins and stimulated by the countertransport effect of cephalexin. In agreement with the transport mechanisms of organic cation, the presence of an H+ gradient ([H+]i greater than [H+]o) induced a marked stimulation of aminocephalosporin uptake, and this uptake was inhibited by HgCl2 and tetraethylammonium. These results suggest that aminocephalosporins can share a common carrier transport system with organic cation in renal brush border membranes, and this system could be a part of the mechanisms of tubular secretion for aminocephalosporins.

Animals↗
PubMed1985

Transport of p-aminohippurate, tetraethylammonium and D-glucose in renal brush border membranes from rats with acute renal failure.

Transport of D-glucose, p-aminohippurate and tetraethylammonium has been studied using renal brush border membrane vesicles isolated from rats with uranyl nitrate-induced acute renal failure (ARF). Initial rate and overshoot magnitude of Na+ gradient-dependent D-glucose uptake were decreased in brush border membrane vesicles from ARF rats compared with normal rats, although there was no significant difference on D-glucose uptake in the presence of equilibrated Na+ between normal and ARF rats. Uptake of p-aminohippurate by membrane vesicles from ARF rats did not differ from normal membrane vesicles. Uptake of tetraethylammonium with or without an H+ gradient was decreased in membrane vesicles from ARF rats compared with normal rats. Dissipation rate of H+ gradient across brush border membranes did not differ between both groups. In vitro incubation of normal brush border membrane vesicles with uranyl nitrate caused no alteration in any substrate transport. However, enzyme activities such as (Na+ + K+)-adenosine triphosphatase in renal cortical homogenate were inhibited markedly in the presence of uranyl nitrate. These results suggest that uranyl nitrate-induced ARF caused alterations in the transport properties of renal brush border membranes and that these transport dysfunctions were not due to the direct effect of uranyl nitrate, but could be secondarily induced after the impairment of the integrity for tubular cells.

Acute Kidney Injury↗
PubMed1985

[Effect of preoperative intra-arterial infusion of adriamycin on locally advanced breast cancer].

The effect of adriamycin (ADM) infused intraarterially as a preoperative procedure was analyzed retrospectively in 15 patients with primary advanced breast cancer. A high clinical response rate (CR+ PR) of 73% (11/15) was obtained by the treatment, and also remarkable degenerative changes of tumor cells were histologically noted in 10 out of 15 surgical specimens (67%). A correlation between the dose of ADM infused and the rate of tumor regression was observed. A significantly higher concentration of ADM was detected in metastatic lymph nodes and tumors obtained 3-4 weeks after intra-arterial infusion of ADM than that in normal mammary gland. As for side effects, alopecia, leukocytopenia, anorexia, nausea and vomiting occurred at high frequencies. The side effects due to this treatment were considered to be tolerable. Prognostically, a good survival rate was not observed using preoperative treatment with intra-arterial ADM infusion.

Adult↗
PubMed1984

Carrier-mediated transport systems of tetraethylammonium in rat renal brush-border and basolateral membrane vesicles.

Transport of [3H]tetraethylammonium, an organic cation, has been studied in brush-border and basolateral membrane vesicles isolated from rat kidney cortex. Some characteristics of carrier-mediated transport for tetraethylammonium were demonstrated in brush-border and basolateral membrane vesicles; the uptake was saturable, was stimulated by the countertransport effect, and showed discontinuity in an Arrhenius plot. In brush-border membrane vesicles, the presence of an H+ gradient ( [H+]i greater than [H+]o) induced a marked stimulation of tetraethylammonium uptake against its concentration gradient (overshoot phenomenon), and this concentrative uptake was completely inhibited by HgCl2. In contrast, the uptake of tetraethylammonium by basolateral membrane vesicles was unaffected by an H+ gradient. Tetraethylammonium uptake by basolateral membrane vesicles was significantly stimulated by a valinomycin-induced inside-negative membrane potential, while no effect of membrane potential was observed in brush-border membrane vesicles. These results suggest that tetraethylammonium transport across brush-border membranes is driven by an H+ gradient via an electroneutral H+-tetraethylammonium antiport system, and that tetraethylammonium is transported across basolateral membranes via a carrier-mediated system and this process is stimulated by an inside-negative membrane potential.

Animals↗
PubMed1984

Carrier-mediated transport of cephalexin via the dipeptide transport system in rat renal brush-border membrane vesicles.

Carrier-mediated transport of aminocephalosporin antibiotics by renal brush-border membrane vesicles has been studied in relation to the transport systems for dipeptides and amino acids. Dipeptides such as L-carnosine (beta-alanyl-L-histidine) and L-phenylalanylglycine competitively inhibited the uptake of cephalexin, but amino acids did not. Cephalexin uptake was stimulated by the countertransport effect of L-carnosine in the normal and papain-treated vesicles, and by the effect of L-phenylalanylglycine only in the papain-treated vesicles. In the papain-treated vesicles, the hydrolysis of dipeptides was markedly decreased, and the specific activity for cephalexin transport was increased approx. 2-fold because of the partial removal of membrane proteins. These results suggest that carrier-mediated transport of cephalexin can be transported by the system for dipeptides in renal brush-border membranes.

Amino Acids↗
PubMed1984

Enzyme activities and sodium-dependent active D-glucose transport in apical membrane vesicles isolated from kidney epithelial cell line (LLC-PK1).

Apical membrane vesicles were isolated from the confluent LLC-PK1 cells by nitrogen cavitation and Mg/EGTA precipitation methods. The specific activities of marker enzymes for apical membranes were enriched 8- to 18-fold relative to those in the homogenate. D-[3H]Glucose uptake into the vesicles was stimulated in the presence of Na+ gradient (overshoot phenomenon), and the values of apparent Km and Vmax for Na+-dependent component of D-glucose uptake were 0.3 mM and 5.8 nmol/mg protein per min, respectively.

Animals↗
PubMed1984

Biochemical, immunological, and structural studies on a sphingolipid activator protein (SAP-1).

Sphingolipid activator protein-1 (SAP-1) is a glycoprotein found in human tissue extracts that stimulates the enzymatic hydrolysis of at least two glycosphingolipids, including GM1 ganglioside and sulfatide. The ability of purified SAP-1 to stimulate GM1 ganglioside hydrolysis by extracts of cultured fibroblasts from patients with beta-galactosidase deficiency was examined, and all patients had a pronounced deficiency (under 10% of control). Using monospecific antibodies against SAP-1, the concentration was determined in cultured fibroblasts by rocket immunoelectrophoresis. Extracts from 15 control cell lines were found to have 0.72 +/- 0.24 micrograms cross-reactive material/mg protein, while cell extracts from 8 patients with GM1 gangliosidosis involving mental retardation were found to have 1.08 +/- 0.17, which is significantly elevated. When the fibroblast extracts were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by electroblotting, multiple bands were observed. Controls were found to have two major bands with estimated molecular weights of 9000 and 9500, and a minor band at 7800. Extracts from patients with GM1 gangliosidosis were found to have multiple bands ranging upward to 13,000. Extracts from patients with the most severe clinical types of GM1 gangliosidosis had almost exclusively high-molecular-weight forms (molecular weights above 10,000). Treatment of SAP-1 from control liver with endoglycosidase D caused a decrease in the Mr 9500 band and increased in the Mr 7800 band. When SAP-1 from GM1 gangliosidosis liver was treated sequentially with neuraminidase, beta-galactosidase, and endoglycosidase D, almost all of it was converted to the forms found in control human liver.

Cells, Cultured↗
PubMed1984

Usefulness of 4-methylumbelliferyl-6-sulfo-2-acetamido-2-deoxy-beta-D-glucopyrano sid e for the diagnosis of GM2 gangliosidoses in leukocytes.

4-Methylumbelliferyl-6-sulfo-2-acetamido-2-deoxy-beta-D-glucopyranoside was synthesized and tested as a substrate for the diagnosis of GM2 gangliosidoses using leukocytes. Less than 2% of normal activity was measured in homogenates from patients with typical Tay-Sachs disease and from a patient with a variant form having 37% Hexosaminidase A by heat denaturation using the usual fluorogenic substrate. An adult patient had 8.5% of normal activity. Three patients with Sandhoff disease were found to have values ranging from 17% to 37% of normal. These values overlap the range found for carriers of Tay-Sachs disease, and suggest that the usefulness of this substrate, while excellent for diagnosing B variants of GM2 gangliosidosis, requires further study. Perhaps when used together with 4-methylumbelliferyl-2-acetamido-2-deoxy-beta-D-glucopyranoside excellent discriminations of patients, carriers and controls will be realized.

Acetylglucosaminidase↗
PubMed1984

Quinidine-induced rise in ajmaline plasma concentration.

A high-performance liquid chromatographic method is described for the simultaneous determination of ajmaline and quinidine in human plasma. With 0.5 ml plasma sample of a ajmaline and quinidine, concentrations as low as 0.001 and 0.01 micrograms ml-1, respectively, could be detected and the technique could be used to investigate the effect of quinidine on the pharmacokinetics of ajmaline. Four healthy subjects were given oral ajmaline (50 mg) alone or in combination with quinidine sulphate (200 mg) on separate occasions. When ajmaline was administered alone, its plasma concentrations were less than 0.03 micrograms ml-1. Quinidine induced a marked increase to give a mean peak concentration of ajmaline which increased from 0.018 micrograms ml-1 after a single administration to 0.141 micrograms ml-1 in combination with quinidine. the area under the ajmaline concentration-time curves was increased 10 to 30-fold by the concurrent administration of quinidine. According to the one compartment open model, the absorption rate constant of ajmaline did not change appreciably, but the elimination rate constant was reduced to approximately 50% of the value in the absence of quinidine. The results indicate the existence of a significant interaction between oral ajmaline and quinidine.

Adult↗
PubMed1984

Effect of aminoglycoside antibiotics on cellular functions of kidney epithelial cell line (LLC-PK1): a model system for aminoglycoside nephrotoxicity.

The effects of aminoglycoside antibiotics on cellular functions of the LLC-PK1 kidney epithelial cell line were studied as a model system for aminoglycoside nephrotoxicity. The treatment with aminoglycoside antibiotics for 3 days caused a decrease in the dome number in the confluent LLC-PK1 cells and an increase in the floating cells in the culture medium. The inhibition of dome formation was dose-dependent and the rank-order of the degree of inhibition was compatible with the rank-order of in vivo nephrotoxicity. Aminoglycosides also decreased the intracellular content of cyclic AMP, with a correlation between the alteration of dome formation and cyclic AMP content. The specific activities of N-acetyl-beta-D-glucosaminidase (marker for lysosomes), aminopeptidase and alkaline phosphatase (marker for apical membranes) and (Na++K+)-adenosine triphosphatase (marker for basolateral membranes) in the homogenate were decreased by gentamicin treatment. Lysosomal and apical membrane enzymes released into the culture medium were increased by gentamicin treatment. The ultrastructural alterations in the lysosomes of gentamicin-treated cells also were observed. Above results suggest that aminoglycoside toxicity to LLC-PK1 cells may be similar to that reported for renal tubules.

Adenosine Triphosphate↗
PubMed1984

[Preservation of the nipple and areola for breast cancer--histopathological study on cancerous involvement of the nipple and areola].

In 141 mastectomy specimens, performed for invasive or non-invasive carcinomas, histopathologic study was performed to assess the extent of nipple-areola involvement by the tumor. In this study, patients were excluded when 1) the tumor was located beneath the areola, 2) nipple and/or areola abnormalities were clinically present. Tumor involvement of the nipple and/or areola was found in 44 of 141 specimens (31%), with intraductal growth in 36 (82%) of 44, stromal invasion in 3 (7%) and ductal & stromal invasion in 5 (11%). Analysis of nipple-areolar involvement with consideration of the different variables indicates that it occurred in association with tumor size, tumor-areola distance and histological type. Such information provides clinically relevant guide lines in decision making for limited breast surgery.

Breast Neoplasms↗