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Biomedical subjects

A Tsuji

Publications and source records attributed to A Tsuji.

At least 145 records · Page 8Linked to original sources
PubMed1998

Seroepidemiological study on prevalence of measles antibodies in Urawa City.

To obtain a precise seroepidemiological understanding of measles antibodies, we analysed hemagglutination inhibition (HI) and neutralizing test (NT) antibodies in different age groups in Urawa City. We examined 1591 serum samples collected from subjects aged from zero day to 95 years. Of these 1591 samples, 1094 were HI antibody positive with a positive rate of 68.7%. Mean HI antibody titer by age was from 2(4.0 +/- 0.82) to 2(5.4 +/- 1.43). Of the 497 samples which were HI antibody negative, 419 were NT positive. HI antibody positive rate and mean antibody titer were decreased at ages 6 to 12 months, and then increased with age. Approximately 5% of school children aged 6 to 15 years were not immune status. The key issue for measles eradication is how to immunize this population.

Adolescent↗
PubMed1998

Stereoselective hepatobiliary transport of the quinolone antibiotic grepafloxacin and its glucuronide in the rat.

A comparative pharmacokinetic study was performed for the optical isomers of grepafloxacin (GPFX), an asymmetric quinolone antibiotic. At steady state in rats receiving a constant infusion of each epimer, R(+)-GPFX and S(-)-GPFX, no marked difference between epimers was observed in plasma concentrations or in biliary and urinary excretion rates. The 3-glucuronides of GPFX are diastereomers. The biliary clearance, defined by the liver concentration of the 3-glucuronide of R(+)-GPFX (R-GPFX-Glu), was twice that of the 3-glucuronide of S(-)-GPFX (S-GPFX-Glu). Marked ATP dependence was observed in the uptake of both R-GPFX-Glu and S-GPFX-Glu by bile canalicular membrane vesicles. The ATP-dependent uptake of R-GPFX-Glu was also greater than that of S-GPFX-Glu. Kinetic analysis of the uptake of these glucuronides by bile canalicular membrane vesicles indicated that the affinity (1/Km) of S-GPFX-Glu for the transporter was 1.7 times higher than that of R-GPFX-Glu, whereas the Vmax of R-GPFX-Glu was 2.9 times greater than that of S-GPFX-Glu. The uptake of both glucuronides was reduced in mutant strain Eisai-hyperbilirubinemia rats, which have a hereditary defect in the bile canalicular multispecific organic anion transport system. Both glucuronides inhibited the ATP-dependent uptake of DNP-SG, a typical substrate for the bile canalicular multispecific organic anion transport system in a concentration-dependent manner, with a Ki of 21.5 microM and 8.8 microM for R-GPFX-Glu and S-GPFX-Glu, respectively. These Ki values were comparable with the corresponding Michaelis-Menten constant values for their uptake (17.3 microM and 10.1 microM, respectively). It is concluded that a major part of the stereoselective transport of these glucuronides across the bile canalicular membrane is mediated by a transporter that is deficient in Eisai-hyperbilirubinemia rats-possibly by the bile canalicular multispecific organic anion transport system.

Animals↗
PubMed1998

Carrier-mediated mechanism for the biliary excretion of the quinolone antibiotic grepafloxacin and its glucuronide in rats.

Grepafloxacin (GPFX) has a comparatively greater hepatobiliary transport than other quinolone antibiotics. The biliary excretion mechanism of GPFX was investigated in a series of in vivo and in vitro studies with Sprague-Dawley rats and the mutant strain Eisai-hyperbilirubinemia rats (EHBR), which have a hereditary defect in their bile canalicular multispecific organic anion transport system (cMOAT). The biliary excretion of the parent drug in EHBR was 38% of that in normal rats, whereas the 3-glucuronide, a main metabolite of GPFX, was scarcely excreted into the bile in EHBR. To clarify the biliary excretion mechanism of GPFX, studies of uptake by bile canalicular membrane vesicle (CMV) were performed. ATP dependence was observed in the uptake of GPFX by CMV, although the extent was not very marked, whereas no ATP-dependent uptake was observed by CMV prepared from EHBR. An inhibition study of the ATP-dependent uptake of the glutathione conjugate, 2,4-dinitrophenyl-S-glutathione (DNP-SG), a typical substrate for cMOAT, was performed in order to differentiate among the affinities of six quinolone antibiotics for this transporter. All quinolone antibiotics inhibited the ATP-dependent uptake of DNP-SG with different half-inhibition concentrations (IC50), and GPFX had the lowest IC50 value. The uptake of GPFX-glucuronide by CMV from normal rats showed a marked ATP dependence, whereas there was little ATP-dependent uptake in EHBR. The K(m) value (7.2 microM) for the higher-affinity component of the glucuronide uptake was comparable to the Ki value (9.2 microM) of the glucuronide in terms of inhibition of the ATP-dependent uptake of DNP-SG, which indicates that DNP-SG and the glucuronide may share the same transporter, cMOAT. The Ki value of the glucuronide observed in this inhibition was less than 1/200 that of the parent, which suggests that the glucuronide had a much higher affinity than the parent drug. These results lead us to conclude that at least a part of the GPFX transport and a major part of its glucuronide transport across the bile canalicular membrane are by a primary active transport mechanism mediated by cMOAT.

Animals↗
PubMed1998

[Strategies for drug delivery to the brain across the blood-brain barrier].

Designing drugs (including peptides) with greater lipophilicity are still effective strategy for the enhancement of the permeability across the blood-brain barrier (BBB), which is considered to be lipoidal membrane barrier of endothelial cells which have tight junctions without fenestrations. However, for the development of brain-specific drug delivery for neuroactive drugs, it may be greater promising strategy to utilize the specific influx transporters existing at the BBB for hexoses, amino acids, monocarboxylic acids, amines or to inhibit the functions of the efflux transporters such as P-glycoprotein which pumps out cytotoxic and/or lipophilic drugs. Attractive approach to the delivery of peptides is to design the peptide to be transported across the BBB via ologopeptide specific transporters, via insulin or transferrin receptor-mediated transcytosis, or via adsorptive-mediated transcytosis specific for positively charged peptides.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

[Treatment of tuberculous meningitis: marker of cure].

A 49-year-old male with tuberculous meningitis was reported. When admitted to our hospital with mild right hemiparesis, he was alert but he developed disorientation 7 days later. A diagnosis of tuberculous meningitis was reached because of elevated levels of adenosine-deaminase at 19.6U/liter in the cerebrospinal fluid. MRI showed a marked enhancement in the basal cisterns and an enhanced intraparenchymal lesion in the brainstem. Chronological changes of MRI findings did not closely correlate with the clinical course. Slight meningeal enhancement on MRI seems to remain for a long time without active tuberculous meningitis, and absence of the meningeal enhancement on MRI is not necessarily appropriate as a marker of cure of tuberculous meningitis.

Adenosine Deaminase↗
PubMed1998

[Predictability of EC/IC bypass function: a retrospective study].

Although the efficacy of extracranial/intracranial bypass for reduction of risk of ischemic stroke has been denied, we have encountered patients in whom bypass operation seems to have improved his or her clinical course. The efficacy of bypass should be evaluated not by the patency of the bypass but by the extent of collateral circulation brought about by the bypass. We retrospectively analyzed our patients to determine whether the extent of bypass flow could be predicted from the results of preoperative studies. In 18 hemispheres of 18 consecutive patients who underwent extracranial/intracranial bypass surgery, correlation between the extent of bypass flow and the multiple preoperative factors including the angiographic findings were investigated. The bypass function was highly predictable in the light of preoperative studies. In all of 10 hemispheres in patients under 70 years of age and with occlusive lesions in the proximal portion of the middle cerebral artery, collateral circulation through the bypass developed to an extensive or a moderate degree. In 9 of 10 hemispheres in which an interval between the latest attack and the diagnosis of hemodynamic failure was 4 weeks or longer, collateral circulation through the bypass was shown to have developed to an extensive or a moderate degree. Our results indicate that extensive or moderate collateral circulation through the bypass can be expected only in patients under 70 years of age, with lesions in the proximal portion of the middle cerebral artery, and in whom an interval between the latest attack and diagnosis of hemodynamic failure was 4 weeks or more.

Adult↗
PubMed1998

[Evaluation of the Swedish Interactive Thresholding Algorithm, a new thresholding algorithm, of the Humphrey field analyzer in normal subjects].

The Swedish Interactive Thresholding Algorithm (SITA) is a new thresholding algorithm that aims to obtain the same quality of visual fields in a shorter examination time than with the conventional up-and-down method. We investigated the correlation between thresholds measured with the SITA algorithm and those with the conventional up-and-down method in 47 eyes of 47 normal subjects. In each test point, thresholds with the SITA accurate and with the SITA fast showed significant correlation with those of the conventional method (r = 0.693, p < 0.0001 and r = 0.689, p < 0.0001, respectively). The mean deviation (MD) in the conventional method and the difference between MD values of the conventional method and SITA accurate and SITA fast were significantly correlated (r = -0.442, p < 0.006 and r = -0.509, p < 0.00092, respectively). The examination times of the SITA accurate and SITA fast were 48% and 27% of the conventional method. Although the new thresholding algorithm enables us to perform perimetric examination with relatively high accuracy, further investigations should be conducted before we apply it to glaucoma cases.

Algorithms↗
PubMed1998

[Low-dose CDDP and continuous 5-FU treatment of advanced gastric cancer with peritoneal dissemination: a case with long disease-free survival].

The patient was diagnosed to have gastric cancer (T3 N3 M0 P3, Stage IV b). We conducted LcFP therapy. CDDP, 7 mg/m2/day, day 1-5 i.v. drip for 2 hours, and 5-FU, 170 mg/m2/day, day 1-7, i.v. continuously for 24 hours. After 3 courses (one course: 4 LcFPs followed by one rest week), down staging (T3 N2 M0 P1. Stage IV a) and improvement of performance status were obtained, and then surgical resection was undertaken. After operation one course of LcFP therapy served as adjuvant chemotherapy. The patient has survived over one year and 8 months to date in a tumor-free condition. LcFP therapy promises to be useful in the clinical management of advanced gastric cancer.

Adenocarcinoma↗
PubMed1998

Hepatic sinusoidal membrane transport of anionic drugs mediated by anion transporter Npt1.

The purpose of our study was to establish the localization of the anion transporter Npt1 in liver and the relevance of Npt1 to carrier-mediated hepatic transport of beta-lactam antibiotics. Immunocytochemical examination of mouse liver with antiserum for Npt1 showed basolateral (sinusoidal) membrane localization. Function of Npt1 was characterized in Xenopus laevis oocytes. Injection of in vitro-transcribed cRNA into oocytes resulted in an increased uptake of [14C]benzylpenicillin (PCG). The Npt1-mediated uptake was saturable with a Michaelis constant (Km) of 0.46 +/- 0.18 mM and a maximum rate (Vmax) of 46.6 +/- 8.5 pmol/60 min/oocyte, and the uptake of [14C]PCG was independent of Na+ and pH, but dependent on chloride ion. Npt1-mediated [14C]PCG uptake was inhibited by several beta-lactam antibiotics and probenecid. Oocytes injected with Npt1-cRNA demonstrated significantly enhanced transport activity for other anionic compounds such as [14C]faropenem, [14C]foscarnet and [3H]mevalonic acid, as well as [14C]PCG, compared with water-injected oocytes. In conclusion, Npt1 is suggested to participate in hepatic sinusoidal membrane transport of organic anions such as beta-lactam antibiotics as well as inorganic anions for the efflux from hepatocyte-to-blood direction.

Animals↗
PubMed1998

An autopsy case of unusual massive gastrointestinal hemorrhaging.

An autopsy case is presented involving massive gastrointestinal hemorrhaging. A 58-year-old woman was found dead with bloody patches on her body. An autopsy revealed a lacerated wound to the mucosa of the stomach and a sharp fish bone was found among bloody contents within the stomach. The duodenum and small intestines contained abundant tarry contents, but the mucosa of the intestinal tract was intact. The cause of death was certified as hemorrhagic shock due to massive bleeding from a wound to the gastric mucosa inflicted by a sharp fish bone. Therefore the possibility that some foreign body has been swallowed must be considered when forensic pathologists investigate cases with bleeding of unknown origin from the alimentary tract.

Animals↗
PubMed1998

Sudden infant death from aspiration of milk due to superior cornual defect of thyroid cartilage.

An autopsy case of a 4-month-old boy who died immediately after being fed by a member of the staff of a day-care centre is described in this report. An autopsy certified that the cause of death was the aspiration of milk. There was no other apparent reason for the aspiration of milk into the trachea except for the left superior cornual defect of the thyroid cartilage. We therefore conclude that it was this defect which led to the aspiration of milk into the trachea.

Animals↗
PubMed1998

Correlation of the peripapillary atrophy area with optic disc cupping and disc hemorrhage.

PURPOSE: To investigate the association of the peripapillary atrophy area with disc cupping area and disc hemorrhage in subjects who underwent ocular examination as part of a routine physical examination. METHODS: We reviewed plain color fundus photographs taken of 12,140 eyes of 6,070 subjects as part of a routine health examination. The refractive error in these eyes was not known. Using a computerized image analysis system, we measured the area of peripapillary atrophy (zone beta), the optic disc, and optic disc cupping by means of planimetry in 8,842 eyes of 4,421 subjects with fundus images of good quality. RESULTS: The ratio of cup area to disc area was significantly greater in eyes with peripapillary atrophy (0.36 + 0.09) than in eyes without peripapillary atrophy (0.34 + 0.07), and the ratio of peripapillary atrophy area to disc area was significantly greater in eyes with disc hemorrhage (0.26 + 0.34) than in those without disc hemorrhage (0.09 + 0.18). Moreover, in eyes with peripapillary atrophy, the ratio of cup area to disc area was significantly larger in eyes with disc hemorrhage (0.48 + 0.08) than in those without disc hemorrhage (0.36 + 0.09). These results remained statistically unchanged even after "glaucomatous" eyes were excluded from the study. CONCLUSION: Peripapillary atrophy appears to be associated with a higher degree of cupping of the optic disc and disc hemorrhage, and the results suggest an association between peripapillary atrophy and glaucomatous optic neuropathy.

Female↗
PubMed1998

Hepatobiliary transport kinetics of HSR-903, a new quinolone antibacterial agent.

HSR-903 is a newly synthesized quinolone antibacterial agent with low toxicity. The biliary and urinary excretion of unchanged HSR-903, its R-isomer, and their glucuronides was determined after iv bolus administration (5 mg/kg) to normal Sprague-Dawley rats (SDR) and Eisai hyperbilirubinemic mutant rats (EHBR). The values for the biliary excretion clearance of HSR-903 and its glucuronide in EHBR were decreased to approximately 40 and 2% of those in SDR, respectively, whereas the values for the urinary excretion clearance of HSR-903 and its glucuronide were comparable in SDR and EHBR. The biliary excretion clearance values for the R-isomer and its glucuronide were approximately 3 times greater than those for HSR-903. These results demonstrated that the enantiomers of HSR-903 and their conjugates were excreted into bile in a stereospecific manner. The hepatic uptake of [14C]HSR-903 in vivo was evaluated by means of integration plot analysis. The results indicated that the hepatic uptake of [14C]HSR-903 was very fast and was blood flow-limited. To clarify the mechanism of excretion of HSR-903 into bile, the uptake and efflux of [14C]HSR-903 were studied using isolated hepatocytes from SDR and EHBR. The initial uptake of HSR-903 by hepatocytes was temperature-dependent, saturable, and stereospecific. Unlabeled HSR-903 (S-isomer), the R-isomer, grepafloxacin, and sparfloxacin significantly inhibited the uptake of [14C]HSR-903. The efflux of [14C]HSR-903 from hepatocytes from EHBR was significantly slower than that from hepatocytes from SDR. The addition of sodium azide or bromosulfophthalein reduced the efflux of [14C]HSR-903. These results demonstrate that HSR-903 is actively excreted into bile via the canalicular multispecific organic anion transporter, which is deficient in EHBR.

Animals↗
PubMed1998

[Evaluation of the Swedish interactive thresholding algorithm, a new thresholding algorithm, of the Humphrey Field Analyzer in glaucoma patients].

The Swedish interactive thresholding algorithm (SITA) is a new thresholding algorithm that aims to obtain the visual fields of the same quality in a shorter examination time than the conventional up-and-down method. We investigated the correlation between the threshold values obtained by SITA and the conventional thresholding algorithm in 30 glaucoma patients. The results of two types of SITA, i.e., SITA accurate and SITA fast, showed a significant correlation with those of the conventional method (r = 0.855, p < 0.0001 and r = 0.833, p < 0.0001, respectively). There was no statistical relation between the mean deviation (MD) of the conventional method and the difference between MD values of the conventional method, and SITA accurate and SITA fast. The examination time of SITA accurate and SITA fast was 50% and 31% shorter, respectively, than that of the conventional method. The difference in threshold of each test point in the conventional and SITA methods was minor except in one with a deep relative defect. These results indicate that SITA can be useful for detecting glaucomatous visual field defects in a shorter time.

Algorithms↗
PubMed1997

Cloning and characterization of a novel human pH-dependent organic cation transporter, OCTN1.

cDNA for a novel proton/organic cation transporter, OCTN1, was cloned from human fetal liver and its transport activity was investigated. OCTN1 encodes a 551-amino acid protein with 11 transmembrane domains and one nucleotide binding site motif. It is strongly expressed in kidney, trachea, bone marrow and fetal liver and in several human cancer cell lines, but not in adult liver. When expressed in HEK293 cells, OCTN1 exhibited saturable and pH-dependent [3H]tetraethyl ammonium uptake with higher activity at neutral and alkaline pH than at acidic pH. Furthermore, treatment with metabolic inhibitors reduced the uptake, which is consistent with the presence of the nucleotide binding site sequence motif. Although its subcellular localization and detailed functional characteristics are not clear at present, OCTN1 appears to be a novel proton antiporter that functions for active secretion of cationic compounds across the renal epithelial brush-border membrane. It may play a role in the renal excretion of xenobiotics and their metabolites.

Adenosine Triphosphate↗
PubMed1997

Carrier-mediated transport of oligopeptides in the human fibrosarcoma cell line HT1080.

To explore the feasibility of targeting human tumor cells via their transport systems, dipeptide uptake was studied in the human fibrosarcoma cell line HT1080 and the human fibroblast cell line IMR-90 by the use of hydrolysis-resistant glycylsarcosine (Gly-Sar). The uptake of [14C]Gly-Sar into HT1080 was time dependent. Kinetic analysis of the concentration dependence of the initial rate of [14C]Gly-Sar uptake showed that a carrier-mediated transport system with a K(m) of 11.4 +/- 3.3 mM and V(max) of 26.8 +/- 4.0 (nmol/15 min/mg protein) and a nonsaturable component (k(d) of 0.80 microl/15 min/mg protein) were responsible for the dipeptide uptake by HT1080 cells. The optimal pH for the maximal uptake was around 6.0. [14C]Gly-Sar uptake was inhibited by various di- and tripeptides and peptide-mimetic drugs, such as bestatin and cefadroxil. [14C]Gly-Sar uptake was not affected by the presence of amino acids or tetra- or pentapeptides. The uptake of cefadroxil was reduced significantly by unlabeled Gly-Sar. Moreover, Gly-Gly and Gly-Leu produced an increase in the apparent K(m) of the uptake of Gly-Sar without altering V(max). On the other hand, dipeptide uptake by IMR-90, which is a normal diploid cell line (not malignant), showed no saturable transport. These results suggest that HT1080 cells take up dipeptides via a pH-dependent transporter. This is the first report showing that a dipeptide transport system, which is similar but not identical to the well-characterized oligopeptide transporters PepT1 and PepT2, exists in fibroblast-derived tumor cells but not in normal fibroblasts. The present finding could be the basis of a novel strategy for the specific delivery of oligopeptide-mimetic anticancer drugs into tumor cells.

Biological Transport↗
PubMed1997

Brain-to-blood active transport of beta-alanine across the blood-brain barrier.

A high-affinity antiluminal uptake system for beta-alanine was demonstrated in primary cultured bovine brain capillary endothelial cells (BCEC) for which K(t) is 66.9 microM. beta alanine uptake was energy-, sodium- and chloride ion-dependent. beta-amino acids strongly inhibited the uptake, while alpha- and gamma-amino acids had a little or no inhibitory effect. In ATP-depleted cells, the uptake was stimulated by preloading beta-alanine or taurine but not by L-leucine. These results suggest that beta-alanine is actively transported across the antiluminal membrane of BCECs that is common to beta-amino acids. The system may function for the efflux from the brain to blood.

Amino Acids↗