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Biomedical subjects

H Saitoh

Publications and source records attributed to H Saitoh.

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

Effect of side chains including the N-methyl-tetrazole-thiol group of beta-lactam antibiotics on transport in cultured kidney epithelial cells LLC-PK1.

In this study, the transcellular transport characteristics of four beta-lactam antibiotics (cefotaxime, cefmenoxime, cefmetazole, and cefotiam) were investigated in a kidney epithelial cell line LLC-PK1, especially focusing on the effect of the N-methyl-tetrazole-thiol (NMTT) group attached to 7-amino-cephalosporanic acid. There were no directional differences between the apical-to-basolateral and basolateral-to-apical transport of cefotaxime, cefmenoxime, and cefmetazole, suggesting that the NMTT group does not influence the transcellular transport behaviors of beta-lactam antibiotics. In contrast, cefotiam transport across LLC-PK1 cell monolayers was 1.3-fold greater in the basolateral-to-apical direction than in the apical-to-basolateral direction. It is considered that the ionization of nitrogen in the N-dimethylaminoethyl group attached to NMTT is a factor in the secretory-oriented movement of cefotiam. The transcellular transport of cefotiam in both directions was significantly depressed at a low temperature (4 degrees C) and by 2,4-dinitrophenol. The basolateral-to-apical transport of cefotiam was also shown to be concentration-dependent. These results suggest that a specialized transport process might participate in the transcellular transport of cefotiam. The lipophilicities of these beta-lactam antibiotics were not correlated to the degree of transcellular transport, directly.

Animals↗
PubMed1998

Uptake of doxorubicin by cultured kidney epithelial cells LLC-PK1.

The renal handling of doxorubicin (DXR) was investigated using a kidney epithelial cell line, LLC-PK1. The uptake of DXR by LLC-PK1 cells cultured on plastic dishes was shown to be temperature and concentration dependent. The initial uptake of DXR was slightly saturable. The Km and Vmax of the saturable component were calculated to be 20.2 microM, and 0.355 nmol/mg protein/10 min, respectively. The release of DXR from LLC-PK1 cells was very slow at 37 degrees C and almost negligible at 4 degrees C, indicating that most of the DXR in the cells irreversibly binds to cellular constituents and that only a slight amount of unbound DXR participates in the efflux out of the cells. DXR uptake at 37 degrees C was significantly decreased in the presence of 2,4-dinitrophenol. However, organic cations and aminoglycoside antibiotics, such as tetraethylammonium, N1-methylnicotinamide, guanidine, gentamicin and neomycin, did not inhibit DXR uptake, suggesting that a process distinct from the organic cation transport system and absorptive endocytosis might be involved in the uptake of DXR by LLC-PK1 cells.

Alkaline Phosphatase↗
PubMed1998

A rapid assay of granisetron in biological fluids from cancer patients.

A convenient high-performance liquid chromatography (HPLC) was developed for the rapid assay of granisetron (GRN) in biological fluids, such as serum, urine, and pleural effusion, from cancer patients. Extrelut-1 was used for the solid-phase extraction. HPLC was carried out using a LiChroCART cartridge column packed with Lichrospher 100 CN and a mobile phase consisting of 0.1 M acetate buffer (pH 3.5) and acetonitrile (7:3). A fluorescence detector of 290 nm for excitation and 365 nm for emission was used. The standard curve was linear over the range of 2 to 100 ng/ml of GRN. Assay precision, expressed as a coefficient of variation (C.V.), was in the range of 0.9-5.4% in the within-day assay and 2.5-6.9% in the between-day assay, respectively. GRN was well separated on the HPLC chromatogram from drugs such as etoposide, metclopramide, ondansetron, and domperidone which are often used together with GRN. It was suggested that the present method is useful for the rapid monitoring of GRN in the serum, urine, and pleural effusion of patients undergoing cancer chemotherapy.

Antiemetics↗
PubMed1998

[Studies on antioxidant effects of Hypsizigus marmoreus. II. Effects of Hypsizigus marmoreus for antioxidant activities of tumor-bearing mice].

The in vivo effect of Hypsizigus marmoreus on the plasma antioxidant status of tumor-bearing mice was examined. Female DBA/2 mice treated with subcutaneous injection of 3-methylcholanthrene were fed on a basal diet (CE-2) or CE-2 containing 5% fruit bodies of the mushroom for 76 weeks. Antioxidant activities (AOA) of mice with tumor were significantly higher than those of mice without tumor. The high levels of AOA were attributable to the increase of high molecular weight AOA in the plasma. A similar increase in plasma AOA was also observed in sarcoma-180 solid tumor-bearing mice. The mushroom feeding exhibited a potent antitumor effect and caused a significant decrease in lipid peroxide levels (as thiobarbituric acid reactive substances; TBARS). These results suggest that the increase of AOA in the plasma of tumor-bearing mice is one of the mechanism of cancer preventive effects and also suggest that Hypsizigus marmoreus might play a role in decreasing TBARS by controlling AOA induction.

Agaricales↗
PubMed1998

Detection of a local slow potential preceding the surface QRS complex during non-preexcited impulse propagation--a phenomenon reflecting anterograde concealed conduction through the accessory pathway?

A case of Wolff-Parkinson-White (WPW) syndrome with several interesting electrophysiologic findings is presented. Although manifest preexcitation had not been documented in clinical routine check-ups for the 2 years before the ablation session, an intermittent preexcitation emerged after an initial unsuccessful radiofrequency current delivery directed at the subvalvular mitral annulus 1 cm distal from the subsequent successful ablation site. During intermittent manifestation of preexcitation, the following observations were made: (1) during manifest preexcitation, a possible Kent potential was recorded at the successful ablation site; (2) during non-preexcited impulse propagation, a local slow potential preceding the QRS complex (pre-QRS potential) was clearly observed at the same site; (3) the pre-QRS potential disappeared during orthodromic atrioventricular reciprocating tachycardia, spontaneous atrial premature contraction and after the subsequent successful ablation; and (4) when the pre-QRS potential was obvious, a small change in QRS morphology of the body-surface ECG was appreciable, compared with that during beats of negative pre-QRS potential. A comparable preceding component was also detected in a signal-averaged ECG. It is considered that the pre-QRS potential might be related to the anterograde concealed conduction through the accessory pathway.

Electrophysiology↗
PubMed1998

Suppression of gene expression and production of interleukin 13 by dexamethasone in human peripheral blood mononuclear cells.

We examined the effect of dexamethasone on the gene expression and production of interleukin (IL)-13 by human peripheral blood mononuclear cells from healthy controls. The gene expression was assessed semiquantitatively by sequential transcription polymerase chain reaction and Southern blot analysis, and the production of this cytokine was assessed by enzyme-linked immunosorbent assay (ELISA). Dexamethasone suppressed IL-13 gene expression induced by stimulation with phytohemagglutinin and phorbol 12-myristate 13-acetate in a dose-dependent manner, with 96% suppression at 10(-6) M, and also suppressed the increased production of IL-13. This is suggested to be one of the mechanisms by which glucocorticoids suppress allergic inflammation.

Anti-Inflammatory Agents↗
PubMed1998

[Transjugular intrahepatic portosystemic shunt for the treatment of refractory ascites].

Five cirrhotic patients with refractory ascites were treated with transjugular intrahepatic portosystemic shunt (TIPS). Before TIPS, although patients were received salt restriction (5 g/day), diuretic therapy (furosemide 112 mg/day, spironolactone 140 mg/day), albumin infusion and paracentesis, ascites did not show improvement. After TIPS, urine volume and urinary sodium excretion increased significantly. Mean body weight decreased significantly from 73 kg before TIPS to 63 kg a month after TIPS. Improvement of ascites after TIPS were associated with a significant reduction in the dose of diuretics. On discharge, complete resolution of ascites was found in 2 patients and mild ascites remained in 3 other patients. Four patients presented 6 episodes of shunt stenosis in the follow-up period, and were treated with balloon dilatation. Ascites increased on shunt dysfunction and showed improvement after balloon dilatation. Post-TIPS encephalopathy was seen in 2 patients and one of 2 was disabled. In conclusion, although post-TIPS shunt dysfunction and encephalopathy are common. TIPS is an effective therapy for refractory ascites in patients with cirrhosis.

Ascites↗
PubMed1998

[Evaluation of a newly developed broth microdilution test method to determine minimum inhibitory concentrations (MICs) of antimicrobial agents for mycobacteria].

We developed a new broth microdilution antimycobacterial susceptibility test for determination of minimum inhibitory concentration (MICs) using an air-dried microplate containing serially diluted antimicrobial agents and the modified Middlebrook 7H9 broth. The eight agents included were streptomycin (SM), isoniazid (INH), rifampicin (RFP), ethambutol (EB), kanamycin (KM), levofloxacin (LVFX), sparfloxacin (SPFX) and clarithromycin (CAM). Serial dilutions of the agents (128 micrograms/ml to 0.125 micrograms/ml) were prepared in microplates, and were reconstituted by inoculation of 0.2ml of cell suspensions (approximately 3 x 10(5) cells/ml). The test plates were incubated at 36 degrees C in 5% CO2, and the growth endpoints were read visually after 5-day, 7-day and 10-day incubations. Four ATCC reference strains, Mycobacterium tuberculosis, M. avium, M. kansasii and M. intracellulare, were repeatedly tested at three sites. Of 480 determination against eight agents, 455 (94.8%), 470 (97.9%) and 455 (94.8%) of the MICs read after 5-day, 7-day and 10-day incubations fell within 3log2 dilutions, respectively. The MICs gradually elevated during the incubation, however those of 7-day incubation were highly precise and easily determined. A total of 160 clinical isolates of M. tuberculosis and 114 of nontuberculous mycobacteria were tested against eight agents. As for the primary drugs (SM, INH, RFP and EB), most isolates of M. tuberculosis were highly susceptible with MIC90, < or = micrograms/ml. Both LVFX and SPFX were also active. The MICs against nontuberculous mycobacteria distributed in a wide range, and the activities of RFP, LVFX, SPFX and CAM were more potent. These results demonstrate this newly developed test method to be a practical, rapid, quantitative and nonradiometric alternative for the determination of MICs in clinical mycobacteriology laboratories.

Antitubercular Agents↗
PubMed1998

[The clinical usefulness of urinary pyridinoline and deoxypyridinoline as potential markers of bone metastasis in patients with prostate cancer].

The levels of probable markers of bony metastatic disease were measured to evaluate their efficacy as predictors of disease and therapeutic outcome. Urinary pyridinoline and deoxypyridinoline were measured in patients with benign prostatic hyperplasia, clinically localized prostate cancer and prostate cancer with bone metastases. Also, urinary pyridinoline and deoxypyridinoline were compared in 2 groups of patients with metastatic prostate cancer of the bone who demonstrated progression or positive response to treatment. Urinary pyridinoline and deoxypyridinoline were determined by high performance liquid chromatography and were normalized to urinary creatinine. Levels of urinary pyridinoline and deoxypyridinoline in urine in patients with bony metastatic prostate cancer were significantly greater than levels in patients with benign prostatic hyperplasia or localized prostate cancer. Serial measurement of urinary pyridinoline and deoxypyridinoline was correlated with a positive response to treatment (decreased) and with clinical progression of disease (increased) before detection of new bone lesions by bone scintigraphy. Measurement of urinary pyridinoline and deoxypyridinoline may provide a useful marker of prostate cancer metastatic to bone and may be useful in monitoring the response to treatment.

Aged↗
PubMed1998

[Autonomic nervous function of the patients with neurally mediated syncope].

Although diagnosis of neurally mediated syncope (NMS) using head-up tilt (HUT) test has been established, the exact mechanism of NMS has not yet been elucidated. We evaluated beta and alpha-adrenergic function in NMS patients by pharmacological autonomic function test. The alpha-adrenergic sensitivity of NMS patients was significantly lower than that of control subjects. The patients who need low dose isoproterenol for provocation of syncope showed higher beta-adrenergic sensitivity than patients who developed syncope without isoproterenol. Thus, pharmacological autonomic function test was useful for evaluation of NMS patients.

Adolescent↗
PubMed1997

RanBP2 associates with Ubc9p and a modified form of RanGAP1.

Ran is a small GTPase required for nuclear transport in eukaryotic cells [Gorlich, D. & Mattaj, I. W. (1996) Science 271, 1513-1518]. Mutants in Ran also show defects in mRNA processing, cell cycle regulation, and other aspects of nuclear function [Rush, M. G., Drivas, G. & D'Eustachio, P. (1996) BioEssays 18, 103-112; Sazer, S. (1996) Trends Cell Biol. 6, 81-85]. In an effort to understand the role of Ran in these diverse processes, we previously characterized 10 Ran interacting proteins (Rips) from Xenopus egg extracts. In this report, we present further characterization of a complex containing three of these Rips: p340(RanBP2), p88, and p18. We have cloned the Xenopus homologue of RanGAP1, and we show here that p88 is a modified form of this protein. In RanGAP assays, the p340(RanBP2)-p88-p18 complex contains GTPase-activating protein activity, indicating that RanGAP1 is not inactivated by modification. Rather, modification of RanGAP1 appears to be linked to its association with p340(RanBP2) because we did not observe unmodified RanGAP1 in p340(RanBP2) immunoprecipitates. We have also characterized p18, and we found that it is the Xenopus homologue of Ubc9p, an E2 ubiquitin-conjugating enzyme that is required for cell cycle regulation [Seufert, W., Futcher, B. & Jentsch, S. (1995) Nature (London) 373, 78-81]. Using antibodies directed against Xenopus Ubc9p, we have confirmed that Ubc9p associates with p340(RanBP2) in Xenopus extracts. These results suggest Ubc9p's role in cell cycle regulation may involve either modification of nuclear transport substrates or the nuclear transport machinery.

Amino Acid Sequence↗
PubMed1997

Detection of surfactant protein-A gene transcript in the cells from pleural effusion for the diagnosis of lung adenocarcinoma.

PURPOSE: To determine whether detecting surfactant protein-A (SP-A) gene transcript in the cells from pleural effusion is useful for the diagnosis of lung adenocarcinoma. PATIENTS AND METHODS: We performed reverse transcription polymerase chain reaction (RT-PCR) analysis of SP-A gene transcript in the cells of pleural effusion from 42 consecutive patients with pleural effusion, including 7 patients with primary lung adenocarcinoma before their treatments. RESULTS: A cDNA segment of SP-A was amplified from the pleural fluid cells of all patients with primary lung adenocarcinoma, indicating the presence of the SP-A gene transcript. None of the remaining patients, including those with metastatic lung adenocarcinoma, showed positive for the SP-A gene transcript. CONCLUSION: These findings indicate that RT-PCR analysis of the SP-A gene transcript in pleural effusion is useful for the diagnosis of primary lung adenocarcinoma.

Adenocarcinoma↗
PubMed1997

Four-channeled aortic dissection and rupture.

A four-channeled aortic dissection is quite rare, which is a highly life-threatening situation predisposing to aortic rupture. We report a successful management of a four-channeled aortic dissection and an aortic rupture in a 59-year-old woman with Marfan's syndrome 11 years after an initial Bentall procedure for DeBakey type I dissection. The total arch and the descending thoracic aorta were replaced under deep hypothermia and circulatory arrest.

Adult↗
PubMed1997

Restricted intestinal absorption of some beta-lactam antibiotics by an energy-dependent efflux system in rat intestine.

PURPOSE: The purpose of this study was to examine factors limiting the intestinal absorption of orally inactive beta-lactam antibiotics. METHODS: Permeation behaviors of various beta-lactam antibiotics across rat intestinal segments were evaluated in vitro using diffusion cells. RESULTS: Poorly absorbed beta-lactam antibiotics, like cephaloridine and cefoperazone, commonly exhibit greater serosal-to-mucosal permeation than mucosal-to-serosal permeation, while cephalexin permeation was greater in the mucosal-to-serosal direction. In the absence of D-glucose, secretory-oriented permeation of cephaloridine and cefoperazone disappeared. Addition of sodium azide into an experimental buffer including D-glucose significantly and selectively enhanced mucosal-to-serosal permeation of cephaloridine and cefoperazone. Although benzylpenicillin, ampicillin, and amoxicillin all showed secretory-oriented permeation, the tendency to permeation was greatest with benzylpenicillin and least with amoxicillin. Probenecid stimulated mucosal-to-serosal permeation of cephaloridine, but verapamil and p-aminohippuric acid had no significant effect on it. CONCLUSIONS: It has been suggested that mechanisms which induce secretory-oriented permeation of orally inactive beta-lactam antibiotics are factors limiting intestinal absorption of such antibiotics. This energy-demanding efflux system was distinct from P-glycoprotein-mediated transport. A free alpha-amino group in the molecule is an important factor for reducing an affinity with the efflux system.

Animals↗
PubMed1997

Prodrug and analog approaches to improving the intestinal absorption of a cyclic peptide, GPIIb/IIIa receptor antagonist.

PURPOSE: The purpose of this study was to test whether structural modifications improve the intestinal absorption of DMP 728 (cyclo(D-Abu-NMeArg-Gly-Asp-Amb)), a GPIIb/IIIa receptor antagonist. METHODS: In vitro permeabilities of prodrugs and analogs of DMP 728 across excised rat intestinal segments were determined. RESULTS: n-Butyl and n-octyl esters of DMP 728 were relatively stable during in vitro permeation of rat intestine. Intestinal permeation rates of these compounds were no greater than that of DMP 728, even though the octyl ester was much more lipophilic. A pivaloyloxymethyl ester, which was hydrolyzed to DMP 728 during intestinal permeation, also did not improve permeability. In another approach, analogs with an additional methyl substituent on various amide nitrogens were evaluated. Cyclo(D-Val-NMeArg-Gly-Asp-NMeAmb), cyclo(D-Abu-diN-MeLys-Gly-Asp-Amb), and cyclo(NMeGly-NMeArg-Gly-Asp-Amb) each had about 2-fold greater permeability than DMP 728. Two other analogs with improved permeability were linear Ac-D-Abu-NMeArg-Gly-Asp-Amb and a DMP 728 derivative in which the Asp was rearranged. An analog in which the charged amino acids were replaced by neutral amino acids had permeability similar to DMP 728. CONCLUSIONS: Within this series of peptides, hydrogen bonding tendency and structural constraint influenced intestinal permeation, but not always in ways consistent with the literature, whereas charge and lipophilicity were not shown to influence intestinal permeability. The failure of these approaches to improve permeation more significantly could be due to the influence of secretory transport.

Animals↗
PubMed1997

A high homology exists in N-terminal amino acid sequences of delta-endotoxins between Lepidoptera-specific and Coleoptera-specific Bacillus thuringiensis strains.

The 130 kDa parasporal inclusion proteins of the Lepidoptera-specific Bacillus thuringiensis reference strains for four H serovars were examined for sequences of 14 N-terminal amino acids. The four sequences fell into a single category, MNRNNQNEYEVIDA, and were dissimilar to any of the established sequences for Lepidoptera- and/or Diptera-killing crystal proteins. They were highly related to the reported sequence of the 130 kDa protein of the strain Buibui (serovar japonensis), which is specific for scarabaeid coleopterans.

Amino Acid Sequence↗