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C Ishii

Publications and source records attributed to C Ishii.

At least 37 records · Page 2Linked to original sources

Cloning and characterization of the yeast RAD1 homolog gene (mus-38) from Neurospora crassa: evidence for involvement in nucleotide excision repair.

A Neurospora crassa gene encoding a product with homology to the Saccharomyces cerevisiae Rad1 nucleotide excision repair (NER) protein was isolated by degenerate PCR. The predicted protein consists of 892 amino acids with a molecular weight of 100.4 kDa, and 32-37% identity to the XPF/ERCC4 protein family. The homolog was mapped to the left arm of linkage group I, the location of the mus-38 gene. Subsequently, gene inactivation and complementation studies identified the RAD1 homolog as mus-38. Immunological assays showed that the mus-18 (UV-specific endonuclease) and mus-38 strains have partial and normal UV-damage excision activities, respectively, but removal of thymine dimers and TC (6-4) photoproducts is abolished in the mus-18 mus-38 double mutant. The double mutant also was synergistically more sensitive to UV than either single mutant. The data suggest that mus-38 may participate in a different NER pathway from that involving the mus-18 gene.

Amino Acid Sequence↗

Infrahyoid spread of deep neck abscess: anatomical consideration.

The aim of this study was to determine the pathway of infrahyoid extension of the oropharyngeal abscess considering the anatomy of the fascial spaces by cross-sectional imaging. CT scans and MR images were retrospectively reviewed in ten patients with known infrahyoid extension of oropharyngeal abscesses (eight with acute tonsillitis, two with acute phlegmonous oropharyngitis). In seven of eight patients tonsillar abscesses descended along the deep cervical fascia converging on the hyoid bone and further accumulated in the anterior cervical space through which extension to the mediastinum took place in four patients. In seven patients the abscesses involved the retropharyngeal space at the infrahyoid neck. In two of these seven patients the abscesses directly extended down into the upper mediastinum through the retropharyngeal space. In one patients of the seven mediastinal spread of an abscess occurred through the posterior cervical space, not through the retropharyngeal space. Cross-sectional imaging is valuable in the evaluation of deep neck abscesses and the pathway of spread. The anterior cervical space in the infrahyoid neck is important for mediastinal extension of pharyngeal abscesses.

Abscess↗

Early diagnosis of herpes encephalopathy using fluid-attenuated inversion recovery pulse sequence.

This study describes the usefulness of fluid-attenuated inversion recovery (FLAIR) pulse sequence for early diagnosis and treatment of herpes encephalitis. An 8-year-old boy with suspected herpes simplex encephalitis was examined by magnetic resonance imaging at 3 days post-symptom onset. Lesions in the right thalamus and insular cortex were detected by conventional T2-weighted images and images from FLAIR pulse sequence. Bilateral temporal lesions, however, were only detected by FLAIR images.

Child↗

Interactions of plaunotol with bacterial membranes.

Plaunotol, a cytoprotective antiulcer agent, has a bactericidal effect against Helicobacter pylori, which may result from interaction of this compound with the bacterial cell membrane. The purpose of the present study was to confirm that plaunotol interacts with the H. pylori membrane. Membrane fluidities were measured using two stearic acid spin labels, namely 5-doxyl-stearic acid (in which the nitroxide group is located in the upper portion of the bacterial cell membrane) and 16-doxyl-stearic acid methyl ester (in which the nitroxide group is located deeper in the bacterial cell membrane), by means of electron spin resonance. The membrane fluidities of plaunotol-treated cells were significantly increased in the measurements made using the two spin labels. We also attempted to isolate plaunotol-resistant H. pylori in vitro by two different methods. To assess the level of resistance that could be reached, H. pylori was passaged five times on an agar plate containing subinhibitory concentrations of plaunotol or metronidazole. To measure the rate of development of resistance, H. pylori was grown with subinhibitory concentrations (0.25 x MIC) of plaunotol or metronidazole, and quantitatively plated on to medium containing 4 x MIC of the compounds. This treatment was repeated once more. No plaunotol-resistant colonies were selected by the two methods. H. pylori developed resistance to metronidazole easily and at a relatively high rate. The mechanism by which plaunotol directly fluidizes and destroys the H. pylori membrane might make it difficult for this organism to develop resistance to plaunotol. It was confirmed that the bactericidal effects of plaunotol were also shown against Staphylococcus aureus, Streptococcus pneumoniae, Neisseria gonorrhoeae, Moraxella catarrhalis and Haemophilus influenzae. No such effect was seen against Escherichia coli and Pseudomonas aeruginosa.

Anti-Bacterial Agents↗

[Usefulness of CO2 US angiography in treating hepatocellular carcinoma].

We evaluated the usefulness of CO2 US angiography in the detectability of and the effectiveness of TAE and/or PEIT for hepatocellular carcinoma (HCC). Twenty-three patients with HCC underwent CO2 angiography during the interventional procedure to treat HCC after examination of CT and conventional US. CO2 US angiography was observed on the US monitor by injecting CO2 microbubbles through a catheter placed in the hepatic artery. Contrast materials for CO2 US angiography were 3 ml of CO2 microbubbles prepared by vigorously mixing 3 ml of normal saline with 3 ml of 20% Intralipid, 3 ml of 20% albumin or 3 ml of the patient's own blood. In all patients, CO2 US angiography revealed equal or superior tumor detectability as compared with CT, conventional US and angiography. For demonstrating the inner structure of HCC, the image of CO2 microbubbles mixed with Intralipid was better than that of CO2 microbubbles mixed with albumin. In 9 of 23 patients, CO2 US angiography depicted nodules that had not been seen in the other images. TAE was performed in 21 patients with HCC who showed hypervascularity. In one patient in whom it was difficult to clearly depict the small lesion of HCC by conventional angiography and US, PEIT was successful under CO2 US angiography. The detectability of HCC was higher in CO2 US angiography than in CT, conventional US or angiography. The distribution of blood supply to HCC was observed easily by CO2 US angiography. In TAE of HCC, CO2 US angiography was useful to determine the dose of embolization materials without having to perform repeated angiography. It was possible to perform PEIT easily for non-detectable tumors without CO2 US angiography. CO2 US angiography was useful to evaluate the stage of HCC and to perform TAE and PEIT.

Aged↗

Development of non-insulin-dependent diabetes mellitus in the double knockout mice with disruption of insulin receptor substrate-1 and beta cell glucokinase genes. Genetic reconstitution of diabetes as a polygenic disease.

Non-insulin-dependent diabetes mellitus (NIDDM) is considered a polygenic disorder in which insulin resistance and insulin secretory defect are the major etiologic factors. Homozygous mice with insulin receptor substrate-1 (IRS-1) gene knockout showed normal glucose tolerance associated with insulin resistance and compensatory hyperinsulinemia. Heterozygous mice with beta cell glucokinase (GK) gene knockout showed impaired glucose tolerance due to decreased insulin secretion to glucose. To elucidate the interplay between insulin resistance and insulin secretory defect for the development of NIDDM, we generated double knockout mice with disruption of IRS-1 and beta cell GK genes by crossing the mice with each of the single gene knockout. The double knockout mice developed overt diabetes. Blood glucose levels 120 min after intraperitoneal glucose load (1.5 mg/g body wt) were 108 +/- 24 (wild type), 95 +/- 26 (IRS-1 knockout), 159 +/- 68 (GK knockout), and 210 +/- 38 (double knockout) mg/dl (mean +/- SD) (double versus wild type, IRS-1, or GK; P < 0.01). The double knockout mice showed fasting hyperinsulinemia and selective hyperplasia of the beta cells as the IRS-1 knockout mice (fasting insulin levels: 0.38 +/- 0.30 [double knockout], 0.35 +/- 0.27 [IRS-1 knockout] versus 0.25 +/- 0.12 [wild type] ng/ml) (proportion of areas of insulin-positive cells to the pancreas: 1.18 +/- 0.68%; P < 0.01 [double knockout], 1.20 +/- 0.93%; P < 0.05 [IRS-1 knockout] versus 0.54 +/- 0.26% [wild type]), but impaired insulin secretion to glucose (the ratio of increment of insulin to that of glucose during the first 30 min after load: 31 [double knockout] versus 163 [wild type] or 183 [IRS-1 knockout] ng insulin/mg glucose x 10(3)). In conclusion, the genetic abnormalities, each of which is nondiabetogenic by itself, cause overt diabetes if they coexist. This report provides the first genetic reconstitution of NIDDM as a polygenic disorder in mice.

Animals↗

Change of plasma 1,5-anhydro-D-glucitol levels after the onset of diabetes in spontaneous diabetes prone BB/Wor/(/)Tky rats.

Plasma 1,5-anhydro-D-glucitol (AG) is a marker of the diabetic state and also reflects the glycosuria induced by hyperglycemia but not by renal pathology. To investigate the benefits of the AG determination in order to diagnose diabetes in BB/Wor/(/)Tky rats, AG was measured in non-diabetic (n = 104) and diabetic (n = 113) BB/Wor/(/)Tky rats. AG was significantly higher in non-diabetic rats than in diabetic rats (25.2 +/- 9.3 vs 4.1 +/- 7.4 micrograms/ ml, mean +/- SD, p < 0.001). The best cut-off level for AG (8.5 micrograms/ml) was highly specific (100%) for ruling out diabetes and fairly sensitive (82.3%) to detect diabetes. Based on the AG cut-off levels, 90% of false-negative diabetic rats (18/20) were observed within 4 days after the onset of diabetes, which corresponded to 38.3% in diabetic rats (18/47) at that time. The false-negative diabetic rats and positive rats could be effectively distinguished based on the cumulative points given according to the urinary glucose after the onset of diabetes. 1 point for each cross [+] indicating glycosuria using the Testape, i.e. 2 or less points false negative and 4 or more points for diabetic rats in the first 4 days. In conclusion, there is a close inverse relation between the level of plasma AG and the amount of glycosuria detected just after the onset of overt diabetes in BB/Wor/(/)Tky rats.

Animals↗

In vitro and in vivo antibacterial activities of CS-834, a novel oral carbapenem.

CS-834 is a novel oral carbapenem antibiotic. This compound is an ester-type prodrug of the active metabolite R-95867. The antibacterial activity of R-95867 was tested against 1,323 clinical isolates of 35 species and was compared with those of oral cephems, i.e., cefteram, cefpodoxime, cefdinir, and cefditoren, and that of a parenteral carbapenem, imipenem. R-95867 exhibited a broad spectrum of activity covering both gram-positive and -negative aerobes and anaerobes. Its activity was superior to those of the other compounds tested against most of the bacterial species tested. R-95867 showed potent antibacterial activity against clinically significant pathogens: methicillin-susceptible Staphylococcus aureus including ofloxacin-resistant strains, Streptococcus pneumoniae including penicillin-resistant strains, Clostridium perfringens, Neisseria spp., Moraxella catarrhalis, most members of the family Enterobacteriaceae, and Haemophilus influenzae (MIC at which 90% of strains are inhibited, < or =0.006 to 0.78 microg/ml). R-95867 was quite stable to hydrolysis by most of the beta-lactamases tested except the metallo-beta-lactamases from Stenotrophomonas maltophilia and Bacteroides fragilis. R-95867 showed potent bactericidal activity against S. aureus and Escherichia coli. Penicillin-binding proteins 1 and 4 of S. aureus and 1Bs, 2, 3, and 4 of E. coli had high affinities for R-95867. The in vivo efficacy of CS-834 was evaluated in murine systemic infections caused by 16 strains of gram-positive and -negative pathogens. The efficacy of CS-834 was in many cases superior to those of cefteram pivoxil, cefpodoxime proxetil, cefdinir, and cefditoren pivoxil, especially against infections caused by S. aureus, penicillin-resistant S. pneumoniae, E. coli, Citrobacter freundii, and Proteus vulgaris. Among the drugs tested, CS-834 showed the highest efficacy against experimental pneumonia in mice caused by penicillin-resistant S. pneumoniae.

Administration, Oral↗

Evidence for association between the class I subset of the insulin gene minisatellite (IDDM2 locus) and IDDM in the Japanese population.

Although the shortest (class I) minisatellite (i.e., variable number of tandem repeats [VNTR]) alleles in the 5' region of the insulin gene are positively associated with IDDM in Caucasians, the majority of Japanese are homozygous for class I alleles. Here, we determined the exact length, in number of repeat units (RUs), of class I alleles in Japanese subjects. The distribution of class I alleles in Japanese was trimodal, with peaks located at 32/33, 41, and 44 RUs. The shortest component (i.e., 1S [25-38 RUs]) alleles were significantly increased in the IDDM group compared with the control group (54 vs. 46%; P = 0.040). The 1S/1S genotype was significantly increased in the IDDM patients (34 vs. 20%; P = 0.005; relative risk 2.1). Furthermore, the transmission disequilibrium test of Japanese families with 1S/1M or 1S/1L heterozygous parents confirmed the association of 1S alleles; 17 alleles of 1S and 6 alleles of 1M (39-41 RUs) or 1L (42-44 RUs) were transmitted to affected offspring (P = 0.022). In addition, we found tight linkage of 1S with allele 9 of the tyrosine hydroxylase gene microsatellite and allele (-) of the IGF-II gene Apa I polymorphism, but neither 9 nor (-) alleles were significantly associated with IDDM. The present study suggests that a class I subset may have a role in IDDM susceptibility in Japan. It was revealed that the difference between 1S alleles and 1M or 1L alleles is almost consistently characterized by a sequence variation generated by deletion of two copies of an ACAGGGGTCC CGGGG repeat element, implying that sequence variation of class I alleles may influence disease susceptibility.

Adolescent↗

[Combination effect between panipenem and vancomycin on highly methicillin-resistant Staphylococcus aureus].

We investigated the in vitro and in vivo combination effects between panipenem (PAPM) and vancomycin (VCM) on highly methicillin-resistant strains of Staphylococcus aureus (MRSA) isolated from various clinical specimens. Examination of combination between panipenem and vancomycin using checkerboard titration showed a good effect with mean fractional inhibitory index of 0.32 +/- 0.12 on 40 MRSA strains, and the effects were judged as synergistic against 33 strains (83%) and additive against 7 strains (17%). In the combination of PAPM and VCM at 1/4 MIC each against exponentially growing MRSA, bactericidal activity was found when PAPM was added at 1 hour or 2 hours prior to VCM-addition, and PAPM with VCM was added simultaneously, although bactericidal activity was scarcely demonstrated when VCM was added at 1 hour or 2 hours prior to PAPM-addition. Bactericidal activity was enhanced against MRSA in the combination of PAPM and VCM at 1/4 MIC each for MRSA than the bactericidal activity of VCM at 1 MIC alone, and the combination showed a strong bactericidal activity against P. aeruginosa. VCM alone, however, had no bactericidal activity in the in vitro mixed cultures of the two bacteria. Furthermore, the combination of PAPM and VCM induced a marked damage to cell surface and bacteriolysis against MRSA and P. aeruginosa in the mixed cultures, although VCM alone induced only slight morphological alterations. Penicillin-binding proteins (PBPs) including MRSA-specific PBP 2' were decreased greatly in the amounts in MRSA-cells with the increase of VCM-treated concentration. The combination therapy of PAPM and VCM showed a greater efficacy than the therapeutic efficacy of each antibiotic alone against mixed infection in burned mice caused by MRSA and P. aeruginosa, and the activity was judged as synergistic based on the FED index smaller than 0.34.

Animals↗

In-vitro and in-vivo antibacterial activity of plaunotol, a cytoprotective antiulcer agent, against Helicobacter pylori.

Recently, some antiulcer agents have been reported to have antibacterial activity against Helicobacter pylori, which is highly associated with gastritis and peptic ulcers. In-vitro and in-vivo activity of plaunotol, a cytoprotective antiulcer agent, against H. pylori was investigated. Antibacterial activity of plaunotol against a standard strain (NCTC 11637) and 14 clinical isolates was compared with those of other cytoprotective antiulcer agents: benexate, sofalcone, teprenone, cetraxate, and gefarnate, by an agar dilution method. The MIC50 and MIC90 of plaunotol against 15 strains were 6.25 and 12.5 mg/L, respectively, making it the most potent of the cytoprotective antiulcer agents. The bactericidal effect of plaunotol was investigated using an in-vitro killing assay. Plaunotol at concentrations of more than 6 mg/L induced a rapid reduction of culture turbidity, with an extensive loss of viability, within 30 min. Observation by scanning electron microscopy revealed that plaunotol caused autolysis and treated cells were deformed. In-vivo activity of plaunotol against H. pylori was examined in a nude mouse gastritis model. Plaunotol significantly decreased the number of H. pylori in the stomach of nude mice. In addition, the antiulcer agent enhanced the antibacterial activity of amoxycillin or clarithromycin in the infection model.

Amoxicillin↗

Bactericidal effect of plaunotol, a cytoprotective antiulcer agent, against Helicobacter pylori.

In order to investigate the bactericidal effect of plaunotol, an oily antiulcer agent, against Helicobacter pylori, comparative studies were conducted using its derivatives, M-4, M-5, and M-6, whose hydrophobicity decreased in the order of plaunotol > M-6 > M-5 > M-4 by log P determination. Plaunotol rapidly reduced the viability of H. pylori in vitro, and cell death was associated with cell lysis. In addition, plaunotol showed eightfold stronger bactericidal activity against H. pylori than M-6 and M-5, while the compound with the lowest hydrophobicity, M-4, showed no bactericidal activity. The bactericidal activities of plaunotol and its derivatives were related to the hydrophobicity of these compounds. To investigate a possible interaction between these compounds and the cell membrane of H. pylori, their effects on liposomal membranes prepared from phosphatidylethanolamine and cardiolipin, which are known to be present in the membrane of H. pylori, were determined by detection of glucose release from the liposomes. Plaunotol showed eight-fold higher activity than M-6 and M-5, while M-4 showed no activity. The effects of plaunotol and its derivatives on liposomal membrane were therefore related to their bactericidal activities. In addition, it was confirmed that the bactericidal effect of plaunotol against H. pylori was neutralized by the liposomal membrane, and that plaunotol led to an increase in permeability of the membrane, as evidenced by measurement of the leakage of 260 nm absorbing-material from H. pylori. These results suggest that the bactericidal effect of plaunotol against H. pylori is due to the interaction between this compound and the bacterial cell membrane.

Anti-Bacterial Agents↗

Evaluation of nitric oxide formation from nitrates in pig coronary arteries.

To clarify the hypothesis that organic nitrates are converted to nitric oxide (NO) via nitrite ion (NO2-) by glutathione S-transferase, the metabolic conversion of four nitrates was examined in pig coronary arteries and compared with that in rat liver. Nitrates caused the relaxation of the artery muscles with the order of nitroglycerin > isosorbide dinitrate > nicorandil > or = nipradilol, whereas the order of NO formation in the arteries was nitroglycerin > isosorbide dinitrate > nipradilol > nicorandil. The same order of NO formation from the nitrates was also observed in liver cytosol. Nicorandil may cause more relaxation than nipradilol by both NO releasing and other (unknown) actions. Although the order of the potency in NO2- formation from the nitrates in liver cytosol was the same as that seen in NO formation, NO2- was not detected in pig coronary arteries. Thus NO2- formation from the nitrates correlated with NO formation in liver cytosol but not in pig arteries. When nonenzymatic and enzymatic NO formations from nitroglycerin were examined in the arteries, the enzymatic NO formation, which was not inhibited by glutathione S-transferase inhibitors, was 13% of the total NO. These results indicate that in pig coronary arteries, nitrates release NO mostly through a nonenzymatic manner, although there is a slight amount of enzymatically produced NO, and glutathione S-transferase may not contribute to the enzymatic NO formation.

Animals↗