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Biomedical subjects

H Oka

Publications and source records attributed to H Oka.

At least 181 records · Page 10Linked to original sources

Total structures and antimicrobial activity of bacitracin minor components.

Total structures of 13 minor components of bacitracin (BC) were proposed, and their antimicrobial activities were investigated. The components of BC including bacitracins A (BC-A) and F (BC-F) were isolated by preparative HPLC and were hydrolyzed under acidic conditions. The resulting amino aids were derivatized with 1-fluoro-2,4-dinitrophenyl-5-L-alanineamide and were separated by HPLC to determine their absolute configurations. It was found that the N-terminal amino acids of BC-A and its related components were epimerized during the hydrolysis to yield their enantiomers. The formation of these artifactual amino acids suggests that our previously proposed structures of the BC minor components are incorrect; therefore, the structures were corrected based on these results. The structures of the BC minor components were the same as that of BCs-A and -F except that one to three of the L-isoleucines, including the N-terminal one, were replaced by L-valines. These structures were confirmed by tandem mass spectrometry under fast atom bombardment (FAB) conditions and Frit-FAB liquid chromatography/mass spectrometry. Based on the UV spectra of the BC components determined by photodiode array detection-HPLC analysis, a new systematic nonmenclature was proposed for the minor components. The isolated components were also used for the determination of their minimal inhibition concentrations and it was found that BC-A is 2 approximately 8 times more potent than the other minor components against strains of Micrococcus luteus and Staphylococcus aureus.

Amino Acid Sequence↗

[Histopathological and immunohistochemical evaluation of lymph node metastasis in superficial esophageal cancer--with reference to the expression of E-cadherin and alpha-catenin].

We compared node-negative patients (13 cases) with node-positive patients (17 cases) with submucosal cancer of the esophagus, to assess the relationship between clinicopathological factors and lymph node metastasis. We also investigated the expression of E-cadherin, an intercellular adhesion molecule (27 cases), and alpha-catenin, an undercoat protein of adherence junction (16 cases) by immunohistochemical staining to evaluate the association between intercellular adhesiveness and lymph node metastasis in superficial esophageal cancer. There was no significant difference between the node-negative and node-positive groups in other clinicopathological factors and tumor size, while the frequency of lymphatic invasion in the node-positive group was statistically higher than that in the node-negative group (p < 0.05). The frequency of lymph node metastasis in 14 cases with preserved expression of E-cadherin was significantly lower than that in 13 cases with reduced or negative expression (7.1% vs. 46.2%: p < 0.05). Moreover, all three patients with negative expression of alpha-catenin had lymph node metastasis, while only one of 13 patients with preserved or reduced expression of alpha-catenin had lymph node metastasis (100% vs. 7.7%: p < 0.01). In conclusion, we have found that the evaluation of both E-cadherin and alpha-catenin expression might be of great value in predicting lymph node metastasis in superficial esophageal cancer.

Adult↗

[Usefulness of every-other day administration of proton pump inhibitors from the standpoint of continuous 48-hour pH measurements-- Comparison of cimetidine, omeprazole, and lansoprazole].

We compared the usefulness of proton pump inhibitors (PPIs) every other day, with H2-blocker, in terms of inhibitory effect on gastric acid secretion. The dosages were as follows; cimetidine (CIM), 800mg and 400mg every day; omeprazole (OPZ) 20mg, and lansoprazole (LPZ), 30mg every other day. We continuously measured intragastric pH and calculated the time that pH was maintained at pH4 or more (pH4 holding time). The pH4 holding time as a part of total measurement time was significantly longer in the PPI every other day groups than in the H2-blocker groups, but there were no significant differences between the groups during the night. In PPI every other day groups, pH4 holding time of daytime period was suggested to be longer than on H2-blocker groups. In conclusion, their efficacy was greater than in the CIM group, and they appear to have a broad range of applications to the treatment of peptic ulcer.

2-Pyridinylmethylsulfinylbenzimidazoles↗

[Characteristics of regional sympathetic dysfunction in acutely ischemic myocardium assessed by 123I-metaiodobenzylguanidine imaging: impairment of myocardial norepinephrine uptake or retention].

To characterize regional cardiac sympathetic dysfunction due to myocardial ischemia, we examined 123I-metaiodobenzylguanidine (MIBG) myocardial distribution of initial 15-min and 4-hr delayed SPECT images in 14 patients with recent myocardial infarction (MI), 25 patients with vasospastic angina which was angiographically proven with elgonovine maleate (Gp VSAP) and 16 patients with chest pain syndrome and normal CAG findings (GpCP). In those with MI, the study was serially done at 2 weeks after (Gp MI-1) and at 3 months after the onset of MI (Gp MI-2). We estimated regional tracer uptake in 20 segments of tomographic images by using a 4-point scoring system (0 = normal, 1 = mild, 2 = moderate, 3 = severe reduction) and calculated the total defect score (IDS). In all patients with MI, the area of reduced MIBG uptake was more extensive than the 201Tl perfusion defect in the acute stage (Gp MI-1) indicating the presence of viable but denervated myocardial tissue. Also, the MIBG defect was persistently observed from initial (TDS: 24 +/- 13) to delayed imaging (TDS: 26 +/- 12). However, in the chronic stage (Gp MI-2), the initial MIBG uptake improved (TDS: 18 +/- 9) but the delayed uptake remained almost the same (TDS: 22 +/- 10) indicating high washout of MIBG from the ischemic myocardium. Fourteen in Gp VSAP and 14 in Gp CP showed the regional MIBG defect in the delayed image more extensively than in the initial image indicating high washout of MIBG in the involved myocardial regions. These results suggest that neuronal uptake of MIBG is impaired in the acute stage of MI although neuronal retention of MIBG is predominantly impaired in the chronic stage of MI or in Gps VSAP and CP.

3-Iodobenzylguanidine↗

[Detection of Helicobacter pylori by culture and the 13C-urea breath test using an automated breath 13C analyzer].

Up to now, the diagnosis of H. pylori infection has been made by the breath test using 13C-urea. In this study, 13C-urea breath samples were tested in 34 patients (peptic ulcer scar 17, chronic gastritis 17 cases) with an automated breath 13C analyzer (ABCA. Europa Scientific, Crewe, UK) and compared with the results of endoscopical diagnosis for H. pylori infection. Endoscopic and 13C-urea breath test (13C-UBT) were performed before eradicative medication. We described a modified protocol for the growth grade of H. pylori colonies in microbiology (H. pylori score), and for the delta 13C area under curve (AUC; permil*hr) obtained from each sample of expired breath. There was a significant correlation between delta 13C-AUC and the delta 13C level of each sample, but the correlation coefficient obtained at 10min (R2 = 0.582) was lower than that obtained at the other four time points (20min; 0.891, 30min; 0.949, 40min; 0.946, 50min; 0.946, 60min; 0.820). The delta 13C-AUC well correlated with H. pylori score (p < 0.01), none of 26 H. pylori positive patients detected by culture was 13C-UBT negative (delta 13C-AUC < 8.2 permil*hr in mean + 2SD of H. pylori negative group). In conclusion, 13C-UBT using ABCA has high sensitivity and specificity, and it provides a non-invasive method for the detection of H. pylori urease activity.

Breath Tests↗

Origin of ciliated craniopharyngioma: pathological relationship between Rathke cleft cyst and ciliated craniopharyngioma.

Histological study was undertaken on ciliated craniopharyngioma and Rathke cleft cyst, to know the origin of ciliated craniopharyngioma. Subjects were 7 cases with symptomatic Rathke cleft cysts and a ciliated craniopharyngioma. Light and electron microscopic observations were made on surgically resected specimens of the 8 cases. The ciliated craniopharyngioma was composed mainly of papillary type of craniopharyngioma and of dispersed ciliated columnar epithelium including goblet cells. Four cases with Rathke cleft cyst showed squamous metaplasia of which the basal cells were histologically similar to that of papillary type of craniopharyngioma. Other 3 cases of Rathke cleft cyst, basal cells were revealed to have tonofilaments and desmosomes. It seems possible that ciliated craniopharyngioma has derived from the basal cells of Rathke cleft epithelium.

Adult↗

Identification of unlawful food dyes by thin-layer chromatography-fast atom bombardment mass spectrometry.

A thin-layer chromatographic-fast atom bombardment mass spectrometric (TLC-FAB-MS) method incorporating an analyte condensation technique was established for the identification of the 27 food dyes consisting the twelve dyes permitted for use in foods and the fifteen unlawful dyes in Japan. The use of magic bullet [1,4-dithiothreitol-1,4-dithioerythritol (3:1)] as a matrix allowed the measurement of the FAB mass spectra of the food dyes except for Food Blue No. 2 (Indigo Carmine). The separation was performed on a C18-modified silica gel TLC plate using the following two solvent systems: methanol-acetonitrile-5% aqueous sodium sulphate solution (3:3:10) and methyl ethyl ketone-methanol-5% aqueous sodium sulphate solution (1:1:1). The condensation technique for concentration of a diffuse sample spot on the TLC plate improved the detection limit 4-20-fold with good reproducibility. The method was successfully applied to the identification of unlawful dyes in imported foods.

Chromatography, Thin Layer↗

Determination of mirosamicin in animal tissues by high-performance liquid chromatography.

A simple and rapid method using high-performance liquid chromatography (HPLC) for the determination of mirosamicin in animal tissues has been developed. The drug was extracted with 0.3% metaphosphoric acid-methanol (7:3, v/v), and the extracts were cleaned on a Bond Elut SCX (500 mg) cartridge. The HPLC separation was performed on a Puresil 5C18 column (150 x 4.6 mm I.D.) with 0.05 M phosphate buffer (pH 2.5)-acetonitrile (70:30) as the mobile phase at a flow-rate of 0.5 ml/min; the drug was detected at 230 nm with 0.04 AUFS. The calibration graph was linear from 5 to 100 ng. The recoveries of microsamicin from various animal tissues fortified at 1.0 microgram/g were 83.7-88.6% with a relative standard deviation (R.S.D.) of 2.0-5.7%. The detection limit was 0.05 microgram/g.

Animals↗

E-cadherin and alpha-catenin expression in human esophageal cancer.

Intercellular adhesion of the epithelial tissue is mainly regulated by the E-cadherin (E-cad) molecule. alpha-Catenin (alpha-cat) is one of the E-cad-associated cytoplasmic proteins that forms a linkage to the cytoskeleton and regulates E-cad function. To investigate the mechanism of dysfunction in cell-cell adhesion in cancerous tissues, we examined E-cad and alpha-cat expression by immunohistochemical staining on 46 human esophageal cancers using our specific monoclonal antibodies. By grading of E-cad and alpha-cat expression as uniformly positive (+), heterogeneous (+/-), or uniformly negative (-), the 46 tumors could be classified into 9 (20%) E-cad(+)/alpha-cat(+), 15 (33%) E-cad(+/-)/alpha-cat(+/-), 21 (46%) E-cad(+/-)/alpha-cat(-), and 1 (2%) E-cad(-)/alpha-cat(-). Twenty-five (54%) of the 46 tumors showed a similar expression of both molecules, while the other 21 tumors (46%) showed E-cad(+/-)/alpha-cat(-). Thus, although the expression of alpha-cat was significantly correlated with that of E-cad, in some tumors the reduction of alpha-cat was greater. Regarding the clinicopathological features, the reduction of alpha-cat expression, as well as that of E-cad, was significantly associated with tumor dedifferentiation, infiltrative growth, and lymph node metastasis (P < 0.01). Furthermore, the frequency of lymph node metastasis in E-cad(+/-)/alpha-cat(-) tumors was significantly higher (90%) than in E-cad(+)/alpha-cat(+) tumors (22%) (P < 0.01) or in E-cad(+/-)/alpha-cat(+/-) tumors (47%) (P < 0.05). These results suggest that not only E-cad but also alpha-cat are important regulators of intercellular adhesion and that alpha-cat is also involved in invasion and metastasis. In particular, reduction of alpha-cat expression is more correlated with invasive phenotype and lymph node metastasis than E-cad expression in human esophageal cancer.

Adult↗

Inhibition of topoisomerase II by a novel antitumor cyclic depsipeptide, BE-22179.

BE-22179, a novel cyclic depsipeptide antibiotic having two 3-hydroxyquinoline moieties, inhibited the DNA-relaxing activity of L1210 topoisomerase II completely at 0.08 microM. This effect was far stronger than that of VP-16. However, it did not show any marked effect on topoisomerase II-mediated DNA cleavage. BE-22179 was ineffective in inhibiting the DNA relaxation by topoisomerase I at concentrations up to 10 microM, but showed DNA-intercalating ability (DNA unwinding) at 30 microM. The structure of BE-22179 is quite novel for a topoisomerase II inhibitor. Echinomycin, a quinoxaline antibiotic structurally related to BE-22179, interfered with DNA relaxation by topoisomerase II, though the effect was not due to inhibition of the catalytic activity of topoisomerase II but to conformational change of DNA based on its intercalation into DNA. Therefore, the potent inhibitory activity on topoisomerase II might not be a common activity of quinoxaline antibiotics, but might rather be specific to BE-22179. BE-22179 prevented DNA synthesis as well as RNA synthesis in L1210 cells and inhibited the growth of the cells. However, it remains unclear to what extent the topoisomerase II inhibition was responsible for the cytotoxicity of BE-22179.

Animals↗

PEBP2 alpha B/mouse AML1 consists of multiple isoforms that possess differential transactivation potentials.

A murine transcription factor, PEBP2, is composed of two subunits, alpha and beta. There are two genes in the mouse genome, PEBP2 alpha A and PEBP2 alpha B, which encode the alpha subunit. Two types of the alpha B cDNA clones, alpha B1 and alpha B2, were isolated from mouse fibroblasts and characterized. They were found to represent 3.8- and 7.9-kb transcripts, respectively. The 3.8-kb RNA encodes the previously described alpha B protein referred to as alpha B1, while the 7.9-kb RNA encodes a 387-amino-acid protein, termed alpha B2, which is identical to alpha B1 except that it has an internal deletion of 64 amino acid residues. Both alpha B1 and alpha B2 associate with PEBP2 beta and form a heterodimer. The alpha B2/beta complex binds to the PEBP2 binding site two- to threefold more strongly than the alpha B1/beta complex does. alpha B1 stimulates transcription through the PEBP2 site about 40-fold, while alpha B2 is only about 25 to 45% as active as alpha B1. Transactivation domain is located downstream of the 128-amino-acid runt homology region, referred to as the Runt domain. Mouse chromosome mapping studies revealed that alpha A, alpha B, and beta genes are mapped to chromosomes 17, 16, and 8, respectively. The last two genes are syntenic with the human AML1 on chromosome 21q22 and PEBP2 beta/CBF beta on 16q22 detected at the breakpoints of characteristic chromosome translocations of the two different subtypes of acute myeloid leukemia. These results suggest that previously described chimeric gene products, AML1/MTG8(ETO) and AML1-EAP generated by t(8;21) and t(3;21), respectively, lack the transactivation domain of AML1.

Amino Acid Sequence↗

Correlation of altered Q-T interval and sympathetic nervous system dysfunction in diabetic autonomic neuropathy.

We examined the relationship between the Q-T interval and autonomic dysfunction in 74 diabetic patients and age-matched controls. The expected Q-T interval was standardized as a function of the R-R interval in 646 healthy controls, and the delta Q-T defined as the difference from the expected value. Propranolol increased delta Q-T, confirming this as a parameter of autonomic function. No relationship between delta Q-T and duration of disease, glucose control, retinopathy or proteinuria was observed. However, significant correlations were found between the delta Q-T and delay of nerve conduction velocity, orthostatic hypotension, altered Valsalva ratio, abnormal Valsalva overshoot, cold pressor response, decreased norepinephrine concentration and sympathetic function score in diabetic patients.

Adult↗

Radiological study of symptomatic Rathke's cleft cysts.

We investigated the relationship between radiological findings and the nature of the cyst fluid and histological findings of six Rathke's cleft cysts. The results show that the majority (five of six cases) of symptomatic Rathke's cleft cysts exhibit no enlargement of the sella turcica on plain x-rays, which may be helpful in differentiating cystic pituitary adenoma in the radiological diagnostic process. Three cases with large cysts showing high-intensity T1-weighted magnetic resonance images harbored abundances of cholesterol crystal and hemosiderin pigment in the cyst walls. The high signal intensity in magnetic resonance images of Rathke's cleft cysts may be explained by hemorrhage and a deposition of cholesterol crystal and may be considered in certain cases of Rathke's cleft cyst, especially when they are large.

Adult↗

Prospective study of alpha-fetoprotein in cirrhotic patients monitored for development of hepatocellular carcinoma.

The usefulness of measurements of serum alpha-fetoprotein elevation for diagnosis of the development of hepatocellular carcinoma was evaluated by a prospective study of 260 patients with cirrhosis. Hepatocellular carcinoma was found in 55 patients during the 5-yr follow-up, excluding 7 found to have hepatocellular carcinoma in the first 6 mo. The cumulative incidence of hepatocellular carcinoma was 26% in the 185 patients who had alpha-fetoprotein levels below 20 ng/ml at the time of entry and 46% in the 68 patients who had alpha-fetoprotein levels of 20 ng/ml or more but below 200 ng/ml. In 169 of the patients, serum levels of alpha-fetoprotein were assayed regularly for at least 2 yr. The incidence of hepatocellular carcinoma development in the 36 patients who had repeated transient increases in alpha-fetoprotein to above 100 ng/ml was 36%. This was significantly higher than the incidence in the 99 patients who had alpha-fetoprotein levels consistently below 20 ng/ml. Thus patients who had alpha-fetoprotein levels of 20 ng/ml or more, who had transient increases in alpha-fetoprotein or who had both should be treated as being in a super-high-risk group for hepatocellular carcinoma. Frequent and careful examination by ultrasonography of such patients is recommended.

Carcinoma, Hepatocellular↗