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Biomedical subjects

T Oshima

Publications and source records attributed to T Oshima.

At least 91 records · Page 5Linked to original sources
PubMed2000

Type 2 angiotensin II receptor is downregulated in cardiomyocytes of patients with heart failure.

BACKGROUND: The human heart expresses type 2 angiotensin (AT(2)) receptor, but the function is poorly defined. METHODS: In the present study, we investigated (1) the cellular localization of the AT(2) receptor and (2) the relationship between the AT(2) receptor protein expression and the cardiac function of patients with ischemic heart disease. The receptor localization was assessed by immunohistochemistry and the protein expression was quantified by Western blotting in atrial tissues freshly obtained from 22 patients undergoing coronary artery bypass graft surgery (63.0+/-11.0 years old; male ratio, 85%). Prior to the surgery, blood was drawn for determination of atrial-natriuretic hormone level and the left ventricular function was assessed by ultrasound cardiography. RESULTS: The results of immunohistochemistry showed that the AT(2) receptor was localized to cardiomyocytes and was not present in fibroblasts, vascular smooth muscles, or vascular endothelium. Atrial tissues showed various degrees of structural remodeling, but the localization of the AT(2) receptor was not altered in any tissue sections. The amount of the AT(2) receptor was negatively correlated with end-diastolic left ventricular diastolic dimension (r=-0.56, P<0.01), calculated left ventricular mass index (r=-0.51, P<0.02) and the plasma atrial natriuretic peptide (ANP) concentration (r=-0. 62, P<0.01) and positively correlated with left ventricular ejection fraction (r=0.48, P<0.05). CONCLUSIONS: (1) The AT(2) receptor is localized to cardiomyocytes independently of the cardiac function. (2) Left ventricular dysfunction is associated with decreased expression of myocardial AT(2) receptor protein.

Adult↗
PubMed2000

Cisplatin-induced apoptotic cell death in Mongolian gerbil cochlea.

Cisplatin is well known to cause cochleotoxicity. In order to determine the underlying mechanisms of cisplatin-induced cell death in the cochlea, we investigated the apoptotic changes and the expression of bcl-2 family proteins controlling apoptosis. Mongolian gerbils were administered 4 mg/kg/day cisplatin consecutively for 5 days. The cisplatin-treated animals showed a significant deterioration in the responses of both distortion product otoacoustic emissions and the endocochlear potential as compared with those of the age-matched controls, suggesting outer hair cell and stria vascularis dysfunction. The presence of DNA fragmentation revealed by a terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling method was recognized in the organ of Corti, the spiral ganglion, and the stria vascularis in the cisplatin-treated animals whereas almost negative results were obtained in the control animals. The nuclear morphology obtained by Hoechst 33342 staining revealed pyknotic and condensed nuclei, confirming the presence of the characteristic features of apoptosis. A significant increase and reduction in the number of bax- and bcl-2-positive cells, respectively, following cisplatin treatment was observed in the cells of the organ of Corti, the spiral ganglion, and the lateral wall. These findings suggest a critical role for bcl-2 family proteins in the regulation of apoptotic cell death induced by cisplatin. The underlying mechanisms of the cisplatin-induced cell death are discussed.

Animals↗
PubMed2000

A comparison of angiotensin-converting enzyme inhibitors, calcium antagonists, beta-blockers and diuretic agents on reactive hyperemia in patients with essential hypertension: a multicenter study.

OBJECTIVES: The purpose of this study was to compare the effect of different antihypertensive agents, calcium antagonists, angiotensin-converting enzyme (ACE) inhibitors, beta-blockers and diuretic agents on endothelial function. BACKGROUND: Endothelial dysfunction is a component of essential hypertension, and various antihypertensive drugs may be able to restore normal function. METHODS: Forearm blood flow (FBF) was measured in 296 patients with essential hypertension, including 46 untreated subjects using strain-gauge plethysmography during reactive hyperemia and after sublingual administration of nitroglycerin (NTG). Forty-seven normotensive subjects were similarly evaluated as control subjects. RESULTS: The FBF during reactive hyperemia in the 296 hypertensive patients was significantly less than that in age-matched normotensive subjects. The increase in FBF after administration of sublingual NTG was similar in both groups. Systolic and diastolic blood pressures and forearm vascular resistance were greater in the untreated group than in the four treated groups and did not differ with respect to the antihypertensive agent used. The maximal FBF response from reactive hyperemia was significantly greater in the ACE inhibitor-treated group than in the group treated with calcium antagonists, beta-blockers, diuretic agents, or nothing (40.5 +/- 5.2 vs. 32.9 +/- 5.8, 34.0 +/- 5.6, 32.1 +/- 5.9, and 31.9 +/- 5.8 ml/min per 100 ml tissue, p < 0.05, respectively). Reactive hyperemia was similar in the calcium antagonist, beta-blocker, diuretic and untreated groups, and changes in FBF after sublingual NTG administration were similar in all groups. The infusion of NG-monomethyl-L-arginine, a nitric oxide (NO) synthase inhibitor, abolished the enhancement of reactive hyperemia in hypertensive patients treated with ACE inhibitors. CONCLUSIONS: These findings suggest that ACE inhibitors augment reactive hyperemia, an index of endothelium-dependent vasorelaxation, in patients with essential hypertension. This augmentation may be due to increases in NO.

Adrenergic beta-Antagonists↗
PubMed2000

Type 1A dopamine receptor expression in the heart is not altered in spontaneously hypertensive rats.

We have recently demonstrated that type 1A dopamine (D1A) receptor is expressed in the rat heart, but its function still remains unknown. In the present study, we investigated possible changes in the expression level and the distribution of the cardiac D1A receptor in the development of left ventricular hypertrophy in spontaneously hypertensive rats/Izumo strain (SHR/Izm) at the ages of 4, 8, and 20 weeks. We examined D1A receptor protein distribution by immunohistochemistry and gene expression by competitive polymerase chain reaction (competitive PCR). In SHR/Izm, compared with the age-matched Wistar Kyoto rats/Izmo strain (WKY/Izm), blood pressure and heart/body weight ratio were significantly increased at 8 and 20 weeks. By immunohistochemistry, the D1A receptor was localized in cardiomyocytes and vascular smooth muscle cells of coronary arteries, but not in interstitial fibrotic tissue. D1A receptor distribution was not changed either by the strain or the age. Competitive PCR analysis showed that the D1A receptor mRNA level was significantly higher at 4 weeks than at 8 and 20 weeks in both strains of rats and that there was no significant difference in D1A receptor mRNA between SHR/Izm and WKY/Izm at any age (43.2 +/- 10.4 attomol x 10(-3)/L v 43.1 +/- 11.2 attomol x 10(-3)/L at 4 weeks, P = not significant, 3.9 +/- 0.9 attomol x 10(-3)/L v 4.0 +/- 1.3 attomol x 10(-3)/L at 8 weeks, P = not significant, 3.0 +/- 1.2 attomol x 10(-3)/L v 1.9 +/- 1.6 attomol x 10(-3)/L at 20 weeks, P = not significant). These results do not support the hypothesis that changes in D1A receptor expression are associated with the development of left ventricular hypertrophy in SHR.

Animals↗
PubMed2000

Penetration by a giant gastric ulcer induced by a nonsteroidal anti-inflammatory drug.

A patient presented with penetration by a giant gastric ulcer resulting from treatment with a nonsteroidal anti-inflammatory drug. A test for Helicobacter pylori proved negative. Treatment with a combination of an inhibitor of gastric acid secretion and prostaglandin substitution therapy with misoprostol resulted in closure of the perforation and cicatrization of the gastric ulcer without the need for laparotomy.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Identification of Thermus thermophilus HB8 tRNA (Gm18) methyltransferase gene.

For the purpose of identification of the gene for Thermus thermophilus tRNA (Gm18) methyltransferase [tRNA (guanosine-2'-)-methyltransferase, EC 2.1.1.34], the purified enzyme from native source was analyzed by the peptide-mass mapping. The target gene encoded the amino acid sequences of the obtained peptides was searched in data from Thermus thermophilus HB8 genome-sequencing project. We found the target gene AB05130, which was expected to encode a protein composed of 194 amino acid residues and the molecular mass of this protein was calculated as 22083. The recombinant protein was expressed in E. coli as an active form. The Gm18 formation activity of the purified recombinant protein was confirmed by in vitro methylation followed by two-dimensional thin layer chromatography and Liquid Chromatography/Mass Spectrum analysis of substrate tRNA.

Base Sequence↗
PubMed2000

Crystal structures of 3-isopropylmalate dehydrogenases with mutations at the C-terminus: crystallographic analyses of structure-stability relationships.

Thermal stability of the Thermus thermophilus isopropylmalate dehydrogenase enzyme was substantially lost upon the deletion of three residues from the C-terminus. However, the stability was partly recovered by the addition of two, four and seven amino acid residues (called HD177, HD708 and HD711, respectively) to the C-terminal region of the truncated enzyme. Three structures of these mutant enzymes were determined by an X-ray diffraction method. All protein crystals belong to space group P2(1) and their structures were solved by a standard molecular replacement method where the original dimer structure of the A172L mutant was used as a search model. Thermal stability of these mutant enzymes is discussed based on the 3D structure with special attention to the width of the active-site groove and the minor groove, distortion of beta-sheet pillar structure and size of cavity in the domain-domain interface around the C-terminus. Our previous studies revealed that the thermal stability of isopropylmalate dehydrogenase increases when the active-site cleft is closed (the closed form). In the present study it is shown that the active-site cleft can be regulated by open-close movement of the minor groove located at the opposite side to the active-site groove on the same subunit, through a paperclip-like motion.

3-Isopropylmalate Dehydrogenase↗
PubMed2000

The initial step of the thermal unfolding of 3-isopropylmalate dehydrogenase detected by the temperature-jump Laue method.

A temperature-jump (T-jump) time-resolved X-ray crystallographic technique using the Laue method was developed to detect small, localized structural changes of proteins in crystals exposed to a temperature increase induced by laser irradiation. In a chimeric protein between thermophilic and mesophilic 3-isopropylmalate dehydrogenases (2T2M6T), the initial structural change upon T-jump to a denaturing temperature (approximately 90 degrees C) was found to be localized at a region which includes a beta-turn and a loop located between the two domains of the enzyme. A mutant, 2T2M6T-E110P/S111G/S113E, having amino acid replacements in this beta-turn region with the corresponding residues of the thermophilic enzyme, showed greater stability than the original chimera (increase of T:(m) by approximately 10 degrees C) and no T-jump-induced structural change in this region was detected by our method. These results indicate that thermal unfolding of the original chimeric enzyme, 2T2M6T, is triggered in this beta-turn region.

3-Isopropylmalate Dehydrogenase↗
PubMed2000

H(2)O(2)-mediated permeability: role of MAPK and occludin.

H(2)O(2)-mediated elevation in endothelial solute permeability is associated with pathological events such as ischemia-reperfusion and inflammation. To understand how H(2)O(2) mediates increased permeability, we investigated the effects of H(2)O(2) administration on vascular endothelial barrier properties and tight junction organization and function. We report that H(2)O(2) exposure caused an increase in endothelial solute permeability in a time-dependent manner through extracellularly regulated kinase 1 and 2 (ERK1/ERK2) signal pathways. H(2)O(2) exposure caused the tight junctional protein occludin to be rearranged from endothelial cell-cell junctions. Occludin rearrangement involved redistribution of occludin on the cell surface and dissociation of occludin from ZO-1. Occludin also was heavily phosphorylated on serine residues upon H(2)O(2) administration. H(2)O(2) mediates changes in ERK1/ERK2 phosphorylation, increases endothelial solute permeability, and alters occludin localization and phosphorylation were all blocked by PD-98059, a specific mitogen-activated protein (MAP) or ERK kinase 1 inhibitor. These data strongly suggest that H(2)O(2)-mediated increased endothelial solute permeability involves the loss of endothelial tight junction integrity through increased ERK1/ERK2 activation.

Cell Membrane↗
PubMed2000

Expression and localization of angiotensin subtype receptor proteins in the hypertensive rat heart.

The cellular localization of the AT(2) receptor and the regulation of its expression in hypertrophied left ventricle are not well known. We compared the expression of the cardiac AT(1) and AT(2) receptor in spontaneously hypertensive rats/Izumo strain (SHR/Izm) and Wistar Kyoto rats/Izumo strain (WKY/Izm), ages 4, 12, and 20 wk, by means of immunohistochemistry and Western blot analysis. In SHR/Izm, compared with WKY/Izm, blood pressure (161 +/- 2 vs. 120 +/- 2 mmHg at 12 wk, P </= 0.01, and 199 +/- 3 vs. 123 +/- 3 mmHg at 20 wk, P </= 0.01) and heart-to-body weight ratio (3.76 +/- 0.07 vs. 3.06 +/- 0.06 mg/g at 12 wk, P </= 0.01, and 3.90 +/- 0.08 vs. 3.01 +/- 0.12 mg/g at 20 wk, P </= 0.01) were significantly elevated. There was no difference in these values between the two strains at 4 wk of age. Histologically, 20-wk-old SHR/Izm demonstrated myocardial hypertrophy, a thickening of the smooth muscle layer of the intracardiac arteries, and perivascular fibrosis. By immunohistochemistry, the AT(2) receptor was localized to cardiomyocytes and vascular endothelial cells, but not in the vascular smooth muscle cells. No major AT(2) receptor signal was observed in perivascular fibrosis at any age in either strain of rats. No difference was detected in this localization between the two strains. By Western blotting, a single 44-kDa band for the AT(2) receptor and a single 60-kDa band for the AT(1) receptor were detected in ventricles from both strains of rats at all ages. Densitometric analysis demonstrated that the AT(2) receptor 44-kDa band was decreased by 20% at 12 wk and 32% at 20 wk (P < 0.01) in SHR/Izm compared with WKY/Izm. The intensity of the AT(1) receptor 60-kDa band was increased by 57% in 20-wk-old SHR/Izm compared with WKY/Izm (P < 0.05). There was no significant difference in the intensity of the 44- or 60-kDa bands in 4-wk-old animals of either strain. We demonstrated a decrease in the AT(2) receptor and an increase in the AT(1) receptor protein with no change in their localizations in hypertrophied left ventricular myocytes of SHR/Izm.

Angiotensins↗
PubMed2000

A case of extramedullary plasmacytoma arising from the nasal septum.

A rare case of extramedullary plasmacytoma arising from the nasal septum with localized amyloid deposition is reported. A 75-year-old woman presented with a history of post-nasal discharge and nasal obstruction for several months. Endonasal endoscopic observation revealed the presence of a mass arising from her nasal septum with an extension to the nasopharynx. No cervical lymph nodes were palpable. The biopsy specimen was diagnosed as a plasmacytoma (IgG, lambda-light chain type). Both serum myeloma-protein and urine Bence-Jones protein were negative. Bone marrow biopsy, a chest radiograph, total body skeletal survey and 67Ga- and 99mTc-scintigrams showed no other systemic lesions. These findings confirmed the diagnosis of extramedullary plasmacytoma in the nasal septum. The patient received irradiation of 40 Gy without clinically detectable reduction of tumour size. The patient eventually underwent complete resection of the tumour by KTP/532 laser under endonasal endoscopic control. Pathologically, the tumour mass was composed mainly of amyloid deposition with a marked reduction of tumour cells. This indicated the radiosensitiveness of tumour cells, which was clinically masked by the increased amyloid deposition. The clinical presentation, pathological features and surgical procedures are described with a review of the literature.

Aged↗
PubMed2000

Characterization of JOK-1, a human gastric epithelial cell line.

Human gastric epithelial cells were isolated from samples of human gastric lining and immortalized with simian virus 40 (SV40) to generate the stable human gastric epithelial cell line "JOK-l." These cells express conventional epithelial markers (vimentin, cytokeratin-18, occludin, N- and E-cadherins, beta-catenin, ZO-1, ZO-2, mucin, epithelial specific antigen) as well as SV40 large T-antigen. These cells rapidly externalized E-cadherin in response to acidic medium, and exhibited epithelial-like barrier properties that are also regulated by media pH. In contrast, the kidney epithelial cell line "MDCK" also expresses several epithelial markers (vimentin, cytokeratin-18, occludin, N- and E-cadherin, beta-catenin, ZO-1, ZO-2, epithelial specific antigen), but does not express mucin, or large T-antigen. However, MDCK rapidly internalize their E-cadherin from the cell surface and increase the solute flux in an acidic medium. These data suggest that the JOK-1 cell line is a potentially useful cell line for developing models of gastric epithelial function, development, and disease.

Antigens, Polyomavirus Transforming↗