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Biomedical subjects

Y Okano

Publications and source records attributed to Y Okano.

At least 91 records · Page 5Linked to original sources
PubMed1998

Impaired regional fatty acid uptake and systolic dysfunction in hypertrophied right ventricle.

UNLABELLED: Little information is available regarding the determinants of systolic contractile function of the hypertrophied right ventricle (RV). The purpose of this study was to clarify the relationship between myocardial metabolism and contractile function in the hypertrophied RV due to pulmonary hypertension (PH). METHODS: Iodine-123-labeled 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) and 99mTc-sestamibi (MIBI) SPECT were performed to calculate the RV-to-left ventricle (LV) tracer uptake ratio (RV/LV) in 21 patients with PH (6 with primary PH and 15 with chronic thromboembolic PH). The patients also underwent electron-beam CT to assess RV ejection function (RVEF) and percentage systolic wall thickening (%SWT) and right heart catheterization to measure mean pulmonary arterial pressure (mPAP). RESULTS: There were significant positive correlations between mPAP and MIBI-RV/LV (r = 0.89, p < 0.001) and between mPAP and BMIPP-RV/LV (r = 0.86, p < 0.001). However, 8 patients showed lower BMIPP-RV/LV than MIBI-RV/LV, indicating the impairment of myocardial fatty acid uptake in the RV. These patients had lower RVEF and %SWT compared to those with normal myocardial fatty acid uptake (RVEF = 28% +/- 10% compared to 40% +/- 9% and %SWT = 33% +/- 27% compared to 74% +/- 30%, respectively; p < 0.05 for both comparisons). Although mPAP did not differ between the groups, the RVEF-mPAP and %SWT-mPAP regression lines drawn from the patients with impaired myocardial fatty acid uptake were located below the lines from the patients with normal myocardial fatty acid uptake, suggesting disproportionately decreased RV myocardial contractility for a given mPAP in patients with impaired myocardial fatty acid uptake. The patients with the impaired fatty acid uptake in the RV had a significantly higher death rate (log-rank test, p < 0.05). CONCLUSION: The results from this preliminary study suggest that myocardial fatty acid uptake is impaired in the failing hypertrophied RV due to PH.

Fatty Acids↗
PubMed1997

Sonodynamically-induced in vitro cell damage enhanced by adriamycin.

Sonodynamically-induced cell damage and active oxygen generation enhanced by adriamycin (ADM) were compared in the same in vitro insonation set-up. Significant enhancement of the rates of both ultrasonically-induced cell damage and nitroxide generation was demonstrated with 40-160 microM ADM. Both rates correlated very well resulting in a correlation coefficient of more than 0.99. The enhancement of both rates was suppressed by 10 mM histidine. These results are consistent with the hypothesis that ultrasonically-generated active oxygen plays a major role in the sonodynamically-induced cell damage enhanced by ADM.

Animals↗
PubMed1997

Generation of active oxygen species from advanced glycation end-products (AGE) under ultraviolet light A (UVA) irradiation.

To clarify a possible role of advanced glycation end-products (AGE) on photoaging of human skin, the interaction between AGE and ultraviolet A light (UVA) was examined from both a biological and chemical perspective. Human dermal fibroblasts that were exposed to UVA in the presence of AGE bound with bovine serum albumin (AGE-BSA) exhibited a significant decrease of cell viability as compared to control cells, which were exposed to UVA in the absence of AGE-BSA. Further, UVA-irradiated AGE-BSA reduced nitroblue tetrazolium to its formazan, but the reaction was inhibited by addition of superoxide dismutase in the system. UVA dose-dependent formation of H2O2 in AGE-BSA was also observed. An ESR spin-trapping study revealed the generation of unstable free radicals in AGE-BSA under UVA irradiation. After addition of Fe2+ in the system, an ESR spectrum due to the formation of hydroxyl radicals was observed. On the basis of these results, the authors propose that AGE is an important factor for promoting photoaging in the skin via generation of active oxygen species involving .O2-, H2O2, and .OH.

Cell Survival↗
PubMed1997

Shortening of Doppler-derived deceleration time of early diastolic transmitral flow in the presence of pulmonary hypertension through ventricular interaction.

Deceleration time (DT) of the early transmitral flow velocity has recently been highlighted as a simple, noninvasive indicator of pulmonary arterial wedge pressure. In patients with pulmonary hypertension without left-sided heart disease, however, increased right ventricular pressure may result in an abnormal ventricular septal motion, which may impact on left ventricular (LV) early diastolic filling. We sought to determine if DT may be influenced by the severity of pulmonary hypertension in patients without left-sided heart disease. Doppler-derived transmitral flow and hemodynamic parameters were simultaneously assessed in 26 patients with pulmonary hypertension (primary pulmonary hypertension = 11; chronic thromboembolism = 15). Transmitral Doppler variables including DT were correlated with hemodynamics and LV deformity index measured in early diastole with 2-dimensional echocardiography. DT significantly correlated with the total pulmonary resistance (r = -0.70, p <0.001). Multivariate analysis revealed that DT was independently determined by total pulmonary resistance, but not by pulmonary arterial wedge pressure, heart rate, or patient's age in our study population. DT showed a correlation with LV deformity index (r = -0.74, p <0.001). These results indicate that DT may shorten in association with the severity of pulmonary hypertension and that the shortened DT in pulmonary hypertension may be attributable to right ventricular pressure overload which causes geometric changes.

Adult↗
PubMed1997

Cell cycle-dependent expression and spindle pole localization of a novel human protein kinase, Aik, related to Aurora of Drosophila and yeast Ipl1.

Mutations in Aurora of Drosophila and related Saccharomyces cerevisiae Ipl1 kinase are known to cause abnormal chromosome segregation. We have isolated a cDNA encoding a novel human protein kinase of 402 amino acids with a predicted molecular mass of 45.9 kDa, which shares high amino acid identities with the Aurora/Ipl1 protein kinase family; hence the cDNA is designated as aik (aurora/IPL1-related kinase). Amino acid sequence of C-terminal kinase domain of Aik shares 86, 86, 72, 59, and 49% identity with those of Xenopus XLP46APK and XLP46BPK, mouse STK-1, Aurora of Drosophila, and yeast Ipl1, respectively, whereas N-terminal domain of Aik shares high homology only with those of XLP46APK and XLP46BPK. Northern and Western blotting analyses revealed that Aik is expressed highly in testis and various proliferating cells including HeLa cells. In HeLa cells, the endogenous levels of aik mRNA and protein contents are tightly regulated during cell cycle progression. Both of these levels are low in G1/S, accumulate during G2/M, and reduce rapidly after mitosis. Its protein kinase activity is also enhanced at mitosis as inferred by exogenous casein phosphorylation. Immunofluorescence studies using a specific antibody have shown that Aik is localized to the spindle pole during mitosis, especially from prophase through anaphase. These results strongly suggest that Aik is a novel member of a protein kinase family possibly involved in a centrosome function(s) such as chromosome segregation or spindle formation.

Amino Acid Sequence↗
PubMed1997

Mild mitral regurgitation reduces exercise capacity in patients with idiopathic dilated cardiomyopathy.

We evaluated 30 patients with dilated cardiomyopathy (New York Heart Association functional Class II or III with medical treatment) to assess the effect of mild mitral regurgitation (MR) on exercise capacity in patients with congestive heart failure. They were classified into two groups based on results of left ventriculography: MR present (n = 10) and MR absent (n = 20). The severity of the MR by left ventriculography was grade I (mild) in all patients with MR. Steady-state hemodynamic data and angiographic data did not differ significantly between the two groups. Heart rate and systolic blood pressure at rest and in response to symptom-limited exercise testing did not differ between the groups. However, the peak work load was significantly lower in the group with MR than that in the group without MR (101 +/- 32 vs. 142 +/- 29 W, respectively; p < 0.005). Peak oxygen uptake and peak oxygen pulse were also significantly lower in the group with MR than in that without MR (peak oxygen uptake: 18 +/- 23 +/- 5 ml/min/kg; p < 0.05, peak oxygen pulse: 6.6 +/- 2.6 vs. 9.5 +/- 2.7 ml/min/beat: p < 0.01, respectively). Thus, mild MR had a detrimental effect on the exercise capacity in patients with dilated cardiomyopathy.

Adult↗
PubMed1997

Characteristics of pulmonary artery pressure waveform for differential diagnosis of chronic pulmonary thromboembolism and primary pulmonary hypertension.

OBJECTIVES: The accurate diagnosis of chronic pulmonary thromboembolism (CPTE) is a prerequisite for life-saving surgical interventions. To help in the differential diagnosis of CPTE and primary pulmonary hypertension (PPH), we characterized the configuration of the pulmonary artery pressure waveform. BACKGROUND: Because CPTE predominantly involves the proximal arteries, whereas PPH involves the peripheral arteries, we hypothesized that patients with CPTE would have stiff or high resistance proximal arteries, whereas those affected by PPH would have high resistance peripheral arteries. These differences in the primary lesions would make arterial pulsatility relative to mean pressure larger in CPTE than in PPH. METHODS: In 34 patients with either CPTE (n = 22) or PPH (n = 12) whose pulmonary systolic pressure was > or = 50 mm Hg, we measured pulmonary artery pressure using a fluid-filled system that included a balloon-tipped flow-directed catheter. RESULTS: To quantify the magnitude of pulsatility relative to mean pressure, we normalized pulse pressure by mean pressure, hereinafter referred to as fractional pulse pressure (PPf). PPf was markedly higher in CPTE than in PPH (mean [+/-SD] 1.41 +/- 0.20 and 0.80 +/- 0.18, respectively, p < 0.001) and was diagnostic in separating the two groups without overlap. Similarly, the coefficient of variation of pulmonary artery pressure also separated the two groups without overlap (0.45 +/- 0.06 and 0.25 +/- 0.06, respectively, p < 0.001). Fractional time to half the area under the pressure curve separated the two groups reasonably well (0.35 +/- 0.02 and 0.43 +/- 0.03, respectively, p < 0.001). CONCLUSIONS: The analysis of pulsatility of pulmonary artery pressure is useful in the differential diagnosis of CPTE and PPH.

Adult↗
PubMed1997

Impaired left ventricular myocardial metabolism in patients with pulmonary hypertension detected by radionuclide imaging.

To assess whether left ventricular myocardial metabolism is affected by the presence of right ventricular pressure overload, we performed 123I-beta-methyl-iodophenyl pentadecanoic acid (123I-BMIPP) and 99Tc(m)-sestamibi (99Tc(m)-MIBI) single photon emission tomography in 24 patients with pulmonary hypertension and in 10 control subjects. The left ventricle was divided into six regions using a short-axis tomogram at the mid-ventricular level. The relative regional uptake (RRU, %) was determined for each region as the ratio of the regional uptake per pixel to the maximum uptake in the six regions. Right heart catheterization was performed to obtain mean pulmonary arterial pressure. 123I-BMIPP uptake in the septum and the adjacent myocardium of the left ventricle was lower in patients with pulmonary hypertension than in control subjects (septal RRU, 75 +/- 6 vs 85 +/- 4%; anteroseptal RRU, 76 +/- 6 vs 86 +/- 3%; posteroseptal RRU, 75 +/- 4 vs 84 +/- 4%; P < 0.001). The reduction in 99Tc(m)-MIBI uptake was confined to the septum in patients with pulmonary hypertension (79 +/- 5 vs 85 +/- 5%; P < 0.05). Interestingly, the septal RRU of 123I-BMIPP and the sum of the septal, anteroseptal and posteroseptal RRUs of 123I-BMIPP were negatively correlated with mean pulmonary arterial pressure (r = -0.70 and -0.55, respectively; P < 0.01). In conclusion, myocardial metabolism in the interventricular septum and the adjacent regions of the left ventricle may be impaired in proportion to the degree of pulmonary hypertension.

Adult↗
PubMed1997

Effect of exercise on plasma adrenomedullin and natriuretic peptide levels in myocardial infarction.

1. We investigated the effect of exercise on plasma adrenomedullin, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) concentrations and studied the relationship between these peptides and haemodynamic parameters in nine patients with old myocardial infarction (MI) and in eight normal subjects. 2. The exercise protocol consisted of two fixed work loads (40 and 80 W) for 4 min each and venous blood samples were taken at rest, during each exercise stage and after exercise while monitoring the mean arterial pressure (MAP) and heart rate (HR). In MI, pulmonary arterial pressure (PAP), pulmonary capillary wedge pressure (PCWP), left ventricular end-diastolic pressure (LVEDP) and cardiac output (CO) were measured throughout exercise. 3. Adrenomedullin levels did not significantly increase with exercise. Adrenomedullin levels correlated with PAP and PCWP at rest (P < 0.05). Atrial natriuretic peptide levels correlated with PAP, PCWP and LVEDP throughout exercise (P < 0.05) but, on multiple regression analysis, PCWP correlated only with ANP (P < 0.01). Brain natriuretic peptide levels correlated with LVEDP throughout exercise (P < 0.01) and its increment correlated closely with basal BNP levels at rest (P < 0.01). 4. These results suggest that adrenomedullin does not respond to the acute haemodynamic changes of exercise, whereas ANP responds to it and PCWP is the major stimulus factor. Brain natriuretic peptide responds to exercise in proportion to the basal synthesis of BNP in patients with left ventricular dysfunction and LVEDP may play a role in increasing BNP during exercise.

Adrenomedullin↗
PubMed1997

Mutations in the gyrA and parC genes in fluoroquinolone-resistant clinical isolates of Pseudomonas aeruginosa.

We determined partial sequences of the gyrA and parC genes of the fluoroquinolone-susceptible strain ATCC 27853 and 22 clinical isolates of Pseudomonas aeruginosa. While a single amino acid change in GyrA with or without a change in ParC was found in 14 isolates with decreased susceptibility to fluoroquinolones, 3 higher-level fluoroquinolone-resistant isolates had a double amino acid change in GyrA and a single amino acid change in ParC.

Amino Acid Sequence↗
PubMed1997

In vivo selection of Klebsiella pneumoniae strains with enhanced quinolone resistance during fluoroquinolone treatment of urinary tract infections.

We report two cases of failure of fluoroquinolone treatment of urinary tract infections with Klebsiella pneumoniae strains harboring quinolone resistance-associated alterations in GyrA and ParC and in vivo selection of posttreatment isolates with enhanced fluoroquinolone resistance. Active efflux leading to decreased accumulation of a drug enhanced fluoroquinolone resistance in one posttreatment isolate, and an additional mutation in parC resulting in an additional amino acid change in ParC was associated with increased resistance in the other.

Aged↗
PubMed1997

cDNA cloning, characterization, and chromosome mapping of UBE2E2 encoding a human ubiquitin-conjugating E2 enzyme.

A cDNA encoding a human ubiquitin-conjugating enzyme (E2) with N-terminal extension (UBE2E2/UbcH8) was isolated. Amino acid sequence within the UBC domain of UBE2E2 shares over 90% identity with human UbcH6, mouse UbcM2, and Drosophila UbcD2, whereas the N-terminal region shows little amino acid sequence similarity with known proteins. The UBE2E2 gene is transcribed in various tissues as a 1.9-kb transcript. The UBE2E2 protein formed a thioester bond with ubiquitin in an E1-dependent manner, indicating that the gene product is a functional E2 enzyme. The UBE2E2 gene was assigned to human chromosome 3p24.2 by fluorescence in situ hybridization.

Amino Acid Sequence↗
PubMed1997

Assignment of STK6 to human chromosome 20q13.2-->q13.3 and a pseudogene STK6P to 1q41-->q42.

Fluorescence in situ hybridization analysis of human STK6 encoding a mitotic centrosomal protein kinase, Aik, revealed two signals in chromosome bands 20q13.2-->q13.3 and 1q41-->q42. Somatic cell hybrid panel analyses showed the existence of an identical sequence to STK6 cDNA on chromosome 20, and a processed pseudogene on chromosome 1. These results suggest that STK6 is localized at 20q 13.2-->q13.3 and a pseudogene STK6P at 1q41-->q42.

Aurora Kinase A↗
PubMed1997

Crescentic glomerulonephritis and elevated antimyeloperoxidase antibody in a patient with Churg-Strauss syndrome.

A 45-year-old man with a long history of bronchial asthma was admitted to the National Cardiovascular Center with complaints of severe pain, swelling, and ecchymoses of the lower extremities. A diagnosis of Churg-Strauss syndrome was made because of marked eosinophilia, vasculitis, and a history of asthma. Urinalysis revealed severe proteinuria and microscopic hematuria. A renal biopsy demonstrated extensively crescentic glomerulonephritis. The antineutrophil cytoplasmic antibody against myeloperoxidase (MPO-ANCA) level, determined by enzyme-linked immunosorbent assay (ELISA), was 494 ELISA units. Under treatment with prednisolone, the symptoms and eosinophilia improved within 3 days. The MPO-ANCA level decreased to its lowest value, and renal function was ameliorated within 3 months. The patient has been followed regularly on an ambulatory basis with a regimen of prednisolone.

Anti-Inflammatory Agents↗
PubMed1997

Immunohistochemical studies of proliferating cell nuclear antigen and cathepsin D in transitional cell carcinoma of the urinary bladder.

Immunohistochemical staining for proliferating cell nuclear antigen (PCNA) and cathepsin D was performed on 60 transitional cell carcinoma (TCC) specimens from 60 patients with bladder cancer. The percentage of PCNA-positive cells (PCNA-labelling index) was determined by counting 500 or 1,000 cells, and cathepsin D expression was graded according to the extent of immunoreactivity to anti-cathepsin D antibody. The PCNA-labelling index was significantly higher in high-grade and high-stage tumors compared to that in low-grade and low-stage tumors. Cathepsin D was highly positive in grade-1 tumors. In contrast, 82% of grade-3 tumors and 76% of advanced tumors showed negative or low reactivity to anti-cathepsin D. Groups of high PCNA-labelling index and negative cathepsin D had significantly poorer prognoses compared to those of the low PCNA group and cathepsin D highly positive group, respectively, in univariate analyses. However, neither of these two factors were independent prognostic factors in multivariate analyses. These results suggest that the PCNA-labelling index and cathepsin D expression may indicate the malignant potential of TCC and may be able to provide additional information for predicting survival when stratifying for grade of bladder cancer.

Adult↗
PubMed1997

Successful thromboendarterectomy for chronic pulmonary embolism in a patient with systemic lupus erythematosus and antiphospholipid syndrome.

Chronic pulmonary thromboembolism is known to be associated with poor prognosis with conservative medical treatment. Pulmonary thromboendarterectomy for chronic pulmonary thromboembolic disease is a potentially lifesaving procedure that prevents right-sided cardiac failure as a result of secondary pulmonary hypertension caused by pulmonary thromboembolism. We report a rare case of systemic lupus erythematosus with antiphospholipid syndrome in a patient who presented with pulmonary hypertension secondary to chronic proximal multiple pulmonary thromboembolism. To our knowledge, this is the first case report of chronic pulmonary thromboembolism complicated by systemic lupus erythematosus with antiphospholipid syndrome. Thromboendarterectomy was performed with satisfactory results.

Adult↗