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Biomedical subjects

Hiroaki Kawano

Publications and source records attributed to Hiroaki Kawano.

At least 19 recordsLinked to original sources
PubMed2007

Fibrotic response to angiotensin II is blunted in the kidney, but not in the heart, in insulin-sensitive long-lived transgenic dwarf rats.

Insulin resistance is a characteristic feature of cardiovascular and renal diseases, and angiotensin II (Ang II) has been suggested to induce insulin resistance. The aims of this study were to elucidate the effect of chronic Ang II infusion on vascular reactivity and organ damage in insulin-sensitive rats. We confirmed the following three points. First, there was no significant difference in pressor response to chronic Ang II infusion (600 ng/kg/min) between insulin-sensitive transgenic rats (Tg) and control rats (C). Second, there was no significant difference in cardiac hypertrophy and fibrosis by chronic Ang II infusion between the two groups. However, third, fibrotic response to chronic Ang II infusion evaluated by histopathological scoring in the kidney was significantly decreased in insulin-sensitive transgenic rats (renal fibrosis and nephropathy score: C+Ang II vs Tg+Ang II; 2.5 vs 1.3; p<0.05). Furthermore, the expression of TGF-beta, a fibrosis indicator, was also significantly suppressed in the kidneys of the transgenic rats (TGF-beta1/GAPDH ratio: C+Ang II vs Tg+Ang II; 1.15 vs 0.81; p<0.05). This result indicates that the growth hormone/insulin-like growth factor-1 axis is critically involved in the development of renal injury and fibrosis, rather than hypertension, cardiac hypertrophy, and cardiac fibrosis induced by chronic Ang II administration.

Angiotensin II↗
PubMed2006

The relationship between endothelial function in the brachial artery and intima plus media thickening of the coronary arteries in patients with chest pain syndrome.

Endothelial dysfunction precedes the development of clinical atherosclerosis. A decrease in endothelium-derived nitric oxide activity shows impaired vasodilator function and causes arterial intimal hyperplasia or thickening. Others and we have reported the close relation of endothelial function in brachial artery and coronary artery. To compare the flow-mediated endothelium-dependent vasodilation (FMD) in brachial artery and the intima+media area in coronary artery, we measured brachial artery vasodilator response following transient occlusion with high resolution ultrasound transducer and intima+media area in coronary arteries with intravascular ultrasound in 25 patients with normal coronary angiograms (age 61.6+/-8.7 years old, men 14 and women 11). FMD was measured at least 7 days after the cessation of all vasodilators. The mean FMD of 25 patients was 3.83+/-2.38%, the mean intima+media area in coronary arteries of 25 patients was 39.9+/-15.5% of total vessel wall. FMD has a close negative relation with the largest percent intima+media area (r=-0.77, p<0.01). Especially, the patients whose FMD was less than 3.83% had larger percent intima+media area than those whose FMD was 3.83% or more (48.7+/-10.7% versus 30.3+/-14.2%, p<0.01). There is an intima+media thickening even in the patients who had normal coronary angiograms, and that the percent intima+media area correlated with FMD. The measurement of FMD is useful for screening the coronary artery intima+media thickening noninvasively. The pathogenesis of acute coronary syndrome has been reported to be the plaque rupture even in the patients with normal coronary angiograms. Thus, we must pay much attention in the patients with impaired FMD even in the normal coronary angiograms.

Aged↗
PubMed2006

Prognostic value of flow-mediated dilation of the brachial artery in patients with cardiovascular disease.

OBJECTIVE: Endothelial dysfunction is thought to represent the initial stage in the development of atherosclerosis. Recently, noninvasive examination of endothelial function has become possible using flow-mediated endothelium-dependent dilation of the brachial artery (FMD) during reactive hyperemia. We examined whether FMD has prognostic value for the prediction of subsequent cardiovascular events. METHODS: Patients were followed prospectively every month until the occurrence of the cardiovascular events. PATIENTS: The study subjects comprised 221 consecutive patients (men 108, mean age 61.4+/-10.6, ischemic heart disease 152, cardiomyopathy 28, arrhythmia 12, valvular disease 5, congenital heart disease 3, and cardioneurosis 21). The mean FMD was 4.77+/-2.85% and this value was used to divide the patients into the 2 groups (Group 1: FMD > or =4.7%; Group 2: FMD <4.7%). RESULTS: There were 110 patients in Group 1 (men 36, mean age 60.5+/-10.9), and 111 patients in Group 2 (men 72, mean age 62.2+/-10.3). Patients were followed until the occurrence of at least 1 of the major clinical cardiovascular events. Seven cardiovascular events occurred in Group 1 (6.4%, 1.14 events per 100 patient-years), while 16 occurred in Group 2 (2.88 events per 100 patient-years). Kaplan-Meier analysis demonstrated a significantly higher probability of developing cardiovascular events in Group 2 than in Group 1. CONCLUSION: The present results demonstrated that the magnitude of FMD in the brachial artery was a good predictor of subsequent cardiovascular events.

Aged↗
PubMed2006

The major outer membrane protein rOmpB of spotted fever group rickettsiae functions in the rickettsial adherence to and invasion of Vero cells.

The role of one of the major outer membrane proteins, rOmpB, of spotted fever group rickettsiae was examined. Antibodies generated against native rOmpB inhibited plaque formation by Rickettsia japonica in Vero cells when applied at the time of inoculation of the rickettsiae. However, antibodies to heat-denatured rOmpB did not. Moreover, the soluble recombinant rOmpB also inhibited plaque formation to some extent. Thus it seems that rOmpB functions at least in the adherence of rickettsiae to host cells. To obtain direct evidence of its function in the adherence to and invasion of Vero cells, we generated Escherichia coli transformed by the vector pET-22b(+) inserted with the ompB open reading frame of R. japonica. The recombinant bacteria expressed a 165-kDa protein consistent with the precursor of rOmpB. The protein reacted with monoclonal antibodies to heat-labile epitopes of rOmpB. Immunofluorescence of the recombinant bacteria demonstrated surface expression of the protein. It was shown by light microscopy and transmission and scanning electron microscopy that the bacteria adhered to and invaded Vero cells. Thus, although the recombinant precursor rOmpB was not processed on the outer membrane of E. coli, it functions during these steps. The manner of entry was similar to that of rickettsiae although at a slower rate.

Animals↗
PubMed2006

Pravastatin decreases blood pressure in hypertensive and hypercholesterolemic patients receiving antihypertensive treatment.

BACKGROUND: Previous studies have suggested that the lipid-lowering agents, statins, may help reduce blood pressure (BP). The goal of the present study was to characterize the effect of pravastatin on BP in hypercholesterolemic and hypertensive patients already receiving antihypertensive drugs. METHODS AND RESULTS: Eighty-two patients with hypercholesterolemia were retrospectively studied before and after 3 months of treatment with pravastatin. Forty-four patients had hypertension (HT group) and were receiving antihypertensive treatment, while the remaining 38 patients were normotensive (NT group). Patients in the HT group were further subdivided into those with uncontrolled or controlled BP. Pravastatin treatment significantly reduced systolic BP (SBP) in the HT group (134+/-16 to 130+/-13 mmHg, p<0.005) but not in the NT group (124+/-10 to 123+/-9 mmHg, p=0.52), despite the fact that treatment significantly reduced low-density lipoprotein cholesterol in both groups (HT group 178+/-27 to 132+/-17 mg/dl, p<0.0001; NT group 169+/-27 to 125+/-21 mg/dl, p<0.0001). Further, pravastatin significantly decreased SBP in the uncontrolled BP group (148+/-7 to 138+/-12 mmHg, p<0.005) but not in the controlled BP group (122+/-10 to 123+/-9 mmHg, p=0.72). CONCLUSION: Concomitant use of statins and antihypertensive drugs could result in improved BP control in hypertensive patients with hypercholesterolemia.

Adult↗
PubMed2006

Sex differences of risk factors for acute myocardial infarction in Japanese patients.

BACKGROUND: Acute myocardial infarction (AMI) is prevalent and has serious consequences including re-infarction and death. Although the risk factors for AMI have been extensively studied in Western countries, they are less well documented in Japan. To determine the risk factors for AMI, we performed a case-control study in unselected patients with AMI. METHODS AND RESULTS: Risk factors were assessed in 1,925 consecutive patients with a first AMI (age, 28-103 years old; men, 1,353; women, 572), who were admitted to one of the major institutes in Japan, and in 2,279 age-and sex-matched population-based controls. Hypertension (odds ratio (OR), 4.80; 95% confidence interval (CI), 3.80 to 5.95; p < 0.01), diabetes (OR, 3.44; 95% CI, 2.50 to 4.75; p < 0.01), current smoking (OR, 3.39; 95% CI, 2.78 to 4.18; p < 0.01), family history (OR, 1.84; 95% CI, 1.30 to 2.62; p < 0.01), and hypercholesterolemia (OR, 1.28; 95% CI, 1.00 to 1.62; p < 0.05) were all independent risk factors for AMI. However, obesity (OR, 1.13; 95% CI, 0.92 to 1.50; NS) was not. Hypertension (OR, 4.80; 95% CI, 3.80 to 6.02; p < 0.01), current smoking (OR, 4.00; 95% CI, 3.02 to 5.00; p < 0.01), and diabetes (OR, 2.9; 95% CI, 2.00 to 4.04; p < 0.01) were all independent risk factors for AMI in men. In contrast, only current smoking (OR, 8.22; 95% CI, 3.98 to 18.88; p < 0.01), diabetes (OR, 6.12; 95% CI, 3.78 to 12.02; p < 0.01), and hypertension (OR, 5.04; 95% CI, 2.92 to 7.52; p < 0.01) were independent risk factors for AMI in women. Hypercholesterolemia was an independent risk factor for AMI in men (OR, 1.52; 95% CI, 1.00 to 1.98; p < 0.05), but not in women. CONCLUSIONS: Hypertension, diabetes, current smoking, family history and hypercholesterolemia are associated with AMI in Japanese patients, and the importance of the risk factors for AMI differs between men and women. Hypertension, current smoking, diabetes and family history are the most important risk factors in men, whereas current smoking, diabetes, hypertension and family history are the most important risk factors in women. Hypercholesterolemia is an independent risk factor for AMI in men, but not in women. To the best of our knowledge, this is the first clinical study to define the relative importance of risk factors for AMI in Japanese patients.

Adult↗
PubMed2006

Long-term efficacy of edaravone in patients with acute myocardial infarction.

BACKGROUND: The effect of edaravone, a free radical scavenger, on long-term prognosis and its efficacy with regards to scavenging injurious free radicals in patients with acute myocardial infarction (AMI) was examined. METHODS AND RESULTS: One hundred and one initial AMI patients were randomly assigned to receive 30 mg edaravone (n = 50) or a placebo (n = 51) intravenously just before reperfusion. The infarct size, using serum biomarkers and Q-wave formations, and the incidence of reperfusion arrhythmia between the groups were compared. Cardiovascular event-free curves were estimated by using the Kaplan - Meier method. In addition, the serum thioredoxin levels, an oxidative stress marker, to assess the antioxidant effect of edaravone was determined. In all cases, successful reperfusion was obtained within 6 h after the onset of symptoms. Infarct size and reperfusion arrhythmia were significantly attenuated in the edaravone group compared with the placebo group (p = 0.035 and p = 0.031). The cumulative event-free rate was significantly higher in the edaravone group than in the placebo group (p = 0.045). Serum thioredoxin levels were significantly lower in the edaravone group than in the placebo group throughout the acute phase. CONCLUSIONS: The present study suggests that the edaravone administration just prior to reperfusion might reduce oxidative stress and improve the long-term clinical outcomes of AMI patients.

Acute Disease↗
PubMed2005

Usefulness of preprocedural platelet aggregation to predict restenosis after percutaneous coronary intervention.

We investigated whether the assessment of small platelet aggregates before percutaneous coronary intervention (PCI) could predict restenosis after PCI. This was a prospective cohort study that enrolled 189 consecutive patients who had coronary artery disease. In multiple logistic regression analysis, higher levels of preprocedural small platelet aggregates were independently associated with restenosis after PCI. Measurement of small platelet aggregates may serve as a useful clinical variable for stratifying patients who present for PCI.

Aged↗
PubMed2005

Pressure-regulated biosynthesis of cytochrome bd in piezo- and psychrophilic deep-sea bacterium Shewanella violacea DSS12.

The genes of cytochrome bd-encoding cydAB were identified from a deep-sea bacterium Shewanella violacea DSS12. These showed significant homologies with known cydAB gene sequences from various organisms. Additionally, highly conserved regions that are important for the enzymatic function were also conserved in cydA of S. violacea. Based on the results, transcriptional analysis of cydAB operon and cydDC operon (required for assembly of cytochrome bd) of S. violacea in microaerobic condition was performed under the growth condition of various pressures. The gene of cydA was expressed even under the condition of atmospheric pressure and its expression was enhanced with pressurization. On the other hand, the expression of cydC was strongly depressed under the condition of atmospheric pressure compared with the case under high pressure. It appeared spectrophotometrically that loss of cytochrome bd in S. violacea under atmospheric pressure shown in previous study is caused mainly by the loss of cydDC. Further, under the growth condition of atmospheric pressure, either less amount or no d-type cytochrome was expressed compared with the case of high-pressure condition even if the organism was grown under alkaline condition or in the presence of uncoupler, which are the inducible condition of d-type cytochrome in Escherichia coli. These results suggested that the significant amount of d-type cytochrome expression is specific event under the growth condition of high pressure.

Amino Acid Sequence↗
PubMed2005

Plasma thioredoxin levels in patients with unstable angina.

Plasma levels of human thioredoxin are indicative of the responses against oxidative stress. We measured the plasma thioredoxin levels in patients with unstable angina in order to examine the relationships between subsequent clinical course and plasma thioredoxin levels before and after treatment for unstable angina. Blood was sampled both on admission and after treatment in 44 patients with unstable angina. In addition, blood samples were obtained from 41 patients with stable exertional angina and 41 patients with chest pain syndrome after admission. The plasma levels of thioredoxin were the highest in the unstable angina group among three groups (p<0.001). Treatment of unstable angina decreased the plasma thioredoxin levels (p<0.01). We divided the patients with unstable angina into two groups according to the plasma thioredoxin levels on admission and after treatment. There was a significant difference in Braunwald's classification between the high thioredoxin and the low thioredoxin group on admission, as analyzed by the chi2 test with Yates's correction (p<0.05). Moreover, there was a significant difference in incidence of recurrent anginal attacks at rest between the high thioredoxin and the low thioredoxin group after treatment, as analyzed by the chi2 test with Yates's correction (p<0.001). The present study demonstrated that plasma thioredoxin levels are significantly increased in patients with unstable angina compared to those with stable exertional angina and chest pain syndrome. Thioredoxin levels were associated with recurrent myocardial ischemia in patients with unstable angina.

Aged↗
PubMed2005

Urinary 8-hydroxy-2'-deoxyguanosine levels increase after reperfusion in acute myocardial infarction and may predict subsequent cardiac events.

We assessed serial changes in oxidative stress in patients with acute myocardial infarction by measuring urinary 8-hydroxy-2'-deoxyguanosine excretion. The urinary 8-hydroxy-2'-deoxyguanosine creatinine levels peaked at 4 hours after reperfusion therapy and the levels were higher in the cardiac event group than in the noncardiac event group before and after reperfusion.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2005

Levels of the adipocyte-derived plasma protein, adiponectin, have a close relationship with atheroma.

INTRODUCTION: Inflammation is a key process in atherosclerotic formation. Structural changes in the carotid arterial wall including detection of focal plaques are measured as the intima-media thickness (IMT) providing an index of atheroma. Coronary arterial plaques may be considered as vascular structural changes. Distensibility of the arteries can be assessed by functional changes in pulse wave velocity (PWV) providing an index of sclerosis. Adiponectin has potential antiatherosclerotic properties. We hypothesized that adiponectin was associated with atherosclerotic vascular changes involved in inflammation. MATERIALS AND METHODS: We enrolled 142 patients with coronary artery disease (CAD) and 108 control patients, matched for age, sex, and body mass index (BMI) with CAD patients. We investigated the relationship between adiponectin, C-reactive protein (CRP), and atherosclerotic vascular changes. RESULTS: CRP (p=0.0009), high-density lipoprotein cholesterol (HDL-C; p=0.02), and IMTmax (p=0.02) were determinants of adiponectin independent of glucose intolerance (p=0.0001), BMI (p=0.002), and CAD (p=0.03), all of which have been significantly associated with adiponectin (r=0.38). Adiponectin was not correlated with PWV. CRP, glucose intolerance, and HDL-C that correlated with adiponectin were inversely correlated with IMTmax and CAD. CRP was negatively correlated with HDL-C (r=-0.24, p=0.0002) and positively correlated with glucose intolerance (r=0.15, p=0.01). CONCLUSIONS: Adiponectin has a close relationship with CRP, IMTmax, CAD, HDL-C, and other established risk factors. CRP, glucose intolerance, and HDL-C are common mediators between adiponectin and atheromatous vascular changes, which are contrary to each other. The exacerbation of atherogenesis may be involved in a decrease of adiponectin through abnormal glyco- and lipid-metabolism by promoting inflammation.

Adiponectin↗
PubMed2005

Cloning and characterization of the rpoE gene encoding an RNA polymerase sigmaE factor from the deep-sea piezophilic Shewanella violacea strain DSS12.

The rpoE gene encoding an RNA polymerase sigmaE subunit was isolated from a gamma-phage library of the deep-sea piezophilic and psychrophilic bacterium Shewanella violacea strain DSS12. Structual analysis showed that the gene organization of the fragment containing S. violacearpoE was the l-aspartate oxidase-coding gene, rpoE, rseA, rseB and rseC in that order, the same as in the case of Photobacterium profundum SS9 and Escherichia coli K-12. The cloned gene, 576 bp in length, was found to encode a protein consisting of 192 amino acid residues with a molecular mass of 21,806 Da. Amino acid alignment of the RpoE protein showed that the functional domains responsible for DNA recognition, DNA melting, core binding, and RseA interaction were highly conserved. We purified hexahistidine-fused RpoE protein by constructing an overexpression plasmid. Core-binding analysis revealed that the cloned RpoE protein has the ability to bind with core RNA polymerase as a sigma factor.

Amino Acid Sequence↗
PubMed2005

Valsartan decreases type I collagen synthesis in patients with hypertrophic cardiomyopathy.

BACKGROUND: Fibrosis, as well as myocyte hypertrophy, is the major determinant of prognosis in hypertrophic cardiomyopathy (HCM). Valsartan, an angiotensin II type 1 receptor blocker, may improve myocardial fibrosis in patients with HCM. METHODS AND RESULTS: Twenty-three patients with HCM were randomly divided into 2 groups: 11 patients had valsartan added to conventional treatment (V group) and 12 patients received the conventional therapy (C group). Plasma concentrations of brain natriuretic peptide (BNP), troponin T (TnT), aldosterone (ALDO), procollagen type I (PIP) and procollagen type III aminoterminal peptide (PIIINP) were measured before and 12 months after this study. Left ventricular wall thickness (LVWT) and ejection fraction (LVEF) were measured by echocardiography. PIP was decreased in the V group (123.2+/-63.1 ng/ml to 102.8+/-37.6, p<0.05), but unchanged in C group (110+/-40.5 ng/ml to 119.9+/-47.4, p=0.22). ALDO concentration was unchanged in the V group (88.5+/-26.2 pg/ml to 91.2+/-26.8, p=0.27), and increased in C group (92.6+/-36.6 ng/ml to 116.0+/-33.3, p<0.05). BNP, PIIINP, and TnT were unchanged by the treatment. There was no significant difference between the 2 groups in either LVWT or LVEF. CONCLUSION: Valsartan suppresses the synthesis of type I collagen in patients with HCM and this was associated with suppression of the increase in ALDO.

Adult↗
PubMed2005

Protein-DNA interactions under high-pressure conditions, studied by capillary narrow-tube electrophoresis.

The method of electrophoretic mobility shift assay under high-pressure conditions was improved using a high-pressure electrophoresis apparatus with capillary narrow-tube gel. It was found that the protein-DNA complex in the gel was stained as a high-resolution spot with ethidium bromide. Using this method, it was found that the behavior under high-pressure conditions of the protein-DNA complex composed of NtrC protein and its target promoter DNA is important for the pressure-regulated transcription process, and it was confirmed that the complex was dissociated above a pressure of 70 MPa.

Atmospheric Pressure↗
PubMed2005

Identification of rpoBC genes encoding for beta and beta' subunits of RNA polymerase in a deep-sea piezophilic bacterium, Shewanella violacea strain DSS12.

RNA polymerase from cells of the deep-sea bacterium Shewanella violacea DSS12 was purified using three chromatographic steps. An in vitro transcription assay indicated that the purified enzyme was sigma(70) containing RNA polymerase. The enzyme activity was inhibited in the presence of rifampicin when the sensitive domain was targeted. The rpoBC genes encoding for the beta and beta' subunits of RNA polymerase were cloned and their nucleotide sequences determined. Expression plasmids, designated pQSVB and pQSVC, to overproduce these proteins were constructed, and the proteins were purified using a Ni(2+) affinity column. In vitro reconstitution using all proteins for the holoenzyme (alpha, beta, beta', sigma(70)) was carried out and the activity of the recombinant RNA polymerase was detected.

Amino Acid Sequence↗