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Biomedical subjects

Masao Moroi

Publications and source records attributed to Masao Moroi.

At least 19 recordsLinked to original sources

Genome-Wide Association Study of Contrast Media Hypersensitivity in Japanese Patients.

Iodinated contrast media (ICM), commonly used in radiological tests such as coronary angiography, can cause hypersensitivity reactions (HSRs). The mechanism of ICM HSRs is thought to be complex; while IgE-mediated allergic reactions appear to be involved, the details remain unclear. This study aims to elucidate the pathogenesis of ICM HSRs through genetic analysis. To date, a few case-control studies have been conducted exclusively on East Asians, but the results have been inconclusive and have not been replicated.We conducted a multistage GWAS for ICM HSRs in Japanese individuals. The study population comprised 153 cases with ICM HSRs (ranging from mild to severe form), 632 controls with no history of ICM-induced allergies, and < 38,721 individuals from the general population. We identified genome-wide significant association signals in the HLA region and also found that these signals originated from the three HLA alleles-B*52:01, C*12:02, DRB1*15:02-previously reported in a Korean candidate gene study. Using instrumental variable analysis with a polygenic score for pediatric asthma (PGSasthma) as a proxy, we demonstrated that ICM HSRs are associated with the allergic predisposition thought to be shared by asthma and ICM HSRs. There was a significant difference in the distribution of PGSasthma between ICM HSR patients and non-disease controls (per-SD odds ratio: 1.26, P = 0.021).Our genome-wide approach shows that HLA alleles are among the genetic factors underlying ICM HSRs. Furthermore, it provides evidence for the potential usefulness of predicting the risk of developing ICM HSRs based on allergic predisposition.

Allergic predisposition↗

MDCT detection of double right coronary artery arising from a single ostium in the right sinus of Valsalva: report of 2 cases.

Double right coronary artery arising from a single ostium in the right sinus of Valsalva is an extremely rare coronary artery variation. Differentiating this variation from high take off of a large right ventricular branch is often difficult in conventional coronary angiography. In two cases, multidetector-row computed tomography (MDCT) identified double right coronary artery. MDCT allows three-dimensional comprehension of the coronary artery anatomy and it is thought to be useful to distinguish this variation from a large right ventricular branch.

Abnormalities, Multiple↗

Effect of pravastatin and atorvastatin on glucose metabolism in nondiabetic patients with hypercholesterolemia.

OBJECTIVE: The aim of this study was to assess the effects of hydrophilic pravastatin and lipophilic atorvastatin on glucose metabolism and lipid metabolism in non-diabetic patients with hypercholesterolemia. METHODS: Fasting plasma glucose (FPG), hemoglobin A(1c) (HbA(1c)), total cholesterol (TC), low-density lipoprotein cholesterol (LDLC), high-density lipoprotein cholesterol (HDLC), and triglyceride (TG) levels were determined before and after statin treatment. PATIENTS: A total of 44 nondiabetic patients (FPG < or =125 mg/mL; HbA(1c) <5.8%) undergoing treatment with either pravastatin (n=21) or atorvastatin (n=23) for hypercholesterolemia were investigated. RESULTS: FPG level in the pravastatin but not atorvastatin group was significantly lowered after vs before treatment. Accordingly, the HbA(1c) level in the atorvastatin but not in the pravastatin group was significantly increased. As expected, both TC and LDL-C levels were significantly lowered in both groups. In particular, the TC level in the atorvastatin group was more remarkably and significantly improved than in the pravastatin group. On the other hand, the HDL-C level in the pravastatin group but not in the atorvastatin group was significantly increased after the administration period. The TG level was unaffected in both groups. CONCLUSION: Pravastatin was suggested to act favorably, while atorvastatin adversely, regarding it's effects on glucose metabolism in nondiabetic hypercholesterolemic patients, although atorvastatin exerted more potent cholesterol-lowering effects compared with pravastatin.

Aged↗

Pioglitazone ameliorates insulin resistance and diabetes by both adiponectin-dependent and -independent pathways.

Thiazolidinediones have been shown to up-regulate adiponectin expression in white adipose tissue and plasma adiponectin levels, and these up-regulations have been proposed to be a major mechanism of the thiazolidinedione-induced amelioration of insulin resistance linked to obesity. To test this hypothesis, we generated adiponectin knock-out (adipo-/-) ob/ob mice with a C57B/6 background. After 14 days of 10 mg/kg pioglitazone, the insulin resistance and diabetes of ob/ob mice were significantly improved in association with significant up-regulation of serum adiponectin levels. Amelioration of insulin resistance in ob/ob mice was attributed to decreased glucose production and increased AMP-activated protein kinase in the liver but not to increased glucose uptake in skeletal muscle. In contrast, insulin resistance and diabetes were not improved in adipo-/-ob/ob mice. After 14 days of 30 mg/kg pioglitazone, insulin resistance and diabetes of ob/ob mice were again significantly ameliorated, which was attributed not only to decreased glucose production in the liver but also to increased glucose uptake in skeletal muscle. Interestingly, adipo-/-ob/ob mice also displayed significant amelioration of insulin resistance and diabetes, which was attributed to increased glucose uptake in skeletal muscle but not to decreased glucose production in the liver. The serum-free fatty acid and triglyceride levels as well as adipocyte sizes in ob/ob and adipo-/-ob/ob mice were unchanged after 10 mg/kg pioglitazone but were significantly reduced to a similar degree after 30 mg/kg pioglitazone. Moreover, the expressions of TNFalpha and resistin in adipose tissues of ob/ob and adipo-/-ob/ob mice were unchanged after 10 mg/kg pioglitazone but were decreased after 30 mg/kg pioglitazone. Thus, pioglitazone-induced amelioration of insulin resistance and diabetes may occur adiponectin dependently in the liver and adiponectin independently in skeletal muscle.

Adiponectin↗

Ultrasound attenuation behind coronary atheroma without calcification: mechanism revealed by autopsy.

When performing intravascular ultrasound studies, the backward echo image can show marked attenuation, although there are no calcified deposits and it may be impossible to detect the intraplaque architecture. The pathology underlying this phenomenon was investigated in autopsy specimens. We hypothesize that the mechanism responsible for the attenuation involves micro-calcification and lipid in unstable plaques causing ultrasonic wave reflection and dispersion.

Atherosclerosis↗

Independent risk factors for progression of coronary atherosclerosis in hemodialysis patients.

Not uncommonly, hemodialysis patients with normal results in myocardial perfusion tests can still have a cardiac event within 2 years of evaluation. We examined possible risk factors for progression of coronary atherosclerosis in hemodialysis patients. We prospectively evaluated ability of myocardial perfusion imaging carried out under pharmacologic stress to predict 2-year outcomes in 77 hemodialysis patients, specifically thallium-201 single-photon emission computed tomography (SPECT) using high-dose adenosine triphosphate as the stressor. The primary end-point was a cardiac event (cardiac death, non-fatal acute coronary syndrome, or hospitalization for acute ischemic heart failure). Factors independently influencing duration until a cardiac event in hemodialysis patients were identified using stepwise multiple regression analysis. Myocardial perfusion defects were shown in 36 patients. Patients with a perfusion defect were more likely to have cardiac events than those with normal perfusion (78% vs. 15%, P < 0.001). Time until occurrence of a cardiac event in hemodialysis patients showed a significant, independent association with known coronary artery disease [regression coefficient (RC) = -3.391, P = 0.046], elevated C-reactive protein (RC = -5.813, P = 0.005), and a reversible myocardial perfusion defect (RC = -7.386, P < 0.001). An analysis based on the 'best cut-off' of CRP as identified on the basis of the ROC curve augmented the positive and negative predict value of CRP for the prediction of coronary events to 65 and 74%, respectively. Myocardial perfusion SPECT and measuring the plasma concentration of CRP might be useful for the prediction of hemodialysis patients with progression of coronary atherosclerosis.

Adenosine Triphosphate↗

Prognostic value of stress myocardial perfusion imaging in patients with mildly impaired systolic left ventricular function or left ventricular asynergy without chest pain but with suspected coronary artery disease.

BACKGROUND: The prognostic value of myocardial perfusion imaging (MPI) was investigated in patients with mildly impaired left ventricular (LV) function who had no chest pain but were suspected to have coronary artery disease (CAD). METHODS AND RESULTS: Consecutive patients (n=72, mean age =67) who had no chest pain but with mildly impaired systolic LV function (mean LV ejection fraction =52%) or LV asynergy and suspected to have CAD were followed up for 4.9 years after stress MPI. The follow-up time was censored at the occurrence of cardiac death, hospitalization for congestive heart failure (CHF), acute coronary syndromes (ACS), or revascularization. Images were scored using a 20-segment model and a 0-4 scale, and then the summed stress, rest, and difference scores (SDS) were calculated. During follow-up, there were 2 cases of cardiac death, 8 of hospitalization for CHF, 4 of ACS and 2 of revascularization. Cox regression demonstrated that SDS >or=4 was an excellent predictor of cardiac events in all patients (hazard ratio =4.2, p=0.01), and especially in diabetic patients (hazard ratio =28.4, p=0.01). CONCLUSION: Stress MPI is useful for predicting cardiac events and may be performed in patients without chest pain if they have mildly impaired systolic LV function or LV asynergy.

Acute Disease↗

Presence and severity of Chlamydia pneumoniae and Cytomegalovirus infection in coronary plaques are associated with acute coronary syndromes.

Although an association between Chlamydia pneumoniae (Cpn) or Cytomegalovirus (CMV) infection and coronary atherosclerosis has been reported, such an association is less clear for acute coronary syndromes (ACS). The purpose of this study was to investigate the pathogenic roles of Cpn and CMV infection of coronary plaques in ACS. We divided 38 coronary plaque specimens obtained from 38 patients who underwent directional coronary atherectomy or thrombectomy into an ACS group (n = 21) and a non-ACS group (n = 17). Cpn and CMV in specimens were stained using immunohistochemical techniques and analyzed quantitatively. The detection rate for either Cpn- or CMV-positive cells in ACS patients was slightly higher compared with non-ACS patients. Detection rates for both Cpn- and CMV-positive cells were significantly higher in ACS patients than in non-ACS patients (P = 0.010). Furthermore, the density of Cpn- and CMV-positive cells in plaques was significantly higher in ACS patients than in non-ACS patients (P < 0.003). The results indicate that the presence and severity of Cpn and CMV infection in coronary plaques are greater in patients with ACS compared with non-ACS patients. We conclude that infection with Cpn and CMV in coronary plaques may be involved in the pathogenesis of ACS.

Aged↗

Coronary artery fistula with an associated aneurysm detected by 16-slice multidetector row computed tomographic angiography.

We describe a case of a 60-year-old man with effort-induced angina pectoris. Coronary angiography showed an aneurysm in the proximal left anterior descending coronary artery. It was unclear whether it was a coronary artery aneurysm or a coronary fistula with an associated aneurysm. Three-dimensional reconstruction images from 16-slice multidetector row computed tomographic (MDCT) angiography showed an aneurysm that drained into the pulmonary artery. Images from 16-slice MDCT coronary angiography can be helpful in understanding complex coronary artery anatomy.

Coronary Aneurysm↗

Chlamydia pneumoniae immunoreactivity in coronary artery plaques of patients with acute coronary syndromes and its relation with serology.

BACKGROUND: An association between Chlamydia pneumoniae (Cpn) infection and coronary artery disease has been reported and examined by different techniques. However, its immunoreactivity in coronary artery plaques of patients with acute coronary syndrome (ACS) and its relation with serology are less well defined. METHODS: We divided 40 coronary plaque specimens from 40 patients who underwent thrombectomy or directional coronary atherectomy into an ACS group (n = 22) and a non-ACS group (n = 18). Cpn in specimens was detected immunohistochemically and compared quantitatively. Serum immunoglobulin (Ig)A and IgG antibodies to Cpn and high-sensitivity C-reactive protein (hs-CRP) were measured. The relation between serology and immunohistochemical analysis was also investigated. RESULTS: Cpn immunopositive cells per square millimeter (Cpn+ cells/mm2) in the ACS group were significantly more numerous than in the non-ACS group (median 7.44 vs 1.50, P = .0018). Cpn IgA seropositivity rates and titers in the ACS group were significantly higher than those in the non-ACS group (86.3% vs 22.2%, P = .0002; median titer 1.403 vs 0.545, P = .003). There were no differences in IgG antibodies between the 2 groups. The hs-CRP values (in milligrams per liter) in ACS group were significantly higher than in non-ACS group (median 2.8 vs 1.2, P = .0019). Serum IgA titers in patients with at least 5 Cpn+ cells/mm2 in the specimens were significantly higher than in patients with fewer Cpn+ cells (median 1.52 vs 0.86, P = .026). There was no difference in serum hs-CRP values in patients with more Cpn+ cells but a trend to an increase. CONCLUSION: Immunohistology frequently detected Cpn in coronary plaques; Cpn+ cells were more prevalent in plaques associated with ACS, and Cpn IgA but not IgG titers were increased with ACS and with high densities of Cpn+ cells within plaque.

Acute Disease↗

Prediction of cardiac events in patients with transient left ventricle dilation on stress myocardial perfusion SPECT images.

BACKGROUND: The purpose of this study was to investigate cardiac events in patients with transient left ventricle (LV) dilation on stress myocardial perfusion single-photon emission computed tomography images (MPI). METHODS AND RESULTS: Consecutive patients (n=53, 31 males, mean age 71 years) with transient LV dilation on thallium-201 stress MPI (treadmill: 21, pharmacologic: 32) were followed for 17 months. Follow-up time was censored at the occurrence of cardiac death, congestive heart failure, acute coronary syndrome, or revascularization. Images were scored and then the summed stress score (SSS), summed rest score, and summed difference score were calculated. Cardiac death occurred in 3 patients, hospitalization occurred in 8 patients, and revascularization occurred in 20 patients. The combined cardiac event rate was 59% (76% for exercise stress vs 47% for pharmacologic stress, p=0.034). Cox regression analysis demonstrated that a combination of higher SSS and slow washout rate was the best predictor of cardiac events (hazard ratio =3.3, p=0.029). CONCLUSIONS: A high cardiac event rate is associated with transient LV dilation on thallium-201 stress MPI. The event rate is particularly high for exercise stress MPI. Furthermore, a combination of the SSS and thallium-201 slow washout is the best predictor of cardiac events in patients with transient LV dilation.

Aged↗

Evaluation by multislice computed tomography of atherosclerotic coronary artery plaques in non-culprit, remote coronary arteries of patients with acute coronary syndrome.

BACKGROUND: Patients with acute coronary syndrome (ACS) frequently have vulnerable plaques in the remote coronary arteries, suggesting that ACS is part of the pan-coronary process. In the present study the computed tomography (CT) plaque density in non-culprit atherosclerotic coronary artery lesions was evaluated by multislice computed tomography (MSCT) in patients with ACS and non-ACS. METHODS AND RESULTS: MSCT was performed in 21 patients with ACS and 53 patients with non-ACS: 16 of the 21 ACS patients (76%) and 30 of the non-ACS 53 patients (57 %) had non-calcified plaques in the non-culprit coronary arteries (p=0.18). CT-low-density plaques (CT density <68 Hounsfield units (HU)) were more frequent in the ACS group (13/16 patients, 81%) than in the non-ACS group (13/30 patients, 43%, p=0.03). In addition, the CT density of the non-culprit lesion was significantly lower in patients with ACS than in those with non-ACS (44.1+/-22.9 and 77.3+/-33.7 HU, respectively). CONCLUSION: Patients with ACS more frequently had CT-low-density plaques in the non-culprit, remote arteries than those with non-ACS, which suggests that ACS treatment should focus not only on stabilizing the culprit lesion but also on systemic stabilization of non-culprit lesions.

Aged↗

Intramyocardial injection of fibroblast growth factor-2 plus heparin suppresses cardiac failure progression in rats with hypertensive heart disease.

A reduction of coronary flow reserve has been reported in patients with hypertensive heart disease (HHD), which suggests that myocardial ischemia may contribute to the progression to cardiac failure in HHD. Therefore, we evaluated whether fibroblast growth factor (FGF)-2 and/or heparin, which induce angiogenesis, may affect cardiac function in the setting of HHD. We used Dahl salt sensitive (DS) rats as an HHD model. Direct intramyocardial injection of 100 microg of FGF-2 plus 1.28 microg of heparin (n = 6), 100 microg of FGF-2 (n = 6), 1.28 microg of heparin (n = 6) or saline (n = 6) were performed in 9-week-old rats. Echocardiography was performed to evaluate cardiac function at 9, 11, and 13 weeks of age. Plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) concentrations were measured at 8 and 13 weeks of age. DS rats were killed 4 weeks after myocardial injection (at 13 weeks of age), and myocardial capillary density was assessed by von Willebrand factor staining. Injection of FGF-2 plus heparin significantly decreased left ventricular end-diastolic diameter (P < 0.0001) and left ventricular end-systolic diameter (P < 0.0001), significantly improved the reduction of left ventricular fractional shortening (P = 0.0005), significantly decreased plasma ANP (P < 0.0001) and BNP (P = 0.016) concentrations, and significantly increased myocardial capillary density (P = 0.0002) compared with injection of saline. These findings indicate that intramyocardial injection of FGF-2 plus heparin suppresses the progression of cardiac failure in DS rats. FGF-2 plus heparin administration may be a new therapeutic strategy for the treatment of HHD.

Animals↗

Prognostic value of stress myocardial perfusion imaging using adenosine triphosphate at the beginning of haemodialysis treatment in patients with end-stage renal disease.

BACKGROUND: Non-invasive detection of coronary artery disease (CAD) remains difficult in patients with end-stage renal disease (ESRD). This study evaluated the ability of pharmacologic stress myocardial perfusion imaging to predict cardiac events in patients with ESRD. METHODS: A prospective study was carried out in 49 consecutive patients with ESRD. Thallium-201 single photon emission computed tomography (SPECT) using high-dose adenosine triphosphate (ATP) was performed within 1 month of the beginning of haemodialysis. The study end-point was a cardiac event or the 1-year anniversary of the SPECT study. RESULTS: Twenty-four patients (17 diabetics, 57% and seven non-diabetics, 37%) had myocardial perfusion defects. The remaining 25 patients had normal perfusion images. Fifteen patients had non-fatal cardiac events and two patients died of a cardiac cause. All patients who had non-fatal cardiac events underwent myocardial revascularization and survived until the end of follow-up. The 1-year cardiac event-free survival rate was 34% among patients with perfusion defects and 96% among patients without perfusion defects (P<0.001). The presence of a myocardial perfusion defect was the only independent predictor of 1-year cardiac events both in overall (HR, 49.91; 95% CI, 5.15-484.00; P<0.001) and in diabetic patients (HR, 33.72; 95% CI, 2.96-383.5; P = 0.005). Diabetes and an increased C-reactive protein were associated with the progression of CAD. CONCLUSIONS: Normal myocardial perfusion imaging by stress thallium-201 SPECT using high-dose ATP performed within 1 month after the beginning of haemodialysis treatment is a powerful predictor of cardiac event-free survival in patients with ESRD.

Cardiovascular Diseases↗

Insulin receptor substrate 2 plays a crucial role in beta cells and the hypothalamus.

We previously demonstrated that insulin receptor substrate 2 (Irs2) KO mice develop diabetes associated with hepatic insulin resistance, lack of compensatory beta cell hyperplasia, and leptin resistance. To more precisely determine the roles of Irs2 in beta cells and the hypothalamus, we generated beta cell-specific Irs2 KO and hypothalamus-specific Irs2 knockdown (betaHT-IRS2) mice. Expression of Irs2 mRNA was reduced by approximately 90% in pancreatic islets and was markedly reduced in the arcuate nucleus of the hypothalamus. By contrast, Irs2 expression in liver, muscle, and adipose tissue of betaHT-IRS2 mice was indistinguishable from that of control mice. The betaHT-IRS2 mice displayed obesity and leptin resistance. At 4 weeks of age, the betaHT-IRS2 mice showed normal insulin sensitivity, but at 8 and 12 weeks, they were insulin resistant with progressive obesity. Despite their normal insulin sensitivity at 8 weeks with caloric restriction, the betaHT-IRS2 mice exhibited glucose intolerance and impaired glucose-induced insulin secretion. beta Cell mass and beta cell proliferation in the betaHT-IRS2 mice were reduced significantly at 8 and 12 weeks but not at 10 days. Insulin secretion, normalized by cell number per islet, was significantly increased at high glucose concentrations in the betaHT-IRS2 mice. We conclude that, in beta cells and the hypothalamus, Irs2 is crucially involved in the regulation of beta cell mass and leptin sensitivity.

Animals↗

Concentrations of hepatocyte growth factor, basic fibroblast growth factor, and vascular endothelial growth factor in pericardial fluid and plasma.

Some angiogenic factors, including hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF), have been reported to promote angiogenesis and improve myocardial perfusion in experimental models of ischemic heart disease. These factors are produced in various tissues, including myocardium. We measured the concentrations of HGF, bFGF, and VEGF by enzyme-linked immunosorbent assay in plasma and in pericardial fluid sampled during open heart surgery (12 patients with ischemic heart disease and 17 with nonischemic heart disease). HGF levels were significantly higher in plasma than in pericardial fluid (12.0 +/- 1.8 versus 0.26 +/- 0.04 ng/mL, P < 0.0001). On the other hand, bFGF levels were significantly higher in pericardial fluid than in plasma (243.5 +/- 50.9 versus 49.6 +/- 7.8 pg/mL, P = 0.009). VEGF levels were not significantly different between pericardial fluid and plasma (47.2 +/- 17.6 versus 24.5 +/- 3.6 pg/mL, P = 0.23). Concentrations of angiogenic factors in pericardial fluid and in plasma were not significantly different between patients with ischemic and nonischemic heart disease. These results suggest that the production, secretion, and kinetics of HGF, bFGF, and VEGF are different. These angiogenic factors may have different pathophysiologic roles.

Aged↗