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Biomedical subjects

Fumitaka Ohsuzu

Publications and source records attributed to Fumitaka Ohsuzu.

At least 55 records · Page 3Linked to original sources

Effect of chronic stress and sleep deprivation on both flow-mediated dilation in the brachial artery and the intracellular magnesium level in humans.

BACKGROUND: Chronic mental and physical stress has been suggested to be a trigger for cardiovascular events. In addition, a reduction in levels of intracellular magnesium has been reported to cause vasoconstriction while enhancing platelet-dependent thrombosis. HYPOTHESIS: The purpose of this study was to investigate whether chronic stress affects endothelial function and intracellular magnesium levels in humans. METHODS: Flow-mediated dilation (endothelium-dependent vasodilation) and sublingual nitroglycerin-induced dilation (0.3 mg, endothelium-independent vasodilation) were measured in the brachial artery in 30 healthy male college students, aged 22 +/- 1 years, using high-resolution ultrasound both before and immediately after a 4-week final term examination period. Erythrocyte magnesium concentration was measured simultaneously. All students had chronic sleep deprivation for 4 weeks, during which sleep lasted < 80% of that on ordinary days; in addition, the students were under great stress to pass the examination. This condition was considered to be chronic stress. RESULTS: Chronic stress decreased flow-mediated dilation and erythrocyte magnesium concentration (from 7.4 +/- 3.0 to 3.7 +/- 2.3%, p < 0.05; from 5.7 +/- 0.4 to 5.5 +/- 0.4 mg/ml, p < 0.05, respectively). The change in flow-mediated dilation correlated significantly with that of the erythrocyte magnesium concentration (r = 0.43, p < 0.05), but not with nitroglycerin-induced dilation. CONCLUSIONS: Chronic stress was found to attenuate endothelial function, which may also be associated with a reduction in the intracellular magnesium level in humans.

Adult↗

An oxidized low-density lipoprotein receptor gene variant is inversely associated with the severity of coronary artery disease.

BACKGROUND: A lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) is the major receptor of oxidized LDL in endothelial cells. The expression of LOX-1 was shown to be upregulated in atherosclerotic lesions. Recently, LOX-1 gene polymorphism (G501C) was reported to be associated with myocardial infarction (MI). HYPOTHESIS: Our study was undertaken to elucidate the association between this polymorphism and coronary artery disease (CAD). METHODS: We evaluated LOX-1 gene polymorphism using Invader assay in 586 patients undergoing coronary angiography. RESULTS: Study patients were categorized into three groups: normal/minimal stenosis (< or =25%) (n = 128); mild stenosis (26-50%) (n = 39); and significant stenosis (>50%) (n = 419). Of the 419 patients with significant stenosis, 163 had single-vessel, 165 had double-vessel, and 91 had triple-vessel disease. Myocardial infarction was present in 171 patients. The frequency of LOX- 1 gene variants (C/C or C/G) was lower in patients with significant than in those with normal/minimal stenosis (36 vs. 49%, p < 0.01). The frequency of LOX-1 gene variants did not differ between patients with and without MI (34 vs. 37%). However, a stepwise decrease in the frequency of such variants was found depending on the severity of CAD: 49% in normal/minimal stenosis, 41% in mild stenosis, 39% in single-vessel, 35% in double-vessel, and 32% in triple-vessel disease. Multivariate analysis demonstrated LOX-1 gene variants to be inversely associated with the presence of significant stenosis (odds ratio = 0.61; 95% confidence interval = 0.41-0.92). CONCLUSIONS: The LOX-1 gene variants at 501 were found to be inversely associated with the severity of CAD. This polymorphism may be modifying the severity of CAD.

Aged↗

A patient with a Mycobacterium avium complex infection complicated by systemic lupus erythematosus.

A 41-year-old woman was admitted to our hospital because of fever and polyarthralgia. A diagnosis of systemic lupus erythematosus (SLE) was made based on the findings of polyarthritis, leukocytopenia, lymphocytopenia, proteinuria, and positive reactions for antinuclear antibody (ANA) and anti-double strand (ds)DNA antibody. She had also been suffering from a pulmonary Mycobacterium avium complex (MAC) infection with such symptoms as cough and sputum for the past 3 years. Antimicrobial drugs for MAC infection were administered first, and later she was given cyclophosphamide pulse therapy, consisting of methylprednisolone (8 mg/day) and mizoribine (100 mg/day). Owing to these therapeutic regimens, SLE was successfully treated without an exacerbation of the MAC infection. The risk factors for MAC infection and SLE are also discussed.

Adult↗

Panniculitis in a patient with mixed connective tissue disease.

A 51-year-old woman who had been suffering from mixed connective tissue disease (MCTD) for 8 years developed an erythematous rash with pain and tenderness on her left leg. A skin biopsy revealed septal panniculitis with multiple lymphangiectasis. No vasculitis was observed. An increase in her prednisolone dose from 5 mg to 20 mg/day led to an improvement in these lesions. Panniculitis is very rare in MCTD. The clinical significance of panniculitis in MCTD is also discussed.

Journal Article↗

In vivo magnetic resonance evaluation of associations between aortic atherosclerosis and both risk factors and coronary artery disease in patients referred for coronary angiography.

BACKGROUND: Magnetic resonance imaging was recently reported to detect atherosclerotic plaques in thoracic and abdominal aortas. METHODS: Using magnetic resonance imaging, we investigated associations of risk factors and plasma inflammatory markers with plaques in both thoracic and abdominal aortas in 102 patients undergoing coronary angiography. Associations between coronary artery disease (CAD) and aortic plaques were also evaluated. RESULTS: Plaques in thoracic and abdominal aortas were detected in 61% and 90% of patients, respectively. Age and systolic blood pressure correlated with plaque extents in both the aortas. Serum LDL cholesterol level correlated with plaque extent in the thoracic aorta (r(s) = 0.42). The degree of smoking correlated with plaque extent in the abdominal aorta (r(s) = 0.43). In multivariate analysis, age and systolic blood pressure were associated with plaques in both the aortas. The LDL cholesterol and smoking were characteristically associated with plaques in the thoracic and abdominal aortas, respectively. Regarding inflammatory markers, fibrinogen and C-reactive protein levels correlated with total plaque extent in the aortas (r(s) = 0.50 and r(s) = 0.51). Compared with 24 patients without CAD, 78 with CAD more often had plaques in the thoracic (71% vs 29%) and abdominal (95% vs 75%) aortas. Although plaque extents in both the aortas correlated with the severity of CAD, only thoracic plaques were independently associated with CAD. CONCLUSIONS: The thoracic and abdominal aortas may have different susceptibilities to risk factors. However, plasma inflammatory markers appear to reflect total extent of aortic atherosclerosis. Although aortic plaques are common in patients with CAD, only thoracic plaques are an independent factor for CAD.

Aged↗

Association of Mycoplasma pneumoniae infection with coronary artery disease and its interaction with chlamydial infection.

Mycoplasma pneumoniae (MP) seropositivity was reported to be associated with coronary events. MP organisms were detected with Chlamydia pneumoniae (CP) in coronary plaques. We investigated MP and CP seropositivity in 549 patients undergoing coronary angiography. Coronary artery disease (CAD) was found in 396 patients, of whom 154 had myocardial infarction (MI). MP seropositivity was more prevalent in patients with CAD than without CAD (14% versus 6%, P < 0.01). The highest prevalence was found in patients with MI. In contrast, the prevalence of CP seropositivity was similar in patients with and without CAD (62% versus 59%). To clarify interaction with CP infection, 549 patients were divided into two groups with and without CP seropositivity. Among patients with CP seropositivity, MP seropositivity was more prevalent in patients with CAD than without CAD (17% versus 5%, P < 0.01), whereas among patients without CP seropositivity, MP seropositivity did not differ between patients with and without CAD (9% versus 6%). In multivariate analysis, MP seropositivity was associated with CAD only in patients with CP seropositivity (odds ratio = 5.1, 95% CI = 1.8-14.9). Thus, MP seropositivity was associated with CAD. However, this association was confined to patients with CP seropositivity. Coinfection by MP and CP may be an important cofactor for CAD.

Aged↗

Effects of chronic sleep deprivation on autonomic activity by examining heart rate variability, plasma catecholamine, and intracellular magnesium levels.

Chronic sleep deprivation is associated with cardiovascular events. In addition, autonomic activity determined from the levels of the heart rate variability (HRV), plasma catecholamine, and intracellular magnesium (Mg) are important in the pathophysiology of cardiovascular events. This study therefore aimed to determine the effects of chronic sleep deprivation on autonomic activity by examining the HRV, plasma catecholamine, and intracellular magnesium levels. Thirty (30) healthy male college students ranging in age from 20 to 24 years of age (average 22 +/- 1 years; mean +/- SD) with no coronary risk factors such as hypertension, diabetes mellitus, hyperlipidemia or a family history of premature coronary artery disease (CAD) were included in the study. Over a 4-week period, the volunteers' plasma levels of epinephrine, norepinephrine, and erythrocyte-Mg were measured. The study was made during the 4 weeks before and immediately after college finals exams. HRV, obtained from 24-hour ambulatory ECG monitoring, included time and frequency domain indices. The HRV indices and erythrocyte-Mg decreased while norepinephrine increased during chronic sleep deprivation. It is concluded that chronic sleep deprivation causes an autonomic imbalance and decreases intracellular Mg, which could be associated with chronic sleep deprivation-induced cardiovascular events.

Adult↗

Assessment of autonomic activity during daily life of patients with head-up tilt-induced prolonged asystole.

Autonomic activity is important in the pathophysiology of neurally mediated syncope (NMS) patients diagnosed by the head-up tilt (HUT) test, and prolonged systole induced by HUT is associated with a malignant vasovagal syndrome. This study investigated whether or not daily autonomic activity evaluated by heart rate variability (HRV) assessed through 24-hour ambulatory ECG monitoring was augumented in HUT-induced asystole (AS; > 30 s) and whether or not HRV differed between NMS patients with and without AS. Ambulatory ECG monitoring was performed in 176 patients with suspected NMS and in 62 age-matched healthy control subjects (C group, age: 36 +/- 13 yr), with HRV time and frequency domain indices measured within 48 hours of HUT. Six patients displayed prolonged AS (PAS group, age: 33 +/- 12 yr), and 109 patients had positive HUT (P group, age: 29 +/- 17 yr), while 61 patients had negative HUT (N group, age: 40 +/- 18 yr). Several HRV indices in the P group were higher than those in the N and C groups. However, HRV indices did not differ between the P group and the PAS group. It is concluded that impairment of autonomic activity specifically related to orthostatic stress could be important in the pathophysiology of HUT-induced prolonged asystole, while impairment of autonomic activity in daily life is not as important in NMS patients with HUT-induced prolonged asystole.

Activities of Daily Living↗

Day-to-day variability of the long-term fractal component of heart rate variability (beta) and the effect of an antianginal agent in patients with silent myocardial ischemia.

The deterioration of the long-term fractal component of heart rate variability (beta) is reported in patients with organic heart disease. To examine the day-to-day variability of beta and to study the effects of nipradilol (NIP), an antianginal agent, on beta in patients with coronary artery disease (CAD), we performed 24-hour ambulatory ECG (AECG) in 24 patients with silent myocardial ischemia (SMI) and obtained the conventional frequency domain heart rate variability (HRV) indices and beta using the MemCalc system. Patients were divided into two groups: group I consisted of 10 patients (64 +/- 5 years of age) for the assessment of the day-to-day variability of beta; group II comprised 14 patients (60 +/- 6 years of age) for evaluation of the effect of NIP (3 mg b.i.d). In group I, AECG was repeated twice a week, while AECG was recorded before NIP treatment (placebo) and on the last day of the 4-week NIP treatment in group II. In group I, there was significant correlation between the values of beta on day 1 and day 2 (r = 0.79, p < 0.05), the difference being 0.09 +/- 0.15 (coefficient of variance: 6.8%). Bland and Altman's analysis indicated that the results were easily reproducible, making this approach feasible for clinical use. In group II, NIP significantly decreased the values of beta by 10.6% (from -1.23 +/- 0.09 to -1.18 +/- 0.07; p < 0.05). NIP also significantly increased the conventional HRV indices. The degree of decrement of beta by NIP was larger than that of the day-to-day variability. In conclusion, a day-to-day variability exists in beta in patients with SMI, but its value is relatively small. A daily dose of 6 mg NIP ameliorates beta and overcomes this variability.

Adrenergic alpha-Antagonists↗

Levels of annexin IV and V in the plasma of pregnant and postpartum women.

Annexin (Anx) V is pivotal in the maintenance of pregnancy by preventing the activation of blood coagulation. The homology of the amino acid sequence between Anx IV and Anx V is highest in Anx family proteins. However, little is known about the roles of Anx IV in pregnancy. The aim of this study is to clarify the roles of circulating Anx IV and Anx V in normal pregnancy. Subjects were non-pregnant women (n = 50), 120 pregnant women, and maternal subjects just after delivery (n = 53) or postpartum (n = 67). Anx IV in the plasma of non-pregnant women was at a concentration 20 times that of Anx V. The plasma levels of Anx IV suddenly increase after delivery, but Anx V levels remain low during this period. Anx IV and Anx V exert similar levels of anticoagulant activity. Anx IV protein was expressed on the basal surface of syncytiotrophoblasts; Anx V protein, on the apical surface of syncytiotrophoblasts. These results suggest that Anx IV enters the maternal bloodstream just after delivery and might play a role in preventing disseminated intravascular coagulopathy, and that Anx V helps to prevent clotting in the placenta during pregnancy.

Adult↗

Whole-heart dipyridamole stress first-pass myocardial perfusion MRI for the detection of coronary artery disease.

A whole-heart coverage MRI sequence, which employes a hybrid of fast gradient echo and echo planar acquisition imaging (FastCard EchoTrain), has recently been developed. Using this sequence, a first-pass myocardial perfusion MRI was shown to be a good noninvasive modality for detecting coronary artery disease (CAD) in a clinical setting. In addition, the clinical usefulness of delayed enhanced MRI has recently been reported. The objectives of this study were (1) to investigate the accuracy of dipyridamole stress first-pass myocardial perfusion MRI for diagnosing CAD (> 50% stenosis) and (2) to clarify whether additional delayed enhancement MRI has any clinical significance. We performed first-pass myocardial perfusion MRI in 102 consecutive patients (66 +/- 9 years old) suspected to have CAD or new lesions in patients with well-documented prior myocardial infarction (MI). Using a 1.5 T cardiac MR imager (GE CV/i), eight short axis MR images of the left ventricle were acquired by injecting gadolinium (0.1 mmol/kg) under dipyridamole infusion stress (0.56 mg/kg). Fifteen minutes later, aminophylline (250 mg) was injected and first-pass perfusion MRI was repeated in the resting state in order to evaluate both the presence of perfusion defect and delayed enhancement. The presence of perfusion defect and delayed enhancement was determined based on a visual qualitative analysis by the agreement of two separate readers who were blinded to any clinical information. Based on the stress and rest findings, no defect, reversible defect, or fixed defect with or without delayed enhancement was recorded in any patient. The MR findings revealed 76 CAD patients, including 24 MI patients with new lesions and 26 patients without CAD on coronary angiography. The presence of stress perfusion defect had a 93% sensitivity and an 85% specificity for diagnosing CAD. A fixed defect showed an 86% sensitivity and a 66% specificity for diagnosing a prior MI. Patients with a fixed defect with delayed enhancement had more significant stenosis in the infarct related artery than in those without any enhancement (11/26 vs 15/20, P < 0.05). Dipyridamole stress first-pass myocardial perfusion MRI using the FastCard EchoTrain was found to be a clinically useful and accurate modality for diagnosing CAD.

Aged↗

Pulmonary vein dimensions and variation of branching pattern in patients with paroxysmal atrial fibrillation using magnetic resonance angiography.

UNLABELLED: Pulmonary veins are the most frequent origin of focal and paroxysmal atrial fibrillation. Although radiofrequency ablation has been attempted for the treatment of focal and paroxysmal atrial fibrillation, the anatomy of the pulmonary vein is still not fully understood. To investigate the dimensions and anatomical variation of the pulmonary vein in patients with paroxysmal atrial fibrillation, we performed breath-hold gadolinium enhanced magnetic resonance (MR) angiography using a 1.5 T cardiac MR imager (GE CV/i) in 32 patients with paroxysmal atrial fibrillation (61 +/- 8 years old), 11 patients with chronic atrial fibrillation (64 +/- 9 years old), and 26 patients with normal sinus rhythm (55 +/- 15 years old). Three dimensional images of the pulmonary veins were thus obtained, and the diameters of the most proximal portion of the left or right superior pulmonary vein and left or right inferior pulmonary vein were measured. Pulmonary vein branching variations were determined by a visual qualitative analysis by two separate readers' agreements, who were blinded to any clinical information. We focused on the existence of a complex-branching pattern draining into the orifice of four pulmonary veins. Patients with either paroxysmal atrial fibrillation or chronic atrial fibrillation showed larger superior pulmonary veins than those with normal sinus rhythm (mean +/- SD; in the left superior pulmonary vein, 20 +/- 3 mm, 23 +/- 3 mm vs 16 +/- 3 mm, P < 0.05; in right superior pulmonary vein, 19 +/- 4 mm, 19 +/- 2 mm vs 16 +/- 2 mm, P < 0.05). Complex-branching pattern was frequently observed in inferior pulmonary veins in patients with either paroxysmal atrial fibrillation or chronic atrial fibrillation; 25/32 patients with paroxysmal atrial fibrillation, 11/11 patients with chronic atrial fibrillation, compared to 7/26 patients with normal sinus rhythm. Complex-branching patterns were not observed in superior pulmonary veins in any patients in this cohort. CONCLUSION: In patients with paroxysmal atrial fibrillation or chronic atrial fibrillation, significant pulmonary vein dilation occurred mainly in the superior pulmonary veins, while a complex-branching pattern was frequently observed in the inferior pulmonary veins. These MR angiographic findings might be useful when performing radiofrequency ablation procedures and catheter manipulation for the treatment of paroxysmal atrial fibrillation.

Aged↗

The roles of cytokines, inflammation and immunity in vascular diseases.

Recent findings regarding the roles of cytokines, inflammation and immunity during the development of atherosclerosis were reviewed. Especially, the relationships among pro-inflammatory cytokines such as interleukin (IL)-1, IL-18 and osteopontin, and anti-inflammatory cytokines such as IL-1 receptor antagonist, IL-10 and IL-18 binding protein to inflammation and atherosclerosis were investigated and are described in detail. In addition, helicobacter pylori and C pneumoniae infections to inflammations regarding the persistence of inflammation have been pointed out. A pro-inflammatory genotype or haplotype and toll-like receptors have been shown to be involved in human atherosclerosis. Atherosclerosis might therefore be a specific form of the chronic inflammatory process. In addition to hyperlipidemia, infections, cytokines and immunity might also be involved in the development of atherosclerosis. Certain treatments that reduce coronary risk also limit inflammation. Statins possess multiple pleiotropic effects such as an anti-inflammatory effect in addition to a lipid-lowering effect.

Cytokines↗

[Soluble elastin fragments in serum are elevated in aortic dissection].

OBJECTIVES: We aimed to establish an enzyme-linked immunosorbent assay (ELISA) for measuring soluble elastin fragments (sELAF) in serum and to reveal its usefulness in diagnosing acute aortic dissection. BACKGROUND: Acute aortic dissection is a life-threatening disease of the aorta. However, the diagnosis is still frequently missed, especially at onset. The establishment and clinical availability of simplified laboratory test(s) to help diagnose and screen acute aortic dissection patients is therefore urgently needed. METHODS AND RESULTS: An ELISA to measure sELAF in serum was developed using the newly created double monoclonal antibodies which recognize the different epitopes of human aortic elastin. Twenty-five acute aortic dissection patients, 50 patients with acute myocardial infarction, and 474 healthy individuals were enrolled in the study. The sELAF levels from healthy subjects gradually increased with aging. When the cutoff point for positivity was set at the mean + 3SD above the mean of those in healthy subjects at each age, 16 acute aortic dissection patients (64.0%) were found to be positive, while only one acute myocardial infarction patient was positive (2.0%). Acute aortic dissection patients with either an open or a partially open pseudolumen were found to be 88.9% positive for sELAF, while those with its early closure was 0% positive. The difference in the sELAF levels between acute aortic dissection patients with and without a thrombotic closure of false lumen was significant (60.3 +/- 15.6 vs 135.4 +/- 53.2 ng/ml, p < 0.005). CONCLUSIONS: The sELAF level in serum may be a useful marker for helping both diagnose and screen acute aortic dissection, while also helping distinguish acute aortic dissection from acute myocardial infarction.

Acute Disease↗

A mitochondrial DNA variant associated with left ventricular hypertrophy in diabetes.

Diabetes was reported to be associated with a mitochondrial (mt) DNA mutation at 3243 and variants at 1310, 1438, 3290, 3316, 3394, 12,026, 15,927, and 16,189. Among these mtDNA abnormalities, those at 3243, 3316, 15,927, and 16,189 were also suggested to cause cardiomyopathies. We investigated the prevalence of such mtDNA abnormalities in 68 diabetic patients with LV hypertrophy (LVH), 100 without LVH, and 100 controls. Among the 9 mtDNA abnormalities, those at 3243, 3316, and 15,927 tended to be more prevalent in diabetic patients with LVH than in those without LVH (1%, 1%, and 4% vs. 0%, 0%, and 0%). Notably, the variant at 16,189 was more prevalent in diabetic patients with LVH than without LVH (46% vs. 24%, [Formula: see text] ). The odds ratio for LVH was 3.0 (95% CI, 1.5-6.1) for the 16,189 variant. A common mtDNA variant at 16,189 was found to be associated with LVH in diabetic patients.

DNA Mutational Analysis↗

Deficiency of interleukin-1 receptor antagonist promotes neointimal formation after injury.

BACKGROUND: The cytokine interleukin (IL)-1 is an important mediator of inflammation and cardiovascular disease. Activity of this cytokine is modulated endogenously via the IL-1 receptor antagonist (IL-1Ra). The role of IL-1Ra in neointima formation after injury, however, is poorly understood. METHODS AND RESULTS: Using IL-1Ra-deficient (IL-1Ra-/-; backcrossed 8 generations into the C57BL/6J background) and wild-type (IL-1Ra+/+) mice, we investigated neointimal formation 3 weeks after femoral artery injury induced by an external vascular cuff model. Intima and media thicknesses were measured, and the intima/media ratio was calculated. The mean intimal thickness and the intima/media ratio of IL-1Ra-/- mice increased by 249% (31.8+/-2.9 microm [n=10] versus 9.1+/-0.7 microm [n=10]; P<0.0001) and 257% (2.5+/-0.2 versus 0.7+/-0.1; P<0.0001), respectively, compared with IL-1Ra+/+ mice. No significant differences were observed in the medial thickness. Control immunostaining for IL-1Ra in injured vessels localized IL-1beta and the endogenous inhibitor in the endothelium and inflammatory cells of the adventitia in IL-1Ra+/+ but not IL-1Ra-/- mice. CONCLUSIONS: The absence of IL-1Ra promotes neointimal formation in mice after injury. These results suggest that endogenous IL-1Ra may suppress other occlusive vascular responses to injury, such as atherosclerosis and restenosis after angioplasty.

Animals↗

Soluble elastin fragments in serum are elevated in acute aortic dissection.

OBJECTIVE: We aimed to establish an enzyme-linked immunosorbent assay for measuring soluble elastin fragments (sELAF) in serum and to reveal its usefulness in diagnosing acute aortic dissection (AAD). METHODS AND RESULTS: An enzyme-linked immunosorbent assay to measure sELAF in serum was developed by using the newly created double monoclonal antibodies, which recognize the different epitopes of human aortic elastin. Twenty-five AAD patients, 50 patients with acute myocardial infarction (AMI), and 474 healthy individuals were enrolled in the study. The sELAF levels from healthy subjects gradually increased with aging. When the cutoff point for positivity was set at the mean+3 SD (ie, 3 SD above the mean in healthy subjects at each age), 16 AAD patients (64.0%) were found be positive, whereas only 1 AMI patient was found to be positive (2.0%). AAD patients with either an open or a partially open pseudolumen were found be 88.9% positive for sELAF, whereas those with its early closure were 0% positive. The difference in the sELAF levels between AAD patients with and without a thrombotic closure of false lumen was significant (60.3+/-15.6 versus 135.4+/-53.2 ng/mL, respectively; P<0.005). CONCLUSIONS: The sELAF level in serum may be a useful marker for helping in the diagnosis and screening of AAD and may also help to distinguish AAD from AMI.

Acute Disease↗