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Biomedical subjects

Jitsuo Higaki

Publications and source records attributed to Jitsuo Higaki.

At least 19 recordsLinked to original sources
PubMed2007

Cardiac imaging using 256-detector row four-dimensional CT: preliminary clinical report.

PURPOSE: Along with the increase of detector rows on the z-axis and a faster gantry rotation speed, the spatial and temporal resolutions of the multislice computed tomography (CT) have been improved for noninvasive coronary artery imaging. We investigated the feasibility of the second specification prototype 256-detector row four-dimensional CT for assessing coronary artery and cardiac function. MATERIALS AND METHODS: The subjects were five patients with coronary artery disease. Contrast medium (40-60 ml) was intravenously administered at the rate of 3-4 ml/s. The patient's whole heart was scanned for 1.5 s to cover at least one cardiac cycle during breathholding without electrocardiographic gating. Parameters used were 0.5 mm slice thickness, 0.5 s/rotation, 120 Kv, and 350 mA, with a half-scan reconstruction algorithm (temporal resolution 250 ms). Twenty-six transaxial datasets were reconstructed at intervals of 50 ms. RESULTS: The assessability of the coronary arteries in AHA segments 1, 2, 3, 5, 6, 7, 9, and 11 was visually evaluated, resulting in 29 of 32 (90.9%) segments being assessable. Functional assessment was also performed using animated movies without banding artifacts in all cases. CONCLUSIONS: The 256-detector row four-dimensional CT can assess the coronary artery and cardiac function using data during 1.5 s without banding artifacts.

Aged↗
PubMed2006

Attenuation of inflammatory vascular remodeling by angiotensin II type 1 receptor-associated protein.

To explore the role of angiotensin II Type 1 receptor-associated protein (ATRAP) in vascular remodeling, we developed transgenic mice for mouse ATRAP cDNA and examined remodeling after inflammatory vascular injury induced by polyethylene cuff placement. In ATRAP transgenic (ATRAP-Tg) mice, ATRAP mRNA was increased 3- to 4-fold in the heart, aorta, and femoral artery. ATRAP-Tg mice showed no significant change in body weight, systolic blood pressure, heart rate, and heart/body weight ratio. However, cell proliferation and neointimal formation in the injured artery were attenuated in ATRAP-Tg mice. The increase in NADPH oxidase activity and the expression of p22(phox), a reduced nicotinamide-adenine dinucleotide/reduced nicotinamide-adenine dinucleotide phosphate oxidase subunit, after cuff placement was also attenuated in ATRAP-Tg mice. Moreover, activation of extracellular signal-regulated kinase, signal transducer and activator of transcription 1, and signal transducer and activator of transcription 3 after cuff placement was significantly reduced in ATRAP-Tg mice. Pressor response and cardiac hypertrophy induced by angiotensin II infusion and pressure overload were also attenuated in ATRAP-Tg mice. These results suggest that ATRAP plays an important role in vascular remodeling as a negative regulator.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Eplerenone with valsartan effectively reduces atherosclerotic lesion by attenuation of oxidative stress and inflammation.

OBJECTIVE: Angiotensin II contributes to atherogenesis, mainly through oxidative stress and inflammation. Recent data suggest that aldosterone is implicated in some effects of angiotensin II. We hypothesized that aldosterone could directly contribute to oxidative stress and atherosclerotic lesion formation. METHODS AND RESULTS: Male apolipoprotein E-deficient mice 6 weeks of age were placed on a normal diet or 1.25% high-cholesterol diet. After 6 weeks of the high-cholesterol diet, a marked increase in atherosclerotic lesion formation was observed in the aorta, accompanied by significant elevation of plasma cholesterol level. Production of superoxide anion and expression of NAD(P)H oxidase subunit p47phox, tumor necrosis factor-alpha, and monocyte chemoattractant protein-1 in the aorta were increased with the high-cholesterol diet. Eplerenone (1.67 g/kg in high-cholesterol diet) did not affect blood pressure or plasma cholesterol but decreased the atherosclerotic area by nearly 70% (P<0.05), associated with attenuation of oxidative stress and inflammatory response. Valsartan (0.5 mg/kg per day) also decreased the atherosclerotic lesion, whereas coadministration of valsartan and eplerenone further decreased it. Moreover, aldosterone (0.1 micromol/L) enhanced NADPH oxidase activity in cultured vascular smooth muscle cells. CONCLUSIONS: These results suggest that aldosterone may play a critical role in atherogenesis subsequent to oxidative stress in part independent of angiotensin II-mediated signaling, and that eplerenone could prevent atherosclerosis by attenuating oxidative stress and inflammation.

Aldosterone↗
PubMed2006

Coexistence of three distinct adrenal tumors in the same adrenal gland in a patient with primary aldosteronism and preclinical Cushing's syndrome.

A 62-year-old woman was admitted to our hospital because of hypokalemia. Physical examination revealed no signs of excessive adrenocortical steroid production, as are found in Cushing's syndrome. Her plasma renin activity (PRA) was suppressed (0.10 ng/ml per h), and her serum aldosterone level was high (30.0 ng/dl). PRA was not increased after a renin-releasing test. Her plasma adrenocorticotropic hormone (ACTH) level was low (<5 pg/ml), but her serum cortisol level was normal (21.0 microg/dl). Administration of 8 mg dexamethasone did not suppress her plasma cortisol level. Finally, she was diagnosed with clinical primary aldosteronism associated with preclinical Cushing's syndrome. Magnetic resonance image revealed three sequential nodular masses (each 15 mm x 15 mm) in the right adrenal gland. A right adrenalectomy was performed by endoscopy. The three removed tumors appeared to have different characteristics. Microscopic examination revealed that the upper and lower tumors were adrenocortical adenomas, and the middle tumor was a black adenoma. Immunohistochemical staining for the enzymes involved in cortisol biosynthesis suggested that the upper tumor secreted aldosterone, whereas either or both of the two other tumors secreted cortisol. Surprisingly, at 33 years of age, she had been diagnosed with Cushing's syndrome, due to a cortisol-producing adrenocortical adenoma, and she had received a left adrenalectomy. Clinically and pathophysiologically, this was a very rare case.

Adenoma↗
PubMed2006

Assessment of left ventricular wall motion using 16-channel multislice computed tomography: comparison with left ventriculography.

PURPOSE: Using the raw data from coronary computed tomography (CT) angiography, multislice CT (MSCT) can be used to evaluate cardiac function. However, the accuracy of left ventricular (LV) wall motion assessment by MSCT has not been thoroughly investigated. We investigated whether 16-channel MSCT could accurately assess LV wall motion by comparing its results with those of conventional biplane left ventriculography (LVG). MATERIALS AND METHODS: The study included 20 patients with various kinds of heart disease. All patients underwent both contrast-enhanced MSCT and biplane LVG. Using a retrospective electrocardiography-gating technique, 10 phases over one cardiac cycle were extracted. The left ventricle was divided into seven segments according to the American Heart Association classification. Wall motion was scored as follows: 1, normal; 2, mild to moderate hypokinesis; 3, severe hypokinesis; 4, akinesis; 5, dyskinesis; and 6, aneurysm. The scores obtained by MSCT were compared with those obtained by LVG. The wall motion scores were analyzed using the chi-squared independence test (6 x 6 contingency table). RESULTS: Wall motion could be assessed in all segments of the 20 patients using interactive multiplanar animation. Among a total of 140 segments in 20 patients, scores in 118 were concordant between MSCT and LVG (118/140, 84.3%). CONCLUSION: The 16-MSCT can accurately assess LV wall motion.

Adult↗
PubMed2006

Plasma osteopontin levels are higher in patients with primary aldosteronism than in patients with essential hypertension.

BACKGROUND: The incidence of cardiovascular events is higher in patients with primary aldosteronism (PA) than in patients with essential hypertension (EHT). Aldosterone has been shown to play an important role in the development of vascular inflammation and myocardial fibrosis in animal models. Elevated serum inflammatory cytokine is an independent cardiovascular risk factor in patients with EHT. In the present study, we compared levels of inflammatory cytokines between patients with PA and EHT. METHODS: The study subjects were 15 patients with PA and 15 age-matched patients with EHT. Serum interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), high sensitive C-reactive protein (hsCRP), and plasma osteopontin (OPN) levels were measured by enzyme-linked immunosorbent assays. RESULTS: Systolic and diastolic blood pressure (BP) did not differ between the PA and EHT patient groups. Levels of serum IL-6 (P = .563), TNF-alpha (P = .480), and hsCRP (P = .870) did not differ between the two groups. In contrast, plasma OPN levels in patients with PA were significantly higher than those in patients with EHT (P < .0001). There was no relationship between BP and plasma OPN levels in patients with PA. CONCLUSIONS: The present study showed that plasma OPN levels were higher in patients with PA than in patients with EHT.

Adult↗
PubMed2006

The effect of losartan and amlodipine on serum adiponectin in Japanese adults with essential hypertension.

BACKGROUND: Adiponectin, an adipocyte-derived protein, is reduced in patients with hypertension and insulin resistance (IR). Angiotensin II receptor blockers (ARBs) have been reported to improve IR and reduce albuminuria. The purpose of this study was to evaluate the influence of an ARB and a calcium channel blocker on serum adiponectin levels in Japanese patients with hypertension who were treated with losartan or amlodipine for 3 months. METHODS: Patients with essential hypertension (EHT) were randomized to treatment prospectively with losartan (50-100 mg/d) or amlodipine (5-10 mg/d) for 3 months. Patients with renal damage and/or macroproteinuria were excluded. The urine albumin/creatinine ratio, homeostasis model assessment (HOMA) index, adiponectin concentration, and tumor necrosis factor-alpha (TNF-alpha) concentration of each patient were evaluated before and after 3 months of treatment. When the HOMA index exceeded 1.73, a patient was considered to have IR. RESULTS: All 40 participants completed both 3-month treatment periods. Study patients were primarily male (52.5%) with a mean (SD) age of 63.8 (10.6) years and a mean body weight of 60.7 (10.8) kg. Patients with EHT and diabetes mellitus (n = 9) and IR (n = 12) had significantly lower adiponectin concentrations than patients who had EHT without diabetes or IR (n = 19; mean [SD], 7.84 [5.54] vs 12.81 [7.36] microg/mL, P = 0.034; and 6.12 [3.04] vs 12.81 [7.36] microg/mL, P = 0.004, respectively). Adiponectin concentrations correlated negatively with body mass index (r = -0.393; P = 0.012) and HOMA index (r = -0.440; P = 0.005) and positively with high-density lipoprotein cholesterol (r = 0.441; P = 0.004) before treatment. Systolic blood pressure was significantly decreased in patients treated with losartan (n = 20; mean [SD], 166 [19] to 140 [15] mm Hg; P < 0.001) or amlodipine (n = 20; 164 [15] to 136 [15] mmHg; P < 0.001), and diastolic blood pressure also was significantly decreased with losartan (93 [14] to 83 [10] mm Hg; P = 0.031) or amlodipine (96 [12] to 82 [10] mm Hg; P < 0.001). Losartan increased adiponectin concentrations (9.56 [6.75] to 10.36 [6.94] microg/mL; P = 0.038), whereas amlodipine had no significant effect (9.67 [6.62] to 10.01 [6.79] microg/mL). The difference in TNF-alpha concentration before and after treatment with losartan and amlodipine did not reach statistical significance (mean [SD], 15.2 [1.4] to 14.8 [1.5] pg/mL; and 14.3 [1.4] to 14.5 [1.7] pg/mL, respectively). CONCLUSION: In this study, Japanese adults with EHT had significant increases in adiponectin after 3 months of treatment with 50 to 100 mg/d of losartan, but not with 5 to 10 mg/d of amlodipine.

Adiponectin↗
PubMed2006

Osteopontin and carotid atherosclerosis in patients with essential hypertension.

OPN (osteopontin), a pro-inflammatory cytokine, has recently emerged as a key factor in both vascular remodelling and the development of atherosclerosis. However, the relationship between OPN and atherosclerosis in patients without symptomatic cardiovascular disease is not clear. Therefore we measured plasma OPN levels and evaluated the correlation between plasma OPN levels and atherosclerosis as target organ damage in patients with EHT (essential hypertension). Plasma OPN levels were measured in 76 patients with EHT using a solid-phase sandwich ELISA. IMT (intima-media thickness), and V(d) and V(s) (mean diastolic and systolic flow velocities respectively) were evaluated by carotid ultrasound. The V(d)/V(s) ratio, an index of peripheral arterial resistance, was also calculated. The patients were divided on the basis of median OPN levels into a high-OPN group and a low-OPN group. The mean IMT and aldosterone levels were higher (P=0.024 and 0.031 respectively) and V(d)/V(s) was lower (P=0.007) in the high-OPN group than in the low-OPN group. Plasma OPN levels were positively correlated with mean IMT (r=0.308, P=0.0068) and negatively with V(d)/V(s) (r=-0.293, P=0.010). Stepwise regression analysis revealed that OPN was an independent determinant of mean IMT (P=0.007) and V(d)/V(s) (P=0.009), and aldosterone was an independent determinant of OPN. These results suggest that OPN plays a role in the development of atherosclerosis and may be a potential clinical marker for the prediction of atherosclerosis in patients with EHT.

Adult↗
PubMed2006

Effect of inhaled bronchodilators on air trapping in patients with stable asthma.

Air trapping is frequently observed during high-resolution computed tomography (HRCT) of patients with asthma, but whether the condition is reversible has not been thoroughly investigated. The aim of the present study was to evaluate reversibility of air trapping in response to bronchodilator. Ten never-smokers with stable asthma enrolled in the study. Spirometry and HRCT were performed before and after bronchodilator inhalation. Air trapping remained unchanged, although significant reversibility of FEV(1) was observed. Air trapping scores correlated significantly with airway wall thickness. These observations suggest that air trapping is irreversible and that it represents structural remodeling of small airways in patients with stable asthma.

Administration, Inhalation↗
PubMed2006

Valsartan reduces serum cystatin C and the renal vascular resistance in patients with essential hypertension.

A high level of albuminuria and increased renal vascular resistance are associated with hypertensive renal damage. In this study, the authors investigated the effect of the angiotensin II receptor blocker, valsartan, on renal function and intrarenal hemodynamics in non-diabetic patients with essential hypertension. A prospective three-month study of the effects of valsartan, 40-80 mg/day, was performed in 30 hypertensive patients. As an assessment of renal function, serum creatinine, urine albumin/creatinine (Alb/Cr) ratio, and serum cystatin C levels were evaluated. Doppler ultrasonography of the kidney was performed for the evaluation of renal hemodynamics. Peak-systolic, end-diastolic, and mean velocities of interlobar arteries were evaluated, and the pulsatility index (PI) and resistive index (RI) were calculated. It was determined that patients with microalbuminuria had higher levels of serum cystatin C, PI, and RI compared to patients without microalbuminuria. Valsartan treatment significantly reduced systolic and diastolic blood pressure and decreased the Alb/Cr ratio. Serum creatinine was not changed, whereas serum cystatin C levels were significantly reduced. Valsartan treatment significantly decreased the PI in all patients and both PI and RI in patients with microalbuminuria. These results suggest that the angiotensin II receptor blocker, valsartan, is able to improve renal function by reducing renal vascular resistance in hypertensive patients, especially in patients with microalbuminuria, and may prevent future renal failure in patients with essential hypertension.

Adult↗
PubMed2006

Image fusion of coronary tree and regional cardiac function image using multislice computed tomography.

BACKGROUND: Although trials of image fusion, such as positron emission computed tomography and multislice spiral computed tomography (MSCT), have already demonstrated clinical usefulness, fusion of the coronary artery image and functional image by MSCT alone has not been reported yet. Here, a new idea of data analysis is proposed in which both regional cardiac function and the responsible coronary arteries can be assessed by a fused image. METHODS AND RESULTS: The study group comprised 5 patients with coronary artery disease. At the first procedure, 3 dimensional (D) volume rendering coronary artery (3D-CTA) was extracted. At the second procedure, the systolic regional wall thickening was calculated and the color 3D functional surface map of systolic wall thickening (3D-SWT) was generated. At the final procedure, 3D-SWT was superimposed on the left ventricular surface with 3D-CTA using a transparency. In all 5 patients, image fusion of the coronary tree and cardiac function was correctly generated. Image fusion can be displayed as clear 3D images, offering better orientation to help assess both the coronary artery and regional function. CONCLUSIONS: Image fusion of coronary computed tomography angiography and the functional map by MSCT is potentially a new method of assessing both the coronary artery and cardiac function.

Coronary Angiography↗
PubMed2006

Regression of atherosclerosis by amlodipine via anti-inflammatory and anti-oxidative stress actions.

We examined whether amlodipine, an L-type calcium channel blocker (CCB), has an inhibitory effect on oxidative stress and inflammatory response, and thereby atherosclerosis, in apolipoprotein E-deficient (ApoEKO) mice. Adult male ApoEKO mice (6 weeks of age) were fed a high-cholesterol diet (HCD) for 8 or 10 weeks with or without oral administration of amlodipine (3 mg/kg/day) for 10 weeks or for only the last 2 weeks of the HCD. After HCD feeding, atherosclerotic lesion formation, in situ superoxide production and nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase activity were evaluated in the proximal aorta. The expressions of NADPH oxidase subunits (p47(phox) and rac-1), monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were determined with immunohistochemistry and quantitative real-time reverse-transcription polymerase chain reaction. After 8 to 10 weeks of HCD administration to ApoEKO mice, marked atherosclerotic lesion formation was observed in the proximal aorta. In the atherosclerotic lesion, superoxide production, the expression of NADPH oxidase subunits, and NADPH oxidase activity were enhanced, and the expressions of MCP-1, ICAM-1, and VCAM-1 were increased. These changes were suppressed in mice that were treated with amlodipine for 10 weeks concomitant with HCD administration, with no significant change in blood pressure and plasma cholesterol level. We also observed that treatment with amlodipine for only the last 2 weeks regressed the atherosclerotic lesions with a decrease in oxidative stress and vascular inflammation. Inhibition of the atherosclerotic lesion area and lipid area in the proximal aorta by amlodipine was correlated with its inhibitory actions on oxidative stress, inflammation and the production of adhesive molecules. These results suggest that amlodipine not only inhibits atherosclerotic lesion formation, but also regresses atherosclerosis, and that these effects are at least partly due to inhibition of oxidative stress and inflammatory response.

Amlodipine↗
PubMed2006

Sex-related differences in the relations of insulin resistance and obesity to left ventricular hypertrophy in Japanese hypertensive patients.

Echocardiographically determined left ventricular (LV) hypertrophy is a powerful, independent predictor of cardiovascular morbidity and mortality. Both insulin resistance and obesity have a well-known association with LV hypertrophy. However, whether or not there are sex-related differences in the relations of insulin resistance and obesity to LV hypertrophy has never been systematically explored in Japan. We enrolled 91 never-treated hypertensive patients (49 men and 42 women) to assess the possible relations of insulin resistance and obesity to LV geometry. Insulin resistance was estimated using the homeostasis model assessment (HOMA) formula. Echocardiographically determined LV mass and relative wall thickness were measured as markers of LV geometry. In addition, body mass index (BMI) was calculated as weight (kg) divided by height (m)2 as a marker of obesity. Independent determinants of LV mass in male hypertensive patients were HOMA value (p < 0.0001) and age (p = 0.034). BMI did not bear a significant relation to LV mass. In comparison, in female hypertensive patients BMI was an independent determinant of LV mass (p = 0.011). The HOMA value did not bear a significant relation to LV mass in the female hypertensive patients. In conclusion, these findings indicate the presence of sex-related differences in the relations of insulin resistance and obesity to LV hypertrophy in Japanese hypertensive patients. The effect of obesity on LV geometry was greater in female hypertensive patients than in male hypertensive patients.

Aged↗
PubMed2006

Impairment of instantaneous autonomic regulation relates to blood pressure fall immediately after standing in the elderly and hypertensives.

The relation between changes in blood pressure and changes in autonomic activity over a very short period of time has not been reported thus far. To examine this relation, we here introduced a new method of power spectrum analysis with wavelet transformation, which has very fine time resolution and is able to assess changes in autonomic activity quantitatively even during movement. Our subjects were 15 hypertensive and 17 normotensive subjects. A head-up tilt test was performed in all subjects, and during the test, electrocardiogram and blood pressure were recorded continuously. The power spectrums for both parameters were calculated simultaneously every 5 s using wavelet transformation. The high frequency of the RR interval of the electrocardiogram (RR-HF) and low frequency of systolic blood pressure (SBP-LF) were defined and calculated as markers of parasympathetic and alpha-1 receptor blocker, bunazosin-sensitive sympathetic activity, respectively. Focusing on the changes for 2 min immediately after head-up tilting, it was found that the changes in SBP-LF and RR-HF were significantly delayed, by at least 40 s, in hypertensives compared with normotensives and also in elderly compared with non-elderly subjects. Multiple regression analysis demonstrated that the instantaneous change in RR-HF was the most important confounding factor for a fall in blood pressure immediately after head-up tilting. In conclusion, real-time changes in autonomic activity calculated by wavelet transformation may provide sensitive and useful information about acute changes in cardiovascular regulation, such as delayed reaction of the autonomic regulation after head-up tilting, that may be major causes of the blood pressure fall in hypertensive and elderly subjects.

Adult↗
PubMed2006

[Increasing menace of cardiovascular diseases in the era of obesity].

Epidemiological reports show that about half of all adults suffer from hypertension, and the incidence of diabetes mellitus, dyslipidemia and obesity is markedly increasing in Japan. Recent progress in gene determination has shown that lifestyle-related diseases, including hypertension, are multigenetic diseases. In particular, renin-angiotensin genes play an important role in the pathogenesis of hypertension. Upregulation of the transcription of angiotensinogen and angiotensin-converting enzyme genes increases blood pressure and cardiovascular organ damage through increased levels of angiotensin II. In this review, I first introduce the history of the recognition, understanding and the development of treatment for hypertension. Secondly, the basic relationship of the pathogenesis between hypertension and the new concept of metabolic syndrome will be shown, and the usefulness of angiotensin II receptor antagonist for hypertensive patients with obesity and/or metabolic syndrome. Finally, I will reveal the utility of gene diagnosis for acute myocardial infarction and cerebral infarction by detecting the polymorphism of renin-angiotensin genes. On the other hand, the positive correlation between blood pressure and body mass index is affected by the Gln27Glu genotype of the beta2-adrenoceptor gene. These studies investigating the gene-environmental relationship will contribute to the development of tailor-made medicine in the future.

Adiponectin↗