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Biomedical subjects

M Miyagawa

Publications and source records attributed to M Miyagawa.

At least 19 recordsLinked to original sources

Analysis of gene expression in peripheral blood eosinophils from patients with atopic dermatitis and in vitro cytokine-stimulated blood eosinophils.

Investigation of differentially expressed genes in eosinophils of patients with allergic diseases such as atopic dermatitis (AD) will provide important information for elucidating possible mechanisms of pathology. To identify novel genes that are expressed in AD, we compared gene expression in samples of peripheral blood eosinophils from AD patients and healthy volunteers. RNA was extracted from peripheral blood eosinophils. The expression of various genes, such as those for cytokine receptors, eosinophil activation marker, platelet activating factor (PAF) receptor, eosinophil-specific granular proteins and apoptosis-related genes, was confirmed using real-time reverse transcription-polymerase chain reaction (RT-PCR). Peripheral blood eosinophils of healthy volunteers were also isolated and stimulated for introduction of various cytokines. RNA was extracted and gene expression was monitored. Several genes, such as those for cytokine receptors (granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor alpha and beta chain and interleukin (IL)-3 receptor alpha chain), CD44 and PAF receptor were expressed at significantly higher levels in AD patients than in healthy volunteers. In addition, the anti-apoptotic genes, bcl-2 and bcl-xL, were expressed at increased levels in AD patients. No single gene expression correlated with clinical markers, such as eosinophil count or IgE levels. Expression of GM-CSF receptor beta chain and IL-3 receptor alpha chain in isolated blood eosinophils of healthy volunteers was stimulated by IL-5, IL-4, interferon (IFN)-gamma and GM-CSF. Expression of bcl-2 and bcl-xL was also increased after stimulation with IL-5, IL-4 or IFN-gamma. The in vitro enhancement of cytokine-stimulated gene expression correlated well with the enhancement observed in clinical samples of eosinophils, suggesting that cytokines may affect gene expression in vivo in eosinophils of patients with AD.

Adolescent↗

Twenty-four-hour Tl-201 delayed scan underestimates myocardial viability in patients with acute myocardial infarction after percutaneous transluminal coronary angioplasty.

BACKGROUND: Myocardial viability in area at risk of acute myocardial infarction (AMI) after reperfusion therapy may be underestimated by the 24-hour images due to reverse redistribution (r-RD). METHODS: Subjects were 37 AMI patients in whom Tc-99m pyrophosphate (PYP)/Tl-201 dual-isotope SPECT was positive. The 24-hour delayed scan was performed with only a Tl window. One month later, follow up rest Tl SPECT was performed to evaluate myocardial viability. In early (at PYP/Tl-201 dual-isotope SPECT), 24-hour, and one month follow up Tl studies, Tl uptake in the area of AMI was scored into four grades: 3 as normal to 0 as severely reduced. The scores were evaluated. RESULTS: Among the 37 AMI lesions, there were 16 r-RD, 3 RD, 16 fixed defect (FD) and 2 normal (positive PYP and normal Tl). Mean Tl scores were early; 1.4 +/- 1.1, 24-hr; 0.9 +/- 0.9 and one month; 1.3 +/- 1.1. The 24-hour Tl score was lower than the early and one month Tl scores (p < 0.01). CONCLUSION: Reverse redistribution is frequently observed in an area at risk where PYP SPECT was positive. Nuclear medicine physicians should be aware of the existence of frequent r-RD in Tl scan to avoid the underestimation of myocardial viability in the acute phase after PTCA.

Aged↗

Usefulness of (123)I-BMIPP with myocardial imaging for evaluation of the efficacy of drug therapy in patients with chronic heart failure.

BACKGROUND: Fatty acid is a main source of cardiac energy in aerobic conditions. We used iodine-123-beta-methyl-iodophenyl pentadecanoic acid ((123)I-BMIPP) myocardial scintigraphy to study the efficacy of the angiotensin-converting enzyme inhibitor (ACEI) enalapril in the treatment of chronic heart failure (CHF) by evaluating its therapeutic effects on myocardial fatty acid metabolism. METHODS AND RESULTS: New York Heart Association functional class status, left ventricular end-diastolic diameter, percent fractional shortening, the ratio between early and late peaks of flow velocity, (123)I-BMIPP myocardial-to-mediastinal uptake ratio, and mean washout rate were measured in 42 patients (31 men and 11 women; mean age, 58 +/- 3 years) with CHF before treatment and 3 months after treatment. There was a significant correlation between myocardial fatty acid metabolism and other variables as well as between the degree of improvement in myocardial fatty acid metabolism and the degree of improvement in other variables. CONCLUSIONS: Enalapril improved symptoms and cardiac function in patients with CHF. These improvements significantly correlated with improvement of (123)I-BMIPP metabolism in the myocardium. (123)I-BMIPP scintigraphy is useful for evaluating the efficacy of drug therapy for CHF based on myocardial fatty acid metabolism.

Angiotensin-Converting Enzyme Inhibitors↗

Gene expression accompanied by differentiation of cord blood-derived CD34+ cells to eosinophils.

To clarify the relation between the expression of genes such as eosinophil-specific granular proteins and cytokine receptors and the pathogenesis of allergic disease, cord blood-derived CD34+ cells were cultured and differentiated into eosinophils. Gene expression in the cells during the differentiation was determined by real-time reverse transcription PCR (ABI PRISM 7700). CD34+ mononuclear cells cultured with stem cell factor, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-3, and IL-5 in Iscove's MEM, and proliferated until the 2nd week, when the cell number reached a plateau. Under these conditions, more than 90% of the cells differentiate into mature eosinophils in 3 weeks. The expression of major basic protein and eosinophil-derived neurotoxin in the treated cells increased until week 2 and decreased between week 2 and 3. However, the expression of membrane receptor genes, such as IL-5 receptor (alpha chain), IL-3 receptor (alpha chain), GM-CSF-alpha receptor, GM-CSF-beta receptor, CC chemokine receptor 3, interferon-gamma receptor, platelet-activating factor receptor and leukotriene D4 receptor, increased until the 3rd week of eosinophil maturation. Our study suggests that the in vitro eosinophil differentiation and maturation model is useful for clarifying the relation between eosinophil-specific gene expression during allergic diseases and the progression of the disease.

Antigens, CD34↗

Prognostic value of iodine-123-metaiodobenzylguanidine imaging and cardiac natriuretic peptide levels in patients with left ventricular dysfunction resulting from cardiomyopathy.

This study assessed the prognostic value of Iodine-123-metaiodobenzylguanidine (MIBG) imaging and of the plasma level of cardiac natriuretic peptides in patients with left ventricular dysfunction resulting from cardiomyopathy. Predictors of cardiac death or hospitalization related to progressive heart failure were examined in 171 patients with chronic heart failure (96 patients with idiopathic cardiomyopathy and 75 patients with ischemic cardiomyopathy). All patients underwent MIBG imaging at rest and other hemodynamic studies. During a mean (+/-SD) follow-up period of 27+/-11 months, 11 patients died from heart failure and 16 required hospitalization. High MIBG washout was an independent predictor of cardiac death (relative risk [RR] = 1.158, p<0.0001) whereas the plasma level of brain natriuretic peptide (BNP: relative risk [RR] = 1.005, p<0.0001) and high MIBG washout (relative risk [RR] = 1.094, p<0.0001) were predictors of progressive heart failure (ie, combined cardiac death and hospitalization). Accelerated myocardial adrenergic nerve activity as assessed by MIBG imaging and the plasma levels of BNP are powerful predictors of the patient's prognosis.

3-Iodobenzylguanidine↗

Stress and coping behavior in patients with diabetes mellitus.

Diabetes mellitus is a disease which must be controlled over the lifetime of a patient. We investigated the issues of stress and coping for diabetes mellitus which may influence self-management. In addition, we examined the association of these factors with blood glucose control, in order to review self-management instructions for diabetes mellitus. The study included 153 patients with diabetes mellitus. The patients were divided into two subgroups: good-control group, comprising patients with glycohemoglobin (HbA1c) values less than 7.0%; and poor-control group, comprising those with HbA1c values of 7.0% or more. All patients responded to a questionnaire regarding stress tolerance, Jalowiec and Power's coping scale and awareness of diabetes mellitus. Stress tolerance was not significantly different between the good-control and poor-control groups. No significant gender differences in coping score were evident for the good-control group. However, in the poor-control group, the coping score in men was significant higher than that in women. The problem-oriented coping score for men in the poor-control group was significantly higher than that for the good-control group (p < 0.01). In a comparison of awareness of diabetes mellitus, the proportion of patients who replied that they were rigidly following diabetes treatment was higher in the poor-control group than the good-control group. Patients with diabetes mellitus may have a knowledge of the disease and a strong will to resolve problems. This is especially true for male patients in that their will appeared to be stronger, but they may not have the resolve to establish appropriate behavior patterns. In the future, methods for evaluating self-management should be included in diabetes education.

Adaptation, Psychological↗

The influence of left ventricular geometry on coronary vasomotion in patients with essential hypertension.

The objective of this study was to assess the influence of left ventricular (LV) geometric pattern on coronary vasomotion in patients with essential hypertension. We studied 34 hypertensive patients, who had never been treated, with angiographically normal coronary arteries. Patients were classified into four LV geometric patterns by echocardiography: normal, concentric remodeling, eccentric hypertrophy, and concentric hypertrophy. The responses of coronary vasomotion in left anterior descending artery to vasoactive agents (acetylcholine, isosorbide dinitrate, adenosine triphosphate) were examined using a Doppler guidewire and quantitative coronary angiography. The percent increase in coronary blood flow evoked with acetylcholine (endothelium-dependent vasomotion) showed lowest in concentric hypertrophy, followed by eccentric hypertrophy, concentric remodeling, and normal geometry. The significant linear relationship between acetylcholine-induced coronary blood flow and LV mass was noted. There was no difference in the percent increase in coronary blood flow evoked with isosorbide dinitrate (endothelium-independent vasomotion of conduit vessel) among the four groups. The percent increase in coronary blood flow evoked with adenosine triphosphate (endothelium-independent vasomotion of resistant vessel) was significantly lower in patients with concentric hypertrophy than in the other three groups. The results in this study suggest that coronary vasomotion may be associated with LV geometry in patients with hypertension. The endothelium-dependent vasodilation is impaired progressively as LV hypertrophy advances. The endothelium-independent vasodilation of microvessels is impaired only in concentric hypertrophy. This advanced abnormality of coronary vasomotion may contribute to the high cardiovascular morbidity and mortality in patients with concentric hypertrophy.

Acetylcholine↗

Tc-99m PMT hepatobiliary scintigraphy in the differential diagnosis of extrahepatic metastases and hepatocellular carcinoma.

PURPOSE: The authors evaluated the utility of hepatobiliary scintigraphy for tissue characterization of extrahepatic metastases from hepatocellular carcinoma (HCC) using Tc-99m N-pyrydoxyl-5-methyltriptophane (Tc-99m PMT). METHODS: We examined 13 patients with HCC (29 extrahepatic metastases and 3 benign bone lesions) and 5 patients with other cancers (15 extrahepatic metastases). Thirty minutes to 6 hours after intravenous administration of Tc-99m PMT, planar (all 47 lesions) and SPECT (42 lesions) images were obtained. Accumulation of Tc-99m PMT in the lesion was evaluated visually by comparing bone scintigraphy, computed tomography, magnetic resonance imaging, or all of these. RESULTS: Findings were positive in 12 of 13 patients with HCC and extrahepatic metastases (16 of 29 on planar imaging and 21 of 26 on SPECT). Findings in all three benign bone lesions and 15 metastatic lesions from non-HCC primary lesions were negative (0 of 18 on planar imaging, 0 of 16 on SPECT). There were no false-positive findings in these lesions. Lesion-by-lesion sensitivity, specificity, accuracy, and positive and negative predictive values were 55%, 100%, 72%, 100%, and 58% by planar imaging and 81%, 100%, 88%, 100%, and 76% by SPECT, respectively. CONCLUSIONS: Because of the high specificity and reasonable sensitivity, Tc-99m PMT appears to be useful for the differential diagnosis of extrahepatic metastases from HCC. SPECT improves the detectability of small or faint accumulation in metastases from HCC.

Aged↗

Antiphospholipid syndrome with acute myocardial infarction and portal vein occlusion: a case report.

A 62-year-old woman was admitted to hospital because of chest oppression and abdominal discomfort. Coronary arteriography revealed that the proximal left anterior descending artery had a large thrombus with TIMI (Thrombolysis in Myocardial Infarction) Grade 3 flow. On the second hospital day, she had sudden hematemesis because of esophageal varices. Her general condition became stable with conventional therapy. On the 20th hospital day, coronary arteriography and arterial portography showed that the thrombus had diminished. Arterial portography also revealed total occlusion of the portal vein as well as giant gastric varices. She was diagnosed as antiphospholipid syndrome, based on the presence of lupus anticoagulant. The treatment of this case was very complicated because of the bleeding from the esophageal varices induced by the anticoagulant therapy for the thrombus. Prednisolone was administered for 1 month, but no remarkable effects were observed. Therefore, she was treated with endoscopic sclerotherapy for the esophageal varices and anticoagulant therapy for prevention of thrombosis.

Acute Disease↗

Two- and three-dimensional CT ventriculography: a new application of helical CT.

OBJECTIVE: We propose a new application of helical CT, CT ventriculography, which can produce two-dimensional (2D) and three-dimensional (3D) images of different cardiac phases (plus animation). We sought to determine the accuracy of CT ventriculography for assessing left ventricular volumes. MATERIALS AND METHODS: With a single breath-hold, the patient's entire heart was scanned with an ECG-gating technique (3-mm-thick collimation, 2 mm per rotation table speed, 0.8 sec per rotation, and 50 rotations through 10 cm in total). Using a 0.2-mm (0.08-sec) interval (10 slices per rotation) overlapping reconstruction, about 500 axial slices were obtained and reordered to separate different cardiac cycles. Then, 2D cardiac axes and 3D images were reconstructed and animated movies of the 2D and 3D images were produced. In 21 patients, the left ventricular end-diastolic volume, end-systolic volume, and ejection fraction were assessed and compared with left ventriculography. Correlations and agreements between CT and left ventriculography were determined. RESULTS: Close correlations between CT and left ventriculography were obtained (r = 0.95, 0.98, and 0.91, for end-diastolic volume, end-systolic volume, and left ventricular ejection fraction, respectively; p < 0.0001 for all values). The limits of agreement between CT and left ventriculography were 44.3 to -44.5 ml for end-diastolic volume, 19.8 to -29.0 ml for end-systolic volume, and 19.7% to -9.5% for left ventricular ejection fraction. CONCLUSION: This cardiac application of helical CT provides a clear morphology along the cardiac axes and 3D images and an assessment of left ventricular volumes (end-diastolic volume, end-systolic volume, and left ventricular ejection fraction).

Adult↗

Rat liver in vivo replicative DNA synthesis test for short-term prediction of nongenotoxic (Ames-negative) hepatocarcinogenicity: a collaborative study of the Nongenotoxic Carcinogen Study Group of Japan.

A collaborative study was conducted to evaluate whether a replicative DNA synthesis (RDS) test using the rat liver can detect nongenotoxic (Ames-negative) hepatocarcinogens with three or seven daily administrations at dose-levels effective in long-term bioassays. The assay methods were well-validated by the 14 participants. Of six compounds tested, carbon tetrachloride (50 and 100 mg/kg), clofibrate (125 and 250 mg/kg), diethylstilbestrol (0.125 and 0.25 mg/kg) and urethane (100 mg/kg) gave positive results, methyl carbamate (200 and 400 mg/kg) exerted equivocal effects, and D,L-ethionine (125 mg/kg) failed to elevate RDS. These findings suggest that the RDS test can detect many nongenotoxic rat hepatocarcinogens with short-term administration at dose-levels used in long-term bioassays.

Animals↗

Repeat-assessment of 1,4-dioxane in a rat-hepatocyte replicative DNA synthesis (RDS) test: evidence for stimulus of hepatocyte proliferation.

1,4-Dioxane is a nongenotoxic hepatocarcinogen but in our previous replicative DNA synthesis (RDS) studies with the [3H]thymidine (TdR)-technique, it failed to increase hepatocyte RDS values when given by gavage to male F344 rats as a single 2000 mg/kg body weight dose. However, in a current series of trials with TdR, it showed equivocal responses 24 or 48 hr following treatment with 2000 mg/kg in time-course experiments, and positive responses 24 hr following 1000, 1500 and 2000 mg/kg in dose-response experiments. An increased RDS incidence was also observed at the dose of 2000 mg/kg with data for 5-bromo-2'-deoxyuridine (BrdU)-incorporation. These present findings thus support the hypothesis that a capacity to induce cell proliferation may play a key role in 1,4-dioxane hepatocarcinogenesis.

Animals↗

Relationship between insulin resistance and cardiac sympathetic nervous function in essential hypertension.

BACKGROUND: It has been suggested that hyperinsulinemia and insulin resistance participate in the pathogenesis of hypertension, in part by activating sympathetic activity. OBJECTIVE: We aimed to examine the relationship between insulin resistance and cardiac sympathetic nervous function in patients with essential hypertension using 123I-metaiodobenzylguanidine (MIBG) cardiac scintigraphy. METHODS AND RESULTS: Twenty-eight patients (18 men) with essential hypertension and 11 (seven men) control individuals with a mean age of 55.8+/-3.3 years were recruited. Patients with diabetes mellitus, congestive heart failure or coronary artery disease were excluded from this study. To evaluate insulin resistance, we used steady-state plasma glucose (SSPG; mg/dl) levels measured by the SSPG method. To evaluate cardiac sympathetic nervous function, we calculated the heart-to-mediastinum ratio from the delayed MIBG image (H:M-D) and the mean washout rate (WOR, %). There were significant differences (P<0.01) in SSPG, H:M-D and WOR between the essential hypertension and control individual groups (125 versus 103 mg/dl, 2.2 versus 2.4, and 32 versus 23%, respectively). Stepwise regression analysis showed that SSPG and plasma norepinephrine level are independent predictors for the cardiac sympathetic nervous function obtained from MIBG scintigraphy. CONCLUSIONS: These findings indicate that insulin resistance is significantly related to activation of the cardiac sympathetic nervous function associated with left ventricular hypertrophy in patients with essential hypertension.

3-Iodobenzylguanidine↗

Prognostic value of dipyridamole-thallium myocardial scintigraphy in patients with Kawasaki disease.

BACKGROUND: Although coronary artery lesions are critical complications of Kawasaki disease, their long-term outcome is still unclear. It is sometimes difficult to monitor progressive changes from aneurysms to stenotic lesions because coronary angiography (CAG) cannot be repeated very often, especially in infants. Our prospective study was designed to evaluate the prognostic value of dipyridamole-thallium single-photon-emission CT (SPECT) in the long-term follow-up of patients with Kawasaki disease. METHODS AND RESULTS: Of 459 consecutive patients with Kawasaki disease, coronary aneurysms were detected in 90 cases by echocardiography during the acute stage. After paired studies of selective CAG and SPECT were conducted, all patients were followed up and monitored for the occurrence of any cardiac events for > or =8 years. During the follow-up interval, there were 15 cardiac events (1 death, 5 infarctions, 2 coronary artery bypass graft operations, and 7 occurrences of unstable angina). Of patients who had some event, thallium redistribution was found on SPECT in 14 (93%, P<0.001). Of the various clinical and scintigraphic image variables, the presence of thallium redistribution was the best multivariate independent predictor of a late cardiac event (chi2=57.8, P<0.0001). The number of aneurysms detected on CAG added minimal statistical improvement to the model (chi2=1.9, P=0.0009). CONCLUSIONS: Dipyridamole-thallium SPECT is safely performed and is useful and important for risk stratification in the long-term follow-up of patients with Kawasaki disease.

Age of Onset↗

Effects of probucol and cilostazol alone and in combination on frequency of poststenting restenosis.

The present study was conducted to assess the preventive effect of combined treatment with probucol, an antioxidant, and cilostazol, a phosphodiesterase inhibitor, against poststenting restenosis. Study patients were randomized to 4 modality groups 1 week before stenting: control, probucol (500 mg/day), cilostazol (200 mg/day), and probucol plus cilostazol. Treatment on these modalities was conducted from 5 prestent days until the poststenting follow-up evaluation (6 poststenting months). All patients received aspirin (81 mg/day). The efficacy of each modality against restenosis was evaluated in a total 126 patients with 165 coronary arterial lesions, using a quantitative method. The decrease in luminal diameter at the poststenting follow-up was 1.04 +/- 0.57 mm for controls, 0.88 +/- 0.82 mm for those taking probucol, 0.61 +/- 0.59 mm for those taking cilostazol (p <0.05 vs control), and 0.40 +/- 0.52 mm (p <0.01 vs control) for the combined treatment group. Restenosis rate per segment was 31.7% for controls, 16.7% for the probucol group, 12.5% for the cilostazol group (p <0.05 vs control), and 9.5% for the combined treatment group (p <0.05 vs the control). Neither mortality, myocardial infarction, stent thrombosis, or coronary bypass surgery, nor any serious complications were observed in the combined treatment group. Combined treatment with probucol and cilostazol has thus proved safe and effective in preventing acute poststenting complications and suppressing chronic restenosis.

Adult↗

Effects of chemical stimulation of the rostral ventrolateral medulla on cerebral and renal microcirculation in spontaneously hypertensive rats.

We investigated whether microcirculatory responses elicited by excitation of intrinsic neurons in the rostral ventrolateral medulla (RVLM) are altered in spontaneously hypertensive rats (SHR). SHR and Wistar-Kyoto rats (WKY) were anesthetized with chloralose, paralyzed with tubocurarine, and artificially ventilated. Cerebral and renal blood flows (CBF and RBF) were simultaneously measured using laser-Doppler flowmetry. Chemical stimulation of the RVLM neurons by microinjection of L-glutamate increased arterial pressure (AP) and heart rate in both SHR and WKY. Stimulation of the RVLM neurons also elicited stimulus-locked increase in CBF and decrease in RBF in both groups. The % changes in CBF and RBF were dose-dependent as stimulus intensity was increased and did not differ significantly between the SHR and WKY groups. Cerebral and renal vascular resistance (CVR and RVR) levels were calculated from changes in CBF or RBF and those in mean AP. The percent reduction in CVR and percent elevation in RVR were dose-dependent and did not differ significantly between the two groups. The data indicate that cerebral and systemic microcirculatory responses elicited by excitation of the RVLM neurons do not differ between SHR and WKY.

Animals↗