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Biomedical subjects

Y Kagaya

Publications and source records attributed to Y Kagaya.

At least 19 recordsLinked to original sources
PubMed2005

Feasibility of rapid-sequence 31P magnetic resonance spectroscopy in cardiac patients.

PURPOSE: To determine the clinical feasibility of rapid-sequence phosphorus-31 magnetic resonance spectroscopy (31P-MRS) of the heart with cardiac patients using a 1.5T clinical MR system. MATERIAL AND METHODS: Twenty cardiac patients, i.e. dilated cardiomyopathy (DCM) 13 cases, hypertrophic cardiomyopathy (HCM) 3 cases, hypertensive heart diseases (HHD) 3 cases, and aortic regurgitation (AR) 1 case were examined using rapid cardiac 31P-MRS. Complete three-dimensional localization was performed using a two-dimensional phosphorus chemical-shift imaging sequence in combination with 30-mm axial slice-selective excitation. The rapid-sequence 31P-MRS procedure was phase encoded in arrays of 8 x 8 steps with an average of 4 acquisitions. The total examination time, including proton imaging and shimming, for the rapid cardiac 31P-MRS procedure, ranged from 10 to 15 min, depending on the heart rate. Student's t test was used to compare creatine phosphate (PCr)/adenosine triphosphate (ATP) ratios from the cardiac patients with those of the control subjects (n = 13). RESULTS: The myocardial PCr/ATP ratio obtained by rapid 31P-MRS was significantly lower (P < 0.001) in DCM patients (1.82 +/- 0.33, mean +/- SD), and in patients with global myocardial dysfunction (combined data for 20 patients: 1.89 +/- 0.32) than in normal volunteers (2.96 +/- 0.59). These results are similar to previous studies. CONCLUSION: Rapid-sequence 31P-MRS may be a valid diagnostic tool for patients with cardiac disease.

Adenosine Triphosphate↗
PubMed2001

Gene expression and in situ localization of diacylglycerol kinase isozymes in normal and infarcted rat hearts: effects of captopril treatment.

Diacylglycerol (DG) kinase (DGK) terminates signaling from DG, which serves as an activator of protein kinase C (PKC), by converting DG to phosphatidic acid. DGK is thus regarded as an attenuator of the PKC activity. In rats, five DGK isozymes have been cloned, but little is known about their role in the heart. In this study, the spatiotemporal expression of DGK isozymes was investigated in rat hearts under a normal condition and after myocardial infarction (MI) by in situ hybridization histochemistry and immunohistochemistry. In normal left ventricular myocardium, DGKalpha, DGKepsilon, and DGKzeta mRNAs were expressed evenly throughout the myocardium, although the DGKalpha expression was very low. In infarcted hearts, the expression of DGKzeta was enhanced in the peripheral zone of the necrotic area and at the border zone 3 and 7 days after MI, and to a lesser extent in the middle layer of the granulation tissue 21 days after MI. The enhanced DGKzeta expression in the infarcted and border areas could be attributed to granulocytes and macrophages. In contrast, the expression of DGKepsilon in the infarcted and border areas was lower than that in the viable left ventricle (LV) throughout the postoperation period. Furthermore, DGKepsilon expression in the viable myocardium 21 days after MI decreased significantly compared with left ventricular myocardium in the sham-operated rats and was completely restored by treatment with captopril. Our results demonstrate that three DGK isozymes are expressed in the heart and that each isozyme might have different functional characteristics in the healing and LV remodeling after MI.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Increased von Willebrand factor in the endocardium as a local predisposing factor for thrombogenesis in overloaded human atrial appendage.

OBJECTIVES: We investigated immunoreactive von Willebrand factor (vWF), a platelet adhesion molecule, in the endocardial endothelium and its relationship to thrombogenesis in the human atrial appendage. BACKGROUND: Intra-atrial thrombogenesis is generally thought to be induced by blood stasis in the atrial appendage involved with atrial fibrillation (AF). Little attention has been paid to alterations of the endocardial endothelium on which the thrombus develops. METHODS: Atrial appendage tissue was obtained at heart surgery or at autopsy from AF and non-AF cardiac patients and from noncardiac patients. Immunohistochemistry for endothelial cell markers including vWF, CD31, CD34 and endothelial nitric oxide synthase (eNOS) and platelet glycoprotein Ib/IX or IIb/IIIa was performed and semiquantitatively graded. RESULTS: In contrast to the apparent immunostaining for CD31, CD34 and eNOS, only focal or little immunoreactive vWF was seen in the endocardium of noncardiac patients. Immunoreactive vWF in the endocardial endothelium was increased in most cardiac patients, particularly in the left, but not in the right, atrial appendage of patients with mitral valvular disease, irrespective of whether AF was present. Platelet adhesion/thrombus formation in the endocardium was found in limited sites in which the overlying endothelium was deficient in eNOS and CD34. When warfarin-treated cases were excluded, there was a significant correlation between the immunohistochemical grade for vWF and the degree of platelet adhesion/thrombus formation in the endocardium. CONCLUSIONS: Immunoreactive vWF in the endocardial endothelium was increased in overloaded human atrial appendage, which may be a local predisposing factor for intraatrial thrombogenesis.

Adult↗
PubMed2001

[18F] labeled diacylglycerol analogue as a potential agent to trace myocardial phosphoinositide metabolism.

Phosphoinositide metabolism plays an important role in cardiac pathophysiology. To investigate whether [18F]diacylglycerol could be used to trace myocardial phosphoinositide metabolism, lipids were extracted from rat myocardium after the injection. 1-[8-[18F]fluorooctanoyl]-2-palmitoylglycerol and 1-[8-[18F]fluoropalmitoyl]-2-palmitoylglycerol were predominantly metabolized to phosphatidylethanolamine and triacylglycerol, respectively. The radioactivity incorporated into phosphoinositide metabolism was 51, 44, 32, and 30% 3, 5, 10, and 30 minutes after the injection of 1-[4-[18F]fluorobutyryl]-2-palmitoylglycerol, respectively. 1-[4-[18F]fluorobutyryl]-2-palmitoylglycerol might be a potential tracer to evaluate myocardial phosphoinositide metabolism early after the injection.

Animals↗
PubMed2001

Contribution of Na+/Ca2+ exchanger to the regulation of myogenic tone in isolated rat small arteries.

The contribution of the Na+/Ca2+ exchanger to the myogenic vascular tone was examined in rat isolated skeletal muscle small arteries (ASK) with pronounced myogenic tone and mesenteric small arteries (AMS) with little myogenic tone. Myogenic tone was assessed by the vascular inner diameter at transmural pressures of 40 and 100 mmHg. To depress the Na+/Ca2+ exchanger, the extracellular Na+ concentration ([Na+]o) was lowered from 143 to 1.2 mM by substituting choline-Cl for NaCl. The ASK developed significant myogenic tone and constricted further in low [Na+]o. Nifedipine (1 microM) reduced both myogenic tone and low [Na+]o-induced contraction. Because the membrane potential of ASK was not changed by low [Na+]o (-35 +/- 2 mV at 143 mM [Na+]o, -37 +/- 3 mV at 1.2 mM [Na+]o), depolarization-induced Ca2+ influx was not a cause of the low [Na+]o-induced contraction. The AMS did not develop significant myogenic tone. Although low [Na+]o also constricted AMS, the magnitude of constriction was significantly weaker than that in ASK (17 +/- 4 vs. 47 +/- 6%, P < 0.01, at 58 mM Na+). With Bay K 8644, AMS developed myogenic tone, and low [Na+]o-induced constriction was significantly increased. In conclusion, Na+/Ca2+ exchanger may play an important role in regulating myogenic tone, likely via mediating Ca2+-extrusion.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed2001

Microvolt T wave alternans in human cardiac hypertrophy: electrical instability and abnormal myocardial arrangement.

INTRODUCTION: Although T wave alternans (TWA) is a promising risk marker for myocardial electrical instability, it remains unclear how the presence of TWA is related to myocardial damage. METHODS AND RESULTS: TWA was measured in 28 patients with hypertrophic cardiomyopathy (HCM), 29 patients with hypertensive left ventricular hypertrophy (HLVH), and 15 normal volunteers using a CH2000 system. The amplitude of TWA (Valt) was measured at the lead with the maximum amplitude. Cardiac biopsy was performed in 12 HCM patients, who were divided into two groups (severe and mild) based on histologic findings of myocardial disarray and fibrosis. TWA was positive (Valt > 1.9 microV) in 61% of HCM and 31% of HLVH, despite a nearly identical left ventricular mass index (176 +/- 65 g/m2 vs 175 +/- 39 g/m2). Valt at heart rate = 110 beats/min was significantly greater in HCM with severe disarray and fibrosis than in HCM with mild disarray and in HLVH. CONCLUSION: In HCM patients, a positive TWA test probably is related to abnormal myocardial arrangement (disarray) and/or fibrosis, and it may reflect electrical instability of the myocardium.

Aged↗
PubMed2001

Nonselective endothelin receptor antagonist initiated soon after the onset of myocardial infarction may deteriorate 24-hour survival.

To investigate the effects of endothelin blockade initiated immediately after the onset of myocardial infarction on survival and left ventricular remodeling, treatment with the nonselective receptor antagonist TAK-044 (n = 22) or saline (n = 19) for 3 weeks was initiated immediately after coronary ligation in rats. The 24-h survival rate was significantly lower in the TAK-044 group than in the saline group. The systolic blood pressure 24 h after the onset of myocardial infarction was similar in the saline and TAK-044 groups, although it was significantly lower in the TAK-044 group during the 3-week protocol. Heart weight/tibial length was significantly increased in the TAK-044 group compared with the saline group. As all deaths in the TAK-044 group occurred within 24 h after myocardial infarction, we performed additional experiments using a separate group of rats 12-16 h after myocardial infarction. Plasma and myocardial endothelin-1 levels were significantly increased, and a bolus injection of TAK-044 significantly reduced left ventricular dP/dtmax in these rats that had had a myocardial infarction compared with sham-operated rats. Endothelin receptor blockade initiated immediately after the onset of myocardial infarction may deteriorate acute-phase survival and left ventricular remodeling. Inhibition of the positive inotropic action of endothlin-1 may partially explain the increased 24-h mortality.

Animals↗
PubMed2001

Stretch and quick release of rat cardiac trabeculae accelerates Ca2+ waves and triggered propagated contractions.

Rapid shortening of active cardiac muscle [quick release (QR)] dissociates Ca2+ from myofilaments. We studied, using muscle stretches and QR, whether Ca2+ dissociation affects triggered propagated contractions (TPCs) and Ca2+ waves. The intracellular Ca2+ concentration was measured by a SIT camera in right ventricular trabeculae dissected from rat hearts loaded with fura 2 salt, force was measured by a silicon strain gauge, and sarcomere length was measured by laser diffraction while a servomotor controlled muscle length. TPCs (n = 27) were induced at 28 degrees C by stimulus trains (7.5 s at 2.65 +/- 0.13 Hz) at an extracellular Ca2+ concentration ([Ca2+]o) = 2.0 mM or with 10 microM Gd3+ at [Ca2+]o = 5.2 +/- 0.73 mM. QR during twitch relaxation after a 10% stretch for 100-200 ms reduced both the time between the last stimulus and the peak TPC (PeakTPC) and the time between the last stimulus and peak Ca2+ wave (PeakCW) and increased PeakTPC and PeakCW (n = 13) as well as the propagation velocity (Vprop; n = 8). Active force during stretch also increased Vprop (r = 0.84, n = 12, P < 0.01), but Gd3+ had no effect (n = 5). These results suggest that Ca2+ dissociation by QR during relaxation accelerates the initiation and propagation of Ca2+ waves.

Actin Cytoskeleton↗
PubMed2001

Declining trend in the in-hospital case-fatality rate from acute myocardial infarction in Miyagi Prefecture from 1980 to 1999.

The case-fatality rate from acute myocardial infarction (AMI) appears to have been declining in recent decades, so the present study reviewed the trend in in-hospital case-fatalities from AMI in Miyagi Prefecture, Japan, 1980-1999. The causes of death and the effects of gender and age on the trend were also analyzed. From the AMI registration database of the Miyagi Study Group for AMI, 12,961 cases of AMI were analyzed. The 30-day in-hospital case-fatality was calculated from the data for 1980-1999: data for causes of death were available for 1980-1997, and the data concerning primary percutaneous transluminal coronary angioplasty (PTCA) for AMI were available for 1997-1999. The in-hospital case-fatality rate declined from 17.0% in the early 80s to 7.3% in the late 90s (approximately 57% reduction). The in-hospital case-fatality rate was higher in female patients. Rhythm failure substantially decreased in the late 1980s. Pump failure is decreasing, but is still the biggest problem. The in-hospital case-fatality rate was significantly lower in patients received PTCA. The declining trend in the in-hospital case-fatality rate suggests the benefits of current therapeutic procedures, including primary PTCA, for AMI. Pump failure is an important target for further decreasing the trend.

Adult↗
PubMed2001

Effect of transient stretch on intracellular Ca2+ during triggered propagated contractions in intact trabeculae.

Transient stretch of cardiac muscle during a twitch contraction may dissociate Ca2+ from myofilaments into the cytosol at the moment of quick release of the muscle. We studied the effect of stretch and quick release of trabeculae on changes in intracellular Ca2+ ([Ca2+]i) during triggered propagated contractions (TPCs). Trabeculae were dissected from the right ventricle of 9 rat hearts. [Ca2+]i was measured using electrophoretically injected fura-2. Force was measured using a silicon strain gauge and sarcomere length was measured using laser diffraction techniques. Reproducible TPCs (n = 13) were induced by trains of electrical stimuli (378 +/- 19 ms interval) for 7.5 s at [Ca2+]o of 2.0 mM (27.9 +/- 0.2 degrees C). The latency of the TPC force and the underlying increase in [Ca2+]i was calculated from the time (TimeF) between the last stimulus and the peak of TPC force (PeakF), or the time (TimeCa) between the last stimulus and the peak of the increase in [Ca2+]i during the TPCs (PeakCa). As a result of a 10% increase in muscle length for 150-200 ms during the last stimulated twitches, TimeF and TimeCa decreased and PeakF and PeakCa increased significantly (n = 13). In addition, transient stretch sometimes induced a twitch contraction subsequent to the accelerated TPC and its underlying increase in [Ca2+]i. These results suggest that Ca2+ binding and dissociation from the myofilaments by the stretch and quick release of muscle may modulate the TPC force and the underlying increases in [Ca2+]i and play an important role in the induction of arrhythmias.

Actin Cytoskeleton↗
PubMed2000

Long-term right ventricular volume overload increases myocardial fluorodeoxyglucose uptake in the interventricular septum in patients with atrial septal defect.

BACKGROUND: Several studies have shown that long-term right ventricular (RV) overload in animal models alters myocardial energy substrate metabolism. However, whether long-term RV volume overload alters this metabolism in the human is unclear. METHODS AND RESULTS: We performed positron emission tomography with [(18)F]fluorodeoxyglucose (FDG) and single-photon emission tomography (SPECT) with [(201)Tl]TlCl (Tl) and [(123)I]15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) in 11 patients with atrial septal defect (ASD) and 11 control subjects. In the FDG study, we calculated myocardial metabolic rate of glucose (MMR) in interventricular septum (IVS) and left ventricular (LV) free wall. MMR was significantly increased in IVS compared with LV free wall in the ASD patients (420+/-35 versus 333+/-32 mol x kg(-1) x min(-1); P<0.05) but not in the control group (347+/-27 versus 357+/-25 mol x kg(-1) x min(-1)). In both ASD and control groups, SPECT count was not significantly different between IVS and LV free wall in Tl (ASD, 160+/-11 versus 177+/-12; control, 141+/-12 versus 157+/-14 counts per 15 minutes) and BMIPP studies (ASD, 203+/-14 versus 212+/-18; control, 162+/-16 versus 176+/-16 counts per 15 minutes). MMR in the IVS/LV free wall ratio in the ASD group significantly correlated with indices related to RV volume overload. CONCLUSIONS: Given the assumption that long-term RV volume overload did not affect the lumped constant, the present study suggests that, unlike myocardial perfusion or fatty acid analogue uptake, myocardial glucose utilization in IVS relative to LV free wall is increased in relation to long-term RV volume overload in patients with ASD.

Adult↗
PubMed2000

Regional and temporal profiles of phorbol 12,13-dibutyrate binding after myocardial infarction in rats: effects of captopril treatment.

Phosphoinositide turnover and protein kinase C (PKC) mediate the signaling of angiotensin II, which plays a pivotal role in ventricular remodeling after myocardial infarction (MI). To determine whether PKC is activated after MI, rat hearts after MI were subjected to in vitro quantitative autoradiography with [3H]phorbol 12,13-dibutyrate (PDBu), which is highly selective for PKC. [3H]PDBu binding in the infarcted area increased significantly compared with the non-infarcted region 7 and 21 days after MI, but not 1 and 3 days and 10 months after MI. [3H]PDBu binding in the noninfarcted area was similar to that in the sham-operated rats. Immunohistochemical analysis revealed that abundant macrophages (7 days after MI), fibroblasts, and myofibroblasts (7 and 21 days after MI) occupied the infarcted region. To investigate whether myocardial [3H]PDBu binding is affected by captopril, hearts were subjected to in vitro autoradiography with [3H]PDBu after 1- or 3-week captopril treatment or no treatment. Captopril treatment significantly suppressed [3H]PDBu binding in the infarcted area 3 weeks after MI, but not 1 week after MI nor in the noninfarcted areas. These results suggest that PKC is upregulated during the healing and fibrogenic process after MI and that captopril treatment suppresses the upregulation in the infarcted area.

Analysis of Variance↗
PubMed2000

Interaction between L-type Ca2+ channels and sarcoplasmic reticulum in the regulation of vascular tone in isolated rat small arteries.

A dysfunction of the sarcoplasmic reticulum (SR) causes an increase in the myogenic tone of rat skeletal muscle small arteries (A(SK)), but not that of mesenteric small arteries (A(MS)). We hypothesized that the difference depends on the activity of voltage-dependent Ca2+ channels in these vessels. To test this, we measured the membrane potential of these vessels and examined ryanodine-induced constrictions by manipulating the activity of voltage-dependent Ca2+ channels. The isolated vessels were cannulated to control the transmural pressure. To assess the vascular tone, the inner diameter was measured with a video-digitizing system. The membrane potential of A(SK) was more depolarized between 20 to 100 mm Hg of transmural pressure. A(MS) was not constricted by the Ca2+ channel agonist Bay K 8644 (1 nM(-1) microM) alone, but substantially constricted in the presence of ryanodine (1 microM). Ryanodine also augmented the KCl (20 mM)-induced constriction. In A(SK), the Ca2+ channel blocker nisoldipine fully dilated the ryanodine-induced constriction: however, the ryanodine-induced constriction was less susceptible to nisoldipine than was the myogenic and phenylephrine-induced constriction caused mainly by increased Ca2+ influx. In conclusion, the contribution of the SR function to Ca2+ metabolism depends on the activity of dihydropyridine-sensitive Ca2+ channels. The dysfunction of SR by ryanodine may impair the Ca2+ extrusion rather than increase Ca2+ influx in rat small arteries.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed2000

Visualization of myocardial phosphoinositide turnover with 1-[1-(11)C]-butyryl-2-palmitoyl-rac-glycerol in rats with myocardial infarction.

UNLABELLED: Phosphoinositide turnover mediates the signaling of angiotensin II, which plays a pivotal role in ventricular remodeling after myocardial infarction (MI). We tested the hypothesis that phosphoinositide turnover can be visualized by 1-[1 -(11)C]butyryl-2-palmitoyl-rac-glycerol (11C-DAG) in both infarcted and noninfarcted myocardium after MI in rats. METHODS: Rats received an injection of 11C-DAG 7 d after left coronary artery ligation, and myocardial lipids were extracted from both infarcted and noninfarcted areas of myocardium (n = 3). Metabolites of 11C-DAG were determined by thin-layer chromatography. Quantitative autoradiography of hearts was performed to visualize myocardial phosphoinositide turnover in rats that received an injection of 11C-DAG 1 d (n = 3) and 7 d (n = 5) after MI and 7 d after a sham operation (n = 3). Quantitative autoradiography with 201TlCl was also performed to evaluate myocardial blood flow in rats 7 d after MI (n = 3). Cells occupying the infarcted myocardium were identified by immunohistochemistry. RESULTS: The radioactivity incorporated into the intermediates of phosphoinositide turnover was predominant in both the infarcted (67.1% +/- 5.2% of the total activity) and the noninfarcted (57.4% +/- 3.2%) myocardium. 11C-DAG radioactivity in the infarcted region normalized to that in the noninfarcted region was 1.09 +/- 0.04 in rats 7 d after MI, which was significantly higher than that in rats 1 d after MI (0.38 +/- 0.03, P < 0.001). 201Tl radioactivity in the infarcted region normalized to that in the noninfarcted region was only 0.19 +/- 0.01 7 d after MI. 11C-DAG radioactivity in the noninfarcted region normalized to that in the right ventricular free wall tended to be increased in rats 1 and 7 d after MI compared with the sham-operated rats; the differences, however, were not statistically significant (1.30 +/- 0.15, 1.20 +/- 0.07, and 1.13 +/- 0.02, respectively). Immunohistochemistry revealed that abundant fibroblasts, myofibroblasts, and macrophages occupied the infarcted myocardium 7 d after MI, but the cellularity was low during the first day after MI. CONCLUSION: These data suggest that 11C-DAG may be useful for visualizing regions with activated phosphoinositide turnover after MI. Because wound healing and fibrogenic processes are important factors of ventricular remodeling, 11C-DAG and PET may offer new information benefiting patient management after MI.

Animals↗
PubMed1999

RAV1, a novel DNA-binding protein, binds to bipartite recognition sequence through two distinct DNA-binding domains uniquely found in higher plants.

We have cloned and characterized two novel DNA binding proteins designated RAV1 and RAV2 from Arabidopsis thaliana. RAV1 and RAV2 contain two distinct amino acid sequence domains found only in higher plant species. The N-terminal regions of RAV1 and RAV2 are homologous to the AP2 DNA-binding domain present in a family of transcription factors represented by the Arabidopsis APETALA2 and tobacco EREBP proteins, while the C-terminal region exhibits homology to the highly conserved C-terminal domain, designated B3, of VP1/ABI3 transcription factors. Binding site selection assays using a recombinant glutathione S-transferase fusion protein have revealed that RAV1 binds specifically to bipartite recognition sequences composed of two unrelated motifs, 5'-CAACA-3' and 5'-CACCTG-3', separated by various spacings in two different relative orientations. Analyses using various deletion derivatives of the RAV1 fusion protein show that the AP2 and B3-like domains of RAV1 bind autonomously to the CAACA and CACCTG motifs, respectively, and together achieve a high affinity and specificity of binding. From these results, we suggest that the AP2 and B3-like domains of RAV1 are connected by a highly flexible structure enabling the two domains to bind to the CAACA and CACCTG motifs in various spacings and orientations.

Amino Acid Sequence↗
PubMed1999

Diacylglycerol delays pH(i) overshoot after reperfusion and attenuates contracture in isolated, paced myocytes.

Although protein kinase C (PKC) plays a pivotal role in ischemic preconditioning, it is not clear what the end effector is that protects the myocardium. In isolated, paced (1.25 Hz, 36-37 degrees C) adult rat cardiomyocytes, the effects of PKC preactivation by diacylglycerol on cell motion, intracellular Ca(2+) concentration ([Ca(2+)](i); indo 1), and intracellular pH (pH(i); seminaphthorhodafluor-1) during simulated ischemia-reperfusion (I/R) were investigated. The degree of reperfusion-induced contracture was significantly attenuated in the myocytes pretreated with 10 microM 1, 2-dioctanoyl-sn-glycerol (DOG; n = 19) compared with the untreated myocytes (n = 23, P < 0.02). There were no differences in twitch amplitude, end-diastolic [Ca(2+)](i), or peak-systolic [Ca(2+)](i) during I/R between the DOG-pretreated and untreated myocytes. Although there were no differences in pH(i) during ischemia, the pH(i) overshoot during reperfusion was significantly delayed in the DOG-pretreated myocytes compared with the untreated myocytes (n = 17 for each, P < 0.01). Chelerythrine completely abolished the favorable effects of DOG on the reperfusion-induced contracture and the pH(i) overshoot. These data suggest that diacylglycerol attenuates I/R injury in isolated, paced cardiomyocytes, which may be related to the slower pH(i) overshoot during reperfusion.

Alkaloids↗