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Biomedical subjects

K Urasawa

Publications and source records attributed to K Urasawa.

At least 19 recordsLinked to original sources
PubMed2001

Effects of nonionic contrast media on platelet aggregation: assessment by particle counting with laser-light scattering.

Intravascular radiographic contrast media used in angiography, particularly nonionic contrast media, may cause activation of platelets. This study was designed to determine which properties of nonionic contrast media were potentially responsible for this action. Platelet aggregation after adenosine diphosphate stimulation was studied in the platelet rich plasma obtained from 37 patients who underwent left ventriculography using the highly sensitive method of particle counting with laser-light scattering. Platelet activation by contrast media was studied in the platelet rich plasma from healthy volunteers using flow cytometric analysis to detect platelet degranulation as P-selectin expression. There was a significant decrease in platelet aggregation in patients injected with ioxilan or iomeprol compared with patients injected with iohexol. There was a significant increase in P-selectin expression with the three groups of contrast media compared to control. The platelet activation with ioxilan or iomeprol was significantly less compared to the activation with iohexol. The comparison showed that previous generalization regarding platelet activation by nonionic contrast media might not be valid. It is presumed that the higher osmolality of iohexol may contribute to the increase in platelet aggregation and activation.

Angiography↗
PubMed2001

Vascular smooth muscle cell proliferation is effectively suppressed by the non-specific growth factor inhibitor suramin.

The purpose of this study was to investigate the effects of the non-specific growth factor inhibitor suramin on smooth muscle cell proliferation in vitro and in vivo. Cultured vascular smooth muscle cells (VSMC) were stimulated by platelet-derived growth factor (PDGF) and cellular DNA synthesis assessed by [3H]-thymidine uptake. Suramin dose-dependently inhibited DNA synthesis in VSMC, and 100 microM of suramin completely suppressed the PDGF-AB-induced cellular DNA synthesis. Rabbit carotid arteries were injured by the balloon catheter, and then suramin locally delivered using a porous balloon catheter over ten minutes. Three weeks after the vascular injury, the extent of intimal thickening was compared between the suramin-treated and control rabbits. The neointimal formation triggered by balloon-mediated vascular injury was suppressed significantly and dose-dependently by locally infused suramin, and the intima to media area ratios of the control and 1 mM suramin-treated animals were 48.8+/-14.9 and 12.2+/-6.0%, respectively (p < 0.01. n = 6 for each group). These results suggest that one time local administration of suramin was sufficient to suppress neointimal formation after balloon-mediated vascular injury, and that pharmacological intervention targeting the growth factor's signaling pathways could be a promising approach to prevent smooth muscle cell proliferation in various proliferative vascular diseases.

Animals↗
PubMed2000

Intracoronary delivery of adenovirus encoding adenylyl cyclase VI increases left ventricular function and cAMP-generating capacity.

BACKGROUND: We tested the hypothesis that intracoronary injection of a recombinant adenovirus encoding adenylyl cyclase type VI (AC(VI)) would increase cardiac function in pigs. METHODS AND RESULTS: Left ventricular (LV) dP/dt and cardiac output in response to isoproterenol and NKH477 stimulation were assessed in normal pigs before and 12 days after intracoronary delivery of histamine followed by intracoronary delivery of an adenovirus encoding lacZ (control) or AC(VI) (1.4x10(12) vp). Animals that had received AC(VI) gene transfer showed increases in peak LV dP/dt (average increase of 1267+/-807 mm Hg/s; P=0.0002) and cardiac output (average increase of 39+/-20 mL. kg(-1). min(-1); P<0.0001); control animals showed no changes. Increased LV dP/dt was evident 6 days after gene transfer and persisted for at least 57 days. Basal heart rate, blood pressure, and LV dP/dt were unchanged, despite changes in cardiac responsiveness to catecholamine stimulation. Twenty-three hour ECG recordings showed no change in mean heart rate or ectopic beats and no arrhythmias. LV homogenates from animals receiving AC(VI) gene transfer showed increased AC(VI) protein content (P=0.0007) and stimulated cAMP production (P=0.0006), confirming transgene expression and function; basal LV AC activity was unchanged. Increased cAMP-generating capacity persisted for at least 18 weeks (P<0.0002). CONCLUSIONS: Intracoronary injection of a recombinant adenovirus encoding AC provides enduring increases in cardiac function.

Adenoviridae↗
PubMed2000

Usefulness of early diastolic flow propagation velocity measured by color M-mode Doppler technique for the assessment of left ventricular diastolic function in patients with hypertrophic cardiomyopathy.

Flow propagation velocity (FPV) of left ventricular (LV) filling flow has been shown to be a useful index for the evaluation of LV diastolic function, which is relatively independent of preload in myocardial infarction and dilated cardiomyopathy, but the usefulness of FPV for hypertrophic cardiomyopathy (HCM) has not yet been determined. In 23 HCM patients and 26 control subjects, peak transmitral flow velocities in early diastole (E) and during atrial contraction (A), E/A ratio, deceleration time of E velocity, and isovolumic relaxation time were measured with the conventional Doppler technique, and FPV was measured from color M-mode Doppler images of LV filling flow. The time constant of LV isovolumic pressure decay (tau) was measured by a micro-manometer-tipped catheter in all HCM patients and 13 control subjects. Flow propagation velocity was significantly lower and deceleration time was significantly greater in HCM patients than in the control subjects, though no significant differences were observed in the other noninvasive indexes. Tau was significantly prolonged in HCM patients compared with that of control subjects (54+/-12 cm/s and 32 +/-7 cm/s, respectively; P<.0001). While the conventional indexes did not correlate with tau among the 36 patients in whom invasive studies were performed, FPV correlated well with tau (r = -0.76, P<.0001). Flow propagation velocity is a useful noninvasive index for the assessment of LV diastolic function in patients with HCM.

Adolescent↗
PubMed1999

Enhanced GRK5 expression in the hearts of cardiomyopathic hamsters, J2N-k.

GTP binding protein-coupled receptor kinase 5 (GRK5) cDNA was cloned from the hearts of Syrian hamsters. The hamster GRK5 cDNA contained 1770 nucleotides encoding 590 amino acids, and the nucleotide sequence had 89.6% homology to the human homologue. An inbred cardiomyopathic hamster strain, J2N-k, was used to investigate the alteration of GRK5 mRNA expression in the setting of congestive heart failure. M-mode echocardiography revealed significant dilatation of the left ventricle and a decrease of left ventricular contractility in 20-week-old J2N-k hamsters compared with age-matched control hamsters, J2N-n. Semi-quantitative RT-PCR showed that GRK5 mRNA expression in the hearts of J2N-k was significantly higher than in those of J2N-n (J2N-k 60.3 +/- 13.3, J2N-n 25.8 +/- 17.2 arbitrary units, p < 0.005, n = 6 in each group). These results suggest that an enhanced GRK5 expression might play a role in the reduced responsiveness to catecholamines in failing hearts via beta-adrenergic receptor phosphorylation.

Aging↗
PubMed1999

Fibromuscular dysplasia involving coronary arteries--a case report.

The authors report a young patient with fibromuscular dysplasia involving multivessels including coronary arteries. If young patients have chest pain on effort, fibromuscular dysplasia of coronary arteries must be considered. As fibromuscular dysplasia is a chronic progressive disease and some cases progress rapidly in a few months, careful follow-up and comprehensive medical management may be necessary in such patients.

Adult↗
PubMed1998

Chronic effects of enalapril and amlodipine on cardiac remodeling in cardiomyopathic hamster hearts.

This study examined the effects of long-term treatments with the angiotensin-converting enzyme inhibitor, enalapril, and the calcium antagonist, amlodipine, on the morphologic changes, progressive left ventricular dysfunction, and gene expression of the ryanodine receptor (RyR) and phospholamban (PLN) in dilated cardiomyopathy. From the ages of 5 through 20 weeks, dilated cardiomyopathic hamsters, BIO53.58 (BIO), and control hamsters, F1b, orally received either enalapril or amlodipine. Cardiac function was assessed by echocardiography. At the age of 20 weeks, the collagen volume fractions were analyzed by the stereologic method. RyR and PLN messenger RNAs (mRNAs) were examined by Northern blot in the amlodipine group. In BIO, the reduction of left ventricular percentage of fractional shortening was attenuated in the enalapril group (p < 0.05) and amlodipine group (p < 0.001), and the increase in the collagen volume fraction and the loss of myocytes were suppressed in the amlodipine group compared with the untreated group. RyR mRNA level decreased in BIO (p < 0.01) compared with F1b, but PLN mRNA level was unchanged. RyR and PLN mRNA levels were unaffected by the treatment with amlodipine. Enalapril and amlodipine prevent progressive remodeling and reduce cardiac dysfunction in BIO. Amlodipine prevents fibrosis and cell death without modifying RyR and PLN mRNA levels in BIO.

Amlodipine↗
PubMed1998

[Transgenic animals].

Molecular biological technique has enabled us to create numerous transgenic animals characterized by enhanced or reduced expression of target gene products. These animal models are very useful not only to study the physiological roles of target gene products but also to evaluate the clinical usefulness of newly developed drugs and other therapeutic measures. Unfortunately, we still do not have a genetically engineered animal model that spontaneously develops acute coronary syndrome. However, there are several transgenic mice showing abnormal lipid metabolism and developing premature atherosclerosis. In this chapter, recent advance in the field of atherosclerotic animal models will be summarized.

Acute Disease↗
PubMed1996

Alteration of extracellular matrix in dilated cardiomyopathic hamster heart.

The purpose of this study was to characterize the collagen in hereditary dilated cardiomyopathic hamster hearts, and to examine the participation of the collagen in the occurrence and progression of cardiomyopathy. BIO 53.58 hamsters (5, 10, 20 weeks old) were used as the model of dilated cardiomyopathy. Flb hamsters were used as controls. The collagen content was almost constant at any age in the Flb hamsters, but increased with age in BIO 53.58 hamsters. Type III collagen increased significantly in BIO 53.58 hamsters at 10 weeks. The acetic acid solubility of collagen decreased in BIO 53.58 hamsters as the fibrosis progressed, but was unchanged in controls. Reducible crosslinks showed a tendency to decrease progressively in BIO 53.58 hamsters. There were no differences between Flb and BIO 53.58 hamsters at 5 weeks, but its expression in BIO 53.58 hamsters at 10 and 20 weeks of age increased compared to Flb controls. These findings indicate that in the early phase of cardiomyopathy the extracellular matrix of the myocardium is rich in type III collagen. In the later phase, the matrix resembles that of hard tissues, whose collagen is mainly of type I collagen and is insoluble. These data suggest that the increased collagen synthesis may impair the cardiac function in the development of cardiomyopathy.

Animals↗
PubMed1996

Enhanced expression of beta-adrenergic receptor kinase 1 in the hearts of cardiomyopathic Syrian hamsters, BIO53.58.

We cloned an entire encoding sequence of beta-adrenergic receptor kinase 1 (beta ARK1) cDNA from the hearts of Syrian hamsters through reverse transcription and subsequent polymerase chain reaction. The cloned cDNA contained 2067 nucleotides coding 689 amino acids. The sequence had 95% homology to rat beta ARK1 and 90% homology to human homologue. Cardiomyopathic Syrian hamster, BIO53.58, has been used as a model animal of congestive heart failure. M-mode echocardiography confirmed that left ventricular contractility of 20-week-old BIO53.58 was markedly reduced. The expression of beta ARK1 mRNA in the hearts of BIO53.58 was significantly increased compared to control hamsters, F1b, suggesting that the enhanced beta ARK1 expression is acting as a negative feedback mechanism in order to maintain intracellular homeostasis against accelerated stimulation by catecholamines via phosphorylation of beta-adrenergic receptor.

Aging↗
PubMed1996

A new approach for evaluation of left ventricular diastolic function: spatial and temporal analysis of left ventricular filling flow propagation by color M-mode Doppler echocardiography.

OBJECTIVES: To evaluate left ventricular diastolic function and differentiate the pseudonormalized transmitral flow pattern from the normal pattern, the propagation of left ventricular early filling flow was assessed quantitatively using color M-mode Doppler echocardiography. BACKGROUND: Because the propagation of left ventricular early filling flow is disturbed in the left ventricle with impaired relaxation, quantification of such alterations should provide useful indexes for the evaluation of left ventricular diastolic function. METHODS: Study subjects were classified into three groups according to the ratio of early to late transmitral flow velocity (E/A ratio) and left ventricular ejection fraction: 29 subjects with an ejection fraction > or = 60% (control group); 34 with an ejection fraction < 60% and E/A ratio < 1 (group I); and 25 with ejection fraction < 60% and E/A ratio > or = 1 (group II). The propagation of peak early filling flow was visualized by changing the first aliasing limit of the color Doppler signals. The rate of propagation of peak early filling flow velocity was defined as the distance/time ratio between two sampling points: the point of the maximal velocity around the mitral orifice and the point in the mid-left ventricle at which the velocity decreased to 70% of its initial value. High fidelity manometer-tipped measurement was performed in 40 randomly selected subjects. RESULTS: The rate of propagation decreased in groups I and II compared with that in the control group (33.8 +/- 13.8 [mean +/- SD] and 30.0 +/- 8.6 vs. 74.3 +/- 17.4 cm/s, p < 0.001, respectively) and correlated inversely with the time constant of left ventricular isovolumetric relaxation and the minimal first derivative of left ventricular pressure (peak negative dP/dt) (r = 0.82 and r = 0.72, respectively). CONCLUSIONS: Spatial and temporal analysis of filling flow propagation by color M-mode Doppler echocardiography was free of pseudonormalization and correlated well with the invasive variables of left ventricular relaxation.

Blood Flow Velocity↗
PubMed1995

Quantification of signalling components and amplification in the beta-adrenergic-receptor-adenylate cyclase pathway in isolated adult rat ventricular myocytes.

We have investigated the stoichiometric relationship of proteins involved in beta-adrenergic-receptor-mediated signal transduction in isolated rat cardiac myocytes. These cells contain about 2.1 x 10(5) beta-adrenergic receptors per cell, as determined by radio-ligand-binding assays. We have assessed the amount of Gs alpha present in myocyte membranes by immunoblotting using a purified glutathione S-transferase-Gs alpha fusion protein as a standard for quantification. By this method, we determined that cardiac myocytes contain about 35 x 10(6) and 12 x 10(6) molecules per cell of the 45 and 52 kDa forms of Gs alpha, respectively. [3H]Forskolin binding assays were used to assess the formation of high-affinity forskolin binding sites representing Gs alpha-adenylate cyclase complexes occurring in response to Gs alpha activation. Quantification of the adenylate cyclase complexes was facilitated by the permeabilization of cells with saponin. The addition of isoprenaline (isoproterenol) and guanosine 5'-[gamma-thio]trisphosphate to saponin-permeabilized myocytes results in the formation of 6 x 10(5) Gs alpha-adenylate cyclase complexes. Taken together, the data presented here demonstrate that, in a physiologically relevant setting, G-protein is present in large stoichiometric excess relative to both receptor and effector. In addition, we show that, overall, only modest signal amplification occurs between receptor and adenylate cyclase. Thus adenylate cyclase (rather than Gs) is the component distal to receptor that limits agonist-mediated increases in cyclic AMP production. Although limited data are as yet available for other G-protein-regulated effectors, we hypothesize that the stoichiometry of signalling components and the extent of signal amplification described for the beta-adrenergic response pathway will be applicable to other G-protein-coupled hormone receptor systems.

Adenylyl Cyclases↗
PubMed1995

Developmental regulation of the alpha-subunit of Gq/G11 as determined by quantitative immunoblot analysis.

We have used immunoblot analysis with glutathione and S-transferase fusion proteins as protein standards to examine expression of G alpha q/11 in membrane preparations from different organs and to assess changes during normal development. Adult rat tissues expressed 4-25 pmol/mg membrane protein G alpha q/11, with neonates expressing two to three times higher levels in several tissues (brain, heart, liver, and kidney). By contrast, levels of Gaq/11 in lung were similar in adults and neonates. A Gaq-specific antiserum confirmed the high expression in neonatal brain, heart, liver and kidney. Our results show that Gaq is developmentally regulated in many rat tissues.

Amino Acid Sequence↗
PubMed1995

Cytosolic localization of beta 3-subunit of heterotrimeric GTP binding protein in rat hearts.

The expression of three different subtypes of GTP binding protein beta-subunits (beta 1, beta 2 and beta 3) was examined in rat hearts at both mRNA and protein levels. Among three subtypes, beta 3 mRNA was more abundant in ventricles while beta 1 and beta 2 mRNAs were expressed ubiquitously among ventricles, atria and aortas. The immunodetectable beta 1- and beta 3-proteins were predominantly found in the cytosolic fraction of rat ventricles. In this study, we demonstrate ventricle-specific expression of beta 3-subunit and localization of G protein beta 3-subunit in the cytosol of rat hearts. This unusual cytosolic localization of G protein beta 3-subunit might indicate subtype-specific function of G protein beta (gamma)-subunits in rat hearts.

Animals↗
PubMed1994

[A questionnaire survey on urinary incontinence and urinary disturbances in the institutionalized elderly with senile dementia].

We carried out a questionnaire survey concerning urinary disturbances, among nursing home patients. The answers were obtained from 1,038 elderly including 355 males and 683 females. Ages, spanned 50-99, with an average age of 79.1. Of the 1,038 respondents which we obtained through our survey for management of urination, 35.8% of the total said that they are able to urinate without incontinence. Those able to urinate with incontinence accounted for 23.6% of the total. However, 40% of all patients required an adult diaper throughout the day to control their urinary functions. Patients suffering from neurological disorders accounted for 70% of respondents, and a correlation was seen between the extent of dementia and ADL, and excretory control. Urinary functioning in both men and women was found to grow increasingly difficult with age, and medical problems involving urinary difficulty appear to increase with the advance of the aging process. The representative groups for this survey were limited to elderly people in nursing homes, many of whom suffer from neurological disorders such as cerebral infarction. It was found that both male and female patients experience a variety of urinary disturbances.

Aged↗
PubMed1993

Downregulation of cardiac guanosine 5'-triphosphate-binding proteins in right atrium and left ventricle in pacing-induced congestive heart failure.

The extent to which congestive heart failure (CHF) is dependent upon increased levels of the cardiac inhibitory GTP-binding protein (Gi), and the impact of CHF on the cardiac stimulatory GTP-binding protein (Gs) and mechanisms by which Gs may change remain unexplored. We have addressed these unsettled issues using pacing-induced CHF in pigs to examine physiological, biochemical, and molecular features of the right atrium (RA) and left ventricle (LV). CHF was associated with an 85 +/- 20% decrease in LV segment shortening (P < 0.001) and a 3.5-fold increase (P = 0.006) in the ED50 for isoproterenol-stimulated heart rate responsiveness. Myocardial beta-adrenergic receptor number was decreased 54% in RA (P = 0.004) and 57% in LV (P < 0.001), and multiple measures of adenylyl cyclase activity were depressed 49 +/- 8% in RA (P < 0.005), and 44 +/- 9% in LV (P < 0.001). Quantitative immunoblotting established that Gi and Gs were decreased in RA (Gi: 59% reduction; P < 0.0001; Gs: 28% reduction; P < 0.007) and LV (Gi: 35% reduction; P < 0.008; Gs: 28% reduction; P < 0.01) after onset of CHF. Reduced levels of Gi and Gs were confirmed by ADP ribosylation studies, and diminished function of Gs was established in reconstitution studies. Steady state levels for Gs alpha mRNA were increased in RA and unchanged in LV, and significantly more GS alpha was found in the supernatant (presumably cytosolic) fraction in RA and LV membrane homogenates after CHF, suggesting that increased Gs degradation, rather than decreased Gs synthesis, is the mechanism by which Gs is downregulated. We conclude that cardiac Gi content poorly predicts adrenergic responsiveness or contractile function, that decreased Gs is caused by increased degradation rather than decreased synthesis, and that alterations in beta-adrenergic receptors, adenylyl cyclase, and GTP-binding proteins are uniform in RA and LV in this model of congestive heart failure.

Adenylyl Cyclases↗