Biomedical subjects

N Yamazaki

Publications and source records attributed to N Yamazaki.

At least 163 records · Page 9Linked to original sources

PubMed1990

Clinical significance of plasminogen activator inhibitor activity in patients with exercise-induced ischemia.

To assess the fibrinolytic system in patients with exercise-induced ischemia and its relation to ischemia and severity of coronary artery disease (CAD), 47 patients with CAD confirmed by results of coronary angiography underwent symptom-limited multistage exercise thallium-201 emission computed tomography. All patients with CAD had exercise-induced ischemia as assessed from thallium-201 images. Pre- and peak exercise blood samples from each patient and preexercise blood samples from control subjects were assayed for several fibrinolytic components and were also assayed for plasma adrenaline. The extent of ischemia was defined as delta visual uptake score (total visual uptake score in delayed images minus total visual uptake score in initial images) and the severity of CAD as the number of diseased vessels. In the basal condition, plasminogen activator inhibitor (PAI) activity was significantly higher in patients with exercise-induced ischemia as compared to control subjects (p less than 0.01), although there were no significant differences in other fibrinolytic variables between the two groups. Moreover, PAI activity in the basal condition displayed a significantly positive correlation with the extent of ischemia (r = 0.47, p less than 0.01). Patients with exercise-induced ischemia were divided into two groups (24 with single-vessel disease and 23 with multivessel disease). There were no significant differences in coronary risk factors, hemodynamics, or plasma adrenaline levels during exercise between single-vessel and multivessel disease except that delta visual uptake score was significantly higher in multivessel disease (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

Interaction of atrial muscarinic receptors with three kinds of GTP-binding proteins.

Purified porcine atrial muscarinic acetylcholine receptors were reconstituted into lipid vesicles with three different G proteins (Gi, Go and Gn)1 purified from porcine cerebrum. All the G proteins interacted with the receptor as evidenced by GTP-sensitive high affinity binding with acetylcholine, and stimulation by acetylcholine of GTP gamma S binding and GTPase activities. The curves of displacement by acetylcholine of [3H]QNB binding were explained by assuming two sites with the same affinity for [3H]QNB but different affinities for acetylcholine. The proportion of the high affinity site increased from 3 to 7% up to 82 to 83% of total binding sites with increasing G protein concentration, and essentially the same results were obtained with the three G proteins. The GTPase activities of Gi, Go and Gn in the reconstituted vesicles were 2.7-, 1.7- and 1.6-times higher, respectively, in the presence of 1 mM acetylcholine than those in the presence of 10 microM atropine. An obvious enhancement by acetylcholine of the GTP gamma S binding was observed in the presence of 10 to 100 microM GDP, while the enhancement was minimal, if at all, in the absence of GDP. When the molar ratios of reconstituted Gi, Go and Gn to muscarinic receptors were 54, 84 and 107, respectively, the acetylcholine-induced increase in the [35S]GTP gamma S binding was as much as 12, 35 and 27 mol with Gi, Go and Gn, respectively, per mole of the receptor molecule, indicating that the muscarinic receptors interact with G proteins catalytically.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1990

Alterations of human erythrocyte membrane fluidity by oxygen-derived free radicals and calcium.

Two possible reasons for the structural alterations of cell membranes caused by free radicals are lipid peroxidation and an increase in the intracellular calcium ion concentration. To characterize the alterations in membrane molecular dynamics caused by oxygen-derived free radicals and calcium, human erythrocytes were spin-labeled with 5-doxyl stearic acid, and alterations in membrane fluidity were quantified by electron spin resonance spectrometry. The in vitro generation of oxygen free radicals, using hypoxanthine (0.43 mM) plus xanthine oxidase (0.07 U/mL) decreased membrane fluidity, and the addition of superoxide dismutase and catalase inhibited the effect on membrane fluidity of the hypoxanthine-xanthine oxidase system. Hydrogen peroxide (0.1 and 1 mM) also decreased membrane fluidity and caused alterations to erythrocyte morphology. In addition, a decrease in membrane fluidity was observed in erythrocytes incubated with 2.8 mM CaCl2. On the other hand, incubation of erythrocytes with calcium-free solution decreased the changes in membrane fluidity caused by hydrogen peroxide. These results suggest that changes in membrane fluidity are directly due to lipid peroxidation and are indirectly the result of increased intracellular calcium concentration. We support the hypothesis that alterations of the biophysical properties of membranes caused by free radicals play an important role in cell injury, and that the accumulation of calcium amplifies the damage to membranes weakened by free radicals.

Calcium↗

PubMed1990

Exercise-induced silent myocardial ischemia: evaluation by thallium-201 emission computed tomography.

Factors associated with silent myocardial ischemia (SMI) during exercise testing were studied by means of thallium-201 emission computed tomography (ECT) in 471 patients. Coronary angiography was done in 290, of whom 167 were found to have significant coronary artery disease (CAD). Exercise-induced ischemia and its severity were defined with ECT. During exercise 108 (62%) of 173 patients with ischemia and 57 (50%) of 115 with ischemia and angiographically documented CAD had no chest pain. One third of the patients showed an inconsistency between scintigraphic ischemia and ischemia ST depression. Age, sex, prior myocardial infarction, and diabetes mellitus were not related to SMI. Patients with SMI had less severe ischemia despite a higher peak double product compared to those with painful ischemia. Among 91 with prior myocardial infarction and exercise-induced ischemia, 51 with periinfarction ischemia had a higher frequency of SMI than did 14 with ischemia remote from the prior infarct zone despite similarities in the severity of ischemia. In conclusion, factors localized within ischemic myocardium such as less severe ischemia or adjacency to a prior infarct made SMI more prevalent.

Angina Pectoris↗

PubMed1990

Heterogeneity in cellular response and intracellular distribution of Ca2+ concentration during and after metabolic inhibition.

STUDY OBJECTIVE: To characterise cell injury during myocardial hypoxia and reoxygenation, [Ca2+]i was measured in guinea pig ventricular myocytes using digital images of fura-2 fluorescence. DESIGN: [Ca2+]i and cell morphology were measured during and after the perfusion of 2 mmol.litre-1 sodium cyanide (NaCN). EXPERIMENTAL MATERIAL: 28 ventricular myocytes isolated from guinea pig hearts. MEASUREMENTS AND MAIN RESULTS: Eight out of 28 cells became rounded during the perfusion with NaCN, and [Ca2+]i increased from 48 (SEM 6) nmol-litre-1 to 163(24) (p less than 0.01) before cell rounding, and to 311(46) (p less than 0.01) after cell rounding. Ten cells were rounded after the washout of NaCN, and [Ca2+]i increased to 252(41) nmol.litre-1 before cell rounding (p less than 0.01), and to 314(48) after cell rounding (p less than 0.01). Intracellular distribution of [Ca2+]i was heterogeneous in some cells with high [Ca2+]i. The values of [Ca2+]i before and after cell rounding, during and after the perfusion of NaCN, were significantly lower than those during the perfusion of strophanthidin (0.1 mmol.litre-1). CONCLUSIONS: There appeared to be a mixed population of myocytes, some showing normal [Ca2+]i and shape, and others showing high [Ca2+]i and contracture, during the perfusion or the washout of NaCN. Ca2+ overload alone is unlikely to be the main and the only mechanism of cell injury during myocardial hypoxia/reoxygenation. Other mechanisms such as membrane disturbance could be involved.

Animals↗

PubMed1990

SPECT imaging with Tl-201 and Ga-67 in myocardial sarcoidosis.

Two patients with myocardial sarcoidosis are presented, both of whom underwent SPECT imaging with Tl-201 and Ga-67. The first had Ga-67 myocardial uptake with a Tl-201 defect, which disappeared with corticosteroid therapy. The second had multiple Tl-201 defects without Ga-67 uptake, which persisted despite corticosteroid therapy. Therefore, the combination of Tl-201 and Ga-67 imaging may be useful for recognizing myocardial sarcoidosis and for predicting the response to corticosteroid therapy.

Adrenal Cortex Hormones↗

PubMed1990

Changes in plasminogen activator inhibitor 1 and tissue-type plasminogen activator during exercise in patients with coronary artery disease.

As depressed fibrinolysis is implicated in the pathogenesis of coronary artery disease, we have studied the activation of fibrinolysis during maximal, symptom-limited exercise in a group of 68 men. After exercise they were divided, according to their coronary angiography and exercise 201Tl emission computed tomography results, into three groups. Group 1: persons with normal exercise 201Tl emission computed tomography results and no underlying diseases who served as controls; group 2: patients with coronary artery disease without exercise-induced myocardial ischemia, and group 3: patients with coronary artery disease with transient, exercise-induced myocardial ischemia. Before and at peak exercise we measured the plasminogen activator activity (PAA) in the euglobulin fraction of plasma by an amidolytic method and the concentrations of tissue plasminogen activator (t-PA), activator-inhibitor complex - plasminogen activator inhibitor 1 (PAI-1) complexed with t-PA - and total PAI-1 by enzyme immunoassay. The concentration of free PAI-1 in plasma was calculated by subtraction of the concentration of activator-inhibitor complex from that of total PAI-1. Under basal conditions, group 3 had significantly higher free and total PAI-1 levels than group 1. There were no statistically significant differences between the three groups in PAA, t-PA, and activator-inhibitor complex levels. At peak exercise, group 1 showed the highest release of t-PA accompanied with highest increases in PAA as well as in activator-inhibitor complex, the proportion of released t-PA antigen not bound to PAI-1 being highest in group 1. Free PAI-1 decreased significantly, but there were no differences between individual groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

Myocardial free carnitine and fatty acylcarnitine levels in patients with chronic heart failure.

To study the tissue carnitine level in patients with chronic heart failure, we obtained biopsy specimens of the left ventricular papillary muscle from 8 patients with mitral valve disease undergoing valve replacement surgery. As a control group autopsy specimens from 7 patients without heart disease were obtained within 4 hours of death. The free carnitine level in the heart was significantly lower in patients with chronic heart failure than in the control group (412 +/- 142 nmol/g wet tissue vs 769 +/- 267; p less than 0.01, mean +/- SD). The long-chain acylcarnitine level was significantly higher in chronic heart failure than in the control group (532 +/- 169 nmol/g wet tissue vs 317 +/- 72; p less than 0.01). The total carnitine level in chronic heart failure was similar to that in the control group (1321 +/- 170 nmol/g wet tissue vs 1315 +/- 377). These results show that in failing myocardium the fatty acid metabolism may be impaired, and administration of carnitine may be worth trying to treat chronic heart failure.

Adult↗

PubMed1990

Efficacy of combination therapy with mexiletine and a low dose of propranolol for premature ventricular arrhythmias.

The clinical efficacy of combination therapy with mexiletine and propranolol was investigated in several centres. Twenty-four-hour Holter electrocardiograms were recorded and the severity of ventricular premature beats (VPBs) was assessed on the basis of the frequency of VPBs and according to the criteria of Lown. Forty-eight cases with VPBs received single treatment with mexiletine (300 mg/day). Single treatment with mexiletine was effective in 26 out of 48 cases (54%). Nineteen cases in which the single treatment with mexiletine was not sufficiently effective received combination therapy with mexiletine (300 mg/day) and a low dose of propranolol (30 mg/day). After the combination therapy, significant decreases in the frequency of VPBs were found in 11 out of 19 cases (58%), and lowering of the severity of the grade was found in 4 cases (30.8%). Thirteen out of 19 cases given combination therapy changed to single treatment with propranolol. A change in treatment from combination therapy to single treatment with propranolol was assessed as "undesirable" in 8 out of 13 cases (61.5%). During single treatment with mexiletine, side effects were found in 1 out of 48 cases (2.1%), and during the combination therapy in 1 out of 19 cases (5.2%). Thus, combination therapy with mexiletine and a low dose of propranolol was shown to be useful for patients with VPBs.

Adult↗

PubMed1990

Arrhythmia after the release of inhibited oxidative phosphorylation.

Automaticities due to delayed afterdepolarizations, elicited upon reoxygenation, are thought to be caused by Ca overload. Since tissue Ca uptake upon reoxygenation has been reported to be closely related to metabolic inhibition during hypoxic perfusion, the relationship between the degree of metabolic inhibition during hypoxia and reoxygenation-induced arrhythmias was investigated in guinea pig papillary muscles. (1) Arrhythmias occurred after 60 min substrate-free hypoxia, but not after 30 min hypoxia. The chance of automaticities was closely related with the increase in resting tension achieved during hypoxic period. The incidence of arrhythmias was, however, lower after 90 or 120 min hypoxia. (2) There were arrhythmias after 20-30 min hypoxia with glycolytic inhibition (20 mM 2-deoxyglucose + 5 mM acetate). On the other hand, 60-min hypoxia in the presence of 5 mM glucose did not elicit arrhythmias on reoxygenation. (3) Stimulation of glycolysis (50 mM glucose) during substrate-free hypoxia prolonged the action potential duration, but did not cause arrhythmias. Washout of cyanide (1 mM) after 60 min perfusion in the presence of oxygen, caused arrhythmias and aftercontractions. These results suggest that the degree of metabolic inhibition during hypoxia is closely related to Ca overload and the resultant arrhythmias upon reoxygenation. The release of inhibited oxidative phosphorylation, rather than the reintroduction of oxygen per se, was thought to be the key mechanism of reoxygenation-induced arrhythmias.

Animals↗

PubMed1990

[A study on the relationship between natriuresis and renally formed dopamine in the rat].

This study was undertaken to elucidate the relationship between natriuresis and renally formed dopamine in pentobarbital-anesthetized rats that were loaded with 0.9% NaCl. Infusion of dopamine resulted in marked increases in urinary free dopamine excretion, plasma free dopamine concentration, urine volume and urinary sodium excretion. Infusion of carbidopa markedly decreased urinary free dopamine excretion, but did not affect urine volume and urinary sodium excretion. Infusion of L-dopa markedly increased urinary free dopamine excretion and plasma free dopamine concentration, but did not affect urine volume and urinary sodium excretion. When carbidopa was infused with L-dopa or dopamine, carbidopa significantly inhibited the increase in urinary and plasma free dopamine induced by L-dopa, but did not inhibit the increases in urinary and plasma free dopamine, urinary sodium excretion and urine volume induced by dopamine. These data indicated that there is no correlation between renally formed dopamine and natriuresis, and furthermore suggested that renally formed dopamine is not essential for natriuresis.

Animals↗

PubMed1990

[Peridurograms in patients with lumbar disc herniations].

The epidural space lies between the dural tube and the inside wall of the spinal canal. It contains fibrous tissues which adhere snugly to both walls filling the dead space between them. In the space, there are a large number of venous vessels anteriorly, a little fat tissue posteriorly and nerve roots laterally. The space can be examined clinically by a peridurographic technique in which the epidural space is filled with an iodine contrast medium. In patients with lumbar intervertebral disc herniation (IDH), this examination is useful to determine the location of the prolapsed nucleus pulposus and the pathological adherent condition by the filling defect of contrast medium. For the purpose of determining the pathology of the prolapsed nucleus pulposus, peridurographic examinations were performed on 40 patients with IDH and the following results were obtained: 1) The existence and location of the IDH were shown by the peridurograms. 2) Adhesion around the involved and uninvolved nerve roots was shown in proportion to clinical symptoms.

Adolescent↗

PubMed1990

Protective effects of adrenoceptor-blocking agents on myocardial injury induced by epinephrine in mice.

Employing propranolol as a non-selective beta-blocker, atenolol, acebutolol and metoprolol as selective beta 1-blockers, butoxamine as a selective beta 2-blocker, labetalol as an alpha- and beta-blocker, and phentolamine as an alpha-blocker, we compared the effects of these adrenoceptor-blocking agents to reduce the degree of the myocardial injury induced by epinephrine in mice. Epinephrine in a single dose of 4 mg/kg/day, s.c., daily for 7 days, caused widely extended lesions, necrosis and fibrosis in the myocardial fibers, and degeneration in the residual myocardial fibers. The adrenoceptor-blocking agents in a dose of 10 mg/kg/day, s.c., given 30 minutes prior to epinephrine to each mouse daily for 7 days, had reduced the degree of the myocardial injury induced by epinephrine. The blockers, all, effectively suppressed the injury. Although metoprolol and butoxamine were less effective on the protection of the cardiotoxicity than phentolamine, the other blockers prevented the cardiotoxicity with the same degree as phentolamine did. These findings suggest that not only alpha- but also beta 1- and beta 2-adrenoceptors play critical roles in producing the myocardial injury.

Adrenergic alpha-Antagonists↗

PubMed1990

Isolation of Staphylococcus hyicus subsp. hyicus from pigs affected with exudative epidermitis and experimental infection of piglets with isolates.

Five strains of Staphylococcus hyicus subsp. hyicus were isolated: three strains (P-1, P-2 and P-3) from the crust on the body surface of 6-month-old pigs on a farm in Aomori prefecture, and two (P-5 and P-6) from both the crust on the body surface and the joint of a 1-month-old piglet with exudative epidermitis (EE) on another farm. The characterization of the isolates and the experimental infection of the piglets with strain P-1 were carried out. Subcutaneous inoculation with the bacterial suspension (10(10) CFU) produced EE to all nine piglets. Eight of them had exudation and exfoliation within 24 hr of infection. Histopathologically, disappearance of stratum corneum and necrosis with vacuolar degeneration of prickle cells were remarkable in the epidermis. Infiltration of neutrophils and lymphocytes were observed in the dermis. The results clearly indicate that S. hyicus is responsible for incrustation of the body surface of weanling pigs and exudative epidermitis in young piglets.

Animals↗

PubMed1990

[Analysis of anti HMW.MAA antibodies in sera of melanoma patients using antiidiotypic monoclonal antibodies].

The immunogenicity in patients with melanoma of three high molecular weight melanoma associated antigens (HMW.MAA) defined by murine monoclonal antibodies (MoAb) was investigated. For this end sera from patients with melanoma (stage I, IV) and normal individuals were tested by inhibition assay and sandwich assay using antiidiotypic MoAb to anti HMW.MAA MoAb. In inhibition assay, sera were tested for their ability to inhibit the binding of murine antiidiotypic MoAbs to biotin conjugated anti HMW.MAA MoAbs. Some of the sera from patients with melanoma significantly inhibited the binding of antiidiotypic MoAb to anti HMW.MAA MoAb in comparison with that from normal individuals. In sandwich assay, sera were tested for their ability to bind to precoated murine antiidiotypic MoAb and to biotin conjugated anti HMW.MAA MoAbs. Positive findings suggest the existence of anti HMW.MAA antibodies in sera were showed in several sera from the patients, which were less in frequency than that in inhibition assay. These results suggest that HMW.MAA could elicit the immune response in some melanoma patients and also suggest that the assay anti HMW.MAA MoAb in sera will help us to understand the prognosis of the patients and to evaluate the usefulness of treatment with antiidiotypic MoAb as vaccine therapy.

Antibodies, Monoclonal↗

PubMed1989

Effects of L-carnitine and palmitoylcarnitine on membrane fluidity of human erythrocytes.

Amphiphilic compounds such as long-chain acyl carnitine accumulate in ischemic myocardium and potentially contribute to the myocardial damage, and the role of carnitine in protecting the heart against ischemic damage is interesting. It has been reported that palmitoylcarnitine causes alterations in the membrane molecular dynamics, so this study was designed to investigate whether L-carnitine had a stabilizing effect of membrane fluidity using the spin-label technique. Human erythrocytes were spin-labeled with 5-doxylstearic acids, and membrane fluidity was quantified by measuring the change in the order parameter S. The administration of palmitoylcarnitine (100 microM) altered the membrane fluidity of erythrocytes and caused significant morphological changes. L-carnitine (2mM) decreased the alteration of the fluidity of erythrocytes incubated with palmitoylcarnitine (100 microM), and improved the morphological changes in erythrocytes. These results show that L-carnitine has a stabilizing effect of membrane fluidity as a result of interaction with the palmitoylcarnitine which has a detergent effect.

Carnitine↗

PubMed1989

Dual loading of the fluorescent indicator fura-2 and 2,7-biscarboxyethyl-5(6)-carboxyfluorescein (BCECF) in isolated myocytes.

Isolated rat heart myocytes were loaded with both the Ca2+ sensitive fluorescent probe fura-2/AM and the fluorescent pH indicator 2,7-biscarboxyethyl-5(6)-carboxyfluorescein (BCECF/AM). Changes in [Ca2+]i and pHi were measured simultaneously using digitized video fluorescence microscopy. In measurement of [Ca2+]i and pHi, the ratios of dual-loaded cells were not different from single-loaded cells. Using this method, [Ca2+]i and pHi in myocytes were 48 +/- 7 nM and 7.17 +/- 0.05. It is concluded that [Ca2+]i and pHi could be measured simultaneously in isolated myocyte using dual-loading of fura-2 and BCECF.

Animals↗

PubMed1989

Effects of long-chain acyl carnitine on membrane fluidity of human erythrocytes.

Amphiphilic compounds such as long-chain acyl carnitines accumulate in ischemic myocardium and potentially contribute to the myocardial damage. To characterize alterations in membrane molecular dynamics produced by palmitoylcarnitine, human erythrocytes were spin-labeled with 5-doxylstearic acid, and membrane fluidity was quantified by measuring the changes in the order parameter derived from ESR spectra. Palmitoylcarnitine induced triphasic alterations in membrane fluidity of human erythrocytes. The membrane fluidity increased for 5 min, then decreased in a concentration-dependent manner. At higher concentrations (100 and 150 microM) of palmitoylcarnitine, membrane fluidity increased again after 30 and 20 min of the incubation, respectively. Addition of 2.8 mM CaCl2 resulted in a significant decrease in membrane fluidity and enhanced the alterations in membrane fluidity caused by palmitoylcarnitine. The results suggest that alterations in molecular dynamics are one mechanism through which long-chain acyl carnitine could play an important role in ischemic injury.

Acetylcarnitine↗