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Biomedical subjects

N Yamazaki

Publications and source records attributed to N Yamazaki.

At least 19 recordsLinked to original sources
PubMed1992

Decrease in heart mitochondrial creatine kinase activity due to oxygen free radicals.

This study was undertaken to examine the effects of oxygen free radicals on mitochondrial creatine kinase activity in rat heart. Xanthine plus xanthine oxidase (superoxide anion radical generating system) reduced mitochondrial creatine kinase activity both in a dose- and a time-dependent manner. Superoxide dismutase showed a protective effect on depression in creatine kinase activity due to xanthine plus xanthine oxidase. Hydrogen peroxide inhibited creatine kinase activity in a dose-dependent manner, this inhibition was protected by the addition of catalase. In order to understand the detailed mechanisms by which oxygen free radicals inhibit mitochondrial creatine kinase activity, the effects of oxygen free radicals on mitochondrial sulfhydryl groups were examined. Mitochondrial sulfhydryl groups contents were decreased by xanthine plus xanthine oxidase or hydrogen peroxide; this depression in sulfhydryl groups contents was prevented by the addition of superoxide dismutase or catalase. N-Ethylmaleimide (sulfhydryl group reagent) expressed inhibitory effects on the creatine kinase activity both in a dose- and a time-dependent manner; dithiothreitol or cysteine (sulfhydryl group reductant) showed protective effects on the creatine kinase activity depression induced by N-ethylmaleimide. Dithiothreitol or cysteine also blocked the depression of mitochondrial creatine kinase activity caused by xanthine plus xanthine oxidase or hydrogen peroxide. These results lead us to conclude that oxygen free radicals may inhibit mitochondrial creatine kinase activity by modifying sulfhydryl groups in the enzyme protein.

Animals↗
PubMed1992

Exercise testing and thallium-201 emission computed tomography in patients with intraventricular conduction disturbances.

The specificity of exercise thallium-201 emission computed tomography for coronary artery disease was assessed in patients with intraventricular conduction disturbances. Eighty-seven patients were studied: 33 with right bundle branch block (RBBB), 11 with RBBB and left-axis deviation, 11 with left (L)BBB, 12 on right ventricular pacing, and 20 with Wolff-Parkinson-White (WPW) syndrome. A control group of 349 consecutive patients with normal intraventricular conduction was also examined. The specificity of diagnosis of coronary artery disease in patients with LBBB (30%), right ventricular pacing (44%) or RBBB plus left-axis deviation (50%) was significantly lower than in patients with normal intraventricular conduction (94%; p less than 0.01). In contrast, there was no significant difference between specificity in patients with RBBB (86%) or WPW syndrome (90%) and patients with normal intraventricular conduction. Perfusion defects were found in the anterior, septal and inferior segments in patients with LBBB, and in the septal and inferior segments in patients with RBBB plus left-axis deviation despite the absence of coronary stenosis. Furthermore, diffuse slow washout was seen more often in patients with WPW syndrome (35%) than in controls who had normal intraventricular conduction (11%; p less than 0.05), despite a good exercise performance in the former group. This study suggests that there is an increased incidence of abnormal perfusion and clearance during exercise thallium-201 emission computed tomography in patients with intraventricular conduction disturbances.

Aged↗
PubMed1992

Hemoglobin Kansas found in a patient with polycythemia.

A 62-year-old woman, long suspected of having heart disease, was admitted to our hospital for thorough examination. Her hemoglobin level was 17.7 g/dl and her 2.3-DPG level was 8.90 microM/ml RBC. The patient proved to have polycythemia, hemoglobin Kansas, and diabetes mellitus. To our knowledge, this is the third case of hemoglobin Kansas in the world.

2,3-Diphosphoglycerate↗
PubMed1992

Studies on carbohydrate-binding proteins using liposome-based systems--I. Preparation of neoglycoprotein-conjugated liposomes and the feasibility of their use as drug-targeting devices.

1. Five types of neoglycoprotein-coupled liposomes were prepared in order to investigate their potential utility as new types of drug-targeting devices which exploit cellular functions of carbohydrate-binding proteins. 2. These preparations were shown to be stable at 37 degrees C for 24 hr and at 7 degrees C over 4 months. 3. An inhibition assay in an in vitro system using human adenocarcinoma cells indicated the high affinity binding of neoglycoprotein-conjugated liposomes. The inhibitory potency correlated with both the type and the amount of immobilized neoglycoproteins on liposomes. 4. A tissue distribution assay in an in vivo system using Ehrlich solid tumor-bearing mice showed the feasibility of the application of [125I]neoglycoprotein-conjugated liposomes as drug-targeting devices, based on carbohydrate-protein interactions.

Carbohydrate Metabolism↗
PubMed1992

Cytosolic Ca2+ concentration and pH of diabetic rat myocytes during metabolic inhibition.

To investigate the role of Ca2+ metabolism and pH in diabetic cardiomyopathy, intracellular Ca2+ concentration ([Ca2+]i) and intracellular pH (pHi) of isolated myocytes were measured simultaneously using fura-2 and BCECF. We used diabetic (D.M.) rats at 8 weeks after the injection of streptozotocin (45 mg/kg, i.v.). (1) [Ca2+]i of D.M. myocytes was lower than that of controls (53 +/- 3 and 75 +/- 5 nM, mean +/- S.E., P less than 0.01). There was no difference in pHi (7.06 +/- 0.02 in D. M., 7.07 +/- 0.02 in control). There was no difference in the percentage of non-rounded cells at 30 min after the perfusion of glucose-free solution which contained 2 mM sodium cyanide (NaCN) between D.M. and controls (53% and 52%). When cells were rounded, the value of [Ca2+]i was significantly lower in D.M. myocytes than that in controls (172 +/- 21 and 421 +/- 106 nM, P less than 0.05). (2) When the cells were shortened or rounded in the high [Ca2+]o solution (24.5 mM), [Ca2+]i of D.M. rats was significantly lower than that of control rats. (3) The percentage of non-rounded cells at 30 min after the perfusion of NaCN increased in controls by 50 mM glucose (95%, P less than 0.01), but not in D.M. (47%). Insulin (25 mU/ml) and glucose (15 mM) increased the percentage of non-rounded cells in D.M. after 30 min perfusion with NaCN (88%, P less than 0.01 v.s. 53% without glucose nor insulin). It is suggested that there are disturbances of Ca2+ metabolism in D.M. myocytes, and that there is a close relation between cell injury and glucose utilization during metabolic inhibition.

Animals↗
PubMed1992

Evaluation of the micronucleus test using a Chinese hamster cell line as an alternative to the conventional in vitro chromosomal aberration test.

The in vitro micronucleus (MN) test was carried out simultaneously with the conventional chromosomal aberration (CA) test on 11 clastogenic chemicals or spindle poisons with different modes of action using a Chinese hamster cell line (CHL). The method of slide preparation for the MN test was the same as that for the conventional metaphase analysis, except that 1% acetic acid in methanol was used as the cell suspension medium for air-drying (to preserve the cytoplasm around the nucleus). All chemicals tested induced micronuclei reproducibly and dose-dependently in good agreement with the results of metaphase analysis (r = 0.99). Since the MN test methodology is simple and the observation of MN is less subjective than that of CA, we conclude that the in vitro MN test would be a good alternative to the conventional CA test for screening the genotoxicity of chemicals.

Acetates↗
PubMed1992

Augmentation of beta adrenergic receptors in cardiomyopathic hamsters (BIO 14.6) with heart failure.

OBJECTIVE: The aim was to characterise the transmural distribution of beta adrenergic receptors in failing myocardium in cardiomyopathy. METHODS: Using a quantitative autoradiographic technique with 125I-cyanopindolol (ICYP), the density and transmural distribution of beta adrenergic receptors were compared between eight cardiomyopathic BIO 14.6 Syrian hamsters with heart failure and six normal age matched controls (BIO 14.6HAM). RESULTS: Binding of ICYP to transmural slices of hamster myocardium was rapid, saturable, stereoselective, and displaceable by antagonists. The binding isotherm showed a significant increase in the total tissue content of beta adrenergic receptors in the failing myocardium of cardiomyopathic hamsters: 15.3(SEM 1.6) fmol.mg-1 protein v 9.4(1.2) fmol.mg-1 protein in normal myocardium of control hamsters (p < 0.05). There was no difference in receptor affinity. Quantitative autoradiography showed regional heterogeneity of beta adrenergic receptors in cardiomyopathic hamsters, with an increase of beta adrenergic receptor density in the septal and subendocardial regions. In addition, the regions with increased interstitial fibrosis corresponded to the sites of increased beta adrenergic receptor density. CONCLUSIONS: The transmural distribution of beta adrenergic receptor is heterogeneous in the failing myocardium of cardiomyopathic hamsters and an increased beta adrenergic receptor density may be associated with the development of cardiomyopathy.

Animals↗
PubMed1992

Intracellular Ca2+ concentration and pHi during metabolic inhibition.

To study the changes in intracellular Ca2+ concentration ([Ca2+]i) and pH (pHi) during metabolic inhibition, rat ventricular myocytes were dual loaded with the acetoxymethyl esters of fura-2 (fura-2/AM) and 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF/AM) and perfused with 2 mM sodium cyanide (NaCN). The percent of rod-shaped cells was 30% of the control after 30 min NaCN in the absence of glucose. [Ca2+]i increased from 82 +/- 8 to 151 +/- 25 (SE) nM (P less than 0.05) when cells were shortened, and to 421 +/- 106 nM (P less than 0.05) when cells were rounded. There was a positive relationship between pCai and pHi (r = 0.425, P less than 0.01). When 50 mM glucose was added during NaCN, there were no significant changes in [Ca2+]i and the percent of rod-shaped cells after 30 min. The pHi of rod-shaped cells, however, decreased to 6.95 +/- 0.03 (P less than 0.01). Although the acidic solution (70% O2-30% CO2) decreased pHi to 6.90 +/- 0.05 (P less than 0.01), there were no changes in the cell shape or [Ca2+]i. The addition of NaCN for 30 min decreased the rod-shaped cells to 18% of the control. Mild acidosis did not cause the changes in cell shape or [Ca2+]i. There was also no protection of the NaCN-induced changes in cell shape by intracellular acidosis. It is likely that the changes in cell shape during metabolic inhibition were related to the depletion of metabolic energy and the increase in [Ca2+]i.

Analysis of Variance↗
PubMed1992

L-carnitine treatment for congestive heart failure--experimental and clinical study.

To evaluate the therapeutic efficacy of l-carnitine in heart failure, the myocardial carnitine levels and the therapeutic efficacy of l-carnitine were studied in cardiomyopathic BIO 14.6 hamsters and in patients with chronic congestive heart failure and ischemic heart disease. BIO 14.6 hamsters and patients with heart failure were found to have reduced myocardial free carnitine levels (BIO 14.6 vs FI, 287 +/- 26.0 vs 384.8 +/- 83.8 nmol/g wet weight, p less than 0.05; patients with heart failure vs without heart failure, 412 +/- 142 vs 769 +/- 267 nmol/g p less than 0.01). On the other hand, long-chain acylcarnitine level was significantly higher in the patients with heart failure (532 +/- 169 vs 317 +/- 72 nmol/g, p less than 0.01). Significant myocardial damage in BIO 14.6 hamsters was prevented by the intraperitoneal administration of l-carnitine in the early stage of cardiomyopathy. Similarly, oral administration of l-carnitine for 12 weeks significantly improved the exercise tolerance of patients with effort angina. In 9 patients with chronic congestive heart failure, 5 patients (55%) moved to a lower NYHA class and the overall condition was improved in 6 patients (66%) after treatment with l-carnitine. L-carnitine is capable of reversing the inhibition of adenine nucleotide translocase and thus can restore the fatty acid oxidation mechanism which constitutes the main energy source for the myocardium. Therefore, these results indicate that l-carnitine is a useful therapeutic agent for the treatment of congestive heart failure in combination with traditional pharmacological therapy.

Adult↗
PubMed1992

Effect of L-carnitine on the cellular distribution of carnitine and its acyl derivatives in the ischemic heart.

The purpose of this study was to investigate the cellular distribution of carnitine and its acyl derivatives in the normal and ischemic myocardium, and the effects of exogenous 1-carnitine on this distribution and mitochondrial function in the ischemic dog heart. Under non-ischemic conditions, about 93% of the total cellular carnitine was located in the cytosolic compartment and 6.5% in the mitochondrial compartment. Sixty minutes of ischemia induced a decrease in the cytosolic free carnitine content, but caused the accumulation of long-chain acylcarnitine in the cytosolic and mitochondrial compartments. Treatment with 1-carnitine (30 or 100 mg/kg, i.v.) inhibited the mitochondrial accumulation of long-chain acylcarnitine. Free fatty acid (FFA) metabolism in the mitochondria differs from that in the cytosol. So, it is necessary to investigate the changes in FFA metabolism in both of these cellular compartments. Our results suggest that 1-carnitine has a protective effect on the ischemic heart by selectively reducing mitochondrial accumulation of long-chain acylcarnitine.

Acylation↗
PubMed1992

Crossover trial comparison of enalapril maleate and trichlormethiazide in the treatment of essential hypertension: emphasis on the quality of life.

Enalapril and trichlormethiazide were compared with respect to effects on the quality of life in a crossover study of 36 patients with hypertension. Multiple-choice 34-item questionnaires with three possible answers (severe, mild and none) per question were used to assess symptoms and mood. Twenty patients were initially given enalapril and 16 were initially given trichlormethiazide. There was no significant difference in the antihypertensive efficacy of the 2 drugs. Treatment with enalapril resulted in significant improvement in 11 of the 34 items, and a tendency for another 4 items to improve. Treatment with trichlormethiazide resulted in significant improvement in only 5 items and a tendency to improve in 2. When enalapril and trichlormethiazide were compared, significantly greater improvement in 2 items and a tendency toward greater improvement in 4 items was seen with enalapril treatment. Thus, enalapril was found to be more efficacious than trichlormethiazide with respect to quality of life in patients with hypertension.

Aged↗
PubMed1992

Localization of exercise-induced myocardial ischemia with ST depression.

This study was undertaken to determine whether the site of ST depression on 12-lead exercise electrocardiography can identify the ischemic site assessed by myocardial Tl-201 emission computed tomography in 409 patients with transient defects. ST depression in some leads was more frequent in those with inferior or lateral ischemia than in those with anterior ischemia. In 214 patients with ST depression and no ST elevation, however, the frequency of ST depression in each lead was similar between those with and without anterior ischemia. In 63 patients with ST depression, single vessel disease and no infarction, the frequency of ST depression in each lead was similar among those with anterior, inferior and lateral ischemia. Moreover, in patients with abnormal Q waves, the site of ST depression was not related to the location of ischemia. In conclusion, the site of exercise-induced ST depression could not be used to determine an ischemic region.

Arteriosclerosis↗
PubMed1992

Coronary artery disease in patients with arteriosclerosis obliterans of the lower extremities or aortic aneurysm.

Routine coronary angiography was performed in order to determine the incidence and clinical condition of coronary artery disease in 37 patients with arteriosclerosis obliterans or aortic aneurysm. Coronary angiography demonstrated significant stenosis in 12 (57%) of 21 patients with arteriosclerosis obliterans and in 7 (44%) of 16 patients with aortic aneurysm. The prevalence of risk factors for arteriosclerosis was similar for patients with arteriosclerosis obliterans and those with aortic aneurysm, and similar for patients with and without coronary artery stenosis. But coronary artery disease is often silent in patients with arteriosclerosis obliterans.

Aged↗
PubMed1992

Purification and characterization of tRNA(adenosine-1-)-methyltransferase from Thermus thermophilus HB27.

A58, the conserved adenosine residue in the T psi C loop of tRNAs, is methylated to m1A 58 in an extreme thermophile, Thermus thermophilus HB27. The enzyme catalyzing this methyltransfer reaction was purified from the thermophle. The substrate specificity of the enzyme was investigated by using tRNA fragments. The enzyme can transfer the methyl group to the 3'-half fragment of E. coli initiator tRNA, indicating that the main recognition site of the enzyme exists in the 3' half of tRNA including the T-loop and the T-stem.

Escherichia coli↗
PubMed1992

[Usefulness and limitations of ECG-gated myocardial single-photon emission computed tomography with 99mTc-methoxy-isobutyl-isonitrile (MIBI) in patients with prior myocardial infarction].

To evaluate the relationship between regional wall motion and 99mTc-methoxy-isobutyl-isonitrile (MIBI) uptake, ECG-gated single-photon emission computed tomography (SPECT) with 99mTc-MIBI was performed in 20 patients with prior myocardial infarction. The left ventricular images at end-diastole (ED) and end-systole (ES) were divided into 39 segments, respectively. Based on circumferential profile analysis, relative uptake (%EDc, %ESc), percent count increase (% delta C), and normalized percent count increase (% delta Cn) were analyzed in each segment and compared with regional wall motion indices assessed by echocardiography and left ventriculography. ECG-gated SPECT with 99mTc-MIBI provided high contrast tomograms of the left ventricular myocardium. %EDc and %ESc showed good correlations with regional wall motion indices. % delta C and % delta Cn, however, showed lower correlations compared with %EDc and %ESc. In conclusion, high-quality left ventricular images were obtained with 99mTc-MIBI ECG-gated SPECT, but quantitative analysis based on only percent count increase (% delta C) have limitations for evaluation of regional wall motion.

Aged↗