[Physiological and biochemical changes in ischemic myocardium].
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Calcium↗
Biomedical subjects
N Yamazaki
Publications and source records attributed to N Yamazaki.
[Pulmonary diseases due to toxic gases, irritant gases and fumes].
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Gas Poisoning↗
Isolation and characterization of cDNA clones and a genomic clone encoding rat mitochondrial adenine nucleotide translocator.
Two cDNA clones encoding rat mitochondrial adenine nucleotide translocator were isolated from libraries constructed from mRNAs of heart and liver. These two clones corresponded to the heart-skeletal muscle type (ANT1) and fibroblast type (ANT2), respectively. A genomic clone encoding rat ANT1 was also isolated and characterized.
Amino Acid Sequence↗
Modification of contractile proteins by oxygen free radicals in rat heart.
This study was undertaken to investigate the effects of oxygen free radicals on myofibrillar creatine kinase activity. Isolated rat heart myofibrils were incubated with xanthine+xanthine oxidase (a superoxide anion radical-generating system) or hydrogen peroxide and assayed for creatine kinase activity. To clarify the involvement of changes in sulfhydryl groups in causing alterations in myofibrillar creatine kinase activity, 1) effects of N-ethylmaleimide (sulfhydryl groups reagent) on myofibrillar creatine kinase activity, 2) effects of oxygen free radicals on myofibrillar sulfhydryl groups content, and 3) protective effects of dithiothreitol (sulfhydryl groups-reducing agent) on the changes in myofibrillar creatine kinase activity due to oxygen free radicals were also studied. Xanthine+xanthine oxidase inhibited creatine kinase activity both in a time- and a concentration-dependent manner. Superoxide dismutase (SOD) showed a protective effect on the depression in creatine kinase activity caused by xanthine+xanthine oxidase. Hydrogen peroxide inhibited creatine kinase activity in a concentration-dependent manner; this inhibition was prevented by the addition of catalase. N-ethylmaleimide reduced creatine kinase activity in a dose-dependent manner. The content of myofibrillar sulfhydryl groups was decreased by xanthine+xanthine oxidase; this reduction was prevented by SOD. Furthermore, the depression in myofibrillar creatine kinase activity by xanthine+xanthine oxidase was protected by the addition of dithiothreitol. Oxygen free radicals may inhibit myofibrillar creatine kinase activity by modifying sulfhydryl groups in the enzyme protein. The reduction of myofibrillar creatine kinase activity may lead to a disturbance of energy utilization in the heart and may contribute to cardiac dysfunction due to oxygen free radicals.
Animals↗
Verapamil induced reduction of the myocardial beta-adrenoceptor density in BIO 14.6 cardiomyopathic Syrian hamsters.
In general, it is recognized that prolonged exposure to catecholamine leads to a reduction in the beta-adrenoceptor density (downregulation). However, it has been previously reported that the myocardial beta-adrenoceptor densities and norepinephrine levels significantly increase in the hearts of BIO 14.6 cardiomyopathic hamsters in the early stage. The mechanism of the increased beta-adrenoceptor density is not clearly elucidated, and it can not be excluded that this phenomenon may be a secondary effect. The purpose of this study was to assess the effect of verapamil on the density of beta-adrenoceptors in the heart of BIO 14.6 cardiomyopathic hamsters. The total number of beta-adrenoceptors in untreated BIO 14.6 hamsters was significantly higher at 90 days of age (30.4 +/- 2.2 v.s. 25.9 +/- 1.4 fmol/mg protein, p < 0.05). BIO 14.6 hamsters received daily intraperitoneal injections of 5 mg/kg verapamil for 70 days, from an age of 20 days. Verapamil protected against progressive myocardial damage (total damage; 8.2 +/- 0.7 v.s. 0.4 +/- 0.2%/area, p < 0.05) and the myocardial beta-adrenoceptor density returned to that of the normal control group (26.9 +/- 3.0 fmol/mg protein). Conversely, verapamil did not have an effect on the number of myocardial beta-adrenoceptors in normal golden hamsters. This study showed that verapamil protected against progressive myocardial damage and myocardial beta-adrenoceptor density returned to those of normal hamsters. These results suggest that an increased number of beta-adrenoceptors in the early stage of BIO 14.6 cardiomyopathic hamsters may be involved in the secondary pathogenesis of cardiomyopathy.
Animals↗
31P-NMR magnetization transfer study of reperfused rat heart.
The relationships between pressure rate product (PRP) and flux (PCr-->ATP) or flux(Pi-->ATP) were studied in isolated perfused rat hearts by the method of saturation transfer using 31P-NMR during the preischemic and reperfusion periods. The hearts were made ischemic for 15 min, followed by 60 min of reperfusion. PRP was almost completely depressed, and recovered to 60% of the control level (preischemic period) after reperfusion. The ATP level during reperfusion was significantly decreased, whereas there was no significant change in PCr level. Pi level of reperfused hearts was significantly higher than that in the control. Both flux(PCr-->ATP) and flux(Pi-->ATP) were significantly decreased during the reperfusion period (both p < 0.05). However, the flux(PCr-->ATP)/PRP ratio during reperfusion did not differ from that of the control. This result indicates that the decrease in flux(PCr-->ATP) was matched by a similar decrease in cardiac performance. In contrast, the flux(Pi-->ATP)/PRP ratio during reperfusion was significantly decreased compared to that of control. These results suggest that the stunned heart needs less ATP turnover in proportion to its depressed contractile activity, and flux(Pi-->ATP) may lmit the recovery of postischemic performance.
Adenosine Triphosphate↗
Reversal of perfusion defect on resting thallium-201 emission computed tomography in stunned myocardium and coronary spasm.
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Aged↗
Chromosomal aberrations induced in vitro by 3,7- and 3,9-dinitrofluoranthene.
The chromosomal aberration test using a Chinese hamster cell line (CHL) was carried out with 3,7- and 3,9-dinitrofluoranthene (DNF) with and without exogenous metabolic activation (rat liver S9 mix). The highest dose tested was limited to 20 micrograms/ml because of the compounds' insolubility in dimethyl sulfoxide. Both DNFs induced chromosomal aberrations in the absence of S9 mix; the frequency was not very high. Results were reproducible, but without clear dose-response relationships. Neither DNF induced chromosomal aberrations in the presence of S9 mix. Both DNFs did not induce polyploid cells under any conditions.
Aneuploidy↗
Effects of hydrogen peroxide on stimulatory guanine nucleotide-binding protein in rat heart.
This study was undertaken to examine the effects of hydrogen peroxide on stimulatory guanine nucleotide-binding protein (Gs), and coupling in the beta-adrenergic receptor-Gs-adenylate cyclase system in rat heart, in vitro. Cardiac membranes were preincubated with various concentrations (0.1, 1, and 10 mM) of hydrogen peroxide at 30 degrees C for 5, 10, 30 and 60 min. Although the assay of beta-adrenergic receptors involving [3H]-dihydroalprenolol ([3H]-DHA) binding revealed that the maximal number of binding sites (Bmax) was not altered, the dissociation constant (Kd) for [3H]-DHA was increased in the presence of 1 mM and 10 mM hydrogen peroxide (control 0.68 +/- 0.16 nM, vs 1 mM H2O2 1.13 +/- 0.16, 10 mM H2O2 1.01 +/- 0.12). Conversely, no significant changes in Gs activities were observed in hydrogen peroxide-treated groups. Adenylate cyclase activity (stimulated by forskolin) was significantly reduced by 10 mM hydrogen peroxide after a 5 min preincubation period (control 277.1 +/- 19.2 pmol cAMP/mg protein/min, H2O2 230.3 +/- 14.9). The amounts of cyclic AMP produced by the stimulation of membranes with GTP, GTP+(l)-isoproterenol, guanylimidodiphosphate (Gpp(NH)p) or Gpp(NH)p+(l)-isoproterenol were significantly lower in 10 mM hydrogen peroxide-treated groups than those in controls (GTP: control 57.6 +/- 5.6 pmol cAMP/mg protein/min vs H2O2 46.4 +/- 6.9, GTP+(l)-isoproterenol: control 83.9 +/- 10.2 vs H2O2 67.7 +/- 10.3, Gpp(NH)p: control 77.5 +/- 8.8 vs H2O2 61.0 +/- 8.6, Gpp(NH)p+(l)-isoproterenol: control 105.0 +/- 13.1 vs H2O2 83.9 +/- 12.2, forskolin: control 223.2 +/- 13.8 vs H2O2 182.8 +/- 18.4).(ABSTRACT TRUNCATED AT 250 WORDS)
Adenylyl Cyclase Inhibitors↗
Dual-tracer autoradiography with thallium-201 and iodine-125 MIBG in BIO 14.6 cardiomyopathic Syrian hamsters.
Dual-tracer imaging of the heart with 125I-metaiodobenzylguanicline (MIBG) and 201Tl can simultaneously demonstrate the distribution of sympathetic nerve endings and the underlying myocardial perfusion. A quantitative dual-tracer autoradiographic study with 201Tl and 125I-MIBG was performed to investigate changes in the distribution of cardiac sympathetic innervation with the progression of cardiomyopathy in BIO 14.6 hamsters. The distribution of 201Tl was uniform in control hamsters and BIO 14.6 hamsters at all stages of cardiomyopathy. In contrast, a reduction in MIBG accumulation occurred in the endocardial region of the left ventricular free wall and the left ventricular aspect of the interventricular septum in BIO 14.6 hamsters at 3 and 8 months of age. Thus, there was an uncoupling of the left ventricular distribution of 201Tl and 125I-MIBG in BIO 14.6 hamsters. In addition, interstitial fibrosis was increased in the interventricular septum, the subendocardial region of the left ventricular free wall, and the right ventricular wall, which were the sites of reduced MIBG accumulation. This study shows that dual myocardial imaging with MIBG and 201Tl may be useful for investigating patients with cardiomyopathy.
3-Iodobenzylguanidine↗
Effects of phospholipase C on action potentials and intracellular Ca2+ concentration in guinea pig heart.
To clarify the role of phospholipase C (PLC) in arrythmias and cell injury during myocardial ischemia/reperfusion, we studied its effects on electrophysiology and [Ca2+]i in guinea pig hearts. After exposure to PLC (1 and 2 U/ml), the action potential durations of right ventricular papillary muscles were decreased. Delayed afterdepolarizations were observed in all of the preparations, and some developed into triggered activities. Developed tension decreased after an initial increase for the first 5 min, while resting tension increased consistently. The effects of PLC (0.02, 0.1, and 0.2 U/ml) on [Ca2+]i of ventricular myocytes were measured using fura-2 fluorescence. The ratio of rod-shaped cells to all cells decreased in a time- and a concentration-dependent manner. Perfusion with 0.1 U/ml PLC elevated [Ca2+]i from 56 +/- 5 nM to 245 +/- 47 nM before cell rounding, and to 1167 +/- 172 nM after cell rounding, suggesting that PLC causes Ca2+ overload. In conclusion, activation of PLC may play a role in arrhythmias and cell injury during ischemia/reperfusion. The increase in [Ca2+]i during ischemia/reperfusion may activate phospholipase, which would further increase [Ca2+]i to form a vicious cycle.
Action Potentials↗
Ca2+ transients and cell shortening in diabetic rat ventricular myocytes.
To investigate the role of abnormal Ca2+ metabolism in the diminished contractile function of diabetic myocardium, we measured the Ca2+ transients and cell contraction of diabetic rat myocytes. Isolated diabetic (8 weeks after 40 mg/kg streptozotocin, i.v.) and normal myocytes were loaded with acetoxymethyl ester of indo-1 (indo-1/AM). Ca2+ transients and cell circumferential shortening were measured simultaneously, using high temporal resolution video image analysis. The diastolic base and systolic peak of Ca2+ transients were significantly lower in diabetic myocytes than in normal myocytes (peak ratios: 0.49 +/- 0.02 vs 0.56 +/- 0.01, p < 0.05; base ratios: 0.43 +/- 0.01 vs 0.48 +/- 0.01, p < 0.01, Mean +/- SE). The cell circumferential shortening of diabetic myocytes was also significantly lower than that of normal myocytes (2.9 +/- 0.3% vs 5.2 +/- 0.9%, p < 0.05). Although isoproterenol (10(-8) and 10(-7) M) increased the peak of Ca2+ transients in both diabetic and normal myocytes, the peak value of Ca2+ transients in the diabetic group was significantly lower than that in the normal group. The decreased Ca2+ transients may be responsible for the decreased contractile function in diabetic myocardium.
Animals↗
Effects of propranolol and diltiazem on the rate of high-energy phosphate metabolism in reperfused rat hearts--31P-NMR saturation transfer study.
The relationships between pressure rate product (PRP) and flux (PCr-->ATP) or flux (Pi-->ATP) were studied in isolated perfused rat hearts by the saturation transfer method using 31P-NMR. The effects of propranolol and diltiazem on phosphate metabolism were also studied. After a 40 min preischemic period, the hearts were subjected to a 15 min period of ischemia, followed by 60 min of reperfusion. Propranolol (0.4-1.2 microM) or diltiazem (3.0-6.0 microM) was infused for 30 min before ischemia and reinfused after reperfusion for 60 min. The flux (PCr-->ATP)/PRP ratio at reperfusion did not differ from that at preischemia. This value was also not affected by propranolol or diltiazem treatment. However, the flux (Pi-->ATP)/PRP ratio at reperfusion was significantly less than that at preischemia. Moreover, this value was significantly improved by propranolol or diltiazem treatment. This study demonstrates that 1) flux (PCr-->ATP) has a good correlation with cardiac performance, 2) stunned myocardium needs less ATP turnover for survival of its depressed contractile activity, and 3) flux (Pi-->ATP) can limit recovery of postischemic performance. Protective effects of propranolol and diltiazem are exerted on the flux (Pi-->ATP), i.e. ATP derived from glycolytic flux, in the reperfused heart.
Animals↗
Inhibition of head and neck tumor cell colony growth by lymphokine activated killer cells.
The antiproliferative effect of lymphokine activated killer (LAK) cells on head and neck tumor cells has not previously been elucidated. We studied the inhibitory effects of recombinant interleukin-2 activated lymphocytes on tumor colony formation in semisolid agar, using head and neck tumor cells prepared from established tumor cell lines (K562, HT29, HLaC78) and xenografted head and neck squamous cell carcinomas on nude mice (XKN, XLL, XFL, XKF). LAK cells demonstrated a significant inhibitory effect on colony formation. The effects of LAK cells on cultured tumor cell lines were evaluated in a dose dependent manner using effector: target ratios. In addition, the colony formation of tumor cells derived from xenografted nude mouse was inhibited by LAK cells. These results suggest that LAK cells generate an antiproliferative effect on head and neck tumor cells.
Adenocarcinoma↗
Establishment of a cisplatin-resistant KB cell line and its characterization.
A KB cell line resistant to cisplatin (KB-rc cell) was successfully established by exposing KB cells to a gradually increasing dose of cisplatin in vitro. The concentration of cisplatin required for 50% inhibition of KB-rc cell proliferation was 1.0 micrograms/ml, while that of KB cells was 0.5 micrograms/ml. Studies of KB-rc cell kinetics after treatment with cisplatin, using flow cytometry, showed that the G2M phase block was inhibited on day 3, and that G0G1 phase cells started to increase on day 5. Therefore, cisplatin-resistance is related to inhibition of the G2M phase block. The decrease of KB-rc cell viability with cisplatin was accelerated by the addition of a Ca antagonist (verapamil) and S phase cells increased on day 3. Verapamil may therefore be useful for enhancement of the effect generated by cisplatin on cisplatin-resistant tumor cells.
Carcinoma, Squamous Cell↗
Experimental and clinical evaluation of DNA ploidy with use of double staining of keratin/DNA by flow cytometer in head and neck tumor.
As a basic study, an analysis was made, using flow cytometry (FCM), of a mixture of KB cells and lymphocytes after Propidium Iodide (PI)- Fluorescein Isothiocyanate (FITC) double strain. As a result, DNA histogram of only KB cells could be drawn. As a clinical application an analysis was made, using FCM, of tumor of the head and neck after double stain. It enabled the drawing of DNA histogram of only epithelial cells (cancer cells). Changes in DNA histogram of keratin positive cells were classified into three types: Type I: the same diploid type as whole cells, Type II: the same aneuploid type as them, and Type III: the different aneuploid type as them. Among 22 cases of malignant tumor there were 3 cases of Type I, 6 cases of Type II, and 13 cases of Type III. This method could contribute greatly to the detection of cancer cells and DNA diagnosis, and thus be useful clinically.
Biomarkers, Tumor↗
Effect of silane coupling agents with a bisfunctional hydrolyzable group.
Improvement of the siloxane layer on minerals by using a bisfunctional silane, such as 1,6-bis(trichlorosilyl) hexane and 1,8 bis(trichlorosilyl)octane, and the effects on adhesion of methacrylic resin to glass plates treated with the silanes were studied. The tensile bond strength of the resin to the glass plate treated with bisfunctional silane alone was high (about 20MPa) in spite of the fact that the molecule contains no double bonds. Furthermore, a mixture of bisfunctional silane and 3-methacryloxypropyltrichlorosilane showed an excellent effect for tensile bond strength and water-resistance. Based on the results, it is suggested that the better water resistant adhesion of the mixed silane depends on the higher degree of crosslinking in the siloxane phase and on the formation of an interpenetrating polymer network between the siloxane layer and the matrix resin.
Adhesiveness↗
A basic study of a new adhesive lining cement applied emulsion of hydrophobic polymer.
To diminish the effect of water on the adhesive durability of lining cement, an experimental lining cement using a hydrophobic polymer as the cement liquid was studied. The polymers were styrene-butadien-alkyl acrylate copolymer (SBA copolymer) and carboxylated styrene-butadien-alkyl acrylate copolymer (CSBA copolymer) and were used as aqueous emulsions. The cement powder consisted of alkaline silicate and calcium disilicate. The pH values of the immersion water of the cement prepared from emulsion of SBA copolymer (SBA cement) was almost the same as that of calcium hydroxide cement. The compressive and diametral tensile strengths of SBA cement gradually increased over time in water. The bond strengths of cement prepared from the CSBA copolymer emulsion containing five percent carboxyl groups by weight were superior to those of calcium hydroxide cement.
Acrylic Resins↗