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Biomedical subjects

Y Yui

Publications and source records attributed to Y Yui.

At least 73 records · Page 4Linked to original sources

Decreased sulfhydryl groups of serum albumin in coronary artery disease.

We hypothesized that oxidative processes in myocardial tissues initiated by ischemia also cause the same kind of changes in blood proteins and lead to oxidation of sulfhydryl groups (SH). To test this hypothesis, the ratio (%MA) of mercaptalbumin to total albumin (= mercaptalbumin + nonmercaptalbumin) and the total SH contents of serum were measured in patients with coronary artery disease. There was a positive correlation between %MA and total SH contents and both values were reduced in proportion to the severity of the coronary artery disease. Furthermore, these values were lower early hours after the onset of acute myocardial infraction than 4 weeks later. These results support our hypothesis, and may provide a basis for the administration of agents which can counteract oxidative stress in order to protect myocardium in patients with coronary artery disease.

Adult↗

Cytosolic and membrane-bound nitric oxide synthase.

Cytotoxic activated macrophages were sonicated and centrifuged. The activity of nitric oxide (NO) synthase was present in the supernatant and independent of Ca2+. The pellets were washed three times and treated with buffer containing 0.1% Triton X-100 or buffer alone, followed by centrifugation. The supernatant containing Triton X-100 showed NO synthase activity that was dependent on Ca2+, whereas the supernatant without the detergent had little activity. These data suggest that there are two forms of NO synthase: cytosolic and membrane-bound enzymes.

Amino Acid Oxidoreductases↗

A new type of vasodilator, HA1077, an isoquinoline derivative, inhibits proliferation of bovine vascular smooth muscle cells in culture.

The effects of a newly developed vasodilator agent, HA1077 [1-(5-isoquinolinesulfonyl)-homopiperazine hydrochloride], were investigated on the proliferation of cultured bovine aortic vascular smooth muscle cells (VSMC). HA1077 (10-100 microM) inhibited both fetal calf serum-induced proliferation and [3H]thymidine incorporation into DNA of the growth-arrested VSMC in a dose-dependent manner. When quiescent cells were stimulated with platelet-derived growth factor followed by insulin, HA1077 (1-30 microM), administered together with either stimulation, showed dose-dependent inhibition of [3H]thymidine incorporation. Further reduction of [3H]thymidine incorporation was observed when HA1077 was present at both stimulations, suggesting that HA1077 suppresses DNA synthesis acting in both competence and progression stages. After stimulation with fetal calf serum, quiescent VSMC started and ceased DNA synthesis in 15 to 18 hr and 24 hr, respectively. HA1077 inhibited [3H]thymidine incorporation when it was added either from 12 hr to 15 hr or from 21 hr to 24 hr after serum stimulation. In addition, when percent inhibition of [3H]thymidine incorporation by continuous exposure to HA1077 was examined as a function of the time it was added, reductions of the value were observed at 0 to 3 hr, 12 to 18 hr and 21 to 24 hr. Thus, we concluded that HA1077 suppresses DNA synthesis of bovine VSMC acting at the G0/G1 and the G1/S phase transitions and also in the S phase of the cell cycle. It is suggested that this agent may act as a potent inhibitor of VSMC proliferation as well as a vasodilator.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Stabilizing factor(s) of nitric oxide (NO) synthetase.

We found that the cytosol of rat peritoneal polymorphonuclear neutrophils contains factor(s) that can stabilize an unstable enzyme, nitric oxide synthetase, in the cytosol. This enzyme has been purified to a single protein from the cytosol. Its half-life was 3 hours at 4 degrees C and was prolonged to greater than 24 hours by the stabilizing factor in the cytosol. The molecular weight of the stabilizing factor was greater than 100,000. Its activity was lost by the treatment with heating or alkali for 1 min or with acid for 5 min. It did not adhere to the carboxymethyl or diethylaminoethyl column at neutral pH. This stabilizing factor(s) may play a role in the regulation of the nitric oxide synthetase.

Amino Acid Oxidoreductases↗

Lipoproteins are inhibitors of endothelium-dependent relaxation of rabbit aorta.

The present study was performed to investigate plasma inhibitors of endothelium-dependent relaxation other than hemoglobin and low-density lipoprotein (LDL). We purified an inhibitor that contained a protein of 28,000 Da from human plasma by ammonium sulfate precipitation and serial chromatography. NH2-terminal sequence analysis revealed the protein to be homologous with human apolipoprotein A-I (Apo A-I), a major apolipoprotein of high-density lipoprotein (HDL). Very low-density lipoprotein (VLDL), LDL, and HDL obtained from rabbit plasma reversed endothelium-dependent relaxation of rabbit aorta induced by acetylcholine (ACh) and A23187 but did not inhibit relaxations induced by nitroglycerin or nitric oxide. These inhibitory activities were lost by delipidation of lipoproteins, and there were no differences in the inhibitory activity among these three lipoproteins on the basis of phospholipid concentration. Moreover, phospholipids such as phosphatidylcholine, phosphatidylinositol, and sphingomyelin reversed relaxations by ACh and A23187. Thus all lipoproteins inhibit endothelium-dependent relaxation, and this nonspecific inhibition seems to be due to the inhibition of production or release of endothelium-derived relaxing factor by phospholipids in the lipoprotein complex.

Animals↗

Prostaglandin I2 half-life regulated by high density lipoprotein is decreased in acute myocardial infarction and unstable angina pectoris.

To investigate the prostaglandin I2 (PGI2) half-life regulated by high density lipoprotein (HDL) in patients with coronary artery disease (CAD), we determined the stability of PGI2 and serum apolipoprotein A-I (Apo A-I) and apolipoprotein A-II (Apo A-II) levels in four age-matched groups of patients: controls (n = 17), angina pectoris (n = 18), unstable angina pectoris (n = 17), myocardial infarction (n = 19) (acute phase, 3.6 +/- 1.7 hours from onset; subacute phase, 75 +/- 15 hours from onset in the same patients). Serum PGI2 half-life and total serum Apo A-I levels were lower in the CAD group than in the control group. PGI2 was least stable in patients with unstable angina and the acute phase of myocardial infarction. In these patients, the molar ratio of Apo A-I to Apo A-II and HDL-associated Apo A-I levels were decreased, and free Apo A-I levels were increased. After in vitro incubation of HDL with increasing amounts of Apo A-II, Apo A-I in HDL was displaced by Apo A-II, with the parallel decrease in stability of PGI2. Free Apo A-I cannot stabilize PGI2. HDL-associated Apo A-I, whose amount is affected by Apo A-II, stabilized PGI2 and correlated well with stability of PGI2 in patients with CAD and control patients. Decreased PGI2 half-life may play an important role in the pathogenesis of atherosclerosis and thrombus formation in the coronary arteries, especially thrombus formation during an acute coronary event.

6-Ketoprostaglandin F1 alpha↗

Increased hydrolysis of cholesteryl ester with prostacyclin is potentiated by high density lipoprotein through the prostacyclin stabilization.

Prostacyclin (PGI2) has been reported to stimulate activities of acid cholesteryl ester hydrolase (ACEH; EC 3.1.1.13) and neutral cholesteryl ester hydrolase (NCEH; EC 3.1.1.13) in the smooth muscle cells leading to a decrease in intracellular cholesteryl ester. Recently, we have found that the half-life of PGI2 was prolonged through stabilization by HDL. HDL is known to have anti-atherogenic properties, although its precise mechanism has not been fully clarified. We therefore hypothesized that HDL can exert anti-atherogenic action by augmenting PGI2-stimulated increases in the activities of ACEH and NCEH. After incubation with PGI2 and HDL, a cell homogenate was made from which the activities of ACEH and NCEH were assessed. HDL significantly augmented the PGI2-induced increase in the activities of both enzymes. This effect of HDL was abolished in the absence of PGI2. Elevated intracellular levels of cyclic AMP were maintained for longer periods by HDL. The increase in both intracellular cyclic AMP levels and enzyme activities disappeared in the presence of an inhibitor of adenylate cyclase, 2'5'-dideoxyadenosine. Radiolabeled smooth muscle cells demonstrated a significant loss in total cholesterol and cholesteryl ester after treatment with PGI2 and HDL, due to the increase in cholesteryl ester hydrolytic activities. These data suggest that HDL enhanced the PGI2-stimulated hydrolysis of cholesteryl ester and augmented the PGI2-induced reduction of cellular cholesteryl ester content by stabilizing PGI2.

Animals↗

The dynamic changes of plasma tissue-type plasminogen activator level and the activity of its inhibitor during coronary vasospasm.

This study aimed to examine the dynamic changes of the fibrinolytic system during coronary vasospasm. Tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor (PAI) and fibrinopeptide A (FPA) levels were measured in the great cardiac venous and arterial blood of 9 patients with clinically and angiographically proven vasospastic angina and 11 controls. Before ergonovine provocation, although there was no difference between the above 2 groups in t-PA levels in the aorta or the great cardiac vein, the PAI level in patients with variant angina was lower than in the controls both in the aorta (4.2 +/- 3.5 IU/ml vs 10.9 +/- 5.2 IU/ml) and in the great cardiac vein (2.3 +/- 2.9 IU/ml vs. 11.9 +/- 4.9 IU/ml). During ergonovine-induced coronary vasospasm in patients with variant angina, the t-PA level in the great cardiac vein significantly increased from 3.4 +/- 0.7 ng/ml to 4.4 +/- 0.5 ng/ml (p less than 0.05), but it did not change in the aorta. The maximal dose of ergonovine (0.4 mg) induced mild diffuse coronary vasoconstriction in the controls, and this diffuse coronary vasoconstriction induced a reduction of PAI levels in the great cardiac vein from 11.9 +/- 4.9 IU/ml to 9.5 +/- 4.8 IU/ml (p less than 0.05). FPA levels in the great cardiac vein did not change during ergonovine-induced coronary vasospasm in either group. Thus, the coronary vasospasm induced the release of t-PA from endothelial cells of coronary vessels and resulted in the reduction in the PAI activity in the great cardiac vein.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Intravenous recombinant tissue-type plasminogen activator in patients with acute myocardial infarction--a report from the multicenter thrombolysis trial.

The efficacy and safety of intravenous infusion of human tissue-type plasminogen activator (rt-PA), developed in Japan (TD-2061), were investigated in 205 patients (154 men and 51 women) with evolving myocardial infarction (EMI). TD-2061 was given at a rate of 3.2 to 50 mg over 1 h after angiographic documentation of complete or subtotal (99%) occlusion. Nineteen patients were excluded as they did not meet the inclusion criteria. A total of 186 patients were divided into 6 groups according to the total dose given: Group I, 3.2 mg, 10 patients (pts); Group II, 6.4 mg, 15 pts; Group III, 12.8 mg, 15 pts; Group IV, 25.6 mg, 38 pts; Group V, 33.3 mg, 70 pts; Group VI, 50.0 mg, 38 pts. Ages ranged from 30 to 70 years (mean 60 +/- 1). Coronary angiography was done at 30 min and 1 h. In patients with TIMI grades 0 and 1, reperfusion was accomplished after 1 h in 22% of Group I, 50% of Group II, 64% of Group III, 70% of Group IV, 67% of Group V, and 74% of Group VI patients. Complications were hypotension, nausea and vomiting, bradycardia and bleeding at the puncture site. These findings suggest that clot-selective coronary thrombolysis can be induced in patients with EMI by means of human tissue-type plasminogen activator without concomitant induction of a severe systemic lytic state. The optimal dose for Japanese patients is considered to be 33.3-50.0 mg from the standpoint of reperfusion.

Adult↗

Mechanism for the generation of active smooth muscle inhibitory factor (IF) from bovine retractor penis muscle (BRP).

The active smooth muscle inhibitory factor (IF) is generated by acidifying the extracts from the bovine retractor penis muscle (BRP). The activated IF is very similar to endothelium-derived relaxing factor (EDRF). However, the mechanism for the generation of active IF is yet unknown. From reverse-phase high performance liquid chromatographic data, the activities of nitrite loss were closely related to the contents of both sulfhydryl (SH) groups and L-cysteine. Thus, under acidic conditions, RSH and nitrite in the extracts are considered to react as follows: RSH + HNO2----RSNO + H2O, RSNO----(1/2) RSSR + NO, NO + (1/2)O2----NO2, NO2 + (1/2)H2O----(1/2)HNO2 + (1/2)HNO3. In addition to NO, RSNO is also a labile but potent vasodilator. Thus, activated IF seems to consist of RSNO and NO, and thiol-containing small molecules (molecular weight of less than 1,000) from BRP are closely involved in the generation of active IF.

Animals↗

Comparative analysis of physicochemical and immunochemical properties of the two major allergens from Dermatophagoides pteronyssinus and the corresponding allergens from Dermatophagoides farinae.

Two major allergens, DP1 (Der p I) and DP2 (Der p II), were isolated from the whole culture extract of Dermatophagoides pteronyssinus, and the physicochemical and immunochemical properties of these allergens were compared with those of the corresponding allergens from Dermatophagoides farinae, DF1 (Der fI) and DF2 (Der fII). On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, polyacrylamide gel isoelectric focusing and amino acid analysis, both DP1 and DP2 were demonstrated to have close physicochemical similarity with DF1 and DF2, respectively. On immunodiffusion with the use of rabbit antisera, the two Der I allergens showed the reaction of typical partial identity, while the two Der II allergens showed the reaction of almost complete identity. Radioallergosorbent test (RAST) and RAST absorption experiments with the use of sera from mite-allergic patients showed that human IgE antibody response to the Der I allergens was directed against both cross-reactive and species-specific determinants. In contrast, IgE antibodies to the Der II allergens were demonstrated to react almost completely to cross-reactive determinants.

Allergens↗

[Effects of hypopressure on blood gases and spirograms of patients suffering from chronic respiratory failure].

We examined the effects of hypopressure on blood gases and spirograms of patients suffering from chronic respiratory failure, and compared them with those of normal subjects, using the environmental control unit (ECU). The patients consisted of 2 with idiopathic interstitial pneumonia (IIP), 1 with pulmonary fibrosis due to RA, 3 with bronchiectasis, 2 with chronic bronchitis and 1 with diffuse panbronchiolitis (DPB). We examined their blood gases and spirograms under the condition of 760 mmHg pressure, 25 degrees C temperature and 60% humidity. Then the pressure of ECU decreased to 670 mmHg in 20 minutes, while the temperature and humidity were kept the same. The patients stayed in the hypopressured ECU for 1 hour, and were reexamined. The pressure of 670 mmHg is that of an altitude of about 1,000 m and that of the cabin pressure of commercial aircraft flying at about 9,000 m. The PaO2 of the patients decreased from 74.7 +/- 13.8 torr to 61.8 +/- 9.5 torr significantly. We found, however, the significant decrease of PaO2 in normal subjects from 97.2 +/- 7.8 torr to 80.4 +/- 6.5 torr under the same conditions. The rates of the decreased gases were almost same in both groups. Some patients showed remarkable decreases in VC and FEV1.0 under the hypopressure. No patients or control subject complained of subjective symptoms.

Adult↗

Two linear plasmid-like DNA elements simultaneously maintained in Pleurotus ostreatus.

Two linear plasmid-like DNA elements, designated pLP01 and pLP02, have been isolated from a strain of Pleurotus ostreatus, an edible basidiomycete. pLP01 (10.0 kb) and pLP02 (9.4 kb) were found in mitochondrial preparations of the fungus and appear to have 5' ends blocked by association of a protein. Proteinase K cleavability of the 5'-terminal protein of pLP01 was higher than that of pLP02, indicating that the terminal proteins of both plasmid-like elements are distinct from one another. pLP01 and pLP02 were estimated to be present to the extent of 1-2 copies each per mitochondrial genome equivalent. The two plasmid-like elements had no homology between them and also were not homologous with the mitochondrial and nuclear genomic DNAs of the fungus.

Basidiomycota↗

Isocratic determination of arachidonic acid 5-lipoxygenase products in human neutrophils by high-performance liquid chromatography.

A high-performance liquid chromatographic method was developed to determine arachidonic 5-lipoxygenase products in calcium ionophore-stimulated neutrophils. This procedure allows the simultaneous measurement of leukotriene B4 (LTB4) and its omega-oxidation products without using a gradient elution system. 20-Carboxy-LTB4, 20-hydroxy-LTB4, 6-trans-LTB4, 12-epi-6-trans-LTB4, LTB4 and 5s,12s-dihydroxyeicosatetraenoic acid can be separated and quantitated by reversed-phase chromatography using isocratic elution. The generation and degradation of 5-lipoxygenase products by human neutrophils following stimulation with calcium ionophore have been examined by this method.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Phospholipid analysis of human eosinophils: high levels of alkylacylglycerophosphocholine (PAF precursor).

The phospholipid composition and fatty acid profiles of human eosinophils were studied. Extremely high levels of ether phospholipids were found in this type of cell, such as alkylacylglycerophosphocholine (GPC) and alkenylacylglycerophosphoethanolamine (GPE); these two ether phospholipids accounted for about three-fourths of the choline and ethanolamine glycerophospholipids (CGP and EGP), respectively. Fatty acid analyses revealed that very large portions of arachidonic acid (20:4) were esterified to alkylacyl-GPC (92.0% in CGP) and alkenylacyl-GPE (86.6% in EGP), respectively. While high amounts of alkylacyl-GPC and the abundance of 20:4 in this ether phospholipid have been observed in other types of blood cells of various animals, these percentages for human eosinophils are the highest among such cells. These results suggest that alkyl and alkenyl ether phospholipids play essential roles in human eosinophils in various physiological and pathological conditions.

Eosinophils↗