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Y Etoh

Publications and source records attributed to Y Etoh.

At least 55 records · Page 3Linked to original sources
PubMed1990

Synthesis and structure-activity relationships of human renin inhibitors designed from angiotensinogen transition state.

The synthesis and the structure-activity relationships of renin inhibitors designed from the angiotensinogen transition state are described. These inhibitors contained residues modified at P1-P1', P2, and P4-P3. Decrease in the size of side chain alkyl group in norstatine analog at P1 diminished the inhibitory activities of the compounds. Compound 5j, which contained valine residue instead of histidine residue at P2, inhibited potently cathepsin D (IC50 = 6.0 x 10(-9) M) and pepsin (IC50 = 3.5 x 10(-7) M) to the same extent as renin (IC50 = 8.5 x 10(-10) M), and thus was not specific for renin. The reduction of the beta-carbonyl group to methylene group in beta-carbonylpropionyl residue at P4-P3 decreased the potency about 2 orders against human renin (5i: IC50 = 1.1 x 10(-7) M vs. 1: IC50 = 2.4 x 10(-9) M). These results confirmed the rationality of our analysis of the interaction between an orally potent human renin inhibitor 1 and the active site of human renin using modeling techniques, showing that 1 fits the active site of renin favorably. The experimental details of the synthesis are presented.

Amino Acid Sequence↗
PubMed1990

[A case of alder (Alnus sieboldiana) pollinosis and its prevalence among the residents of a densely forested area].

The first patient with alder (Alnus sieboldiana Matsumura) pollinosis in Japan visited our clinic in April 1987. The patient was a 54 year old housewife who had lived in Kobe at the foot of Mt. Rokko since 1972, and had been suffering from the pollinosis for three years. In 1988, prevalence studies of A. sieboldiana in densely planted area close to the patient's house were performed using pollen count, immunological examinations and a population survey by questionnaire. A remarkably high prevalence rate of the pollinosis was demonstrated.

Adolescent↗
PubMed1989

Identification of the two types of specific receptor for activin/EDF expressed on Friend leukemia and embryonal carcinoma cells.

Activin and inhibin are polypeptide factors which control the release of follicle stimulating hormone(FSH) from pituitary cells. The recent finding that erythroid differentiation factor(EDF) is identical to activin showed the multifunctional feature of this protein. To identify the specific receptor for activin, the binding of 125I-labeled activinA was investigated for a number of culture cell lines. Friends leukemia cell, which can be differentiated by activin, and embryonal carcinoma(EC) cells(PCC3, P19 and F9), were found to express 3500-20,000 per cell of activin receptors. Scatchard plot analysis of the binding data shows that the receptors on those cells could be divided into two groups with different Kd values. The Kd values of high and low affinity receptors are 0.15-0.4 nM and 1.5-3.0 nM respectively. The proportion of the number of the high and low affinity receptors was varied in each cell. Inhibin was able to compete for activin binding to both types of receptors, although the binding affinity was about 50-200 fold lower than that of activinA. Transforming growth factor-beta had no binding ability to the activin receptors.

Activins↗
PubMed1989

Synergistic effect of antithrombin III, activated protein C and heparin on the inhibition of the tissue thromboplastin-mediated coagulation.

The synergistic effect of antithrombin III (ATIII), activated protein C (APC) and heparin on the tissue thromboplastin (TP)-mediated coagulation cascade was studied. APC prolonged the activated partial thromboplastin time of human plasma with increasing APC concentration but affected the prothrombin time only slightly. Neither ATIII nor heparin prolonged the prothrombin time by itself, while a mixture of APC and heparin strongly inhibited the coagulation. When the effects of APC, heparin and ATIII on the TP-mediated coagulation were examined with a solution consisting of prothrombin, factor V, factor VII, factor X and fibrinogen at physiological concentrations, the coagulation time was prolonged only slightly by the APC-heparin or ATIII-heparin mixture. However, the coagulation time was prolonged markedly by simultaneous addition of APC, ATIII and heparin to the solution. Inhibition of thrombin activity by the ATIII-APC-heparin mixture was weak as compared with that by the ATIII-heparin mixture after a 1-min incubation, but after a 2-min incubation the inhibitory activities were equal. Suppression of thrombin activity by the ATIII-APC-heparin mixture was supposed to be due to the inhibition of the interaction between ATIII and heparin on thrombin by APC because the APC-ATIII-heparin complex was detected by crossed immuno-electrophoresis but not by sodium dodecyl sulfate (SDS)-polyacrylamide electrophoresis. When the inhibitory effect of APC alone or the APC-heparin mixture on the platelet prothrombin converting activity (PPCA) was examined, heparin accelerated the PPCA inhibition by APC.(ABSTRACT TRUNCATED AT 250 WORDS)

Antithrombin III↗
PubMed1989

An orally active renin inhibitor: cyclohexylnorstatine-containing dipeptide (KRI-1314).

In our continuing search for low molecular weight, human renin inhibitors, a dipeptide derivative, morpholino-naphthyl-acyl-histidyl-cyclohexyl-norstatine (KRI-1314), was newly synthesized and estimated for oral effectiveness. This compound inhibited plasma renin from humans and from Japanese monkeys in vitro, with 50% inhibitory concentrations (IC50) of 4.7 x 10(-9) and 2.4 x 10(-8) mol/l, respectively. The mean blood pressure of sodium-depleted Japanese monkeys was lowered significantly after intravenous injection or oral administration of KRI-1314. The maximum reduction was attained 3 h after oral administration at a dose of 10 mg/kg. Plasma renin activity (PRA) was halved 1 h after oral administration of KRI-1314, and this inhibition persisted for more than 5 h. results suggest that KRI-1314, a potent, orally effective and long-lasting renin inhibitor, may become one of a new class of antihypertensive agent.

Administration, Oral↗
PubMed1988

Prevention of vasospastic angina by alcohol ingestion: report of 2 cases.

The authors report 2 patients with vasospastic angina in whom alcohol ingestion was effective in preventing angina. Coronary angiography revealed no organic coronary stenosis but demonstrated coronary artery spasm during angina attacks. In 1 patient, alcohol ingestion every six hours completely suppressed frequent spontaneous angina. In the other patient, alcohol ingestion markedly prolonged the duration of the exercise on treadmill testing by preventing exercise-induced coronary spasm.

Alcoholic Beverages↗
PubMed1987

Erythroid differentiation factor stimulates hydrolysis of polyphosphoinositide in Friend erythroleukemia cells.

We examined an early action of erythroid differentiation factor (EDF), a polypeptide which induces differentiation of Friend murine erythroleukemia (MEL) cells. (Eto et al., Biochem. Biophys. Res. Commun. 142: 1095-1103, 1987). In MEL cells, EDF caused a rapid and transient increase in cytoplasmic concentration of free calcium, [Ca2+]c. EDF increased [Ca2+]c even in the absence of extracellular calcium. When [3H]inositol-labeled MEL cells were incubated with EDF, EDF rapidly increased radioactivity in inositol trisphosphate, bisphosphate and monophosphate. EDF also increased [3H] diacylglycerol in [3H]arachidonate-labeled MEL cells. These results indicate that EDF increases [Ca2+]c by stimulating hydrolysis of polyphosphoinositide.

Activins↗
PubMed1987

Field desorption tandem mass spectrometry of anthracycline antibiotics, cosmomycin A, B, A', B', C and D.

Field desorption mass spectrometry was applied to a series of underivatized anthracycline, cosmomycins, to obtain fragment ions which were mass analysed using the linked scan technique without using collision activated dissociation. The daughter spectra of the various protonated compounds contain sugar sequence information which is in the mass spectra. The mass spectrometric data make it clear that field desorption tandem mass spectrometry can become a valuable additional technique for the structural analysis of anthracyclines.

Anthracyclines↗
PubMed1987

Purification and characterization of levanase from Actinomyces viscosus ATCC 19246.

The extracellular levanase of Actinomyces viscosus ATCC 19246 was purified about 3,701-fold in 11% yield from the bacterial culture supernatant by means of ammonium sulfate precipitation, followed by DE52 column chromatography, Sephadex G-100 gel filtration, hydroxylapatite column chromatography, and Bio-Gel A 1.5m gel filtration. The molecular weight of the enzyme was estimated to be 89,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme was optimally reactive at pH 6.0 and at 45 degrees C. The activity was inhibited by MnCl2, BaCl2, FeCl3, ZnCl2, HgCl2, and EDTA at a final concentration of 1 mM. The inhibition by EDTA was recovered by adding CaCl2 or MgCl2. The enzyme specifically hydrolyzed levan, but not sucrose, raffinose, melezitose, inulin, and dextran. These results indicate that the purified enzyme is specific for fructan (i.e., levan), which mainly consists of beta-(2,6) linkages.

Actinomyces↗
PubMed1986

Human renin inhibiting dipeptide.

KRI-1177, a dipeptide containing nor-statine inhibited renin activity in human and Japanese monkey plasma to a markedly greater extent than that in dog, rabbit and rat plasma. The systemic blood pressure of anesthetized monkeys was lowered by intravenous injections of this compound which also reduced plasma renin activity and concentration of angiotensins. KRI-1177 appears to selectively inhibit primate renin activity, thereby producing hypotension.

Animals↗
PubMed1986

Involucrin acts as a transglutaminase substrate at multiple sites.

Involucrin is a keratinocyte protein with a specialized function in terminal differentiation. Synthesized initially as a soluble protein, it later becomes a preferred substrate for a membrane-bound transglutaminase and becomes cross-linked into an insoluble envelope. When a crude keratinocyte extract containing about 2% involucrin is heated to 95 degrees, most proteins precipitate, but all of the involucrin remains in solution, where it is over 90% pure. This step has been incorporated into a simplified procedure for purification of the protein. Like intact involucrin, polypeptide fragments formed by the tryptic hydrolysis of involucrin are good substrates for the keratinocyte transglutaminase. Evidently amino acid residues participating in the enzyme-catalyzed cross-linking are distributed at numerous sites along the involucrin molecule.

Binding Sites↗
PubMed1985

Adult-onset acid maltase deficiency in siblings.

Two siblings who developed adult form acid maltase deficiency (AMD) are reported. The elder sister, a 30-year-old Japanese woman whose parents are cousins was admitted because of respiratory disturbance which she noticed two years previously. The muscle histology demonstrated numerous acid phosphatase positive vacuoles filled with PAS positive materials, and the muscle enzyme assay demonstrated a reduction of acid maltase activity, thus confirming a diagnosis of acid maltase deficiency of adult form. Her younger sister, a 25-year-old woman who had no obvious history of muscle weakness was admitted because of coma due to subarachnoideal hemorrhage and died two days later. Postmortem examination revealed the rupture of a fusiform aneurysm of the basilar artery whose wall showed vacuolar degeneration, and the histological and biochemical examination revealed that she had also AMD of the adult form. It is considered that the fragility of arterial wall, caused by vacuolar degeneration due to AMD, resulted as the rupture of aneurysm. Immunologically cross reactive material against acid maltase antibody was not detected. To our knowledge, this family is considered to be the third of AMD of the adult form reported in Japan.

Adult↗
PubMed1984

Effects of etafenone on myocardial energy metabolism as studied by an organ redoximeter and biochemical analyses.

Direct recording of reduced nicotinamide adenine dinucleotide (NADH) fluorescence was conducted with an organ redoximeter in isolated perfused guinea pig heart. Cross-clamping of the aortic inflow line resulted in an increase in NADH fluorescence. After etafenone (10(-6) M), there was a significant prolongation of the time to the detectable or the maximum increase in NADH fluorescence. The magnitude of the increase in NADH fluorescence tended to be reduced (135% as compared with 145% in the control group). Supplemental chemical analyses revealed a significant increase in creatine phosphate, adenosine triphosphate (ATP) and total adenine nucleotide in the etafenone-pretreated group 15 min after postischemic reperfusion, although the ischemia-induced changes were not improved by this compound. It was suggested that the better recovery of myocardial high energy phosphate levels produced by etafenone was brought about by a decrease in oxygen consumption due to a decrease in mechanical performance of the heart and possibly by a better resynthesis of ATP.

Animals↗
PubMed1984

The sequence and correlation of the changes in several parameters of energy metabolism induced by ischemic insult in heart muscle.

Samples of myocardium with varying degrees of ischemia were obtained from subendo- and subepicardium of nonischemic, ischemic border and center zones of canine left ventricles to assess the sequence of rapid alterations of several parameters of energy metabolism induced by myocardial ischemia. Ischemia was induced by occluding the left anterior descending coronary artery. The contents of creatine phosphate (CP) and ATP decreased significantly. There was a significant accumulation of lactate. The redox potential (Eh) and phosphorylation potential (l') also decreased sharply, but only a slight decrease in energy charge (E.C.) was noted. A close correlation was found between ATP and total adenine nucleotide (r = 0.99). There were various degrees of linear correlation between other parameters, except for ATP (and total adenine nucleotide) and Pi, and CP and l', which were uncorrelated. The sequence of rapid alterations in the parameters of energy metabolism induced by ischemia was: (1) l' and CP, (2) Pi, ATP and Eh, and finally (3) lactate and E.C. A significant increase of the heart rate and a decline of the mean blood pressure and left ventricular pressure (LVP) were also observed in association with a slight change in the maximum rate of rise of the left ventricular pressure (dP/dtmax).

Adenine Nucleotides↗
PubMed1984

[An autopsy case of malignant histiocytosis showing a phenotype of S100 +lysozyme].

A 37-year-old Japanese man was admitted to our hospital because of high fever. The peripheral blood showed pancytopenia with a few erythrophagocytic histiocytes. A bone marrow aspirate revealed 12% immature histiocytes and 7% leukoerythrophagocytic histiocytes. A postmortem examination showed an infiltrative proliferation of immature histiocytes and erythrophagocytic histiocytes in the sinusoid of the liver, the urinary bladder, etc. These findings were consistent with malignant histiocytosis. In addition, these abnormal histiocytes showed a phenotype of S 100 protein +lysozyme.- In agreement with Watanabe's report, our findings suggest that malignant histiocytosis is the neoplasm of T-zone histiocytes.

Adult↗