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Y Matsuda

Publications and source records attributed to Y Matsuda.

At least 595 records · Page 33Linked to original sources
PubMed1994

Essential role of myosin light chain kinase in the mechanism for MgATP-dependent priming of exocytosis in adrenal chromaffin cells.

Ca(2+)-induced exocytosis in chromaffin cells now seems to consist of at least two distinct steps:MgATP-dependent Ca(2+)-dependent priming of the secretory apparatus, and Ca(2+)-dependent MgATP-independent step that triggers exocytosis (Bittner and Holz, 1992). Recently we found that a specific inhibitor of myosin light chain kinase (MLCK), wortmannin, inhibits Ca(2+)-induced catecholamine release from digitonin-permeabilized chromaffin cells, suggesting an implication of MLCK in the mechanisms of Ca(2+)-induced exocytosis (Imaizumi et al., 1992b). To elucidate further the implication of MLCK in the mechanism of exocytosis, we studied the effects of wortmannin and a peptide inhibitor (SM-1) corresponding to the pseudosubstrate domain of MLCK on MgATP-dependent and MgATP-independent release in digitonin-permeabilized chromaffin cells. Ca(2+)-induced exocytosis from the permeabilized cells in the presence of MgATP was inhibited by both SM-1 and wortmannin. Inhibitory effect of wortmannin on the rate of release induced by 10 microM Ca2+ in the presence of MgATP was much prominent in the later phase (1-10 min), although the initial rate was also decreased. SM-1 strongly inhibited ATP-dependent release without affecting Ca(2+)-dependent ATP-independent release at all. In addition, priming effect of MgATP that underlies Ca(2+)-dependent ATP-independent release was remarkably reduced by both wortmannin and SM-1. These results suggest that MLCK plays an essential role in ATP-dependent priming of Ca(2+)-induced exocytosis in chromaffin cells.

Adenosine Triphosphate↗
PubMed1994

Ca++ mobilization mediated by endothelin ETA receptor in endothelium of rabbit aortic valve.

The mechanism of Ca++ mobilization induced by endothelins (ETs) and the receptor subtype responsible for this effect were examined in the endothelium of rabbit aortic valve. In the endothelium loaded with fura-2, ET-1 (1-100 nM) induced large transient increase followed by small sustained increase in cytosolic Ca++ level ([Ca++]i) in a concentration-dependent manner. ET-3 induced only a small increase in [Ca++]i at higher concentrations (100-300 nM) than ET-1, whereas a selective ETB agonist, 100 nM IRL 1620 (succinyl-[Glu9, Ala11,15]ET-1 8-21), was ineffective. A selective ETA antagonist, 3 microM BQ-123, (cyclo [-Asp-Pro-Val-Leu-Trp-]) but not a selective ETB antagonist, 10 microM RES-701-1 [cyclic (Gly1-Asp9) (Gly-Asn-Trp-His-Gly-Thr-Ala-Pro-Asp- Trp-Phe-Phe-Asn-Tyr-Tyr-Trp)], inhibited the effects of ET-1 and ET-3. The sustained increase in [Ca++]i induced by ET-1 was abolished by 30 microM La , although 100 nM nicardipine was ineffective. In the absence of external Ca++ (with 0.5 mM EGTA), ET-1 induced only a transient increase in [Ca++]i, which was inhibited by an inhibitor of Ca+(+)-ATPase in endoplasmic reticulum, 1 microM thapsigargin. However, an inhibitor and an activator of Ca+(+)-induced Ca+(+)-release channel, 10 microM ryanodine and 10 mM caffeine, did not change [Ca++]i. These results suggest that, in the endothelium of rabbit aortic valve, only the ETA receptor mediates the effects of ETs to increase [Ca++]i, which is attributable to the release of Ca++ from thapsigargin-sensitive and ryanodine-insensitive Ca++ stores and also to the Ca++ influx through La (-)sensitive and dihydropyridine-insensitive Ca++ channels.

Amino Acid Sequence↗
PubMed1994

Mechanochemical synthesis of bioactive material: effect of environmental conditions on the phase transformation of calcium phosphates during grinding.

The effect of environmental conditions on the crystalline transformation of metastable calcium phosphates during grinding was investigated using X-ray diffractometry and fourier transformed infrared spectroscopy. A mixture of CoA and dicalcium phosphate anhydrate (DCPA, CaHPO4) did not transform after grinding in air. On the other hand, CaO and dicalcium phosphate dihydrate (DCPD, CaHPO4 2H2O) were converted into a noncrystalline solid. Mixtures of DCPD and Ca(OH)2 transformed into low-crystallinity hydroxyapatite after grinding in air. When ground under N2, a mixture of Ca(OH)2 and DCPD did not transform into hydroxyapatite, whereas that of DCPD: Ca(OH)2: CaCO3 = 1:0.8: 0.2 did. The results of X-ray diffraction of FT-IR spectra suggested that the presence of carbon dioxide in the grinding system was necessary for transformation from metastable calcium phosphates to hydroxyapatite.

Air↗
PubMed1994

[A national surveillance study on alcoholic liver disease in Japan (1986-1991)].

National surveillance studies on alcoholic liver disease (ALD) in Japan were performed in 1978 and 1985, by a previous Japanese study group for ALD (Takeuchi group). In the present study, a subsequent nationwide surveillance study was performed from 1986 to 1991 and the results were compared with the previous two studies. In order to clarify the etiological relationships between hepatitis C virus (HCV) infection and ALD, an analysis was also done according to the new diagnostic criteria of ALD which was proposed by this group (Takada group). By the criteria of the Takeuchi group, the incidence of ALD was not significantly different during 1986 to 1991. However, the incidence of hepatocellular carcinoma (HCC) in alcoholic cirrhosis (AL-LC) clearly increased during this period. The analysis including the results of the previous study indicate that incidence of ALD reached a plateau in 1980 and then features of ALD in Japan entered a stable stage. However, HCC in AL-LC continued to show a linear increase from 1976 to 1991. Analysis with the new criteria of the Takada group was done in cases of 1990 and 1991. Approximately 2 out of 3 cases of ALD were caused by alcohol alone, and the remaining cases were caused by a combination of alcohol and HCV. Cases caused only by HCV were very rare. The main etiology in patients with alcoholic hepatitis and fibrosis was alcohol alone and that in chronic hepatitis of heavy drinkers was a combination of alcohol and HCV. In half of the patients with AL-LC, the etiology was alcohol alone and in the other half patients, it was a combination of both factors. In most patients with HCC, the etiology was a combination of alcohol and HCV, indicating that HCV infection may be important for the development of HCC in alcoholics.

Carcinoma, Hepatocellular↗
PubMed1994

RES-701-1, a novel, potent, endothelin type B receptor-selective antagonist of microbial origin.

The unique cyclic peptide designated RES-701-1 blocked the binding of 125I-labeled endothelin (ET)-1 to bovine cerebellar membranes. ETB receptors are predominant in bovine cerebellum. However, in bovine lung membranes, where both ETA and ETB receptors are expressed, RES-701-1 inhibited 125I-ET-1 binding by up to 70%; RES-701-1, in the presence of the ETA-selective antagonist BQ-123 at 1 microM, displaced 125I-ET-1 binding completely. With membranes from transfected Chinese hamster ovary cells expressing the human ETA or ETB receptors, RES-701-1 inhibited 125I-ET-1 binding to the ETB receptor with an IC50 value of 10 nM but had no effect on 125I-ET-1 binding to the ETA receptor. Thus, RES-701-1 is highly specific for the ETB receptor; it has no effect on a number of other receptors. RES-701-1 selectively inhibited the ET-1-induced increase in intracellular Ca2+ concentration in COS-7 cells expressing the ETB receptor but did not inhibit the Ca2+ transient in ETA-expressing cells. When injected intravenously (250 nmol/kg) into anesthetized rats, RES-701-1 abolished the initial depressor response to ET-1 but enhanced the subsequent pressor response. These results suggest that RES-701-1 is a potent and specific antagonist for the ETB receptor and that RES-701-1 will be a powerful tool for understanding the physiological roles of this receptor.

Animals↗
PubMed1994

Neurites induced by staurosporine in PC12 cells are resistant to colchicine and express high levels of tau proteins.

Staurosporine, a protein kinase inhibitor, induces neurite outgrowth in pheochromocytoma cells and, therefore, may serve as a potential prototype for neurotropic drugs. The principal aim of the present study was to characterize the cytoskeletal properties of neurites induced in pheochromocytoma cells by staurosporine, in comparison to those induced by nerve growth factor, with emphasis on tubulin and tau proteins. Two major findings are described: a) staurosporine rapidly induces outgrowth of neurites that are resistant to colchicine treatment; and b) staurosporine treatment causes a rapid increase in tau protein levels, with a time course similar to the initiation of its neurotropic effects. The following observations exclude tubulin as the cellular target for staurosporine action: a) the level, cellular distribution, and assembly properties of tubulin are not affected by staurosporine treatment; and b) colchicine uptake, its binding to tubulin, and its interference with tubulin polymerization are not changed by staurosporine. On the other hand, staurosporine treatment causes a transient, dose-dependent increase in tau protein levels. This increase, which is already evident after 1 hr, reaches a maximum of 2 to 3 fold after 5 hr of treatment and declines to basal level within the next 10 to 15 hr. The rapid, transient increase of tau protein levels induced by staurosporine is reminiscent of its neurotropic properties. Here we characterize and compare the cytoskeletal properties of neurites induced by treatment with staurosporine and with nerve growth factor, and we offer a mechanistic explanation for the rapid stabilization of staurosporine induced neurites.

Alkaloids↗
PubMed1994

Is apoptosis involved in alcoholic hepatitis?

Apoptosis is a type of cell death which is clearly distinguishable from necrosis in its morphological and biochemical features. To clarify the role of apoptosis in alcoholic liver injury, we investigated the expression of apoptosis-related Lewis(Le)(y) antigen by immunohistochemistry in liver samples from patients suffering from alcoholic liver disease. Liver biopsy samples were taken from 20 patients who drank more than 80 g of ethanol per day on average. Indirect immunohistochemical staining was carried out using anti-cytokeratin and anti-Le(y) antibodies. To examine the relationship between Mallory bodies and apoptosis, double staining was performed using both antibodies. In alcoholic hepatitis, many Mallory bodies were stained with anti-cytokeratin antibody in hepatocytes of the centrilobular area. Le(y) antigen was also detected in hepatocytes in the same area. Immunohistochemical double staining showed that some of the hepatocytes containing Mallory bodies were stained with anti-Le(y) antibody. Few hepatocytes expressing Le(y) antigens, however, were observed in other types of alcoholic liver disease, including steatosis, fibrosis and cirrhosis. From these results, it is suggested that apoptosis may also be involved in alcoholic hepatitis and that hepatocytes containing Mallory bodies can be eliminated by apoptosis.

Apoptosis↗
PubMed1994

Pregnancy complicated by liver dysfunction: possible pathogenesis of vasospasm.

BACKGROUND: Acute fatty liver of pregnancy, the syndrome of hemolysis, elevated liver enzymes, and low platelet count (HELLP), and severe preeclampsia form a disease spectrum. We report a case that showed a vasospastic phenomenon supported angiographically and hematologically. CASE: A 31-year-old Japanese woman presented at 37 weeks gestation with a 1-week history of nausea, vomiting and general fatigue. She underwent cesarean delivery for fetal distress. Liver dysfunction and disseminated intravascular coagulopathy were detected. The celiac angiogram showed vascular narrowing and irregularity of the vascular wall. Serum endothelin and the ratio of thromboxane B2 to 6-keto-prostaglandin F1 alpha were increased at the same time. The patient experienced rapid resolution of symptoms and laboratory abnormalities in the immediate postoperative period. CONCLUSION: A pregnancy complicated by liver dysfunction showed a vasospastic phenomenon, which may suggest the presence of a vasospastic syndrome.

Adult↗
PubMed1993

Renal vascular and sympathetic nerve responses to hypotension induced by platelet-activating factor in anesthetized dogs.

This experiment was designed to determine renal sympathetic and renal vascular responses to platelet-activating factor (PAF)-induced hypotension in anesthetized dogs with and without systemic baroreceptor denervation. The left kidney was perfused at a constant flow, and renal perfusion pressure and efferent left renal sympathetic nerve activity were measured simultaneously. Intrarenal injection of PAF (1.25-5.0 x 10(-2) micrograms/kg, n = 6) produced a dose-dependent increase in renal perfusion pressure without any change in systemic blood pressure. An intravenous injection of PAF (10 micrograms/kg) to intact animals (n = 7) caused an initial increase in renal nerve activity (157 +/- 14%) followed by a gradual reduction below baseline (72 +/- 7%) with concomitant systemic hypotension (from 116 +/- 7 to 46 +/- 6 mmHg). Renal perfusion pressure increased significantly from 84 +/- 2 to 161 +/- 33 mmHg concomitant with an increase in renal nerve activity at 1 min and was maintained at this elevated level throughout the experiment. Similar responses of renal nerve activity and renal perfusion pressure were found in animals with complete systemic baroreceptor denervation (n = 7). These results suggest that renal vascular response during PAF-induced hypotension may presumably be mediated by a direct vasoconstrictor effect of PAF on the renal vasculature and that baroreceptor reflex is not involved in either renal sympathetic or renal vascular changes.

Animals↗
PubMed1993

Ca2+ entry pathways activated by the tumor promoter thapsigargin in human platelets.

Thapsigargin-activated Ca2+ entry into platelets was examined in the presence of S-145, a thromboxane A2 receptor antagonist, to inhibit indirect effects by endogenously formed prostaglandin H2/thromboxane A2. With external Ca2+ present, 0.2 microM thapsigargin caused a prompt increase in intracellular Ca2+ concentration ([Ca2+]i) followed by a gradual increase. Pretreatment with 6 microM wortmannin, a specific inhibitor of myosin light chain kinase, partly inhibited the increase in [Ca2+]i. In Ca(2+)-free EGTA buffer, thapsigargin induced a smaller increase in [Ca2+]i, and subsequent addition of Ca2+ to the buffer caused a further prompt increase in [Ca2+]i, demonstrating external Ca2+ entry. Wortmannin only partly inhibited this entry of external Ca2+. The wortmannin-insensitive Ca2+ entry pathway remained open for more than 6 min in Ca(2+)-free buffer. On the other hand, when receptor agonists such as thrombin and U46619 were substituted for thapsigargin, activation of the wortmannin-insensitive Ca2+ entry was transient (Hashimoto et al., J. Biol. Chem (1992) 267, 17078-17081). In the presence of S-145 and wortmannin, thapsigargin stimulated phosphorylation of neither the 20-kDa myosin light chain nor the 47-kDa protein, a substrate of protein kinase C. These results suggest that thapsigargin induces external Ca2+ entry by two mechanisms: (1) a mechanism involving myosin light chain kinase; (2) a mechanism, not activated by receptor agonists, that is independent of the major protein kinases of platelets.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1993

Inhibition of histamine secretion by wortmannin through the blockade of phosphatidylinositol 3-kinase in RBL-2H3 cells.

The surface engagement of high affinity immunoglobulin E receptor (Fc epsilon RI) of rat basophilic leukemia 2H3 (RBL-2H3) cells induced histamine secretion and leukotriene release following activation of the tyrosine kinase Lyn together with phosphatidylinositol 3-kinase (PI3-kinase). Wortmannin inhibited the activity of partially purified PI3-kinase from calf thymus, as well as the PI3-kinase activity in anti-PI3-kinase p85 immunoprecipitates from RBL-2H3 cells, at a concentration as low as 1.0 nM and with IC50 values of 3.0 nM, but did not inhibit PI4-kinase activity. The inhibition of PI3-kinase by wortmannin was irreversible. Wortmannin inhibited both Fc epsilon RI-mediated histamine secretion and leukotriene release up to 80% with IC50 values of 2.0 and 3.0 nM, respectively. Wortmannin inhibited PI3-kinase activity in intact cells up to 80% with an IC50 value of 2.0 nM, which is almost equal to those for PI3-kinase in vitro and for histamine secretion and leukotriene release. With anti-wortmannin antibody, we have shown that wortmannin binds to the 110-kDa protein, but not to PI3-kinase 85-kDa regulatory subunit both in vitro and in whole cells. Furthermore, there was a positive correlation between the potencies of wortmannin derivatives as inhibitors of PI3-kinase and as inhibitors of histamine secretion. Wortmannin had no effect on the activation of the tyrosine kinase Lyn. These results suggest that PI3-kinase is involved in the signal transduction pathway responsible for histamine secretion following stimulation of Fc epsilon RI and that wortmannin blocks these responses through direct interaction with the catalytic subunit of this enzyme.

Androstadienes↗
PubMed1993

Antagonist for atrial natriuretic peptide receptors ameliorates glomerular hyperfiltration in diabetic rats.

To evaluate the possible contribution of atrial natriuretic peptide (ANP) to the development of glomerular hyperfiltration, we examined the effect of non-peptide competitive antagonist for biological receptors of ANP, HS-142-1, on glomerular filtration rate (GFR) and renal plasma flow (RPF) in diabetic rats. Increased GFR and RPF in diabetic rats were significantly ameliorated by the injection of HS-142-1, while blood pressure remained unchanged. Urinary cyclic GMP excretion was significantly higher in diabetic rats than in control rats and HS-142-1 decreased urinary cGMP excretion significantly. These results indicate that atrial natriuretic peptide contributes to the development of glomerular hyperfiltration and hyperperfusion in diabetes and HS-142-1 might be useful in the treatment of them.

Animals↗
PubMed1993

The neuroprotective properties of ES-242s, novel NMDA receptor antagonists, in neuronal cell culture toxicity studies.

ES-242-1, a novel bioxanthracene of microbial origin, blocked glutamate-induced neuronal death in a dose-dependent manner at concentrations ranging from 0.01 to 1.0 microM, but not the neuronal death caused by kainic acid or quisqualic acid. ES-242-1 also prevented cell death induced by 2,4-methanoglutamate, which is a specific agonist for the NMDA receptor. ES-242-1 showed protective effects in cultured neurons prepared from cerebellum and septum as it did in cultured hippocampal neurons but to different extents. There was a positive correlation between the potencies of ES-242s as inhibitors of ligand binding to the NMDA receptor and as inhibitors of neuronal death. Hypoxic treatment for 4 h under 95% N2 and 5% CO2 caused neuronal death of the cultured hippocampal neurons. Again, ES-242-1 at 1.0 microM was effective to protect neurons against hypoxic injury. ES-242 compounds are new chemical entities possessing neuroprotective properties useful in the treatment of diseases involving glutamate toxicity.

Animals↗
PubMed1993

Biological receptors mediate anti-proliferative action of atrial natriuretic peptide in cultured mesangial cells.

The mechanism of anti-proliferative action of atrial natriuretic peptide (ANP) was examined in cultured mesangial cells. HS-142-1, a selective antagonist for ANP biological receptors, inhibited ANP-induced cellular cGMP accumulation and prevented ANP-induced inhibition of both serum-stimulated incorporation of 3H-thymidine and cell proliferation. Des-[Gln18, Ser19, Gly20, Leu21, Gly22]-ANP4-23-NH2 (C-ANP) failed to inhibit 3H-thymidine incorporation. These results indicate that anti-proliferative action of ANP is mediated by the biological receptors in cultured mesangial cells.

Animals↗
PubMed1993

Aromatase activity in human hepatocellular carcinoma. Relationship with the degree of histologic differentiation.

Human hepatocellular carcinomas (HCC) were examined aromatase activity, an enzyme that converts androgen into estrogen. Such activity was detected in all 13 specimens of HCC (mean activity, 120 fmol/30 min/mg microsomal protein). The activity tended to be lower in the HCC tissue than in the surrounding liver tissue (mean activity, 230 fmol/30 min/mg microsomal protein), although it was higher in the HCC tissue from three of eight patients with Edmondson's Grade 2 disease. This relationship was not found in the five with Grade 3 disease. On the whole, aromatase activity was significantly higher in specimens from patients with Edmondson's Grade 2 tumors than in the less differentiated Grade 3 type (P < 0.05). These observations suggested that aromatase activity was present in human HCC and was related to the degree of histologic differentiation.

Aged↗
PubMed1993

Differences of intravenous nitroglycerin responses in left ventricular systolic and end-diastolic pressures and coronary artery diameters during long-term treatment with cutaneous nitroglycerin patches.

The differences of intravenous nitroglycerin responses in left ventricular (LV) systolic and end-diastolic pressures and in coronary artery diameters (cross-tolerance) were investigated in patients receiving nitroglycerin patches. During diagnostic cardiac catheterization, graded doses of 50, 100, and 150 mcg of intravenous nitroglycerin were given. Left ventricular systolic and end-diastolic pressures and left coronary arteriograms were obtained during each dose. Twenty patients with coronary artery disease were studied. Before cardiac catheterization, 10 received nitroglycerin patch (patch group), and 10 did not (control group). In the control group, graded intravenous nitroglycerin doses of 50, 100, and 150 mcg caused decrease in LV systolic pressure of 18 +/- 7%, 20 +/- 5%, and 23 +/- 6%, respectively. In the patch group, the same intravenous nitroglycerin doses decreased LV systolic pressure by 12 +/- 6% (p < 0.05), 19 +/- 7% (NS), and 18 +/- 6% (p < 0.05), respectively, (p value: vs. control group). At the same intravenous nitroglycerin doses, LV end-diastolic pressures were decreased by 48 +/- 14%, 52 +/- 17%, and 56 +/- 9%, respectively, in the control group. However, there were no significant differences in LV end-diastolic pressure between the two groups for any of the three intravenous nitroglycerin doses. The same intravenous nitroglycerin doses caused increase in diameter of the left anterior descending coronary artery and circumflex coronary artery in the control group, which was attenuated significantly in the patch group. Tolerance may develop in LV systolic pressure and coronary artery diameters, whereas it may not develop in LV end-diastolic pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗
PubMed1993

Assessment of right ventricular diastolic filling in patients with coronary artery disease.

To assess right ventricular (RV) diastolic filling in coronary artery disease (CAD), with special reference to the involved lesions of the coronary arteries and left ventricular (LV) systolic function, gated radionuclide ventriculography was performed at rest in 106 patients with single-vessel CAD. Based on the site of coronary arterial involvement, patients were classified into three groups: left anterior descending CAD, right CAD, and left circumflex CAD. Patients in each group were further subdivided according to normal or decreased LV ejection fraction, resulting in six groups. Seventeen normal subjects were examined as a control group. Time-activity and its first-derivative curves were computed for the right and left ventricles. RV systolic function was normally preserved in all six groups, even when LV systolic function was damaged severely. The ratio of peak RV filling rate to peak RV ejection rate was significantly decreased in all six groups compared with that in control subjects, indicating that RV filling was impaired in patients with CAD. The ratio was below the lower limit of normal in 14 (23%) of 62 patients with normal LV systolic function and in 13 (30%) of 44 patients with impaired LV systolic function. None of the control subjects showed a decreased ratio of peak RV filling rate to peak RV ejection rate. Thus, in patients with CAD, RV filling is impaired, which may be independent of the site of coronary arterial involvement and of the LV or RV systolic function.

Adult↗