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Biomedical subjects

M Kohno

Publications and source records attributed to M Kohno.

At least 271 records · Page 15Linked to original sources
PubMed1995

alpha-Guanidinoglutaric acid as a free radical generator.

alpha-Guanidinoglutaric acid (alpha-GGA) was first isolated from the cobalt-induced epileptic focus of cat cerebral cortex by us in 1980. alpha-GGA could induce behavioral convulsion as well as electroencephalography-documented epileptic seizures, when it was administered into the brain. alpha-GGA was also found to be a potent nitric oxide synthase inhibitor, suggesting that suppression of this activity may result in epileptic seizures. It is now observed that alpha-GGA generates reactive oxygen species as superoxide and hydroxyl radicals in aqueous solution. These findings suggest that reactive oxygen species may damage cell membranes, thus leading to neuronal depolarization, which is closely related to epileptogenesity.

Electron Spin Resonance Spectroscopy↗
PubMed1995

Promotion of nitric oxide formation by heparin in cultured aortic endothelial cells from spontaneously hypertensive rats.

1. The present study examined the effect of heparin on nitric oxide (NO) formation and cyclic guanosine 3', 5'-monophosphate (cGMP) levels in cultured aortic endothelial cells (EC) from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. 2. Bradykinin (BK), adenosine diphosphate (ADP), Ca2+ ionophore A23187 (Io) and endothelin-3 (ET-3) stimulated the production of NO and cGMP. No significant difference was observed in both NO and cGMP production in EC between WKY and SHR. 3. Heparin enhanced BK-, ADP-, Io- and ET-3-stimulated NO and cGMP production. These enhancements by heparin in EC were significantly greater in SHR than in WKY. 4. Both NO formation and cGMP production stimulated by the agonists and/or heparin were blocked in the presence of NG-monomethyl-L-arginine (LNMMA, 10(-5) mol/L). 5. Increased sulphur level was observed on heparin-treated SHR EC surface compared with that on control SHR EC or on heparin-treated WKY EC surface. 6. These results suggest that heparin promotes agonist-induced NO-cGMP response in cultured EC from SHR.

Animals↗
PubMed1995

Promotion of nitric oxide formation by heparin in cultured aortic endothelial cells from spontaneously hypertensive rats.

1. The present study examined the effect of heparin on nitric oxide (NO) formation and cyclic guanosine 3', 5'-monophosphate (cGMP) levels in cultured aortic endothelial cells (EC) from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. 2. Bradykinin (BK), adenosine diphosphate (ADP), Ca2+ ionophore A23187 (Io) and endothelin-3 (ET-3) stimulated the production of NO and cGMP. No significant difference was observed in both NO and cGMP production in EC between WKY and SHR. 3. Heparin enhanced BK-, ADP-, Io- and ET-3-stimulated NO and cGMP production. These enhancements by heparin in EC were significantly greater in SHR than in WKY. 4. Both NO formation and cGMP production stimulated by the agonists and/or heparin were blocked in the presence of NG-monomethyl-L-arginine (LNMMA, 10(-5) mol/L). 5. Increased sulphur level was observed on heparin-treated SHR EC surface compared with that on control SHR EC or on heparin-treated WKY EC surface. 6. These results suggest that heparin promotes agonist-induced NO-cGMP response in cultured EC from SHR.

Animals↗
PubMed1994

Bromocriptine protects mice against 6-hydroxydopamine and scavenges hydroxyl free radicals in vitro.

Pretreatment with bromocriptine (5 mg/kg, i.p., 7 days) completely protected against the decrease in mouse striatal dopamine and its metabolites induced by intraventricular injection of 6-hydroxydopamine after intraperitoneal administration of desipramine, but similar pretreatment with L-DOPA/carbidopa (75/7.5 mg/kg, i.p., 7 days) showed only partial protective effect. Furthermore, in an in vitro system that generated.OH from FeSO4-H2O2, bromocriptine dose-dependently reduced the number of .OH radicals. These findings indicate that bromocriptine has a neuroprotective effect against neurotoxins such as 6-hydroxydopamine, probably due, in part, to its hydroxyl radical scavenging activity and inhibiting effect on dopamine turnover rate. This suggests that early introduction of bromocriptine in the therapy of Parkinson's disease may be superior to treatment with L-DOPA alone.

Animals↗
PubMed1994

Tumor necrosis factor is markedly synergistic with interleukin 1 and interferon-gamma in stimulating the production of nerve growth factor in fibroblasts.

A possible interaction between tumor necrosis factor-alpha (TNF) and other cytokines/growth factors in stimulating the production of nerve growth factor (NGF) in Swiss 3T3 cells was studied. TNF's stimulatory activity on fibroblast NGF production was synergized by interleukin-1 alpha (IL-1 alpha), IL-1 beta and interferon-gamma (IFN-gamma), but was antagonized by transforming growth factor-beta (TGF-beta). The most remarkable synergistic effect was observed between TNF and IL-1 alpha/beta; as little as 0.003 ng/ml of IL-1 beta markedly enhanced TNF's stimulatory activity on NGF production in the cells. These findings reinforce the idea that TNF, in concert with IL-1 alpha/beta, plays an essential role in regulating the regeneration of peripheral nerves following injury through an indirect mechanism by which it stimulates NGF production in fibroblasts.

3T3 Cells↗
PubMed1994

Tyrosine phosphorylation and activation of mitogen-activated protein kinases by thrombin in human platelets: possible involvement in late arachidonic acid release.

Thrombin induced tyrosine phosphorylation of 41-kDa and 43-kDa mitogen-activated protein (MAP) kinases in human platelets which was detectable at 1 min and peaked at 2 min after thrombin stimulation as assessed by immunoprecipitation and immunoblotting. The kinase activity, measured by phosphorylation of myelin basic protein, increased concurrently with tyrosine phosphorylation. The present results indicate that thrombin activates MAP kinases which may not be involved in aggregation and secretory responses but may play a role in the late arachidonic acid release via activation of cytosolic phospholipase A2 in human platelets.

Arachidonic Acid↗
PubMed1994

Radical scavenger effect of Boschniakia rossica.

To elucidate the mechanism of the invigorating and antisenile action of the dried herb of Boschniakia rossica (Boschniakiae Herba), the free radical scavenging activity of its 50% ethanol extract (BR) was examined using an electron spin resonance spectrometer. The scavenging activity of plasma from Fisher-334 rats with continuous administration of BR was also examined. The concentrations showing 50% inhibition of the free radical of BR on the 1,1-diphenyl-2-picrylhydrazil (DPPH) radical, superoxide radical and hydroxyl radical were 0.003%, 0.06% and 9.67%, respectively. Plasma from the rats with BR administered clearly showed higher free radical scavenging activity compared with that of normal control rats. These findings suggest that Boschniakia rossica has strong free radical scavenging activity and consequently it has inhibitory effects on the disorders caused by free radical production in living tissue.

Administration, Oral↗
PubMed1994

Heparin inhibits endothelin-1 production in cultured rat mesangial cells.

The present study was designed to examine whether heparin inhibits basal or stimulated endothelin-1 production by arginine vasopressin (AVP) and platelet-derived growth factor (PDGF) in cultured rat mesangial cells. In addition, the reversibility of the heparin effect on mesangial cell endothelin-1 production was examined. AVP and PDGF stimulated endothelin-1 secretion in a concentration-dependent manner in these cells. Heparin (10 to 100 U/ml) exhibited concentration-related inhibition of AVP- and PDGF-stimulated endothelin-1 secretion. Heparin also had weak but significant inhibitory effects on basal endothelin-1 secretion in these cells. The protein kinase (PKC)-activating phorbor ester, phorbor myristate acetate (PMA), stimulated endothelin-1 secretion and heparin inhibited PMA-stimulated endothelin-1 secretion. In addition, the inhibitory effect of heparin was completely abolished in PKC-depleted mesangial cells. Mesangial cells which were exposed to a high concentration (100 U/ml) of heparin for 24 hours were capable of producing endothelin-1 after a short lag period of removal of heparin from the culture medium. These mesangial cells also showed recovery of responses to AVP and PDGF by secreting a significantly greater amount of endothelin-1 than the non-stimulated level. These results indicate that heparin potently inhibits mesangial cell endothelin-1 production, especially when stimulated by AVP or PDGF. This inhibitory effect of heparin is probably PKC dependent, and reversible.

Animals↗
PubMed1994

Influence of left ventricular regional nonuniformity on afterload-dependent relaxation in intact dogs.

The time course of systolic loading conditions is considered an important factor in affecting left ventricular (LV) relaxation. However, the exact underlying mechanisms remain controversial. The goal of this study was to evaluate the role of the change in loading sequence on LV regional wall motion and LV relaxation. Early and late systolic loading were produced by constricting the ascending aorta and the descending aorta, respectively, in seven anesthetized dogs. In two pairs of cardiac beats with a comparable peak LV pressure during the mild and moderate constrictions of the ascending or descending aorta, we measured LV time constant (T) of LV pressure decay and determined regional nonuniformity in basal and apical segmental motion during the isovolumic relaxation period (by Lew's method). Constriction of the descending aorta led to a significant delay of the timing of peak LV pressure, associated with an increase in T, end-systolic pressure, and the regional nonuniformity between the two segments. T was correlated well with the amount of the nonuniformity, suggesting that LV regional nonuniformity between basal and apical regions might be involved in the complex mechanism of afterload-dependent relaxation.

Animals↗
PubMed1994

Cardiac hypertrophy and brain natriuretic peptide in experimental hypertension.

The blood pressure was decreased after chronic treatment with enalapril, MK-954, and hydralazine in deoxycorticosterone acetate (DOCA)-salt-induced malignant hypertension of spontaneously hypertensive rats (SHR); however, ventricular weight and plasma brain natriuretic peptide (BNP) concentration were decreased after enalapril and MK-954 but not after hydralazine. The BNP secretory rates from the ventricle in enalapril- and MK-954-treated DOCA-salt SHR were decreased to approximately 50% of those in untreated DOCA-salt SHR. The BNP secretory rate from the ventricle was positively correlated with ventricular weight in untreated and treated DOCA-salt SHR. In contrast, acute administration of captopril or MK-954 did not decrease the BNP secretory rate from the heart. Results suggest that the decrease in plasma BNP after enalapril and MK-954 is attributed to a decline in the secretion from the ventricle but not from the atrium. The reduction in ventricular mass appeared to be related to this decline.

Animals↗
PubMed1994

Dopamine DA1 receptors on vascular smooth muscle cells are regulated by glucocorticoid and sodium chloride.

The modulation of dopamine DA1 receptors of cultured rat renal arterial smooth muscle cells by glucocorticoid and sodium chloride was studied. At a concentration of 10 nM, the synthetic glucocorticoid dexamethasone increased maximum receptor binding but had no effect on the dissociation constant. However, the maximum binding of [3H]Sch-23390 in cells treated with 100 mM sodium chloride did not change. However, the dissociation constant for DA1 receptor was increased by adding sodium chloride. The glucocorticoid effect on DA1 of arterial smooth muscle cells became apparent after hours of incubation in the presence of the steroid and was significantly inhibited by cycloheximide (10 micrograms/ml) or by the glucocorticoid receptor antagonist RU-38486, indicating that the effect required protein synthesis through glucocorticoid receptors. Treatment of cells with 1 microM dexamethasone for 24 h increased basal and DA1-stimulated adenylate cyclase activity. Basal adenylate cyclase was decreased by sodium chloride in a dose-dependent manner. These results suggest differential control of DA1 receptors on vascular smooth muscle cells by glucocorticoid or sodium chloride.

Adenylyl Cyclases↗
PubMed1994

Phosphoinositide turnover signaling stimulated by ET-3 in endothelial cells from spontaneously hypertensive rats.

Endothelin (ET) B-type receptor-mediated signal transduction after stimulation with ET-3 was examined in cultured aortic endothelial cells obtained from spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. The purpose of this study was to elucidate ETB receptor-mediated response in endothelial cells from hypertensive rat models. Non-isopeptide-selective displacement and affinity in these binding experiments suggest that aortic endothelial cell receptors for ET-3 correspond to ETB receptor subtypes. These receptors for ET-3 were similar in WKY and SHR endothelial cells. ETB receptor mRNA expression in cultured endothelial cells was also similar in WKY and SHR. However, the cytosolic free Ca2+ level in the absence of extracellular Ca2+ as well as the inositol 1,4,5-trisphosphate level in response to ET-3 were greater in endothelial cells from SHR than in those from WKY. Phospholipase C and protein kinase C activities after stimulation with ET-3 were also greater in SHR than in WKY. The 6-ketoprostaglandin F1 alpha production was also augmented in SHR, although nitric oxide formation and guanosine 3',5'-cyclic monophosphate production after stimulation with ET-3 were similar in WKY and SHR. We conclude that the phosphoinositide turnover signaling stimulated by ET-3 is augmented in cultured aortic endothelial cells from SHR compared with those from WKY.

Animals↗
PubMed1994

Endothelin modulates the mitogenic effect of PDGF on glomerular mesangial cells.

We showed that two isoforms of platelet-derived growth factor (PDGF), AB and BB, stimulate the secretion of endothelin (ET)-1 from cultured rat mesangial cells. Then, we examined whether PDGF AB and BB stimulate mesangial cell proliferation through the modulation of the endogenous production of ET-1 in these cells. Mitogenesis experiments were assessed by tritiated thymidine incorporation into DNA under highest concentrations (10 ng/ml) of PDGF AB and BB in the presence and absence of anti-ET-1 antiserum or a selective A-type endothelin receptor (ETA receptor) antagonist, BQ-123. PDGF AB and BB potently stimulate thymidine incorporation. This stimulation was significantly attenuated in the presence of either anti-ET-1 antiserum or BQ-123 (10(-7)-10(-5)M). Results suggest that PDGF AB and BB stimulate ET-1 secretion in rat mesangial cells through PDGF beta-receptors, and endogenously produced ET-1 serves to modulate the mitogenic effect of PDGF AB and BB, probably via ETA receptors in these cells.

Animals↗
PubMed1994

Purification, characterization, and crystallization of two types of lipase from Rhizopus niveus.

The purification and some properties of two types of lipase (Lipase I and Lipase II) from Rhizopus niveus are described. The enzymes were purified to homogeneity by column chromatographies on DEAE-Toyopearl (1 pass) and CM-Toyopearl (2 passes). Lipase I consists of two polypeptide chains [a small peptide with sugar moiety (A-chain) and a large peptide of molecular weight 34,000 (B-chain)]. Lipase II has a molecular weight of 30,000 consisting of a single polypeptide chain. Lipase I appeared to be converted to Lipase II by limited proteolysis by a specific protease a small amount of which is in the culture supernatant from Rh. niveus, because one of the peptides formed has the same N-terminal sequence and C-terminal amino acid as Lipase II, as well as the molecular mass estimated by SDS-PAGE. Lipase I had a pH optimum of 6.0-6.5 and a temperature optimum of 35 degrees C, while, for Lipase II these values were pH 6.0 and 40 degrees C. Both enzymes were obtained in the crystalline state using the hanging drop method of vapor diffusion and PEG as the precipitating agents.

Amino Acid Sequence↗
PubMed1994

Heparin suppresses endothelin-1 peptide and mRNA expression in cultured endothelial cells of spontaneously hypertensive rats.

Heparin given sc consistently lowers blood pressure in spontaneously hypertensive rats (SHR). This study was designed to examine heparin's effect on vasoconstrictor endothelin-1 production in cultured aortic endothelial cells (EC). Aortic EC from SHR and normotensive Wistar Kyoto rats (WKY) were cultured and incubated with or without different concentrations of heparin. Heparin suppressed endothelin-1 release and endothelin-1 mRNA expression in a dose- and a time-dependent fashion in both WKY and SHR. The suppressive effects were more augmented in SHR than in WKY: SHR versus WKY--endothelin-1 level at 6 h = 8 +/- 1.8 versus 14 +/- 2.2 pg/10(6) cells (P < 0.01) and mRNA expression--85 versus 52% maximal inhibition by heparin, 10 U/mL (=70 micrograms/mL) (P < 0.01). When heparin was added with transcriptional inhibitor actinomycin D and incubated for 30 min, no further inhibition of endothelin-1 mRNA level measured after another 30 minutes was observed compared with the endothelin-1 mRNA level in cultured EC of SHR treated with just actinomycin D at 30 min. These results suggest that heparin regulates endogenous endothelin-1 production by cultured EC, probably at the transcriptional level, and that this effect is more marked in SHR than in WKY.

Animals↗
PubMed1994

Suprasellar ectopic pituitary adenoma--case report.

A 33-year-old female presented with suprasellar ectopic pituitary adenoma manifesting as visual disturbances. Preoperative magnetic resonance imaging demonstrated intact pituitary gland and suprasellar cystic tumor, with a preoperative diagnosis of craniopharyngioma. At surgery, the tumor was identified as a suprasellar ectopic pituitary adenoma with intracapsular hematoma. There was no communication between the tumor and intrasellar structures. Total removal of the tumor immediately improved the severe visual disturbance. Ectopic pituitary adenoma should be considered in the differential diagnosis of a suprasellar lesion with intact pituitary gland.

Adenoma↗