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Biomedical subjects

S Morimoto

Publications and source records attributed to S Morimoto.

At least 469 records · Page 26Linked to original sources
PubMed1989

Radioimmunoassay of human platelet-derived growth factor using monoclonal antibody toward a synthetic 73-97 fragment of its B-chain.

A mouse monoclonal antibody toward a 73-97 fragment of human platelet-derived growth factor (hPDGF) B-chain was used to develop a radioimmunoassay (RIA) for serum hPDGF. By the single step procedure of the double antibody technique, the measurable range was 10-1,000 micrograms/l. The coefficients of variation within and between series were 10.2% and 12.1% respectively, and satisfactory dilution curves were obtained for sera from healthy subjects. The hPDGF levels in all plasma samples from 15 healthy subjects examined were below the detection limit (10 micrograms/l), whereas the mean hPDGF concentration (+/- SD) in serum samples of 60 healthy subjects was 31.9 +/- 20.4 micrograms/l. This value was significantly (p less than 0.01) higher than the mean for 21 patients with idiopathic thrombocytopenic purpura (12.6 +/- 4.5 micrograms/l). There was a significant positive (r = 0.481, p less than 0.01) but not a strong (r2 = 0.23) correlation between the peripheral blood platelet counts and serum hPDGF levels of all subjects. This RIA system should be useful clinically for measurement of serum hPDGF.

Antibodies, Monoclonal↗
PubMed1989

Effects of endothelin on renal function and renin secretion in anesthetized rats.

The infusion of endothelin into the renal artery of anesthetized rats at 1 ng/kg per min, a dose with no influence on renal function, had no effect on the basal levels of plasma renin activity (PRA) and renin secretory rate (RSR), but significantly inhibited the isoproterenol-induced increases in PRA and RSR. Endothelin, 2 ng/kg per min, elicited significant decreases in renal hemodynamics and in urine formation but the mean arterial pressure was not affected. The possibility that endothelin may participate in controlling renal function and renin secretion in vivo warrants further attention.

Anesthesia↗
PubMed1989

Effects of valinomycin on calcium mobilization in vascular smooth muscle cells induced by angiotensin II.

The effect of the specific potassium (K+) ionophore valinomycin on increase in intracellular calcium concentration [( Ca2+]i) was studied in vascular smooth muscle cells (VSMC). Valinomycin at more than 10(-9) M dose-dependently suppressed phasic increase in [Ca2+]i in VSMC induced by angiotensin II (AII) in both control and Ca2+-free solution, indicating that it suppressed the release of Ca2+ from intracellular Ca2+ stores. Nicorandil and cromakalim, which are both K+ channel openers, also suppressed the increases in [Ca2+]i induced by AII in the Ca2+ free solution. However, valinomycin did not suppress AII-induced production of inositol 1,4,5-trisphosphate (IP3), which is known to mediate the release of Ca2+. These results indicate that decrease of intracellular K+ induced by valinomycin suppressed the release of Ca2+ from intracellular Ca2+ stores induced by IP3.

Angiotensin II↗
PubMed1989

Endothelin immunoreactivity in medium from cultured porcine aortic endothelial cells correlates with the biological activity.

Using the radioimmunoassay (RIA) of endothelin (ET), we measured immunoreactive ET (IR-ET) in culture medium of porcine aortic endothelial cells. The immunoreactivity in the medium was compared with the biological activity. The amount of IR-ET released into the medium was calculated at 250-350 pg/10(6) cells/hr. The amount of IR-ET released into the culture medium increased progressively with 3-24 hr of incubation and corresponded to the increase in medium-induced vasoconstriction of rat isolated aorta. When the vasoconstrictor activities in the culture medium were plotted against the IR-ET concentration determined by RIA, the concentration-response curve showed similarity to that obtained with synthetic porcine ET. This RIA system will be a useful for investigating mechanisms of ET secretion from endothelial cells.

Animals↗
PubMed1989

Purification and partial characterization of a thiol proteinase activating prokallikrein from the rat kidney cortex.

The rat kidney cortex contains at least three kinds of prokallikrein-activating proteinase, and among these the one with the highest molecular weight was purified by a procedure including chromatography on CM-cellulose, concanavalin A-Sepharose, organomercurial-Sepharose 4B and Sephadex G-100. The resulting preparation was apparently homogeneous, as assessed by SDS-polyacrylamide gel electrophoresis. The molecular weight was estimated to be 57,000. The optimal pH for the activation of prokallikrein by the preparation, termed activator I, was around 4.5. Activator I was inhibited by E-64, iodoacetate and leupeptin, but not by PMSF and phosphoramidon. In immunodiffusion analysis, the antiserum to activator I formed an immunoprecipitin arc with the extract from the kidney cortex or submandibular gland, but not with that from the pancreas. These results indicate that activator I is a thiol proteinase with a molecular weight of 57,000. A proteinase immunologically identical with activator I appears to be present in the submandibular gland.

Amino Acids↗
PubMed1989

Activation of inactive kallikrein in the rat kidney during low sodium intake.

A method was developed to measure the protease responsible for activation of inactive kallikrein in the rat kidney. The renal protease was evaluated by incubating the purified rat urinary inactive kallikrein with the renal cortical extract in the presence of cysteine at pH 5.0. The renal cortical extract produced a dose- and time-dependent activation of the inactive kallikrein. Levels of the renal protease responsible for activation of inactive kallikrein remained unchanged with dietary sodium restriction. On the other hand, urinary excretion of total, active, and inactive kallikrein increased significantly during low sodium intake, with no change in the ratio of active to total kallikrein. These results suggest that low sodium intake stimulates the biosynthesis of inactive kallikrein but not the activation of this kallikrein precursor in the kidney.

Animals↗
PubMed1989

Elongation factor 2 as the major substrate for Ca2+/calmodulin-dependent protein kinase in rat adrenal glomerulosa cells.

We have previously shown the existence of the major substrate protein of Mr 100,000 (substrate 100 K protein) for Ca2+/calmodulin (CaM)-dependent protein kinase in rat adrenal glomerulosa cells. In the present study, the identity of the substrate 100 K protein to elongation factor 2 (EF-2) was investigated. In a 105,000 g-supernatant fraction (cytosol), the protein of Mr 100,000 with the pI (isoelectric point) value of 6.7 was phosphorylated in the presence of calcium and CaM. The optical densities of this phosphorylated band were greatly enhanced in the presence of the EF-2 purified from pig liver (1 microgram) [20-23-fold, n = 5] when compared with those in the absence of the component. In the presence of the purified EF-2, the phosphorylation of Mr 100,000 was detected only in the presence of calcium alone or calcium plus CaM. This phosphorylation in the presence of calcium alone was completely inhibited in the presence of the CaM antagonist pimozide (500 microM), showing the existence of endogenous CaM in the cytosol. In the same fraction, the ADP-ribosylated protein of Mr 100,000 was detected in the presence of diphtheria toxin (fragment A) and (adenylate-32P) NAD, indicating the presence of EF-2 in the cytosol from rat adrenal glomerulosa cells. These results suggest that the substrate 100 K protein may be identical to EF-2 in rat adrenal glomerulosa cells.

Adenosine Diphosphate Ribose↗
PubMed1989

Effects of Bay K 8644 on renal function and renin secretion in anesthetized rats.

Our previous study on kidney cortical slices showed that Bay K 8644, a dihydropyridine calcium channel agonist, produced a dose-dependent inhibitory action on the release of renin. The present study was performed to examine the effect of Bay K 8644 on renal function and renin secretion in vivo. When Bay K 8644 was directly infused into the renal artery of anesthetized rats, 2 micrograms/kg/min had no effect on renal blood flow (RBF) and glomerular filtration rate (GFR), but decreased urine flow (UF), urinary sodium excretion (UNaV) and fractional sodium excretion (FENa) by about 30%, 55% and 35%, respectively, thereby suggesting that Bay K 8644 enhanced the tubular reabsorption of water and sodium. When 10 micrograms/kg/min were infused, RBF, GFR, UF, UNaV and FENa decreased to about 95%, 70%, 35%, 35% and 30% of each control value. The administration of Bay K 8644 at 10 micrograms/kg/min did not influence the basal levels of plasma renin activity (PRA) and renin secretion rate (RSR), but did inhibit significantly isoproterenol-induced increasing effects on PRA and RSR. These results indicate that the activation of voltage-dependent calcium channels with Bay K 8644 influences the control of renal function and renin secretion in vivo.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1989

The endothelium-derived vasoconstrictor peptide endothelin inhibits renin release in vitro.

The effect of endothelin, a newly identified endothelium-derived vasoconstrictor peptide, on renin release from rat kidney cortical slices was examined. Endothelin produced a concentration-dependent inhibition of renin release and this inhibitory effect was dependent on extracellular calcium. The dihydropyridine calcium channel blockers nifedipine and nicardipine did not antagonize the inhibitory effect induced by endothelin. On the other hand, nifedipine completely antagonized the extracellular high potassium- or Bay K 8644-induced inhibition of renin release. The endothelin-induced inhibition of the release was markedly blocked by the addition of Co2+. Similar blocking effects of Co2+ were also observed with extracellular high potassium or Bay K 8644. Thus, endothelin exerts an inhibitory action on renin release in vitro, in a calcium-dependent manner. This inhibition may be mediated by the increased calcium influx through dihydropyridine-insensitive calcium channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1989

Association of increased intracellular free Ca2+ by platelet-derived growth factor with mitogenesis but not with proteoglycan synthesis in chondrocytes--effect of suramin.

The effects of platelet-derived growth factor (PDGF) on the intracellular free Ca2+ concentration [( Ca2+]i) in chondrocytes were studied with a fluorescent Ca2+ indicator, fura 2, and compared with the effects of PDGF on mitogenesis and proteoglycan synthesis. PDGF evoked phasic and then tonic increase in [Ca2+]i dose-dependently in quiescent cultures of chondrocytes, and it also stimulated both DNA and proteoglycan syntheses dose-dependently similar to somatomedins. Suramin, which inhibits the interaction of PDGF with its receptors, caused dose-dependent inhibition of both the PDGF-evoked increase in [Ca2+]i and stimulation of DNA synthesis by PDGF. However, suramin rather enhanced the proteoglycan synthesis induced by PDGF without affecting the basal level of proteoglycan synthesis directly. These results suggest that [Ca2+]i may be an important signal for the action of PDGF on cell proliferation in chondrocytes, and that the initial signal for proteoglycan synthesis is different from that for DNA synthesis induced by PDGF after the activation of PDGF receptor.

Animals↗
PubMed1989

Cathepsin B and L activities in gastric cancer tissue: correlation with histological findings.

Cathepsin B and L activities in cancerous and noncancerous mucosal tissues from 29 patients with gastric cancer were determined with a small amount of tissue homogenate. Both enzyme activities were significantly higher in cancerous tissues than in noncancerous tissues. The cathepsin B activity was higher with decreasing differentiation of the cancerous tissues, and also with increasing depth of invasion and metastasis to regional lymph nodes. Significantly high cathepsin B activity was observed in specimens of poorly differentiated adenocarcinomas, as well as in specimens from patients with extensive metastasis to n2 or n3 lymph nodes. These results suggest that high cathepsin B activity is characteristic of gastric cancer which invades and metastasizes. Therefore, in cases of marked elevation of cathepsin B activity in cancerous tissues, relatively extensive resection may be necessary to obtain a cure.

Adenocarcinoma↗
PubMed1989

Saposin A: second cerebrosidase activator protein.

Saposin A, a heat-stable 16-kDa glycoprotein, was isolated from Gaucher disease spleen and purified to homogeneity. Chemical sequencing from its amino terminus and of peptides obtained by digestion with protease from Staphylococcus aureus strain V-8 demonstrated that saposin A is derived from proteolytic processing of domain 1 of its precursor protein, prosaposin. Processing of prosaposin (70 kDa) also generates three other previously reported saposin proteins, B, C, and D, from its second, third, and fourth domains. Similar to saposin C, saposin A stimulates the hydrolysis of 4-methylumbelliferyl beta-glucoside and glucocerebroside by beta-glucosylceramidase and of galactocerebroside by beta-galactosylceramidase, mainly by increasing the maximal velocity of both reactions. Saposin A is as active as saposin C in these reactions. Saposin A has no significant effect on other sphingolipid and 4-methylumbelliferyl glycoside hydrolases tested. Saposin A has two potential glycosylation sites that appear to be glycosylated. After deglycosylation, saposin A had a subunit molecular mass of 10 kDa and was as active as native saposin A. However, reduction and alkylation abolished the activation. A three-dimensional model comparing saposins A and C reveals significant sequence homology between them, especially preservation of conserved acidic and basic residues in their middle regions. Each appears to possess a conformationally rigid hydrophobic pocket stabilized by three internal disulfide bridges, with amphipathic helical regions interrupted by helix breakers.

Amino Acid Sequence↗
PubMed1989

Ca2+ binding to skeletal muscle troponin C in skeletal and cardiac myofibrils.

Ca2+ binding to skeletal muscle troponin C in skeletal or cardiac myofibrils was measured by the centrifugation method using 45Ca. The specific Ca2+ binding to troponin C was obtained by subtracting the amount of Ca2+ bound to the CDTA-treated myofibrils (troponin C-depleted myofibrils) from that to the myofibrils reconstituted with troponin C. Results of Ca2+ binding measurement at various Ca2+ concentrations showed that skeletal troponin C had two classes of binding sites with different affinity for Ca2+. The Ca2+ binding of low-affinity sites in cardiac myofibrils was about eight times lower than that in skeletal myofibrils, while the high-affinity sites of troponin C in skeletal or cardiac myofibrils showed almost the same affinity for Ca2+. The Ca2+ sensitivity of the ATPase activity of skeletal troponin C-reconstituted cardiac myofibrils was also about eight times lower than that of skeletal myofibrils reconstituted with troponin C. These findings indicated that the difference in the sensitivity to Ca2+ of the ATPase activity between skeletal and cardiac CDTA-treated myofibrils reconstituted with skeletal troponin C was mostly due to the change in the affinity for Ca2+ of the low-affinity sites on the troponin C molecule.

Adenosine Triphosphatases↗
PubMed1989

Amino acid sequence of porcine cardiac muscle troponin C.

Troponin C is the Ca2+-receptive protein located on the thin filament of striated and cardiac muscle. We have determined the amino acid sequence of troponin C obtained from porcine cardiac muscle by sequencing and aligning the lysyl endopeptidase and Staphylococcus aureus V-8 protease peptides. It was composed of 161 amino acid residues with a blocked N-terminus. The sequence of porcine cardiac troponin C was identical with that of bovine cardiac troponin C.

Amino Acid Sequence↗
PubMed1989

Inhibitory effect of nisoldipine on angiotensin-II-induced renal actions in anesthetized dogs.

Renal effects of nisoldipine, a potent calcium channel blocker, were examined in anesthetized dogs. Intrarenal arterial infusion of nisoldipine (2, 10, and 50 ng/kg per min) had no effect on mean systemic blood pressure and heart rate and there was no significant change in renal hemodynamics during infusion of various doses of the drug. Urine flow and urinary excretions of sodium, chloride, and potassium were increased by nisoldipine in a dose-related manner. Fractional excretions of sodium and chloride were markedly elevated with the highest dose given thereby indicating that tubular reabsorptions of sodium and chloride were inhibited by nisoldipine. Nisoldipine (50 ng/kg per min) abolished the decreasing effects of angiotensin-II on glomerular filtration rate, urine flow, and urinary excretion of electrolytes but not the decrease in renal blood flow by the peptide. Angiotensin-II-induced reduction of fractional excretion of electrolytes was completely blocked by nisoldipine. Renal responses to norepinephrine were unaffected by nisoldipine. Thus, nisoldipine administered intrarenally to anesthetized dogs exerts a diuretic action by way of tubular effects, as is the case with other dihydropyridine calcium channel blockers. Nisoldipine seems to effectively antagonize the renal response to angiotensin-II. Thus, the preferential inhibition of angiotensin-II-induced antidiuresis may mean that nisoldipine interferes with stimulatory effects of angiotensin-II on the renal tubular reabsorption of electrolytes and water.

Anesthesia↗
PubMed1989

Diuretic effect induced by intrarenal infusion of nisoldipine in anaesthetized dogs.

1. Renal effects of nisoldipine, a potent calcium channel blocker, were examined in anaesthetized dogs. 2. Intrarenal arterial infusion of nisoldipine (10, 50 ng/kg per min) did not influence mean systemic blood pressure and renal haemodynamics, but did cause dose-related increases in urine flow and urinary excretion of electrolytes. During nisoldipine infusion at the higher dose, the levels of fractional excretion of sodium, potassium and chloride were significantly elevated. 3. In the lithium clearance study, fractional lithium excretion, an index of fractional sodium excretion in the proximal tubules, was unchanged even with the higher dose of nisoldipine, whereas fractional sodium excretion in the distal tubules markedly increased. 4. Nisoldipine elicited a significant increment in osmolar clearance without altering the reabsorption of free water. 5. Thus, intrarenal administration of nisoldipine at a non-hypotensive dose to anaesthetized dogs produced a significant diuretic effect without alteration in renal haemodynamics. Results in lithium clearance and free water clearance studies suggest that nisoldipine exerts a diuretic action by inhibiting sodium transport at the distal nephron segments beyond the proximal tubules.

Anesthesia↗
PubMed1989

Cross sectional echocardiographic anatomy of common atrioventricular valve in atrial isomerism.

The morphology of the common atrioventricular valve and its relation to the ventricles was assessed by cross sectional echocardiography in 17 patients with atrial isomerism--four with left isomerism and 13 with right isomerism. In 13 patients the atrioventricular valve consisted of four leaflets: a large anterosuperior leaflet, two lateral leaflets, and a posteroinferior leaflet. The remaining four patients had two anterosuperior leaflets. Five patients had hearts with a double inlet right ventricle and all of them had a rudimentary left ventricle. All the commissures were attached to the right ventricle. Five patients showed severe right ventricular dominance. The atrioventricular morphology in these five hearts differed from that in the patients with the usual atrial arrangement, concordant atrioventricular connection, and hypoplasia of the left ventricle. Only the anterosuperior leaflet bridged the rudimentary left ventricle, and the posteroinferior leaflet was tethered to the ventricular septal crest. Six patients had a biventricular atrioventricular connection and two of them showed mild right ventricular dominance. The atrioventricular morphology in these hearts was the same as that seen in the patients with usual atrial arrangement and a concordant atrioventricular connection. The remaining patient showed dominance of the left ventricle. Only the anterosuperior leaflet bridged the rudimentary right ventricle in this heart.

Adolescent↗