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Biomedical subjects

K Fukuo

Publications and source records attributed to K Fukuo.

At least 55 records · Page 3Linked to original sources
PubMed1993

Calciseptine binding to a 1,4-dihydropyridine recognition site of the L-type calcium channel of rat synaptosomal membranes.

Calciseptine (CaS) is a natural peptidic L-type Ca2+ channel blocker consisting of 60 amino acids with four disulfide bonds. The effects of synthetic CaS on the binding of various ligands to Ca2+ channels of rat brain synaptosomal membranes were studied. The membranes possessed specific binding sites for L-type Ca2+ channel ligands [3H]nitrendipine, [3H]diltiazem and [3H]verapamil, derivatives of 1,4-dihydropyridine, benzothiazepine and papaverine, respectively, and also for N-type Ca2+ channel ligand omega-[125I]-conotoxin GVIA (omega-[125I]CTX). Lineweaver-Bulk plot analysis disclosed that CaS competitively inhibited the binding of [3H]nitrendipine, with maximal binding capacity of 0.19 pmol/mg protein and dissociation constant (Kd) of 290 nM, being about 10(3) times the Kd value of [3H]nitrendipine. Similar to nitrendipine, CaS noncompetitively enhanced the binding of [3H]diltiazem, but did not affect the binding of [3']verapamil. CaS at up to 10.0 microM did not affect the binding of omega-[125I]CTX. These observations indicate that CaS shares the properties of 1,4-dihydropyridine derivatives, and allosterically modulates the binding of other L-type Ca2+ channel ligands.

Animals↗
PubMed1993

Nitric oxide mediates interleukin-1-induced prostaglandin E2 production by vascular smooth muscle cells.

We examined the possible participation of nitric oxide (NO) in the activation of cyclooxygenase, a heme-containing enzyme, induced by interleukin-1 (IL-1) in vascular smooth muscle cells (VSMC). IL-1 induced a delayed and prolonged release of both NO and prostaglandin E2 (PGE2) from VSMC. NG-monomethyl-L-arginine (L-NMMA), an inhibitor of NO synthesis, partially but significantly inhibited the PGE2 release induced by IL-1, whereas it completely inhibited the IL-1-induced NO production. The inhibitory effects of L-NMMA on IL-1-induced production of both NO and PGE2 were partially reversed by a 10-fold excess of L-arginine. In addition, coincubation with superoxide dismutase enhanced the IL-1-induced PGE2 release from VSMC. In contrast, 8-bromo-cyclic GMP did not stimulate PGE2 release. Furthermore, 0.2 mM sodium nitroprusside directly stimulated PGE2 release from VSMC. These findings suggest that NO at least in part mediates the IL-1-induced PGE2 production, and that NO may be one of the important signals for the activation of cyclooxygenase to produce PGE2 in VSMC.

Animals↗
PubMed1993

Captopril inhibits endothelin-1 secretion from endothelial cells through bradykinin.

Incubation with captopril, an angiotensin I converting enzyme inhibitor, for 24 hours at concentrations up to 10(-7) M inhibited endothelin-1 secretion by endothelial cells. This inhibition of endothelin-1 secretion was reversed by coincubation with 3 x 10(-3) M NG-nitro-L-arginine, an inhibitor of nitric oxide synthesis. Furthermore, captopril enhanced the production of nitric oxide in endothelial cells, suggesting that enhancement of nitric oxide production participates in captopril-induced inhibition of endothelin-1 secretion. Moreover, in the presence of 10(-6) M D-Arg,[Hyp3,Thi5,8,D-Phe7]-bradykinin, a bradykinin B2 receptor antagonist, captopril did not inhibit but rather stimulated endothelin-1 secretion, whereas bradykinin inhibited endothelin-1 secretion, and this inhibition by bradykinin was reversed by coincubation with NG-nitro-L-arginine. In addition, enhancement of nitric oxide production induced by either captopril or bradykinin was inhibited by D-Arg,[Hyp3,Thi5,8,D-Phe7]-bradykinin. Although 10(-6) M des-Arg9-[Leu8]-bradykinin, a bradykinin B1 receptor antagonist, did not affect nitric oxide production by bradykinin, it enhanced the inhibition of endothelin-1 secretion by bradykinin. Furthermore, 10(-7) M des-Arg9-bradykinin, a bradykinin B1 receptor agonist, stimulated endothelin-1 secretion by endothelial cells. These findings suggest that angiotensin I converting enzyme inhibitor inhibits endothelin-1 secretion by the accumulation of endogenous bradykinin in endothelial cells and that the inhibition of endothelin-1 secretion by bradykinin is mediated via B2 receptors.

Arginine↗
PubMed1993

Effects of beraprost sodium, a stable analogue of prostacyclin, on hyperplasia, hypertrophy and glycosaminoglycan synthesis of rat aortic smooth muscle cells.

The effects of beraprost sodium, a stable analogue of prostacyclin, on the syntheses of DNA, protein and glycosaminoglycans (GAG) of cultured vascular smooth muscle cells (SMC) were studied. SMC were isolated from the thoracic aorta of male Wistar rats. The syntheses of DNA, protein and GAG of SMC were determined by incorporations of [3H]thymidine, [3H]leucine and [35S]sulfuric acid, respectively. Insulin at a concentration of 10(-6) M stimulated DNA synthesis 4 fold compared to control. Beraprost sodium suppressed the insulin-stimulated DNA synthesis dose-dependently at concentrations greater than 10(-7) M and suppressed it by 68% at 10(-5) M. Platelet derived growth factor (PDGF) at a concentration of 20 ng/ml stimulated DNA synthesis 6 fold compared to control. Beraprost sodium suppressed the PDGF-stimulated DNA synthesis dose-dependently at concentrations greater than 10(-7) M and suppressed it by 51% at 10(-5) M. Beraprost sodium suppressed GAG synthesis dose-dependently at concentrations greater than 10(-7) M and suppressed it by 49% at 10(-5) M. However, beraprost sodium at concentrations up to 10(-5) M did not affect protein synthesis. These results indicate that beraprost sodium suppressed the proliferation and GAG synthesis of SMC but did not affect hypertrophy. Beraprost sodium may be a potent antiarteriosclerotic agent through suppression of hyperplasia of SMC and modification of matrix protein.

Animals↗
PubMed1992

[A case of Hashimoto's thyroiditis associated with renal tubular acidosis, Sjögren syndrome and empty sella syndrome].

This report describes a 48-year old female patient with Hashimoto's thyroiditis, distal-type renal tubular acidosis (d-RTA), Sjögren syndrome (SjS), and empty sella syndrome (ESS). She has been receiving replacement of thyroxine for Hashimoto's thyroiditis since 1967. She felt muscle weakness and numbness in the extremities and was found to have low serum potassium (2.9 mEq/l) in 1987. Since then she has been administrated potassium chloride orally. She was admitted to our hospital because of recurrence of muscle weakness and numbness of the extremities in November 1990. Laboratory examination revealed that her serum levels of antimicrosomal antibody and anti-thyroglobulin antibody were highly positive (MCHA: x 2(10) x 100, and TGHA: x 100). Furthermore, she was revealed to have 1) d-RTA by oral tolerance tests with the administration of NH4Cl and NaHCO3, 2) SjS by Schirmer test and sialography, and 3) ESS by computed tomography and magnetic resonance imaging examinations of the pituitary. Association of Hashimoto's thyroiditis, d-RTA, SjS and ESS in this case may possibly be caused by common autoimmune mechanism.

Acidosis, Renal Tubular↗
PubMed1992

Effect of ipriflavone on bone mineral density and calcium-related factors in elderly females.

The effects of ipriflavone (7-isopropoxy-3-phenyl-4H-1-benzopyran-4-one) on bone mineral density (BMD) of the 3rd lumbar vertebra and on calcium (Ca)-related factors, including serum calcitonin (CT) levels before and after rapid calcium infusion (4 mg/kg for 5 minutes), were studied in 11 elderly female subjects (80 +/- 2 years of age, mean +/- SE). Ipriflavone (IP) administration (600 mg/day, 7 months) resulted in inhibition of BMD loss in 7 patients (responders, mean change of BMD value 2.2 +/- 2.3%), whereas 4 patients showed a loss of BMD (nonresponders, mean change of BMD value -13.1 +/- 2.6%) compared with pretreatment values. The responder group showed a significant increase in mean pretreatment serum CT levels (from 20 +/- 2 pg/ml to 42 +/- 7 pg/ml, P < 0.05) after treatment with IP, and a significant decrease in the mean basal serum level of corrected Ca (from 9.6 +/- 0.2 mg/dl to 8.7 +/- 0.1 mg/dl, P < 0.01) after treatment with IP; nonresponders did not show these changes. For responders, both the percentage of change and the maximal value of serum CT in response to Ca infusion were maintained at rather high levels, both before and after IP treatment; nonresponders showed almost no response to a stimulation test for CT. These findings suggest that IP inhibits bone loss in elderly female subjects possibly through the mechanism of increasing CT secretion.

Aged↗
PubMed1992

Participation of decreased serum cholesteryl ester transfer activity, independent of increased serum lipoprotein(a), in angina pectoris in normolipemic elderly subjects.

The cholesteryl ester transfer activity (CETA) is a measurement of the transfer of cholesteryl ester from HDL to VLDL, LDL or peripheral cells. Its role in the development of early coronary heart disease is not clear. In the present study, serum levels of CETA, lipoprotein(a) [Lp(a)] and other lipid-related factors were compared in 10 normal young subjects, 28 healthy elderly subjects and 14 normolipemic elderly patients with angina pectoris. Compared to the young normals and healthy elderly subjects, the elderly patients with angina pectoris showed significantly decreased mean serum CETA levels, and significantly increased mean serum levels of Lp(a) and apoprotein B. These results may indicate that decreased serum values of CETA participate in the development of angina pectoris in normolipemic elderly patients.

Adult↗
PubMed1992

Circulating suppressing factor for the muscarinic acetylcholine receptor in patients with senile dementia of the Alzheimer type.

Circulating suppressing factor for the binding of quinuclidinyl benzilate (QNB), an antagonist for the muscarinic acetylcholine receptor, to the synaptic membranes was evaluated in 48 patients with senile dementia of the Alzheimer type (SDAT), in 17 patients with the vascular type dementia (VTD) and in 11 nondemented elderly subjects (NE). The mean suppression rate on the binding in the SDAT group was significantly greater than that in the NE group, although that in the VTD group was similar to that in the NE group. Moreover, the percent QNB binding was significantly (p < 0.05) correlated with the score of the mini-mental state in the SDAT group. The circulating suppressing factor may participate in the pathogenesis of SDAT.

Aged↗
PubMed1992

[An 88-year-old female case of hyperalphalipoproteinemia associated with deficiency of cholesteryl-ester transfer activity].

An 88-year-old female was admitted to our hospital for examination of hyperalphalipoproteinemia. The high level of her serum high-density lipoprotein cholesterol (HDL-C, 148 mg/dl) was due to cholesterol amount of HDL2-C but not HDL3-C, and serum cholesteryl ester transfer activity (CETA) was at a non-detectable level. Despite her age, apparent atherosclerotic changes were not observed. She may be the oldest case of hyperalphalipoproteinemia, possibly due to deficiency of serum CETA.

Aged↗
PubMed1992

[Dysuria in male elderly outpatients evaluated by a questionnaire survey].

We surveyed complaints of dysuria in male elderly outpatients by questionnaire survey. Seven hundred and twenty outpatients (39 aged 30-39, 63 aged 40-49, 170 aged 50-59, 229 aged 60-69, and 219 aged 70 or more) visiting our outpatient internal medicine clinics were asked by a questionnaire about the subjective symptoms of dysuria, including frequencies of nocturia, prolongation of the start of urination, straining at urination, and residual urine, graded as asymptomatic, mild, moderate and severe. The subjects were divided into three groups as to the dysuria; normal group without symptoms or one mild symptom, borderline group with two or more mild symptoms, and dysuria group with one moderate or severe symptom or more. The rates of the patients in the dysuria group were increased with age, being 15%, 16%, 21%, 31% and 53%, respectively, in the above-mentioned age groups. This finding emphasized the importance of questions about dysuria in elderly patients also in internal medicine outpatient clinics, and of differential diagnosis for the causal factor(s) for dysuria in elderly patients including benign prostate hypertrophy.

Adult↗
PubMed1992

Bradykinin suppresses endothelin-induced contraction of coronary, renal and femoral arteries through its B2-receptor on the endothelium.

Effect of bradykinin (BK) on endothelin-1 (ET-1)-induced vasoconstriction and its mechanism were investigated. The development of isometric force of arterial rings of canine coronary, renal and femoral arteries was recorded using a organ bath containing Krebs-Henseleit buffer aerated with 95% O2 and 5% CO2. ET-1 at more than 10(-9) M dose-dependently induced vascular contraction similarly among the three arteries. BK at more than 10(-8) M dose-dependently suppressed the ET-1-induced vasoconstriction only in the presence of endothelium, and the effect of BK was largest in the coronary arteries. The BK-induced suppression was not affected by addition of des-Arg9-[Leu8]-BK, an antagonist for B1-receptor, but did be completely reversed by addition of B2-receptor antagonist (10(-6) M) [D-Arg0,Hyp3,Thi5,8,D-Phe7]-BK. The BK's suppression of the ET-1-induced vasoconstriction was partly reversed by additions of each 10(-5) of Ng-nitro-L-arginine, a substrate inhibitor of nitric oxide, methylene blue, an inhibitor of soluble guanylate cyclase, or indomethacin, an inhibitor of cyclooxygenase. The reversing effects of methylene blue and indomethacin were additive. BK suppresses the ET-1-induced vasoconstriction through B2-receptor on the endothelium. Both endothelial nitric oxide and prostaglandin(s) are participated in the BK's effect.

Animals↗
PubMed1992

Effects of manidipine hydrochloride on proliferation and glycosaminoglycan synthesis of cultured vascular smooth muscle cells.

The effects of manidipine hydrochloride, a calcium channel blocker, on the proliferation and the synthesis of glycosaminoglycans (GAG) in cultured rat aortic vascular smooth muscle cells (VSMC) were studied. Mandipine hydrochloride suppressed the DNA synthesis of VSMC dose dependently at concentrations of more than 10(-8) M. Mandipine hydrochloride 10(-6) M suppressed proliferation of VSMC to 50% of the control value. Manidipine hydrochloride stimulated the synthesis of GAG at concentrations above 10(-11) M. Manidipine hydrochloride 10(-8) M stimulated synthesis of GAG to 450% of control. Our findings suggest that because mandipine hydrochloride suppresses proliferation and stimulates GAG synthesis of VSMC, it may be an anti-arteriosclerotic agent.

Animals↗
PubMed1992

EDTA induces differentiation and suppresses proliferation of promyelocytic leukemia cell line HL-60--possible participation of zinc.

Effects of ethylenediaminetetraacetic acid (EDTA), a chelator of divalent cations, on the proliferation and differentiation of human promyelocytic leukemia cell line HL-60 were examined. Incubation of HL-60 cells with 200 microM of EDTA suppressed cell proliferation, and induced differentiation assessed by reductivity of nitro blue tetrazolium and activity of alpha-naphthyl butyrate esterase. These effects were inhibited by zinc (Zn) dose-dependently at concentrations of up to 20 microM, but not by other divalent cations including Ca, Mg, Fe, Cu, Ni, or Cd. Although addition of 200 microM EDTA for 24 hr decreased the c-myc mRNA level of HL-60 cells, coaddition of 20 microM of Zn also reversed this effect on c-myc mRNA level. Treatment with EDTA did not change the half-life time of degradation of c-myc mRNA after addition of actinomycin D (5 micrograms/ml). These findings suggest that Zn deficiency suppresses c-myc gene transcription which is followed by suppression of proliferation and induction of differentiation of HL-60 cells.

Blotting, Northern↗
PubMed1991

Interleukin-6 stimulates proliferation of cultured vascular smooth muscle cells independently of interleukin-1 beta.

The effects of interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) on proliferation of cultured vascular smooth muscle cells (VSMCs) were investigated. Treatment with IL-6 caused a rapid increase in the c-myc mRNA level, and resulted in increases in DNA synthesis and cell number. IL-1 beta stimulated the DNA synthesis of the cells. EGF showed synergistic and PDGF or IL-1 beta showed additive effects with IL-6 on the DNA synthesis. These results suggest that IL-6, independently of IL-1 beta, may be important in the proliferation of VSMCs.

Animals↗
PubMed1991

Exaggerated natri-calci-uresis and increased circulating levels of parathyroid hormone and 1,25-dihydroxyvitamin D in patients with senile hypertension.

Renal handling of Na and Ca in response to physiological saline infusion (20 ml/kg i.v. for 2 h) was compared between 27 hypertensive (mean +/- SD age 79.8 +/- 9.2 years) and 44 normotensive (79.1 +/- 4.1 years) senile females. Compared to the normotensive group, the hypertensive group showed statistically significant decreases in the basal values of serum Ca and PRA, and significant increases in basal circulating levels of parathyroid hormone and 1,25(OH)2D and in urinary excretions of Na, Ca and Pi in the 2-hour urine specimens during the saline infusion. These results suggest that the excessive excretions of Ca and Pi associated with exaggerated natriuresis may participate in aberration of Ca metabolism in low-renin hypertensive seniles.

Absorption↗
PubMed1991

Intracellular signal transduction evoked by low-density lipoprotein in vascular smooth muscle cells.

Low-density lipoprotein (LDL) is a well-known causal factor in the development of arteriosclerosis. In the present study, we evaluated LDL-evoked cellular signal transduction in cultured rat vascular smooth muscle cells (VSMC). The addition of LDL at concentrations of more than 50 ng/ml, and apolipoprotein B (Apo-B) at more than 5 ng/ml, induced rapid but transient increases in the inositol 1,4,5-trisphosphate (InsP3) level, and caused rapid phasic and subsequent tonic increases in cytosolic free Ca2+ concentration [( Ca2+]i) in a dose-dependent manner in VSMC. LDL and Apo-B also caused transient acidification followed by Na(+)-dependent and amiloride-sensitive alkalization of the cells due to stimulation of a Na+/H+ exchanger. The enhancement of thymidine incorporation induced by the addition of LDL correlated well with the degree of increment of [Ca2+]i increases by the lipoprotein. These results suggest that an increase in [Ca2+]i mediated by InsP3 and intracellular alkalization may function as an important signal for enhanced DNA synthesis induced by LDL in VSMC.

Amiloride↗