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T Muraki

Publications and source records attributed to T Muraki.

At least 37 records · Page 2Linked to original sources
PubMed1999

A shear-induced in vitro platelet function test can assess clinically relevant anti-thrombotic effects.

Morphological features of haemostatic plugs formed in vitro under high shear forces were investigated. Electron microscopy confirmed the relevance of such haemostatic plug to a platelet-rich arterial thrombus, which is formed in vivo . In rat blood samples, the effects of anticoagulants and various antiplatelet agents on platelet reactivity (rate of haemostatic plug formation) and subsequent coagulation of the flowing blood were investigated. Haemostasis did not occur in citrated blood, and heparin greatly inhibited the shear-induced platelet reaction. Aspirin (1 mM), a thromboxane A(2) receptor antagonist (5 microM), a stable prostacyclin (0.55 nM), a stable prostaglandin E(1) (141 nM) and a phosphodiesterase inhibitor (100 microM) were tested. All these agents exerted significant inhibitory effect on shear-induced platelet reaction, including the inhibition of the very first phase of platelet plug formation, due to aggregation of shear-activated platelets. Except for the phosphodiesterase inhibitor, which prolonged clotting time, none of the above agents affected dynamic coagulation. These results suggest that the employed in vitro shear-induced thrombosis/haemostasis test can reveal in vivo the antithrombotic effect of various agents independently of their mechanism of action.

Journal Article↗
PubMed1998

Beta-adrenoceptor antagonist propranolol potentiates hypotensive action of natriuretic peptides.

Beta-adrenoceptor antagonists are known to increase plasma atrial natriuretic peptide (ANP) levels despite their hypotensive action. The aim of the present study was to examine the role of the ANP system in the antihypertensive effects of a beta-adrenoceptor antagonist. We investigated the effects of propranolol (75 mg kg(-1) day(-1), p.o., 4 weeks) on the ANP system in stroke-prone spontaneously hypertensive rats. Plasma ANP levels were significantly higher in the propranolol group than in the control group. Both receptor densities and mRNA levels of ANP(C) receptor were significantly decreased in the lung as the major site of ANP clearance from the circulation. In contrast, both central venous pressure and ANP mRNA levels in the heart were not significantly different between the two groups. Under both basal and ANP-stimulated conditions, the cGMP content in the aorta was significantly greater in the propranolol group than in the control group, whereas the basal and stimulated cGMP content of the kidney was similar in the two groups. Inhibition of endogenous ANP action by a specific ANP receptor antagonist, HS-142-1, produced a greater increase of blood pressure in the propranolol group than in the control group. These results suggest potentiation of natriuretic peptide activity as a new antihypertensive mechanism of the beta-adrenoceptor antagonist propranolol.

Adrenergic beta-Antagonists↗
PubMed1998

Effects of cyclosporine and FK506 on in vitro high shear-induced platelet reactivity in rat and human non-anticoagulated blood.

BACKGROUND: The immunosuppressants cyclosporine and FK506 have been used successfully in clinical transplantation, but both agents have various side effects. We have previously found that cyclosporine is prothrombotic and that FK506 is antithrombotic in an in vivo system. The aim of the present study was to assess the effects of these agents on platelet reactivity and coagulation using an in vitro shear-induced hemostatic platelet plug-forming instrument, the hemostatometer. METHODS: A purpose-built hemostatometer was constructed in our laboratory. The effects of cyclosporine and FK506 on platelet reactivity and coagulation were assessed under high shear stress using non-anticoagulated rat and human blood. RESULTS: FK506 significantly inhibited both platelet reactivity and coagulation. Cyclosporine also significantly inhibited coagulation, but a proaggregatory effect was observed at a final blood concentration of 0.05 mg/ml. CONCLUSIONS: The present in vitro results support our previous in vivo findings regarding the prothrombotic and antithrombotic effects of cyclosporine and FK506, respectively.

Adult↗
PubMed1998

Antiinflammatory potency of dehydrocurdione, a zedoary-derived sesquiterpene.

OBJECTIVE AND DESIGN: Dehydrocurdione, a sesquiterpene isolated from zedoary, was tested for in vivo and in vitro antiinflammatory actions. MATERIALS: Analgesic effect was tested in ICR mice by the acetic acid-induced writhing method. Antipyretic effect was studied in Sprague-Dawley rats treated with baker's yeast. Antiinflammatory activities were tested in Wistar rats with carrageenan-induced paw edema and adjuvant-induced chronic arthritis. In vitro analyses included the capabilities to inhibit cyclooxygenase activity, and to scavenge free radicals as determined by electron paramagnetic resonance (EPR). RESULTS: Oral administration of dehydrocurdione (40 to 200 mg/kg) mitigated the writhing reflex. induced by acetic acid and the fever elicited by baker's yeast. A higher dose (200 mg/kg) of dehydrocurdione was required to inhibit the carrageenan-induced paw edema. Oral administration of dehydrocurdione at 120 mg/kg/day for 12 days significantly reduced chronic adjuvant arthritis. Unlike indomethacin (IC50: 0.1 microM), dehydrocurdione showed minimal cyclooxygenase inhibition. However, dehydrocurdione (100 microM to 5 mM) significantly reduced free radical formation from hydrogen peroxide and ferrous iron determined by EPR spectrometry using 5,5'-dimethyl-1-pyrroline-N-oxide as a spin trap agent. CONCLUSION: In addition to the well-known effect of zedoary as a stomachic, dehydrocurdione, the major component of Curcuma zedoaria Roscoe has antiinflammatory potency related to its antioxidant effect.

Acetic Acid↗
PubMed1998

Molecular characterization of the mouse mtprd gene, a homologue of human TPRD: unique gene expression suggesting its critical role in the pathophysiology of Down syndrome.

We and others recently isolated a human TPRD gene, possessing a motif of the tetratricopeptide repeat (TPR), from the Down syndrome-critical region (DCR) of chromosome 21q22.2. In this study, we isolated a mouse homologue of TPRD cDNA, mtprd, and examined its expression profile in mouse embryos. The gene was mapped to mouse chromosome 16C3.3-4, consistent with the location of DCR, and encodes 1,979 amino acid residues with 76% identity to TPRD. The mtprd protein has three units of the TPR motif with 91% homology to TPRD. The protein also has two regions homologous to several matrix proteins with 86 and 70% identities to those of TPRD. Several splicing variants of the 5' portion of the open reading frame of mtprd were identified by RT-PCR and sequencing of mRNAs. In situ hybridization showed that mtprd is ubiquitously expressed in mouse embryos but predominantly in the central nervous system, including the telencephalon, mesencephalon, and metencephalon. These results suggest that the TPRD gene is one of the genes responsible for not only the morphological anomalies but also the neurological abnormalities observed in Down syndrome. The presence of splicing variants indicates that the protein may also have several isoforms in mice.

Amino Acid Sequence↗
PubMed1998

Deletion polymorphism of the angiotensin converting enzyme gene predicts persistent proteinuria in Henoch-Schönlein purpura nephritis.

OBJECTIVE: To study the influence of deletion/insertion polymorphism in the 16th intron of the angiotensin converting enzyme (ACE) gene on clinical manifestations of Henoch-Schönlein purpura nephritis. STUDY DESIGN: Cross sectional study. ACE gene polymorphism was determined in patients (4-15 years old at onset) with Henoch-Schönlein purpura nephritis (n = 40) and compared with that in patients with IgA nephropathy (n = 79). MAIN OUTCOME MEASURES: ACE genotypes, systemic blood pressures, urine protein excretion rate, haematuria, creatinine clearance, serum ACE activities. RESULTS: The initial clinical manifestations of both Henoch-Schönlein purpura nephritis and IgA nephropathy were no different among homozygotes for insertion (II) and deletion (DD), and heterozygotes (ID) for the ACE gene. In patients with Henoch-Schönlein purpura nephritis, the incidence of moderate to heavy proteinuria at four and eight years after onset was more than five times higher in the DD genotype than in the II or ID genotypes. No such trend was seen in patients with IgA nephropathy. The number of patients with Henoch-Schönlein purpura nephritis in whom proteinuria resolved at four and eight years after onset was significantly lower in the DD genotype compared with the II genotype, whereas no differences were detected among the three different genotypes in patients with IgA nephropathy. Plasma ACE activities in patients with the DD genotype were significantly higher than in those with non-DD genotypes. CONCLUSIONS: The ACE DD genotype predicts persistent proteinuria in Henoch-Schönlein purpura nephritis. The proteinuria might be related to a defective angiotensin system which is genetically determined by the D/I polymorphism.

Adolescent↗
PubMed1998

Potentiation of natriuretic peptide action by the beta-adrenergic blocker carvedilol in hypertensive rats: a new antihypertensive mechanism.

Treatment with a beta-adrenergic blocker (beta-blocker) in hypertension is associated with increased plasma atrial natriuretic peptide (ANP) levels despite a decrease in cardiac overload. The mechanism and pathophysiological significance of the phenomenon remain unclear. To clarify the role of the ANP system in the antihypertensive effects of the beta-blocker, we investigated the effects of carvedilol (30 mg/kg x day, orally, for 4 weeks) on the ANP system in stroke-prone spontaneously hypertensive rats (SHR-SP/Izm). Plasma ANP levels showed a significant increase despite a significant decrease in blood pressure and heart rate in the carvedilol group. Although ANP messenger RNA levels in the heart did not change, messenger RNA levels of the natriuretic peptide-C (NP-C) receptor as a clearance receptor showed a significant decrease in both the aorta and lung in the carvedilol group. NP-C receptor densities were also significantly decreased in the lung in this group. The biological half-life of exogenous ANP in circulating blood was prolonged in the carvedilol group compared with that in the control group. Administration of the ANP receptor antagonist, HS-142-1, resulted in a greater increase in systolic blood pressure in the carvedilol group than in the control group. In addition, both basal and ANP-stimulated cGMP contents in the aorta were significantly higher in the carvedilol group. These results suggest that carvedilol potentiates the hypotensive action of ANP by increasing plasma ANP levels and enhancing the vascular response to ANP. These effects were closely related to the down-regulation of the NP-C receptor. The newly found mechanism seems to account for a sizable portion of the antihypertensive effects of carvedilol and could be of potential importance in the treatment of cardiovascular disease with beta-blockers.

Adrenergic beta-Antagonists↗
PubMed1998

Effect of tazarotene, an acetylenic retinoid, on human dermal fibroblast.

The inhibitory effect of tazarotene, an acetylenic retinoid, on human dermal fibroblast in vitro was compared to that of all-trans-retinoic acid. The proliferation of fibroblasts was inhibited by both retinoids at the concentration of 1 microM after 5 days of culture. Synthesis of DNA and collagen was inhibited by both retinoids concentration-dependently up to 10 microM, although tazarotene was weaker in the inhibition of collagen synthesis. These results suggest the possible usefulness of tazarotene in the treatment of fibrotic diseases.

Bromodeoxyuridine↗
PubMed1998

The effect of acute cold exposure and norepinephrine on uncoupling protein gene expression in brown adipose tissue of monosodium glutamate-obese mice.

Abnormal regulation of mitochondrial uncoupling protein (UCP) gene expression was studied in brown adipose tissue (BAT) of monosodium glutamate (MSG)-induced obese mice. UCP mRNA levels in control mice increased markedly after acute cold exposure; however, MSG-obese mice showed an impaired response. In contrast, an injection of norepinephrine (NE) induced a comparable increase in UCP mRNA levels in control and MSG-obese mice. These results suggest that the impairment in the cold-induced increase in UCP mRNA is due to a deficient sympathetic input to BAT and/or to a diminished response of BAT to endogenous NE, which constitutes the mechanism of impaired thermoregulation in obese mice in a cold environment.

Adipose Tissue, Brown↗
PubMed1998

Evidence for modulation of osteocalcin containing gamma-carboxyglutamic acid residues synthesis by insulin-like growth factor-I and vitamin K2 in human osteosarcoma cell line MG-63.

The effect of insulin-like growth factor-I (IGF-I) and 2-methyl-3-all-trans-tetraphenyl-1,4-naphtoquinone (vitamin K2) on the synthesis of osteocalcin containing gamma-carboxyglutamic acid (Gla) residues which is the physiologically relevant form in bone metabolism was studied in cultured human osteoblast-like (MG-63) cells. Both IGF-I and vitamin K2 stimulated 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)-induced osteocalcin containing Gla secretion in a concentration-dependent manner. This stimulatory effect of IGF-I and vitamin K2 was additive. Vitamin K2-enhanced osteocalcin containing Gla secretion was selectively suppressed by 3-(alpha-acetonyl-benzyl)-4-hydroxy-coumarin (warfarin). The stimulatory effect of IGF-I was completely abolished by the presence of cycloheximide; in contrast the effect of vitamin K2 was still observed in the presence of cycloheximide. Treatment of MG-63 cells with IGF-I caused an approximately 2.2-fold increase in osteocalcin mRNA levels (determined by reverse transcription-polymerase chain reaction). Vitamin K2 had no effect on either the stimulation of mRNA level by IGF-I or the basal level. IGF-I-stimulated osteocalcin containing Gla secretion was inhibited by one of its binding proteins (insulin-like growth factor binding protein-4) in a concentration-dependent manner. These findings suggest that the modes of action of IGF-I and vitamin K2 on 1.25(OH)2D3-induced osteocalcin containing Gla secretion in MG-63 cells are different.

1-Carboxyglutamic Acid↗
PubMed1997

Cationic amino acid transporter-2 mRNA induction by tumor necrosis factor-alpha in vascular endothelial cells.

Nitric oxide (NO) synthesis may be coupled to the activity of the cellular L-arginine transporter, namely the cationic amino acid transporter. The present study examined tumor necrosis factor (TNF)-alpha-induced alterations in the gene expression of the cationic amino acid transporter (CAT) and NO production in human umbilical vein endothelial cells. In quiescent endothelial cells, CAT-1 mRNA expression, determined by reverse transcription-polymerase chain reaction, was dominant to that of CAT-2. TNF-alpha (10 ng/ml for 1-24 h) induced a time-dependent increase in CAT-2 but not CAT-1 expression. Moreover, TNF-alpha (1-30 ng/ml) treatment for 6 h induced a concentration-dependent increase in CAT-2 mRNA expression. The upregulation of CAT-2 expression by TNF-alpha was associated with enhanced nitrite accumulation in the culture medium (70% increase compared with vehicle-treated cells at 24 h). Thus, induction of the cationic amino acid transporter may constitute one mechanism for the TNF-alpha-induced NO production in human umbilical vein endothelial cells.

Amino Acid Transport Systems, Basic↗
PubMed1997

Nitric oxide mediates down regulation of lipoprotein lipase activity induced by tumor necrosis factor-alpha in brown adipocytes.

We previously reported that tumor necrosis factor-alpha (TNF-alpha)/cachectin suppresses lipoprotein lipase activity and its gene expression in brown adipocytes differentiated in culture. Recent evidence suggests that the effect of TNF-alpha over various cells is related to the enhanced production of nitric oxide (NO). The present study examined whether the suppressive effect of TNF-alpha on lipoprotein lipase activity is mediated by production of NO in the brown adipocytes. A reverse transcription-polymerase chain reaction (RT-PCR) assay revealed that TNF-alpha caused a concentration- and time-dependent expression of inducible NO synthase in brown adipocytes. Increasing concentrations of TNF-alpha (0.5-50 ng/ml) for 24 h resulted in a concentration-dependent decrease in lipoprotein lipase activity with reciprocal increase in nitrite production in the medium. The suppressive effect of TNF-alpha on lipoprotein lipase activity was significantly prevented by NO synthase inhibitors, NG-nitro-L-arginine methyl ester (L-NAME) and aminoguanidine, but not by D-NAME, an inactive isomer. Furthermore, 8-bromoguanosine 3',5'-cyclic monophosphate, cell permeant cGMP, suppressed lipoprotein lipase activity and 1 H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one, a selective inhibitor for soluble guanylate cyclase, restored the TNF-alpha-suppressed lipoprotein lipase activity. These results suggest that TNF-alpha stimulates brown adipocytes to express inducible NO synthase, followed by production of NO, which in turn mediates the suppressive effect of TNF-alpha on lipoprotein lipase activity. The effect of NO is mediated, at least partly, through production of cGMP.

Adipocytes↗
PubMed1997

Role of nitric oxide, prostaglandins and tyrosine kinase in vascular endothelial growth factor-induced increase in vascular permeability in mouse skin.

We investigated role of nitric oxide (NO), prostaglandins (PG) and tyrosine kinase in vascular endothelial growth factor (VEGF)-induced increase in vascular permeability in mouse skin. Subcutaneous injection of VEGF (0.5-2.0 ng/site) induced dose- and time-dependent increase in vascular permeability at the injection site determined by a leakage of Pontamine sky blue. VEGF (1 ng/site)-induced dye leakage was partially inhibited by N(G)-nitro-L-arginine methyl ester (an inhibitor for both constitutive and inducible NO synthase) (5 and 10 mg/kg, i.v.) and by aminoguanidine (a selective inducible NO synthase inhibitor) (5-20 mg/kg, i.v.), but not by an inactive enantiomer, N(G)-nitro-D-arginine methyl ester (10 mg/kg, i.v.). Pretreatment with an intraperitoneal injection of indomethacin (a nonselective cyclooxygenase inhibitor) (5 mg/kg) or N-(2-cyclohexyloxy-4-nitrophenyl) methanesulphonamide (a cyclooxygenase-2 selective inhibitor) (1-100 microg/kg) almost completely inhibited the effect of VEGF (1 ng/site). Coadministration of PGE2 (3 and 30 nmol/site) with VEGF did not restore the inhibitory effect of indomethacin on VEGF (1 ng/site)-induced increase in vascular permeability. Lavendustin A (a selective tyrosine kinase inhibitor) (10 and 50 microg/kg, s.c.) dose-relatedly inhibited the VEGF (1 ng/site)-induced increase in dye leakage, whereas its negative control, lavendustin B (10 microg/kg, s.c.) had no effect. Another tyrosine kinase inhibitor, genistein (2.5 mg/kg, s.c.) also inhibited the response. Cycloheximide (a protein biosynthesis inhibitor) (35 mg/kg, s.c.) suppressed the response of VEGF (1 ng/site). Histologically, no cellular infiltration was observed in the area of VEGF injection. These results suggest that increased vascular permeability induced by VEGF is mediated by local production of NO and arachidonic acid metabolites other than PGE2, which are most probably produced by inducible NO synthase and cyclooxygenase-2, respectively. Protein tyrosine kinase-mediated phosphorylation and synthesis of any new proteins are likely to be required in this effect of VEGF in mouse skin.

Animals↗
PubMed1997

Estrogen and parathyroid hormone regulate insulin-like growth factor binding protein-4 in SaOS-2 cells.

The effect of 17beta-estradiol and parathyroid hormone (PTH) on the expression of insulin-like growth factor-binding protein-4 (IGFBP-4) messenger RNA (mRNA) was studied in the cultured human osteoblast-like SaOS-2 cells. Treatment of SaOS-2 cells with PTH for 3 h caused 3.3-fold increase in IGFBP-4 mRNA levels which was determined by reverse transcription-polymerase chain reaction. 17beta-Estradiol had no effect on either the stimulation of mRNA level by PTH or the basal level. Together with our previous report that 17beta-estradiol inhibits the PTH-induced reduction of IGFBP-4 proteolysis in these cells, the results obtained may help to explain the mechanisms of determining IGFBP-4 availability by systemic hormones in osteoblast cells.

Blotting, Western↗
PubMed1997

Iodothyronine deiodinases in a mammalian hibernator, the chipmunk (Tamias asiaticus).

We examined the activities of iodothyronine deiodinase, a key enzyme for thyroid hormone metabolism, in selected tissues of the chipmunk (Tamias asiaticus), a mammalian hibernator, of both sexes in the summer season. Reverse T3 5'-deiodinase (5'-D) activity was the highest in the liver followed by the kidney; T4 5'-D activity was the highest in brown adipose tissue (BAT) and T3 5'-deiodinase (5-D) activity was the highest in the testes followed by the brain. Distributions of three types of deiodinase activities in liver kidney BAT, and brain were comparable to other mammals reported, except that the type III deiodinase was unique in testes. The 5'-D activity of liver and kidney of chipmunks was 52% and 24%, respectively, of male rats and the 5-D activity of brain and testes of chipmunks was 227% and 567%, respectively of male rats. In addition, the cold exposure increased BAT 5'-D activity in chipmunks as reported in the ground squirrels. Our results indicated that tissue distribution of deiodinases and response to cold exposure in BAT in hibernators are similar to nonhibernators. However, there was a quantitative difference of rT3 5'-D and T3 5-D activities in some tissues between chipmunks and rats, indicating different local thyroid hormone metabolisms in hibernators and nonhibernators.

Adipose Tissue, Brown↗
PubMed1997

Expression of von Willebrand factor, P-selectin (CD62P) and thrombomodulin in human endothelial cells in culture modulated by cyclosporin A.

Endothelial cells were isolated from human umbilical veins and from saphenous veins and were cultured in the presence and absence of cyclosporin A (CSA). Cell morphology and growth characteristics were monitored continuously by video recording microscopy. The cells and culture supernatants were analysed for von Willebrand Factor (VWF), P-Selectin (CD62P) and thrombomodulin (TM) by immunocytochemistry and immunoassay. CSA had little effect on confluent cells in culture. In contrast, the characteristics of both umbilical vein and saphenous vein cells were markedly altered when CSA was added to subconfluent cultures. Under these conditions, CSA did not appear to be directly cytotoxic at the concentrations used but marked changes in cell morphology including the appearance of large multinucleate forms were recorded. Increased amounts of VWF and TM were detected in the culture supernatants of cells grown continuously in the presence of CSA and correspondingly depressed expression of cell associated antigens was observed. Heterogeneous and depressed distribution of CD62P was seen after 5-6 days culture but cellular expression of this ligand did not appear to be affected specifically by the presence of CSA. In addition, mechanically disrupted confluent endothelial cells failed to recover in the presence of CSA as effectively as similar cells grown in the absence of CSA. The results showed that CSA disturbed actively growing cells more severely than quiescent cells and might help to clarify the role of CSA in vascular disturbances in vivo.

Cells, Cultured↗
PubMed1997

Defective stimulation of thyroxine 5'-deiodinase activity by cold exposure and norepinephrine in brown adipose tissue of monosodium glutamate-obese mice.

In order to examine the possible change in the thyroid hormone metabolism in the monosodium glutamate (MSG)-obese mice, we determined the iodothyronine deiodinase activity of brown adipose tissue (BAT), liver and kidney of male and female mice. There was no significant difference in the type II thyroxine 5'-deiodinase (T4 5'DII) activity in BAT between MSG-obese and control mice when they were kept at the ambient temperature of 22 degrees C. T4 5'DII activity in BAT of control mice increased markedly after exposure to cold (4 degrees C) for 4 h; however, the extent of cold-induced increase in T4 5'DII activity in BAT of MSG-obese mice was greatly reduced. Injection of norepinephrine (NE) (0.8 mg/kg, s.c.) 4 h previously increased T4 5'DII activity in BAT of control mice, but NE-induced increase in T4 5'DII activity was also markedly reduced in BAT of MSG-obese mice. Both cold- and NE-induced increase in T4 5'DII activity was greater in female, although similar tendency was obtained in male mice. Type I 3,3',5'-triiodothyronine deiodinase (rT3 5'DI) activity of liver and kidney, and serum thyroxine (T4) and 3,5,3'-triiodothyronine (T3) levels in MSG-obese mice were essentially the same as those of the control male and female mice irrespective of cold exposure. These results suggest that defective stimulation of T4 5'DII activity of BAT by cold in the MSG-obese mice is due to deficient sympathetic input to BAT and/or to diminished response of BAT to NE, and may contribute to a possible cause of inability of MSG-obese mice to maintain body temperature under cold exposure.

Adipose Tissue, Brown↗