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Biomedical subjects

A Kuwabara

Publications and source records attributed to A Kuwabara.

At least 19 recordsLinked to original sources
PubMed2006

Anti-inflammatory sesquiterpenes from Curcuma zedoaria.

From the methanolic extract of the rhizome of Curcuma zedoaria, we isolated anti-inflammatory sesquiterpene furanodiene (1) and furanodienone (2) along with new sesquiterpene compound 3 and known eight sesquiterpenes, zederone (4), curzerenone (5), curzeone (6), germacrone (7), 13-hydroxygermacrone (8), dehydrocurdione (9), curcumenone (10), and zedoaronediol (11). Their structures were elucidated on the basis of spectroscopic data. The anti-inflammatory effect of isolated components on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation of mouse ears were examined. Compounds 1 and 2 suppressed the TPA-induced inflammation of mouse ears by 75% and 53%, respectively, at a dose of 1.0 micromol. Their activities are comparable to that of indomethacin, the normally used anti-inflammatory agent.

Animals↗
PubMed2006

[Early results of new style aortosaphenous vein graft connector in coronary artery bypass grafting].

We retrospectively studied early clinical results of PAS-Port (PP) system. Fifty patients who underwent coronary artery bypass surgery with saphenous vein graft (SVG) from April 2004 to May 2005 were enrolled in this study. PP was tried for 36 SVGs in 32 patients. In 2 patients, SVG 4.0 mm in diameter could not be loaded into the device. In other 2 patients, anastomosis with PP was failed and followed by hand-sewing under aortic clamp or with Heartstring. Anastomosis with PP was successfully completed for 34 SVGs in 30 patients (group P) and conventional hand-sewing was performed for 23 SVGs in 20 patients (group C). The target vessels for SVG were similar between the 2 groups. No complication occurred in the use of PP. Postoperative angiography before discharge was performed for 31 SVGs in 27 patients (90.0%) in group P and 20 SVGs in 17 patients (85.0%) in group C. The patency rate of SVG was 96.8% in group P and 100% in group C. In conclusion, early results of PP were satisfactory compared with those of conventional hand-sewing. Severely sclerotic aorta and oversized SVG should be excluded because of possibility for incomplete deployment of the inner flange in PP.

Aged↗
PubMed2005

General rule for displacive phase transitions in perovskite compounds revisited by first principles calculations.

A recent high pressure experiment on LaAlO3 has revealed that the compound is an exception for the "general rule" of displacive phase transition associated with zone-boundary phonons. In the present study, the experimental result is successfully confirmed by first principles calculations. The pressure dependence of phonon frequencies as well as the phase transition pressure is quantitatively well reproduced. We found that the behavior is not peculiar to LaAlO3 but rather ubiquitous. RAlO3 (R = La, Nd, Sm, and Gd) and LaGaO3 can be classified in the same group.

Journal Article↗
PubMed2002

[Right atrial lipoma with calcification in ascending aorta; report of a case].

A 67-year-old male was diagnosed to have a right atrial tumor by echocardiography incidentally. Computed tomography (CT) indicated a mass which showed very low radiodensity and magnetic resonance imaging (MRI) [T1-weighted] showed the high signal intensity of tumor. We could predict the mass as lipoma. Tumor removal was performed under cardio-pulmonary bypass and under ventricular fibrillation because of the calcification in ascending aorta. Microscopically the tumor was consisted of mature adipose tissue. The postoperative course was uneventful. Cardiac lipomas are rare tumors. CT and MRI are better investigations for preoperative diagnosis. After surgical excision the prognosis is excellent.

Aged↗
PubMed2001

Sphingosine 1-phosphate may be a major component of plasma lipoproteins responsible for the cytoprotective actions in human umbilical vein endothelial cells.

Sphingosine 1-phosphate (S1P), a novel lipid mediator, is concentrated in the fraction of lipoproteins that include high density lipoprotein (HDL) and low density lipoprotein (LDL) in human plasma. Here, we show that oxidation of LDL resulted in a marked reduction in the S1P level in association with a marked accumulation of lysophosphatidylcholine (LPC). We therefore investigated the role of the lipoprotein-associated lipids especially S1P in the lipoprotein-induced cytoprotective or cytotoxic actions in human umbilical vein endothelial cells. The viability of the cells gradually decreased in the absence of serum or growth factors in the culture medium. The addition of oxidized LDL (ox-LDL) accelerated the decrease in the cell viability. LPC and 7-ketocholesterol mimicked ox-LDL actions. On the other hand, HDL and LDL almost completely reversed the serum deprivation- or ox-LDL-induced cytotoxicity. Exogenous S1P mimicked cytoprotective actions. Moreover, the S1P-rich fraction and chromatographically purified S1P from HDL exerted cytoprotective actions, but the rest of the fractions did not. The cytoprotective actions of HDL and S1P were associated with extracellular signal-regulated kinase (ERK) activation and were almost completely inhibited by pertussis toxin and PD98059, an ERK kinase inhibitor. The HDL-induced action was specifically desensitized in the S1P-pretreated cells. Taken together, these results indicate that the lipoprotein-associated S1P and the lipid receptor-mediated signal pathways may be responsible for the lipoprotein-induced cytoprotective actions. Furthermore, the decrease in the S1P content, in addition to the accumulation of cytotoxic substances such as LPC, may be important for the acquisition of the cytotoxic property to ox-LDL.

Cells, Cultured↗
PubMed2001

Extracellular mechanism through the Edg family of receptors might be responsible for sphingosine-1-phosphate-induced regulation of DNA synthesis and migration of rat aortic smooth-muscle cells.

Exogenous sphingosine 1-phosphate (S1P) increased cytosolic Ca(2+) concentration, stimulated thymidine incorporation (DNA synthesis) and inhibited cell migration in rat aortic smooth-muscle cells (AoSMCs). Although exogenous sphingosine, a substrate of sphingosine kinase or a precursor of S1P, markedly induced the intracellular accumulation of S1P, the lipid failed to mimic the S1P-induced actions. In contrast, dihydrosphingosine 1-phosphate (DHS1P), an S1P receptor agonist, duplicated these S1P actions even though DHS1P was approx. 20-50-fold less potent than S1P. The pharmacological properties of DHS1P for the S1P receptor subtypes Edg-1, Edg-3, Edg-5 and Edg-6 were compared in Chinese hamster ovary (CHO) cells that were overexpressing the respective receptor. In these S1P-receptor-overexpressing cells, DHS1P was approx. 20-30-fold less potent than S1P for the displacement of [(3)H]S1P binding and inositol phosphate response in Edg-5-expressing CHO cells, as was the case for AoSMCs. However, it was slightly (not more than 3-fold) less potent than S1P in cells expressing Edg-1, Edg-3 or Edg-6. Of the above-mentioned four types of S1P receptor, Edg-5 was abundantly expressed in AoSMCs, as demonstrated by Northern blotting. These results suggest that the intracellular accumulation of S1P is not necessary for the S1P-induced Ca(2+) response, for the stimulation of DNA synthesis or for the inhibition of cell migration. Thus these S1P-induced actions might be mediated through extracellular (or cell-surface) S1P receptors in AoSMCs: Edg-5 might be a most important receptor subtype.

Animals↗
PubMed2000

Interaction of sphingosine 1-phosphate with plasma components, including lipoproteins, regulates the lipid receptor-mediated actions.

The concentration of sphingosine 1-phosphate (S1P) in plasma or serum is much higher than the half-maximal concentration of the sphingolipid needed to stimulate its receptors. Nevertheless, the inositol phosphate response to plasma or serum mediated by Edg-3, one of the S1P receptors, which was overexpressed in Chinese hamster ovary cells, was much smaller than the response expected from the total amount of S1P in these samples. The inositol phosphate response to exogenous S1P was markedly attenuated in the presence of charcoal-treated low-S1P serum. The inhibitory effect was lost by boiling but not by dialysis of the serum. The inhibitory action of the serum was specific to S1P and was associated with the trapping of exogenous S1P; the inositol phosphate response to P(2)-purinergic agonists was somewhat enhanced by the charcoal-treated serum. Among the components of plasma or serum, lipoproteins such as low-density and high-density lipoproteins showed a stronger activity for trapping S1P than lipoprotein-deficient serum. Consistent with this observation, we detected a 15-100-fold higher amount of S1P per unit amount of protein in lipoproteins than in the lipoprotein-deficient serum. Thus even though the protein content of the lipoprotein fraction contributes to only 4% of the total protein content of plasma or serum, more than 60% of S1P is distributed in this fraction. These results suggest that the tight binding of S1P to the components of serum or plasma, including lipoproteins, may interfere with the S1P binding to its receptors and thereby attenuate the lipid-receptor-mediated actions in the cells.

Animals↗
PubMed2000

Sphingosine 1-phosphate stimulates proliferation and migration of human endothelial cells possibly through the lipid receptors, Edg-1 and Edg-3.

Sphingosine 1-phosphate (S1P) stimulates thymidine incorporation (DNA synthesis), cell growth and cell migration in human aortic endothelial cells (HAECs). The extent of the S1P-induced responses are comparable to those stimulated by vascular endothelial growth factor, one of the most potent stimulators of angiogenesis. These responses to S1P were mimicked by dihydrosphingosine 1-phosphate, an S1P receptor agonist, and inhibited by pertussis toxin (PTX), an inactivator of G(i)/G(o)-proteins. S1P also induced activation of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (p38 MAP kinase). The activation of these enzymes was inhibited again by PTX and also by suramin, a non-selective receptor antagonist. S1P-induced DNA synthesis and ERK activation were inhibited by PD98059, an ERK kinase inhibitor, but not by SB203580, a p38 MAP kinase inhibitor. In contrast, cell migration and p38 MAP kinase activation, in response to S1P, were inhibited by SB203580 but not by PD98059. In HAECs, high-affinity S1P binding activity and expression of Edg-1 and Edg-3 mRNA were detected. These results suggest that S1P might be a novel angiogenesis factor and that the lipid-induced proliferation and migration of endothelial cells are possibly mediated through cell-surface S1P receptors, Edg-1 and Edg-3, which are linked to signalling pathways.

Antineoplastic Agents↗
PubMed2000

Circulating interleukin-6 significantly correlates to thyroid hormone in acute myocardial infarction but not in chronic heart failure.

To investigate relationships between thyroid states and the cardiac endocrine system, we analyzed thyrotropin (TSH), thyroid hormone, plasma levels of interleukin-6 (IL-6) and brain natriuretic peptide (BNP) in 50 patients with chronic heart failure (CHF), in 30 patients with heart failure from acute myocardial infarction (AMI), and in 15 controls. Plasma levels of IL-6 and BNP in both CHF and AMI were significantly elevated, while free triiodothyronine (FT3) was significantly decreased compared to controls. FT3/free thyroxine (FT4) ratio was significantly decreased in CHF but not in AMI compared to controls. In CHF, diuretic treatment diminished circulating BNP but not IL-6, while diuretic treatment increased FT3/FT4 ratio. In AMI, FT3/FT4 ratio was significantly decreased 72 h compared to 12 h after the onset of AMI, while BNP and IL-6 were significantly increased 72 h compared to 12 h after the onset of AMI. In both CHF and AMI, BNP significantly correlated with FT4. On the other hand, significant correlations between IL-6 and FT3, and between IL-6 and FT3/FT4 ratio were detected in AMI but not in CHF. This preliminary study suggests that IL-6, BNP and thyroid hormone reflect ventricular dysfunction in both acute and chronic heart failure, and that IL-6 significantly relates to circulating thyroid hormone in AMI but not in CHF.

Aged↗
PubMed2000

Sphingosine 1-phosphate stimulates insulin secretion in HIT-T 15 cells and mouse islets.

Sphingosine is involved in the regulation of cellular processes as a second messenger in various kinds of cells. Since the possible involvement of sphingosine has not been investigated in pancreatic beta-cells, we determined the expression of putative sphingosine 1-phosphate (S1P) receptors and the effect of sphingosine on pancreatic beta-cell function using a clonal Hamster beta-cell line, HIT-T 15 cells and isolated mouse islets. We showed the expression of putative S1P receptors, Edg-3 and AGR16/H218 in HIT-T 15 cells. Ten and 20 microM S1P significantly stimulated insulin secretion for 10 minutes in HIT-T 15 cells. Ten microM S1P significantly increased insulin secretion from isolated mouse islets. Ten microM S1P obviously increased intracellular Ca2+ concentration ([Ca2+]i). Fifty nM nifedipine did not affect the S1P stimulation of insulin secretion in HIT-T 15 cells. Two microM U73122 (phospholipase C inhibitor) completely deleted 10 microM S1P-induced stimulation of insulin secretion for 10 minutes, but U73343 (an inactive analogue of U73122) did not. S1P dose-dependently inhibited intracellular cyclic AMP levels. Pretreatment with 100 ng/ml pertussis toxin (PTX) partially, but significantly attenuated an increase of insulin secretion by 10 microM S1P. These data suggested that PTX-sensitive G-protein-dependent pathway may, at least in part, be involved in an increase of non-glucose stimulated insulin secretion by S1P through the activation of phospholipase C-Ca2+ system.

3T3 Cells↗
PubMed2000

Involvement of circulating interleukin-6 and its receptor in the development of euthyroid sick syndrome in patients with acute myocardial infarction.

OBJECTIVE: In patients with acute myocardial infarction (AMI), low triiodothyronine (T(3)) levels with normal or subnormal levels of thyrotropin (TSH), the euthyroid sick syndrome (ESS), have been reported, however, the mechanism of altered thyroid hormone metabolism is unknown. Recent reports have shown that interleukin-6 (IL-6) plays a key role in the pathogenesis of AMI and ESS. This preliminary study investigates the relationship between thyroid states and plasma levels of IL-6, the soluble IL-6 receptor (sIL-6R), and the soluble transducing 130kDa glycoprotein (sgp130) in AMI. DESIGN AND METHODS: We measured the concentration of TSH, free T(3) (FT(3)), free thyroxine (FT(4)), IL-6, sIL-6R and sgp130 in plasma from 24 patients with AMI and 20 normal controls. RESULTS: All 24 AMI patients showed significantly lower concentrations of FT(3) with normal or subnormal levels of TSH, and higher concentrations of IL-6 and sIL-6R than controls. IL-6 level was correlated with creatine phosphokinase (CPK) and FT(3) levels but not with FT(4 )or TSH levels in patients with AMI. The time course of IL-6 and FT(3 )concentration seemed to be closely linked. sIL-6R level was correlated with CPK and sgp130 levels, but not with FT(3), FT(4) or TSH levels. FT(4 )level was correlated with sgp130 level. CONCLUSION: Patients with AMI develop ESS through activation of IL-6 and its receptor system.

Aged↗
PubMed2000

Contemplation of age-adjusted standard values of lipid profiles in Japan.

In order to establish the age-adjusted standard values of lipids in both sexes in Japan, we examined the plasma levels of total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglyceride levels in 1262 healthy Japanese subjects (male 616, female 646). LDL-cholesterol levels in women increased significantly in relation to menopause as it rises from 112 mg/dL in 40 year olds to 131.2 mg/dL in 50 year olds. Menopause seems to affect the triglyceride levels as well. These age- and sex-dependent changes should be considered in evaluation of patients' lipid profiles.

Adult↗
PubMed1999

Comparison of intrinsic activities of the putative sphingosine 1-phosphate receptor subtypes to regulate several signaling pathways in their cDNA-transfected Chinese hamster ovary cells.

We examined the actions of sphingosine 1-phosphate (S1P) on signaling pathways in Chinese hamster ovary cells transfected with putative S1P receptor subtypes, i.e. Edg-1, AGR16/H218 (Edg-5), and Edg-3. Among these receptor-transfected cells, there was no significant difference in the expressing numbers of the S1P receptors and their affinities to S1P, which were estimated by [(3)H]S1P binding to the cells. In vector-transfected cells, S1P slightly increased cytosolic Ca(2+) concentration ([Ca(2+)](i)) in association with inositol phosphate production, reflecting phospholipase C activation; the S1P-induced actions were markedly enhanced in the Edg-3-transfected cells and moderately so in the AGR16-transfected cells. In comparison with vector-transfected cells, the S1P-induced [Ca(2+)](i) increase was also slightly enhanced in the Edg-1-transfected cells. In all cases, the inositol phosphate and Ca(2+) responses to S1P were partially inhibited by pertussis toxin (PTX). S1P also significantly increased cAMP content in a PTX-insensitive manner in all the transfected cells; the rank order of their intrinsic activity of S1P receptor subtypes was AGR16 > Edg-3 > Edg-1. In the presence of forskolin, however, S1P significantly inhibited cAMP accumulation at a lower concentration (1-100 nM) of S1P in a manner sensitive to PTX in the Edg-1-transfected cells but not in either the Edg-3 or AGR16-transfected cells. As for cell migration activity evaluated by cell number across the filter of blind Boyden chamber, Edg-1 and Edg-3 were equally potent, but AGR16 was ineffective. Thus, S1P receptors may couple to both PTX-sensitive and -insensitive G-proteins, resulting in the selective regulation of the phospholipase C-Ca(2+) system, adenylyl cyclase-cAMP system, and cell migration activity, according to the receptor subtype.

Adenylate Cyclase Toxin↗
PubMed1999

Activation of phospholipase C-Ca2+ system by sphingosine 1-phosphate in CHO cells transfected with Edg-3, a putative lipid receptor.

Sphingosine 1-phosphate (S1P) induces phospholipase C (PLC) activation and Ca2+ mobilization in many types of cells. We examined the possible involvement of Edg-3, one of the putative S1P receptors, in the phospholipase C (PLC)-Ca2+ system. S1P increased the cytoplasmic free Ca2+ concentration without detectable inositol phosphate production in vector-transfected CHO cells. In the Edg-3-transfected cells, however, the S1P-induced Ca2+ response was clearly enhanced, which was associated with a significant production of inositol phosphate. These S1P-induced responses in the Edg-3-transfected cells were inhibited by U73122, a potent PLC inhibitor. We conclude that Edg-3 may be one of the S1P receptors participating in the activation of the PLC-Ca2+ system.

Animals↗
PubMed1999

Contingent negative variation in children with anorexia nervosa.

BACKGROUND: Central catecholamines, particularly dopaminergic and noradrenergic systems, have affected the appetitive behavior in patients with anorexia nervosa (AN). The purpose of this study is to distinguish the characteristics of contingent negative variation (CNV) and postimperative negative variation (PINV), which may reflect the level of catecholamine in children with AN. METHODS: Eight children with AN aged 10 to 15 years and 23 age-matched healthy children were recruited. Contingent negative variation was recorded from the frontal midline (Fz), central midline (Cz) and parietal midline (Pz) referenced to linked earlobes during 30 trials consisting of a warning stimulus and an imperative stimulus with an interstimulus interval of 2 s and an intertrial interval of 10 s. The imperative stimulus of each trial required a button press. RESULTS: Children with AN had a diminished amplitude of the CNV. They had a significantly more attenuated early CNV and late CNV amplitude at Cz than normal children. No significant differences were observed between AN children and normal children in the amplitude of PINV at all three electrode sites. No difference could be found between the two groups in the frequencies of normal and abnormal duration of PINV. CONCLUSION: These findings suggest that early CNV may be diminished by norepinephrine deficiency and late CNV may be attenuated by dopaminergic deficiency in children with AN. Reduced CNV may represent impaired cognitive processes which reflect impaired appetitive behavior in AN children.

Adolescent↗
PubMed1999

[Microsomal antibody].

Microsomal antibody is an antibody for the section of a microsome in thyroid cells. There are two methods of measurements of microsomal antibodies, the semiquantitative microtiter particle agglutination test(MCHA) and the high sensitive assay(RIA, ELISA) for the anti thyroid peroxidase(TPO-Ab). MCHA is broadly useful for the diagnosis of autoimmune thyroid diseases and TPO-Ab is mainly measured in the occult autoimmune thyroiditis. TPO-Ab is expensive to compare with MCHA, in Japan. We recommend that MCHA is used in the routine test and TPO-Ab should be measured in the cases of patients with thyroid goiter and MCHA negative.

Autoantibodies↗
PubMed1998

Stimulatory and inhibitory actions of lysophosphatidylcholine, depending on its fatty acid residue, on the phospholipase C/Ca2+ system in HL-60 leukaemia cells.

We examined the mechanism of action of lysophosphatidylcholine (LPC), which is suggested to be involved in the pathogenesis of atherosclerosis and inflammatory disorders, in HL-60 leukaemia cells. Extracellular 1-palmitoyl LPC increased the intracellular Ca2+ concentration in association with production of inositol phosphate. These actions of LPC were markedly inhibited by treatment of the cells with pertussis toxin and U73122, a phospholipase C inhibitor. The lipid-induced stimulation of the phospholipase C/Ca2+ system was also attenuated in the dibutyryl cAMP-induced differentiated (neutrophil-like) cells, in which phospholipase C activation induced by NaF or formyl-Met-Leu-Phe was enhanced. In contrast with the stimulatory action of 1-palmitoyl LPC, 1-stearoyl LPC was inhibitory for the phospholipase C/Ca2+ system stimulated by NaF as well as by 1-palmitoyl LPC or other Ca2+-mobilizing agonists. In a cell-free system, only an inhibitory effect on phospholipase C activity was observed even by 1-palmitoyl LPC; 1-stearoyl LPC was more inhibitive than 1-palmitoyl LPC. Taken together, these results suggest that atherogenic and inflammatory LPC exerts both stimulatory and inhibitory actions on the phospholipase C/Ca2+ system depending on the species of fatty acid residue of the lipid; the stimulatory effect is possibly mediated through G-protein-coupled receptors; the inhibitory effect might be caused by dysfunction of the components involved in the enzyme system owing to the amphiphilic nature of the lipid. 1-Palmitoyl LPC prefers the former receptor stimulation at least in intact cells, but 1-stearoyl LPC preferentially exerts the latter inhibitory action.

Bucladesine↗