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Y Ouchi

Publications and source records attributed to Y Ouchi.

At least 37 records · Page 2Linked to original sources
PubMed2001

Induction of nuclear orphan receptor NGFI-B gene and apoptosis in rat vascular smooth muscle cells treated with pyrrolidinedithiocarbamate.

NGFI-B is one of the orphan nuclear receptors, and its gene is implicated in the apoptosis of T cells. The aim of this study was to investigate the expression and the role of NGFI-B in vascular smooth muscle cells (VSMCs). Pyrrolidinedithiocarbamate (PDTC) is a modulator of an oxidative state and is reported to induce apoptosis only when the density of VSMCs is low. Under low VSMC density (10 000 cells/cm(2)), addition of PDTC (0.1 to 10 micromol/L) caused apoptosis of VSMCs, which was confirmed by Hoechst 33258 staining under fluorescence microscopy. At low VSMC density, expression of NGFI-B mRNA was induced 1 hour after the addition of PDTC, peaking at 6 hours, and persisted for up to 12 hours. The protein level of NGFI-B was increased 4 hours after PDTC addition and persisted for up to 12 hours. Under low VSMC density, PDTC-induced expression of NGFI-B mRNA was correlated with the magnitude of apoptosis, which was quantified by enzyme immunoassay for histone-associated DNA fragments. In contrast, when the density of VSMCs was high (50 000 cells/cm(2)), PDTC did not induce apoptosis, and the expression of NGFI-B was only transient. This transient expression pattern was also seen when VSMCs were treated with phorbol ester, calcium ionophore, hydrogen peroxide, or angiotensin II, even at low cell density. We next investigated whether the NGFI-B gene may act as a transcription factor under treatment with PDTC by measuring the promoter activity of luciferase reporter plasmids that contained typical NGFI-B-responsive elements. The PDTC-induced transcriptional activity of NGFI-B was 2-fold higher at low cell density than at high cell density. These data demonstrate that NGFI-B can be induced in VSMCs and suggest that NGFI-B may play a role in PDTC-induced VSMC apoptosis.

Animals↗
PubMed2001

Acute and chronic smooth muscle cell apoptosis after mechanical vascular injury can occur independently of the Fas-death pathway.

Vascular smooth muscle cell (VSMC) apoptosis has been demonstrated in vascular lesions, such as atherosclerotic and postangioplasty restenotic lesions. Balloon injury also induces VSMC apoptosis. Fas is a death factor that mediates apoptosis when it is activated by its ligand, FasL. Fas-mediated apoptosis was found to be implicated in the pathogenesis of vascular diseases in which Fas/FasL expression was detected. We investigated whether the Fas/FasL interaction mediated acute and chronic VSMC apoptosis and lesion formation in a vascular injury model that may resemble balloon angioplasty. A large spring wire was inserted into the femoral artery of C3H/HeJ (wild-type), C3H-gld (Fas ligand-/-), and C3H-lpr (Fas-/-) mice. The wire was left in place for 1 minute to denude and expand the artery. Massive apoptosis was observed in medial VSMCs from 1 to 7 hours later. There was no difference in the number of apoptotic cells among the 3 groups of mice 4 hours after injury. At 4 weeks, the injured arteries presented signs of concentric neointimal hyperplasia composed exclusively of VSMCs. There was no difference in the degree of neointima hyperplasia (intima/media ratios were as follows: wild type 1.4+/-0.3, gld 1.0+/-0.2, and lpr 1.3+/-0.2) or in the number of apoptotic nuclei among the 3 groups. These findings suggest the existence of other signaling pathways for acute and chronic VSMC apoptosis, at least that induced by mechanical vascular injury.

Angioplasty, Balloon↗
PubMed2001

Methamphetamine-related psychiatric symptoms and reduced brain dopamine transporters studied with PET.

OBJECTIVE: A positron emission tomography (PET) study has suggested that dopamine transporter density of the caudate/putamen is reduced in methamphetamine users. The authors measured nucleus accumbens and prefrontal cortex density, in addition to caudate/putamen density, in methamphetamine users and assessed the relation of these measures to the subjects' clinical characteristics. METHOD: PET and 2-beta-carbomethoxy-3beta-(4-[(11)C] fluorophenyl)tropane, a dopamine transporter ligand, were used to measure dopamine transporter density in 11 male methamphetamine users and nine male comparison subjects who did not use methamphetamine. Psychiatric symptoms in methamphetamine users were evaluated by using the Brief Psychiatric Rating Scale and applying a craving score. RESULTS: The dopamine transporter density in all three of the regions observed was significantly lower in the methamphetamine users than the comparison subjects. The severity of psychiatric symptoms was significantly correlated with the duration of methamphetamine use. The dopamine transporter reduction in the caudate/putamen and nucleus accumbens was significantly associated with the duration of methamphetamine use and closely related to the severity of persistent psychiatric symptoms. CONCLUSIONS: These findings suggest that longer use of methamphetamine may cause more severe psychiatric symptoms and greater reduction of dopamine transporter density in the brain. They also show that the dopamine transporter reduction may be long-lasting, even if methamphetamine use ceases. Further, persistent psychiatric symptoms in methamphetamine users, including psychotic symptoms, may be attributable to the reduction of dopamine transporter density.

Adult↗
PubMed2001

Association of Gc-globulin variation with susceptibility to COPD and diffuse panbronchiolitis.

Chronic obstructive pulmonary disease (COPD) and diffuse panbronchiolitis (DPB) are both characterized by chronic airflow limitation. Although the aetiology of these diseases is under investigation, it is commonly hypothesized that neutrophils have a major role in the disease pathogenesis. The variation of the genes related to chemotaxis of neutrophils may confer a risk for the development of both COPD and DPB. In the present report, the authors investigated the association between genetic variation that codes for the 416th and 420th amino acid of Gc-globulin, reported to be associated with chemotaxis of neutrophils, and susceptibility to COPD and DPB. Blood samples obtained from patients with COPD (n=63), DPB (n=82), and-control subjects (n=82) were used for the genotyping assay. The proportion of GC*1F homozygotes was significantly higher in the COPD patients than the control subjects (COPD 36.5% versus control 20.7%), and the odds ratio for GC*IF homozygotes was 2.2 (95%, confidence interval 1.1-4.6) for the COPD group. There was no difference on the distribution of the other genotypes (GC*1F-1S heterozygotes, GC*1S homozvgotes, GC*2-1F heterozygotes, GC*2-1S heterozygotes and GC*2 homozygotes) or the allele frequencies among these groups. These findings suggest that the GC*IF gene polymorphism of Gc-globulin may be one of the risk factors for chronic obstructive pulmonary disease. However, no association between this polymorphism of Gc-globulin and susceptibility to diffuse panbronchiolitis was found.

Aged↗
PubMed2001

Circadian variation of autonomic nervous activity in patients with multivessel coronary spasm.

The present study investigated whether the circadian rhythm of sympathovagal activity is related to the severity of coronary spasm or multivessel coronary spasm. Heart rate variability was examined in 22 consecutive patients with vasospastic angina provoked by intracoronary injection of acetylcholine, who had either multivessel spasm (Group M, n=11 ) or single vessel spasm (Group S, n= 11), in 20 subjects without coronary artery disease (Group C) and 20 patients with effort angina who had organic coronary artery stenosis (Group E). The frequency domain indices were analyzed, including low frequency (LF: 0.04-0.15 Hz) and high frequency (HF: 0.15-0.4Hz), the latter being an index of efferent parasympathetic activity, and the ratio (L/H) as an index of sympathovagal balance. The circadian variation of the parameters was analyzed by its pattern and was quantified by the difference of the mean values between daytime and nighttime. Although the HF power increased during nighttime in Groups C and S, this increase was attenuated in Groups E and M. The circadian variation of the L/H ratio (ie, a drop during nighttime) was smaller in the S and M groups than in Groups C and E. Accordingly, in Group M, the circadian variation of both sympathetic and parasympathetic nervous activity was attenuated, but in Group S, the variation of sympathetic nervous activity, but not parasympathetic nervous activity, was decreased. These data suggest that relatively enhanced sympathetic nervous activity at night may be involved in the mechanism underlying multivessel coronary spasm.

Acetylcholine↗
PubMed2001

Reversible left ventricular systolic dysfunction--reversibility of coronary microvascular abnormality.

Reversible left ventricular wall motion abnormalities mimicking myocardial infarction have been reported in patients with a noncardiac illness. Their coronary angiograms do not demonstrate organic stenosis or epicardial coronary vasospasm. In this article, two cases of reversible left ventricular contraction abnormality are presented. Electrocardiography showed deep inverted T waves in precordial leads, and the echocardiography revealed diffuse akinesis of the apical region in the acute phase. Coronary angiography showed no significant stenosis or occlusion in either patient. Thallium scintigraphy showed no defect, while the metaiodobenzylguanidine scintigraphy demonstrated significant defects in the apex. The relative coronary flow reserve ratio, measured with an intracoronary Doppler flow wire, was significantly reduced in both patients. Myocardial contrast echocardiography revealed a reversible perfusion defect in the apex in the acute phase in case 2. Transiently impaired coronary microcirculation was thought to be involved in the pathogenesis of the reversible left ventricular dysfunction observed in these patients.

Aged↗
PubMed2001

[A case of gliomatosis cerebri in an elderly woman].

Gliomatosis cerebri is a rare form of glioma, which diffusely extends to both cerebral hemispheres. Because it sometimes fails to show severe neurological symptoms in spite of diffuse invasion, the antemortem diagnosis is difficult. We report a case of a 77-year-old woman, who was admitted with progressive left hemiparesis and dysarthralgia. Plain CT scan of the brain showed almost no abnormal findings. MRI T2-weighted image revealed widespread and nearly symmetrical extension of a high intensity area from the corpus callosum to the deep white matter of both cerebral hemispheres. Open biopsy of the brain showed glioblastoma multiforme, which finally confirmed the clinical diagnosis of gliomatosis cerebri. We also review the classic and recent literatures.

Aged↗
PubMed2001

A comparison of low versus standard dose pravastatin therapy for the prevention of cardiovascular events in the elderly: the pravastatin anti-atherosclerosis trial in the elderly (PATE).

Treatment with low drug doses is generally recommended in the elderly. However, the efficacy of low dose 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor treatment in elderly hypercholesterolemic patients has never been examined. Therefore, we compared the effect of low-dose with standard dose pravastatin, an HMG CoA reductase inhibitor, on the incidence of cardiovascular events (CVEs) in elderly patients with hypercholesterolemia in a randomized prospective trial. Subjects aged > or = 60 years (73 +/- 6 years) with serum total cholesterol (TC) levels of 220-280 mg/dL were randomized to the low-dose (groupL, 5 mg/day; n=334) or standard dose (groupS, 10-20mg/day; n= 331). Baseline TC levels were similar in the 2 groups (253 +/-15 mg/dL). Patients were followed for 3-5 years (mean 3.9 years). TC levels decreased from baseline by 11-13% in group L and by 15-17% in groupS. TC levels at 1 year in S and L group were 209 +/- 2 mg/ dL (16 +/- 1% decrease) and 221+/- 2 mg/dL (12 +/- 1% decrease), respectively. Forty two and 29 CVEs occurred in group L and S, respectively. The incidence of CVEs was significantly lower in group S than in group L (P = 0.046, generalized Wilcoxon test; P = 0.096, log-rank test). The risk ratio for group S compared with group L was 0.674 (95% confidence interval: 0.423-1.074). Subgroup analyses suggested that the difference in the incidence of CVEs between the 2 groups was more clear in subjects without diabetes mellitus, with TC levels of < 253 mg/dL, and with TG levels of > or = 133 mg/dL. The incidence of CVEs in group S was significantly lower than that in group L in subjects without both diabetes mellitus and previous cardiovascular disease (P = 0.026, generalized Wilcoxon test; P = 0.032, log rank test). These findings suggest that standard-dose pravastatin (10-20 mg/day) is more effective in reducing the incidence of CVEs in the elderly than low dose pravastatin (5 mg/ day), especially in nondiabetic elderly patients with mild hypercholesterolemia or previous cardiovascular disease.

Aged↗
PubMed2001

Absolute changes in regional cerebral blood flow in association with upright posture in humans: an orthostatic PET study.

UNLABELLED: To determine whether hemodynamic parameters are changed by upright posture in healthy middle-aged humans, absolute values of regional cerebral blood flow (rCBF) were investigated for three different orthostatic conditions. METHODS: PET with [15O]H2O and arterial blood sampling were performed on eight middle-aged healthy volunteers while they were sitting passively or standing actively. Absolute rCBF values estimated by the autoradiographic method in regions of interest were compared using ANOVA, and relative changes in rCBF were also analyzed voxel by voxel using statistical parametric mapping (SPM). RESULTS: Physiologic data remained unchanged for different conditions. ANOVA and SPM showed that absolute and relative rCBF levels were significantly elevated in the cerebellar vermis in the standing position compared with those in the supine and sitting positions. In contrast, ANOVA showed that rCBF in the frontal and parietal cortices tended to be lower in the sitting and standing positions than in the supine position. Regression analysis showed that the frontal rCBF measured during standing tended to be inversely correlated with age. CONCLUSION: The results showed that cerebellar vermis activation was more marked in the standing position than in the sitting or supine positions, indicating that the vermis is a neural substrate for controlling voluntary upright posture. Brain perfusion in the distal internal carotid artery region may be subject to orthostatic postural changes in healthy middle-aged humans.

Aging↗
PubMed2001

[Genetic variation of NADPH/NADH oxidase and susceptibility to diffuse panbronchiolitis (DPB) and chronic obstructive pulmonary disease (COPD)].

Diffuse panbronchiolitis (DPB) and chronic obstructive pulmonary disease (COPD) are both characterized by chronic airflow obstruction of unknown etiology. It is hypothesized that neutrophils play the major role in the pathogenesis of these diseases. Recent studies have suggested that genetic factors may be related to individual susceptibility to these diseases. We have investigated the association between the C 242 T polymorphism of p 22 phox, a critical subunit of superoxide-generating NADH/NADPH oxidase, and susceptibility to DPB and COPD. Blood samples obtained from both patients with DPB (n = 82), COPD (n = 53), and control subjects (n = 82) were used for this genotyping assay; and the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were performed to genotype the gene. The frequency of the C allele was 0.91, 0.92, 0.92 in the DPB, COPD, and control groups, respectively. There were no differences in the distribution of the genotype of p 22 phox among these groups, either. We concluded that there is no association between the C 242 T polymorphism of p 22 phox, and susceptibility to DPB and COPD.

Bronchiolitis↗
PubMed2001

Foam cell formation containing lipid droplets enriched with free cholesterol by hyperlipidemic serum.

A monoclonal antibody, ASH1a/256C (256C), which binds to atherosclerotic lesions in Watanabe heritable hyperlipidemic rabbit (WHHL) aorta in vivo, recognizes complex structures of phosphatidylcholine mixed with neutral lipids. In the present study, a cell culture system is described in which foam cells express 256C-positive lipid droplets. J774.1 macrophages were incubated in the presence of a small volume of WHHL serum for 24 h to produce foam cells, which were then incubated without the WHHL serum for 3 days. Oil red O-positive lipid droplets appeared on day 1, and were present in the cells during the whole incubation period. The lipid droplets in the cells were positively immunostained with antibody 256C on day 4, although they were negative on day 1. Expression of the antigenic lipid droplets was also induced by the addition of acetylated LDL or sera from patients with hyperlipidemia. When foam cells were induced by the addition of WHHL serum, cellular content of cholesteryl ester was greatly increased but then decreased to near basal levels by day 4. Concomitantly, cellular free cholesterol increased during the culture period, indicating that the cholesteryl ester changes to free cholesterol by day 4. The lipid droplets in the foam cells on day 4 were positively stained with filipin, a fluorescent probe for free cholesterol, as well as with 256C antibody, indicating that free cholesterol is enriched in antigenic lipid droplets. These observations suggest that hydrolysis and rearrangement of cellular cholesterol take place in foam cells to form complex structures of phosphatidylcholine and free cholesterol in lipid droplets.

Animals↗
PubMed2001

[Discharge planning for home care].

The department of medical social work and discharge planning was established in the University of Tokyo hospital to ensure that patients would receive proper care at a right place. The discharge planning team consists of a physician, a medical social worker and a home care coordinator. The home care coordinator, who coordinates with the home nursing station and the primary care physician, is effective for advance of home care. The role of the home care coordinator is to relieve patients of their anxiety about home care. As a result, the number of home care patients has gradually increased.

Caregivers↗
PubMed2000

An estrogen receptor beta isoform that lacks exon 5 has dominant negative activity on both ERalpha and ERbeta.

An alternatively spliced isoform of human estrogen receptor beta (ERbeta) has been isolated from normal human testis mRNA that is coexpressed with wild-type ERbeta by reverse transcription polymerase chain reaction (RT-PCR). Sequence analysis of the ERbeta isoform PCR product reveals the absence of 139 bp that corresponds to the entire exon 5 of wild-type ERbeta, which predicts to lack part of the hormone-binding domain. The transient expression of the exon 5-deleted isoform of ERbeta (ERbetaDelta5) had no effect on basal transactivation activity of an estrogen-responsive luciferase reporter gene. This finding was in contrast to the previous reports that the exon 5-deleted isoform of ERalpha (ERalphaDelta5) acts as a dominant positive receptor, increasing basal gene transactivation itself. Moreover, when ERbetaDelta5 was cotransfected with the wild-type ERalpha or ERbeta, it behaved as a dominant negative receptor that inhibited not only estradiol-stimulated transactivation by ERbeta but also that by ERalpha. The ligand-independent nuclear localization of ERbetaDelta5 was confirmed by immunohistochemistry, and the coexpression of the isoform and the wild-type receptors could be observed in a single cell that transfected with both receptor cDNAs. These findings indicate that ERbetaDelta5 has a potential as a dominant negative receptor that blocks both ERalpha and ERbeta signaling pathways, suggesting some physiological roles of this isoform as an "ER inhibitor".

Alternative Splicing↗
PubMed2000

Inhibitory effect of angiotensin II type 2 receptor on coronary arterial remodeling after aortic banding in mice.

BACKGROUND: The renin-angiotensin system is thought to be critical for the development of cardiac hypertrophy, whereas the role of the angiotensin II type 2 (AT(2)) receptor in the process is not defined. Using the AT(2) receptor-null (Agtr2-) mouse, we tested the hypothesis that the AT(2) receptor could exert an antigrowth effect in cardiac hypertrophy. METHODS AND RESULTS: Cardiac hypertrophy was induced by suprarenal abdominal aortic banding in 10- to 12-week-old Agtr2- and wild-type (Agtr2+) mice for 6 or 12 weeks. Carotid arterial pressure was not different between the strains, although aortic banding increased arterial pressure by approximately 40 mm Hg. Aortic banding increased the heart-weight/body-weight ratio and the cross-sectional area of cardiomyocytes by 15%, resulting in comparable cardiomyocyte hypertrophy in the 2 strains. In contrast, coronary arterial thickening and perivascular fibrosis, determined by the media/lumen-area ratio and the collagen/vessel-area ratio, respectively, were 50% greater in Agtr2- than in Agtr2+ mice after banding, whereas these parameters were similar in sham-operated mice. Radioligand binding studies using the whole heart and immunohistochemistry showed that AT(2) receptor expression was limited and localized in the coronary artery and perivascular region. CONCLUSIONS: These results suggest that the AT(2) receptor mediates an inhibitory effect on coronary arterial remodeling, such as medial hypertrophy and perivascular fibrosis in response to pressure overload, and an activation of the renin-angiotensin system.

Animals↗