PubMed Health⌕ Search

Biomedical subjects

Y Ouchi

Publications and source records attributed to Y Ouchi.

At least 19 recordsLinked to original sources
PubMed2001

A novel mouse beta-defensin, mBD-6, predominantly expressed in skeletal muscle.

Defensins comprise a family of cationic antimicrobial peptides that is characterized by the conserved 6 cysteine residues. They are expressed in the epithelial cells of various organs and are identified as key elements in the host defense system at the mucosal surface. We isolated a novel mouse beta-defensin gene from the bacterial artificial chromosome DNA containing the mouse beta-defensin-3 gene. The full-length cDNA was cloned from skeletal muscle cDNA and called mouse beta-defensin-6 (mBD-6). The predicted peptide conserved the 6-cysteine motif and had 59% amino acid sequence identity with mouse beta-defensin-3 and 59% identity with mouse beta-defensin-4. We demonstrated the expression of mBD-6 in skeletal muscle in addition to the esophagus, tongue, and trachea. In animal models of endotoxemia, mBD-6 expression was also induced in the lung. mBD-6 showed potent antimicrobial activity against Escherichia coli and would play an important role in host defense in the esophagus, airways, and skeletal muscle. mBD-6 is the first reported beta-defensin predominantly expressed in skeletal muscle. This unique tissue specificity suggests some novel physiological roles of this peptide family.

Amino Acid Sequence↗
PubMed2001

Establishment of L-3,4-Dihydroxyphenilalaninde-induced pharmacological dementia model mouse.

L-3,4-Dihydroxyphenilalaninde (L-DOPA), through its decarboxylation to dopamine, has been used as the most effective therapy for treatment of Parkinson's disease (PD). Despite almost 30 years of clinical experience, doubts remain as to whether L-DOPA has an adverse effect of causing neuronal injury. We therefore examined the effects of L-DOPA on the learning ability of mice in a step-through passive avoidance task. Orally administrated L-DOPA (10-1000 mg/kg) induced irrecoverable cognitive impairment in C57BL/6N mice. The effect of L-DOPA had dose and time dependency. In contrast, D-3,4-Dihydroxyphenilalaninde, which does not pass through the blood-brain barrier, had no effect. These experiments suggest that L-DOPA immediately affected the brain and caused memory deficit. The findings indicate that L-DOPA-treated mice are able to act as a new model for human dementia.

Administration, Oral↗
PubMed2001

Increased anaerobic glycolysis in mitochondrial trifunctional protein-deficient brain.

Deficiency of mitochondrial trifunctional protein (TP), beta-oxidation enzyme, is characterized by recurrent rhabdomyolysis in adult patients. Positron emission tomography was used to measure brain oxygen (CMRO(2)) and glucose (CMRGlc) metabolisms in an adult patient with TP deficiency who had a homozygous G1331A transition of the beta-subunit gene. The molar ratio of oxygen to glucose consumption showed diffuse reduction; CMRO(2) was markedly decreased, whereas CMRGlc increased. Oxidative metabolism may be impaired and anaerobic glycolysis stimulated in the brain of this patient with TP deficiency.

Adult↗
PubMed2001

Estrogen prevents oxidative stress-induced endothelial cell apoptosis in rats.

BACKGROUND: Estrogen replacement attenuates the increased risk of cardiovascular disease in postmenopausal women. Recent studies using an in vitro culture system have shown that estrogen inhibits endothelial cell (EC) apoptosis. The in vivo relevance of this finding, however, is not defined. To do so, we have developed a rat vascular injury model in which EC apoptosis induced by hydrogen peroxide plays a role. METHODS AND RESULTS: Intracarotid arterial administration of 0.01 mmol/L hydrogen peroxide for 5 minutes evoked EC apoptosis after 6 to 24 hours, determined by nuclear staining with Hoechst 33342, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling, and electron microscopy. Apoptosis was associated with EC loss and was followed by EC regeneration at 72 hours and neointima formation at 1 to 2 weeks. Estradiol replacement in ovariectomized female Wistar rats decreased the rate of apoptotic ECs by approximately 50%, assayed by nuclear morphology of en face specimens, resulting in increased remaining ECs and decreased neointima formation. Progesterone did not influence the effects of estradiol on EC apoptosis. CONCLUSIONS: These results provide new insight into the cardioprotective action of estrogen as well as a paradigm of the response-to-injury hypothesis.

Animals↗
PubMed2001

Japanese fermented soybean food as the major determinant of the large geographic difference in circulating levels of vitamin K2: possible implications for hip-fracture risk.

Increasing evidence indicates a significant role for vitamin K in bone metabolism and osteoporosis. In this study, we found a large geographic difference in serum vitamin K2 (menaquinone-7; MK-7) levels in postmenopausal women. Serum MK-7 concentrations were 5.26 +/- 6.13 ng/mL (mean +/- SD) in Japanese women in Tokyo, 1.22 +/- 1.85 in Japanese women in Hiroshima, and 0.37 +/- 0.20 in British women. We investigated the effect of Japanese fermented soybean food, natto, on serum vitamin K levels. Natto contains a large amount of MK-7 and is eaten frequently in eastern (Tokyo) but seldom in western (Hiroshima) Japan. Serum concentrations of MK-7 were significantly higher in frequent natto eaters, and natto intake resulted in a marked, sustained increase in serum MK-7 concentration. We analyzed the relation between the regional difference in natto intake and fracture incidence. A statistically significant inverse correlation was found between incidence of hip fractures in women and natto consumption in each prefecture throughout Japan. These findings indicate that the large geographic difference in MK-7 levels may be ascribed, at least in part, to natto intake and suggest the possibility that higher MK-7 level resulting from natto consumption may contribute to the relatively lower fracture risk in Japanese women.

Aged↗
PubMed2001

Changes in dopamine availability in the nigrostriatal and mesocortical dopaminergic systems by gait in Parkinson's disease.

The basal ganglia play a role in controlling movement during gait. The aim of the present study was to investigate changes in dopamine transporter (DAT) availability in the striatum and extrastriatal region in association with walking exercise in six normal subjects and seven age-matched unmedicated patients with Parkinson's disease. This was done by comparing DAT radioligand uptake in the dopaminergic projection areas after gait with that under the resting condition using a DAT probe, 11C-labelled 2-beta-carbomethoxy-3beta-(4-fluorophenyl) tropane ([11C]CFT) and PET. Physiological parameters were stable during and after gait in both groups. The regions of interest method for measuring differences in [11C]CFT uptake level and voxel-based statistical parametric mapping (SPM96) showed that [11C]CFT uptake in the striatum (specifically the putamen) was decreased by gait to a greater extent in normal subjects, whereas a significant reduction in [11C]CFT uptake was not found in the putamen but in the caudate and orbitofrontal cortex in Parkinson's disease patients. These results are the first in vivo evidence that DAT availability is reduced in the nigrostriatal projection area by basic human behaviour, i.e. gait. Alterations in this availability in Parkinson's disease suggested that shifted activation in the medial striatum and the mesocortical dopaminergic system might reflect the pathophysiology of parkinsonian gait.

Aged↗
PubMed2001

Postural effects on brain hemodynamics in unilateral cerebral artery occlusive disease: a positron emission tomography study.

To investigate effect of assuming of upright posture on brain hemodynamics in patients with unilateral internal carotid or middle cerebral artery occlusion (MCAO), local tissue oxygen extraction fraction (OEF), and postural changes in regional cerebral blood flow (rCBF) during supine and sitting conditions were examined using positron emission tomography (PET) with (15)O-gas steady-state method and H(2)(15)O autoradiographic method. A total of 22 minor stroke patients at relatively early stages participated. The regions of interest method was used for analyzing levels of perfusion and oxygen metabolic parameters, and postural rCBF change within MCAO group was investigated using statistical parametric mapping. Region of interest analyses showed significant rCBF reduction in the cortical and subcortical regions distal to the artery occlusion in CAO patients during sitting. Regression analyses showed that magnitudes of rCBF reduction in those areas were correlated positively with OEF values and inversely with metabolic rates of oxygen (P < 0.05). Statistical parametric mapping for MCAO patients demonstrated further rCBF reduction by sitting in the occlusion-side MCA territory. The current study suggested that assumption of upright posture could exert an adverse effect on local perfusion in hemodynamically compromised patients with major cerebral vessel occlusion, possibly caused by impairment of local autoregulation.

Adult↗
PubMed2001

Tobacco smoke reduces viability in human lung fibroblasts: protective effect of glutathione S-transferase P1.

Cigarette smoking is thought to be a major risk factor in various lung diseases including lung cancer and emphysema. However, the direct effect of cigarette smoke on the viability of lung-derived cells has not been fully elucidated. In this study, we investigated the viability of human lung fibroblast-derived (HFL1) cells to different concentrations of cigarette smoke extract (CSE). CSE induced apoptosis at lower concentrations (10-25%) and necrosis at higher concentrations (50-100%). We also examined the effects of glutathione S-transferase P1 (GSTP1), one of the xenobiotic metabolizing and antioxidant enzymes in the lung, against the cytotoxicity of CSE. Our results indicated that the level of HFL1 cell death was decreased by transfection with a GSTP1 expression vector and was increased by GSTP1 antisense vector transfection. Therefore, transient overexpression and underexpression of GSTP1 appeared to inhibit and enhance the cytotoxic effects of CSE on HFL1 cells, suggesting that GSTP1 may have protective effects against cigarette smoke in the airway cells.

Apoptosis↗
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

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

[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

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↗