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Y Nishio

Publications and source records attributed to Y Nishio.

At least 19 recordsLinked to original sources
PubMed2006

Increased expression of CCAAT/enhancer binding protein-beta and -delta and monocyte chemoattractant protein-1 genes in aortas from hyperinsulinaemic rats.

AIMS/HYPOTHESIS: We evaluated whether hyperinsulinaemia stimulates the expression of transcription factor CCAAT/enhancer binding protein (C/EBP)-beta and C/EBP-delta and leads to the induction of the chemokine (C-C motif) ligand 2 gene (Ccl2, also known as MCP-1) expression in aortas. METHODS: Hyperinsulinaemia was induced by feeding rats a high-fructose diet. CCL2 production was analysed by ELISA. The expression of Ccl2, Cebpb and Cebpd mRNAs was investigated by quantitative RT-PCR. The binding of C/EBP-beta to Ccl2 was assessed by chromatin immunoprecipitation (ChIP) assay. RESULTS: Insulin at a concentration of 10 nmol/l significantly stimulated the expression of Cebpb, Cebpd and Ccl2 mRNAs, depending on activation of phosphatidylinositol 3-kinase (PI3K) in cultured vascular smooth muscle cells. The knock-down of C/EBP-beta with siRNA abolished the insulin-induced Ccl2 mRNA expression. In the aortas from fructose-fed rats, the levels of phosphorylation of Akt/protein kinase B, a downstream effector of PI3K, were also increased. The expression of Cebpb, Cebpd and Ccl2 mRNAs in the aortas from fructose-fed rats were significantly elevated, by 330, 300 and 300%, respectively, compared with those of control-fed rats. The induction Ccl2 mRNA expression in the aortas was significantly correlated with the expression of Cebpb and Cebpd mRNAs in the aortas. Furthermore, the ChIP assay showed elevated binding of C/EBP-beta to the 5' upstream region of Ccl2 in the aortas from fructose-fed rats. CONCLUSIONS/INTERPRETATION: These findings clearly indicate the role of C/EBPs in the mechanism of upregulation of CCL2, an inflammation-related protein, observed in the hyperinsulinaemic state, which may initiate the process of atherosclerosis.

Animals↗
PubMed2006

Actions anchored by concepts: defective action comprehension in semantic dementia.

OBJECTIVE: To study the ability of patients with semantic dementia to understand actions, in order to examine the contribution of semantic memory to action comprehension. METHODS: The ability to comprehend symbolic and instrumental actions was assessed in 6 patients with semantic dementia and 10 healthy controls. The patients were also given the imitation test of meaningful and meaningless actions. RESULTS: In all patients with semantic dementia, comprehension of both symbolic and instrumental actions was defective. The comprehension of symbolic actions was more impaired than that of instrumental actions. Their ability to imitate other's actions was well preserved. CONCLUSION: This study showed that comprehension of action was impaired in semantic dementia, suggesting that semantic memory has an important role in comprehension of human action.

Aged↗
PubMed2006

Pit patterns in rectal mucosa assessed by magnifying colonoscope are predictive of relapse in patients with quiescent ulcerative colitis.

BACKGROUND: Relapse of ulcerative colitis is difficult to predict by routine colonoscopy. A high-resolution video-magnifying colonoscope with chromoscopy enables the observation of colorectal mucosal pit patterns. AIMS: To investigate the association of pit patterns as assessed by magnifying colonoscopy (MCS) with histological inflammation and mucosal chemokine activity in patients with quiescent ulcerative colitis, and to prospectively analyse the prognostic factors that may predict exacerbations. METHODS: MCS was performed in 113 patients with ulcerative colitis in remission. Pit patterns in the rectal mucosa were classified into four MCS grades on the basis of size, shape and arrangement. Mucosal interleukin (IL) 8 activity was measured in biopsy specimens of rectal mucosa and the specimens were assessed for histological disease activity. The patients were then followed until relapse or for a maximum of 12 months. Multivariate survival analysis was carried out to determine the independent predictors of clinical relapse. RESULTS: A positive correlation was identified between MCS grade, histological grade (p = 0.001) and mucosal IL8 activity (p<0.001). Multivariate proportional hazard model analysis showed that MCS grade was a significant predictor of relapse (relative risk 2.06, p = 0.001). Kaplan-Meier estimate of relapse during 12 months of follow-up was found to increase with increasing MCS grade, with values of 0% for grade 1, 21% for grade 2, 43% for grade 3 and 60% for grade 4. CONCLUSION: MCS grading is associated with the degree of histological inflammation and mucosal IL8 activity in patients with quiescent ulcerative colitis, and may predict the probability of subsequent disease relapse in patients with ulcerative colitis in remission.

Adolescent↗
PubMed2005

MPO-ANCA-associated pseudovasculitis in cardiac myxoma.

We describe a case of cardiac myxoma whose clinical presentation mimicked that of polyarteritis nodosa. The serum levels of MPO-ANCA and IL-6 were elevated on laboratory investigation and normalized after the removal of the tumor. We suggest that a 'true' vasculitic mechanism contributes to the pathogenesis of pseudovasculitis in cardiac myxoma.

Adult↗
PubMed2004

A case of delayed brain abscess due to a retained intracranial wooden foreign body: a case report and review of the last 20 years.

A 13-year-old female is presented. When she was six years old, she had fallen, holding wooden chopsticks and got stuck with a chopstick in the right upper eyelid. She was brought to a physician immediately, but a residual foreign body was missed and no particular symptom had developed during 7 years. She visited our department with fever and headache, and a brain abscess and an intracranial foreign body were found on computed tomography (CT) and magnetic resonance image (MRI) 7 years after the penetrating injury. She underwent removal of the object and abscess by craniotomy and recovered without neurological abnormalities. Since intracranial retained wooden foreign bodies frequently cause delayed complications of severe central nervous system infection, surgical removal is necessary even in the absence of symptoms.

Adolescent↗
PubMed2003

Association between polymorphisms in the SPINK5 gene and atopic dermatitis in the Japanese.

Atopy, which is characterized by increased levels of immunoglobulin E (IgE) against common environmental allergens, is considered the strongest predisposing factor for asthma and atopic dermatitis (AD). Mutations in the gene encoding serine protease inhibitor Kazal-type 5 (SPINK5) are responsible for Netherton syndrome, a rare skin disorder characterized by greatly elevated IgE levels with atopic manifestations. A recent study of Caucasian AD families showed that maternally derived alleles of the SPINK5 gene are associated with development of AD and asthma, suggesting the parent-of-origin effect for the development of atopic diseases in the SPINK5 gene. We studied the possible association of the SPINK5 gene for the development of atopic diseases by determining the genotypes of five polymorphisms in a Japanese population. Ttransmission disequilibrium tests revealed an association of SPINK5 polymorphisms with AD but not with asthma. Our data indicate that the SPINK5 gene is associated with AD across ethnicities.

Carrier Proteins↗
PubMed2003

Striatal infarcts mimicking frontotemporal dementia: a case report.

We described a patient with bilateral striatal infarcts, in whom stereotyped and disinhibited behaviors were insidiously emerged over 2 years mimicking frontotemporal dementia (FTD). A positron emission tomography with 18-fluorodeoxy glucose showed a hypometabolism in the frontal lobes, basal ganglia, and thalami. The peculiar behavioral alterations remained unchanged for the following 7 years, suggesting that the disease is not degenerative but of vascular origin. A disruption of the fronto-subcortical circuits at the level of the striatum or the anterior thalamic peduncle is attributable to the FTD-like behavioral and cognitive syndrome.

Aged↗
PubMed2002

Upregulation of mucosal soluble fas ligand and interferon-gamma may be involved in ulcerogenesis in patients with Helicobacter pylori-positive gastric ulcer.

BACKGROUND: Excessive upregulation of gastric epithelial cell apoptosis is speculated to be associated with ulcerogenesis in Helicobacter pylori-positive peptic ulcer disease. H. pylori may have an ulcerogenic effect through induction of gastric epithelial cell apoptosis mediated by infiltrating T cells and their soluble products. METHODS: The contents of soluble Fas ligand (sFasL) and interferon-gamma (IFN-gamma) in organ cultures and the degree of apoptosis and the expression of apoptosis-related proteins in the gastric epithelium were examined using the mucosal tissues obtained from the antrum and the ulcer site in patients with H. pylori-positive gastric ulcer (GU). The molecular mechanisms of gastric epithelial cell apoptosis induced by sFasL and IFN-gamma were analyzed using epithelial cell lines, MKN 45 and KATO III. RESULTS: The mucosal tissues of the ulcer site had substantially higher contents of sFasL and IFN-gamma in organ cultures regardless of its healing stage in association with increased numbers of apoptotic cells and enhanced expression of proapoptotic proteins Bak and Bax in the surface foveolar epithelium as compared with the antral tissues in patients with H. pylori-positive GU. The addition of sFasL caused increases in cytotoxic cell death and caspase-3 activation in MKN 45 and KATO III cells in which IFN-gamma treated cells had more prominent effects than untreated cells. The expression of Bak in MKN 45 cells increased when they were treated with IFN-gamma. CONCLUSIONS: Upregulation of mucosal sFasL and IFN-gamma may be involved in ulcerogenesis in patients with H. pylori-positive GU through induction of gastric epithelial cell apoptosis.

Adult↗
PubMed2001

Endotoxin impairs biliary transport of sparfloxacin and its glucuronide in rats.

The effect of endotoxin on glucuronidation and hepatobiliary transport of quinolone antimicrobial agents was investigated in rats using sparfloxacin and p-nitrophenyl glucuronide as model drugs. The biliary clearance experiments were performed 24 h after a single intraperitoneal injection of endotoxin (1 mg/kg). Endotoxin significantly delayed the disappearance of sparfloxacin from plasma and increased plasma concentration of its glucuronide after intravenous injection of sparfloxacin (10 mg/kg). Significant decreases in the systemic clearance of sparfloxacin and the biliary clearance of sparfloxacin and the glucuronide were observed. Endotoxin had no effect on in vitro glucuronidation activity using p-nitrophenol as a substrate. When p-nitrophenyl glucuronide (8 mg/kg) was administered in endotoxin-pretreated rats, significant decreases in the systemic clearance, biliary clearance and renal clearance of p-nitrophenyl glucuronide were observed. These findings suggest that endotoxin decreases the biliary excretion of sparfloxacin and its glucuronide probably due to impairment of their hepatobiliary transport systems and renal handling.

Animals↗
PubMed2001

Involvement of nuclear transcription factor Sp1 in regulating glucose transporter-1 gene expression during rat trophoblast differentiation.

Glucose transporter-1 (GLUT1) is important in placental glucose transport. However, the mechanism of regulation of placental GLUT1 expression remains to be elucidated. We show here that the level of GLUT1 protein in rat choriocarcinoma cells (Rcho-1) decreased during differentiation. To analyze the regulatory mechanism of rat GLUT1 (rGLUT1) gene expression, we transfected rGLUT1 promoter-chloramphenicol acetyltransferase constructs into Rcho-1 cells. Deletion analysis of the rGLUT1 promoter suggested that the region -76/-53 bp was essential for basal transcriptional activity. Electrophoretic mobility shift assays showed that transcription factors Sp1 and Sp3 bound two GC boxes in the region -99/-33 bp of the rGLUT1 promoter. Mutation analysis of the Sp1 binding sites revealed that the promoter-proximal site located between -76 and -53 bp was essential for basal rGLUT1 promoter activity. Furthermore, the decreased level of GLUT1 may result from a decreased level of Sp1 during differentiation. These findings suggest that Sp1 is involved in the regulation of rGLUT1 gene expression during rat trophoblast differentiation.

Animals↗
PubMed2001

Induction of endothelial nitric-oxide synthase phosphorylation by the raloxifene analog LY117018 is differentially mediated by Akt and extracellular signal-regulated protein kinase in vascular endothelial cells.

Raloxifene is a tissue-selective estrogen receptor modulator. The effect of estrogen on cardiovascular disease is mainly dependent on direct actions on the vascular wall involving activation of endothelial nitric oxide synthase (eNOS) via Akt and extracellular signal-regulated protein kinase (ERK) cascades. Although raloxifene is also known to activate eNOS in the vascular endothelium, the molecular mechanism responsible for this effect remains to be elucidated. In studies of both human umbilical vein endothelial cells and simian virus 40-transformed rat lung vascular endothelial cells (TRLECs), the raloxifene analog LY117018 caused acute phosphorylation of eNOS that was unaffected by actinomycin D and was blocked by the pure estrogen receptor antagonist ICI182,780. Activation of Akt by raloxifene reached a plateau at 15-30 min and declined thereafter, a similar time frame to that of Akt activation by 17beta-estradiol. On the other hand, both activation and phosphorylation of ERK by raloxifene showed a biphasic pattern (peaks at 5 min and 1 h), whereas ERK activation and phosphorylation by 17beta-estradiol reached a plateau at 5 min and declined thereafter. A MEK inhibitor, PD98059, had no effect on the raloxifene-induced Akt activity, suggesting an absence of cross-talk between the ERK and Akt cascades. Either exogenous expression of a dominant-negative Akt or pretreatment of TRLECs with PD98059 decreased the raloxifene-induced eNOS phosphorylation. Moreover, raloxifene stimulated the activation of Akt, ERK, and eNOS in Chinese hamster ovary cells expressing estrogen receptor alpha but not Chinese hamster ovary cells expressing estrogen receptor beta. Our findings suggest that raloxifene-induced eNOS phosphorylation is mediated by estrogen receptor alpha via a nongenomic mechanism and is differentially mediated by Akt- and ERK-dependent cascades.

Animals↗
PubMed2001

Effects of bezafibrate and simvastatin on plasma lipoproteins in hypercholesterolemia resistant to hormone replacement therapy.

OBJECTIVES: Estrogen replacement therapy has favorable effects on serum lipoprotein levels in postmenopausal women with hypercholesterolemia. However, there are some patients who fail to respond to hormone replacement therapy (HRT) to lower the serum cholesterol level. In these cases, a conventional lipid-lowering therapy will be applied in addition to HRT, while the effects of these drugs are not well understood. In this study, we studied the effects of simvastatin and bezafibrate administered in addition to HRT. METHODS: Patients who were hypercholesterolemic even after HRT were randomly assigned to three treatment groups: HRT only (control group, n=10), HRT+simvastatin (10 mg/day, n=10), or HRT+bezafibrate (400 mg/day, n=10). Serum lipids and lipoprotein levels were measured throughout 12 weeks. RESULTS: The serum triglyceride levels were decreased by 24+/-28 and 38+/-13% in the HRT+simvastatin and HRT+bezafibrate groups, respectively. HRT+simvastatin decreased the total cholesterol (21+/-10%) and low-density lipoprotein cholesterol (28+/-12%) levels without affecting the high-density lipoprotein cholesterol (HDL-C) level, while HRT+bezafibrate increased the HDL-C level (12+/-11%). CONCLUSIONS: Treatment with simvastatin or bezafibrate in addition to HRT should be considered in cases of postmenopausal hypercholesterolemia in which HRT alone fails to lower the serum lipoprotein levels.

Bezafibrate↗
PubMed2001

Protein-tyrosine phosphatase-1B negatively regulates insulin signaling in l6 myocytes and Fao hepatoma cells.

Insulin signaling is regulated by tyrosine phosphorylation of the signaling molecules, such as the insulin receptor and insulin receptor substrates (IRSs). Therefore, the balance between protein-tyrosine kinases and protein-tyrosine phosphatase activities is thought to be important in the modulation of insulin signaling in insulin-resistant states. We thus employed the adenovirus-mediated gene transfer technique, and we analyzed the effect of overexpression of a wild-type protein-tyrosine phosphatase-1B (PTP1B) on insulin signaling in both L6 myocytes and Fao cells. In both cells, PTP1B overexpression blocked insulin-stimulated tyrosine phosphorylation of the insulin receptor and IRS-1 by more than 70% and resulted in a significant inhibition of the association between IRS-1 and the p85 subunit of phosphatidylinositol 3-kinase and Akt phosphorylation as well as mitogen-activated protein kinase phosphorylation. Moreover, insulin-stimulated glycogen synthesis was also inhibited by PTP1B overexpression in both cells. These effects were specific for insulin signaling, because platelet-derived growth factor (PDGF)-stimulated PDGF receptor tyrosine phosphorylation and Akt phosphorylation were not inhibited by PTP1B overexpression. The present findings demonstrate that PTP1B negatively regulates insulin signaling in L6 and Fao cells, suggesting that PTP1B plays an important role in insulin resistance in muscle and liver.

Adenoviridae↗
PubMed2001

Mutation and association analysis of the interferon regulatory factor 2 gene (IRF2) with atopic dermatitis.

Interferon regulatory factor 2 (IRF-2) is a member of a family of transcriptional factors involved in the modulation of cellular responses to interferons (IFNs) and viral infection as well as in the regulation of cell growth and transformation. Irf2 knockout mice show T helper 1 (Th1) cell development defect and spontaneous development of an inflammatory skin disease. To determine if there are any mutations in IRF2 associated with development of atopic dermatitis (AD), we screened for mutations in the 5' flanking and coding regions of IRF2 in AD patients and control subjects by single-strand conformational polymorphism (SSCP) analysis. We found three mutations in the promoter region ([-829C>T, -830C>T], -684C>T, and -467G>A), one silent mutation in exon 9 (921G>A), and a 10-bp deletion in the 3' untranslated region (1739[ATCCC]8>6). Among them, the -467G allele and the haplotype of the -467G, 921A, and 1739(ATCCC)8 alleles were transmitted preferentially to AD-affected children (P = 0.02 and P = 0.007, respectively). Our data suggest that IRF-2 plays some role in the development of AD in the Japanese population.

Alleles↗
PubMed2001

Progesterone inhibits transcriptional activation of human chorionic gonadotropin-alpha gene through protein kinase A pathway in trophoblast cells.

The purpose of this study was to analyze the mechanism of transcriptional inhibition of human chorionic gonadotropin-alpha (hCGalpha) gene by progesterone in trophoblast cells. We stably transfected -290 bp hCGalpha promoter-CAT constructs (-290halphaCAT) into Rcho-1 cells and monitored the promoter activities. Differentiation-dependent activation of -290 bp hCGalpha promoter containing a tandem repeat of cAMP response element (CRE) was inhibited by progesterone in a dose-dependent manner. To further analyze the mechanism of the progesterone action, Rcho-1 cells stably transfected with -290halphaCAT were treated with forskolin in the presence of progesterone. Progesterone inhibited forskolin-induced transcriptional activation of hCGalpha gene. Moreover, progesterone inhibited forskolin-induced transcriptional activation of CRE-CRE-tk-CAT. These results suggest that progesterone may inhibit cAMP-induced transcriptional activation of hCGalpha gene through CRE. Although progesterone did not alter the amount of CRE-binding protein (CREB), which is a main transcriptional factor bound to CRE(s) on hCGalpha promoter, progesterone abolished forskolin-induced CREB phosphorylation. In addition, pretreatment with progesterone abolished forskolin-induced activation of nuclear protein kinase A (PKA). In conclusion, progesterone inhibits hCGalpha gene transcription, at least in part, via the CRE region by inhibiting CREB phosphorylation through PKA pathway in trophoblast cells.

Blotting, Western↗
PubMed2001

Coronary endothelial dysfunction in the insulin-resistant state is linked to abnormal pteridine metabolism and vascular oxidative stress.

OBJECTIVES: We investigated whether abnormal pteridine metabolism is related to coronary endothelial dysfunction in insulin-resistant subjects. BACKGROUND: Depletion of tetrahydrobiopterin (BH(4)) and elevation of the 7,8-dihydrobiopterin (BH(2)) (activating and inactivating cofactors of nitric oxide synthase [NOS], respectively) contribute to impairment of NO-dependent vasodilation through reduction of NOS activity as well as increased superoxide anion generation in insulin-resistant rats. METHODS: Thirty-six consecutive nondiabetic, normotensive and nonobese subjects with angiographically normal coronary vessels were studied. Traditional coronary risk factors, plasma pteridine levels, activities of erythrocyte dihydropteridine reductase (DHPR), the recycling enzyme that converts BH(2) to BH(4) and lipid peroxide (LPO) levels were measured and coronary endothelial function was assessed with graded infusions of acetylcholine (ACh). RESULTS: When we divided patients into tertiles based on insulin sensitivity, we observed stepwise decreases in the maximal ACh-induced vasodilation and plasma BH(4)/7,8-BH(2) ratio, and increases in coronary LPO production as insulin sensitivity decreased. The ACh-induced vasodilation was positively correlated with insulin sensitivity, BH(4)/7,8-BH(2) ratio and DHPR activity. Furthermore, BH(4)/7,8-BH(2) was inversely correlated with DHPR activity and insulin sensitivity. In multiple stepwise regression analysis, BH(4)/BH(2) was independently related to ACh-induced vasodilation and accounted for 39% of the variance. However, no significant correlation existed between other traditional risk factors and BH(4)/7,8-BH(2). CONCLUSIONS: These results indicate that both abnormal pteridine metabolism and vascular oxidative stress are linked to coronary endothelial dysfunction in the insulin-resistant subjects.

Acetylcholine↗
PubMed2001

Endoscopic ablation with cyanoacrylate glue for isolated gastric variceal bleeding.

BACKGROUND: Endoscopic ablation with cyanoacrylate glue may achieve gastric variceal obliteration. A prospective evaluation of its therapeutic effects on bleeding gastric varices was conducted, focusing on endoscopic features. METHODS: Thirty-seven patients with bleeding gastric varices underwent endoscopic ablation with cyanoacrylate. RESULTS: Patients with localized-type gastric varices (n = 14) had a better clinical course in terms of recurrent bleeding, variceal eradication, and survival than those with diffuse-type gastric varices (n = 23) after endoscopic ablation with cyanoacrylate. These clinical effects were related to the vascular anatomy of the gastric varices as determined by varicography and 3-dimensional CT. Type 1 vascular anatomy (one varicose vessel without noticeable ramifications) was much more common (86%) in localized-type gastric varices, whereas type 2 vascular anatomy (multiple varicose vessels with complex connecting ramifications) was found almost exclusively (91%) in diffuse-type gastric varices. CONCLUSIONS: Endoscopic ablation with cyanoacrylate is an effective and safe procedure for patients with bleeding gastric varices. Determination of variceal anatomy may be useful for improving treatment strategies for such patients.

Adhesives↗