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Yasuyuki Suzuki

Publications and source records attributed to Yasuyuki Suzuki.

At least 19 recordsLinked to original sources
PubMed2026

Maternal high-fat diet modulates lupus nephritis through fetal Wnt-steroid hormone and epigenetic reprogramming in MRL/lpr mouse offspring.

We previously investigated whether maternal high-fat diet (HFD) exposure alters lupus nephritis (LN) progression in MRL/lpr offspring. Contrary to expectation, maternally HFD-exposed offspring showed delayed and attenuated nephritic progression compared with control diet offspring. The maternal HFD developmental impact on LN remains unclear. Here, integrated amniotic fluid metabolomics and fetal liver transcriptomics revealed that maternal HFD reshaped the intrauterine molecular environment, particularly involving steroid hormone biosynthesis and Wnt/β-catenin-associated regulatory networks. Methylome profiling further demonstrated broad CpG hypomethylation, immune-related differentially methylated region enrichment, and an inverse association between global CpG methylation and oxidative genomic DNA damage. Among candidate regulatory nodes, Axin2, a canonical Wnt/β-catenin target and feedback regulator, emerged as a potential link between fetal nutritional exposure, epigenetic remodeling, and persistent pathway modulation. Although whole-locus and gene body methylation of Axin2 were not markedly altered, promoter-region methylation showed an increasing tendency under maternal HFD exposure. In adult offspring, maternal HFD was associated with reduced Axin2 protein expression, decreased Wnt-responsive transcripts, increased peripheral corticosterone levels, and attenuation of LN progression. The inverse association between Axin2 expression and corticosterone further suggested coupling between suppressed Wnt pathway output and steroid hormone remodeling. Together, these findings support a developmental model in which maternal HFD reshapes the fetal intrauterine environment and establishes a persistent Wnt-steroid hormone-epigenetic regulatory axis that unexpectedly attenuates LN progression in genetically susceptible offspring.

Axin2↗
PubMed2026

Comparison between measured and synthesized posterior lead electrocardiograms during percutaneous coronary intervention-induced myocardial ischemia.

BACKGROUND: Posterior/inferolateral myocardial ischemia is frequently underrecognized on standard 12&#x2011;lead electrocardiography (ECG). Synthesized posterior leads derived from the standard 12&#x2011;lead ECG have been proposed as an alternative to directly measured posterior leads; however, their accuracy under controlled ischemic conditions has not been fully validated. METHODS: We prospectively enrolled 26 consecutive patients undergoing percutaneous coronary intervention (PCI) in whom simultaneously recorded measured and synthesized posterior lead ECGs (V7-V9) were obtained during balloon-induced myocardial ischemia. ST-segment deviation was measured at the ST junction (STJ), 40&#xa0;ms (ST1), and 80&#xa0;ms (ST2) thereafter. Agreement between measured and synthesized posterior leads was assessed using Pearson correlation and Bland-Altman analyses. As an exploratory patient-level analysis, diagnostic performance was compared with reciprocal anterior ST-segment depression (V1-V4). RESULTS: Strong correlations were observed between measured and synthesized posterior lead ST-segment deviations (V7: r&#xa0;=&#xa0;0.89; V8: r&#xa0;=&#xa0;0.86; V9: r&#xa0;=&#xa0;0.83; all P&#xa0;<&#xa0;0.001). Bland-Altman analysis demonstrated minimal systematic bias (within &#xb1;0.004&#xa0;mV) and narrow limits of agreement. Synthesized posterior leads showed higher diagnostic performance than reciprocal anterior ST-segment depression (AUC 0.917 vs. 0.708), although the difference was not statistically significant (DeLong test, P&#xa0;=&#xa0;0.197). Using a 0.05&#xa0;mV threshold, synthesized posterior leads demonstrated 83.3% sensitivity, 100% specificity, and 96.2% overall accuracy. CONCLUSIONS: Synthesized posterior leads closely reproduced measured posterior lead ST-segment deviations during percutaneous coronary intervention (PCI)-induced myocardial ischemia, supporting the technical validity of posterior lead reconstruction. Larger prospective studies are warranted to determine whether synthesized posterior leads provide incremental diagnostic value beyond careful interpretation of the standard 12&#x2011;lead ECG.

Humans↗
PubMed2007

Neutrophil elastase inhibitor, sivelestat, attenuates acute lung injury after cardiopulmonary bypass in the rabbit endotoxemia model.

BACKGROUND: Neutrophil elastase probably contributes to the development of acute lung injury after cardiopulmonary bypass (CPB) in patients with infection or shock. We evaluated whether pretreatment with sivelestat sodium hydrate, a neutrophil elastase inhibitor (EI), can prevent acute lung injury caused by CPB. METHODS: Rabbits were assigned four groups: CPB for 60 minutes, control CPB group; low-dose lipopolysaccharide (LPS) administration without CPB, LPS group; CPB after lipopolysaccharide administration, LPS+CPB group; or preparation with continuous infusion of sivelestat and CPBs after lipopolysaccharide administration, EI group. Blood samples to determine blood gas concentration, plasma elastase activity, and plasma interleukin-8 levels were obtained. Histopathologic examinations of the lung were performed. RESULTS: The decreased arterial oxygen pressure at the end of CPB was observed in the LPS+CPB group only, but was suppressed in the EI group (p < 0.01). Elastase activity was markedly elevated at 120 minutes after CPB, and interleukin-8 levels were markedly elevated at 180 minutes in the LPS+CPB group but were much lower (p < 0.05) in the EI group. Histopathology demonstrated accumulation of polymorphonuclear neutrophils in bronchoalveolar areas in the LPS+CPB group (p < 0.01). Pulmonary myeloperoxidase activity was significantly lower in the LPS+CPB group than in the other groups (p < 0.01). These changes were minimal in the EI group. CONCLUSIONS: The combination of low dose LPS+60 minutes of CPB, but neither intervention alone, produced evidence of acute lung injury in a rabbit model. This did not occur when the animals were pretreated with sivelestat.

Animals↗
PubMed2006

Antinociceptive effect of methyleugenol on formalin-induced hyperalgesia in mice.

The effects of methyleugenol, an essential oil isolated from Asiasari radix, on antinociception were examined using the formalin test in mice. Oral administration of 10 mg/kg methyleugenol significantly decreased the duration of licking and biting behavior in the second phase without affecting that of the first phase, as did diclofenac, a non-steroidal anti-inflammatory drug. Methyleugenol also inhibited pain-related behaviors induced by intrathecal injection of N-methyl-d-aspartic acid (NMDA), while diclofenac did not affect these behaviors. These effects of methyleugenol were suppressed by bicuculline, a gamma-aminobutyric acid(A) (GABA(A)) antagonist. Muscimol, a GABA(A) agonist, displays the same action as methyleugenol with respect to the formalin test and NMDA-induced behaviors. Methyleugenol did not affect cyclooxygenase-1 and -2 activities. These results suggest that the antinociceptive effect of methyleugenol on the second phase of formalin-induced pain may be due to the inhibition of NMDA receptor-mediated hyperalgesia via GABA(A) receptors.

Anesthetics↗
PubMed2006

Simple scoring system for the prediction of the prognosis of severe acute pancreatitis.

BACKGROUND: In severe acute pancreatitis (SAP), it is important clinically to predict the prognosis at the time of admission. Most scoring systems for severity of acute pancreatitis consist of multiple factors and are complicated. This investigation aimed to propose a simple scoring system for the prediction of the prognosis of SAP. METHODS: Prognostic factors were evaluated by receiver operator characteristic curve analyses and multivariate analysis from data that were obtained on admission of 137 patients with SAP. A simple scoring system with 3 most useful factors was made, and its usefulness was investigated in comparison with conventional scoring systems. RESULTS: Three prognostic factors were selected: serum blood urea nitrogen > or = 25 mg/dL, serum lactate dehydrogenase > or = 900 IU/L, and contrast-enhanced computed tomography finding with pancreatic necrosis. On admission, 137 patients were classified from 0 to 3 by the number of positive items (simple prognostic score [SPS]). Mortality rates for patients whose SPS was 0, 1, 2, and 3 were 2% (1/42 patients), 18% (7/40 patients), 48% (12/25 patients), and 67% (20/30 patients), respectively. Furthermore, when usefulness of SPS was compared with conventional scoring systems, the area under the curve by receiver operator characteristic curve analyses in SPS was 0.83; the Ranson score was 0.83; the Japanese severity score was 0.83; the Acute Physiology and Chronic Health Evaluation II score was 0.81, and the Glasgow score was 0.75. After onset, SPS kept almost same levels from day 2 to day 6, and a significant difference was observed between survivors and nonsurvivors from day 1 to day 6. CONCLUSION: This scoring system that comprised 3 items is simple, is feasible for the prediction of prognosis and conventional scoring systems, and is useful for the selection of the extremely severe patients with SAP on admission.

Blood Glucose↗
PubMed2006

Degradation of amyotrophic lateral sclerosis-linked mutant Cu,Zn-superoxide dismutase proteins by macroautophagy and the proteasome.

Mutations in the Cu,Zn-superoxide dismutase (SOD1) gene cause approximately 20% of familial cases of amyotrophic lateral sclerosis (fALS). Accumulating evidence indicates that a gain of toxic function of mutant SOD1 proteins is the cause of the disease. It has also been shown that the ubiquitin-proteasome pathway plays a role in the clearance and toxicity of mutant SOD1. In this study, we investigated the degradation pathways of wild-type and mutant SOD1 in neuronal and nonneuronal cells. We provide here the first evidence that wild-type and mutant SOD1 are degraded by macroautophagy as well as by the proteasome. Based on experiments with inhibitors of these degradation pathways, the contribution of macroautophagy to mutant SOD1 clearance is comparable with that of the proteasome pathway. Using assays that measure cell viability and cell death, we observed that under conditions where expression of mutant SOD1 alone does not induce toxicity, macroautophagy inhibition induced mutant SOD1-mediated cell death, indicating that macroautophagy reduces the toxicity of mutant SOD1 proteins. We therefore propose that both macroautophagy and the proteasome are important for the reduction of mutant SOD1-mediated neurotoxicity in fALS. Inhibition of macroautophagy also increased SOD1 levels in detergent-soluble and -insoluble fractions, suggesting that both detergent-soluble and -insoluble SOD1 are degraded by macroautophagy. These findings may provide further insights into the mechanisms of pathogenesis of fALS.

Amyotrophic Lateral Sclerosis↗
PubMed2006

Double cancer of gall bladder and bile duct not associated with anomalous junction of the pancreaticobiliary duct system.

BACKGROUND: Simultaneous double cancers of the biliary tract are rare. Most of them are thought to be associated with pancreaticobiliary maljunction (PBM); however, the characteristics of tumours without PBM are still unclear. METHODS: Histology, immunoreactivity with carcinoembryonic antigen, carbohydrate antigen 19-9 and p53 and mutations in the K-ras gene were examined in tumours resected from cases of simultaneous double cancers of the biliary tract. RESULTS: Four cases of simultaneous double cancers of the biliary tract were identified among 108 patients with biliary tract cancer (3.7%). None of the four cases associated with PBM, and the results of histological, immunohistochemical and genetic examinations differed between the bile duct and gall bladder cancers in each case. CONCLUSION: Even when they do not associate with PBM, double cancers in the biliary tract are more likely to be the result of multicentric development.

Aged↗
PubMed2006

Risk factors for open-angle glaucoma in a Japanese population: the Tajimi Study.

PURPOSE: To identify the risk factors associated with primary open-angle glaucoma (POAG) in the Tajimi Study. DESIGN: Population-based cross-sectional epidemiologic study. PARTICIPANTS: One hundred nineteen POAG patients and 2755 controls. METHODS: Univariate and multivariate comparison of ocular factors and systemic factors between POAG patients and controls. MAIN OUTCOME MEASURES: Difference in factors between POAG patients and controls, factors associated with POAG patients, and their odds ratio (OR). RESULTS: Intraocular pressure (IOP), age, myopia, and history of hypertension differed between POAG patients and controls in univariate analyses. Multivariate analysis with logistic regression with stepwise selection of variables demonstrated that higher IOP (OR, 1.12 [95% confidence interval (CI), 1.04-1.21]), myopia (ORs, 1.85 [95% CI, 1.03-3.31] for low myopia and 2.60 [95% CI, 1.56-4.35] for moderate to high myopia), and older age (OR, 1.06 [95% CI, 1.04-1.08]) were associated with an increased risk of having POAG. CONCLUSIONS: Although the majority (92%) of POAG patients diagnosed in the Tajimi Study had IOP within the normal range, IOP was still identified as a significant risk factor for POAG. Together with IOP, myopia and age were significant risk factors for having POAG.

Age Factors↗
PubMed2006

Chemical modification of the internal surfaces of cylindrical pores of submicrometer size in poly(ethylene terephthalate).

Chemical modification of the internal surfaces of cylindrical pores with submicrometer pore diameter in a poly(ethylene terephthalate) (PET) film was examined. The modification involved the alkylation of the carboxylic acid on the surfaces with the alkylation reagent containing a fluorescent probe, and it was monitored by observing the change in fluorescent emission intensity. When the N,N-dimethylformamide solution of 4-(bromomethyl)-6,7-dimethoxycoumarin (BrCU), which bore a coumarin fluorophore, was introduced into the pores, the emission and excitation intensities of the membranes increased proportionally with increases of the pore surface areas. Fluorescent spots about 300 nm in diameter, which were located at the positions of the pores, can be observed in the fluorescence microscope image of the membranes, indicating that highly concentrated fluorescent probes are chemically incorporated on the internal surfaces of the cylindrical pores with 210 nm diameter in the membranes. In the reactions of the PET surfaces with BrCU, the fluorescent intensities increased with increases of the contact angles. This result indicates that the hydrophilicity of the internal pore surfaces can be qualitatively modified by controlling the change in the fluorescent intensities.

Journal Article↗
PubMed2006

Aberrant peroxisome morphology in peroxisomal beta-oxidation enzyme deficiencies.

Peroxisomes are ubiquitous organelles in eukaryotic cells and surrounded by a single membrane, and undergo considerable changes in size, shape and number. Peroxisomal disorders are classified into two categories: peroxisome biogenesis disorders (PBDs) and single-enzyme deficiencies (SEDs). Morphologically aberrant peroxisomes called 'peroxisomal ghosts' in PBDs are well known, however, a morphological approach to the study of peroxisomes in SEDs has been rarely reported. Here, we investigated the morphology of peroxisomes in cultured fibroblasts from patients lacking peroxisomal beta-oxidation enzymes, including acyl-CoA oxidase (AOX) or D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein (D-BP). Morphological analysis by immunofluorescence examination using an antibody against catalase revealed a smaller number of large peroxisomes in fibroblasts from these patients. Moreover, immunoelectron microscopy using an antibody against the 70-kDa peroxisomal membrane protein (PMP70) showed large peroxisomes with various horseshoe-shaped membrane structures. These results give an important clue to elucidating the division of peroxisomes and how peroxisomes change in size, shape, number and position within cells, which are subjects for future study.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed2006

Parkin potentiates ATP-induced currents due to activation of P2X receptors in PC12 cells.

Loss-of-function mutations of the parkin gene causes an autosomal recessive juvenile-onset form of Parkinson's disease (AR-JP). Parkin was shown to function as a RING-type E3 ubiquitin protein ligase. However, the function of parkin in neuronal cells remains elusive. Here, we show that expression of parkin-potentiated adenosine triphosphate (ATP)-induced currents that result from activation of the P2X receptors which are widely distributed in the brain and involved in neurotransmission. ATP-induced inward currents were measured in mock-, wild-type or mutant (T415N)-parkin-transfected PC12 cells under the conventional whole-cell patch clamp configuration. The amplitude of ATP-induced currents was significantly greater in wild-type parkin-transfected cells. However, the immunocytochemical study showed no apparent increase in the number of P2X receptors or in ubiquitin levels. The increased currents were attenuated by inhibition of cAMP-dependent protein kinase (PKA) but not protein kinase C (PKC) or Ca2+ and calmodulin-dependent protein kinase (CaMKII). ATP-induced currents were also regulated by phosphatases and cyclin-dependent protein kinase 5 (CDK5) via dopamine and cyclic AMP-regulated phosphoprotein (DARPP-32), though the phosphorylation at Thr-34 and Thr-75 were unchanged or rather attenuated. We also tried to investigate the effect of alpha-synuclein, a substrate of parkin and also forming Lysine 63-linked multiubiquitin chains. Expression of alpha-synuclein did not affect the amplitude of ATP-induced currents. Our finding provides the evidence for a relationship between parkin and a neurotransmitter receptor, suggesting that parkin may play an important role in synaptic activity.

Adenosine Triphosphate↗
PubMed2006

Congenital quadricuspid aortic valve with tetralogy of Fallot and pulmonary atresia.

We report the case of a 4-year-old girl who had quadricuspid aortic valve regurgitation with tetralogy of Fallot and pulmonary atresia. This combination is very uncommon. Aortic valve replacement was performed successfully due to aortic regurgitation which had progressed one year after the total repair. The dilated aortic annulus plus quadricuspid aortic valve may result in progressive aortic regurgitation for a short period.

Aortic Valve↗
PubMed2006

Systolic anterior motion of the mitral valve despite the sliding leaflet technique for repair of the mitral valve.

We report a systolic anterior motion of the anterior mitral leaflet despite employing the sliding leaflet technique for repair of mitral valve regurgitation. A 65-year-old man with chronic, symptomatic mitral regurgitation due to ruptured chordae tendineae underwent mitral valve repair by quadrangular resection of the posterior leaflet and sliding leaflet technique with ring annuloplasty. After weaning from cardiopulmonary bypass, left ventricular outflow obstruction developed and transesophageal echocardiography demonstrated systolic anterior motion of the mitral valve and severe mitral regurgitation. Non-operative treatment resolved the outflow tract obstruction, systolic anterior motion and mitral regurgitation. We conclude that post-repair systolic anterior motion can still occur after the sliding plasty procedure and that medical treatment can successfully resolve systolic anterior motion and outflow tract obstruction in most patients.

Aged↗
PubMed2006

Infective endocarditis with congenital heart disease.

From 1988 to 2005, seven patients were operated at our hospital because of infectious endocarditis (IE) with congenital heart disease (CHD). Underlying CHD included ventricular septal defect (VSD) in 4 (2 previous operations with residual region), atrial septal defect (ASD) in 2 and bicuspid aortic stenosis (AS) in 1. No cases had preventive antibiotic prophylaxis for dental procedures. We could confirm bacteria origin from blood culture in all cases, but two patients had operations without gaining control of the infection. VSD or ASD closure and valve surgery were performed in four patients. One patient had a VSD closure, two patients had valve surgery. There were no operative or hospital deaths and there were no recurrences of IE during the study period. We successfully treated IE with CHD by enough debridement of the infective focus of IE, and valve surgery. It is important for patients with CHD to have preventive antibiotic prophylaxis for dental procedures.

Adolescent↗
PubMed2006

Outcomes of surgery for intraductal papillary mucinous neoplasms of the pancreas.

BACKGROUND: Our objective was to evaluate outcomes of surgery for intraductal papillary mucinous neoplasms of the pancreas (IPMN) in terms of the clinicopathological features. METHODS: Fifty-seven patients with IPMN were examined using clinicopathological analyses to evaluate appropriate surgical treatment, including total pancreatectomy (TP). IPMN was classified into two types: main-duct type (MD, n = 33) and branch-duct type (BD, n = 24). RESULTS: Ultrasound (US) and computed tomography (CT) examinations easily revealed the main site of the lesions. Intraoperative US was the most useful device for diagnosis of lateral spreading, and accuracy rates were 74% for MD and 96% for BD. TP was performed on 16 patients and was appropriate for removing neoplastic lesions with malignancy or malignant potential in 12. Three patients who underwent partial pancreatectomy with involved cancer died of progressive disease. MD is a strong predictive factor in malignancy and indicative of TP. Concerning long-term outcomes, 5 of 16 patients suffered from severe hypoglycemia, and 2 of 16 died from this condition. CONCLUSION: Partial resection with cancer clearance was applied for BD-type IPMN. TP should be performed on selected patients with MD-type IPMN.

Adult↗
PubMed2006

Significant elevation of serum interleukin-18 levels in patients with acute pancreatitis.

BACKGROUND: We have reported that peripheral lymphocyte reduction due to apoptosis is linked to the development of subsequent infectious complications in patients with severe acute pancreatitis and that Th1 (helper T cell type 1)/Th2 (helper T cell type 2) balance tends to cause Th1 suppression in experimental severe acute pancreatitis. It has been reported that interleukin (IL)-18 is a cytokine produced from Kupffer cells and activated macrophages, and that IL-18 acts on Th1 cells and in combination with IL-12 strongly induces production of interferon-gamma. However, the role of IL-18 in acute pancreatitis has not yet been fully understood. METHODS: Serum IL-18 concentrations were determined by an enzyme-linked immunosorbent assay in 43 patients with acute pancreatitis at the time of admission. The relationships with etiology, pancreatic necrosis, severity, blood biochemical parameters on admission, infection, and organ dysfunction during the clinical course and prognosis were analyzed. RESULTS: Serum IL-18 levels in patients with acute pancreatitis (656+/- 11pg/ml) were significantly higher than those in healthy volunteers (126+/- pg/ml). Serum IL-18 levels were significantly positively correlated with the Ranson score and Japanese severity score. Among the blood biochemical parameters on admission, base excess and total protein were significantly negatively correlated with serum IL-18 levels. Moreover, the CD4/CD8 rate of lymphocytes, serum IL-6 levels, and serum IL-8 levels were significantly positively correlated with serum IL-18 levels. On day 7 after admission, the CD4/CD8 rate of lymphocytes and the rate of CD4-positive lymphocytes were significantly positively correlated with serum IL-18 levels. Furthermore, serum IL-18 levels in patients with hepatic dysfunction (980+/- 25pg/ml) were significantly higher than those without hepatic dysfunction (464+/- 8pg/ml). Serum IL-18 levels were not related to infection or prognosis. Elevation of serum IL-18 levels continued during 4 weeks after admission. CONCLUSIONS: These results suggest that serum IL-18 levels are significantly elevated and are correlated with severity in patients with acute pancreatitis and that IL-18 may be closely related to helper T cell response and hepatic dysfunction in this disease.

Acute Disease↗