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Biomedical subjects

Tetsu Watanabe

Publications and source records attributed to Tetsu Watanabe.

26 records · Page 2Linked to original sources
PubMed2003

Aldehyde dehydrogenase 2 and beta3-adrenergic receptor gene polymorphisms: their association with elevated liver enzymes and metabolic syndrome.

Recent studies indicate that some patients with nonalcoholic fatty liver have ongoing liver injury that may progress from steatosis to steatohepatitis or fibrosis. The present study was designed to clarify the clinical features of liver dysfunction observed in the course of workplace physical check-ups in relation to multiple risk factor syndrome including obesity, hyperlipidemia, hypertension, and impaired glucose tolerance, and to clarify the involvement of aldehyde dehydrogenase 2 (ALDH2) and beta(3)-adrenergic receptor (beta3-AR) gene polymorphisms in elevation of liver enzymes. One hundred forty-eight male workers 35 years of age were enrolled. They were requested to answer questionnaires about drinking and smoking habits, and underwent urinalysis, physical and peripheral blood examinations, blood chemistry, electrocardiogram and chest x-rays. The genotypes of ALDH2 and beta3-AR were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The subjects were divided into active ALDH2 or inactive ALDH2 groups. They were also divided into 2 groups according to the beta3-AR genotype. The relationships between ALDH2 and beta3-AR gene polymorphism and the results of the physical examination including liver function tests were analyzed. The subjects were also divided according to the number of components of metabolic syndrome. The prevalence of elevated alanine aminotransferase (ALT) level increased with the accumulation of components of metabolic syndrome. Active ALDH2 was associated with elevated ALT level to a greater degree than beta3-AR polymorphism. Among those with normal body mass index (BMI), the genotypes of ALDH2 and beta3-AR were strongly associated with elevated ALT level. Logistic regression analysis revealed that BMI, triglyceride level, and ALDH2 genotype were associated with ALT elevation. In conclusion, evaluating the genotype of ALDH2 and beta3-AR may assist in predicting and preventing the development of fatty liver which may be related to multiple risk factor syndrome.

Adult↗
PubMed2003

Interferon alfa down-regulates collagen gene transcription and suppresses experimental hepatic fibrosis in mice.

The equilibrium between the production and degradation of collagen is rigorously controlled by a number of growth factors and cytokines. Interferon alfa (IFN-alpha) is now widely used for the treatment of chronic hepatitis C, which can improve serum levels of fibrotic markers and the degree of hepatic fibrosis, not only in patients who responded to therapy but also in those in whom it is ineffective. These findings may suggest that IFN-alpha possesses direct antifibrotic effects in addition to its antiviral activity. However, in contrast to IFN-gamma, which has been shown to suppress collagen gene transcription, little is known about the mechanisms responsible for the antifibrotic effects of IFN-alpha. Here, we report that IFN-alpha, when administered into transgenic mice harboring the alpha2(I) collagen gene (COL1A2) promoter sequence, significantly repressed promoter activation and prevented the progression of hepatic fibrosis induced by carbon tetrachloride injection. Transient transfection assays indicated that IFN-alpha decreased the steady-state levels of COL1A2 messenger RNA (mRNA) and inhibited basal and TGF-beta/Smad3-stimulated COL1A2 transcription in activated hepatic stellate cells (HSC). These inhibitory effects of IFN-alpha on COL1A2 transcription were exerted through the interaction between phosphorylated Stat1 and p300. Blocking of the IFN-alpha signal by overexpressing the intracellular domain-deleted IFN receptor increased basal COL1A2 transcription and abolished the inhibitory effects of IFN-alpha. In conclusion, our results indicate that IFN-alpha antagonizes the TGF-beta/Smad3-stimulated COL1A2 transcription in vitro and suppresses COL1A2 promoter activation in vivo, providing a molecular basis for antifibrotic effects of IFN-alpha.

Animals↗
PubMed2002

Restitution properties and occurrence of ventricular arrhythmia in LQT2 type of long QT syndrome.

INTRODUCTION: The aim of this study was to clarify the ventricular tachyarrhythmia mechanism induced by the I(Kr)-blocking agent E4031, simulating the LQT2 form. Electrophysiologic properties were examined in 13 canines before and after administration of E4031. METHOD AND RESULTS: Thirty-six needle electrodes were inserted into the anterior left ventricular wall. From each needle, local unipolar electrograms were obtained from four intramural sites. Activation time (AT) and activation-recovery interval (ARI) were measured. To evaluate the susceptibility to ventricular arrhythmia, intramural ARI dispersions and the restitution relationship between ARI and diastolic interval were calculated. After E4031 administration, ARI prolonged uniformly in each myocardial layer. However, ARI dispersion was not augmented compared with control. The slope of the ARI restitution curve after E4031 was significantly steeper than control. A steep slope may result from augmented ARI alternans. In 11 of the 13 canines, ventricular tachyarrhythmia was induced by programmed stimulation after E4031, whereas no arrhythmia was induced by the same protocol in control. CONCLUSION: Steepness of electrical restitution may play a major role in arrhythmogenicity in LQT2 hearts.

Animals↗
PubMed2002

Periprosthetic fracture of the tibia associated with osteolysis caused by failure of rotating patella in low-contact-stress total knee arthroplasty.

Periprosthetic fracture of the tibial plateau associated with osteolysis resulting from mechanical failure of the rotating patellar component after total knee arthroplasty with the New Jersey Low-Contact-Stress (LCS) knee (DePuy, Warsaw, IN) has not been reported previously. A 67-year-old woman with rheumatoid arthritis of the left knee had a LCS prosthesis implanted without cement, using a rotating patellar component. Seven years later, a fracture of the lateral tibial plateau occurred owing to an osteolytic defect with no traumatic accident. The rotating patellar bearing over-rotated and locked; consequently, wear occurred between the patellar metal tray and the femoral component. Immunohistochemistry revealed CD68-positive macrophages in the osteolytic region and phagocytosis of metal particles. The osteolytic region was filled with autogenous bone, and all components were exchanged and cemented. The patient's condition became satisfactory with relief of pain.

Aged↗
PubMed2002

Regional prolongation of ARI and altered restitution properties cause ventricular arrhythmia in heart failure.

The mechanism of arrhythmogenicity in heart failure remains poorly understood. We examined the relationship between electrical abnormalities and ventricular arrhythmia by using experimental heart failure models. Sixty unipolar electrograms were recorded from the entire cardiac surface in control dogs (n = 13) and pacing-induced heart failure dogs (n = 16). In failing hearts, activation time (AT) was delayed at the apex, and AT dispersion increased in failing hearts. Activation-recovery intervals (ARI) were prolonged mainly at the apex and ARI dispersion was significantly augmented. The slope of the ARI restitution curve, interaction of diastolic interval, and ARI in failing hearts was significantly steeper than in control hearts. Ventricular fibrillation (VF) was easily induced by programmed stimulation in failing hearts, whereas no arrhythmia occurred in control hearts. Computer simulation studies could reproduce the experimental results. Altering the ARI restitution to the steep slope causes VF in a model heart. It is suggested that electrical remodeling, especially steepness of electrical restitution, may play a role in arrhythmogenicity in failing hearts.

Animals↗
PubMed2002

Effect of ethanol and docosahexaenoic acid on nerve growth factor-induced neurite formation and neuron specific growth-associated protein gene expression in PC12 cells.

It is known that prenatal and postnatal exposure to ethanol can result in hyperactive behavior and learning disturbance in offspring. We have previously shown that docosahexaenoic acid (DHA) ameliorated hyperactivity induced by in utero ethanol exposure in rat pups. The present study is designed to clarify the effects of DHA on neurite outgrowth and gene expression of GAP-43 and SCG10, neuron specific growth-associated proteins (GAPs) in PC12 cells treated with ethanol. Ethanol seemed to enhance the neurite outgrowth induced by nerve growth factor (NGF). DHA administration further increased neurite outgrowth in both NGF alone and the combination of NGF and ethanol treated PC12 cells. DHA treatment increased the levels of both GAP-43 and SCG10 mRNAs, and simultaneous administration of ethanol suppressed the elevation of GAP-43 and SCG10 mRNA enhanced by DHA. The present study has demonstrated, for the first time, the effect of ethanol and DHA on GAPs' gene expression. Interaction of ethanol and docosahexaenoic acid in NGF-induced neurite formation, as well as the mechanisms by which DHA ameliorate the hyperactivity induced by in utero ethanol exposure, are to be elucidated.

Animals↗
PubMedDate not supplied

Interferon therapy for hepatocellular carcinoma patients with low HCV-RNA levels.

BACKGROUND/AIMS: Interferon-alfa is widely used for the treatment of chronic hepatitis C, and has been thought to have a preventive effect on the development of hepatocellular carcinoma. Hepatocellular carcinoma develops from chronic liver diseases such as chronic hepatitis C or liver cirrhosis. We studied the effect of interferon for liver cirrhosis with hepatocellular carcinoma after treating hepatocellular carcinoma itself. METHODOLOGY: To evaluate the preventive effect of this drug on local recurrence and/or new development of primary tumor after clearance of hepatitis C virus, 46 patients with hepatocellular carcinoma with low HCV-RNA level were randomized to receive recombinant interferon-alfa 2b (n = 22) or not (n = 24) after being treated by transcatheter arterial chemoembolization and percutaneous ethanol injection therapy. In the interferon-treated group, patients received 3 million international units of interferon-alfa 2b intramuscularly three times a week for 4 months. In both groups, transcatheter arterial chemoembolization followed by percutaneous ethanol injection therapy was performed as an initial treatment and these therapies were repeated every 4-6 months. Serum HCV-RNA levels of all 46 patients were under 0.5 Meq/mL by branched DNA probe assay. RESULTS: In the interferon-treated group, 11 of the 22 (50%) patients were HCV-RNA negative at the 6 months after completing the course of interferon therapy. HCV-RNA was undetectable during the observation period in 2 of the 24 (9.5%) patients in the untreated group. The survival rate in the interferon-treated group was significantly higher than that in the untreated group (P = 0.01 by the log-rank test). Though there was no significant difference in the incidence of local recurrence in both groups, the incidence of secondary hepatocellular carcinoma was significantly lower in the interferon-treated group than that in the untreated group. Cox proportional hazards regression analysis validated interferon treatment as an independent predictor of hepatocellular carcinoma prognosis. CONCLUSIONS: We concluded that, if HCV-RNA level is low, interferon may be a therapy of choice in combination with transcatheter arterial chemoembolization and percutaneous ethanol injection therapy for the treatment of hepatocellular carcinoma.

Aged↗