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Hita, Japan

Kusano T.,Oita University | Chiang K.-C.,Josai International University | Inomata M.,Oita University | Shimada Y.,Josai International University | And 11 more authors.
BioMed Research International | Year: 2015

Background. Histones play important roles in both host defenses and inflammation related to microbial infection. A peptide mimotope (SSV) was identified from a novel histone H1 monoclonal antibody (16G9 mAb) that was shown to inhibit the mixed lymphocyte reaction. In the present study, an anti-SSV producing hybridoma was established. We investigated the effects of SSV mAb in a mouse acute inflammation model induced by intraperitoneal injection of lipopolysaccharide (LPS). Methods. SSV mAb was generated and characterized. Mice were treated with SSV mAb or a control IgG antibody prior to LPS injection. Evaluation of survival rate and lung tissue on histological score was performed. The levels of inflammatory cytokines and histones H1, H3, and H4 in plasma and lung tissue were measured by ELISA. Results. Competitive ELISA revealed that SSV mAb binds to histone H1. SSV mAb improved lung injury and prolonged the survival of LPS-injected mice. Increased levels of histones H1, H3, and H4 and inflammatory cytokines (TNF-α, IL-1β, and IL-6) in plasma and lung tissue after LPS injection were ameliorated by SSV mAb. Conclusion. SSV mAb is shown to have anti-inflammatory activity and organ-protective effects, highlighting the importance of controlling histone H1 as well as H3 and H4 levels during inflammation. © 2015 Toru Kusano et al.

Tanaka M.,Yokokura Hospital | Ando E.,Iwao Hospital | Simose S.,Kurume University | Hori M.,Kurume University | And 5 more authors.
Hepatology Research | Year: 2014

Aim: Radiofrequency ablation therapy (RFA) combined with transarterial chemoembolization (TACE) (combination therapy) is effective for early-stage hepatocellular carcinoma (HCC). The aim of this study was to compare the long-term effects of combination therapy with supportive care alone for intermediate HCC. Methods: The study included 58 patients with intermediate HCC who received combination therapy (n=34) or supportive care alone (n=24). The inclusion criteria were a single nodule of more than 50mm in diameter or two to three nodules, each measuring more than 30mm in diameter, or more than three nodules, no vascular invasion and no extrahepatic metastasis. Results: The overall survival rates at 1, 2, 3 and 5 years of the combination therapy group (91%, 65%, 53% and 27%, respectively) were significantly better (P<0.0001) than those of the supportive care group (42%, 8%, 8% and 0%, respectively). Multivariate analysis identified treatment modality (combination therapy vs supportive care alone: P<0.0001, risk ratio [RR]=4.290 [95% confidence interval [CI]=2.157-8.529]) and serum α-fetoprotein (P=0.017, RR=2.318 [95% CI=1.166-4.610]) as independent and significant factors of overall survival. Conclusion: The combination of TACE and RFA is a safe and effective therapy in patients with intermediate HCC. © 2013 The Japan Society of Hepatology.

Kao Y.-H.,Chang Gung Memorial Hospital Kaohsiung Medical Center | Jawan B.,Chang Gung Memorial Hospital Kaohsiung Medical Center | Sun C.-K.,Chang Gung Memorial Hospital Kaohsiung Medical Center | Goto S.,Chang Gung Memorial Hospital Kaohsiung Medical Center | And 10 more authors.
Phytomedicine | Year: 2010

Although magnolol is cytoprotective against warm ischemia/reperfusion injury, its effect on cold preservation has not been fully investigated. This study aimed at examining whether magnolol maintains the liver graft integrity after cold preservation and elucidating the underlying mechanisms in terms of apoptotic signaling under both normothermic and hypothermic conditions. After being preserved in Ringer's lactate (RL) at 4 °C for 6 h ex vivo, the magnolol-treated grafts demonstrated significantly higher AST, ALT, and LDH levels in perfusates than those from negative controls. TUNEL staining showed no difference in the number of apoptotic nuclei in both groups, whereas a more intense apoptotic signal in magnolol-treated grafts was shown as compared with the controls. In vitro data showed no significant difference in viability of RL-preserved clone-9 hepatocytes between the magnolol-treated and control groups, while magnolol pretreatment at 30 min before cold preservation prominently induced hepatocyte cell death. RT-PCR and Western blotting analyses revealed a suppression in Bcl-2, but an up-regulation in Bax expression in clone-9 cells after magnolol treatment. Magnolol suppressed the ratios of NF-κB to I-κBα protein contents and I-κBα phosphorylation induced by TNF-α, and potentiated mitochondrial cytochrome c release and subsequent caspase-3 cleavage. Conversely, caspase-3 inhibitor attenuated magnolol-induced hepatotoxicity. We concluded that magnolol could not protect liver grafts from cold ischemia/reperfusion injury. High concentration of magnolol under serum-reduced conditions attenuates NF-κB-mediated signaling and induces intrinsic apoptotic pathway, thereby inducing in vitro hepatotoxicity. © 2009 Elsevier GmbH. All rights reserved.

Iwao T.,Iwao Hospital | Sakai K.,Iwao Hospital | Sata M.,Kurume University
Journal of Diabetes and its Complications | Year: 2013

Aims: Liraglutide improves glycemic control in patients with type 2 diabetes. However, no information is available about an indicator of successful switching to liraglutide monotherapy from complex insulin therapy in Japanese patients with type 2 diabetes. Methods: We studied 69 patients with type 2 diabetes, including 39 consecutive successful patients and 30 consecutive unsuccessful patients from insulin therapy to liraglutide monotherapy. Before switching, we measured urinary C-peptide, fasting C-peptide and postprandial C-peptide at 30, 60 and 120 min loading a test meal. In successful patients, HbA1c and body weight were measured at 4, 8, and 12 weeks after switching. Results: Using univariate analysis, duration of disease was significantly higher in unsuccessful patients than in successful patients. Urinary C-peptide, fasting C-peptide, and postprandial C-peptides were significantly higher in successful patients than in unsuccessful patients. Multiple logistic regression analysis showed that postprandial C-peptide at 60 min was an independent predictor of successful switching to liraglutide monotherapy from insulin therapy (odds ratio, 7.28; 95% confidence interval, 2.89-18.36). In the receiver operating characteristic analyses, 2.9 ng/mL of postprandial C-peptide at 60 min was the best cut-off value, providing that sensitivity and specificity were 95% and 93%, respectively. In the follow-up period, successful patients showed a sustained reduction in HbA1c and body weight without hypoglycemia. Conclusions: Postprandial C-peptide at 60 min is a useful parameter in the prediction of successful switching from insulin therapy to liraglutide monotherapy in Japanese patients with type 2 diabetes. © 2013 Elsevier Inc.

Hori M.,Kurume University | Tanaka M.,Yokokura Hospital | Ando E.,Iwao Hospital | Sakata M.,Kurume University | And 7 more authors.
Hepatology Research | Year: 2014

Aim: The aim of this study was to evaluate the long-term outcome of elderly patients with hepatocellular carcinoma (HCC) aged 75 years or older. Methods: The study included 422 patients with HCC, who were divided into two age groups: 75 years or older (n=140) and younger than 75 (n=282). Outcomes were compared between the two groups. Results: The number of elderly patients treated with supportive care alone (33 patients; 24%) was significantly higher than younger patients (30 patients; 11%, P<0.01). The 1-, 3-, 5- and 7-year overall survival rates of the elderly patients (81%, 55%, 39% and 23%, respectively) were worse than those of younger patients (85%, 64%, 49% and 36%, respectively, P=0.042). However, the overall survival rate of the elderly group after excluding 63 patients treated with supportive care alone, was similar to that of the younger group (P=0.615). Multivariate analysis identified age, total bilirubin levels, albumin levels, serum des-γ-carboxy prothrombin levels, tumor size, number of HCC nodules, vascular invasion, extrahepatic metastasis and treatment modality as independent and significant factors of overall survival. Conclusion: Advanced age is a negative prognostic factor in patients with HCC due to the tendency for frequent use of conservative treatment rather than locoregional or surgical treatment. © 2013 The Japan Society of Hepatology.

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