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Satoshi Miuma,
Tatsuki Ichikawa,
Kazuhiko Arima, Shigeyuki Takeshita,
Toru Muraoka,
Toshihisa Matsuzaki,
Masashi Ootani,
Hidetaka Shibata,
Motohisa Akiyama,
Eisuke Ozawa,
Hisamitsu Miyaaki,
Naota Taura,
Fuminao Takeshima,
Kazuhiko Nakao
[show abstract]
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ABSTRACT: Abnormal sugar metabolism is closely related to chronic liver diseases, including hepatocellular carcinoma (HCC). We previously reported that fasting hyperinsulinemia is a poor prognostic factor for HCC patients. A recent large-scale study has shown that long-term administration of branched chain amino acids (BCAA) reduces the risk of HCC development in obese cirrhotic patients who have been diagnosed with diabetes mellitus, although the mechanism by which it does so is unclear. In this study, we analyzed the expression of vascular endothelial growth factor (VEGF) in HepG2 cells under high-insulin culture conditions, and examined the effect of BCAA on VEGF expression. VEGF secretion was significantly increased by 200 nM of insulin under BCAA deficient conditions, but it was repressed by the addition of BCAA. BCAA activated the mTOR pathway and increase HIF-1α expression under high-insulin culture conditions, however quantitative PCR analysis showed that insulin-induced expression of VEGF mRNAs (VEGF121 and VEGF165) decreased 2 h after the addition of BCAA. The half-lives of both VEGF121 and 165 mRNAs were shortened in the presence of BCAA compared to the absence of BCAA. Therefore it is thought that BCAA regulate VEGF expression mainly at the post-transcriptional level. We also examined which of the Valine, Leucine, and Isoleucine components of BCAA were essential for VEGF mRNA degradation. All three BCAA components were required for acceleration of insulin-induced VEGF mRNA degradation. These results suggest that administration of BCAA may downregulate VEGF expression in patients who have hyperinsulinemia and are in the process of developing HCC.
Journal of Cellular Biochemistry 05/2012; 113(10):3113-21. · 2.87 Impact Factor
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ABSTRACT: A 60-year-old man with alcoholic liver cirrhosis was admitted to our hospital with severe anemia and tarry stool. Upper gastrointestinal
endoscopy revealed grade4 esophageal varices without bleeding and severe portal hypertensive gastropathy (PHG) of the fornix
of the stomach with oozing. These findings suggested that PHG was the cause of progression of anemia. Abdominal computed tomography
demonstrated no enhancement of the main portal vein and its first branches, indicating portal thrombosis and cavernous transformation.
The patient underwent partial splenic embolization (PSE) to reduce portal hypertension. Two months after PSE was performed,
upper gastrointestinal endoscopy showed improvement of PHG and endoscopic variceal ligation was performed to treat the esophageal
varices. Contrast-enhanced CT revealed partial enhancement of the main portal vein indicating improvement of portal thrombosis.
One year after PSE, hemoglobin had increased from 6.0 to 11.0g/dl without blood transfusion. Moreover, albumin level had
risen from 2.8 to 3.7g/dl, cholinesterase from 51 to 150IU/l, and prothrombin time from 47% to 66%. PSE can be an effective
alternative for the management of severe PHG with portal vein thrombosis, and it might also be effective in improving liver
function.
Clinical Journal of Gastroenterology 04/2012; 2(3):218-221.
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Shigeyuki Takeshita,
Tatsuki Ichikawa,
Naota Taura,
Hisamitsu Miyaaki,
Toshihisa Matsuzaki,
Masashi Otani,
Toru Muraoka,
Motohisa Akiyama,
Satoshi Miuma,
Eisuke Ozawa,
Masanori Ikeda,
Nobuyuki Kato,
Hajime Isomoto,
Fuminao Takeshima,
Kazuhiko Nakao
[show abstract]
[hide abstract]
ABSTRACT: Geranylgeranylacetone (GGA), an isoprenoid compound which includes retinoids, has been used orally as an anti-ulcer drug in Japan. GGA acts as a potent inducer of anti-viral gene expression by stimulating ISGF3 formation in human hepatoma cells. This drug has few side effects and reinforces the effect of IFN when administered in combination with peg-IFN and ribavirin. This study verified the anti-HCV activity of GGA in a replicon system. In addition, mechanisms of anti-HCV activity were examined in the replicon cells.
OR6 cells stably harboring the full-length genotype 1 replicon containing the Renilla luciferase gene, ORN/C-5B/KE, were used to examine the influence of the anti-HCV effect of GGA. After treatment, the cells were harvested with Renilla lysis reagent and then subjected to a luciferase assay according to the manufacturer's protocol.
The results showed that GGA had anti-HCV activity. GGA induced anti-HCV replicon activity in a time- and dose-dependent manner. GGA did not activate the tyrosine 701 and serine 727 on STAT-1, and did not induce HSP-70 in OR6 cells. The anti-HCV effect depended on the GGA induced mTOR activity, not STAT-1 activity and PKR. An additive effect was observed with a combination of IFN and GGA.
GGA has mTOR dependent anti-HCV activity. There is a possibility that the GGA anti-HCV activity can be complimented by IFN. It will be necessary to examine the clinical effectiveness of the combination of GGA and IFN for HCV patients in the future.
Journal of Gastroenterology 02/2012; 47(2):195-202. · 4.16 Impact Factor
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Toru Muraoka,
Tatsuki Ichikawa,
Naota Taura,
Hisamitsu Miyaaki, Shigeyuki Takeshita,
Motohisa Akiyama,
Satoshi Miuma,
Eisuke Ozawa,
Hajime Isomoto,
Fuminao Takeshima,
Kazuhiko Nakao
[show abstract]
[hide abstract]
ABSTRACT: The mammalian target of rapamycin (mTOR) is one of the influential molecules for the anti-hepatitis C virus (HCV) action of interferon (IFN). IFN-induced mTOR activity, independent of phosphatidylinositol-3-kinase (PI3K) and Akt, is a critical factor for anti-HCV activity. mTOR activity is involved in signal transducers and activators of transcription (STAT)-1 phosphorylation and nuclear localization, and then double-stranded RNA-dependent protein kinase (PKR) is expressed in hepatocytes. Insulin (INS) is a major cytokine for metabolism and regulates the PI3K-Akt-mTOR signaling pathway in hepatocytes. Changes in mTOR activity have been reported in chronic HCV-infected patients with excess nutrition and INS resistance. Therefore, this experiment investigated whether INS increases anti-HCV activity via mTOR activity. This study used a genome-length HCV RNA (strain O of genotype 1b) replicon reporter system (OR6), derived from HuH7 cells. OR6 cells were pre-treated with rapamycin or LY294002 or siRNA, and the cells were treated with INS (0-300 nmol/l) or IFN (0-50 IU/ml) for 30 min to 48 h. The cells were lysed and analyses were carried out using the Renilla luciferase assay, western blotting or ELISA. INS induced the anti-HCV effects via mTOR activity, independently of STAT-1 tyrosine phosphorylation, in a dose- and time-dependent manner. INS-induced mTOR activation was found to be PI3K-Akt-dependent in OR6 cells. The combination of IFN and INS had an additive anti-HCV effect. The INS-induced mTOR activity was identified to be an anti-HCV signal independent of the STAT pathway in this study. mTOR activity may be associated with the HCV life cycle. Future studies should, therefore, attempt to identify new agents that activate mTOR to promote anti-HCV activity.
Molecular Medicine Reports 11/2011; 5(2):331-5. · 0.42 Impact Factor
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Hiroshi Akahoshi,
Naota Taura,
Tatsuki Ichikawa,
Hisamitsu Miyaaki,
Motohisa Akiyama,
Satoshi Miuma,
Eisuke Ozawa, Shigeyuki Takeshita,
Toru Muraoka,
Toshihisa Matsuzaki,
Masashi Ohtani,
Hajime Isomoto,
Takehiro Matsumoto,
Fuminao Takeshima,
Kazuhiko Nakao
[show abstract]
[hide abstract]
ABSTRACT: The number and ratio of both HBsAg- and HCV Ab-negative hepatocellular carcinoma (HCC-nonBC) cases have been steadily increasing in Japan. The aim of this study was to examine the frequency of detection of HCC-nonBC by screening methods and to elucidate the clinical characteristics of HCC-nonBC compared with those of hepatitis C and/or B virus-associated HCC (HCC-virus). We recruited 624 patients with HCC who were diagnosed between 1982 and 2007 at the Department of Gastroenterology and Hepatology, Nagasaki University Hospital. They were categorized into 2 groups as follows: i) 550 were included in the HCC-virus group: positive for HBsAg and/or positive for HCV Ab, and ii) 74 were included in the HCC-nonBC group: negative for both HBsAg and HCV Ab. The follow-up patterns until the initial detection of HCC and the survival rates were analyzed and compared between the 2 groups. Multivariate analysis identified follow-up, alcohol consumption, albumin level, total bilirubin level, alpha-fetoprotein (AFP) level, and tumor-node-metastasis (TNM) stage as independent and significant risk factors for prognosis. Among the 397 patients with HCC in TNM stage I or II, multivariate analysis identified the cause of liver disease, gender, Child-Pugh score, serum albumin level and TNM stage as independent and significant risk factors for prognosis. We reported that the poor prognoses of patients with HCC-nonBC were attributable to its late detection in an advanced condition due to the absence of a surveillance system for the early detection of HCC. However, in early-stage patients, patients with HCC-nonBC showed significantly better prognosis than those in the HCC-virus group.
Oncology Reports 05/2010; 23(5):1317-23. · 1.84 Impact Factor
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ABSTRACT: The frequency of regulatory T cells (Tregs) may be related to persistent hepatitis C virus (HCV) infection. We studied the alteration of the Treg ratio in peripheral blood mononuclear cells (PBMCs) from chronic hepatitis C patients during combination therapy compared with the Treg ratio in liver-infiltrating lymphocytes (LILs) before therapy.
The study group consisted of 20 patients who were treatment-naive and had high virus titers of HCV genotype 1. Blood samples were collected prior to treatment and at several time points during treatment. All patients received a liver biopsy prior to treatment. Forkhead box P3 (Foxp3)+, CD3+, CD4+ and CD8+ cells in PBMCs and LILs were stained by specific antibodies.
Ten patients had a sustained virological response (SVR), and 10 patients were non-responders. The SVR group had a significant increase in the Foxp3+/CD4+ ratio in PBMCs at 8 and 12 weeks as well as a significant decrease in the Foxp3+/CD4+ ratio and increase in the CD8+/Foxp3+ ratio in LILs.
The evaluation of Tregs, a potentially significant factor for persistent HCV infection, in LILs prior to treatment and in PBMCs during treatment could predict the result of combination therapy.
Intervirology 01/2010; 53(3):154-60. · 2.34 Impact Factor
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Satoshi Miuma,
Tatsuki Ichikawa,
Naota Taura,
Hidetaka Shibata, Shigeyuki Takeshita,
Motohisa Akiyama,
Yasuhide Motoyoshi,
Eisuke Ozawa,
Masumi Fujimoto,
Hiroshi Kawashimo,
Hisamitsu Miyaaki,
Katsumi Eguchi,
Kazuhiko Nakao
[show abstract]
[hide abstract]
ABSTRACT: Impaired glucose tolerance influences the prognosis of hepatocellular carcinoma (HCC), but this mechanism is still not fully understood. We investigated the impact of the fasting serum levels of insulin and adiponectin on the prognosis of HCC and its recurrence. One hundred and forty patients with newly diagnosed HCC were enrolled in the prognosis study. Their fasting serum levels of insulin and adiponectin were determined. Of 140 patients, 59 patients who underwent curative treatment were subjected to analysis of the recurrence-free survival. The 140 patients were divided into two groups by the 50th percentile value of insulin (7.73 microIU/ ml) or total adiponectin (6.95 microg/ml). Kaplan-Meier analysis indicated that high insulin group (>7.73 microIU/ml) exhibited a significantly poorer prognosis than low insulin group (<7.73 microIU/ml) in early stage HCC (P=0.018). In contrast, the level of total adiponectin had no impact on the prognosis of HCC. Multivariate analysis indicated that fasting hyper-insulinemia was an independent risk factor for a poorer prognosis in early stage HCC (P=0.044). Likewise, Kaplan-Meier analysis indicated that the recurrence-free survival of high insulin group was significantly lower than that of low insulin group (P=0.017). The level of total adiponectin had no impact on the recurrence-free survival of HCC. Multivariate analysis indicated that fasting hyperinsulinemia was an independent risk factor for the lower recurrence-free survival of HCC (P=0.049). In conclusion, our study suggests that the fasting insulin level affects the clinical course of early stage HCC.
Oncology Reports 12/2009; 22(6):1415-24. · 1.84 Impact Factor
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Hisamitsu Miyaaki,
Tatsuki Ichikawa,
Kazuhiko Nakao,
Toshihisa Matsuzaki,
Toru Muraoka,
Takuya Honda, Shigeyuki Takeshita,
Hidetaka Shibata,
Eisuke Ozawa,
Motohisa Akiyama,
Satoshi Miuma,
Katsumi Eguchi
[show abstract]
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ABSTRACT: Aims: Suppressor of cytokine signaling 3 (SOCS3) can suppress Janus kinase (JAK)-signal transducers and activators of transcription (STAT) signaling by blocking an IFN-induced protein. In this study, the relationship between SOCS3 and phosphorylation of STAT1 in the liver and outcome of interferon therapy were examined. Methods: Prior to interferon treatment, we immunostained for SOCS3 and phosphorylated-STAT1 (P-STAT1) in 59 liver specimens from chronic hepatitis C virus (CHC) patients and compared the expression of SOCS3 and clinicopathological factors. Fifty-one patients were receiving peg-interferon alpha-2b and ribavirin therapy and also compared interferon therapy effect and the expression of SOCS3. Results: Immunostaining for SOCS3 was mainly seen in the periportal area. The concentration of P-STAT1 nuclei was significantly larger in specimens with < 30% area immunostaining to SOCS3 than those in which this area was >/= 30% (10.6 +/- 8.8 vs. 4.6 +/- 6.1, P = 0.004). SOCS3 immunostaining score was significantly correlated with aspartate amino transferase (r = 0.373, P = 0.003), alanine amino transferase (r = 0.337, P = 0.008), platelets (r = -0.273, P = 0.037), and homeostatic model assessment (r = 0.339, P = 0.008). On univariate analysis and multivariate analysis, SOCS3 immunostaining score (0 or 1) and age (<60 years old) were significant predictors of interferon response (odds ratio 10.888; P = 0.010; odds ratio 3.817, P = 0.045 respectively). Conclusion: SOCS3 expression in the liver prior to interferon therapy was correlated with increased insulin resistance and might be a useful predictor of HCV clearance by interferon therapy.
Hepatology Research 08/2009; 39(9):850-5. · 2.20 Impact Factor
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Tatsuki Ichikawa,
Kazuhiko Nakao,
Hisamitsu Miyaaki,
Susumu Eguchi,
Mitsuhisa Takatsuki,
Masumi Fujimito,
Motohisa Akiyama,
Satoshi Miuma,
Eisuke Ozawa,
Hidetaka Shibata, Shigeyuki Takeshita,
Takashi Kanematsu,
Katsumi Eguchi
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ABSTRACT: Aim: To identify the problems of pegylated interferon (PEG IFN) with ribavirin therapy against hepatitis C virus (HCV) reinfection in living donor liver transplantation (LDLT) patients. HCV kinetics during the PEG IFN with ribavirin therapy were analyzed in LDLT patients, as well as in chronic hepatitis C (CHC) patients. Methods: The study included 80 consecutive HCV infected patients undergoing PEG IFN with ribavirin therapy (64 CHC and 16 LDLT patients) who attended the Nagasaki University Hospital for an initial visit between January 2005 and December 2007. Results: The sustained viral response (VR) rate of the CHC group (80%) was superior to the LDLT group (22%). The viral disappearance rate of the CHC group was also superior to the LDLT group, regardless of the HCV serotype. The HCV core antigen (cAg) titer under treatment in the LDLT group was more than that of the CHC group from day 0 to week 12. The HCV cAg decrease rate of the LDLT group on the first day of treatment was less than that of the CHC group. Conclusion: The HCV infection of a transplanted liver is more refractory to treatment than a non-transplanted liver. The low reduction HCV cAg rate on day 1 is one of the problems of the combination therapy.
Hepatology Research 08/2009; 39(9):856-64. · 2.20 Impact Factor
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Azusa Matsumoto,
Tatsuki Ichikawa,
Kazuhiko Nakao,
Hisamitsu Miyaaki,
Kumi Hirano,
Masumi Fujimito,
Motohisa Akiyama,
Satoshi Miuma,
Eisuke Ozawa,
Hidetaka Shibata, Shigeyuki Takeshita,
Hironori Yamasaki,
Masanori Ikeda,
Nobuyuki Kato,
Katsumi Eguchi
[show abstract]
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ABSTRACT: The interferon-induced Jak-STAT signal alone is not sufficient to explain all the biological effects of IFN. The PI3-K pathways have emerged as a critical additional component of IFN-induced signaling. This study attempted to clarify that relationship between IFN-induced PI3-K-Akt-mTOR activity and anti-viral action.
When the human normal hepatocyte derived cell line was treated with rapamycin (rapa) before accretion of IFN-alpha, tyrosine phosphorylation of STAT-1 was diminished. Pretreatment of rapa had an inhibitory effect on the IFN-alpha-induced expression of PKR and p48 in a dose dependent manner. Rapa inhibited the IFN-alpha inducible IFN-stimulated regulatory element luciferase activity in a dose-dependent manner. However, wortmannin, LY294002 and Akt inhibitor did not influence IFN-alpha inducible luciferase activity. To examine the effect of PI3-K-Akt-mTOR on the anti-HCV action of IFN-alpha, the full-length HCV replication system, OR6 cells were used. The pretreatment of rapa attenuated its anti-HCV replication effect in comparison to IFN-alpha alone, whereas the pretreatment with PI3-K inhibitors, wortmannin and LY294002 and Akt inhibitor did not influence IFN-induced anti-HCV replication.
IFN-induced mTOR activity, independent of PI3K and Akt, is the critical factor for its anti-HCV activity. Jak independent mTOR activity involved STAT-1 phosphorylation and nuclear location, and then PKR is expressed in hepatocytes.
Journal of Gastroenterology 06/2009; 44(8):856-63. · 4.16 Impact Factor
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Shigeyuki Takeshita,
Tatsuki Ichikawa,
Kazuhiko Nakao,
Hisamitsu Miyaaki,
Hidetaka Shibata,
Toshihisa Matsuzaki,
Toru Muraoka,
Takuya Honda,
Masashi Otani,
Motohisa Akiyama,
Satoshi Miuma,
Esuke Ozawa,
Masumi Fujimito,
Katsumi Eguchi
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ABSTRACT: Nutritional support may play an important role in management of liver cirrhosis (LC) associated with unresectable hepatocellular carcinoma (HCC). Total protein and albumin deteriorate in patients with LC undergoing trans-arterial chemoembolization (TACE). Therefore, in this study, we examined the hypothesis that short-term administration of branched-chain amino acids (BCAA) will prevent a fall in total protein and albumin in the perioperative period. The subjects were 56 patients who underwent TACE for HCC between 2004 and 2005 at Nagasaki University Hospital. The patients were randomly placed in the BCAA group (n = 28) or a control group (n = 28). The patients in the BCAA group consumed a snack containing 50 g of BCAA once a day at 10:00 pm starting 1 day before TACE and continuing until 2 weeks after TACE. A comparison of baseline and end point data showed greater decreases in the concentrations of total protein, albumin, cholinesterase, and total cholesterol and in the red blood cell count in the control group compared to the BCAA group. Ammonia levels decreased in the BCAA group and increased in the control group. Our findings indicate that a BCAA supplement taken orally as a late evening snack prevents suppression of liver function by TACE in patients with LC complicated with HCC during the 2-week period after TACE.
Nutrition research (New York, N.Y.) 03/2009; 29(2):89-93. · 1.20 Impact Factor
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Hisamitsu Miyaaki,
Emi Murakami,
Tatsuki Ichikawa,
Kazuhiko Nakao, Shigeyuki Takeshita,
Hidetaka Shibata,
Eisuke Ozawa,
Motohisa Akiyama,
Satoshi Miuma,
Masumi Fujimoto,
Tamotsu Kuroki,
Yoshitsugu Tajima,
Takashi Kanematsu,
Katsumi Eguchi
Liver international: official journal of the International Association for the Study of the Liver 11/2008; 29(5):774-5. · 3.82 Impact Factor
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ABSTRACT: Regulatory T cells (Tregs) play a critical role in chronic viral infections. The role of Tregs in chronic hepatitis B (CHB) and chronic hepatitis C (CHC) is unknown. This study examined the distribution and frequency of forkhead box p3(+) (Foxp3(+)) Tregs in the liver tissue and compared the clinicopathological characteristics of CHB and CHC patients.
Liver needle biopsies were obtained from 26 patients who were hepatitis B surface antigen positive and 27 patients who were hepatitis C virus antibody positive.
The ratio of Foxp3(+) Tregs in CD3(+) T cells was similar in HBV and in HCV cases. In HBV cases, the variables that were positively associated with the ratio of Foxp3(+) Tregs in CD3(+) T cells included the serum alanine aminotransferase level (R=0.402, P=0.025) and the ratio of CD8(+) T cell plus CD56(+) NK cell against CD4(+) T cell (R=0.53, P=0.005). The ratio of Foxp3(+) Tregs in CD3(+) T cells increased more in the severe activity group than in the mild activity group (P=0.04). In HCV cases, the ratio of Foxp3(+) Tregs in CD3(+) T cells increased significantly in terms of the genotype2 (P=0.0002) and male gender (P=0.04). In addition, the ratio of Foxp3(+) Tregs in CD3(+) T cells showed a negative correlation with the ratio of CD8(+) T cell plus CD56(+) NK cell against CD4(+) T cell (R=-0.508, P=0.005) and HCV viral load (R=-0.482, P=0.001).
Liver-targeted regulatory T cells present similarly in CHB and CHC, but their relationship with the effector cell population, the inflammation grade or the viral load is different between CHB and CHC.
Liver international: official journal of the International Association for the Study of the Liver 08/2008; 29(5):702-7. · 3.82 Impact Factor
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ABSTRACT: Portal vein tumor thrombus (PVTT) is observed in a considerable number of hepatocellular carcinoma (HCC) cases. It is an exacerbating factor for patients afflicted with HCC. The sequelae of PVTT are considered to be a contraindication for the treatment of HCC in such patients. The survival of 10 HCC patients with PVTT treated with trans-hepatic arterial continuous injection chemotherapy was compared to 13 HCC patients with PVTT, who received best supportive care only, as a control to validate the efficacy of continuous trans-hepatic arterial injection chemotherapy using an implanted catheter for HCC with PVTT. There were no differences in the liver function and HCC stage between the two groups. The survival was significantly different between the two groups (P=0.01 by the log-rank test). The median survival time was 106 days in the treatment patients, whereas it was 65 days in the control patients. Multivariate analyses showed the therapy to be the only predictor for survival (risk ratio 0.144, P=0.016). The therapy was strongly associated with the PVTT prognosis. In conclusion, the importance of trans-arterial chemotherapy was demonstrated even in advanced dysfunctional cirrhotic HCC patients with PVTT. It is therefore necessary to develop a basic protocol to treat HCC with PVTT.
Oncology Reports 08/2008; 20(2):353-7. · 1.84 Impact Factor
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ABSTRACT: Signal transducers and activators of transcription (STATs) play a critical role in antiviral defense. To better understand pegylated interferon (IFN)-alpha and ribavirin combination therapy resistance, we examined the STAT expression in the liver.
We immunostained Phospho-STAT1 (P-STAT1) and Phospho-STAT3 (P-STAT3) in 59 hepatitis C virus (HCV)-infected liver tissues and compared the expression of these STATs proteins and the clinicopathological factors.
The number of P-STAT1 observed correlated significantly with the body mass index (BMI; p = 0.03) and homeostatic model assessment (p = 0.007). The number of P-STAT3 observed correlated significantly with the ALT level (p = 0.002) and platelet count (p = 0.002). The number of P-STAT1 nuclei in the sustained virological response (SVR) group was significantly larger than in the non-SVR group (p = 0.003). On multivariance analysis, the number of P-STAT1 nuclei (p = 0.004) and age (p = 0.016) were significant predictors of SVR.
P-STAT1 in the liver tissue prior to IFN therapy correlated with an increased BMI and increased insulin resistance, and might be a useful predictor of HCV clearance by IFN therapy. On the other hand, P-STAT3 might play a critical role in the hepatocellular response against inflammatory damage.
Intervirology 02/2008; 51(6):394-9. · 2.34 Impact Factor
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Shigeyuki Takeshita,
Hideki Nakamura,
Atsushi Kawakami,
Tetsuya Fukushima,
Takashi Gotoh,
Tatsuki Ichikawa,
Akira Tsujino,
Hiroaki Ida,
Kan Toriyama,
Tomayoshi Hayashi,
Katsumi Eguchi
[show abstract]
[hide abstract]
ABSTRACT: A 64-year-old man was admitted for alithiasic cholecystitis. Necrotizing vasculitis was detected in a gallbladder obtained at the cholecystectomy. Slight elevation of transaminases, HBe antigens and hepatitis B-DNA (HBV-DNA) were detected in the patient. Intrahepatic necrotizing vasculitis was also detected in the liver biopsy specimen, and he also suffered from peripheral neuropathy of suddenly onset. Based on the diagnosis of hepatitis B-related polyarteritis nodosa, lamivudine was initially administered, followed by plasmapheresis and glucocorticoid steroid therapy. These treatments brought satisfactory improvement of polyarteritis nodosa without exacerbation of liver function.
Internal Medicine 02/2006; 45(3):145-9. · 0.94 Impact Factor
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Hidetaka Shibata,
Tatsuki Ichikawa,
Kazuhiko Nakao,
Hisamitsu Miyaaki, Shigeyuki Takeshita,
Motohisa Akiyama,
Masumi Fujimoto,
Satoshi Miuma,
Shougo Kanda,
Hironori Yamasaki,
Katsumi Eguchi
[show abstract]
[hide abstract]
ABSTRACT: Oxidative stress is known to play a key role in the progression of liver disease, including non-alcoholic steatohepatitis (NASH), which is often accompanied by hyperglycemia. This study examined the influence of high glucose on oxidative stress-induced hepatic cell death. Hc cells, a normal human hepatocyte-derived cell line, were cultured in normal-to-high glucose (5.5-22 mM)-containing medium with varying concentrations (0.01-1 mM) of hydrogen peroxide. In certain experiments, cyclosporine A (CyA), which inhibits the mitochondrial permeability transition (MPT) pore, or Z-VAD-FMK (z-VAD), a pan-caspase inhibitor, were added to the medium. Cell viability was evaluated using a colorimetric assay. The mode of cell death was determined by nuclear staining methods using Hoechst 33258 and Sytox green. Neither high glucose (22 mM) nor 0.05-0.5 mM of hydrogen peroxide alone killed Hc cells. However, a combination of the two induced cell death, causing the nuclei of Hc cells to become expanded rather than condensed, and the nuclear membrane to become weak. CyA, but not z-VAD, blocked cell death. These results suggest that a high glucose condition may cause human hepatocytes to undergo hydrogen peroxide-induced necrotic cell death.
Molecular Medicine Reports 1(3):379-85. · 0.42 Impact Factor
