| JaLCDOI | 10.18926/AMO/53520 |
|---|---|
| FullText URL | 69_3_137.pdf |
| Author | Seki, Hiroyuki| Ikeda, Fusao| Nanba, Shintaro| Moritou, Yuki| Takeuchi, Yasuto| Yasunaka, Tetsuya| Onishi, Hideki| Miyake, Yasuhiro| Takaki, Akinobu| Nouso, Kazuhiro| Iwasaki, Yoshiaki| Nakamura, Minoru| Yamamoto, Kazuhide| |
| Abstract | A predictive marker of the rapid progression to hepatic failure is desired for patients with asymptomatic primary biliary cirrhosis (aPBC). We performed a systematic cohort analysis of 101 patients diagnosed as having aPBC and the rapid progression to liver failure in some, by focusing on cholestasis. Cholestasis was assessed by aberrant keratin7 (K-7) expressions in the patientsʼ hepatocytes. Intralobular expressions of K-7 were found in 9 of the 101 patients. The grades of K-7 expression were significantly associated with the levels of alanine aminotransferase, alkaline phosphatase, and total bilirubin at the time of diagnosis, but not with bile duct loss or cholestasis. Stepwise logistic regression analysis revealed that high grades of K-7 expression correlated positively with high levels of total bilirubin. During the follow-up period, 8 patients developed jaundice, and the mean period until the development of jaundice was 5.2 years. The proportional hazards models for the risk of developing jaundice identified a high grade of aberrant K-7 expression in hepatocytes as the only significant risk factor. Aberrant K-7 expression in hepatocytes can be used as an additional marker to predict rapid progression to liver failure in patients with aPBC at the time of diagnosis. |
| Keywords | primary biliary cirrhosis keratin 7 hepatic failure |
| Amo Type | Original Article |
| Publication Title | Acta Medica Okayama |
| Published Date | 2015-06 |
| Volume | volume69 |
| Issue | issue3 |
| Publisher | Okayama University Medical School |
| Start Page | 137 |
| End Page | 144 |
| ISSN | 0386-300X |
| NCID | AA00508441 |
| Content Type | Journal Article |
| language | English |
| Copyright Holders | CopyrightⒸ 2015 by Okayama University Medical School |
| File Version | publisher |
| Refereed | True |
| PubMed ID | 26101189 |
| Web of Science KeyUT | 000356903000002 |
| JaLCDOI | 10.18926/AMO/52898 |
|---|---|
| FullText URL | 68_5_291.pdf |
| Author | Tsuzaki, Ryuichiro| Takaki, Akinobu| Yagi, Takahito| Ikeda, Fusao| Koike, Kazuko| Iwasaki, Yoshiaki| Shiraha, Hidenori| Miyake, Yasuhiro| Sadamori, Hiroshi| Shinoura, Susumu| Umeda, Yuzo| Yoshida, Ryuichi| Nobuoka, Daisuke| Utsumi, Masashi| Nakayama, Eiichi| Fujiwara, Toshiyoshi| Yamamoto, Kazuhide| |
| Abstract | It is not known how the immune system targets hepatitis C virus (HCV)-infected HLA-mismatched hepatocytes under immune-suppressed conditions after orthotopic liver transplantation (OLT). In addition, the relationship between the HCV-specific immune response and IL28B variants as predictors of HCV clearance has not been well-characterized. We determined the IL28B polymorphisms for 57 post-OLT HCV carriers, and we assessed the HCV-specific immune responses by measuring the peripheral blood mononuclear cell-derived HCV-specific interferon-gamma (IFN-γ) response using an enzyme-linked immunospot assay. At 1-3 years after OLT, patients with no active hepatitis showed higher total spots on the immunospot assay. At＞3 years after OLT, patients with resolved HCV showed higher levels of core, NS3, NS5A, and total spots compared to the chronic hepatitis patients. The IL28B major genotype in the donors correlated with higher spot counts for NS5A and NS5B proteins at 1-3 years after OLT. In the post-OLT setting, the HCV-specific immune response could be strongly induced in patients with no active hepatitis with an IL28B major donor or sustained virological response. Strong immune responses in the patients with no active hepatitis could only be maintained for 3 years and diminished later. It may be beneficial to administer IFN treatment starting 3 years after OLT, to induce the maximum immunological effect. |
| Keywords | interferon gamma ELISPOT assay single nucleotide polymorphisms dendritic cell CD4 T cell |
| Amo Type | Original Article |
| Publication Title | Acta Medica Okayama |
| Published Date | 2014-10 |
| Volume | volume68 |
| Issue | issue5 |
| Publisher | Okayama University Medical School |
| Start Page | 291 |
| End Page | 302 |
| ISSN | 0386-300X |
| NCID | AA00508441 |
| Content Type | Journal Article |
| language | English |
| Copyright Holders | CopyrightⒸ 2014 by Okayama University Medical School |
| File Version | publisher |
| Refereed | True |
| PubMed ID | 25338486 |
| Web of Science KeyUT | 000343269300006 |
| Related Url | http://ousar.lib.okayama-u.ac.jp/metadata/53129 |
| Author | Matsushita, Hiroshi| Ikeda, Fusao| Iwasaki, Yoshiaki| Seki, Hiroyuki| Nanba, Shintaro| Takeuchi, Yasuto| Moritou, Yuki| Yasunaka, Tetsuya| Onishi, Hideki| Miyake, Yasuhiro| Takaki, Akinobu| Nouso, Kazuhiro| Yamamoto, Kazuhide| |
|---|---|
| Published Date | 2014-02 |
| Publication Title | Journal of Gastroenterology and Hepatology |
| Volume | volume29 |
| Issue | issue2 |
| Content Type | Journal Article |
| Author | Ohnishi, Atsuyuki| Miyake, Yasuhiro| Matsushita, Hiroshi| Matsumoto, Kazuyuki| Takaki, Akinobu| Yasunaka, Tetsuya| Koike, Kazuko| Ikeda, Fusao| Shiraha, Hidenori| Nouso, Kazuhiro| Yamamoto, Kazuhide| |
|---|---|
| Published Date | 2012 |
| Publication Title | Digestion |
| Volume | volume86 |
| Issue | issue2 |
| Content Type | Journal Article |
| Author | Takayama, Hiroki| Miyake, Yasuhiro| Nouso, Kazuhiro| Ikeda, Fusao| Shiraha, Hidenori| Takaki, Akinobu| Kobashi, Haruhiko| Yamamoto, Kazuhide| |
|---|---|
| Published Date | 2011-01 |
| Publication Title | Journal of Gastroenterology and Hepatology |
| Volume | volume26 |
| Issue | issue1 |
| Content Type | Journal Article |
| JaLCDOI | 10.18926/AMO/52139 |
|---|---|
| FullText URL | 68_1_17.pdf |
| Author | Moritou, Yuki| Ikeda, Fusao| Iwasaki, Yoshiaki| Baba, Nobuyuki| Takaguchi, Kouichi| Senoh, Tomonori| Nagano, Takuya| Takeuchi, Yasuto| Yasunaka, Tetsuya| Ohnishi, Hideki| Miyake, Yasuhiro| Takaki, Akinobu| Nouso, Kazuhiro| Yamamoto, Kazuhide| |
| Abstract | The impact of hepatic steatosis on interferon therapy for patients with chronic hepatitis C (CHC) has been associated with single-nucleotide polymorphisms (SNP) of IL28B, patatin-like phospholipase domain-containing protein 3 (PNPLA3), and low-density lipoprotein (LDL) receptor. Whether this holds true for Japanese patients, however, remains unresolved. The present study prospectively enrolled 226 Japanese patients with CHC, and investigated the impact of hepatic steatosis and its related SNPs, including rs8099917 of IL28B, rs738409 of PNPLA3, and rs14158 of LDL receptor, on outcomes of peg-interferon and ribavirin therapy. In multivariate logistic regression analysis, significant factors affecting the severity of hepatic steatosis were high body mass index and the minor alleles of IL28B SNP (p＝0.020 and 0.039, respectively). The risk alleles of PNPLA3 SNP also showed weak association (p＝0.059). Severe steatosis and the minor alleles of IL28B SNP were significantly associated with null or partial virological response in patients with HCV genotype 1, as were female gender, and low LDL cholesterol (p＝0.049, and ＜0.001, respectively). The SNP genotype of PNPLA3 and LDL receptor did not have a significant impact on therapeutic outcomes. With respect to the SNP sites examined, the SNP of PNPLA3 has a weak association with severe hepatic steatosis, but not with the outcome of interferon therapy. |
| Keywords | hepatic steatosis genetic polymorphism interferon HCV |
| Amo Type | Original Article |
| Publication Title | Acta Medica Okayama |
| Published Date | 2014-02 |
| Volume | volume68 |
| Issue | issue1 |
| Publisher | Okayama University Medical School |
| Start Page | 17 |
| End Page | 22 |
| ISSN | 0386-300X |
| NCID | AA00508441 |
| Content Type | Journal Article |
| language | English |
| Copyright Holders | CopyrightⒸ 2014 by Okayama University Medical School |
| File Version | publisher |
| Refereed | True |
| PubMed ID | 24553484 |
| Web of Science KeyUT | 000331592800003 |
| Author | Kinugasa, Hideaki| Nouso, Kazuhiro| Takeuchi, Yasuto| Yasunaka, Tetsuya| Onishi, Hideki| Nakamura, Shin-ichiro| Shiraha, Hidenori| Kuwaki, Kenji| Hagihara, Hiroaki| Ikeda, Fusao| Miyake, Yasuhiro| Takaki, Akinobu| Yamamoto, Kazuhide| |
|---|---|
| Published Date | 2012-04 |
| Publication Title | Journal of Gastroenterology |
| Volume | volume47 |
| Issue | issue4 |
| Content Type | Journal Article |
| Author | Kubota, Junichi| Ikeda, Fusao| Terada, Ryo| Kobashi, Haruhiko| Fujioka, Shin-ichi| Okamoto, Ryoichi| Baba, Shinsuke| Morimoto, Youichi| Ando, Masaharu| Makino, Yasuhiro| Taniguchi, Hideaki| Yasunaka, Tetsuya| Miyake, Yasuhiro| Iwasaki, Yoshiaki| Yamamoto, Kazuhide| |
|---|---|
| Published Date | 2009-09 |
| Publication Title | Journal of Gastroenterology |
| Volume | volume44 |
| Issue | issue9 |
| Content Type | Journal Article |
| JaLCDOI | 10.18926/AMO/49042 |
|---|---|
| FullText URL | 66_6_461.pdf |
| Author | Koike, Kazuko| Takaki, Akinobu| Kato, Nobuyuki| Ouchida, Mamoru| Kanzaki, Hirotaka| Yasunaka, Tetsuya| Shiraha, Hidenori| Miyake, Yasuhiro| Yamamoto, Kazuhide| |
| Abstract | Hepatitis C virus (HCV) infection induces several changes in hepatocytes, such as oxidative stress, steatosis, and hepatocarcinogenesis. Although considerable progress has been made during recent years, the mechanisms underlying these functions remain unclear. We employed proteomic techniques in HCV replicon-harboring cells to determine the effects of HCV replication on host-cell protein expression. We examined two-dimensional electrophoresis (2-DE) and mass spectrometry to compare and identify differentially expressed proteins between HCV subgenomic replicon-harboring cells and their “cured” cells. One of the identified proteins was confirmed using enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. Full-length HCV genome RNA replicating and cured cells were also assessed using ELISA. Replicon-harboring cells showed higher expression of retinal dehydrogenase 1 (RALDH-1), which converts retinol to retinoic acid, and the cured cells showed higher expression of retinol-binding protein (RBP), which transports retinol from the liver to target tissues. The alteration in RBP expression was also confirmed by ELISA and Western blot analysis. We conclude that protein expression profiling demonstrated that HCV replicon eradication affected retinol-related protein expression. |
| Keywords | hepatitis C virus retinol-binding protein |
| Amo Type | Original Article |
| Publication Title | Acta Medica Okayama |
| Published Date | 2012-12 |
| Volume | volume66 |
| Issue | issue6 |
| Publisher | Okayama University Medical School |
| Start Page | 461 |
| End Page | 468 |
| ISSN | 0386-300X |
| NCID | AA00508441 |
| Content Type | Journal Article |
| language | English |
| Copyright Holders | CopyrightⒸ 2012 by Okayama University Medical School |
| File Version | publisher |
| Refereed | True |
| PubMed ID | 23254580 |
| Web of Science KeyUT | 000312966100005 |
