Author Iwamuro, Masaya| Okada, Hiroyuki| Harada, Keita| Kanzaki, Hiromitsu| Hori, Keisuke| Kita, Masahide| Kawano, Seiji| Kawahara, Yoshiro| Tanaka, Takehiro| Yamamoto, Kazuhide|
Published Date 2016-12-01
Publication Title Journal of Okayama Medical Association
Volume volume128
Issue issue3
Content Type Journal Article
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
Published Date 2015-06
Publication Title Acta Medica Okayama
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 英語
Copyright Holders CopyrightⒸ 2015 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 26101189
Web of Sience KeyUT 000356903000002
Author Onji, Masahiro| Kanno, Atsuo| Saitoh, Shin-Ichiroh| Fukui, Ryutaro| Motoi, Yuji| Shibata, Takuma| Matsumoto, Fumi| Lamichhane, Aayam| Sato, Shintaro| Kiyono, Hiroshi| Yamamoto, Kazuhide| Miyake, Kensuke|
Published Date 2013-06
Publication Title Nature Communications
Volume volume4
Content Type Journal Article
JaLCDOI 10.18926/AMO/31695
FullText URL fulltext.pdf
Author Yoshioka, Masao| Mizuno, Motowo| Morisue, Yoshiko| Shimada, Morizou| Hirai, Michio| Nasu, Junichirou| Okada, Hiroyuki| Sakaguchi, Kousaku| Yamamoto, Kazuhide| Tsuji, Takao|
Abstract <p>In autoimmune chronic active hepatitis (AIH) and primary biliary cirrhosis (PBC), various autoantibodies including anti-asialoglycoprotein receptor (ASGPR) antibodies have been found in patients' sera. We have previously developed a mouse monoclonal antibody against rat and human ASGPR. In this study, we developed a capture enzyme-linked immunosorbent assay (ELISA) for detection of anti-ASGPR antibodies using this monoclonal antibody and investigated the occurrence of anti-ASGPR antibodies in the sera of patients with various liver diseases. Serum samples were obtained from 123 patients with various liver diseases, including 21 patients with AIH and 40 patients with PBC. In this capture ELISA, the target antigen in the crude rat liver membrane extracts was captured on the ELISA wells by the ASGPR-specific mouse monoclonal antibody. Thus, the cumbersome process of antigen purification was rendered unnecessary. Using this capture ELISA, we detected the anti-ASGPR antibody in 67% of the patients with AIH, in 100% of the patients with PBC, and in 57% of the patients with acute hepatitis type A. However, the anti-ASGPR antibody was rarely detected in patients with other liver diseases such as primary sclerosing cholangitis and obstructive jaundice. Our findings suggest that this capture ELISA would be useful for the detection of anti-ASGPR antibodies in autoimmune liver diseases.</p>
Keywords autoimmue hepatitis primary biliary cirrhosis asialoglycoprotein receptor autoantibodies
Amo Type Article
Published Date 2002-04
Publication Title Acta Medica Okayama
Volume volume56
Issue issue2
Publisher Okayama University Medical School
Start Page 99
End Page 105
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 12002624
Web of Sience KeyUT 000175176900006
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 Kanzaki, Hiromitsu| Uedo, Noriya| Ishihara, Ryu| Nagai, Kengo| Matsui, Fumi| Ohta, Takashi| Hanafusa, Masao| Hanaoka, Noboru| Takeuchi, Yoji| Higashino, Koji| Iishi, Hiroyasu| Tomita, Yasuhiko| Tatsuta, Masaharu| Yamamoto, Kazuhide|
Published Date 2012-06
Publication Title Helicobacter
Volume volume17
Issue issue3
Content Type Journal Article
JaLCDOI 10.18926/AMO/30943
FullText URL fulltext.pdf
Author Miyake, Yasuhiro| Yamamoto, Kazuhide|
Abstract <p>Autoimmune hepatitis (AIH) is a chronic and progressive disease characterized by histological interface hepatitis, hypergammaglobulinemia, and circulating autoantibodies. Multiple factors, including molecular mimicry, a genetic background including major histocompatibility complex class II, and defective function of regulatory T-cells, are involved in the pathogenesis. The diagnosis is made based on the scoring system of the International Autoimmune Hepatitis Group, the sensitivity and specificity of which are90%, respectively. AIH is classified into 3 sub-types based on the profiles of circulating autoantibodies: anti-nuclear antibody and/or smooth muscle antibody-positive (type 1), anti-liver-kidney microsomal antibody-positive (type 2), and anti-soluble liver antigen/liver-pancreas antigen antibody- positive (type 3). Recently, however, the number of atypical cases lacking the usual features has increased-for example, patients with acute-onset or fulminant-type AIH, autoantibody-negative patients, male patients, and patients with bile duct injury-and thus the clinical features of AIH have been diversified. AIH is responsive to immunosuppressive treatment in most cases; however, relapse occurs in more than 80% of patients within 1 year after immunosuppressive treatment withdrawal. The 10-year survival rate and the 10-year hepatocellular carcinoma-free rate are90%, respectively, indicating that some patients reach liver failure or develop hepatocellular carcinoma. To improve the prognosis of these patients, persistent normalization of transaminase is required.</p>
Keywords autoimmune hepatitis epidemiology pathogenesis diagnosis prognosis
Amo Type Review
Published Date 2008-08
Publication Title Acta Medica Okayama
Volume volume62
Issue issue4
Publisher Okayama University Medical School
Start Page 217
End Page 226
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 18766204
Web of Sience KeyUT 000258680900001
Author Saito, Shunsuke| Kato, Jun| Hiraoka, Sakiko| Horii, Joichiro| Suzuki, Hideyuki| Higashi, Reiji| Kaji, Eisuke| Kondo, Yoshitaka| Yamamoto, Kazuhide|
Published Date 2011-09
Publication Title Inflammatory Bowel Diseases
Volume volume17
Issue issue9
Content Type Journal Article
Author Matsubara, Minoru| Shiraha, Hidenori| Kataoka, Jyunro| Iwamuro, Masaya| Horiguchi, Shigeru| Nishina, Shin-ichi| Takaoka, Nobuyuki| Uemura, Masayuki| Takaki, Akinobu| Nakamura, Shinichiro| Kobayashi, Yoshiyuki| Nouso, Kazuhiro| Yamamoto, Kazuhide|
Published Date 2012-10
Publication Title Journal of Gastroenterology and Hepatology
Volume volume27
Issue issue10
Content Type Journal Article
Author Fujikawa, Tatsuya| Shiraha, Hidenori| Yamamoto, Kazuhide|
Published Date 2009-04-01
Publication Title 岡山医学会雑誌
Volume volume121
Issue issue1
Content Type Journal Article
Author Hirakawa, Tomoko| Kato, Jun| Okumura, Yoshihiro| Hori, Keisuke| Takahashi, Sakuma| Suzuki, Hideyuki| Akita, Mitsuhiro| Higashi, Reiji| Saito, Shunsuke| Kaji, Eisuke| Uraoka, Toshio| Hiraoka, Sakiko| Yamamoto, Kazuhide|
Published Date 2012-02
Publication Title Journal of Gastroenterology
Volume volume47
Issue issue2
Content Type Journal Article
JaLCDOI 10.18926/AMO/31715
FullText URL fulltext.pdf
Author Hirai, Michio| Mizuno, Motowo| Morisue, Yoshiko| Yoshioka, Masao| Shimada, Morizou| Nasu, Junichirou| Okada, Hiroyuki| Shimomura, Hiroyuki| Yamamoto, Kazuhide| Tsuji, Takao|
Abstract <p>Anti-idiotype antibodies (Ab2) play an important role in the homeostasis of immune responses and are related to the development and the disease activity of certain autoimmune diseases. The asialoglycoprotein receptor (ASGPR) is considered one of the target antigens in the pathogenesis of autoimmune chronic active hepatitis (AIH). We previously developed a mouse monoclonal antibody (clone 8D7) which recognizes rat and human ASGPR. In this study, to help investigate the anti-ASGPR antibody-anti-idiotype antibody network in patients with AIH, we developed a syngeneic mouse monoclonal Ab2 to the 8D7 anti-ASGPR antibody (Ab1). One clone, designated as 3C8, tested positive for specific reactivity to 8D7-Ab1 and did not bind to other irrelevant immunoglobulins. By competitive inhibition assays, the binding of 8D7-Ab1 to liver membrane extracts, i.e., the crude antigen preparation, was inhibited by 3C8-Ab2 in a dose-dependent manner, and the binding of 8D7-Ab1 to 3C8-Ab2 was inhibited by the liver membrane extracts. In the immunohistochemical analysis, 3C8-Ab2 blocked the specific staining of sinusoidal margins of rat hepatocytes by 8D7-Ab1. These results suggest that 3C8 anti-idiotype antibody recognizes the specific idiotypic determinants within the antigen-binding site of 8D7-Ab1.</p>
Keywords anti-idiotype antibody autoimmune hepatitis asialoglycoprotein receptor monoclonall antibody
Amo Type Article
Published Date 2002-06
Publication Title Acta Medica Okayama
Volume volume56
Issue issue3
Publisher Okayama University Medical School
Start Page 135
End Page 139
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 12108584
Web of Sience KeyUT 000176521200003
Author Higashi, Reiji| Uraoka, Toshio| Kato, Jun| Kuwaki, Kenji| Ishikawa, Shin| Saito, Yutaka| Matsuda, Takahisa| Ikematsu, Hiroaki| Sano, Yasushi| Suzuki, Seiyuu| Murakami, Yoshitaka| Yamamoto, Kazuhide|
Published Date 2010-07
Publication Title Gastrointestinal Endoscopy
Volume volume72
Issue issue1
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
Published Date 2012-12
Publication Title Acta Medica Okayama
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 英語
Copyright Holders CopyrightⒸ 2012 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 23254580
Web of Sience KeyUT 000312966100005
Author Tatsukawa, Masashi| Takaki, Akinobu| Shiraha, Hidenori| Koike, Kazuko| Iwasaki, Yoshiaki| Kobashi, Haruhiko| Fujioka, Shin-Ichi| Sakaguchi, Kohsaku| Yamamoto, Kazuhide|
Published Date 2011-10-21
Publication Title BMC Cancer
Volume volume11
Content Type Journal Article
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
Published Date 2014-10
Publication Title Acta Medica Okayama
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 英語
Copyright Holders CopyrightⒸ 2014 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 25338486
Web of Sience KeyUT 000343269300006
Related Url http://ousar.lib.okayama-u.ac.jp/metadata/53129
Author Takahara, Masahiro| Nemoto, Yasuhiro| Oshima, Shigeru| Matsuzawa, Yu| Kanai, Takanori| Okamoto, Ryuichi| Tsuchiya, Kiichiro| Nakamura, Tetsuya| Yamamoto, Kazuhide| Watanabe, Mamoru|
Published Date 2013-12
Publication Title Immunology Letters
Volume volume156
Issue issue1-2
Content Type Journal Article
Author Yagi, Toru| Kawahara, Yoshiro| Okada, Hiroyuki| Takemoto, Koji| Kato, Jun| Kobayashi, Yoshiyuki| Kawamoto, Hirofumi| Yamamoto, Kazuhide|
Published Date 2008-01-04
Publication Title 岡山医学会雑誌
Volume volume119
Issue issue3
Content Type Journal Article
JaLCDOI 10.18926/AMO/31684
FullText URL fulltext.pdf
Author Ariyoshi, Masanori| MIzuno, Motowo| Morisue, Yoshiko| Shimada, Morizou| Fujita, Shirou| Nasu, Junichirou| Okada, Hiroyuki| Shimomura, Hiroyuki| Yamamoto, Kazuhide| Tsuji, Takao|
Abstract <p>We developed a monoclonal antibody (MoAb) (clone 5E8) against an antigen on the bile canalicular membrane of rat hepatocyte. By immunoblotting, MoAb 5E8 detected a band of 110 kD. In this study, we used the phage display technique to identify the target antigen recognized by MoAb 5E8. We screened a random phage display library expressing 12-mer peptide sequences and identified a peptide sequence, FHFNPYTGHPLT, as an epitope. We compared this peptide sequence with those of dipeptidyl peptidase IV (DPP IV, E.C.3.4.14.5) and Cell-CAM105, which proteins were located by a database search based on the information of tissue localization and approximate molecular weight of the MoAb 5E8 antigen, and sequence similarity with a region in DPP IV (amino acids 225-233) but not with Cell-CAM105 was found. In addition, we immunohistochemically stained various tissues (liver, small intestine, and kidney) of Japanese Fischer 344 rats, known to be deficient for DPP IV, with MoAb 5E8 and showed that the expression of MoAb 5E8 antigen was negligible or weak. In contrast, tissues sampled from the same organs of Sprague-Dawley rats, known to express DPP IV, were positively stained. These findings suggest that the antigen recognized by MoAb 5E8 is DDPIV and its major epitope is located in amino acids at positions 225-233.</p>
Keywords random phage display library dipeptidyl petidase IV monoclonal antibody epitope bile canalicular membrane
Amo Type Article
Published Date 2002-08
Publication Title Acta Medica Okayama
Volume volume56
Issue issue4
Publisher Okayama University Medical School
Start Page 187
End Page 191
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 12199523
Web of Sience KeyUT 000177382600003
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
Published Date 2014-02
Publication Title Acta Medica Okayama
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 英語
Copyright Holders CopyrightⒸ 2014 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 24553484
Web of Sience KeyUT 000331592800003