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Noninvasive estimation of liver fibrosis and response to interferon therapy by a serum fibrogenesis marker, YKL-40, in patients with HCV-associated liver disease

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World Journal of Gastroenterology 2005年第4期11卷 476-481页

作者： Yukiko Saitou Katsuya Shiraki Yutaka Yamanaka Yumi Yamaguchi Tomoyuki Kawakita norihiko yamamoto Kazushi Sugimoto Kazumoto Murata Takeshi Nakano First Department of Internal Medicine Mie University School of Medicine TsuMie 514-8507Japan

AIM: To evaluate the clinical utility of serum fibrosis markers,including YKL-40, in patients with HCV-associated liver disease.METHODS: A total of 109 patients with HCV-associated liver disease were enrolled. We measured serum type Ⅳ collagen, amino-terminal peptide of type Ⅲ procollagen (PⅢP),hyaluronic acid (HA), YKL-40 levels and biochemical.Parameters by RIA or ELISA. Eighty-eight patients underwent liver biopsy, and 67 of 109 patients received interferon (IFN)therapy. We also investigated the relationship between the concentrations of serum fibrosis markers and histological fibrosis scores (METAVIR), and evaluated the changes of the levels of fibrosis markers before and after the IFN therapy.RESULTS: The increase in serum levels of all markers,particularly HA, was correlated with the progression of liver fibrosis (for type Ⅳ collagen, F= 9.076, P＜0.0001; for PⅢP,F= 9.636, P＜0.0001; for HA, F= 13.128, P＜0.0001; and for YKL-40, F= 8.016, P＜0.0001). YKL-40 had strong correlation with HA (r= 0.536, P＜0.0001). Based on the receiver operating curve (ROC), the ability of serum HA exceeded the abilities of other serum markers to determine fibrosis score 4 from fibrosis score 0-3 (AUC = 0.854). While YKL-40 was superior to other fibrosis markers for predicting severe fibrosis (F2-F4) from mild fibrosis (F0-F1) (YKL-40, AUC = 0.809;HA, AUC = 0.805). After IFN therapy, only YKL-40 values significantly decreased not only in the responder group,but also in the nonresponder group (P = 0.03).CONCLUSION: YKL-40 may be a useful non-invasive serum marker to estimate the degree of liver fibrosis and to evaluate the efficacy of IFN therapies in patients with HCV-associated liver disease.

关键词： HA HCV IFN AUC ROC PⅢP RIA AIM

Augmentation of tumor necrosis factor family-induced apoptosis by E3330 in human hepatocellular carcinoma cell lines via inhibition of NFκB

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World Journal of Gastroenterology 2005年第40期11卷 6258-6261页

作者： Yukiko Saitou Katsuya Shiraki Takenari Yamanaka Kazumi Miyashita Tomoko Inoue Yutaka Yamanaka Yumi Yamaguchi Naoyuki Enokimura norihiko yamamoto Keiichi Itou Kazushi Sugimoto Takeshi Nakano First Department of Internal Medicine

AIM: To investigate the reduction of cell viability in human hepatocellular carcinoma (HCC) cell lines induced by inhibition of nuclear factor κB (NFκB). METHODS: HLE, SKHep1, and HepG2 were incubated and E3330 was used to compare the stimulation of some chemotherapeutic drugs with that of TNF family, Fas ligand, TNFα and TNF-related apoptosis-inducing ligand (TRAIL) at the point of the reduction of cell viability by inhibiting NFκB. RESULTS: E3330 decreased NFκB levels in HLE cells stimulated by TNF and TRAIL. The cytotoxicity of the combination of TRAIL, TNFα, Fas ligand, and E3330 increased synergistically in a dose-dependent manner compared to either E3330 alone in all HCC cell lines by MTT assay. However, the combination of some chemotherapeutic drugs and E3330 did not decrease the cell viability. CONCLUSION: Inhibition of NFκB sensitizes human HCC cell lines to TNF-mediated apoptosis including TRAIL, and TRAIL-based tumor therapy might be a powerful potential therapeutic tool in the treatment of human HCC.

关键词：肿瘤坏死因子肝细胞癌 E3330 肿瘤细胞

Risk factors for the recurrence of hepatocellular carcinoma after radiofrequency ablation of hepatocellular carcinoma in patients with hepatitis C

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World Journal of Gastroenterology 2005年第14期11卷 2174-2178页

作者： Yutaka Yamanaka Katsuya Shiraki Kazumi Miyashita Tomoko Inoue Tomoyuki Kawakita Yumi Yamaguchi Yukiko Saitou norihiko yamamoto Takeshi Nakano Atsuhiro Nakatsuka Koichiro Yamakado Kan Takeda First Department of Internal Medicine Mie University School of Medicine 2-174 EdobashiTsuMie 514-8507Japan Department of Radiology Mie University School of Medicine 2-174 EdobashiTsuMie 514-8507Japan

AIM: To analyze the risk factors of hepatocellular carcinoma (HCC) recurrence after radiofrequency ablation (RFA) treatment with HCV-associated hepatitis. METHODS: Twenty-six patients with HCV-associated HCC who were followed-up for more than 12 mo were selected for this study. Risk factors for distant intrahepatic recurrences of HCC were evaluated for patients in whom complete coagulation was achieved without recurrence in the same subsegment as the primary nodule. Twelve clinical and tumoral factors were examined: Age, gender, nodule diameter, number of primary HCC nodule, Child-Pugh classification, serum platelet, serum albumin, serum AST, post RFA AST, serum ALT, post RFA ALT, post RFA treatment.RESULTS: Distant recurrences of HCC in remnant liver after RFA were observed in 14 cases and in the number of primary HCC nodules (P = 0.047), and the serum platelets (P = 0.030), the clear difference came out by the recurrence group and the non-recurrence group. The cumulative recurrence rates after 1 and 2 years were30.8% and 86.8%, respectively for primary multinodular HCC, and 15.4% and 29.5% respectively, for primary uninodular HCC. In addition the 1-year recurrence rates for patients with serum albumin more than 3.4 g/dL and less than 3.4 g/dL were 23.1% for both, but the 2-years recurrence rates were 89.0% and 23.1%, respectively. The number of primary HCC nodules (relative risk, 6.970; P = 0.016) were found to be a statistically significant predictor for poor distant intrahepatic recurrence by univariate analysis.CONCLUSION: Patients who have multiple HCC nodules, low serum platelets and low serum albumin accompanied by HCV infection, should be carefully followed because of the high incidence of new HCC lesions in the remnant liver, even if coagulation RFA is complete.

关键词：肝细胞肿瘤射频消融丙型肝炎疾病传染

Functional expression of a proliferation-related ligand in hepatocellular carcinoma and its implications for neovascularization

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World Journal of Gastroenterology 2005年第30期11卷 4650-4654页

作者： Hiroshi Okano Katsuya Shiraki Yutaka Yamanaka Hidekazu Inoue Tomoyuki Kawakita Yukiko Saitou Yumi Yamaguchi Naoyuki Enokimura Keiichi Ito norihiko yamamoto Kazushi Sugimoto Kazumoto Murata Takeshi Nakano First Department of Internal Medicine

AIM: To detect the expression of a proliferation-related ligand on human hepatocellular carcinoma (HCC) cell lines (SK-Hep1, HLE and HepG2) and in culture medium.METHODS: APRIL expression was analyzed by Western blotting in HCC cell lines. Effects of APRIL to cell count and angiogenesis were analyzed, too.RESULTS: Recombinant human APRIL (rhAPRIL) increased cell viability of HepG2 cells and, in HUVEC, rhAPRIL provided slight tolerance to cell death from serum starvation. Soluble APRIL (sAPRIL) from HLE cells increased after serum starvation, but did not change in SK-Hep1 or HepG2 cells. These cells showed down-regulation of VEGF after incubation with anti-APRIL antibody.Furthermore, culture medium from the HCC cells treated with anti-APRIL antibody treatment inhibited tube formation of HUVECs.CONCLUSION: Functional expression of APRIL might contribute to neovascularization via an upregulation of VEGF in HCC.

关键词：功能表达增殖相关性配合基肝细胞癌血管形成病理机制

Genetic Characterization of Streptococcus pyogenes emm89 Strains Isolated in Japan From 2011 to 2019

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Infectious Microbes & Diseases 2020年第4期2卷 160-166页

作者： Yujiro Hirose Masaya Yamaguchi norihiko Takemoto Tohru Miyoshi-Akiyama Tomoko Sumitomo Masanobu Nakata Tadayoshi Ikebe Tomoki Hanada Takahiro Yamaguchi Ryuji Kawahara Rumi Okuno Hitoshi Otsuka Yuko Matsumoto Yuji Terashima Yu Kazawa Noriko Nakanishi Kaoru Uchida Yumi Akiyama Kaori Iwabuchi Chikara Nakagawa Kazunari yamamoto Victor Nizet Shigetada Kawabata Department of Oral and Molecular Microbiology Osaka University Graduate School of DentistrySuitaOsakaJapan Department of Pediatrics University of California at San Diego School of MedicineLa JollaCAUSA Department of Infectious Diseases Research InstituteNational Center for Global Health and MedicineTokyoJapan Department of Oral Microbiology Kagoshima University Graduate School of Medical and Dental SciencesKagoshimaJapan Department of Bacteriology I National Institute of Infectious DiseasesTokyoJapan Division of Microbiology Osaka Institute of Public HealthOsaka CityOsakaJapan Department of Microbiology Tokyo Metropolitan Institute of Public HealthTokyoJapan Department of Public Health Sciences Yamaguchi Prefectural Institute of Public Health and Environment Yamaguchi CityYamaguchiJapan Microbiological Testing and Research Division Yokohama City Institute of Public HealthYokohamaKanagawaJapan Department of Microbiology Fukushima Prefectural Institute of Public HealthFukushima CityFukushimaJapan Department of Infectious Diseases Kobe Institute of HealthKobeHyogoJapan Department of Bacteriology Toyama Institute of HealthImizuToyamaJapan Infectious Disease Research Division Hyogo Prefectural Institute of Public Health ScienceKakogawaHyogoJapan Department of Health Science Iwate Prefectural Research Institute for Environmental Sciences and Public HealthMoriokaIwateJapan Division of Microbiology Kyoto City Institute of Health and Environmental SciencesKyoto CityKyotoJapan Niigata City Institute of Public Health and the Environment Niigata CityNiigataJapan Skaggs School of Pharmaceutical Sciences University of California at San DiegoLa JollaCAUSA.

Invasive infection caused by Streptococcus pyogenes emm89 strains has been increasing in several countries linked to a recently emergent clade of emm89 strains,designated clade 3.In Japan,the features of emm89 S.pyogenes strains,such as clade classification,remains unknown.In this study,we collected emm89 strains isolated from both streptococcal toxic shock syndrome(STSS)(89 STSS isolates)and noninvasive infections(72 non-STSS isolates)in Japan from 2011 to 2019,and conducted wholegenome sequencing and comparative analysis,which resulted in classification of a large majority into clade 3 regardless of disease severity.In addition,invasive disease-associated factors were found among emm89 strains,including mutations of control of virulence sensor,and absence of the hylP1 gene encoding hyaluronidase.These findings provide new insights into genetic features of emm89 strains.

关键词： clade 3 emm89 streptococcal toxic shock syndrome Streptococcus pyogenes

Non-Hodgkin’s lymphoma: A case of testis lymphoma metastasized to the gallbladder

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Open Journal of Internal Medicine 2012年第1期2卷 11-14页

作者： Yutaka Tsutsumi Reiki Ogasawara Fumiyasu yamamoto Yutaka Yamada Yasuyuki Komatsu Kazuhiko Ichiki Shinich Ito Nobuaki Kurauchi Kazuhiro Kudo norihiko Shimoyama Junji Tanaka Masahiro Asaka Masahiro Imamura Hirohito Naruse Nobuo Masauzi Department of Clinical Pathology Hakodate Municipal Hospital Hakodate Japan Department of Gastroentelology Hokkaido University Graduate School of Medicine Sapporo Japan Department of Gastroenterology Hakodate Municipal Hospital Hakodate Japan Department of Hematology and Oncology Hokkaido University Graduate School of Medicine Sapporo Japan Department of Internal Medicine Hakodate Municipal Hospital Hakodate Japan Department of Surgery Hakodate Municipal Hospital Hakodate Japan Department of Urology Hakodate Municipal Hospital Hakodate Japan

Testis lymphoma (diffuse large B cell lymphoma) metastasized to the gallbladder. The gall bladder is rarely involved in cases of the malignant lymphoma, and lymphoma metastasis from the testis to the gallbladder has not been previously reported. These reports may possibly change by the introduction of PET/CT. Furthermore, although it was a struggle to diagnose this particular case, there is a possibility that we may have been able to recognize metastasis from the testis at an earlier stage if PET/CT had been conducted.

关键词： Testis Lymphoma Gallbladder PET/CT