1.A Case of Acute Hepatitis B by Occult HBV Infection without HbsAg Seroconversion.
Hye Mi JUNG ; Dae Won JUN ; Ji Yeon MIN ; Eun Young DOO ; Kil Woo NAM ; Young Il KWON ; Oh Wan KWON
Korean Journal of Medicine 2012;83(5):619-623
Many studies have recently reported reactivation in hepatitis B surface antigen (HBsAg)-negative subjects with the use of biologic agents such as rituximab. However, occult hepatitis B virus infection itself has little clinical impact. We experienced a case of acute exacerbation caused by occult hepatitis B infection without HBsAg seroconversion. No mutation was found on the major hydrophilic loop of the S protein. The patient recovered from acute exacerbation after antiviral therapy. In conclusion, acute exacerbation can be induced by occult hepatitis B virus infection itself without reactivation. In such a case, antiviral therapy should be considered.
Antibodies, Monoclonal, Murine-Derived
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Hepatitis
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Hepatitis B
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Hepatitis B Surface Antigens
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Hepatitis B virus
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Humans
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Rituximab
3.Microbiological Contamination of Laboratory Mice and Rats in Korea from 2007 to 2008.
Young Suk WON ; Hyo Jung KWON ; Sang Woon KIM ; Jong Tak HAN ; Sae Bhom LEE ; Ki Hoan NAM ; Won Kee YOON ; Kang Hyun KIM ; Oc Sung MOON ; Hyoung Chin KIM
Laboratory Animal Research 2010;26(3):249-255
In order to assess the microbiological contamination of laboratory mice and rats in Korea over the 2-year period from 2007 to 2008, we monitored animals housed in mouse and rat facilities equipped with barrier systems. In a barrier animal facility in Korea, the most important viruses in the identified pathogen were the mouse hepatitis virus (MHV) and Pasteurella (Pa.) pneumotropica, and Staphylococcus aureus was identified as the most common bacterial pathogen in Korea. The most commonly detected parasite in the identified pathogen was Trichomonas spp. in the mouse facilities and Entamoeba spp. in the rat facilities. In many cases, these pathogen-contaminated animals were genetically modified animals obtained from the university. Currently, consistent with the increased transfer of genetically modified animals between domestic and foreign animal facilities, the Pa. pneumotropica and parasites infection rates were shown to have increased as compared to those of the 2004-2006 period. Indeed, the MHV infection rate has been maintained at almost 20% in Korean animal facilities over the past 10 years. These results showed that effective quarantine programs for contaminated genetically engineered mutant mice and the monitoring of regular or irregular MHV monitoring in animal colonies should help to reduce pathogen contamination in Korean animal facilities.
Animals
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Animals, Genetically Modified
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Entamoeba
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Korea
;
Mice
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Murine hepatitis virus
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Parasites
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Pasteurella
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Quarantine
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Rats
;
Sendai virus
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Staphylococcus aureus
;
Trichomonas
4.Microbiological Contamination of Laboratory Mice and Rats in Korea from 2007 to 2008.
Young Suk WON ; Hyo Jung KWON ; Sang Woon KIM ; Jong Tak HAN ; Sae Bhom LEE ; Ki Hoan NAM ; Won Kee YOON ; Kang Hyun KIM ; Oc Sung MOON ; Hyoung Chin KIM
Laboratory Animal Research 2010;26(3):249-255
In order to assess the microbiological contamination of laboratory mice and rats in Korea over the 2-year period from 2007 to 2008, we monitored animals housed in mouse and rat facilities equipped with barrier systems. In a barrier animal facility in Korea, the most important viruses in the identified pathogen were the mouse hepatitis virus (MHV) and Pasteurella (Pa.) pneumotropica, and Staphylococcus aureus was identified as the most common bacterial pathogen in Korea. The most commonly detected parasite in the identified pathogen was Trichomonas spp. in the mouse facilities and Entamoeba spp. in the rat facilities. In many cases, these pathogen-contaminated animals were genetically modified animals obtained from the university. Currently, consistent with the increased transfer of genetically modified animals between domestic and foreign animal facilities, the Pa. pneumotropica and parasites infection rates were shown to have increased as compared to those of the 2004-2006 period. Indeed, the MHV infection rate has been maintained at almost 20% in Korean animal facilities over the past 10 years. These results showed that effective quarantine programs for contaminated genetically engineered mutant mice and the monitoring of regular or irregular MHV monitoring in animal colonies should help to reduce pathogen contamination in Korean animal facilities.
Animals
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Animals, Genetically Modified
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Entamoeba
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Korea
;
Mice
;
Murine hepatitis virus
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Parasites
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Pasteurella
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Quarantine
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Rats
;
Sendai virus
;
Staphylococcus aureus
;
Trichomonas
5.Contribution of IL-17 to mouse hepatitis virus strain 3-induced acute liver failure.
Lin ZHU ; Tao CHEN ; Yulei LU ; Di WU ; Xiaoping LUO ; Qin NING
Journal of Huazhong University of Science and Technology (Medical Sciences) 2012;32(4):552-556
Recently, the Th17 cells and IL-17 have been shown to play a critical role in the immune-mediated liver injury in hepatitis B, while their functions in acute liver failure have not been well elucidated yet. In this study, we primarily investigated the role of IL-17 in the development of mouse hepatitis virus strain 3 (MHV-3)-induced acute liver failure. IL-17 mRNA levels in liver tissue were quantified by using quantitative real-time polymerase chain reaction, and cytokine IL-17 levels in liver tissue and serum were determined by using ELISA in MHV-3-induced murine fulminant hepatitis model. The IL-17 expression levels on CD4(+)T and CD8(+)T cells were determined by using flow cytometry. The correlation between IL-17 level and liver injury was studied. Th17 associated cytokines were also investigated by intracellular staining. Our results showed that the IL-17 expression was significantly elevated in the liver and serum of BALB/cJ mice infected with MHV-3. Moreover, a time course study showed that the percentage of both IL-17-producing CD4(+)T cells and IL-17-producing CD8(+)T cells was increased remarkably in the liver starting from 48 h and peaked at 72 h post-infection. There was a close correlation between hepatic or serum IL-17 concentration and the severity of liver injury defined by ALT level, respectively. Th17 associated cytokines, IL-6, IL-21 and IL-22, were also increased significantly at 72 h post-infection. It was concluded that IL-17 may contribute to the pathogenesis of MHV-3-induced acute liver failure.
Animals
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Female
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Hepatitis, Viral, Animal
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metabolism
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Interleukin-17
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metabolism
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Liver Failure, Acute
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metabolism
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virology
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Mice
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Mice, Inbred BALB C
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Murine hepatitis virus
;
metabolism
6.Establishment of a murine model of hepatic steatosis induced by chronic viral hepatitis.
Lu GAN ; Zhe ZHANG ; Jinqiang GUO ; Qian XIE ; Zijun MENG ; Weiren WAN ; Bingde LUO
Journal of Southern Medical University 2012;32(12):1722-1726
OBJECTIVETo establish a animal model of hepatic steatosis induced by chronic viral hepatitis in C(57)BL/6 mice.
METHODSC(57)BL/6 mice were randomly assigned to control group, high-fat diet group, mouse hepatitis virus strain A59 (MHV-A59) virus infection group, and high-fat diet plus virus infection group. At 13 weeks of the experiment, serum samples were collected to detect MHV antibodies and transaminase and lipid levels. The hepatic pathologies of the mice were examined with Oil red O staining of the frozen sections the and HE staining of paraffin-embedded sections.
RESULTSThe mice in the two virus infection groups showed strong positivity of MHV antibodies in the serum. Compared with the control group, the mice in high-fat diet group and the two virus infection groups had significantly increased AST and ALT levels with also elevated TC and LDL-C levels. The two virus infection groups both exhibited obvious pathologies in the liver characteristic of chronic viral hepatitis with increased lipid accumulation in the hepatocytes.
CONCLUSIONWe have successfully established a mouse model of hepatic steatosis induced by chronic viral hepatitis, which provides the basis for further study of the disease mechanism.
Animals ; Antibodies, Viral ; blood ; Chronic Disease ; Diet, High-Fat ; Disease Models, Animal ; Fatty Liver ; virology ; Hepatitis, Chronic ; virology ; Mice ; Mice, Inbred C57BL ; Murine hepatitis virus
7.Hepatitis B Virus Reactivation in a Surface Antigen-negative and Antibody-positive Patient after Rituximab Plus CHOP Chemotherapy.
Eui Bae KIM ; Dae Sik KIM ; Seh Jong PARK ; Yong PARK ; Kyoung Ho RHO ; Seok Jin KIM
Cancer Research and Treatment 2008;40(1):36-38
Rituximab is a monoclonal antibody that targets B-lymphocytes, and it is widely used to treat non-Hodgkin's lymphoma. However, its use has been implicated in HBV reactivation that's related with the immunosuppressive effects of rituximab. Although the majority of reactivations occur in hepatitis B carriers, a few cases of reactivation have been reported in HBsAg negative patients. However, reactivation in an HBsAg negative/ HBsAb positive patient after rituximab treatment has never been reported in Korea. We present here an HBsAg-negative/HBsAb-positive 66-year-old female who displayed reactivation following rituximab plus CHOP chemotherapy for diffuse large B-cell lymphoma. While she was negative for HBsAg at diagnosis, her viral status was changed at the time of relapse as follows: HBsAg positive, HBsAb negative, HBeAg positive, HBeAb negative and an HBV DNA level of 1165 pg/ml. Our observation suggests that we should monitor for HBV reactivation during rituximab treatment when prior HBV infection or occult infection is suspected, and even in the HBsAg negative/HBsAb positive cases.
Aged
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Antibodies, Monoclonal, Murine-Derived
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B-Lymphocytes
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DNA
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Female
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Hepatitis
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Hepatitis B
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Hepatitis B e Antigens
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Hepatitis B Surface Antigens
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Hepatitis B virus
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Humans
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Korea
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Lymphoma
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Lymphoma, B-Cell
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Lymphoma, Non-Hodgkin
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Organothiophosphorus Compounds
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Recurrence
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Rituximab
8.CD69+NK cells contribute to the murine hepatitis virus strain 3-induced murine hepatitis.
Lin DING ; Tao CHEN ; Xiao-jing WANG ; Li ZHOU ; Ai-chao SHI ; Qin NING
Journal of Huazhong University of Science and Technology (Medical Sciences) 2013;33(4):505-510
The role of hepatic CD69+ natural killer (NK) cells in virus-induced severe liver injury and subsequent hepatic failure is not well defined. In this study, a mouse model of fulminant liver failure (FHF) induced by murine hepatitis virus strain 3 (MHV-3) was used to study the role of hepatic CD69+NK cells in the development of FHF. The CD69 expression in NK cells in the liver, spleen, bone marrow and peripheral blood was detected by using flow cytometry. The correlation between the CD69 level in hepatic NK cells and liver injury was studied. The functional marker (CD107a), and activating and inhibitory receptor (NKG2D and NKG2A) expressed on CD69+NK cells and CD69-NK cells were detected by using flow cytometry. Pro-inflammatory cytokines (IL-9, IFN-γ and TNF-α) were also examined by using intracellular staining. After MHV-3 infection, the number of CD69+NK cells in the liver of BALB/cJ mice was increased markedly and peaked at 72 h post-infection. Similar changes were also observed in the spleen, bone marrow and peripheral blood. Meanwhile, the CD69 expression in hepatic NK cells was highly correlated with the serum level of ALT and AST. The expression of CD107a and NKG2D, as well as the production of TNF-α, IFN-γ and IL-9 in hepatic CD69+NK cells was all significantly up-regulated during 48-72 h post-infection. In contrast, the NKG2A expression was increased in hepatic CD69-NK cells but not in CD69+NK cells. These results suggested that hepatic CD69+NK cells play a pivotal role in the pathogenesis of FHF by enhancing degranulation and cytotoxic ability of NK cells and increasing the production of pro-inflammatory cytokines.
Animals
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Antigens, CD
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immunology
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Antigens, Differentiation, T-Lymphocyte
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immunology
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Coronavirus Infections
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immunology
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Female
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Hepatitis, Viral, Animal
;
immunology
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Killer Cells, Natural
;
immunology
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Lectins, C-Type
;
immunology
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Mice
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Mice, Inbred BALB C
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Murine hepatitis virus
;
immunology
9.KCTD9, a novel potassium channel related gene, was highly expressed in hepatic NK cells and T cells of fulminant hepatitis mice induced by MHV-3.
Yao-Yong ZHOU ; Yong ZOU ; Tao CHEN ; Hong-wu WANG ; Mei-fang HAN ; Bin PI ; Wei-ming YAN ; Dong XI ; Jia-quan HUANG ; Xiao-ping LUO ; Qin NING
Chinese Journal of Hepatology 2011;19(11):833-837
OBJECTIVETo explore the mechanisms of a novel potassium channel gene named KCTD9 (potassium channel tetramerization domain containing 9) in model of fulminant viral hepatitis induced by murine hepatitis virus 3 (MHV-3).
METHODS78 BALB/cJ mice(6 male) were randomly and equally assigned to two groups, model group of fulminant viral hepatitis induced by MHV3 and its control. 75 C3H/HeJ female mice were done into two groups, 39 for model group of chronic hepatitis induced by MHV3, 36 for control. Various samples including spleen, liver and lymphocytes from mice of two model groups and the controls were examined for KCTD9 expression by real time quantitative PCR and Immunohistochemistry. Independent-samples T test or one-way ANOVA were carried out in different groups.
RESULTSIncreased expressions of KCTD9 mRNA was observed in livers of both model mice of fulminant viral hepatitis and chronic hepatitis. Compared with the control mice, the expressions of KCTD9 mRNA were up-regulated by 577.1-, 8.8-, 59.4- and 10.8-fold in hepatic NK cells, CD4+ T cells, CD8+ T cells and splenic NK cells respectively in model mice of fulminant viral hepatitis 48 hr post MHV-3 infection, whereas down-regulation by 43% and 69% in splenic CD4 + T cells and CD8+ T cells were found respectively. In contrast, in model mice of chronic viral hepatitis the expressions of KCTD9 mRNA were down-regulated by 71% and 51% in hepatic CD4+ T cells and NK cells, respectively. The expression of KCTD9 protein was mainly evidenced in infiltrative mononuclear cells of liver as shown by immunohistochemistry. Basal expression was also investigated and showed constitutive expression of KCTD9 in brain, thymus and other organs in BALB/cJ mice.
CONCLUSIONA novel potassium channel gene KCTD9 was highly expressed in hepatic NK cells and T cells of fulminant hepatitis mice induced by MHV-3.
Animals ; CD4-Positive T-Lymphocytes ; immunology ; metabolism ; Female ; Hepatitis, Viral, Animal ; immunology ; metabolism ; virology ; Killer Cells, Natural ; immunology ; metabolism ; Liver ; metabolism ; virology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C3H ; Murine hepatitis virus ; Potassium Channels ; genetics ; metabolism
10.Construction of MHV-A59 damp-heat mouse model and analysis of the relevant indices.
Zhao-hui TANG ; Li-xian SU ; Hua-feng LI ; Jin-qiang GUO ; Bing-de LUO ; Pei-zheng LIN
Journal of Southern Medical University 2010;30(11):2452-2454
OBJECTIVETo explore the impact of inflammation, water metabolism and immune function on the establishment of a mouse model of damp-heat syndrome with MHV-A59 infection.
METHODSTwenty-four mice were randomly divided into control group, virus group, damp-heat group and model group. The peripheral blood CD4(+) and CD8(+) lymphocytes were detected by flow cytometry, and the serum levels of IFN-γ and IL-4 were assayed by ELISA. The expressions of NF-κB and AQP4 in the liver and stomach were determined using immunohistochemistry.
RESULTSThe expression of NF-κB and CD4(+)/CD8(+) ratio in the virus and model groups were significantly higher than those in the damp-heat and control groups, while the expression of AQP4 was significantly higher in the model and damp-heat groups than in the other groups. Compared with the control group, the model group showed a significantly higher ratio of IFN-γ/IL-4.
CONCLUSIONSMHV-A59 virus is the main cause of elevated NF-κB expression and CD4(+)/CD8(+)/ ratio, while damp-heat syndrome is responsible for increased AQP4 expression, and their synergistic effect results in increased IFN-γ/IL-4 ratio. The mouse model established using MHV-A59 virus and the damp-heat factors can mimic damp-heat syndrome described in traditional Chinese medicine theory.
Animals ; Aquaporin 4 ; metabolism ; CD4-CD8 Ratio ; Disease Models, Animal ; Hepatitis, Viral, Animal ; diagnosis ; virology ; Interferon-gamma ; blood ; Interleukin-4 ; blood ; Male ; Medicine, Chinese Traditional ; Mice ; Mice, Inbred BALB C ; Murine hepatitis virus ; NF-kappa B p50 Subunit ; metabolism