High-mobility group box 1 (HMGB1), an abundant nuclear protein that triggers host immune responses, is an endogenous danger signal involved in the pathogenesis of various infectious agents. However, its role in hepatitis C virus (HCV) infection is not known. Here, we show that HMGB1 protein is translocated from the nucleus to cytoplasm and subsequently is released into the extracellular milieu by HCV infection. Secreted HMGB1 triggers antiviral responses and blocks HCV infection, a mechanism that may limit HCV propagation in HCV patients. Secreted HMGB1 also may have a role in liver cirrhosis, which is a common comorbidity in HCV patients. Further investigations into the roles of HMGB1 in the diseases caused by HCV infection will shed light on and potentially help prevent these serious and prevalent HCV-related diseases.Hepatitis C virus (HCV) is one of the major causative agents of hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC) (17, 30). More than 170 million people are estimated to suffer from HCV infection worldwide (17). Chronic and persistent infection is a characteristic feature of HCV pathogenesis (30). During chronic infection, the production of virus particles is limited, and a restricted number of liver cells are infected. As a result, the viral dose in patients' blood generally is lower than that of other hepatitis-causing viruses, such as hepatitis B virus (HBV) (4). Moreover, a large portion of hepatocytes often remains uninfected by the virus even after long-term infection (28). These phenomena indicate the existence of balance between the HCV infection process and host mechanisms that protect against HCV infection. We speculate that innate and adaptive immunities contribute to the balance between infection and protection.High-mobility group box 1 (HMGB1) protein is a highly conserved nuclear protein that participates in DNA organization and the regulation of transcription. In addition to its nuclear function, HMGB1 plays an important role as a cytokine, mediating the responses to infection, injury, and inflammation (1, 2, 29, 42). HMGB1 is released passively from necrotic cells and is actively secreted from activated immune cells, such as macrophages, natural killer cells, and mature dendritic cells (2). The functionality of actively secreted HMGB1 is known to be modulated by posttranslational modifications, such as oxidation (2, 36). Extracellular HMGB1 can function by itself and/or in association with other molecules, including CpG DNA, lipopolysaccharide (LPS), and interleukin-1 (IL-1) (5). HMGB1 induces a variety of cellular responses that contribute to innate immunity, tissue repair, and cell migration through interactions with various receptors that activate multiple signal transduction responses. The Toll-like receptors (e.g., TLR2, TLR4, and TLR9) and the receptor for advanced glycation end products (RAGE) are known receptors for the cytokine functions of HMGB1 (2). TLR4, the major component of the LPS recognition receptor complex, engages in downstream signaling through My...
Infectious mononucleosis due to Epstein-Barr virus (EBV) infection sometimes causes acute hepatitis, which is usually self-limiting with mildly elevated transaminases, but rarely with jaundice. Primary EBV infection in children is usually asymptomatic, but in a small number of healthy individuals, typically young adults, EBV infection results in a clinical syndrome of infectious mononucleosis with hepatitis, with typical symptoms of fever, pharyngitis, lymphadenopathy, and hepatosplenomegaly. EBV is rather uncommonly confirmed as an etiologic agent of acute hepatitis in adults. Here, we report two cases: the first case with acute hepatitis secondary to infectious mononucleosis and a second case, with acute hepatitis secondary to infectious mononucleosis concomitantly infected with hepatitis A. Both cases involved young adults presenting with fever, pharyngitis, lymphadenopathy, hepatosplenomegaly, and atypical lymphocytosis confirmed by serologic tests, liver biopsy and electron microscopic study.
PurposeTo evaluate the diagnostic accuracy of computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography/computed tomography (PET/CT) in predicting pelvic lymph node (LN) metastases in patients with cervical cancer.Materials and MethodsFrom January 2009 to March 2015, 114 patients with FIGO stage IA1-IIB uterine cervical cancer who underwent hysterectomy with pelvic lymphadenectomy and took CT, MRI, and PET/CT before surgery were enrolled in this study. The criteria for LN metastases were a LN diameter ≥1.0 cm and/or the presence of central necrosis on CT, a LN diameter ≥1.0 cm on MRI, and a focally increased FDG uptake on PET/CT. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for pelvic LN metastases were estimated.ResultsThe sensitivity, specificity, PPV, NPV, and accuracy for detection of pelvic LN metastases were 51.4%, 85.9%, 41.3%, 90.1%, and 80.3% for CT; 24.3%, 96.3%, 56.3%, 86.8%, and 84.6% for MRI; and 48.6%, 89.5%, 47.4%, 90.0%, and 82.9% for PET/CT, respectively. The sensitivity of PET/CT and CT was higher than that of MRI (p=0.004 and p= 0.013, respectively). The specificity of MRI was higher than those of PET/CT and CT (p=0.002 and p=0.001, respectively). The difference of specificity between PET/CT and CT was not statistically significant (p=0.167).ConclusionThese results indicate that preoperative CT, MRI, and PET/CT showed low to moderate sensitivity and PPV, and moderate to high specificity, NPV, and accuracy. More efforts are necessary to improve sensitivity of imaging modalities in order to predict pelvic LN metastases.
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