Humans ; Lymphoma, Large B-Cell, Diffuse/genetics* ; Herpesvirus 4, Human/genetics* ; Mutation ; Epstein-Barr Virus Infections/pathology* ; Hepatitis A Virus Cellular Receptor 2/genetics*

Epstein-Barr virus (EBV) causes various acute and chronic diseases. Chronic active EBV infection (CAEBV) is characterized by infectious mononucleosis-like symptoms that persist for more than 6 months with high viral loads in peripheral blood and/or an unusual pattern of anti-EBV antibodies. Severe CAEBV is associated with poor prognosis with severe symptoms, an extremely high EBV-related antibody titer, and hematologic complications that often include hemophagocytic lymphohistiocytosis. However, CAEBV which led to the development of aplastic anemia (AA) has not been reported yet. A 73-year-old woman was admitted to our hospital with intermittent fever, general weakness and elevated liver enzymes. In the serologic test, EBV-related antibody titer was elevated, and real-time quantitative-PCR in peripheral blood showed viral loads exceeding 10(4) copies/microg DNA. Liver biopsy showed characteristic histopathological changes of EBV hepatitis and in situ hybridization with EBV-encoded RNA-1 was positive for EBV. Pancytopenia was detected in peripheral blood, and the bone marrow aspiration biopsy showed hypocellularity with replacement by adipocytes. AA progressed and the patient was treated with prednisolone but deceased 8 months after the diagnosis due to multiple organ failure and opportunistic infection. Herein, we report a rare case of severe CAEBV in an adult patient accompanied by AA and persistent hepatitis.
Aged ; Anemia, Aplastic/*complications ; Carbapenems/therapeutic use ; Chronic Disease ; DNA, Viral/blood ; Epstein-Barr Virus Infections/complications/*diagnosis/pathology ; Female ; Hepatitis/*complications ; Herpesvirus 4, Human/*genetics/isolation & purification ; Humans ; Real-Time Polymerase Chain Reaction ; Severity of Illness Index ; Urinary Tract Infections/drug therapy

BACKGROUND/AIMS: The immunoregulatory molecules programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) are associated with the dysfunction of antiviral effector T-cells, which leads to T-cell exhaustion and persistent viral infection in patients with chronic hepatitis C and chronic hepatitis B. Little is known about the role of PD-1 and CTLA-4 in patients with symptomatic acute hepatitis A (AHA). METHODS: Peripheral blood mononuclear cells were isolated from seven patients with AHA and from six patients with nonviral acute toxic hepatitis (ATH) during the symptomatic and convalescent phases of the respective diseases; five healthy subjects acted as controls. The expression of PD-1 and CTLA-4 on T-cells was measured by flow cytometry. RESULTS: PD-1 and CTLA-4 expression during the symptomatic phase was significantly higher in the T-cells of AHA patients than in those of ATH patients or healthy controls (PD-1: 18.3% vs 3.7% vs 1.6%, respectively, p<0.05; CTLA-4: 23.5% vs 6.1% vs 5.9%, respectively, p<0.05). The levels of both molecules decreased dramatically during the convalescent phase of AHA, whereas a similar pattern was not seen in ATH. CONCLUSIONS: Our findings are consistent with a viral-protective effect of PD-1 and CTLA-4 as inhibitory molecules that suppress cytotoxic T-cells and thereby prevent the destruction of virus-infected hepatocytes in AHA.
Acute Disease ; Adult ; CTLA-4 Antigen/*genetics ; Case-Control Studies ; Female ; Flow Cytometry ; Hepatitis/genetics ; Hepatitis A/*genetics/virology ; Hepatitis A Virus, Human ; Humans ; Male ; *Phenotype ; Programmed Cell Death 1 Receptor/*genetics ; T-Lymphocytes/metabolism

APOBEC3 is a class of cytidine deaminase, which is considered as a new member of the innate immune system, and APOBEC3G belongs to this family. The research about APOBEC3G is a new direction of innate immune defense mechanism against virus. APOBEC3G has the restrictive activity on many viral replications, which deaminates dC to dU in the viral genome and then induces extensive hypermutation. APOBEC3G can also interrupt viral replication at several phases such as reverse transcription, replication, nucleocapsid and so on by non-deamination mechanisms. However, virus can encode viral proteins to counteract the restriction activity of APOBEC3G. Elucidation of the antagonistic interaction between APOBEC3G and the virus will be contributed to development of new antiviral drugs in the future.
APOBEC-3G Deaminase ; Animals ; Cytidine Deaminase ; genetics ; metabolism ; DNA Replication ; Deamination ; HIV-1 ; physiology ; Hepacivirus ; genetics ; physiology ; Hepatitis B virus ; genetics ; physiology ; Humans ; Paramyxoviridae ; genetics ; physiology ; Retroviridae ; physiology ; Virus Replication ; vif Gene Products, Human Immunodeficiency Virus ; metabolism

OBJECTIVES: An outbreak of hepatitis A occurred at a residential facility for the disabled in July 10, 2011. This investigation was carried out to develop a response plan, and to find the infection source of the disease. METHODS: A field epidemiologist investigated the symptoms, vaccination histories, living environments, and probable infection sources with 51 residents and 31 teachers and staff members. In July 25, 81 subjects were tested for the hepatitis A virus antibody, and specimens of the initial 3 cases and the last case were genetically tested. RESULTS: Three cases occurred July 10 to 14, twelve cases August 3 to 9, and the last case on August 29. Among the teachers and staff, no one was IgM positive (on July 25). The base sequences of the initial 3 and of the last case were identical. The vehicle of the outbreak was believed to be a single person. The initial 3 patients were exposed at the same time and they might have disseminated the infection among the patients who developed symptoms in early August, and the last patient might have, in turn, been infected by the early August cases. CONCLUSIONS: The initial source of infection is not clear, but volunteers could freely come into contact with residents, and an infected volunteer might have been the common infection source of the initial patients. Volunteers' washing their hands only after their activity might be the cause of this outbreak. Although there may be other possible causes, it would be reasonable to ask volunteers to wash their hands both before and after their activities.
Adolescent ; Adult ; Antibodies, Viral/metabolism ; Assisted Living Facilities ; Child ; Disabled Persons ; *Disease Outbreaks ; Drinking Water/virology ; Female ; Hepatitis A/*epidemiology ; Hepatitis A Virus, Human/genetics ; Humans ; Interviews as Topic ; Male ; Middle Aged ; RNA, Viral/analysis ; Reverse Transcriptase Polymerase Chain Reaction ; Young Adult

BACKGROUND: The safety of plasma derivatives has been reinforced since 1980s by variable pathogen inactivation or elimination techniques. Nucleic acid amplification test (NAT) for the source plasma has also been implemented worldwide. Recently nanofiltration has been used in some country for ensuring safety of plasma derivatives to eliminate non-enveloped viruses such as parvovirus B19 (B19V) and hepatitis A virus (HAV). We evaluated the efficacy of nanofiltration for the elimination of B19V and HAV. METHODS: To verify the efficacy of nanofiltration, we adopted a 20 nm Viresolve NFP (Millipore, USA) in the scaling down (1:1,370) model of the antithrombin III production. As virus stock solutions, we used B19V reactive plasma and porcine parvovirus (PPV) and HAV obtained from cell culture. And 50% tissue culture infectious dose was consumed as infectious dose. The methods used to evaluate the virus-elimination efficacy were reverse-transcriptase polymerase chain reaction for B19V and the cytopathic effect calculation after filtration for PPV and HAV. RESULTS: B19V was not detected by RT-PCR in the filtered antithrombin III solutions with initial viral load of 6.42x10(5) IU/mL and 1.42x10(5) IU/mL before filtration. The virus-elimination efficacy of nanofiltration for PPV and HAV were > or =10(3.32) and > or =10(3.31), respectively. CONCLUSIONS: Nanofiltration would be an effective method for the elimination of B19V and HAV. It may be used as a substitute for NAT screening of these viruses in source plasma to ensure safety of plasma derivatives in Korea.
Antithrombin III/isolation & purification ; DNA, Viral/analysis ; Filtration/*methods ; Hepatitis A virus/genetics/*isolation & purification ; Humans ; Nanotechnology/*methods ; Parvovirus B19, Human/genetics/*isolation & purification ; RNA, Viral/analysis ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo study the expression and clinical significance of kidney injury molecule-1 (KIM-1) in primary and metastatic renal epithelial neoplasms.

METHODSA total of 136 cases of kidney neoplasms were retrospectively reviewed including 63 primary clear cell renal cell carcinomas (RCCs), 22 papillary RCCs, 13 chromophobe RCCs, 7 oncocytomas, 7 RCCs associated with Xp11.2 translocation/TFE3 gene fusions and 24 metastatic clear cell RCCs. Immunostaining for KIM-1 and kidney-specific-protein (Ksp)-cadherin were performed and the relationship to tumor stage and grade in clear cell RCCs was investigated.

RESULTSExpression of KIM-1 was detected in 77.8% (49/63) of clear cell RCCs, 90.9% (20/22) of papillary RCCs, 1/13 of chromophobe RCCs, 7/7 of RCCs associated with Xp11.2 translocation/TFE3 gene fusions and 87.5%(21/24) of the metastatic RCCs, but not detected in 7 cases of oncocytomas. A diffuse expression of KIM-1 was more frequently observed in Furhman nuclear grade III/IV clear cell RCCs (P = 0.010). Ksp-cadherin expression was mainly observed in chromophobe RCCs and oncocytomas.

CONCLUSIONSKIM-1 is a specific biomarker for injuried kidney proximal tubules and the corresponding neoplasms, and has a high specificity and sensitivity for primary or metastatic clear cell RCCs, papillary RCCs and RCCs associated with Xp11.2 translocation/TFE3 gene fusions. Combination of KIM-1 and Ksp-cadherin immunostaining can lead to a more precise histological classification of primary kidney epithelial neoplasms and improve the diagnostic accuracy of metastatic RCCs.

Adenoma, Oxyphilic ; metabolism ; pathology ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; genetics ; metabolism ; Bone Neoplasms ; metabolism ; secondary ; Cadherins ; metabolism ; Carcinoma, Papillary ; metabolism ; pathology ; Carcinoma, Renal Cell ; genetics ; metabolism ; pathology ; Chromosomes, Human, X ; Gene Fusion ; Hepatitis A Virus Cellular Receptor 1 ; Humans ; Kidney Neoplasms ; genetics ; metabolism ; pathology ; Lung Neoplasms ; metabolism ; secondary ; Membrane Glycoproteins ; metabolism ; Neoplasms, Glandular and Epithelial ; classification ; genetics ; metabolism ; pathology ; Receptors, Virus ; metabolism ; Retrospective Studies ; Translocation, Genetic

Animals ; Antiviral Agents ; pharmacology ; Cell Cycle ; Cell Proliferation ; DNA, Circular ; physiology ; DNA, Viral ; physiology ; Ducks ; Half-Life ; Hepatitis B Surface Antigens ; metabolism ; Hepatitis B Virus, Duck ; genetics ; physiology ; Hepatitis B virus ; genetics ; physiology ; Hepatitis, Viral, Animal ; virology ; Hepatitis, Viral, Human ; virology ; Humans ; Liver ; pathology ; virology ; Virus Replication

PURPOSE: Hepatitis A virus (HAV) has been a leading cause of acute hepatitis in Korea. The reported genotypes of acute hepatitis A in Korea are the subgenotype IA and IB. The aim of the present study is to investigate HAV genotypes in the south-east area of Gyeonggi-do in Korea. MATERIALS AND METHODS: From June 2004 to June 2006, 46 acute hepatitis A patients were enrolled prospectively. All had sporadic acute hepatitis A patients. All suspected cases of acute hepatitis A were tested for IgM anti-HAV antibodies. We sequenced 168 bp of nucleotides of the putative VP1/P2A junction and determined the HAV genotype with reverse transcriptase polymerase chain reaction. The clinical and laboratory results of all patients were recorded. RESULTS: HAV-ribonucleic acid (RNA) was detected in 41 samples out of 46 samples. Among the 41 samples, 25 (60%) were shown to have subgenotype IIIA and the other 16 (40%) were subgenotype IA. Several amino acid substitutions were found. CONCLUSION: In these HAV sporadic cases, IIIA and IA were identified, and this may reflect co-circulation of various genotypes in Korea. This study provides valuable new data on the genetic distribution of HAV and important information to help design appropriate public health measures.
Adult ; Female ; Genotype ; Hepatitis A/*epidemiology/virology ; Hepatitis A Virus, Human/classification/genetics/*physiology ; Humans ; Korea/epidemiology ; Male ; *Molecular Epidemiology ; Phylogeny ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo investigate the relationship between pre-core G1896A point mutation of hepatitis B virus (HBV) and safety of breast feeding.

METHODSSerum and breast milk samples were collected from 62 pregnant women of HBV DNA positive/HBeAg negative. PCR-solid phase hybridization was used to detect the point mutation in pre-core region G1896A of HBV from pregnant women, and HBV DNA loads in sera and breast milk were determined by fluorescence quantitative PCR (FQ-PCR).

RESULTSThe prevalence of point mutation was 61.3% (38/62) in 62 pregnant women with HBsAg positive/HBeAg negative. The positive rate of HBV DNA in breast milk of group with point mutation (28.9%) was similar to that of group without mutation (29.2%, chi2=0.0003, P>0.05). However, The positive rate of HBV DNA in breast milk of group with high HBV loads (56.0%) was significantly higher than that of group with low HBV loads (10.8%, chi2=14.79, P<0.01).

CONCLUSIONThe point mutation in pre-core region G1896A of HBV dose not affect the positive rate of HBV DNA in breast milk and higher HBV DNA loads in serum of pregnant women might increase the risk of mother-infant transmission.

Breast Feeding ; DNA, Viral ; blood ; Female ; Hepatitis B ; transmission ; Hepatitis B virus ; genetics ; Humans ; Milk, Human ; virology ; Point Mutation ; Pregnancy