• Journal of Trauma and Injury
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• v.28 no.1
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• pp.9-14
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• 2015

Purpose: The aim of this study was to estimate the seropositive prevalence of blood-borne infection in neurotrauma patients who underwent emergent surgical intervention, especially patients with hepatitis B virus (HBV), hepatitis C virus (HCV), syphilis and human immunodefIciency virus (HIV). Methods: A retrospective review identified 559 patients with traumatic brain injury and spinal trauma who underwent emergent surgery between 2007 and 2014. We reviewed the medical records and extracted data, including age, sex, location of lesion, result of serologic tests, time interval of admission and surgery after presenting to emergency room. Serologic tests for HBV, HCV, syphilis and HIV were performed and analyzed to determine whether the seropositive results were confirmed by the surgeon before surgery. Results: The majority of the patients were male (74.6%), and the mean age was $55.4{\pm}20.2years$. Most patients underwent surgery due to traumatic brain injury (90.0%). Fifty-three patients (10.0%) showed a positive result on at least one serologic test. Seropositive rates according to pathogens were 0.5% for syphilis, 5.2% for HBV and 3.9% for HCV. No positive results were noted on the serologic tests for HIV. HBV in patients with spinal cord injury and age from 40 to 49 years were associated with high serologic positive rate, and that result was statistically significant. However, no statistically significant differences were found in the other variables. Serologic results could not confirmed before surgery in the majority of the cases (62.1%), and 10.4% of these patients showed seropositive results. Conclusion: The results of this study emphasize the importance of taking precautions and conducting rapid serologic testing in preventing the occupational transmission of blood-borne viruses to health-care workers.

• Journal of Life Science
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• v.15 no.1 s.68
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• pp.38-44
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• 2005

Infection with hepatitis B virus (HBV) is a major health problem worldwide. Although a tremendous amount has been known about HBV, there have been obstacles in the study of HBV due to the narrow host range of HBV limited to humans and primates. In the present study, we investigated the susceptibility to HBV infection of mouse hepatoma cell line, Hepa-1c1c7. In addition, based on that human hepatocytes infected by HBV increase the expression of the pro-inflammatory cytokine TNF-a, the inducibility of TNF-a expression by HBV in the cells was determined. HBV surface antigen (HBsAg) secretion was measured by the microparticle enzyme immunoassay and steady state mRNA expression was analyzed by quantitative competitive RT-PCR. Transient transfection of Hepa-1c1c7 cells with HBV expression vector resulted in a dose-dependent induction of TNF-a expression. Infection of Hepa-1c1c7 cells with the serum of HBV carrier also increased TNF-a mRNA expression. Both in the transfected and infected cells, HBV mRNA was expressed and significant HBsAg secretion was detected. There was no significant variation in $\beta-actin$ mRNA expression by HBV. These results demonstrate that HBV is infectious to Hepa-lc1c7 in vitro and the viral infection induces TNF-a expression, which suggests that Hepa-lc1c7, a mouse hepatoma cell line, may be a possible model system for analysis of various molecular aspects of HBV infection.

• Molecules and Cells
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• v.37 no.1
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• pp.66-73
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• 2014

Myeloid-derived suppressor cells (MDSCs) play an important role in impairing the function of T cells. We characterized MDSCs in two chronic hepatitis C (CHC) cohorts: a cross-sectional group that included 61 treatment-naive patients with CHC, 14 rapid virologic response (RVR) cases and 22 early virologic response (EVR) cases; and a longitudinal group of 13 cases of RVR and 10 cases of EVR after pegylated-interferon-${\alpha}$/ribavirin treatment for genotype 1b HCV infection. Liver samples from 32 CHC patients and six healthy controls were subjected to immunohistochemical analysis. MDSCs frequency in treatment-naive CHC was significantly higher than in RVR, EVR, or healthy subjects and was positively correlated with HCV RNA. Patients infected with HCV genotype 2a had a significantly higher frequency of MDSCs than those infected with genotype 1b. Decreased T cell receptor (TCR) ${\zeta}$ expression on $CD8^+$ T cells was significantly associated with an increased frequency of MDSCs in treatment-naive CHC patients and was restored by L-arginine treatment in vitro. Increased numbers of liver arginase-$1^+$ cells were closely associated with the histological activity index in CHC. The TCR ${\zeta}$ chain was significantly downregulated on hepatic $CD8^+$ T cells in CHC. During antiviral follow up, MDSCs frequency in peripheral blood mononuclear cells was directly correlated with the HCV RNA load in the plasma and inversely correlated with TCR ${\zeta}$ chain expression in $CD8^+$ T cells in both RVR and EVR cases. Notably, the RVR group had a higher frequency of MDSCs at baseline than the EVR group. Collectively, this study provides evidence that MDSCs might be associated with HCV persistence and downregulation of CD8 ${\zeta}$ chain expression.

• Pediatric Infection and Vaccine
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• v.12 no.2
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• pp.186-194
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• 2005

Purpose : Hepatitis A viral infections have been continued after re-emerging since mid 1990s in Korea. The incidence of this disease has been increased in young adults younger than 30 years of age since 2000. This study was performed to evaluate the prevalence of antibody to hepatitis A in Korea(two regions; Incheon and Changwon) in 2005, and was compared with the results of similar studies in mid 1990s. Methods : The study was conducted from January 2005 to June 2005, and consisted of 1,301 enrolled subjects, neonates to 50 years old, living in Incheon and Changwon in Korea. All sera were frozen and stored at $-70^{\circ}C$ until assayed. Anti-HAV IgG antibodies were measured by microparticle enzyme immunoassay(HAVAB, Abbott Lab., IL, USA). Results : The prevalence of anti-HAV IgG was 61.1% in infants younger than 1 year old, 30.5% in 1~5 years, 14.6% in 6~10 years, 1.7% in 11~15 years, 6.5% in 16~20 years, 36.6%in 21~30 years, 77.5% in 31~40 years, and 99.8% in 41~50 years. Statistical differences were not found between male and female, but there was statistical difference in 6~10 years old age group between the two areas. Conclusion : Our study indicate that the prevalence of antihepatitis A virus antibody has shifted from children to old adolescents and young adults. This result suggests that the risk of sudden outbreaks or increasing incidence of hepatitis A viral infections in young adults may be expected in our society. The preventive strategies of hepatitis A including vaccination should be prepared.

• BMB Reports
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• v.42 no.1
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• pp.59-64
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• 2009

Hepatitis B virus (HBV) infection is highly prevalent worldwide. The major challenge for current antiviral treatment is the elevated drug resistance that occurs via rapid viral mutagenesis. In this study, we developed AAV vectors to simultaneously deliver two or three shRNAs targeting different HBV-related genes. These vectors showed markedly better antiviral effects than ones that delivered a single shRNA in vitro. A dual shRNA expression vector (AAV-157i/1694i), which simultaneously expressed two shRNAs targeted the S and X genes of HBV, reduced HBsAg, HBeAg and HBV DNA levels by $87{\pm}4$, $80.3{\pm}2.6$ and $86.2{\pm}7%$ respectively, eight days post-transduction. In a mouse model of prophylactic treatment, HBsAg and HBeAg were reduced to undetectable levels and the serum HBV DNA level was reduced by at least 100 fold. These results indicate that AAV-157i/1694i generates potent anti-HBV effects and that the strategy of constructing multi-shRNA expression vectors may lead to enhanced anti-HBV efficacy and overcome the evading mechanism of the virus and thus the development of drug resistance.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7045-7056
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• 2013

Since the first report of RNA interference (RNAi) less than a decade ago, this type of molecular intervention has been introduced to repress gene expression in vitro and also for in vivo studies in mammals. Understanding the mechanisms of action of synthetic small interfering RNAs (siRNAs) underlies use as therapeutic agents in the areas of cancer and viral infection. Recent studies have also promoted different theories about cell-specific targeting of siRNAs. Design and delivery strategies for successful treatment of human diseases are becomingmore established and relationships between miRNA and RNAi pathways have been revealed as virus-host cell interactions. Although both are well conserved in plants, invertebrates and mammals, there is also variabilityand a more complete understanding of differences will be needed for optimal application. RNA interference (RNAi) is rapid, cheap and selective in complex biological systems and has created new insight sin fields of cancer research, genetic disorders, virology and drug design. Our knowledge about the role of miRNAs and siRNAs pathways in virus-host cell interactions in virus infected cells is incomplete. There are different viral diseases but few antiviral drugs are available. For example, acyclovir for herpes viruses, alpha-interferon for hepatitis C and B viruses and anti-retroviral for HIV are accessible. Also cancer is obviously an important target for siRNA-based therapies, but the main problem in cancer therapy is targeting metastatic cells which spread from the original tumor. There are also other possible reservations and problems that might delay or even hinder siRNA-based therapies for the treatment of certain conditions; however, this remains the most promising approach for a wide range of diseases. Clearly, more studies must be done to allow efficient delivery and better understanding of unwanted side effects of siRNA-based therapies. In this review miRNA and RNAi biology, experimental design, anti-viral and anti-cancer effects are discussed.

• Reproductive and Developmental Biology
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• v.29 no.1
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• pp.49-55
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• 2005

We cloned cDNA of the PGH(porcine growth hormone) gene and constructed retrovirus vector designed to express PGH gene under the regulation of CMV (cytomegalovirus) promoter. To maximize the expression, WPRE(woodchuck hepatitis virus posttranscriptional regulatory element) sequence was placed at the downstream of the PGH gene. After infection with recombinant viruses, approximately 1×10/sup 6/ PFF(porcine fetal fibroblast) cells released PGH protein into the media as much as 1,400 ng. In a subsequent experiment, a modifications of the retrovirus vector was made to express the PGH gene in a teracycline-inducible manner. In PFF cells carrying these viral vector sequences, addition of doxycycline to the media resulted in 2∼6 fold increase in PGH synthesis. In the modified retrovirus vectors, the WPRE sequence also played a role in boosting the effect of the tetracycline induction. This result indicates that our tetracycline-inducible expression system might be a promising candidate in alleviating the complicate physiological problems caused by constitutive expression of the exogenous genes in the transgenic animals.

• Clinical and Experimental Pediatrics
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• v.51 no.11
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• pp.1191-1197
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• 2008

Purpose : Previously, Epstein-Barr virus (EBV) infection was diagnosed by serological examination; currently, many EBV antigen detection methods have been developed and applied clinically for diagnosing EBV infection. To delineate the clinical characteristics of EBV infection, clinical and laboratory findings were evaluated for patients who tested positive in EBV polymerase chain reaction (PCR). Methods : EBV PCR was conducted in 352 patients admitted to the pediatric ward from January 2004 to December 2006, with more than 2 clinical signs such as fever (${\geq}37.5^{\circ}C$), exudative throat infection, lymphadenopathy, hepatitis of unknown etiology, and splenomegaly. The EBV viral gene was detected by PCR in 115 patients (32%), and the clinical characteristics of these patients were evaluated. Laboratory findings such as leukocytosis, thrombocytopenia, atypical lymphocyte, and alteration in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in peripheral blood were examined. The EBV-specific immunoglobulin M antibody (EBV-IgM Ab) was also tested. Results : Most of the children were younger than 8 years (89%), and the male to female ratio was 1.3:1. Exudative throat infection and fever (${\geq}37.5^{\circ}C$) were observed in all patients. Cervical lymph node enlargement was seen in 36 patients (31 %); leukocytosis ($WBC{\geq}10,000/mm^3$), in 54 patients (47%); and atypical lymphocyte (${\geq}20%$), in 28 patients (24%). EBV-IgM Ab was positive in 33 patients (29%). The younger patients had higher ALT levels and higher incidence of positive EBV-IgM Ab than the older patients. Conclusion : The cumulative number of patients diagnosed to have EBV infection by PCR increased markedly for those under 8 years. ALT was higher and EBV-IgM Ab was detected more in younger patients with EBV infection.

• Korean Journal of Poultry Science
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• v.46 no.1
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• pp.31-37
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• 2019

A chicken clathrin-associated adaptor protein $3-{\delta}$ subunit 2 (AP3S2) is a subunit of AP3, which is involved in cargo protein trafficking to target membrane with clathrin-coated vesicles. AP3S2 may play a role in virus entry into host cells through clathrin-dependent endocytosis. AP3S2 is also known to participate in metabolic disease developments of progressions, such as liver fibrosis with hepatitis C virus infection and type 2 diabetes mellitus. Chicken AP3S2 (chAP3S2) gene was originally identified as one of the differentially expressed genes (DEGs) in chicken kidney which was fed with different calcium doses. This study aims to characterize the molecular characteristics, gene expression patterns, and transcriptional regulation of chAP3S2 in response to the stimulation of Toll-like receptor 3 (TLR3) to understand the involvement of chAP3S2 in metabolic disease in chicken. As a result, the structure prediction of chAP3S2 gene revealed that the gene is highly conserved among AP3S2 orthologs from other species. Evolutionarily, it was suggested that chAP3S2 is relatively closely related to zebrafish, and fairly far from mammal AP3S2. The transcriptional profile revealed that chAP3S2 gene was highly expressed in chicken lung and spleen tissues, and under the stimulation of poly (I:C), the chAP3S2 expression was down-regulated in DF-1 cells (P<0.05). However, the presence of the transcriptional inhibitors, BAY 11-7085 (Bay) as an inhibitor for nuclear factor ${\kappa}B$ ($NF{\kappa}B$) or Tanshinone IIA (Tan-II) as an inhibitor for activated protein 1 (AP-1), did not affect the expressional level of chAP3S2, suggesting that these transcription factors might be dispensable for TLR3 mediated repression. These results suggest that chAP3S2 gene may play a significant role against viral infection and be involved in TLR3 signaling pathway. Further study about the transcriptional regulation of chAP3S2 in TLR3 pathways and the mechanism of chAP3S2 upon virus entry shall be needed.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7825-7829
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• 2015

Background: Egypt has the highest prevalence of HCV infection in the world (~14.7%). Around 10-15% of HCV-infected persons will advance to cirrhosis within the first 20 years. The incidence of HCC is expected to grow in the next two decades, largely due to HCV related cirrhosis, and detection of HCC at an early stage is critical for a favorable clinical outcome. No simple reliable non-invasive marker has been available till now. B2M, a non-glycosylated polypeptide composed of 99 amino acids, is one of the components of HLA class I molecules on the surfaces of all nucleated cells. It has been reported that the level of serum B2M is elevated in patients with chronic hepatitis C and HCV-related HCC when compared to HCV-negative patients or healthy donors. Determining the clinical utility of serum B2M as a marker for disease progression in Egyptian patients with HCV related chronic hepatitis, cirrhosis and hepatocellular carcinoma was the aim of the present study. Materials and Methods: In this analytical cross sectional study 92 participants were included in 4 equal groups: Group (1) non cirrhotic chronic HCV; Group (2) HCV related liver cirrhosis; Group (3) HCC on top of HCV,; and Group (4) healthy controls. History taking, clinical examination, routine labs and abdominal ultrasound were conducted for all patients, PCR and Metavir scores for group (1) patients, and triphasic CT abdomen and AFP for Group (3) patients. B2M levels were measured in serum with a fully-automated IMX system. Results: The mean serum B2M level of Group (1) was $4.25{\pm}1.48{\mu}g/ml$., Group (2) was $7.48{\pm}3.04$, Group (3) was $6.62{\pm}2.49$ and Group (4) was $1.62{\pm}0.63$. Serum B2M levels were significantly higher in diseased than control group (p<0.01) being significantly higher in cirrhosis ($7.48{\pm}3.04$) and HCC groups ($6.62{\pm}2.49$) than the HCV group ($4.25{\pm}1.48$) (p<0.01). There was a significant correlation between B2M Level and ALK, total and direct bilirubin and INR (p<0.05), and a significant inverse correlation between B2M level and albumin, total proteins, HB andWBCS values (p<0.05). There was no significant correlation between B2M level and viral load or Metavir score, largest tumour size or AFP (p>0.05). The best B2M cut-off for HCV diagnosis was 2.6 with a sensitivity of 100%, a specificity of 92%, a positive predictive value (PPV) of 97% and a negative predictive value (NPV) of 100%. The best B2M cut-off for HCC diagnosis was 4.55 which yielded sensitivity, specificity, positive predictive value, negative predictive values of 74%, 62%, 39.5, 87.8% respectively (p-value <0.01) while best cut-off for cirrhosis was 4.9, with sensitivity 74 % and specificity 74%.The sensitivity for HCC diagnosis increased upon B2M and AFP combined estimation to 91%, specificity to 79%, NPV to 95% and accuracy to 83%. Conclusions: Serum B2M level is elevated in HCV related chronic liver diseases and may be used as a marker for HCV disease progression towards cirrhosis and carcinoma.