• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.4765-4771
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• 2014

Background: Patients with chronic liver diseases (CLD) may have compromised health related quality of life (HRQoL). Hepatitis B virus (HBV) infection has long been the leading cause of CLD including liver cancer and cirrhosis. Knowledge on different symptom profiles of CLD should help in development of comprehensive treatment and patient care plans. Objective: To access the facets of HRQoL in chronic liver diseases throughout their spectrum of severity. Materials and Methods: A cross-sectional study was conducted in the First Affiliated Hospital of Kunming Medical University in Yunnan Province of China. Both out- and inpatients undergoing treatment protocols for different HBV related liver disease states were consecutively collected from December 2012 to June 2013. ANOVA was used to compare the mean scores of EQ-5D and chronic liver disease questionnaire (CLDQ) among 5 disease groups. The relationship between demographic variables predicting global CLDQ scores and the domains of CLDQ was analysed. Results: A total of 1040 patients including 520 without complications, 91 with compensated cirrhosis, 198 with decompensated cirrhosis, 131 with HCC and 100 with liver failure were recruited. All domains of CLDQ, the means of EQ-5D value and EQ VAS exhibited significant decline with worsening of disease severity from uncomplicated HBV to liver failure. The multivariate regression demonstrated the reduction of mean scores of CLDQ domain at advanced stage. Patients with liver failure and HCC had more HRQoL impairment than other disease states. No effect of patient gender was found. Patient age was associated with 'fatigue' and 'worry' domains (p=0.006; p=0.004) but not with other domains and global scores of CLDQ and ED-5D. Conclusions: The HRQoL in chronic hepatitis B patients is greatly affected by disease states. Care for HBV-related diseases should consider not only the outcomes of treatment strategies but also improvement in patient wellbeing.

• Journal of Microbiology and Biotechnology
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• v.19 no.9
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• pp.1055-1064
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• 2009

Enteroviruses were identified and characterized from patients with aseptic meningitis and other enterovirus-related diseases in Chungnam, Korea from 2005 to 2006. Enteroviruses were isolated from 79 of 519 cases (15.2%) in 2005, and 37 of 386 cases (9.6%) in 2006. Based on partial VP1 sequencing, a total of 116 enterovirus isolates were resolved into 13 types. Prevalent among the Chungnam isolates were echovirus 18 and coxsackievirus B5 in 2005, and echoviruses 5 and 25 in 2006. This is the first time echoviruses 5 and 18 have been identified in Korea since enterovirus surveillance began there in 1993. The temporal distribution of enterovirus epidemics in Chungnam showed a remarkable seasonal pattern, with cases occurring during most of the three months of the summer from June to August. The highest rate of enterovirus-positive cases occurred in patients less than 1 year of age. The ratio of male to female enterovirus-positive patients was approximately 1.8:1. Comparison of the VP1 amino acid sequences of the 15 coxsackievirus B5 isolates with reference strains revealed that all Chungnam isolates are substituted at positions 23 (V231), 19 (S19G), 75 (Y75F), and 95 (N95S). Upon comparing the nine ECV5 isolates with foreign strains, it was found that only the Chungnam isolates, with the exception of Kor06-ECV5-239cn, have P at position 153 and F at position 146. The three ECV9 isolates from 2006 show alterations at amino acids 36, 148, and 154 outside of the BC-loop and at position 84 in the BC-loop, whereas the seven isolates from 2005 and the other ECV9 strains in the database only show the alteration at position 84 (D, I, N, S). The five ECV25 isolates have an S residue at position 134, whereas most of the foreign strains have an N residue.

• IMMUNE NETWORK
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• v.3 no.2
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• pp.126-135
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• 2003

Background: One of the important factors in the prognosis of chronic hepatitis B patient is the degree of replication of hepatitis B virus (HBV). It has been known that HBV DNA polymerase plays the essential role in the replication of HBV. HBV DNA polymerase is composed of four domains, TP (Terminal protein), spacer, RT (Reverse transcriptase) and RNaseH. Among these domains, tyrosine, the $65^{th}$ residue of TP is an important residue in protein-priming reaction that initiates reverse transcription. If monoclonal antibody that recognizes around tyrosine residue were selected, it could be applied to further study of HBV replication. Methods: To produce TP-specific scFv (single-chain Fv) by phage display, mice were immunized using synthetic TP-peptide contains $57{\sim}80^{th}$ amino acid residues of TP domain. After isolation of mRNA of heavy-variable region ($V_H$) and light-chain variable region ($V_L$) from the spleen of the immunized mouse, DNA of $V_H$ and $V_L$ were obtained by RT-PCR and joined by a DNA linker encoding peptide (Gly4Ser)3 as a scFv DNA fragments. ScFv DNA fragments were cloned into a phagemid vector. scFv was expressed in E.coli TG1 as a fusion protein with E tag and phage gIII. To select the scFv that has specific affinity to TP-peptide from the phage-antibody library, we used two cycles of panning and colony lift assay. Results: The TP-peptide-specific scFv was isolated by selection process using TP-peptide as an antigen. Selected scFv had 30 kDa of protein size and its nucleotide sequences were analyzed. Indirect- and competitive-ELISA revealed that the selected scFv specifically recognized both TP-peptide and the HBV DNA polymerase. Conclusion: The scFv that recognizes the TP domain of the HBV DNA polymerase was isolated by phage display.

• 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.

• The Journal of the Korea Contents Association
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• v.12 no.12
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• pp.313-320
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• 2012

A dental treatment room is always exposed to diverse kinds of pathogenic bacteria, and may be a mediating place of cross-infection given being contaminated the interior of a room through several routes in the form of patient's secretion and aerosol. The main agent of preventing cross-infection is a dental hygienist in the dental treatment and the dental treatment room where are scattered about a risk of cross-infection. A dental hygienist needs to have right recognition on infection control before being active as a clinical expert. This infection-control recognition level is influenced from the clinical practice. Accordingly, to survey recognition of infection control, a self-administered questionnaire research was conducted targeting 314 students who are fixed the clinical practice as regular subject in the junior course out of curriculum for the Department of Dental Hygiene at some of 4-year universities. Data collection was performed from December 9, 2011 to February 22, 2012. Except 11 copies of questionnaire with insincere response among the collected materials, 303 copies were finally analyzed by using SPSS WIN 20.0. The following conclusions were obtained. In the infection disease section, both on and off campus showed 4.89 points from 'the importance of recognizing the infections prevention', 4.65 points from 'recognizing the compulsory preventative injection for hepatitis type B', 4.77 points from 'recognizing the necessity of the preventative injection for hepatitis type B', 4.71 points from 'whether practice the prevention in reality or not', and 4.76 points from 'the educational helps to the prevention'. In other words, the section recorded the highest and meaningful points. It is considered to be needed the development in systematic and diverse infection-control educational programs and the differentiated education depending on school year for dental hygiene students.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.6019-6026
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• 2015

Background: The aim of this study was to assess the relationship between IL-18 gene polymorphisms and HBV-related diseases and whether these polymorphisms influence its expression in the Guangxi Zhuang population. Materials and Methods: We enrolled 129 chronic HBV infected (CHB) patients, 86 HBV-related liver cirrhosis (LC) patients and 160 healthy controls in our study. Polymerase chain reaction-restriction fragment length polymorphism methods were used to detect IL-18 gene -607C/A, -137G/C polymorphisms, and an ELISA kit was employed to determine serum IL-18 levels. Results: No correlation was found between the -607C/A polymorphism and risk of HBV-related disease. For the -137G/C polymorphism, the GC genotype and C allele were associated with a significantly lower risk of CHB (95%CI: 0.32-0.95, p=0.034 and 95%CI: 0.35-0.91, p=0.018) and HBV-related LC (95%CI: 0.24-0.89, p=0.022 and 95%CI: 0.28-0.90, p=0.021). A similar decreased risk was also found with the A-607C-137 haplotype. With respect to IL-18 expression, it was significantly lower in both patient groups, but no association was noted between the two polymorphisms in the IL-18 gene and its expression. Conclusions: Our study indicated that the -137C allele in the IL-18 gene may be a protective factor for HBV-related disease, and serum IL-18 level may be inversely associated with CHB and HBV-related LC.

• BMB Reports
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• v.37 no.6
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• pp.741-748
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• 2004

The hepatitis C virus is associated with the development of liver cirrhosis and hepatocellular carcinomas. Among the 10 polyproteins produced by the virus, no function has been clearly assigned to the non-structural 5A (NS5A) protein. This study was designed to identify the hepatocellular proteins that interact with NS5A of the HCV. Yeast two-hybrid experiments were performed with a human liver cDNA prey-library, using five different NS5A derivatives as baits, the full-length NS5A (NS5A-F, amino acid (aa) 1~447) and its four different derivatives, denoted as NS5A-A (aa 1~150), -B (aa 1~300), -C (aa 300~447) and D (aa 150~447). NS5A-F, NS5A-B and NS5A-C gave two, two and 10 candidate clones, respectively, including an AHNAK-related protein, the secreted frizzled-related protein 4 (SFRP4), the N-myc downstream regulated gene 1 (NDRG1), the cellular retinoic acid binding protein 1 (CRABP-1), ferritin heavy chain (FTH1), translokin, tumor-associated calcium signal transducer 2 (TACSTD2), phosphatidylinositol 4-kinase (PI4K) and $centaurin{\delta}$ 2 ($CENT{\delta}2$). However, NS5A-A produced no candidates and NS5A-D was not suitable as bait due to transcriptional activity. Based on an in vitro binding assay, CRABP-1, PI4K, $CENT{\delta}2$ and two unknown fusion proteins with maltose binding protein (MBP), were confirmed to interact with the glutathione S-transferase (GST)/NS5A fusion protein. Furthermore, the interactions of CRABP-1, PI4K and $CENT{\delta}2$ were not related to the PXXP motif (class II), as judged by a domain analysis. While their biological relevance is under investigation, the results contribute to a better understanding of the possible role of NS5A in hepatocellular signaling pathways.

• KSBB Journal
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• v.21 no.4
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• pp.260-266
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• 2006

Methanol induction conditions with various additives for the enhanced production of recombinant hepatitis B surface antigen(HBsAg) were investigated in Pichia pastoris, which can utilize methanol as a carbon source and produce recombinant proteins under the control of strong, tightly-regulated alcohol oxidase(AOX) promoter. The presence of non-methanol carbon sources such as glycerol and glucose fully repressed the expression of AOX promoter. Various additives were tested to improve the production of recombinant protein and it was found that sorbitol could be a good carbon source during methanol induction period. An optimized concentration of amino acid mixture enhanced the production of HBsAg significantly. Pluronic F-68, a non-ionic surfactant, also improved the production of HBsAg without inhibiting cell growth. Addition of oleic acid at 0.01%(v/v) during the induction period showed positive effect on the production of HBsAg. Finally, 1.2%(v/v) of trace salts enhanced the production of HBsAg 1.9 times compared to that of control culture.

• The Korean Journal of Nuclear Medicine
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• v.26 no.2
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• pp.307-311
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• 1992

Anorexia, nausea, and vomiting are one of the most frequent symptoms in viral hepatits patients. These may be due to poorly detoxified substances by dysfunctioned hepatocytes or by gastritis, but the pathophysiology is not totally understood. The symptoms interfere with adequate nutrient intake and are managed by metoclopramide, which accelerates gastric emptying. Thus delayed gastric emptying may well be a contributing factor to such symptoms. To determine such a relationship, we measured gastric emptying time in 11 normal subjects,9 acute (AVH), and 12 chronic B viral hepatitis (CVH) patients. All were males with a mean age of 23 years. An egg was labeled with 0.5 mCi of $^{99m}Tc-sulfur$ colloid, fried, then eaten between 2 slices of bread with 100 cc of water. Anterior and posterior images were taken at 20 minute intervals over a 2 hour period. A geometric mean of activity pertaining to the gastric region was measured, and $T_{1/2}$ was calculated from the time activity curve. $T_{1/2}$ for normal the group was $57.8{\pm}6.3$ minutes while that for the AVH and CVH group was $58.2{\pm}8.2$ (p=0.40) and $64.1{\pm}10.5$ (p=0.09), respectively. There was 1 AVH Patient and 4 CVH patients with prolonged $T_{1/2}$. Anorexia and nausea was seen in 71% and 46% of the patients, respectively. 80% and 60% of the patients with prolonged $T_{1/2}$ had anorexia and nausea, respectively.

• The Korean Journal of Zoology
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• v.28 no.3
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• pp.166-178
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• 1985

In order to express hepatitis B surface antigen $(HB_sAg)$ containing pre-surface antigen region in mammalian calls, 2.7 kb DNA fragment containing pre-surface region-$HB_sAg$ gene poly(A) addition site of HBV genome was cloned into simian virus 40(SV 40) based chimeric vector pSVOB. 2.7 kb DNA fragment was derived from pHBVD 107 containing tandem copies of the HBV genome in a head-to-tail arrangement by Bgl II digestion. Construction of the vector pSVOE involved the incorporation of SV40 sequences spanning the viral origin of replication and 72 bp repeats (enhancer) into a pBR 322 derivative lacking sequences which inhibit replication in mammalian cells. Bam HI linker was inserted at the Pvu II site in the proximity of SV40 late promoter of pSVOE and named as pSVOB. To construct the recombinant plasmid pSVBS, pHBVD 107 was digested with Bgl II to isolate 2.7kb DNA fragment and the fragment was ligated into the Bam HI site of pSVOB by ligation. Preliminary result showed that the recombinant plasmid pSVBS produced $HB_sAg$ in the monkey cell producing large T antigen (COS cell).