• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.2145-2150
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• 2016

Background: Infection with hepatitis B virus (HBV) is a major global public health problem, with a wide spectrum of clinical manifestations. Human cytosolic glutathione-S-transferases (GSTs) include several classes such as alpha (A), mu (M), pi (P), sigma (S), zeta (Z), omega (O) and theta (T). The present study aimed to investigate the role of GST omega genes (GSTO1 and GSTO2) in different groups of patients infected with HBV. Materials and Methods: HBV groups were classified according to clinical history, serological tests and histological analysis into normal carriers (N), acute (A), chronic (CH), cirrhosis (CI) and hepatocellular carcinoma (HCC) cases. The study focused on determination of the genotypes of GST omega genes (GSTO1 and GSTO2) and GST activity and liver function tests. Results: The results showed that GSTO1 (A/A) was decreased in N, A, CH, CI and HCC groups compared to the C-group, while, GSTO1 (C/A) and GSTO1(C/C) genotypes were increased significantly in N, A, CH, CI and HCC groups. GSTO2 (A/A) was decreased in all studied groups as compared to the C-group but GSTO2(A/G) and GSTO2(G/G) genotypes were increased significantly. In addition, GST activities, albumin and TP levels were decreased in all studied groups compared to the C-group, while the activities of transaminases were increased to differing degrees. Conclusions: The results indicate that GSTO genetic polymorphisms may be considered as biomarkers for determining and predicting the progression of HBV infection.

• IMMUNE NETWORK
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• v.2 no.1
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• pp.41-48
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• 2002

Background: Viral antigens presented on the cell surface in association with MHC class I molecules are recognized by CD8+ T cells. MHC restricted peptides are important in eliciting cellular immune responses. As peptide antigens have a weak immunigenicity, pH-sensitive liposomes were used for peptide delivery to induce effective cytotoxic T lymphocyte (CTL) responses. In the previous study, as the HBx peptides could induce specific CTLs in vitro, we tested whether the HLA-A2/$K^b$ transgenic mice that were immunized by HBx-derived peptides could be protected from a viral challenge. Methods: HBx-peptides encapsulated by pH-sensitive liposomes were prepared. $A2K^b$ transgenic mice were immunized i.m. on days one and seven with the indicated concentrations of liposome-encapsulated peptides. Three weeks later, mice were infected with $1{\times}10^7pfu$/head of recombinant vaccinia virus (rVV)-HBx via i.p. administration. The ovaries were extracted from the mice, and the presence of rVV-HBx in the ovaries was analyzed using human TK-143B cells. IFN-${\gamma}$ secretion by these cells was directly assessed using a peptide-pulsed target cell stimulation assay with either peptide-pulsed antigen presenting cells (APCs), concanavalin A ($2{\mu}g/ml$), or a vehicle. To generate peptide-specific CTLs, splenocytes obtained from the immunized mice were stimulated with $20{\mu}g/ml$ of each peptide and restimulated with peptide-pulsed APC four times. The cytotoxic activity of the CTLs was assessed by standard $^{51}Cr$-release assay and intracellular IFN-${\gamma}$ assay. Results: Immunization of these peptides as a mixture in pH-sensitive liposomes to transgenic mice induced a good protective effect from a viral challenge by inducing the peptide-specific CD8+ T cells. Mice immunized with $50{\mu}g/head$ were much better protected against viral challenge compared to those immunized with $5{\mu}g$/head, whereas the mice immunized with empty liposomes were not protected at all. After in vitro CTL culture by peptide stimulation, however, specific cytotoxicity was much higher in the CTLs from mice immunized with $5{\mu}g/head$ than $50{\mu}g/head$ group. Increase of the number of cells that intracellular IFN-${\gamma}$ secreting cell among CD8+ T cells showed similar result. Conclusion: Mice immunized with XEPs within pH-sensitive liposome were protected against viral challenge. The protective effect depended on the amount of antigen used during immunization. XEP-3-specific CTLs could be induced by peptide stimulation in vitro from splenocytes obtained from immunized mice. The cytotoxic effect of CTLs was measured by $^{51}Cr$-release assay and the percentage of accumulated intracellular IFN-${\gamma}$ secreting cells after in vitro restimulation was measured by flow cytometric analysis. The result of $^{51}Cr$-release cytotoxicity test was well correlated with that of the flow cytometric analysis. Viral protection was effective in immunized group of $50{\mu}g/head$, while in the in vitro restimulation, it showed more spectific response in $5{\mu}g$/head group.

• Molecules and Cells
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• v.41 no.5
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• pp.401-412
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• 2018

Oxymatrine (OMT) often used in treatment for chronic hepatitis B virus infection in clinic. However, OMT-induced liver injury has been reported. In this study, we aim to investigate the possible mechanism of OMT-induced hepatotoxicity in human normal liver cells (L02). Exposed cells to OMT, the cell viability was decreased and apoptosis rate increased, the intracellular markers of oxidative stress were changed. Simultaneously, OMT altered apoptotic related proteins levels, including Bcl-2, Bax and pro-caspase-8/-9/-3. In addition, OMT enhanced the protein levels of endoplasmic reticulum (ER) stress makers (GRP78/Bip, CHOP, and cleaved-Caspase-4) and phosphorylation of c-Jun N-terminal kinase (p-JNK), as well as the mRNA levels of GRP78/Bip, CHOP, caspase-4, and ER stress sensors (IREI, ATF6, and PERK). Pre-treatment with Z-VAD-fmk, JNK inhibitor SP600125 and N-acetyl-l-cysteine (NAC), a ROS scavenger, partly improved the survival rates and restored OMT-induced cellular damage, and reduced caspase-3 cleavage. SP600125 or NAC reduced OMT-induced p-JNK and NAC significantly lowered caspase-4. Furthermore, 4-PBA, the ER stress inhibitor, weakened inhibitory effect of OMT on cells, on the contrary, TM worsen. 4-PBA also reduced the levels of p-JNK and cleaved-caspase-3 proteins. Therefore, OMT-induced injury in L02 cells was related to ROS mediated p-JNK and ER stress induction. Antioxidant, by inhibition of p-JNK or ER stress, may be a feasible method to alleviate OMT-induced liver injury.

• Health Policy and Management
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• v.25 no.3
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• pp.149-151
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• 2015

United Nations (UN) adopted 17 global sustainable development agenda to the year 2030 in the 68th general assembly on september, 2015. The global agendas and goals are important for 3 reasons: (1) to adopt the international standard for determining the health status; (2) to identify areas in need of attention; and (3) to advance international cooperation regarding health issues. In the area of infectious diseases, our goals include the eradication of human immunodeficiency virus infection and acquired immune deficiency syndrome, tuberculosis, and malaria as well as a substantial reduction of hepatitis by the year 2030. In the area of non-communicable diseases, our goal is to reduce premature mortality (${\leq}70years$) at least 30% by the year 2030. Preventive activities such as smoking cessation, alcohol abstinence, nutritional measures, and physical activities, should also be promoted intensively nationwide. It is also necessary to establish stringent policies for control hypertension, diabetes, obesity, and hypercholesterolemia. Additionally, environmental health, injury by traffic accident, mental health, and drug and alcohol abuse are important health policies. Furthermore, in the area of international health and cooperation, maternal and child health remain important areas of support for underdeveloped countries. Education and training towards the empowerment of health professionals in underdeveloped countries is also an important issue. The global agenda prioritize resources(manpower and budget) allocation of international organizations such as UN, World Health Organization, United Nations Development Programme, and World Bank. The global agenda also sets the contribution levels of Official Developmental Assistance donor countries. Health professionals such as professors and researchers will have to turn their attention to areas of vital international importance, and play an important role in implementation strategies and futhermore guiding global agenda.

• Journal of Korean Academy of Nursing
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• v.26 no.3
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• pp.605-622
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• 1996

Needle stick injury, in which blood-borne pathogens including Human Immune-Deficiency virus and hepatitis B virus are transmitted, is one of the major occupational hazards that health professionals face everyday. In order to provide basic data for the development of educational programs for health professionals aimed at preventing and effectively managing needle stick injuries, a retrospective descriptive study was carried out .The subjects of the study were 630 health professionals, 499 nurses and 131 physicians, from two university hospitals in Seoul, Korea. Data on episodes of needle stick experiences over the past is months September 1994 through August 1995, were collected between September 1 and 7, 1995. A Questionaire developed by the researcher was used. The frequencies and the percentile score for episodes of needle stick injuries were calculated using the PC-SAS program. The differences and similarities in reference to the structure, career, and specialty variables were analysed by X$^2$-tests. Results are as follows : 1. Of the sample, 521(82.7%) reported a needle stick injury, 33.4% reported 3 or more episodes of needle stick injuries. 2. The needle stick injuries occured in the following processes : process of percutaneous venepuncture for intra-venous injection and infusion(55.3%), medical examination and treatment(48.9%), per-cutaneous venepuncture for blood sampling (46.3%) and intra-muscular injection(42.2%). 3. The study showed that needle stick injuries occured before(19%), during(25%), and after (56%) client treatment. The major causes of needle stick injuries were perceived to be hastiness(82.2%) and carelessness(48.3%). Of these injuries, 91.8% occured in emergency situations. 4. Follow of care for the injury consisted of : treating the injured site immediately using disinfectants(89.7%), reviewing the clinical records of the patient involved(84.2%), immunological investigation for the status of antibodies(11.1%) and self-medication of antibiotics (10.7%). Only 16.3% of the total episodes were founded to have been reported to the administrative unit. 5. The length of clinical experience of the nurses, clinical specialty and length of clinical experience in physicians were found to have influenced the episodes of needle stick injuries ; nurses with less than 1 year and with more than 6 years of clinical experiences had significantly lower levels (X$^2$=25.04, P=.00), surgeons had significantly higher levels (X$^2$=9.89, P=.02) compared to that of internists and interns, higher(X$^2$=4.54, P=.03)than residents.

• 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.

• Journal of Preventive Medicine and Public Health
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• v.27 no.2 s.46
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• pp.175-185
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• 1994

In order to anticipate disease pattern and health problems of Koreans in the 1st part of 21st century (by the year 2020), transition of population characteristics, mortality and morbidity data during the last 30 years Koreans have experienced were reviewed. On the actual basis of epidemiologic transition process that has undergone during last 30 years since 1960 along with socioeconomic development and successful implementation of selective national health policies (family planning, medical insurance and etc.), following changes can be expected in the 21st century in Korea, under the assumption that the current rate of progress is maintained. The population of South Korea alone will be doubled the population of 1960 by the year 2013 : aged Population older than 65 years will be increased from 3.3% in 1960 to 11.4% in 2020 with increased average age of the population from 23.6 year in 1970 to 39.2 year in 2020; urban population from 28% in 1960 to 83% in 2005. GNP/capita has increased tremendously from U.S. $120 in 1970 to $6,749 in 1992, and the government estimated it would be 519,350 in 2010 and $29,460 in 2020. Growth and developmental indices of children, educational achievement and social status of women also showed a remarkable improvement and anticipated to make futher progress. Leading causes of mortality and morbidity have shown a striking change during the last 30 years, from infectious diseases to chronic degenerative diseases and man-made injuries. Occurrence of communicable diseases may become minimal although viral hepatitis, venereal diseases Including AIDS, and well adapted herpes virus infections will maintain their endemic level. Newly evolving infectious agents, however, should be carefully monitored because of rapidly changing environments and human behaviours. Tuberculosis may increase up to the epidemic level when AIDS prevails. Ischemic heart diseases may increase steadily with increasing occurrence of hypertension and diabetes mellitus whereas cerebrovascular diseases may be decreased slowly. Musculaskeletal diseases which contribute a lot to the disability of aged people may be a major health problems due to increased aged population. Mental diseases, particularly that caused by alcohol and drug abuse, and senile dementia may become a prominent health problem. On the other hand injuries caused by traffic and industrial accidents that have shown most striking increase till now may be decreased considerably by intensive intervention. The health policies in the 21st century will be oriented to the health promotion for good quality life rather than life-savings.

• Reproductive and Developmental Biology
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• v.30 no.3
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• pp.157-162
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• 2006

Endogenous 84 amino acid parathyroid hormone(PTH) is synthesized as a pre-pro hormone by the chief cells of the parathyroid glands. Physiological actions of PTH include regulation of bone metabolism, renal tubular reabsorption of calcium and phosphate, and intestinal calcium absorption. In addition, PTH stimulates new bone formation by extraordinary stimulation of osteoblastic activity and decreasing calcium excretion by the kidney. In this study, we constructed and tested retrovirus vectors designed to express the human parathyroid hormone(hPTH) gene under the control of the tetracycline-inducible promoters. To increase the hPTH gene expression at turn-on state, woodchuck hepatitis virus posttranscriptional regulatory element(WPRE) sequence was also introduced into retrovirus vector at downstream region of either the hPTH gene or the sequence encoding reverse tetracycline-controlled transactivator(rtTA). Transformed primary culture cells(porcine fetal fibroblast, PFF, chicken embryonic fibroblast, CEF) were cultured in the medium supplemented with or without doxycycline(tetracycline derivative) for 48 hours, and induction efficiency was measured by comparing the hPTH gene expression level using two step RT-PCR and ELISA Higher hPTH expression($3{\tims}10^4\;pg/ml,\;5.3{\times}10^4\;pg/ml$) and tighter expression control(up to 8 fold) were observed from the vector in which the WPRE sequence was placed at downstream of the hPTH gene. The resulting tetracycline inducible vector system may be helpful in solving serious physiological disturbance problems which have been a major obstacle in successful production of transgenic animals.

• Journal of Preventive Medicine and Public Health
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• v.24 no.2 s.34
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• pp.195-210
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• 1991

Fatty liver is caused by derangement of fat metabolism and can be reversed by removal of contributing factors. The contributing factors of fatty liver is known to be overweight, chronic alcoholism, diabetes mellitus, malnutrition, and drug abuse such as tetracycline. This study was carried out on 1335 persons who visited 'Soon Chun Hyang Human Dock Center' from March to June 1990. In analysis of the data, prevalence of fatty liver diagnosed by ultrasonogram by age and sex, laboratory finding between fatty liver group and normal group, and odds ratio of known contributing factors, were compared. The results obtained are as following ; 1) The prevalence rate of fatty liver diagnosed by ultrasonogram is 29.6% in male and 11.5% in female. 2) Age groups with high prevalences are $40{\sim}50's$ in male (32.0%) and 50's in female (24.5%). 3) The fatty liver shows significant association with style (p<0.05), whereas not with hepatitis B-virus surface antigen (p>0.05). 4) All laboratory values except alkaline phosphatase and bilirubin are elevated significantly in accordance with the degree of fatty liver (p<0.01). 5) Fatty liver diagnosed by ultrasonogram showed so strong associations with body index, triglycerides and gamma-glutamyl transferase for males, and body index and fasting blood sugar for females that these factors may be used as supplementary data in establishing diagnosis of fatty liver. 6) Odds ratio of contributing factors are as follows ; If the odds ratio of below 29 year of age is 1.0 then that of $30{\sim}39$ is 1.74 (p=0.33), $40{\sim}49$ is 2.47 (p=0.10), $50{\sim}59$ is 2.86 (p=0.0570), over 60 is 1.81 (p=0.34). If the odds ratio of female is 1.0 then that of male is 5.67 (p<0.01). If the odds ratio of body index below zero is 1.0 then that of $0{\sim}9$ is 5.08 (p<0.01), $10{\sim}19$ is 12.37 (p<0.01), $20{\sim}29$ is 29.19 (p<0.01), 30 above is 154.02 (p<0.01). If the odds ratio of below 99 mg/dl FBS is 1.0 then that of $100{\sim}120$ is 106 (p=0.76), over 120 is 1.91 (p=0.02). If the odds ratio of below $29{\mu}/1{\gamma}-GT$ is 1.0 then that of $30{\sim}s59$ is 2.11 (p<0.01), $60{\sim}90$ is 1.87 (p<0.05), 90 above is 1.69 (p=0.15). If the odds ratio of below 149 mg/dl TG is 1.0 then $150{\sim}199$ is 1.49 (p=0.05), $200{\sim}250$ is 1.09 (P=0.77), 250 above is 2.53 (p<0.01). In summary, early diagnosis of fatty liver could be made by ultrasonogram supplemented with body index and nm triglyceride. The fatty liver could be preventive by avoiding contributing factors such as obesity, alcohol intake, high blood sugar appropriately.