• Journal of Preventive Medicine and Public Health
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• v.20 no.1 s.21
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• pp.129-136
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• 1987

To determine the hepatitis 8 virus infection rate of the medical school students and appropriate time for immunization with hepatitis B vaccine,355 students in the 1st, 2nd and 3rd grades of Medical School of Kyungpook National University who had not been vaccinated and volunteered to participate in this study were tested for HBsAg, anti-HBs and anti-HBc with radioimmunoassay method (Abbott Lab. kit). A questionnaire was administered to ask the history of transfusion, acupuncture and surgery. HBsAg positive students were retested 16 months after the initial test. Overall HBsAg positive rate was 6.8% and the age adjusted rate for male (7.2%) was higher than that for female (4.9%). Anti-HBs positive rate was 35.3% (36.1% for male, 37.9% for female) and anti-HBc positive rate was 45.5% (46.5% for male,44.7% for female). Overall hepatitis B virus (HBV) infection rate was 49.1% and the infection rate for male (50.3%) was slightly higher than that for female (46.5%). HBsAg positive rate and infection rate were increased as the grade increased but it was attributed to the age distribution of the students. HBaAg positive rate for 20 years old students was 1.7%; 21 years, 6.6%; 22 years, 6.1%; 23 years, 12.2%; and 24 years and older, 6.4%. HBV infection rate showed an increasing trend as age increased; 45.8% for 20 years,41.5% for 21 years, 49.5% for 22 years, 55.5% for 23 years and 59.6% for 24 years and older. The age differences in HBsAg positive rates and HBV infection rates did not reach the statistical significance level of 0.05. However, these findings and similar age differences in HBsAg positive rates and HBV infection rates observed in other study suggest that there is a significant age differences. Study of the same age group in other schools and different social classes is warranted to confirm the age difference. Clarification of the reason for such differences would provide a clue to identify the major route of HBV transmission in this age group. Among 26 HBsAg positive students in the initial test, only one student was active hepatitis patient. Out of 24 students who had follow-up test after 16 months 22 students were positive for HBaAg and two students became HBsAg negative and anti-HBs positive. It is obvious that nearly one-half of the medical school students were infected with HBV before 20 years of age and the HBV infection occurs in medical school. Thus, it is recommended to test all the students for HBV infection soon after the admission to the medical school and immunize all the susceptible students with hepatitis B vaccine and give booster as they start to practice at a hospital.

• Clinical and Experimental Pediatrics
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• v.45 no.10
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• pp.1234-1240
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• 2002

Purpose : This study was carried out to obtain the vaccination rate and age appropriateness of vaccination in children under five years of age in Jeonbuk province. Methods : Eight hundred and fifty infants and children were enrolled in this study. Vaccination rate(Number of vaccinees/Number of subjects), places of vaccination, age appropriateness of vacination were examined by either vaccine record review or interview with parents or guardians. Results : The salient features of the findings were as follows : All subjects were aged under five and mostly under two years of age(68.8%). Places of vaccination were health centers or subcenters( 50.4%), private clinics(44.3%), and general hospitals(5.3%). Routine vaccinations such as BCG, hepatitis B vaccine(HBV), diphtheria, tetanus, acellular pertussis(DTaP) and Trivalent Oral Polio Vaccine(TOPV), measles, mumps, rubella(MMR), and Japaneses B encephalitis(JBE) were vaccinated mostly in health centers or subcenters, while chickenpox(CHP) and haemophilus influenzae vaccines(Hib), which are not routine in Korea, were vaccinated in private clinics. The vaccination rates of BCG(99.2%), HBV(93.5%) and DTaP(96.1%) were very high. But those of MMR(83.7%), CHP(72.5%), JBE(50.2%), and Hib(15.8%) were lower than expected. Considering the age appropriateness of vaccination, some infants and children were not appropriately vaccinated(vaccination rate/age appropriateness of vaccine; HBV, 93.5%/88.4% : DTaP, 94.6%/73.1% : JBE, 50.2%/ 18.5%). Conclusion : The vaccination rate of BCG, HBV, DTaP and TOPV was very high, but MMR, CHP, JBE, and Hib vaccination rate was not high enough to be able to protect against epidemic. We should pay more attention to vaccinating children, and there is a need for a program that will enhance coverage for vaccines.

• IMMUNE NETWORK
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• v.9 no.1
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• pp.20-26
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• 2009

We previously reported that $IFN-{\gamma}$ producing T cell responses induced by the combined therapy of DNA vaccine and lamivudine for one year are important for the induction of sustained virological response (SVR). However, $IFN-{\gamma}$ production is not sufficient to predict sustained viremia control in chronic hepatitis B (CHB) carriers treated. Methods: Twelve CHB carriers were intramuscularly immunized 12 times at a 4-week interval with 8mg of HBV DNA vaccine during the standard lamivudine treatment (100mg/daily/1 year). The level of cytokines during and after the combined therapy in plasma of all 12 CHB carriers treated was determined by each ELISA kit. Six out of 12 CHB carriers revisited the clinic, and their HBV DNA levels were examined. Results: The combined therapy increased plasma IL-12 and IL-12/p40 ratio during the treatment (baseline vs. peak level: $41.8{\pm}8.3$ vs. $163.1{\pm}29.2\;pg/ml$; p<0.01 and $0.96{\pm}0.25$ vs. $3.58{\pm}0.86$; p<0.01, respectively), and the peak level of plasma IL-12 and IL-12/p40 ratio was evoked at 6 to 10 months during the combined therapy. In particular, CHB carriers with SVR had two and three-fold higher level of the peak plasma IL-12 and plasma IL-12/p40 ratio than non-virological responders (NVRs), respectively ($218.0{\pm}41.4$ vs. $108.1{\pm}28.6\;pg/ml$; p=0.09 and $5.35{\pm}1.38$ vs. $1.80{\pm}0.29$; p<0.05, respectively), while p40 level was consistent during the combined therapy. In addition, there was no significant temporal correlation between the peak IL-12/p40 ratio and the elevation of serum alanine amino-transferase (ALT) in this study, contrast to $IFN-{\alpha}$ therapy which induced peak IL-12 level following ALT flares. Conclusion: Our results indicate that the combined therapy induces the increase of plasma IL-12 and IL-12/p40 ratio, which are associated with long-term SVR in CHB carriers.

• Pediatric Infection and Vaccine
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• v.11 no.1
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• pp.73-80
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• 2004

Purpose : The serial clinical findings, biochemical results, and serological hepatitis B virus(HBV) markers in Korean children with chronic HBV infection were analyzed to determine the relationships among these factors. Methods : Ninety children have been chosen from those who have visited to the Department of Pediatrics at St. Vincent's Hospital in The Catholic University of Korea from July 1st, 1995 to June 30th, 2000. The sample patients were followed up for over six months. HBV markers and liver function tests were all performed. Results : All children were asymptomatic at presentation. Eighty-three percent of the children had a history of chronic HBV infection in their families. Eighty-one percent were HBeAg positive, 16% were anti-HBe positive, while 3% were all HBeAg and anti-HBe negative. The prevalence of HBeAg among three age groups : 0~5; 6~10; and 11~15 year-old was 90%, 96% and 61% respectively. The prevalence of HBeAg in less than 10 year-old group was significantly higher than 11~15 year-old group(P=0.001). Serum ALT levels were within 40 IU/L in 64% children, 41~80 IU/L in 17%, 81~200 IU/L in 10%, and beyond 201 IU/L in 9%. The percentage of abnormality of ALT levels in HBeAg positive patients was significantly higher than that of HBeAg negative(P=0.036). Eleven of the 73 HBeAg positive children lost their HBeAg and seroconverted to anti-HBe. In these cases, all had transient elevations in ALT levels before HBeAg seroconversions. The annual rates of spontaneous seroconversion of HBeAg and HBsAg were 9.7% and 0.6%, respectively. Conclusion : Recognition of the dynamics of these changes in viral markers and biochemical findings is needed in the selection and evaluation of therapeutic regimens, establishment of treatment, and calling for controlled trials with adequate follow-up. The hepatitis B carrier state may be asymptomatic in children however, continued surveillance of carriers is important to determine the individual adverse prognostic factors of chronic HBV infections.

• Microbiology and Biotechnology Letters
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• v.14 no.6
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• pp.455-460
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• 1986

Dane particle was prepared from the plasma of chronic HBsAg carrier with high levels of HBsAg activity. DNA extracted front Dane particle core after a DNA polymerase reaction with $\alpha$-($^{32}$P) dNTP, was identified as HBV DNA by liquid scintillation counter and agarose gel electrophoresis-G.M. counting. To produce Hepatitis B surface antigen for use as a vaccine against Hepatitis B virus infection, yeast strains harboring recombinant plasmid with Apase promoter was used. Recombinant plasmid was construced from pHBV 130 and pAN 82, transformed into E coli, and then transferred into yeast strains. HBsAg was produced by derepression in Burkholder minimal medium with controlled inorganic phosphate concentration. The kinetics of HBsAg production was also investigated. Total HBsAg activity increased rapidly between 3 and 6 hours after transfer to phosphate-free medium and reached a maximum at around 9th hour. The transfer into phosphate-free medium after 6 hours in high phosphate cell growth medium gave maximum activity.

• Clinical and Experimental Pediatrics
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• v.63 no.1
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• pp.25-29
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• 2020

Background: Pain during the developmental period may adversely affect developing neuronal pathways and result in adverse neurodevelopmental, cognitive, and behavioral effects in later life. Immunizations, e.g., hepatitis B vaccine (HBV), administered at birth are painful experiences to which neonates are universally subjected. Purpose: Here we aimed to study and compare the effectiveness of various nonpharmacological pain management methods in newborns to enable the development of safe and effective analgesic methods for newborns. Methods: This prospective study was conducted at a tertiary care hospital in the Himalayan region. Three hundred term healthy neonates were divided into 6 groups of 50 each. Groups 1-5 were intervention groups, patients of which received a nonpharmacological intervention (breastfeeding, nonnutritive sucking, rocking, 25% sucrose, or distilled water) before the intramuscular HBV, while patients in group 6 received no intervention. The pain response in each group after the HBV injection was assessed and compared using cry duration and Douleur Aigue Nveau-ne (DAN) score, a behavioral acute pain rating scale for newborns. Results: Cry duration was decreased in all intervention groups, significantly so in the sucrose (19.90 seconds), breastfeeding (31.57 seconds), and nonnutritive sucking (36.93 seconds) groups compared with controls (52.86 seconds). DAN scores decreased significantly (P<0.05) at one or more points i.e. 30, 60, or 120 seconds in the breastfeeding and 25% sucrose intervention groups compared with controls. Conclusion: Oral sucrose and nonnutritive sucking are simple yet underutilized nonpharmacological interventions that effectively reduce pain in newborns.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3595-3604
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• 2015

Hepatocellular carcinoma (HCC) has been one of the most fatal malignant tumors worldwide and its associated morbidity and mortality remain of significant concern. Based on in-depth reviews of serological diagnosis of HCC, in addition to AFP, there are other biomarkers: Lens culinaris agglutinin-reactive AFP (AFP-L3), descarboxyprothrombin (DCP), tyrosine kinase with Ig and eprdermal growth factor (EGF) homology domains 2 (TIE2)-espressing monocytes (TEMs), glypican-3 (GPC3), Golgi protein 73 (GP73), interleukin-6 (IL-6), and squamous cell carcinoma antigen (SCCA) have been proposed as biomarkers for the early detection of HCC. The diagnosis of HCC is primarily based on noninvasive standard imaging methods, such as ultrasound (US), dynamic multiphasic multidetector-row CT (MDCT) and magnetic resonance imaging (MRI). Some experts advocate gadolinium diethyl-enetriamine pentaacetic acid (Gd-EOB-DTPA) MRI and contrast-enhanced US as the promising imaging madalities of choice. With regard to recent advancements in tissue markers, many cuting-edge technologies using genome-wide DNA microarrays, qRT-PCR, and proteomic and inmunostaining studies have been implemented in an attempt to identify markers for early diagnosis of HCC. Only less than half of HCC patients at initial diagnosis are at an early stage treatable with curative options: local ablation, surgical resection, or liver transplant. Transarterial chemoembolization (TACE) is considered the standard of care with palliation for intermediate stage HCC. Recent innovative procedures using drug-eluting-beads and radioembolization using Yttrium-90 may exhibit beneficial effects in HCC treatment. During the past few years, several molecular targeted agents have been evaluated in clinical trials in advanced HCC. Sorafenib is currently the only approved systemic treatment for HCC. It has been approved for the therapy of asymptomatic HCC patients with well-preserved liver function who are not candidates for potentially curative treatments, such as surgical resection or liver transplantation. In the USA, Europe and particularly Japan, hepatitis C virus (HCV) related HCC accounts for most liver cancer, as compared with Asia-Pacific regions, where hepatitis B virus (HBV) may play a more important role in HCC development. HBV vaccination, while a vaccine is not yet available against HCV, has been recognized as a best primary prevention method for HBV-related HCC, although in patients already infected with HBV or HCV, secondary prevention with antiviral therapy is still a reasonable strategy. In addition to HBV and HCV, attention should be paid to other relevant HCC risk factors, including nonalcoholic fatty liver disease due to obesity and diabetes, heavy alcohol consumption, and prolonged aflatoxin exposure. Interestingly, coffee and vitamin K2 have been proven to provide protective effects against HCC. Regarding tertiary prevention of HCC recurrence after surgical resection, addition of antiviral treatment has proven to be a rational strategy.

• Pediatric Infection and Vaccine
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• v.4 no.2
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• pp.240-256
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• 1997

Purpose: To evaluate the hepatitis B vaccination program which has been conducted since 1980, Korea. Methods: This study was carry out self reported questionnaire and serologic test covering 2,072 elementary school students who were born between 1980 and 1987, selected by cluster sampling. The HBV serologic markers (HBsAg, Anti-HBs and Anti-HBc) were tested by radioimmunoassay (RIA). The contents of questionnaire include demographic data of students and parents, vaccination status, vaccination frequency, vaccination age, past history of mother's HBV test. Results: 1) The HBsAg positive rates by sex showed 3.7% for male and 2.7% for female, representing an average rate of 3.4%. The HBsAg positive rates by age group showed 5.6% for 13 years and l.5% for 6 years, representing a tendency of lowering rate as ages being younger. 2) The pre-natal HBV test rate was 10.2%, while post-natal HBV test rate was 42.5%. The test showed that the parents' educational level being higher than others, the pre- and post-natal HBV test showed higher rates. In case the fathers occupation being office worker, the post-natal HBV test showed a higher rate compared with other occupation. 3) Overall vaccination rate was 82.6%, complete vaccination rate 69.8%, booster injection rate 42.8%. The vaccination rate, complete vaccination rate and booster injection rate increased as the age being younger. If the educational level of parents were higher, the vaccination rate, complete vaccination rate and booster injection rate showed higher rates. Younger students showed younger vaccination age, and higher educational background of family showed younger vaccination ages. 4. With regard to positive rate of HBV markers by vaccination age, HBsAg and Anti-HBc positive rate showed higher degrees in the following order; preschool age (1-6 years), school age (6-13 years) and infancy (0-1 year). Anti-HBs positive rate was increased as the frequency of vaccination increased. Five years after initial complete vaccination, minimum protective rate was lowest, 69.6%.

• Pediatric Infection and Vaccine
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• v.25 no.2
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• pp.72-81
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• 2018

Purpose: This prospective study aimed to investigate the therapeutic efficacy of lamivudine in children with chronic hepatitis B virus (HBV) infection. Methods: During July 2003 through October 2015, children with chronic hepatitis B who visited our institution were included in this study. Fifty-five patients, who received first-line treatment of lamivudine (3 mg/kg, 100 mg maximum) for over three months, were enrolled. After initiating lamivudine, alanine aminotransferase (ALT), HBV-DNA, and HBV markers were followed up at 1 month, 3 months, and every 3 months, thereafter. The treatment endpoint was determined as 1) normalization of ALT, 2) HBeAg seroconversion, and 3) anti-HBe positivity for twelve consecutive months. Results: Thirty-one male (56.4%) and 24 female (43.6%) patients were included. The mean age at treatment initiation was 8.1 years. The mean duration of treatment was 23.4 months. ALT normalization was found in 98.2% (54 of 55). Anti-HBe seroconversion was found in 70.6% (36/51). Loss of HBsAg was found in 10.9% (6/55). All biochemical responses occurred under age seven. The rate of virologic response (defined as HBV-DNA <2,000 IU/mL) at six months after treatment initiation was 78.7% (37/47). At twelve months after reaching treatment endpoint, 87.2% (34/39) maintained their virologic response. Resistance to lamivudine was found in 16.4% (9/55). Conclusions: Lamivudine treatment in Korean pediatric patients with chronic hepatitis B showed better outcomes compared with other studies that implemented similar protocols in foreign populations. Further studies are needed to investigate the efficacy of newly recommended antiviral drugs on the Korean pediatric population.

• BMB Reports
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• v.40 no.6
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• pp.1002-1008
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• 2007

PreS domain of Hepatitis B virus (HBV) surface antigen is a good candidate for an effective vaccine as it activates both B and T cells besides binding to hepatocytes. This report deals with overexpression and purification of adr subtype of surface antigen that is more prevalent in Pakistan. PreS region, comprising 119 aa preS1 region plus a 55 aa preS2 region plus 11 aa from the N-terminal S region, was inserted in pET21a+ vector, cloned in E. coli $DH5\alpha$ cells and expressed in E. coli BL21 codon+ cells. The conditions for over expression were optimized using different concentrations of IPTG (0.01-5 mM), and incubating the cells at different temperatures (23-$41^{\circ}C$) for different durations (0-6 h). The cells were grown under the given optimized conditions (0.5 mM IPTG concentration at $37^{\circ}C$ for 4 h), lysed by sonication and the protein was purified by ion exchange chromatography. On the average, 24.5 mg of recombinant protein was purified per liter of culture. The purified protein was later lyophilized and stored at $-80^{\circ}C$.