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Apoptotic Effect of Co-Treatment with Valproic Acid and HS-1200 on Human Osteosarcoma Cells (Valproic acid와 HS-1200의 병용처리가 사람골육종세포에 미치는 세포자멸사 효과에 대한 연구)

  • Kim, Duck-Han;Lee, Kee-Hyun;Kim, In-Ryoung;Kwak, Hyun-Ho;Park, Bong-Soo;Jeong, Sung-Hee;Ko, Myung-Yun;Ahn, Yong-Woo
    • Journal of Oral Medicine and Pain
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    • v.35 no.3
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    • pp.165-175
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    • 2010
  • Valproic acid (VPA) is a well-known anticonvulsive agent and has been used in the treatment of epilepsy for almost 30 years. VPA emerged in 1997 as an antineoplastic agent as well, when findings indicated the substance inhibited proliferation and induced differentiation of primitive neuroectocdermal tumor cells in vivo (Cinatl et al., 1997). Antitmor activity of VPA is associated with its targeting histone deacetylases. Bile acids and their synthetic derivatives induced apoptosis in various kinds of cancer cells and anticancer effects. It has been reported that the synthetic chenodeoxycholic acid (CDCA) derivatives showed apoptosis-inducing activity on various cancer cells in vitro. This study was undertaken to investigate the synergistic apoptotic effect of co-treatment with the histone deacetylases inhibitor, VPA and a CDCA derivative, HS-1200 on human osteosarcoma (HOS) cells. Cell viability was evaluated by trypan-blue exclusion. Induction and augmentation of apoptosis were confirmed by Hoechst staining, flow cytometry (DNA hypoploidy and MMP change), Westen blot analysis and immunofluorescent staining. In this study, HOS cells co-treated with VPA and HS-1200 showed several lines of apoptotic manifestation such as nuclear condensations, the reduction of MMP, the decrease of DNA content, the release of cytochrome c into cytosol, the translocation of AIF onto nuclei, and activation of caspase-7, caspase-3 and PARP whereas each single treated HOS cells did not. Although the single treatment of 1 mM VPA or $25\;{\mu}M$ HS-1200 for 48 h did not induce apoptosis, the co-treatment of them induced prominently apoptosis. Therefore our data provide the possibility that combination therapy of VPA and HS-1200 could be considered as a novel therapeutic strategy for human osteosarcoma.

Gender Roles, Accessibility, and Gendered Spatiality (성역할, 접근성, 그리고 젠더화된 공간성)

  • Kim, Hyun-Mi
    • Journal of the Korean Geographical Society
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    • v.42 no.5
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    • pp.808-834
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    • 2007
  • This study attempts to elucidate manifold dimensions of gendered accessibility experiences. How gender roles(household responsibilities) differentiate accessibility experiences between women and men is explored through the comparison of married dual-earner couples' parental status, using the US Portland activity-travel diary dataset with GIS-based geocomputation results of(time-geography based) space-time accessibility. First, this study shows how gender division of labor within the household still permeates current society, despite the widespread belief of the social change toward a gender-egalitarian society. Then, the study pays special attention to the way gender roles structure individual accessibility experiences of women and men differently, and, in turn, the way such accessibility experiences take a form of gendered spatiality. Gendered spatiality is examined through the analysis of accessibility space as well as activity space in order to ascertain women's home-attached and spatially entrapped characteristics. More household responsibilities throughout a day and, even more, the time constraint of picking up children at the daycare centers after work lead women's possible activity space to be more home-centered. The analysis of the spatio-temporal context of accessibility space makes gendered spatiality visible. However, the findings suggest that behavioral outcomes should be understood with an explicit awareness of constraints individuals face. It is because the revealed activity spaces can be not only an outcome of constraint but also an outcome of choice. Behavioral outcomes should not be treated as a straightforward expression of the level of constraints. It is problematic to expect that behavioral outcomes directly mirror the level of constraints. It is also problematic to suppose that the level of constraints can be straightforwardly elicited from revealed behavioral outcomes.

Analysis and Risk Assessment of N-Nitrosodimethylamine and Its Precursor Concentrations in Korean Commercial Kimchi (국내 유통 김치 중 N-Nitrosodimethylamine과 그 전구물질의 함량 분석 및 안전성 평가)

  • Kang, Kyung Hun;Kim, Sung Hyun;Kim, Sang-Hyun;Kim, Jeong Gyun;Sung, Nak-Ju;Lim, Heekyung;Chung, Mi Ja
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.2
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    • pp.244-250
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    • 2017
  • Dimethylamine (DMA), nitrate, nitrite, and biogenic amines (BA) are precursors of carcinogenic N-nitrosamines. This study investigated contamination levels of DMA, nitrate, nitrite, and BA in various types of Korean commercial kimchi such as Baechu kimchi, Kkakduki, Chonggak kimchi, Matkimchi, ripened Baechu kimchi, and Baek kimchi. The average DMA, nitrate, and nitrite levels in Baechu kimchi were 29.7, 2,178.8, and 3.0 mg/kg, respectively. Low levels of DMA and nitrate were detected in Kkakduki. Tryptamine, putrescine, cadaverine, tyramine, and spermidine were detected in kimchi with exclusion of Baek kimchi and Chonggak kimchi. Tryptamine in Baek kimchi was only present in trace amount, and spermidine was not detected in Chonggak kimchi. The average tryptamine, putrescine, cadaverine, tyramine, and spermidine levels in Baechu kimchi were 15.0, 64.6, 18.0, 44.0, and 7.8 mg/kg, respectively. A low level of tyramine was detected in Kkakduki. In addition, contamination of N-nitrosodimethylamine (NDMA) was detected in Kkakduki at a level of $1.38{\mu}g/kg$. Daily exposure to NDMA in the consumer only group was estimated using average daily Kkakduki consumption and average body weight of the total population. The estimated daily intake of NDMA by Kkakduki was $2.31{\times}10^{-7}mg/kg\;b.w./d.$ The margin of exposure to NDMA for the general population was 259,924. Accordingly, the health risk from NDMA caused by intake of Kkakduki was considered to be very low.

Rapid prenatal diagnosis of chromosome aneuploidies in 943 uncultured amniotic fluid samples by fluorescence in situ hybridization (FISH)

  • Han, Sung-Hee;Kang, Jeom-Soon;An, Jeong-Wook;Lee, An-Na;Yang, Young-Ho;Lee, Kyu-Pum;Lee, Kyoung-Ryul
    • Journal of Genetic Medicine
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    • v.5 no.1
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    • pp.47-54
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    • 2008
  • Purpose : Fluorescence in situ hybridization (FISH) on uncultured amniotic fluid cells offers the opportunity for rapid screening of aneuploidies and has become an integral part of the current practice in many clinical cytogenetics laboratories. Here, we retrospectively analyzed the results of interphase FISH in 943 amniotic fluid samples and assessed the efficiency of FISH for rapid detection of aneuploidies. Methods : Interphase FISH for chromosome 13, 18, and 21 was performed in 943 consecutive amniotic fluid samples for rapid diagnosis of aneuploidies referred from 2004 to 2006. Karyotypes from standard cytogenetic analysis were compared to the FISH results. Results : A total of 45 chromosomal rearrangements (4.8%) were found after conventional cytogenetic analysis of the 943 amniotic fluid. After exclusion of known familiar chromosomal rearrangements and inversions (2.1%, 20/943), 2.7% (25/943) were found to have chromosomal abnormalities. Of this group, 0.7% (6/943) were chromosomal abnormalities not detectable by FISH and 2.0% (19/943) were numerical abnormalities detectable by FISH. All 14 cases of Down syndrome (Classic type, 13 cases; Robertsonian type, 1 case) and 5 cases of trisomy 18 were diagnosed and detected by FISH and there were no false-positive or -negative results (specificity and sensitivity=100%). Conclusion : The present study demonstrates that FISH can provide a rapid and sensitive clinical method for prenatal identification of chromosome aneuploidies. However, careful genetic counseling is essential to explain the limitations of FISH, including the inability to detect all chromosomal abnormalities and the possibilities of uninformative or false-negative results in some cases.

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Evaluation of Uricult Trio Test as a Rapid Screening of UTI in Children with Fever (소아 요로감염 진단에 있어 신속배양검사(Uricult Trio)의 유용성에 관한 연구)

  • Lee, Jin;Kim, Eun Jin;Lee, Taek Jin;Chang, Jin Keun;Cha, Sung-Ho
    • Pediatric Infection and Vaccine
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    • v.17 no.2
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    • pp.74-82
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    • 2010
  • Purpose : The Dipslide culture test is a rapid method for diagnosis of urinary tract infection (UTI). The aim of this study is to determine the diagnostic availability of a urine Dipslide test for evaluation of UTI in febrile children. Methods : Urine specimens from 151 febrile infants were inoculated by a routine blood agar urine culture method and the Dipslide test at the same time. Following incubation for 16-24 hours, the results of the Dipslide test were read at the next visit. Both results of Dipslide and those of routine culture were compared. Results : The mean age of subjects was 15${\pm}$10.6 months. There were 150 infants (99.3%) who had fever with a mean duration of 2.6${\pm}$2.6 days. Thirty two infants (21.2%) were diagnosed as having UTI. Sensitivity and specificity of Uricult Trio CLED medium were 59.4% and 84.8%, respectively. Sensitivity and specificity of Uricult Trio E. coli medium were 60.0% and 96.2%, respectively. The Pearson correlation coefficient between results of Uricult Trio CLED medium and urine culture was 0.438 (P=0.01). Correlation between results of Uricult Trio E. coli medium and urine culture was 0.617 (P=0.01). Conclusion : The Dipslide test requires only 16-24 hours with high specificity in terms of UTI caused by E. coli without the problems associated with specimen delay. This test seems to be helpful for exclusion of UTI in febrile infants and it may reduce unnecessary hospitalization and antibiotic use. However, further studies are required before the product can be recommended as a routine diagnostic tool.

Favorable Outcome in Elderly Asian Patients with Metastatic Renal Cell Carcinoma Treated with Everolimus: The Osaka Urologic Oncology Group

  • Inamoto, Teruo;Azuma, Haruhito;Nonomura, Norio;Nakatani, Tatsuya;Matsuda, Tadashi;Nozawa, Masahiro;Ueda, Takeshi;Kinoshita, Hidefumi;Nishimura, Kazuo;Kanayama, Hiro-Omi;Miki, Tsuneharu;Tomita, Yoshihiko;Yoshioka, Toshiaki;Tsujihata, Masao;Uemura, Hirotsugu
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.4
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    • pp.1811-1815
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    • 2014
  • Background: In clinical trials with no upper age limit, the proportion of older patients is usually small, probably reflecting the more conservative approach adopted by clinicians when treating the elderly. An exploratory analysis of elderly patients in the RECORD-1 Trial showed that patients ${\geq}$ 65 y.o. had superior median PFS than overall RECORD-1 population (5.4 months and 4.9 months, respectively). We investigated the efficacy, relative benefit and safety of Everolimus (EVE) as sequential therapy after failure of VEGFr-TKI therapy for older patients with metastatic renal cell cancer (mRCC), in daily practice. Materials and Methods: 172 consecutive IRB approved patients with mRCC (median age 65, M:F 135/37, 78% clear cell) who received salvage EVE at 39 tertiary institutions between October 2009 and August 2011 were included in this analysis. Some 31% had progressed on sunitinib, 22% on sorafenib, 1% on axitinib, 41% on sequential therapy, and 5% had received other therapy. Patients with brain metastases were not included and 95% of the patients had a ECOG (Eastern Cooperative Oncology Group) performance status (PS) of 0 or 1. Previous radiotherapy was an exclusion criterion, but prior chemotherapy was permitted. Adequate organ function and hematologic parameters were mandatory. EVE administration was approved by the institutional review board at each participating institution and signed informed consent was obtained from all patients. Results: Median time of the whole cohort to last follow-up was 3.5 months (range 0.4-15.2 months). Forty four percent were continuing to take EVE at last followup. There were 86 (50%) patients ${\geq}$ 65 y.o. and 86 (50%) <65 y.o. The percentage of patients who showed PR/SD was higher in the older group than in the younger one (5.9%/61.2% vs 1.2%/46.5%, respectively). Median survival of older patients was also significantly longer (3.5 +/- 0.31 vs 3.1 +/- 0.34, hazard ratio=0.45, CI; 0.255-0.802). Analysis using Cox regression model adjusted for gender, PS, number of metastases, site of metastases, histology, smoking history and age detected an association between age and PFS (p=0.011). The frequency of adverse events in elderly patients treated with EVE was no greater than that in younger patients, although such toxicity may have had a greater impact on their quality of life. Conclusions: Older patients should not generally be excluded from accepted therapies (mTOR inhibitors after failure of VEGFr-TKI therapy) for mRCC.

The Clinical Outcomes of Arthroscopic Repair of Isolated type II SLAP Lesion in Non-athletes (비 운동선수에 있어 단독 제 2형 SLAP 병변의 관절경적 봉합수술의 임상적 결과)

  • Yoo, Jae-Chul;Ahn, Jin-Hwan;Koh, Kyoung-Hwan;Kim, Seung-Yeon
    • Journal of the Korean Arthroscopy Society
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    • v.12 no.3
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    • pp.185-190
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    • 2008
  • Purpose: The purpose of this study is to provide the clinical outcomes of arthroscopic type II SLAP repair in non-athletes, and to compare the clinical outcomes between those who had isolated type II SLAP lesion and those who had combined partial thickness supraspinatus tear that did not required a combined repair. Materials and Methods: From July 2005 to January 2007, 142 consecutive type II SLAP lesions were treated with arthroscopic surgery. The inclusion criteria for the study were; (1) younger than 50 years old; and (2) non-athletes. Exclusion criteria were; (1) prior surgery, fracture or combined recurrent dislocation history on the affected shoulder; (2) combined full thickness rotator cuff tear or PTST (>50% thickness) patient that needed repair; and (3) combined infection, arthritis or inflammatory disease. Remaining 19 patients meet the criteria. Among them, 13 had combined PTRCT that did not require repair (Group I), and 6 had isolated type II SLAP lesion without combined supraspinatus tear (Group II). The mean age was 36.7 years (29~49 years), mean symptom duration was 39.1 months (3~216 months) and mean follow-up was 19.0 months (12~27 months). In all patients, the range of motion of affected shoulder, pain and function visual analogue scale (PVAS, FVAS), the Constant score and UCLA score were evaluated preoperatively and postoperatively. Results: In group I, external rotation at side was decreased significantly (p=0.003),but there were no statistical significant change at the remains(p>0.05). And there were no differences between groups (p>0.05). At the final follow-up, all clinical outcome measurements improved after surgery with statistical significance (p<0.05): UCLA score, $22.8{\pm}5.2$ to $32.8{\pm}2.1$; Constant score, $79.4{\pm}8.6$ to $94.9{\pm}4.3$; PVAS $5.4{\pm}2.7$ to $1.1{\pm}1.4$; FVAS $63.2{\pm}15.3$ to $93.4{\pm}7.3$. But, in group comparison of the mean UCLA score and Constant score, there were no statistical significant differences between two groups. Conclusion: Arthroscopic repair of type II SLAP lesion provided good clinical outcomes in nonathletic population. Combined partial thickness supraspinatus tear does not seem to hamper the final outcome at minimal 1 year follow-up.

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MENTAL REPRESENTATION OF PRESCHOOL CHILDREN:ASSOCIATION WITH PARENTAL MENTAL REPRESENTATION (학령전기 아동의 심적 표상 : 부모에 대한 심적 표상과의 관계를 중심으로)

  • Lee, Kyung-Sook;Lee, Hae-Ran;Shin, Yee-Jin
    • Journal of the Korean Academy of Child and Adolescent Psychiatry
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    • v.10 no.1
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    • pp.21-33
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    • 1999
  • The clinical assessment for preschool children who are known to have problems in selfreporting tends to be dependent on outsiders' reporting. Thus, the direct assessment of children's inner experience, thoughts and feelings is difficult. MacArthur Story-Stem Battery(MSSB) developed to learn more about preschool children's mental representation in play is used in this study to help assess clinical preschool children through developmental study of normal children's mental representation. Fifty five children(32boys and 23girls) who performed MSSB, IQ Test, Peabody Picture Vocabulary Test-Revised(PPVT) were videotaped and were analyzed. The results of this study were as follows:1) Children frequently displayed negative mental representation such as atypical negative response, reparation/guilt, punishment, personal injury and so on during emotionally laden play situation. 2) Mental representation of parent appeared positive, disciplinary, and negative in respective. 3) As a result of factor analysis of MSSB content themes, aggressive, prosocial, and oppositional content theme composites were generated. Aggressive content included atypical negative response, aggression, personal injury, and exclusion. Prosocial content included affection, affiliation, and reparation/guilt. Oppositional content included punishment and non-compliance. 4) Mental representation of parent and content themes showed significant correlation. Positive, negative, and disciplinary representation were significantly correlated for prosocial(r=0.40), aggressive (r=0.52), and oppositional(r=0.75) content theme respectively. 5) Among the correlations between parental mental representations and emotional responses, positive parental representation and anxiety showed significant negative correlation(r=-0.43). 6) Among the correlations between content themes and emotional responses, there were significant positive correlations between aggressive(r=0.28) and oppositional content themes(r=0.29) and distress, and were significant negative correlations between prosocial content theme and concern(r=-0.29) and anxiety(r=-0.43). According to the above results, preschool children frequently displayed negative mental representation in emotionally conflictual play situation. Children with more prosocial themes in their stories exhibit more positive parental mental representation. Also, children with more aggressive themes tend to display more negative parental representation and negative emotional responses.

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Expression of CsRCI2s by NaCl stress reduces water and sodium ion permeation through CsPIP2;1 in Camelina sativa L.

  • Kim, Hyun-Sung;Lim, Hyun-Gyu;Ahn, Sung-Ju
    • Proceedings of the Korean Society of Crop Science Conference
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    • 2017.06a
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    • pp.194-194
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    • 2017
  • Camelina (Camelina sativa L.) is a potential bio-energy crop that has short life cycle about 90 days and contains high amount of unsaturated fatty acid which is adequate to bio-diesel production. Enhancing environmental stress tolerance is a main issue to increase not only crop productivity but also big mass production. CsRCI2s (Rare Cold Inducible 2) are cold and salt stress related protein that localized at plasma membrane (PM) and assume to be membrane potential regulation factor. These proteins can be divide into C-terminal tail (CsRCI2D/E/F/G) or no-tail group (CsRCI2A/B/C/H). However, function of CsRCI2s are less understood. In this study, physiological responses and functional characterization of CsRCI2s of Camelina under salt stress were analyzed. Full-length CsRCI2s (A/B/E/F) and CsPIP2;1 sequences were confirmed from Camelina genome browser. Physiological investigations were carried out using one- or four-week-old Camelina under NaCl stress with dose and time dependent manner. Transcriptional changes of CsRCI2A/B/E/F and CsPIP2;1 were determined using qRT-PCR in one-week-old Camelina seedlings treated with NaCl. Translational changes of CsRCI2E and CsPIP2;1 were confirmed with western-blot using the antibodies. Water transport activity and membrane potential measurement were observed by cRNA injected Xenopus laevis oocyte. As results, root growth rate and physiological parameters such as stomatal conductance, chlorophyll fluorescence, and electrolyte leakage showed significant inhibition in 100 and 150 mM NaCl. Transcriptional level of CsPIP2;1 did not changed but CsRCI2s were significantly increased by NaCl concentration, however, no-tail type CsRCI2A and CsRCI2B increased earlier than tail type CsRCI2E and CsRCI2F. Translational changes of CsPIP2;1 was constitutively maintained under NaCl stress. But, accumulation of CsRCI2E significantly increased by NaCl stress. CsPIP2;1 and CsRCI2A/B/E/F co-expressed Xenopus laevis oocyte showed decreased water transport activity as 61.84, 60.30, 62.91 and 76.51 % at CsRCI2A, CsRCI2B, CsRCI2E and CsRCI2F co-expression when compare with single expression of CsPIP2;1, respectively. Moreover, oocyte membrane potential was significantly hyperpolarized by co-expression of CsRCI2s. However, higher hyperpolarized level was observed in tail-type CsRCI2E and CsRCI2F than others, especially, CsRCI2E showed highest level. It means transport of $Na^+$ ion into cell is negatively regulated by expression of CsRCI2s, and, function of C-terminal tail is might be related with $Na^+$ ion influx. In conclusion, accumulation of NaCl-induced CsRCI2 proteins are related with $Na^+$ ion exclusion and prevent water loss by CsPIP2;1 under NaCl stress.

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Analysis of Immunogenicity after Hepatitis B Vaccination in Korea by Literature Review (문헌 분석에 의한 B형 간염 백신의 항체 양전률의 비교)

  • Roh, Hye Ok;Lee, Woo Gill;Sohn, Young Mo
    • Pediatric Infection and Vaccine
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    • v.5 no.2
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    • pp.245-257
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    • 1998
  • Purpose : Although hepatitis B vaccine has been available to general population in Korea since 1983, it was difficult to compare various types of hepatitis B virus(HBV) vaccines primarily due to the differences in vaccination schedule, dosage, test methods and seropositive antibody level. In this study we reviewed the results of previous studies published in Korea, which include antibody positive rates and antibody titers of various vaccines, and examined the immunogenicity of these HBV vaccines. Methods : Studies published in medical journals, university journals concerning antibody positive rates following hepatitis B vaccination were reviewed. Inclusion criteria were those studies in which seroprotective antibody rate of 10mIU/mL or the sample ratio unit of 10 RU were used as the cut-off value and in which the test methods were RIA or ELISA. Exclusion criteria were; 1) unclear or inconsistent vaccine dosage, 2) no record of antibody titers or seroconversion rate, 3) no defined antibody rate or ratio for positive rating and 4) the vaccination schedule other than 0-1-2 months or 0-1-6 months. Results : 23 out of 52 studies were subjected for the review for seroconversion rates. 1) As for the immunogenicity in each age group, the seroconversion rates of Hepaccine(Cheil Jedang) were 85.1% in infants, 83.3% in children and 62.7% in adults, indicating higher rates in infants and children compared to adults(P<0.01). The seroconversion rates of Hepavax(Korea Green Cross) were 84.7%, 81.1% and 90.8%, indicating higher rates in infants and adults compared to children(P<0.01). 2) The seroconversion rate of Hepavax was 85.6% with 0-1-6 mo. schedule, 78.5% with 0-1-2 mo. schedule with a statistically significant difference(P<0.01). 4) There was no difference of seroconversion rates between the two doses of Hepavax, $5{\mu}g$ and $10{\mu}g$ in infants and children. 5) In adults the seroconversion rates were 62.7% with Hepaccine, 90.8% with Hepavax, and 94.8% with Engerix-B(SmithKline Beecham). Conclusion : In Korea, the incidence of chronic hepatitis B is high and changing the schedule in vaccination cannot contribute to the increase of the serocoversion rate. And in order to maximize immunogenicity, more effective vaccines as well as more proper vaccination methods should be used.

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