Use of Pre-S Protein-Containing Hepatitis B Virus Surface Antigens and a Powerful Adjuvant To Develop an Immune Therapy for Chronic Hepatitis B Virus Infection

Yum, Jung Sun,Ahn, Byung Cheol,Jo, Hyun Jin,Kim, Dong Yeon,Kim, Ki Hyun,Kim, Hyo Sun,Sung, Young Chul,Yoon, Jaeseung,Morrey, John,Moon, Hong Mo American Society for Microbiology 2012 CLINICAL AND VACCINE IMMUNOLOGY Vol.19 No.2

<B>ABSTRACT</B><P>A hepatitis B virus (HBV) vaccine has been developed using a new adjuvant and HBV surface antigens produced from a CHO cell line. The purified HBV surface antigens are composed of L protein, M protein, and S protein in a mixture of 20- and 40-nm-diameter particles and filamentous forms. This HBV surface antigen, formulated with L-pampo, a proprietary adjuvant, induced 10 times more antibody than the same antigen with alum and was capable of inducing strong immune responses in three different HBV transgenic mice. In spite of the presence of a large amount of HBV antigen in the blood, no antibody against HBV surface antigen was normally detected in these transgenic mice. After immunization, the HBV antigen was also cleared from the blood.</P>

Atypical Antipsychotics are Disproportionately Associated with Patients Reporting Increased Eating Drives

Yum Sun Young,Yum Sun Kyoung,Choi Hyung Jin 대한신경정신의학회 2021 PSYCHIATRY INVESTIGATION Vol.18 No.3

What is the optimal fit-for-purpose design in an oncology first-in-human trial?: 3+3 vs. Bayesian logistic regression model

Sun Young Yum 대한임상약리학회 2020 Translational and Clinical Pharmacology Vol.28 No.1

복막투석 환자와 혈액투석 환자에서 내장 비만의 유병률 비교

구영미 ( Young Mi Ku ),김영수 ( Young Soo Kim ),윤선애 ( Sun Ae Yoon ),염근상 ( Keun Sang Yum ),민경희 ( Kyung Hee Min ),정순선 ( Soon Sun Jung ),송호철 ( Ho Cheol Song ),김용수 ( Yong Soo Kim ),정수교 ( Soo Kyo Chung ),김영옥 ( Y 대한신장학회 2008 Kidney Research and Clinical Practice Vol.27 No.4

목적: 최근 고혈압, 당뇨병, 고지혈증, 흡연과 더불어 비만이 심혈관 질환 발생을 유발하는 중요 위험 인자로 대두되고 있다. 본 연구에서는 내장 비만의 양을 측정할 수 있는 복부 지방 전산화단층촬영 (Abdominal fat CT)을 이용하여 단일 기관에서 투석 중인 혈액투석 및 복막투석 환자에서 내장 비만의 유병률을 알아보고자 하였다. 방법: 2007년1월부터 2007년3월까지 가톨릭대학교 의정부성모병원 신장내과 외래에서 투석 치료를 받는 환자를 대상으로 복부 지방 전산화단층촬영을 시행하여 내장 비만 양을 측정하였다. 내장 비만은 복부 내장지방면적이 103.8 cm2 이상인 경우로 정의하였고, 의무기록을 통해 후향적으로 투석기간, 지방수치, 신체질량지수, 당뇨병 여부 등을 분석하였다. 결과: 총 172명의 대상 환자 중 혈액투석 환자는 65명, 복막투석 환자는 67명이었다. 복막투석 환자의 평균체중 (60.1±9.3 kg vs. 67.0±12.2 kg, p=0.000), 평균 BMI (22.7±3.2 kg/m2 vs. 25.0±3.3 kg/m2, p=0.000), 중성지방 양 (146.3±83.2 mg/dL vs. 186.2±122.3 mg/dL, p= 0.031)이 혈액투석 환자에 비해 높았다. 또한 혈액투석군에 비해 평균 내장지방 면적 (97.3±50.2 cm2 vs. 122.8±47.5 cm2, p=0.003), 내장 비만 유병률 (35.4% vs. 56.7%, p= 0.014)이 복막투석군에서 높았으나, 복막투석군에서는 내장 지방면적과 신체질량지수 사이의 유의한 상관관계를 보이지 않았다 (r=0.154, p=0.214). 양 군 모두 고령 환자에서 내장 비만의 유병률이 높았다 (≥65) (p=0.004). 결론: 본 연구를 통해 혈액투석군에 비해 복막투석군의 내장 비만 발생률이 높았다. 추가적인 연구가 필요하겠으나 복막투석 환자에서 대사 증후군의 발생을 예방하기 위한 체중 및 영양 상태의 적극적인 조절이 필요할 것으로 사료된다. Purpose: Visceral obesity is a more reliable indicator of cardiovascular risk factor than BMI. Our study was designed to compare the prevalence of visceral obesity in peritoneal dialysis (PD) patients to hemodialysis (HD) patients with abdominal fat CT in a single center. Methods: In this cross sectional study, the result of abdominal fat CT of dialysis patients was investigated from January, 2007 to March, 2007 in Uijeongbu St. Mary`s Hospital. To evaluate the risk factors related to visceral obesity, we analyzed patients` medical records such as duration of dialysis, lipid profiles, anthropometric data and the presence of DM. Results: We enrolled 65 HD patients and 67 PD patients. PD group had higher mean body weight, mean body mass index (BMI), and triglyceride level, compared to HD group. The PD group had higher visceral fat area, measured by abdominal fat CT than HD group. The prevalence of visceral obesity was higher in PD group than HD group. Visceral fat area showed positive co-relation with BMI in HD group, but did not in PD group. The age related prevalence of visceral obesity was significantly increased in the patients with older age group (>65). Conclusion: Our cross sectional study points to the fact that visceral obesity is more common in PD patients than HD patients. It is necessary to control weight and nutritional status, especially in PD patients for preventing metabolic complications.

월경전불쾌장애의 약물치료 3상 임상 연구 메타분석

염선경 ( Sun Kyoung Yum ),유민지 ( Min Ji Ryu ),박나윤 ( Na Yoon Park ),김성민 ( Seong Min Kim ),이경욱 ( Kyong Wook Yi ),박현태 ( Hyun Tae Park ),신정호 ( Jung Ho Shin ),허준영 ( Jun Young Hur ),김선행 ( Sun Haeng Kim ),김탁 ( T 대한산부인과학회 2012 Obstetrics & Gynecology Science Vol.55 No.3

Premenstrual dysphoric disorder (PMDD) is a common condition that temporarily, but repetitively affects patient`s global function. Patients and physicians alike are often uncertain whether prescription medication for PMDD is sufficiently effective. The primary objective of this analysis is signal detection in efficacy of pharmacological treatments in PMDD. Secondary objective is to review which symptoms are likely to respond to which medications. The review included otherwise healthy women with clinician confirmed diagnosis of PMDD who participated in phase 3 clinical trials for the treatment of PMDD. Twelve pair-wise comparisons of drug and placebo for 2,420 patients with PMDD were performed. Oral contraceptives and selective serotonin receptor inhibitor were effective in alleviating symptoms of PMDD compared to placebo. Both Intermittent and continuous administration were more effective than placebo. This meta-analysis provides a signal that pharmacological treatment of PMDD is effective.

OECD 급성경구투여독성시험 지침의 국내 확립 및 검증

조영래 ( Young Rae Cho ),염영나 ( Young Na Yum ),한의식 ( Eui Sik Han ),곽승준 ( Seung Jun Kwack ),김형섭 ( Hyung Sub Kim ),강미선 ( Mi Sun Kang ),이진영 ( Jin Young Lee ),오재호 ( Jae Ho Oh ),임채형 ( Chae Hyung Lim ),김대성 ( Da 한국동물실험대체법학회 2008 동물실험대체법학회지 Vol.2 No.2

As the study about the non-animal tests came to be internationally active and the interest in the animal welfare gradually became increased, OECD TG (Test Guideline) 401 that has been used since 1987 was abolished in 2002. Because TG401 is acute oral toxicity method depending on survival and death of many animals, it was heavily criticized. Therefore, the three alternative methods were developed. OECD TG420 and TG423 determine the class of chemicals according to GHS (Globally Harmonized Classification System for Chemical Substances and Mixtures) classification and OECD TG425 suggests the predicted LD50 of chemicals using AOT425 program. In this study, 10 chemicals were selected. The internationally admitted TG420, TG423 and TG425 were introduced and established through the method that these chemicals were orally administrated to SD female rats and then, the results were observed. Each chemical belonged to already known GHS class in the study using TG420 and TG423 and predicted LD50 was same or higher in the study using TG425 compared to already known LD50 value. In conclusion, the result of our study confirmed the decrease in the animal number and validated. The international harmonization of the non-animal tests will be pursued through this validation study.

말초혈액을 이용한 초고속 유전독성평가법 개발 연구

안일영 ( Il Young Ahn ),김주환 ( Ju Hwan Kim ),임대현 ( Dae Hyun Lim ),양준영 ( Jun Young Yang ),김소영 ( So Young Kim ),이정선 ( Jung Sun Yi ),염영나 ( Young Na Yum ),임채형 ( Chae Hyung Lim ),이진하 ( Jin Ha Lee ),최기환 ( Ki Hw 한국동물실험대체법학회 2014 동물실험대체법학회지 Vol.8 No.1

To identify mutagenic potential of test substances, in vitro Ames tests are commonly used. Recently revised ICH S2(R1) guideline requires in vivo genotoxicity test if the result of the in vitro test is positive. In addition, a method testing multiple endpoints is required for animal welfare. Therefore we established a flow cytometry-based analysis such as Pig-a gene mutation assay and the micronuclei assay for detection of in vivo genotoxic potential using peripheral blood collected from repeated dose toxicity study. To evaluate these new methods, male Sprague Dawley rats were treated for 3, 14 or 28 days with N-nitro-N-ethylurea (ENU). ENU induced mutations in both reticulocytes (RET) and red blood cells of rats dose-dependently from the Pig-a gene mutation assay. ENU also increased micronucleated reticulocytes frequencies in flow cytometry based micronuclei assay, implying chromosomal damage to hematopoetic cells. These data show that both assays were well established. We additionally evaluated urethane and glycidol for applicability of Pig-a gene mutation assay and in vivo micronuclei assay by flow cytometry. Urethane, compared with vehicle control, did not increase Pig-a gene mutation and micronuclei frequency. Glycidol, compared with vehicle control, did not increase in micronuclei frequency, but Pig-a gene mutation significantly increased in the highest concentration for 28 days. Pig-a gene mutation assay for genotoxicity has many advantages: It can detect mutation in various species including humans, primates and rodents; and is integrated with repeated dose toxicity test without additional usage of animals; and has low spontaneous mutation frequency.

연구논문 : 말초혈액을 이용한 초고속 유전독성평가법 개발 연구

안일영 ( Il Young Ahn ),김주환 ( Ju Hwan Kim ),임대현 ( Dae Hyun Lim ),양준영 ( Jun Young Yang ),김소영 ( So Young Kim ),이정선 ( Jung Sun Yi ),염영나 ( Young Na Yum ),임채형 ( Chae Hyung Lim ),이진하 ( Jin Ha Lee ),최기환 ( Ki Hw 한국동물실험대체법학회 2014 동물실험대체법학회지 Vol.8 No.1

To identify mutagenic potential of test substances, in vitro Ames tests are commonly used. Recently revised ICH S2(R1) guideline requires in vivo genotoxicity test if the result of the in vitro test is positive. In addition, a method testing multiple endpoints is required for animal welfare. Therefore we established a flow cytometry-based analysis such as Pig-a gene mutation assay and the micronuclei assay for detection of in vivo genotoxic potential using peripheral blood collected from repeated dose toxicity study. To evaluate these new methods, male Sprague Dawley rats were treated for 3, 14 or 28 days with N-nitro-N-ethylurea (ENU). ENU induced mutations in both reticulocytes (RET) and red blood cells of rats dose-dependently from the Pig-a gene mutation assay. ENU also increased micronucleated reticulocytes frequencies in flow cytometry based micronuclei assay, implying chromosomal damage to hematopoetic cells. These data show that both assays were well established. We additionally evaluated urethane and glycidol for applicability of Pig-a gene mutation assay and in vivo micronuclei assay by flow cytometry. Urethane, compared with vehicle control, did not increase Pig-a gene mutation and micronuclei frequency. Glycidol, compared with vehicle control, did not increase in micronuclei frequency, but Pig-a gene mutation significantly increased in the highest concentration for 28 days. Pig-a gene mutation assay for genotoxicity has many advantages: It can detect mutation in various species including humans, primates and rodents; and is integrated with repeated dose toxicity test without additional usage of animals; and has low spontaneous mutation frequency.

아리스톨로크산 함유 생약제에 대한 안전성평가연구 : 3개월간 반복투여독성시험을 통한 신장독성평가

황명실,박미선,문지영,이지선,염영나,이효민,신동환,강진석,윤은경,최미나,육미영,장동덕,길광섭,김승희,양기화 식품의약품안전청 2001 식품의약품안전청 연보 Vol.5 No.-

본 실험에서는 아리스톨로크산을 함운하고 있는 생약제중 하나인 마두령(.4risfoforfioe JTurruf)의 90일 반복투여독성시헌을 실f,」하였다. 마두령에서 아리스톨로크산을 정량분석한 결과 마두령 단일 건조븐말의 경운 2.112mg/g, 잉상에서 처방되고 있는 마든령복방 (마두령외 9가지 생약제 복합처방) 건조분말꼭 경무에는 0.066m9/5으로 각각 검출되었다. 본 실험에서 용량설정은 마두령 처리군 (저용량 군; 21.3m9/k9/day (임상용량), 중용량군; 2t3mgfg/day, 고용량군; 2430mg딘g b.w./day), 마두령복방 처리군 (427mg/kg b.w./da?; 임상용량) 및 positive control (아리스톨로크산) 처리군 (저용량군;0.05mgag/da17, 중용량군; 0.Smg/kg/day, 고용량군; 5mg./kg/dal·1으료 하여 랫드에게 경구투여하였다. 마두령단방 처궈근 및 마두령복방 처리군에서 저용량군과 중응량군에서는 잉상관찰 및 생화학적 분석에서 패조군과 유의적인 차이가 없었다. 그러나 마두령단방 고용량근에서는 간, 신장의 상대적인 무계가 증가되었고, 신장의 유두이행상피증식 및 암종이 관찰되었으며, 위에서는 편평세포암종이 관찰되었다. 하자만 간손상이나 간암은 유발하지는 않는 것으로 판단되었다. 결론끌으로 본 실험의 결과에서는 아리스톨로크산 함유 생약제인 마두령이 임상용량인 저응량 처리군에서는 독성을 나타내지 않았으나, 고용쏭으로 장기 복용시켰을 깅우 설치류의 전위부위 및 신장에서 독성이 있음을 알 수 있었다. Chines herbs nephropathy (CHN) has been described in young women who had taken a slimming pills containing some chines herbs. Aristolochic acid (AA), suspected substance as the causal factor of CHN, is known a carcinogen. The Aristolochiae fructus (fruit of Aristolochia contorta) was used in Korean Traditional Medicine consists of appropriate amounts of mixed natural products. Subchronic toxicity of A. furctus containing aristolochic acid was investigated in SD rats. The body weight and clinical signs were observed after orally administration of A. futctus at doses of 21.2, 213, and 2130 mg/kg/day; mixture (including 9 other herbs) at dose of 427 mg/kg/day; aristolochic aicd (Ⅰ+Ⅱ) at doses of 0.05, 0.5, and 5 mg/kg/day for 3 months. At the end of the treatment, high dose treated animals revealed a deficit in final body weight about 25% compared with that of control. Organ weights of kidney, liver, testis, or ovary were increased with dose dependent manner. No changes considered to be due to the administration of A. furctus, mixture or aristolochic acid were in hematological and clinical study. However, significant changes at histopathological study of kidney and stomach were boserved in high-dose treated groups. In conclusion, for human health safety it needs appropriate regulatory actions regarding the use of natural herbal medicines known or suspected of containing aristolochic acid.

Changes in ocular factors according to depth variation and viewer age after watching a three-dimensional display

Yum, Hae Ri,Park, Shin Hae,Kang, Hang-Bong,Shin, Sun Young BMJ Publishing Group Ltd 2014 British journal of ophthalmology Vol.98 No.5

<P><B>Objective</B></P><P>To investigate changes in ocular factors according to the binocular disparity in three-dimensional (3D) images and age after watching 3D display.</P><P><B>Methods</B></P><P>A total of 38 volunteers were enrolled, and they watched a 3D display with a 1° or 3° disparity for 30 min at an interval of 1 week. The near point of accommodation (NPA), near point of convergence (NPC) and tear break-up time (tBUT) of each subject were measured before and after watching the 3D display. In addition, the tear meniscus height and depth were measured using Visante optical coherence tomography and tear osmolarity was measured using TearLab osmometer. A survey of subjective symptoms was also conducted.</P><P><B>Results</B></P><P>NPA and NPC increased after watching the 3D display (p<0.05). NPC and NPA increased more in the 40s–50s group (ie, subjects aged in their 40s and 50s) than in the 20s–30s group (ie, subjects aged in their 20s and 30s) after watching 3D content with a 3° disparity (p<0.05). tBUT and tear meniscus height and depth decreased after watching 3D content (p<0.05). They decreased more in the 40s–50s group than in the 20s–30s group after watching 3D content with a 3° disparity (p<0.05). Recovery times of NPA and NPC were significantly greater after watching 3D content with a 3° disparity and in the 40s–50s group (p<0.05).</P><P><B>Conclusions</B></P><P>Watching a 3D display affects accommodation and convergence abilities and tear dynamics in a transient fashion, especially in the case of 3D images with a large binocular disparity, and in older subjects. These results provide helpful information for establishment of guidelines for 3D equipment manufacturers.</P>