Critical role of bile acid (BA) in the cellular entry and permissiveness of Hepatitis B virus in vitro

Hong‑Jai Lee,Bo‑Young Shin,Jae‑Seung Moon,Ailyn Fadriquela,Selikem Abla Nuwormegbe,Chun‑Chang Ho,Jin‑Su Shin,Jee‑Sang Yoon,Sang‑Kyou Lee,Soo‑Ki Kim 대한독성 유전단백체 학회 2020 Molecular & cellular toxicology Vol.16 No.3

Background Lack of universal replication system for hepatitis B virus with narrow host range and organ tropism has hampered to uncover the pathogenesis of HBV. Previously, we reported the essentiality of humoral milieu and its components toward HBV and hepatitis C virus survival/viability in vitro. Of these components, the precise role of enterohepatic humoral milieu such as bile acid (BA) on HBV cultivation in vitro and in vivo is unknown. Objective We explored whether BA, specifically taurochenodeoxycholic acid (tCDCA) would directly regulate the viral DNA and surface antigen expression of HBV in vitro, consequently rendering HBV to enter into human or murine immortalized hepatocytes, and non-hepatocytes. Result We found that higher concentration of taurochenodeoxycholic acid (tCDCA) is able to preserve the genomic stability of HBV in cell-free DMEM, showing higher the surface antigenicity than taurocholic acid (tCA). In line, we found that in vitro cell culture condition (100 μmol/L of tCDCA coupled with 1 × 108 g e/mL HBV) would be optimal for HBV entry into target cells. Using this, human (HepG2, Huh7), and rodent (Hepa1c1c7, H4-II-E) hepatoma cell lines were infected by HBV, as evidenced by the presence of HBV biomarkers (HBsAg, and HBV DNA in culture supernatant, as well as HBcAg in cell). Further, cellular entry test revealed that HBV is able to infect 12 different non-hepatic cell lines regardless of species, and organ/tissue, consequently reproducing progeny as confirmed by HBV biomarkers. Last, reinfection test showed that the progenies of HBV from immortalized HepG2, and Hepa1c1c7 cells are able to enter into each or vice versa naïve HepG2, and Hepa1c1c7 cells with or without BA. Conclusion This study demonstrates that enterohepatic humoral milieu such as BA, specifically tCDCA would directly regulate HBV DNA and its surface antigen expression in vitro, consequently rendering HBV to enter into human or murine immortalized hepatocytes, and non-hepatocytes. This is the first note to render HBV permissive to human or rodent hepatic and non-hepatic cells via sole manipulation of humoral milieu, thus establishing the platform for in vitro robust replication system of HBV.

The HBV DNA Amounts in Serum Have No relationship with ALT level and Hetergeneous Population Coexits in Chronic Hepatitis B Virus Infection

Chun, Yoon-Keun,Ha, Joo-hun,Hong-Jung-Woo,Oh, Soo-Myung,Kim, Sung-Soo 경희대학교 동서의학연구소 1999 INTERNATIONAL SYMPOSIUM ON EAST-WEST MEDICINE Vol.1999 No.1

Yoon-Keun Chun¹,Joohun Ha□Hong-Jung Woo□, Soo Myung Oh□,Sung Soo Kim□ ¹Department of Molecular Biology, College of Medicine,²Department of Surgery, college of Medicine,³Department of Internal Medicine, College of Oriental Medicine,and ⁴East-Weat Medical Reserch Institute,Kyung Hee University, Seoul, Korea. The HBV DNA Amounts in Serum Have No relationship with ALT level and Hetergeneous Population Coexits in Chronic Hepatitis B Virus Infection. Proceedings of International Symposium on East-West Medicine, Seoul. 212-230, 1999. -Hepatitis B is caused by hepadnavirus. Hepatitis B virus replicates through 3.5kb pregenomic RNA intermediate which is regulated by core promoter. Pathogenesis of hepatitis B virus has been bilieved the result of host immune response. But recently many studies have reported that high level of viral replication caused by mutation in core promoter might result in severs hepatitis. But these studies were performed in vitro, not in vivo. So there is yet debate about which factor, viral of host factor, is more important in pathogenesis of hepatitis B virus. So we measured real viral replication level in 204 chronic hepatitis B patients by quantifying HBV DNA from sera by our novel PCR-based more sensitive method, and compared these results with ALT level measured from same sera, which indicates liver cell damage. Surprisingly there are no significant correlation between HBV DNA quantity and ALT level. Then we cloned core promoter region. In SSCP, we found that many viral mutants coexist in one patient. Base on SSCP result, we chose main viral core promoter type in each patients, which is thought to determine overall viral replication level in this patient. Main type of core promoter region of each 41 patients were directly sequenced. And with these we measured promoter activity by luciferase assay system and compared promoter activity with on another. We found tha there were some differences in promoter activity according to core promoter sequences. And we constructed replication-competent viral constructs with core promoter from 41 patients and Transfected these into HepG2 cell and measured HBV DNA by southern blot. There were also differences in HBV DNA quantity according to core promoter sequences. On these all results we investigated correlation between the effect of HBV core promoter on viral replication in vitro and HBN DNA quantity, ALT level from sera of each patients. We found there is no significant correlation among them. As a result, we concluded that in determining severity chronic hepatitis B patients, host factors of each patient is more important rather than replicative activity of virus itself.

서울의 Penicillinase Producing Neisseria Gonorrhoeae 발생빈도(1996)

김재홍,황동규,전재홍,김윤석,김중환,김용준,이창균,임동진,김현수,조창근,김경문,박상훈,전우형,김희성,이호정,차명수,김갑형,김형석,김석우,황지환,박병순,권오상,이민수,송기훈,성소영,이인섭,부태성 대한화학요법학회 1999 대한화학요법학회지 Vol.17 No.2

Background : In recent years, gonorrhea has been panedemic and remains one of the most commom STDs in the world, especially in developing countries. Objective & Methods: For the detection of a more effective therapeutic regimen and assessing the prevalence of PPNG, we have been trying to study the patients who have visited the VD Clinic of Choong-Ku Public Health Center in Seoul since 1980 by means of the chromogenic cephalosporin method. Results: In 1996, 139 strains of N. gonorrhoeae were isolated, among which 53(39.0%) were PPNG. Conclusion: Our results suggests that after a peak of 74.3% in 1993, the prevalence of PPNG in Seoul is gradually declining.

서울의 Penicillinase Producing Neisseria gonorrhoeae 발생빈도(1998)

김재홍,김준호,반재용,이정우,황성주,정준규,정성태,강진문,조흔정,홍창의,정혜신,이한승,김이선,이봉길,이종호,선영우,한기덕,윤성필,이성훈,안종성,박석범,문승현,조항래,김형섭,류지호,황재영,박준홍,손상욱 한양대학교 의과대학 2001 한양의대 학술지 Vol.21 No.1

In recent years, gonorrhea has been pandemic and remains one of the most common STDs in the world, especially in developing countries. For the detection of a more effective therapeutic regimen and assessing the prevalence of Penicillinase Producing Neisseria gonorrhoeae(PPNG), we have been trying to study the patients who have visited the Venereal Disease Clinic of Choong-Ku Public Health Center in Seoul since 1980 by menas of the chromogenic cephalosporin method. In 1998, 93 strians of N. genorrhoeae were isolated, among which 60(64.5%) were PPNG. The prevalence of PPNG in Seoul, which had been decreased to 39% in 1996 after a peak of 74.3% in 1993, is increased to 64.5% in 1998.

정신분열병에 대한 리스페리돈의 효과 및 안정성

이민수,김용구,김영훈,연병길,오병훈,윤도준,윤진상,이철,정희연,강병조,김광수,김동언,김명정,김상훈,김희철,나철,노승호,민경준,박기창,박두병,백기청,백인호,손봉기,손진욱,양병환,양창국,우행원,이정호,이종범,이홍식,임기영,전태연,정영조,정영철,정인과,정인원,지익성,채정호,한상익,한선호,한진희,서광윤 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.1

연구목적 : 본 시험의 목적은 임상시험 시작전에 연구자들을 대상으로 PANSS Workshop을 통하여 PANSS, ESRS에 대한 국내에서의 표준화 작업을 구축하고 새로운 정신병 치료제인 리스페리돈의 효과와 안정성을 재확인하여 리스페리돈 사용에 대한 적정화를 이루는데 있다. 연구방법 : 1996년 4월부터 1996년 9월까지 국내 39개 대학병원 정신과에 입원중인 혹은 증상이 악화되어 입원하는 정신분열병 환자 377명을 대상으로 다시설 개방 연구를 시행하였다. 1주일간의 약물 배설기간을 가진후, 리스페리돈을 8주간 투여하였고, 기준점, 1주, 2주, 4주, 그리고 8주후에 평가되었다. 용량은 제1일에는 리스페리돈 1mg씩 1일 2회, 제2일에는 2mg씩 1일 2회, 제3∼7일에는 3mg씩 1일 2회 투여하였다. 이후 환자의 임상상태에 따라 임의로 증량할 수 있으며, 최대 일일 16mg을 초과하지 않도록 하였다. 추체외로 증상을 조절하기 위한 투약을 허용하였다. 임상증상 및 부작용의 평가는 PANSS(Positive and Negative Syndrome Scale), CGI(Clinical Global Impression) 그리고 ESRS(Extrapyramidal Symptom Rating Scale)을 사용하였다. 연구결과 : 377명중 343명(91%)이 8주간의 연구를 완결하였다. 치료 종결시점인 8주후 PANSS 총점수가 20% 이상 호전된 경우를 약물 반응군으로 정의할때, 약물반응군은 81.3%였다. 리스페리돈에 반응하는 예측인자로는 발병연령, 이전의 입원 횟수, 유병기간이 관련 있었다. 리스페리돈은 1주후부터 PANSS양성, 음성, 및 일반정신병리 점수상에 유의한 호전을 보여 효과가 빨랐다. CGI의 경우도 기준점에 비해 1주후부터 유의한 감소를 나타내었다. ESRS의 경우, 파킨슨 평가점수는 기준점과 비교해 투여 1주, 2주, 4주후 유의하게 증가되었다가 8주후 기준점과 차이가 없었다. Dystonia 평가점수는 1주후만 유의한 증가를 보였으며, dyskinesia 평가점수는 유의한 차이가 없었다. 혈압, 맥박수의 생명징후 및 일반 혈액학 검사, 생화학적 검사, 심전도 검사에서 유의한 변화는 없었다. 결 론 : 이상의 다시설 개방 임상 연구를 통해 리스페리돈은 정신분열병 환자에서 양성증상뿐만 아니라 음성증상 및 전반적인 증상에도 효과적인 것으로 사료된다. 보다 명확한 평가를 위해서는 다른 항정신병약물과의 이중맹검 연구가 필요할 것으로 생각되며, 또한 장기적 치료에 대한 평가도 함께 이루어져야 하겠다. Objective : The purpose of this study was to investigate the efficacy and safety of risperidone in the treatment of Korean schizophrenic patients. Method : This multicenter open study included 377 schizophrenic patients drawn from 39 university hospitals. After a wash-out period of 1 week, the schizophrenic patients were treated with risperidone for 8 weeks and evaluated at 5 points ; at baseline, and 1, 2, 4 and 8 weeks of treatment. The dose was increased from 2mg/day(1mg twice daily) to 6mg/day(3mg twice daily) during the first week and adjusted to a maximum of 16mg/day over the next 7 weeks according to the patient's clinical response. Medication to control extrapyramidal symptoms was permitted. The psychiatric and neurological status of the patients was assessed by PANSS, CGI, and ESRS scales. Results : 343(91%) of 377 patients completed the 8-week trial period. Clinical improvement, as defined by a 20% or more reduction in total PANSS score at end point, was shown by 81.3% of patients. The predictors of response to risperidone were associated older age, shorter duration of illness, fewer previous hospitalization. Risperidone had rapid onset of action ; a significant decrease of the total PANSS and three PANSS factor(positive, negative, general), and CGI was already noticed at the end of first week. For the ESRS, parkinsonism rating scores were significantly increased until week 4 comparing with baseline. Dystonia rating scores were significantly increased until week 1, and dyskinesia rating scores were not significantly changed during the study. Laboratory parameters including vital sign, EKG, hematological, and biochemical values showed no significant changes during the trial. Conclusions : This study suggests that risperidone is generally safe and effective against both the positive and negative symptoms in our group of patients.

有機農業의 實態와 發展에 관한 事例 硏究 : 忠南 洪城郡 洪東面 有機農家를 中心으로

尹英相,洪性贊,金成敏,具漢謨,申東一,金昌護,姜熙慶 公州大學校 資源科學硏究所 1997 資源科學硏究論文集 Vol.5 No.-

This study was carried out to improve the organic farming system about crop cultivation, compost production and application, plant diseases & pest control, weed control and marketing system of organic farming products to the case study in Chungnam Hongdong area. Agricultural technologies concerning pest & diseases control, weed control and compost production are not established due to lacks of systemized researches by the agricultural scientist, and agricultural machines profitable to this works had not developed yet. In cropping system, reasonable crop rotation had not conducted. The related cultivation of vegetables on the same ground for a long time cause a various plant disease easily. So crop rotation is a reasonable method about soil nutrient utility and soil disease control. It is a good method that introduce the barley and wheat in this field crop system. Those crop have a long root, so can use the other nutrient against the vegetable. In organic farming products, the safety and quality of products by the National Agricultural Products Inspection Center had not inspected except rice, lettus and apple. Inspection is needed for the development of organic farming and mutual confidence between producer and consumer, because the mutual confidence is a major thing to sustain the organic farming. In products marketing, it is more need for the information of organic farming products. Nowaday most products are marketed in Seoul region, but it is not a good method. To search the consumer in near region is a good method for decrease the cost of conveyance and maintain the quality of products. The varieties of distribution structure of organic farming products are required. The products are sold to department store in large city and the prices are about 30% higher than normal products. But when those are supplied in near region, the prices of those are similar to normal products. Direct transactions in near regions is a good method for decrease the cost of conveyance and strength the mutual confidence between producer and consumer.

고출력 펄스 레이저로 증착된 유기필름

홍진수,채희백,안성기,박해윤 순천향대학교 기초과학연구소 2001 순천향자연과학연구 논문집 Vol.7 No.2

유기발광 응용에 성공적으로 사용되어 새로운 물질을 개발할 때 기준으로 사용되는 Alq_3와 TPD필름을 기존의 증착법(열증착법과 스핀코터 기술)을 대체할 수 있는 고출력펄스레이저로 합성하였다. 펠릿 타겟은Q-스위칭 Nd:YAG 레이저의 532 nm와 355 nm를 사용하여 2&10^-6 Torr압력 하에서 용발시킨다. 슬라이드 유리 위에 증착된 필름은 유기발광 디바이스에 사용될 가능성이 있는지 알기 위해 다음과 같은 조사를 하였다: PL,AFM, 흡수 스펙트라, XRD. 355 nm 레이저로 유기필름을 증착하면 532 nm 경우의 필름보다 결합이 적고, 특히 열증착 필름보다 스트레스를 덜 받는다는 사실을 알 수 있다. 또한 타겟의 구조가 Alq_3 다를지라도 레이저 증착법으로 합성된 Alq_3 필름은 열증착과 동일한 구조를 갖는다는 사실을 알 수 있다. 어느 레이저를 사용하건 증착된 필름은 결정구조를 확인할 수 없을 정도로 비정질을 이룬다는 사실을 알 수 있다.

천연자원의 간기능 보호 효과에 관한 연구 : Benzo(a)pyrene에 의한 간기능 장해에 미치는 황금(Scutellaria baicalensis)의 영향 The Effect of Scutellariae Radix on the Benzo(a)pyrene-induced Hepatotoxicity in Rats

윤수홍,조수열,배선희,박상학 효성여자대학교 부설 한국환경위생연구소 1991 환경위생연구 Vol.1 No.1

환경 중의 어디에나 분포하여 인체에 발암작용을 일으키는 대표적인 약물 benzo(a)pyrene를직접 경구투여하고.동시에 간보호물질로서 황금을 전처리 투여하여 그 독성 및 손상 회복호과를 혈청 및 간에서의 효소활성을 측정하여 다음과 같은 결론을 얻었다. 1. 황금 수용액의 전처리로 혈칭에서 LDH, AST 및 ALT활성은 beozo(a)pyrene단독투여군에비하여 감소하였으며 ALT는 2,4주째에 유의성 있는 감소를 보였으나 ALP활성은 전 실험군과 시간경과사이에 별다른 유의성이 없었다. 2. 간장의 LDH, ALP, ALT, AST의 효소활성은 황금수용액의 투여로 benzo(a)pyrene 단독투여군에 비해 유의성 있는 회복을 보였으며 LDH의 경우는 2, 3, 4주에 매우 큰 효과를얻었으며 ALP의 경우 4주째에서 유의성 있게 회복되는 경향을 보였다. This study was conducted in an attempt to investigate the effectsof Scutellariae Radix on the activities of serum and liver enzyme and to evaluatethe utility of Scultellariae Radix as a hepatotropic agents in liver disease The results were as follows ; 1. Significantly increased enzyme activity was noted in benzo(a)pyrene-intoxica-ted rats. 2. Scutellariae Radix administration prevented the leackage of LDH, ALP, ALTand AST in serum. 3. Scutellariae Radix administration did not affect on the serum ALP activity. 4. The B(a) P induced liver toxicity was significantly decreased in ScutellariaeRadfx administration.

工業敎育大學의 實驗實習施設 共同活用 및 運營에 關한 硏究

尹錫天,牟相榮,權五憲,千炳善,周赫鍾,李永臣,金健中,羅聲雄,洪錫雨,吳德成,盧泰天 충남대학교 공업교육연구소 1983 論文集 Vol.6 No.2(A)

The College of Engineering was specialized to have a sole function for supplying technical high school teachers in 1977 and referred to as the College of Industrial Education according to the Government's policy. The economic impact mainly due to the oil-crises caused a severe problem to this college, namely discrepancy of supply to demand scale. Accordingly the number of student enrollment was to be fluctuated from 479 in 1979 through 800 in 1979 and 900 in 1980 to 430 in 1981. And the engineering departments have been attached to this Engineering Education College since 1981. These circumstanses met singnificant inefficiency in facility operation. This program aims at providing an overall relocation of the college facilities and preparing the practical system to make the joint-operation possible taking into account circulation, academic stream, budget, maintenance, etc. However this study could not get optimal spacing but some trade-off, considering the current situation.

뇌파조절을 통한 학습능력 향상의 실증분석연구

윤상원,서용성,홍순욱 永同工科大學校 1996 硏究論叢 Vol.2 No.1

효율적인 STC수행의 기반 연구가 될 수 있는 학습방법론으로서, 뇌파조절이 가해지는 환경하에서 학습효율 향상의 변화정도를 정성적 및 정량적 실험을 실시하였다. 그 결과를 바탕으로 뇌파조절이 학생들의 학습능력에 어느정도 영향을 미치는가에 대해 통계적분석 방법으로 검증하여, 새로운 학습방번론을 모색하고자 한다. 실험분석결과 뇌파조절을 이용한 학습방법은 각 개인의 심리적, 육체적 상태를 개선해 줄 뿐만아니라, 학습효율도 증진시킬 수 있음을 보여 주었으며, 이는 실제 학교수업에 적용가능성이 클 것으로 사료된다. Under the circumstances of brain wave control, qualitative experiments (English word tests, IE subject tests, brain wave measurnments, music effect analysis) and Quantitative experiments (psychological , physical , scholastic evaluation) are executed to examine the level of learning improvements, which are the basic study for special topices course. On the base of the results, we verify the effectiveness of such an educational method for low level students using statistcal analysis and explore a new learning methodolgy. Through this study, we find that learning method using the effects of brain wave control not only makes better the physical and the psychological state of each student, but also advances the learning effectiveness, which is considered to apply a practical teaching extensively.