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.

취업대비 기사자격증 취득을 위한 효과적 학습지도 방안에 관한 연구

홍순욱,윤상원,서용성 永同大學校 1997 硏究論叢 Vol.3 No.1

지난 2년간 STC를 수행하면서 경험한 바에 의하면, 기사시럼을 준비하기 위하여 시중에서 구입한 연습 문제집에 실린 일부 문제들이 내포한 모호성 때문에 많은 학생들이 어려움을 겪고 있다는 것을 알게 되었다. 이는 학생들이 전공지식을 학습하는데 있어서 비효율을 초래하는 주요 요인들 가운데 하나일 것이다. 본 논문은 학생들이 스스로 자신들의 지식을 확장하고 조직화할 수 있도록 「기출문제 수정출제법(PRST)」이라는 새로운 개념을 도입함으로써 그와 같은 부정적인 효과를 최소화하려는 구체적인 노력을 보여주고 있다. PRST는 5단계로 구성되어 있는데, 이를 통하여 학생들과 지도교수는 모호성을 제거하고 문제를 개선하는 작업을 함께 하게 된다. 이를 위하여 시스템적 접근의 관점에서 Dick의 모형을 채택하는데, 이 모형은 교수설계를 위한 기본틀을 제공해 주며, 본 연구에서 다룰 하나의 기능은 그러한 교수설계 모형 가운데 일부가 된다. 교수설계 모형에 있어서 8개의 기능 가운데, 일련의 개선된 연습 문제들을 제작하는 것이 학생들에게 우선적으로 도움이 될 것이라는 관점에서 수업교재의 개발이라는 기능이 가장 긴급하다고 판단되었다. 본 연구의 목적에 부합하는 적절한 연구의 방향과 범위를 결정하기 위하여 기존 문제들에 대한 사전 조사연구가 수행되었다. 그리고 두 과목에 대한 연습 문제집의 제작과 학생들의 학습 동기부여를 위하여 여름방학 STC기간에 PRST가 시험적으로 적용되었다. 제작된 연습 문제집 가운데 하나가 문제집의 양호도라는 측면에서 6개의 7점 Likert척도로 학생들에 의하여 인지적으로 평가되었다. 그 결과, 새로 구성된 연습 문제집이 기존의 연습 문제집보다 여러 각도에서 더 양호하다고 판정된다. 이것은 통계적 적용상의 한계에도 불구하고, 본 연구에서 제안된 PRST 뿐만 아니라 제작된 연습문제집의 질적 부분의 타당성은 최소한 뒷받침된다는 것을 의미한다고 하겠다. By what we have experienced in STC for the last two years, we can see that a number of students have been suffering from the ambiguities of some problems contained in exercise books which are available at the market for preparing the National Certificate of Engineering. This seems one of the primary factors that bring on inefficiencies in learning expertise. This paper reports our concrete efforts to minimize such a negative force by introducing a new concept of「process for Revise of Sample Test(PRST)」, so that students can be able to organize and expand their knowledge in a good manner. PRST consists of five stages that enable students and the instructor work together on improving problems by getting rid of ambiguities. From the viewpoint of systems approach, Dick's model is adopted to provide a framework for an instructional design which designates a function we deal with in this study. Among the eight functions in the model, the development of class material is considered to be most urgent in that it would be of highly benefit to students to make series of improved exercise problems. Preliminary investigation of existing problems is conducted to figure out right direction and scope for the purpose of our research. PRST is, then, tentatively applied during the summer STC not only to produce exercise books for two different subjects, but to motivate students. One of the produced exercise books is examined perceptively by students in terms of goodness using six seven-point Likert scales. The result shows that the newly constructed exercise book is, on the perception basis, likely to be better than existing books. This implies that the quality of the produced book, as well as the proposed PRST, is validated at least positively in spite of statistical limitation.

PSM을 적용한 반도체 산업에서의 재해예방 사례연구

윤용구,홍성만,손제성,박범 대한설비관리학회 2003 대한설비관리학회지 Vol.8 No.2

It is a semiconductor product industry womed out enormous of loss that happened to accident for during in production exist to leakage, fire, explosion, using to variable chemical material of application, treatment, storage. This is presented to that improvement example for study, research, investigation of PSM in semiconductor industry and so processed to follow as theory consideration for PSM in semiconductor industry. This study did the object of research that S company is point to appointment and so give a account of S company PSM contents, searching to conclusion of PSM and consideration of problem and injury prevention for PSM expansion. From now on, PSM of semiconductor-injury is bring up improvement of problem, large-scale -company of semiconductor.

응급의료 정보전달매체로서의 구급활동일지의 유용성

윤영철,안성훈,이경호,전형대,김원율,조영식,성백문,김홍용,김경환,구본관 대한응급의학회 1998 대한응급의학회지 Vol.9 No.2

Regulation for new standardized rescue record form of the 119 EMS system was established by law from February 1, 1988. We have recently evaluated the effectiveness of the record form. Records of 192 patients who visited the Emergency department of Sangggye Paik Hospital, Inje University by the 119 EMS system from February 1 to February 28, 1998 were analyzed statistically according to the contents of the record form. In conclusion, the new standardized rescue record form of the 119 EMS system was effective in giving information of patients' history and analysing of the 119 EMS system. But, Detailed modification of the record form about disease entities is needed for proper initial evaluation of emergent patient.

Benzo(a)pyrene에 의해 유도된 간기능 장해에 미치는 쑥의 효과

윤수홍,조수열,박은주,김성중 한국환경독성학회 1992 환경독성보건학회지 Vol.7 No.1

Mugwort has been used as a Korean folk medicine in treating liver diseases acting as an analgesics, sedative, diuresis, choleretics. This study was perfomed to evaluate the effect of mugwort extracts on the changes of enzyme activities, lipid accumulation of the serum and liver, when hepatotoxicity was induced by benzo(a)pyrene. The results are as follows: 1. Mugwort water extract administration prevented the increase of serum and liver AST, ALT, LDH, γ-GTP, liver ALP activities and bilirubin content caused by B(a)P injection. 2. The increase of serum and liver ALT, LDH, γ-GTP, serum AST activities and liver bilirubin contents in B(a)P treated group were decreased by mugwort methanol extract treatment. 3. Serum and liver total cholesterol, phospholipid, triglyceride level and serum HDL-cholesterol level were increased by B(a)P treatment. After combined treatment of mugwort water and methanul extracts, these lipid content were significantly decreased. 4. The hepatotropic effect of mugwort water extract and after-treatment against B(a)P induced hepatotoxicity was superior to that of methanol extract and pretreatment.

특발성 자발성 신장 파열 1예

윤재철,김원,조규종,홍정석,이미우,장성은,오세현,임경수 대한응급의학회 2001 대한응급의학회지 Vol.12 No.4

Primary aldosteronism is a syndrome characterized by hypertension, hypokalemia, suppressed plasma renin activity, and elevated serum aldosterone levels. Conn first described it 1955 in association with adrenal cortical adenoma(Conn's syndrome). Today, it can be divided into at least six distinctive sub-groups. The diagnosis of primary aldosteronism is usually suspected when the patient presents with poorly controlled hypertension with hypokalemia. The main issues in the evaluation of primary aldosteronism are to differentiate an adenoma from hyperplasia and to localize the adenoma. Basic hormonal studies and computed tomographic(CT) scanning can be used effectively for that differentiation. An adenoma is one of a few potentially curable forms of hypertension, and it is best treated by removing the adrenal tumor. We experienced a case of a typical adrenal adenoma. The patient was a 37-year-old male who had experienced in both his legs over a period of several days a weakness due to hypokalemia. He was diagnosed using basic hormonal studies and adrenal CT scanning. After, he received laparoscopic adrenalectomy and was discharged with improved condition.