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.

경막 내 colistimethate 투여로 치료한 다제 내성 cinetobacter baumannii 뇌실염

홍유아,유진홍,김진진,모은영,안건희,정희경,김진석,이현정,정미향,윤승배 대한감염학회 2009 감염과 화학요법 Vol.41 No.4

Acinetobacter species is a non-fermentative aerobic gram-negative coccobacillus that is an important pathogen found in nosocomial infections. Recently, multi-drug resistant Acinetobacter baumannii (MDR-AB) infections have been increasing and pose a serious problem. Most such infections present as bacteremia, pneumonia, or a wound infection; however, CNS infections are very rare. We herein present a case of ventriculitis caused by MDR-AB in a 37-year old man after a neurosurgical intervention. The patient was successfully treated with intrathecal colistimethate.

Cytokine and Tumor Environments

Jin Tae Hong1*, Ju Kyung Song, Sun Mi Kwon, Byung Woo Ahn, Youngsoo Kim, Sang Bae Han 충북대학교 동물의학연구소 2012 Journal of Biomedical and Translational Research Vol.13 No.1

Cytokines are known to function as regulatory molecules that can be produced by virtually every nucleated cell type in the body, including lymphocytes, monocytes/macrophages, epithelial cells, fibroblasts, and many others. Cytokines include lymphocyte-derived factors (lymphokines), monocyte-derived factors (monokines), hematopoietic factors (colony-stimulating factors), connective tissue/growth factors, and chemotactic chemokines. Cytokines released in response to infection can affect tumor development in different ways. When exposed to infectious agents, cytokines are secreted by sentinel cells, such as macrophages and dendritic cells. These cytokines include interleukin 1 (IL-1) and tumor necrosis factor-α, as well as others, such as IL-6, IL-12, and IL-18. When released in sufficient quantities, these molecules can cause inflammation. Chronic inflammation is highly associated with tumor initiation, promotion, and progression. In this article, we review the roles and mechanisms of cytokines in tumor development.

정신보건법의 주요 쟁점 조항에 대한 선진국과의 사례 비교

홍진표,황순찬,박수빈,서동우,정은기,김진학,박종익,안주연,김수정,장홍석 大韓神經精神醫學會 2009 신경정신의학 Vol.48 No.2

Objectives The Mental Health Act is an initiative aimed at changing and shaping mental health services and protecting human rights of persons with mental disorders. Since the Mental Health Act was legislated in 1995, four amendments have been made according to the issues that arose from public concerns. However, there are still many debates about the human rights protection of the mentally iII. This study aimed to provide information regarding major aspects of the Mental Health Act by comparing them among several developed countries. Methods Current Mental Health Acts of the state of Michigan in the United States, Scotland in England, the state of Victoria in Australia, and Japan were reviewed. Issues regarding the Korean Mental Health Act were collected from seminar materials, news media contents, and mental health professionals Results The definition of subjects in Korean Mental Health Act was more inclusive than other countries and was derived from a medical classification of mental illness. Family members or guardians were granted important responsibilities for deciding the involuntary admission of mentally ill patients in Korea and Japan. In Western countries, Mental Health Review Tribunals or courts have the primary responsibility for important decisions about mentally ill patients. The regulation of immediate dis- charge after request by voluntarily admitted patients was not enacted in all countries except Korea. The mandatory procedure for involuntary admission in Western countries includes an individual case review with personal interview by a Mental Health Review Tribunal or court. Conclusion The Korean Mental Health Act appears to meet the basic standards of Guidelines from international organizations. Our traditional culture and inherent health systems seem to influence the legal regulation of mental health service and might be related to the problems of human rights protection of mentally ill patients in Korea.

Mongolian Gerbil과 CJU/A Mouse의 와우에서 βNADPH Diaphorase의 발현 양상

추무진,김진섭,송창근,신시옥,진홍률 대한이비인후과학회 1999 대한이비인후과학회지 두경부외과학 Vol.42 No.11

고호모시스테인증과 동반된 소뇌출혈 1예

홍석찬,안재영,조수진,정진상,이광호,홍승철,변홍식 대한신경과학회 1999 대한신경과학회지 Vol.17 No.3

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.

한국 일 도시지역 청소년의 우울 증상 유병률과 관련요인에 대한 연구

조성진,전홍진,김무진,김장규,김선욱,류인균,조맹제 大韓神經精神醫學會 2001 신경정신의학 Vol.40 No.4

연구 목적 : 한국의 일 도시지역에 거주하는 청소년의 우울 증상의 유병률과 관련요인을 밝힘으로써 청소년 정신건강 증진을 위한 기초 자료를 수집하기 위하여 실시되었다. 방 법 : 연구 대상은 부천시에 거주하는 중학교나 고등학교에 재학중인 청소년 71,102명 가운데에서 무작위 집락 표본 추출법에 의해 선정된 2,203명이었으며, 이들에 대해서 CES-D(the Center for Epidemiologic Studies Depression Scale)와 사회인구학적 정보에 대한 문항이 들어 있는 설문을 실시하였다. 설문은 직접 학교를 방문하여 수행하였다. 선정된 2,203명의 청소년 가운데에 CES-D문항을 완성한 학생은 1,972명으로 반응률은 89.5%였다. 결 과 : 1) CES-D의 절단점을 16점으로 하여 계산한 '가능한' 우울 증상의 유병률은 중학생의 경우에 남학생 34.6%, 여학생 44.7%였으며, 고등학생의 경우에는 남학생 43.8%, 여학생 49.6%였다. 2) CES-D의 절단점을 25점으로 하여 계산한 '명확한' 우울증 증상의 유별률은 중학생의 경우에 남학생 18.4%, 여학생 20.7%였으며, 고등학생의 경우에는 남학생 21.4%, 여학생 23.9%였다. 3)종교, 인문계와 실업계의 여부에 따라서 우울 증상의 유병률에는 유의한 차이가 없었다. 4) 성,학년, 생활수준에 대한 자신의 평가, 가족의 구조, 성적에 대한 만족도의 다섯 가지 변수에 대해 CES-D점수가 16점 이상인 우울 증상의 유무에 따라서 로지스틱 회귀 분석을 시행하였을 때 성적에 대해 불만적 하는 군에서 매우 만족하는 군에 비해서 8.850배의 상대 위험도를 보였다. 생활 수준을 중하정도라고 대답한 군은 상이라고 대답한 군에 비해서 2.007배의 상대 위험도를 보였다. 여학생은 남학생에 비해서 1.307배의 상대 위험도를 보였다. 5) 우울 증상에 있어서 남학생과 여학생의 비율은 전체 군에서 1:1.38이며 중학생의 경우에는 1:1.88, 고등학생의 경우에는 1:1.13으로 나타났다. 고등학생에 있어 남학생의 우울 증상이 증가하는 것은 학업과 입시에 대한 부담과 관련된 것으로 생각되었다. 결 론 : 한국 일 도시거주 중고등학생에서 CES-D로 측정한 우울 증상은 남학생의 34.3%, 여학생의 47.5%에서 나타날 정도로 흔하다. 특히 학업 성적에 대해 불만족 하는 군에서 높은 우울 증상의 상대 위험률을 보이며, 고등학생에서 남학생의 우울증의 유병률이 높아지는 것은 이 지역 학생들이 학업에 대한 높은 부담을 가지고 있다는 것을 알 수 있었다. 따라서 이들에 대한 특별한 관심이 요구된다. Objective : We tried to see the prevalence and correlates of symptoms of depression in an adolescent population in Korea, and collected the basal data for mental health promotion of adolescents. Method : We sampled 2,203 adolescents among 71,102 adolescents living in Puchon City in Korea by the randomized clustered sampling method. The Center for Epidemiologic Studies Depression scale(CES-D) was used to measure depressive symptoms. The measurements were conducted through visiting schools. Of the 2,203 adolescents(aged 13 to 18) who were sampled, 1,972 persons completed CES-D and sociodemographic questions. The response rate was 89.5%. Result : 1) The prevalence rate of 'probable' depressive symptoms with cutoff point 16 was 34.3% in the boys and 47.5% in the girls. 2) The prevalence rate of 'definite' depression symptoms with cutoff point 25 was 17.4% in the boys and 20.6% in the girls. 3) We could not find any meaningful difference in the average of CES-D from the districts where they live, the course of their education, and their religions. 4) We used the logistic regression analysis to find the risk factor for adolescent depression in these samples. Among the variables degree, it was most important risk factor in adolescent depression to dissatisfy with their school degrees. Compared it with fully satisfied group, the odds ratio was 8.850. The group of mid to low socioeconomic status had the odds ratio 2.007 compared with high socioeconomic status. The girls had the odds ratio 1.307 compared with the boys. 5) The male versus female ratio was 1: 1.38 in the total students and 1 : 1.88 in the middle school students, and 1 : 1.13 in the high school students. The male versus female ratio was relatively low in the high school students. It was the result of the high prevalence of depressive symptoms in the high school boys, and it was due to the large burden to their school degrees. Conclusion : The depressive symptoms checked by CES-D were very common among adolescents in Korean urban area. The prevalence of depressive symptoms was 34.3% in the boys and 47.5% in the girls. The result that male versus female ratio was relatively low in the high school adolescents, and the group that were dissatisfied with the school degrees had high risk of depressive symptoms, revealed that the students had large burden to their school degrees and so they needed special concerns.

중·고등학교 청소년의 자살사고 및 자살시도의 유병률과 자살시도의 위험요인에 관한 연구

조성진,전홍진,김장규,서동우,김선욱,함봉진,서동혁,정선주,조맹제 大韓神經精神醫學會 2002 신경정신의학 Vol.41 No.6

연구목적 : 지역사회에 거주하고 있는 중·고등학교 청소년들을 대상으로 자살 사고 및 자살시도의 빈도, 성별과 연령(13∼15세 vs 16∼18세)에 따른 자살사고 및 시도의 빈도에 차이가 있는지 여부, 자살사고 및 자살시도가 있는 청소년의 특징, 그리고 자살시도의 위험요인을 알아보고자 하였다. 방 법 : 부천시에 소재하고 있는 중학교 24개교 및 고등학교 20개교의 청소년 71,102명중에서 무작위 집락 표본 추출범으로 청소년 2,203명(남자 1,105명, 여자 1,098명)을 조사대상으로 선정하였다. 자살시도 및 자살사고의 정의에 관한 항목은 Moscicki가 사용한 자살행동에 관한 4항목 중 2항목을 사용하였다. 우울증에 대한 조사도구는 the Center for Epidemiologic Studies Depression Scale, 알코올 의존에 대한 조사도구는 Composite International Diagnostic Interview의 알코올 의존 관련 항목을 사용하였다. 조사자료 통계는 빈도, 백분율, chi-square test, 단변인 및 다변인 로지스틱 회귀분석을 사용하였다. 결 과 : 본 조사연구의 분석결과를 통계적으로 유의한 차이를 보인 항목으로 살펴보면 다음과 같다. 1) 전체 대상자의 자살 사고률은 30.7%, 자살 시도률은 5.3%인 것으로 조사되었다. 남자 대상자의 자살 사고률과 시도률은 26.9%, 3.4%이었고, 여자 대상자의 자살 사고률과 시도률은 34.9%, 7.3%인 것으로 조사되었다. 성별에 따라 자살 사고률과 시도률에 통계적으로 유의한 차이가 있었다. 2) 연령(학년)을 13∼15세(중학교)와 16∼18세(고등학교)의 두 연령층으로 조사하였을 때, 중학생의 자살 사고률과 시도률은 30.1%, 4.3%이었고, 고등학생의 자살 사고률과 시도률은 31.6%, 6.4%인 것으로 조사되었다. 연령에 따른 자살 사고률에는 통계적으로 유의한 차이가 없으나 자살 시도률에는 유의한 차이가 있었다. 3) 전체 조사 대상자를 대상으로 시행한 다변인 로지스틱 회귀 분석 결과에 의하면, 자살 시도의 위험요인이 여자, 알코올 의존, 중등도 및 중증 우울 증상인 것으로 조사되었다. 남녀별로 시행한 단변인 로지스틱 회귀 분석 결과에 의하면, 남자는 알코올 의존이 있을 때, 여자는 알코올 의존, 중등도 및 중증의 우울 증상이 있을 때 자살시도의 위험성이 높았다. 결 론 : 본 연구에서 자살 사고률 및 자살 시도률이 각각 29.6%(남자 25.6%, 여자 33.7%)와 5.31%(남자 3.3%, 여자 7.3%)인 점과 자살시도의 위험요인이 우울 증상의 정도, 알코올 의존인 점을 고려할 때 알코올 의존 및 우울 증상의 조기발견과 치료, 그리고 자살 사고자 및 자살 시도자에 대한 정신의학적 접근과 추적관찰에 대한 방안이 강구되어야 할 것으로 생각된다. Objectives : Aims of this study were 1) to estimate prevalence rates of suicidal ideation and suicide attempt, 2) to find out whether the gender difference and age difference(13-15 years vs 16-18 years) for suicide behaviors exist, 3) to analyse correlates of suicide attempts among junior and high school adolescents aged 13-18 years old. Methods : A self-administered questionnaire was used in a cluster random sample of 2,203 school adolescents(male 1,105, female 1,098). Data were obtained on a wide range of constructs including suicidal ideation and attempts during past 2 weeks, depressive symptoms, symptoms of DSM-IV alcohol dependence, family structure, socioeconomic status, smoking, satisfaction with school achievements, and subjective health status. Chi-square test were done for analysing gender difference and age difference of suicide behaviors. Statistical analyses including uni-variate and multi-variate logistic regression analysis were done for each sex, respectively. Results : 1) The prevalence of suicide ideation during past 2 week was 30.7% in the total sample. The prevalence rates of male and female ideators were 26.9% and 34.9% respectively. The prevalence of suicide attempt during past 2 week was 5.3% in the total sample. The prevalence of suicide attempt in males was 3.4% and 7.3% in females. 2) Gender difference was significant. That is, female respondents showed higher rate of suicidal ideation and suicide attempt. In our study age difference was found only at the rate of suicide attempt. That is, older adolescents(16-18 years) showed only statistically significant higher rate of suicide attempt than younger adolescents(13-15 years). 3) Multi-variate logistic regression analysis revealed that the correlates for suicide attempt were female, moderate to severe depressive symptoms, alcohol dependence in the total sample. In males the correlate for suicide attempt was alcohol dependence. In females, were moderate to severe depressive symptoms, and alcohol dependence. Conclusion : Depressive symptoms, alcohol dependence, presence of suicidal ideation were strong predictors for suicide attempts. This suggest that early detection of treatment of depression and alcohol dependence is important and psychiatric approach and follow-up be needed for the prevention of suicide.

급성 골수성 백혈병 환자에서 관해 유도 항암 화학요법 후 발생한 베르니케 뇌증

황진원,정재현,서광원,최병진,송영진,김종윤,이은지,임홍규,이상민 인제대학교 2009 仁濟醫學 Vol.30 No.-

Wernicke's encephalopathy is characterized by the triad of ocular symptoms, ataxia, and mental confusion and neuropsychiatric condition generally caused by acute thiamine deficiency. Although it is common in the severe alcoholics, several other causes also have been identified, such as total parenteral nutrition (TPN) use, hyperemesis gravidarum, anorexia nervosa, hemodialysis, uremia, and acquired immunodeficiency syndrome(AIDS). Chemotherapy in patient with malignanacy and long term total parenteral nutrition following bone marrow transplantation are related with Wernicke's encephalopathy. A 48-year-old woman had been treated with Daunorubicin and Cytarabine for remission induction chemotherapy of acute myeloblastic leukemia and intravenous hyperalimentation due to persistent hematochezia and ileus caused by infiltration of leukemic cell in terminal ileum. She suddenly complained of diplopia, tremor, and mental confusion at 32th day after chemotherapy and generalized tonic-clonic seizure at 34th day after chemotherapy. The diagnosis of Wernicke's encephalopathy was made with clinical presentations and brain MRI. Brain MR T2-weighted & Flair image revealed a high signal intensity lesions bilaterally at the medial thalamus and peri-acueductal grey matter of the midbrain. The patient was successfully treated with vitamin B1. We presented a case of acute Wernicke's encephalopathy developed after remission induction chemotherapy followed by intravenous hyperalirnentation in a patient with acute myeloblastic leukemia.