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.

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.

구리 지역에서 조사한 고혈압의 인지도, 치료률 및 관리률

홍철호,김순길,홍택원,이제,신진호,이재웅,김경수,김정현,임헌길,이방헌 대한간질학회 2003 대한간질학회지 Vol.9 No.1

혈전 발생의 위험 인자가 없는 환자에서 급성 신우신염에 의해 유발된 신정맥 혈전증 및 폐색전증

이광수,김아름,이승연,정주홍,김미정,이진수,정문현,홍기천,조순구 대한감염학회 2009 감염과 화학요법 Vol.41 No.5

Renal vein thrombosis (RVT) is not an uncommon condition amongst patients with nephrotic syndrome or malignancy. Septic pulmonary embolism (SPE) is associated with risk factors such as intravenous drug use, pelvic thrombophlebitis, and suppurative processes in the head and neck. However, acute pyelonephritis is a rare cause of RVT and SPE. Case reports on RVT and SPE due to acute pyelonephritis are rare. In most of the earlier cases, patients had underlying conditions such as diabetes mellitus, renal carcinoma, calyceal stones, and hyperhomocysteinemia. We report a case of acute pyelonephritis complicated by RVT and SPE that occurred in a patient without any predisposing risk factors for thromboembolism. RVT and SPE were diagnosed using computed tomography and ventilation/perfusion scan. The patient recovered with antibiotics and anticoagulation therapy without any surgical interventions.

표면근전도와 적외선체열촬영을 이용한 요통의 평가

이강진,최인성,이소영,한재영,이삼규,채홍재,이성과,문재동 대한산업의학회 2001 대한직업환경의학회지 Vol.13 No.3

목적 : 요통환자에서 요통의 유무와 강도를 평가하고자 표면근전도를 이용하여 근육 활동성의 차이를 검증하였고 적외선체열촬영을 이용하여 제표면 온도의 변화를 측정하였다. 방법 : 요통환자군 16명과 대조군 16명에 대하여 요부에 부착한 표면전극에서 얻은 근전도 신호와 적외선체열촬영 결과를 비교하였다. 교란요인의 영향을 배제하기 위하여 연령과 성별 그리고 비만도에 따라 정상 대조군과 요통환자군을 짝짓기하여 각각 16명씩 선정하였다. 결과 : 정적표면근전도 실시 결과 우측의 경우 중앙값이 요통환자군에서 198.1 ㎶, 정상대조군에서는 161.3 ㎶로 통계적으로 유의한 차이가 있었고(p<0.01), 좌측은 요통환자군에서 194.2 ㎶, 정상대조군에서 180.5 ㎶로 유의한 차이는 없었다. 동적표면근전도 실시 결과 재신전시와 굴곡시 근전위의 비가 우측의 경우 요통환자군에서 중앙값이 1.12였고 정상 대조군은 1.39로서 두 군간에 유의한 차이가 있었고(p=0.027), 좌측의 경우도 요통환자군에서는 1.08이었고 정상 대조군에서는 1.21로 유의한 차이가 있었다(p=0.036). 적외선체열촬영결과 ΔT가 0.5 ℃ 이상의 차이가 있을 때 이상이 있는 것으로 정하면, 요통환자군에서는 16명 모두 이상자로 판정되었고, 정상 대조군에서는 16명중 3명이 이상자로 판정되어 민감도는 100 %, 특이도는 81.3 % 였다. 표면근전도를 이용한 요통의 진단은 민감도가 78.6 %이고 특이도가 72.2 %였으며, 적외선체열촬영은 민감도가 100 %였고 특이도가 87.5 %였다. 결론 : 이러한 결과로 볼 때 표면근전도 검사법과 적외선체열촬영은 요통을 간접적으로 평가하는데 도움이 되는 검사법이며, 적외선체열촬영이 표면근전도검사법에 비하여 보다 정확한 검사법으로 판단된다. Objectives : We studied the efficacy of surface electromyography(SEMG) and digital infrared theimographic imaging (DITI) in the assessment of low back pain both(LBP) Methods : We compared electromygraphic signals from electrodes placed in the lumbar area and the digital theimographic images in 16 LBPpatients and 16 control subjects. The LBP patients and the control subjects were matched for age, gender, and body mass index(BMI) to adjust for any confounding effects Results : In the static analyses of SEMG, median value was 198.1 ㎶ for the controls on the right side, and they were 194.2 ㎶ and 180.5㎶ on left side respectively. There was a statistically significant difference between the two groups on the right side(p<0.01), but not on the left side. In the dynamic analyses of the SEMG, the median values of the extension per flexion ratio of right side were 1.12 for LBP patients and 1.39 for controls. and those on the left side were 1.08 and 1.21 respectively. There were statistically significant differences in both sodes(p<0.05). The sensitivity and specificity were 100% and 81.3% in DITI, 78.6% and 72.2% in SEMG. Conclusions : These results indicate that SEMG and DITI are useful methods for indirect assessments of LBP, and that DITI is more sensitive and specific than SEMG.

간암 환자에 합병된 Citrobacter braakii 패혈증 1례 보고

이해미,배성하,이수남,이정우,신아영,류시영,이수연,윤문희,한선영,한남익,이영석,유진홍 대한감염학회 2010 감염과 화학요법 Vol.42 No.3

Citrobacter species is a gram-negative bacilli that can cause opportunistic infections in immunocompromised hosts. Citrobacter braakii refers to the genomospecies 6 of the Citrobacter freundii complex. There are no detailed studies on infections caused by this newly identified specific genetic species in Korea. We herein report a case of a patient with hepatocellular carcinoma who, after undergoing transcatheter arterial chemoembolization, developed biloma which later progressed to C.braakii sepsis and did not respond to treatment. To our knowledge, this is the first reported case in Korea on C. braakii infection resulting in septic shock in a patient with malignancy in Korea.

서울의 Penicillinase Producing Neisseria Gonorrhoeae 발생빈도(1994)

김재홍,안진균,정성재,김영태,김중환,김시영,이석종,이홍렬,서호석,김경훈,권혁진,정우권,고우석,이용석,안필수,오준규,오용섭 대한화학요법학회 1996 대한화학요법학회지 Vol.14 No.1

Background : In recent years gonorrhoea has been panendemic and remains one of the most common Sexually Transmitted Diseases in the world, especially in developing countries. Objective & Method : For the detection of a more effective therapeutic regimen and assessing the prevalence of Penicillinase Producing Neisseria Gonorrhoeae(PPNG), Ive 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 1994, 168 strains of N. gonorrhoeae were isolated, among which 109 (64,9% ) were PPNG. Conclustion : Our results suggests that the prevalence of PPNG in Seoul is still increasing.

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.

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.