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.

홍씨 앞방각측정법의 임상적 유용성

강신희,박기호,홍철,김동명,Shin Hee Kang,M,D,Ki Ho Park,M,D,Chul Hong,M,D,Dong Myoung Kim,M,D 대한안과학회 2007 대한안과학회지 Vol.48 No.3

Purpose: To compare the Hong`s grading method, utilized for slit-lamp grading of the mid-peripheral angle, with other conventional grading methods. Actual angle was measured by ultrasound biomicroscopy (UBM) for comparison. Methods: Fifteen eyes with narrow angles and eighteen eyes with wide angles were studied. The average age of thirty-three subjects was 46.8±19.2, and the male to female ratio was 1:3.7. The mid-peripheral angle was graded by Hong`s, van Herick`s and Spaeth`s grading system. The actual anterior chamber angle was evaluated by UBM and the correlation between each grading system and actual angle was investigated. Results: The results from the Hong`s grading (r=0.802, R2=0.643, p<0.01), Spaeth`s grading (r=0.728, R2=0.530, p<0.01) and van Herick`s grading (r=0.618, R2=0.382, p<0.01) methods correlated significantly with the actual angles. Conclusions: The Hong`s grading method was an easy and effective tool to evaluate anterior chamber angle. In addition, the results of the Hong`s grading method were closer to the actual angle than the other methods.

광선각화증, 보웬병, 편평상피세포암에서 Ki-67, Cyclin A, p53, p16의 발현 양상

이효진 ( Hyo Jin Lee ),신동훈 ( Dong Hoon Shin ),최종수 ( Jong Soo Choi ),김기홍 ( Ki Hong Kim ) 대한피부과학회 2012 대한피부과학회지 Vol.50 No.4

Background: Actinic keratosis (AK) and bowen`s disease (BD) are pre-cancerous diseases, and are regarded as an early squamous cell carcinoma (SCC). AK and BD can be progressed into SCC. In this process, tumor suppressor and cell proliferative proteins may play important roles. Objective: To investigate the differences of expression patterns of the immunohistochemical (IHC) staining and useful markers for differential diagnosis in AK, BD and SCC. Methods: Biopsy had proven 17 cases of AK, 20 cases of BD and 17 cases of SCC, which were all selected. IHC staining for Ki-67 and cyclin-A, as cell proliferative markers, p53 and p16 as tumor suppressor markers, were performed. Labeling index (LI) and distribution pattern of IHC expressions were measured. Results: LI of Ki-67 in AK, BD and SCC were 30.6%, 60.2% and 54.8%, respectively. LI of cyclin-A in AK, BD and SCC were 9.2%, 24.4% and 24.1%, respectively. LI of p53 in AK, BD and SCC were 20.7%, 37.9%, and 39.9%, respectively. LI of p16 in AK, BD and SCC were 10.6%, 38.3% and 39.9%, respectively. Lower 1/3 was the most frequent distribution pattern in AK in all IHC stains, full thickness lower 2/3 were the most frequent distribution pattern in BD and SCC in all IHC stains. Conclusion: LI and distribution pattern of Ki-67, cyclin-A, and p16, as well as the distribution pattern of p53 may be useful markers to differentiate AK from BD and SCC. Higher degree and full-thickness distribution pattern IHC expressions in all stains may be helpful in the diagnosis of BD, rather than AK. (Korean J Dermatol 2012;50(4):290∼298)

수영-스트레스에 의한 腦 Catecholamine 代謝의 變動에 있어서 甲狀腺-機能의 役割에 關한 硏究

洪起男,申炅浩,金炯健,全普權 고려대학교 의과대학 1989 고려대 의대 잡지 Vol.26 No.3

Effects of hyper-and hypothyroidism in the swim-stress(SS) induced changes of plasma corticosterone(CS) level and brain norepinephrine(NE) metabolism were studied in male mice pretreated with 1-thyroxine sodium(4㎎/㎏, i.p. inj. once a day for 5 days; T₄) and propylthiouracil (fed ad lib in 0.01% drinking water for 5 weeks : PTU). The circadian rhythm of spotaneous motor activity was not significantly altered by T₄ and PTU, respectively. The plasma thyroxine level was markedly increased by T₄ but reduced by PTU and the plasma thyrotropin level was markedly increased by PTU but decreased by T₄. The plasma CS level was not changed by PTU but moderately increased by T₄ Clonidine slightly increased the plasma CS level, but the clonidine effect was significantly enhanced by T₄-pretreatment. The brain NE and 3-methoxy-4-hydroxyphenylglycol(MHPG) contents were little affected by T₄ but significantly decreased by PTU. ThE SS-induced increase of plasma CS level was moderately decreased by PTU but increased by T₄. However, clonidine significantly inhibited the SS-induced increase, and the inhibitory effect of clonidine was little significantly affected by PTU and T₄ respectively. The brain MHPG content and MHPG/NE ratio were significantly decreased by clonidine bur increased by SS. THe clonidine-induced decrease of brain MHPG/NE ratio were not altered by PYTU or T₄. The SS-induced, and the inhibitory effect of clonidine was not affected by PTU and T₄ respectively. These results suggest 1) that the alteration of thyroidal function little affects the changes of brain NE in responses to swim-stress, but the stress-induced change of plasma corticosterone level may be somewhat modulated by the thyroidal function, and 2) that the hypothalamo-pituitary-adrenocortical stimulation in response to swim-stress seems to be mediated via hypothalamic noradrenergic activation, and the stress response may inhibited by the agonistic activity of clonidine on the presynaptic α₂-adrenoceptor.

무증상으로 발견된 담낭-담관 누공을 동반한 Mirizzi 증후군 1예

홍진희,전태주,서지영,서동대,오태훈,신원창,최원충,신은아,김기환 인제대학교 2009 仁濟醫學 Vol.30 No.-

Mirizzi's syndrome is a rare complication of the gallstone disease, characterized by narrowing of the common bile duct (CBD) due to chronic extrinsic compression of an impacted gallstone in the cystic duct or the neck of the gallbladder. The impacted gallstone may erode into the bile duct, causing cholecystocholedochal fistula. The patients generally have history of repeated attacks of jaundice and abdominal pain. But there is no report about asymptomatic Mirizzi syndrome with cholecystocholedochal fistula which were found incidentally. So herein we present our clinical experience with a case of asymptomatic Mirizzi syndrome with cholecystocholedochal fistula in a young female.

Morphine의 血漿 Corticosterone增加作用에 미치는 Clonidine과 Alpha-Methyldopa의 抑制性 效果의 比較

洪基成,全普權,申萬鍊 고려대학교 의과대학 1986 고려대 의대 잡지 Vol.23 No.1

There is much disagreement on the role of adrenoceptor in the ACTH liberation from the adenohypophysis. In this paper, the influences of several adrenoceptor blockades on the inhibitory effect of clonidine and alpha-methyldopa on the morphine-induced increase of plasma corticosterone level in male mice were studied. The results obtained were summarized as follows; 1. Clonidine(100 and 500㎍/kg), alpha-methyldopa(30 and 230mg/kg) and naloxone(1 and 4mg/kg), respectively, showed the dose-dependent inhibitory effect on the morphine-induced increase of plasma corticosterone level. 2. Clonidine(500㎍/kg) did not affect the increase induced by- ACTH(5U/kg), picrotoxin (4mg/kg) or cold-swim stress of plasma corticosterone level. 3. Alpha-methyldopa( 250mg/kg) did not affect the ACTH-induced increase of plasma corticosterone level but significantly suppress the picrotoxin-induced increase, and it rather enhanced the increase induced by cold-swim of plasma corticosterone level. 4. The inhibitory effect of clonidine on the morphine-induced increase of plasma corticosterone level was not affected by prazosin(1mg/kg), propranolol(1mg/kg) and haloperidol (1mg/kg) but significantly suppressed by phenoxybenzamine(1mg/kg) and yohimbine(1mg/kg). 5. The inhibitory effect of alpha-methyldopa on the morphine-induced increase was not affected by prazosin and haloperidol but significantly suppressed by phenoxybenzamine, yohimbine and propranolol. These results suggest that the inhibitory effect of clonidine on the morphine-induced increase of plasma corticosterone level may be mainly mediated by its property as an alpha₂-adrenoceptor agonist, but the inhibitory effect of alpha-methyldopa may be somewhat different from that of clonidine and may be mediated by its action as alpha₂-adrenoceptor agonist and other nonselective actions.

南江銀魚에서의 橫川吸蟲의 被襄幼蟲 感染率 調査

愼鍾旭,文武洪,朴琦緖 慶尙大學校 1976 論文集 Vol.15 No.-

An investigation on incidence of the metacercaria of Metagonimus yokogawai in a total of 576 sweetfishes, Plecoglossus altivelis originated from the Nam River was carried out. The results obtained are sumarized as follows: 1. The infection rate of the metacercaria of Metagonimus yokogawqi in the inspected fishes was 100 percent and the average number of the metacercaria in each fish was estimated as 57 with the range of 6 to 217. 2. The distribution of metacercaria in the four divided parts fo fish was varied by the different parts. The incidences of the metacercaria in the muscle and subcutaneous tissues, in the fins, in the head and in the scales were 64.5 percent, 26.7 percent, 6.7 percent and 2.1 percent respectively. 3. The number of the metacercaria in each fish was increased according to the increase of body weight of fish. 4. The number of the metacercaria in each fish generally increased in the course of the inspection from July to October.

船舶機關의 補修

申基弘 여수대학교 1991 論文集 Vol.5 No.-

For the improvement of the marine engine maintenance, we need their best working with honesty of the peaple in this field as well as closed and powerfull government support. In particular, engineer, who are on duty for the engine operation of the ship during her sailing, have to understand maintenance, trouble with it's repair and efficient operating way of the engine in order to have successful engine managine, prolong engine life and economic opreating. So, they can contribute to develop and inprove of maintenanee with safe sailing of the ship.

대구지방 두부백선에 대한 임상 및 진균학적 관찰

신동훈,김경수,김기홍 대한의진균학회 1998 대한의진균학회지 Vol.3 No.2

Background: The incidence and causative dermatophytes of tinea capitis has been changed with time. Objective: The purpose of this study was to investigate the clinical and mycological features of tinea capitis in Taegu. Methods: We evaluated the clinical and mycologic aspects of tinea capitis in 39 patients registered in Yeungnam University Hospital from January 1981 to June 1998. Results and Conclusion: The incidence of tinea capitis was 1.3% of 3,077 total dermatophytoses. The ratio of male to female patients was 1.6:1. Although most of the patients were children under the age of If, adult patients with tinea capitis were 23.1% of the cases. Frontal scalp was the most frequent site of tinea capitis. The most common causative organism of tinea capitis was Microsporum canis. Trichophyton rubrum and Trichophyton verrucosum were isolated, also.

Hemochromatosis의 1예

신기영,양영선,최하진,홍숙희 인제대학교 1982 仁濟醫學 Vol.3 No.3

Hemochromatosis는 간 경변증 피부 색소 침착 당뇨병 심부전을 주 증상으로 나타나는 질환인데 본 교실에서는 본증 1예를 경험하고 문헌 고찰과 함께 보고하는 바이다. We have seen a patient with hemochromatosis, who has been clinically studied. A 73 year old man, who had been a heavy alcohol drinker since young, was admitted to our hospital with complaints of right upper abdominal pain, dyspnea, general weakness and fatigue. The typical bronze coloration of skin, liver and skin involvements with iron deposition were demonstrated. The serum iron and total iron binding capacity were elevated up to 187ng/dl and 216ng/dl respectively. Urinary iron excretion was 60.42ug per 24hrs.