Requirement of β subunit for the reduced voltage-gated Na+ current of a Brugada syndrome patient having novel double missense mutation (p.A385T/R504T) of SCN5A

Na Kyeong Park,Seong Woo Choi,Soon-Jung Park,JooHan Woo,Hyun Jong Kim,Woo Kyung Kim,Sung-Hwan Moon,Hun-Jun Park,Sung Joon Kim 대한생리학회-대한약리학회 2024 The Korean Journal of Physiology & Pharmacology Vol.28 No.4

Mutations within the SCN5A gene, which encodes the α-subunit 5 (NaV1.5) of the voltage-gated Na+ channel, have been linked to three distinct cardiac arrhythmia disorders: long QT syndrome type 3, Brugada syndrome (BrS), and cardiac conduction disorder. In this study, we have identified novel missense mutations (p.A385T/R504T) within SCN5A in a patient exhibiting overlap arrhythmia phenotypes. This study aims to elucidate the functional consequences of SCN5A mutants (p.A385T/R504T) to understand the clinical phenotypes. Whole-cell patch-clamp technique was used to analyze the NaV1.5 current (INa) in HEK293 cells transfected with the wild-type and mutant SCN5A with or without SCN1B co-expression. The amplitude of INa was not altered in mutant SCN5A (p.A385T/R504T) alone. Furthermore, a rightward shift of the voltage-dependent inactivation and faster recovery from inactivation was observed, suggesting a gain-of-function state. Intriguingly, the coexpression of SCN1B with p.A385T/R504T revealed significant reduction of INa and slower recovery from inactivation, consistent with the loss-of-function in Na+ channels. The SCN1B dependent reduction of INa was also observed in a single mutation p.R504T, but p.A385T co-expressed with SCN1B showed no reduction. In contrast, the slower recovery from inactivation with SCN1B was observed in A385T while not in R504T. The expression of SCN1B is indispensable for the electrophysiological phenotype of BrS with the novel double mutations; p.A385T and p.R504T contributed to the slower recovery from inactivation and reduced current density of NaV1.5, respectively.

Structural basis for the ATP-independent proteolytic activity of LonB proteases and reclassification of their AAA+ modules.

An, Young Jun,Na, Jung-Hyun,Kim, Myung-Il,Cha, Sun-Shin Microbiological Society of Korea 2015 The journal of microbiology Vol.53 No.10

<P>Lon proteases degrade defective or denature proteins as well as some folded proteins for the control of cellular protein quality. There are two types of Lon proteases, LonA and LonB. Each consists of two functional components: a protease component and an ATPase associated with various cellular activities (AAA+ module). Here, we report the 2.03 -resolution crystal structure of the isolated AAA+ module (iAAA+ module) of LonB from Thermococcus onnurineus NA1 (TonLonB). The iAAA+ module, having no bound nucleotide, adopts a conformation virtually identical to the ADP-bound conformation of AAA+ modules in the hexameric structure of TonLonB; this provides insights into the ATP-independent proteolytic activity observed in a LonB protease. Structural comparison of AAA+ modules between LonA and LonB revealed that the AAA+ modules of Lon proteases are separated into two distinct clades depending on their structural features. The AAA+ module of LonB belongs to the -H2 & Ins1 insert clade (HINS clade)- defined for the first time in this study, while the AAA+ module of LonA is a member of the HCLR clade.</P>

골반경수술 146예에 대한 임상적 고찰

나준희,김용만,남주현,김영탁,김종혁,목정은 울산대학교 의과대학 1995 울산의대학술지 Vol.4 No.2

Pelviscopic surgery has been reported to have minimal tissue damage and bleeding, and to reduce cost and recovery time for patients undergoing a variety of procedures. The field of gynecologic operations that can be performed by pelviscopic procedures has expanded rapidly. This report is a retrospective review of 146 cases of pelviscopic surgery from January, 1991 to February 1996 to evaluate the efficacy of pelviscopic surgery in gynecologic patients. The results of this review were summarized as follows; 1. The majority of patients was between 21 and 40 years of age(84.2%), mean age was 33.1 years. 2. Preoperative clinical indications were adnexal mass 77 cases(52.7%), ectopic pregnancy 48 cases(33.9%), uterine myoma 9 cases(6.2%), and etc. 3. Types of surgery were salpingectomy 43 cases(29.5%), salpingoophorectomy 41cases(28.1%), LAVH 9 cases(6.2%) and etc. 4. The previous operation history was found in 34 cases(23.3%), and the type of previous operation were Cesarean section 11 cases(32.4%), appendectomy 10 cases(29.4%), and there were 5 cases of previous history of ectopic pregnancy. 5. The mean duration of hospitalization was 5.8 days.

Insecticidal toxicities of carvacrol and thymol derived from Thymus vulgaris Lin. against Pochazia shantungensis Chou & Lu.

Jun?Hwan Park,Na-Hyun Lee,Sang-Guei Lee,Hoi-Seon Lee 한국농약과학회 2017 한국농약과학회 학술발표대회 논문집 Vol.2017 No.4

전신성 홍반성 루프스 환자에서 발생한 자가 면역성 간염 1례

김준재,백나나,김현정,전태주,서동대,오태훈,최원충 인제대학교 2008 仁濟醫學 Vol.29 No.-

SLE 환자에서 간 효소 수치의 상승은 여러 가지 원인에 의하여 드물지 않게 관찰될 수 있다. 이 중 자가 면역 기전에 의해 발생되는 질환으로 자가 면역성 간염과 SLE에 동반된 간염이 있으며, 두 가지 질환의 감별은 환자의 예후 및 치료에 중요하다. 따라서 간 조직 검사를 포함한 정확한 진단 기준으로 조기에 진단하여야 하며, 이에 따른 적절한 치료를 통해서 간 부전 및 비가역적 간경변증으로 진행을 방지할 수 있을 것으로 사료된다. Patients with systemic lupus erythematosus (SLE) have a 25-50% chance of developing abnormal liver tests in their lifetime and various causes are related to elevation of liver enzyme, such as hepatic involvement of lupus, hepatotoxic drug, viral infection, autoimmune hepatitis and so on. Discrimination of autoimmune hepatitis from SLE-associated hepatitis is important because complications and therapy are quite different, although both are autoimmune syndromes. Here we are presenting a case of SLE patient with type I autoimmune hepatitis proved with liver biopsy.

치주병원균에 대한 유산균의 억제효과

정하나,김영준,정현주,오종석 전남대학교 치과대학 1999 전남치대논문집 Vol.11 No.1

This study was performed to evaluate the effect of hydrogen peroxide-producing Lactobacillus acidophilus V-20 on the replication of periodontal pathogens, Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis. When A. actinomycetemcomitans and P. gingivalis were incubated alone and in the combination with L. acidophilus V-20, the viable cell numbers of A. actinomycetemcomitans and P.gingivalis were compared between those cultures. The effect of S. mutans, E. durans, and L. lactis on the replication of A. actinomycetemcomitans and P. gingivalis was also evaluated. The change of periodontal indexes(probine depth, gingival index, GCF volume) and the viable cell numbers of A. actinomycetemcomitans and black pigmented bacteroides in subgingival plaque sample were evaluated following gargling of fermented milk made from L.acidophilus V-20 for 1 month on patients with periodontal disease in maintenance phase. In the mixed culture of L. acidophilus V-20 and A. actinomycetemcomitans or P. gingivalis, the replication of A. actinomycetemcomitans or P. gingivalis was completely inhibited. But in the mixed culture of P. gingivalis and hydrogen peroxide-nonproducing Lactobacillus casei, the viable cell numbers of P. gingivalis was not decreased when compared with the numbers in the mixed culture of P. gingivalis and L. acidophilus V-20. In the mixed culture of A. actinomycetemcomitans and S. mutans, E. durans, or L. lactis, the viable cell number of A. actinomycetemcomitans was not almost changed when compared with the numbers in the culture of A. actinomycetemcomitans alone. And in the mixed culture of P. gingivalis and E. durans or L. lactis, the viable cell numbers of P. gingivalis was not almost changed compared with the counts in the culture of P. gingivalis alone. But the replication of P. gingivalis was completely inhibited in the mixed culture of P. gingivalis and S. mutans. When the change of periodontal indexes following gargling of fermented milk was compared with baseline, probing depth and gingival index were not changed, but GCF volume was significantly decreased(p<0.05). And when the viable cell numbers of microorganisms in subgingival plaque sample were compared with baseline, total viable cell number was almost unchanged and the viable cell numbers of A. actinomycetemcomitans and black pigmented bacteroides were significantly decreased(p<0.05). These results suggest that L. acidophilus V-20 inhibit the replication of A. actinomycetemcomitans and black pigmented bacteroides by the formation of hydrogen peroxide.

임상검체에서 분리된 그람 음성 세균들에 대한 Isepamicin의 시험관내 항균력

권현희,박수진,소민욱,박현구,최성호,김미나,최상호,정진용,우준희,김양수 대한감염학회 2006 감염과 화학요법 Vol.38 No.6

Background : The increasing incidence of multidrug-resistant gram-negative bacteria causing nosocomial infections is an important clinical problem. Isepamicin is a recently developed aminoglycoside which has been known to have potent activity against gram-negative organisms. We evaluated the in vitro activities of isepamicin and other aminoglycosides against a large number of gram-negative organisms. Materials and Methods : We tested the in vitro antimicrobial activities of isepamicin, amikacin, gentamicin, and tobramycin against 566 gram-negative organisms collected between January 2006 and June 2006 in Asan Medical Center. Minimal inhibitory concentrations (MICs) were determined and interpreted according to the recommendations of Clinical and Laboratory Standard Institute (CLSI). The breakpoint MIC used for interpretation of isepamicin was MIC≤16 ㎍/mL as susceptible, 32 ㎍/mL as intermediate, and 64 ㎍/mL as resistant. Results : The MIC_(50)/MIC_(90) of isepamicln for Escherichia coli, Klebsiella pneumon/ae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterobacter cloacae were 1/2, 0.5/>128, 4/16, 16/>128, and 1/2 ㎍/mL, respectively. The susceptibilities for E. coli, K. pneumoniae, P. aeruginosa, A. baumannii, and E. cloacae were 100%, 86.4%, 89.7%, 50.0%, and 96.6%, respectively. For E. coli, K. pneumoniae, P. aeruginosa, and E. cloacae, isepamicln had better in vitro activities than gentamicin and tobromycin, and had similar activities with amlkacin. For A. baumanii, all four tested aminoglycosides had similar in vitro activities. Conclusion : Isepamicin had excellent in vitro activities against gram-negative organisms, except A. baumanii. The overall in vitro activities were similar with amikacin. 목적 : 그람 음성 세균은 다양한 지역사회 및 병원 획득 감염의 원인균이다. 최근에는 병원 감염을 일으키는 그람 음성 세균에서 항균제 내성균의 출현과 확산이 큰 문제가 되고 있다. Isepamicin은 최근에 소개된 gentamicin B의 유도체로 외국에서의 연구에 의하면 그람 음성 세균들에 대한 항균력이 우수함이 보고 된 바 있다. 본 연구에서는 우리나라의 임상 균주들을 대상으로 그람 음성세균에서 isepamicin의 시험관내 항균력을 기존의 아미노배당체 제재들과 비교하여 평가하고자 하였다. 재료 및 방법 : 2006년 1월에서 6월 사이에 서울아산병원 환자에서 분리된 Escherichia coli 113 균주, Klebsiella pneumoniae 110 균주, Pseudomonas aeruginosa 117 균주, Acinetobacter baumannii 108 균주, 그리고 Enterobacter cloacae 118 균주를 대상으로 isepaimcin, amikacin, gentamicin, tobramycin에 대한 최소억제농도(minimal inhibitory concentration, MIC)를 한천 희석법(Mueller-Hinton Agar)을 이용하여 측정하였다. 감수성여부는 CLSI 기준에 따랐으며, isepamicin은 MIC≤16㎍/mL를 감수성, MIC=32 ㎍/mL를 중등도 내성, MIC≥64 ㎍/mL를 내성으로 판정하였다. 결과 : Isepamicm의 E. coli, K. pneumoniae, P. aeruginosa, A baumannii, E. cloacae에 대한 MIC_(50)/MIC_(90)은 각각 1/2, 0.5/>128, 4/16, 16/>128, 1/2 ㎍/mL였고, 항균제 감수성률은 차례대로 100%, 86.4%, 89.7%, 50.0%, 96.6%였다. 기존 아미노배당체 제재들과 비교하면 E. coli, K. pneumoniae, P. aeruginosa, E. cloacae에서는 amikacin과 비슷한 감수성률을 보였고, gentamicin과 tobramycin보다 높은 감수성률을 보였다. A baumannii의 경우 isepamicin의 감수성률이 50.0%로 비교적 낮았지만 amikacin, gentamicin, tobramycin도 각각 50.0%, 46.3%, 47.2%의 감수성률을 나타내어 4가지 항균제가 모두 비슷한 항균력을 보였다. 결론 : Isepamicin은 그람 음성 세균들에 있어 기존의 아미노배당체 제재들과 비교했을 때 amikacin과는 동등한 시험관내 항균력을 보이고 gentamicin, tobramycin보다 뛰어난 시험관내 항균력을 보여 사용이 유망한 아미노배당체 중 하나라 생각된다.

소아 심장 CT 검사시 Dual Source CT의 High pitch mode를 이용한 선량감소에 관한 연구

이예나(Ya Na Lee),강헌효(Heon Hyo Kang),손성실(Sung Sil Son),박찬혁(Chan Hyuk Park),현진경(Jin Kyung Hyun),신명호(Myung Ho Shin),김준혁(Jun Hyuk Kim),강동원(Dong Won Kang) 대한CT영상기술학회 2012 대한CT영상기술학회지 Vol.14 No.1

I. Purpose This study examines if accurate images can be realized with less dose than sequential mode, one of the existing methods applying DSCT’s high-pitch mode in pediatric cardiography. II. Materials and Methods For 20 patients who came to our hospital from Jan. 1 to Jun. 30, 2011, a test was carried out using MDCT 128 channel dual source; Somatom Definition Flash (Siemens Medical System: Germany). As the test method, the veins of the lower limbs of the patients were secured and contrast medium of 7ml was injected at 0.3ml/s anda CT scan was carried out about 36 s. later. Af first, sequential mode was used, and then high-pitch mode was followed as follow-up examination. The DLP (Dose Length Product) provided by the equipment and effective dose were compared for the assessment of the dose exposed to the patients, after the CT scan. The effective does was calculated by multiplying children’s chest index: 0.021 of the effective dose rate of EUR16262 (European Guide) to DLP value. The images scaned in high-pitch method were compared and assessed quantitatively by a heart decoding specialist and 2 radiologists if the typical diseases of pediatric cardiacs such as coarctation of aorta, atresia of the pulmonary artery and Tetralogy of Fallot can be assessed. III. Results When it was compared to sequential mode, one of the existing cardiography, the effective dose exposed to the patient had decrease by 32% in high-pitch mode. As a result of a comparison with imaging assessment, it was also evaluated as a better imaging than sequential mode IV. Conclusion Pediatric Cardiography using high pitch in Dual source MDCT showed superior effects on the reduction of exposed does than sequential mode, which is considered a useful testing method. 목적 본 연구에서는 소아 심장 검사 시 DSCT의 High-pitch mode를 적용하여 기존의 검사방법 중 하나인 Sequential mode보다 적은 선량으로도 정확한 영상을 구현할 수 있는지 알아본다. 대상 및 방법 2011년 1월 1일부터 6월 30일까지 본원에 내원한 20명의 환자를 대상으로 하여 MDCT 128 channel dual source; Somatom Definition Flash(Siemens medical system: Germany) 장비를 사용하여 검사를 시행하였다. 검사방법은 환자의 하지에 정맥을 확보하고 조영제를 0.3 ml/s로 7ml를 주입한 후 36초 후에 CT검사를 하였다. 처음에는 Sequential mode로 검사한 후 추적 검사할 땐 High-pitch mode로 검사한다. 환자가 받은 피폭선량의 평가는 선량평가는 CT검사 후 장비에서 제공하는 DLP(dose length product)와 유효선량(effective dose)를 비교하였다. 유효선량은 DLP 값에 EUR16262(European Guide) 유효선량비 중 소아 흉부 지수 0,021을 곱하여 계산하였다. 검사한 영상을 심장 판독 전문의 1명과 방사선사 2명이 high-pitch mode로 검사한 영상을 소와 심장의 대표적 질환인 대동맥협착증, 폐동맥 폐쇄증, 팔로씨 사증을 평가할 수 있는지 비교하여 정성적으로 평가하였다. 결과 기존의 심장 검사방법 중 하나인 Sequential mode와 비교했을 때 High pitch mode로 검사했을 때에 32%의 선량 감소 효과가 있었다. 또한 영상 평가 비교 결과 Sequential mode 보다 좋은 영상으로 평가되었다. 결론 Dual source MDCT로 소아심장 검사를 할 때 high pitch mode를 이용하면 sequential mode로 검사했을 때보다 환아가 받는 피폭선량은 낮고 더 우수한 영상을 획득하여 심장질환을 진단하는데 유용한 검사법으로 사료된다.

그레이브스병에서 방사성 요오드 치료에 따른 갑상선 자극 호르몬 수용체 결합억제 면역글로불린(Thyrotropin Binding Inhibitory Immunoglobulin, TBII)의 변화

조영석,권기현,이준철,나소영,이효진,홍우정,이유선,김군순,송민호,김영건,노흥규 충남대학교 의학연구소 2003 충남의대잡지 Vol.30 No.2

Prediction of thrapeutic response to radioiodine in Graves' disease is poorly understood. Although thyrotropin binding inhibitor immunoglobulin(TBII) level is a strong index for relapse after antithyroid drug medication, conflicting results are reported regarding its prognostic significance in Graves' disease treated with RAI. This study is dengned to evaluate possible relationship between post-treatment hypothyroidism and TBII in Graves' disease treated with RAI. Fourty two patient with Graves' disease after radioiodine treatment were studied retrospectively. The subject were divided into hypothyroid group and euthyroid or hyperthyroid group. We evaluated the association of hypothyroidism and TBII with radioiodine treatment dose. The mean age of hypothyroid group was 48±11 years and euthyroid or hyperthyroid group was 47±12 years. There was no difference in two groups. And there was no significant difference in post- treatment TBII between two groups(49.9±28.5%, 29.9±14.3%, p-value >0.05). The treatment-dose had no influence on post-treatment thyroid state. Euthyroid or hyperthyroid group was done with 13.6±6.9mCi and hypothyroid group was 17.0±10.4mCi(p-value > 0.05). TBII had no prognostic significance on long-term hypothyrodism in Graves' disease treated with radioiodine. And, treatment-dose had no influence on post-treatment thyroid state.

폐렴구균 감염증에서 항생제 내성의 임상적 의미 : Asian Network for Surveillance of Resistant Pathogens(ANSORP) Study

정숙인,기현균,손준성,고관수,김나영,장현하,오원섭,백경란,이남용,김신우,이혁,--,송재훈 대한감염학회 2003 감염과 화학요법 Vol.35 No.5

목적 : 전 세계적으로 폐렴구균의 페니실린을 포함한 β-lactam과 마크로라이드 및 퀴놀론 계열의 항생제에 대한 내성이 급격히 증가하여 임상적으로 문제가 되고 있으나, 시험관내 내성이 실제 임상적 예후에 미치는 영향에 대해서는 아직까지 논란이 되고 있다. 본 연구는 폐렴구균의 항생제 내성률이 높은 아시아 지역에서 항생제 내성이 폐렴구균 감염증의 임상경과에 미치는 영향을 평가하기 위하여 시행되었다. 방법 : ANSORP에서 주관한 전향적 임상 연구로서 1999년 11월부터 2001년 8월까지 아시아 지역 11개국의 14개 기관에서 진단된 침습성 폐럼구균 감염증 환자를 대상으로 내성 균주 감염의 위험요인, 임상양상, 예후 등의 임상적 분석을 시행하였다. 결과 : 총 646명 환자의 평균연령은 30.1세(6일-89세)였고, 이전 3개월 내에 항생제 사용력이 있는 환자는 159명(32.4%)이었다. 질환별로는 폐렴이 377예(58.4%)로 가장 많았고, 중이염 67예, 뇌수막염 66예(10.2%), 일차성 균혈증 65예(10.1%)였다. 총 646균주 중 347균주(53.7%)가 페니실린 비감수성(중등도 내성 23.1%, 고도 내성 23.1%)이었고, 페니실린에 대한 MIC_(90)은 0.03㎍/mL에서 4㎍/mL까지의 분포를 보였다. 페니실린 비감수성 균주에 의한 감염증과 차이가 없었다. 페니실린 내성 폐렴구균 폐렴에 의한 사망률은 페니실린 감수성 폐렴구균 폐렴에 의한 사망률과 차이가 없었다(p=0.846). Erythromycin에 대한 고도 내성을 보이는 균주의 비율이 매우 높았으나, 실제 임상상이나 치사율에는 영향을 미치지 않았다(p=0.092). 페니실린 비감수성 폐렴구균에 의한 뇌수막염의 치사률도 감수성 균주에 의한 사망률과 차이가 없었다(p=0.059). 결론 : 본 연구의 결과 페니실린 및 베타 락탐 제제에 대한 시험관 내성은 폐렴구균 폐렴이나 뇌수막염의 임상상이나 치사율에 영향을 미치지 않는 것으로 확인되었다. 이는 내성의 정도와 연관될 것으로 생각되므로, 향후 고도 내성 균주가 증가할 때 추가 검증을 요한다. 아울러 macrolide 및 퀴놀론계 항생제 내성의 임상적 의미에 대한 후속 연구가 필요할 것으로 사료된다. Background : Despite the widespread emergence of antimicrobial resistance among pneumococcal strains worldwide, clinical implications of in vitro resistance still remain an open question. To evaluate the clinical impact of pneumococcal resistance in Asian countries where the prevalence of pneumococcal resistance was reported to be highest in the world, ANSORP has performed a prospective, multinational surveillance study with cases with invasive pneumococcal diseases in Asian countries. Methods : In vitro susceptibility of pneumococcal isolates was determined by broth microdilution tests with 16 antimicrobial agents. All enrolled cases of pneumococcal infections were analyzed with regard to demographic data, clinical features, risk factors and mortality. Results : A total of 646 patients with pneumococcal infections were enrolled from 14 centers in 12 countries between the period from November 1999 to August 2001. Pneumonia (58.4%) was the most common clinical disease followed by bacteremia (33.4%), otitis media (10.4%), and meningitis (10.2%). Among 646 isolates, 347 (53.7%) were penicillin non-susceptible (intermediate 23.1%, resistant 30.7%). MIG_(90)s for penicillin ranged from 0.03 (India) to 4.0 ㎍/mL (Korea, Taiwan, Vietnam, and Hong Kong). Overall mortality from pneumococcal diseases by penicillin non-susceptible strains was not different from that by susceptible strains. Pneumococcal pneumonia caused by penicillin- or erythromycin-resistant strains showed similar mortality, severity of illness, or complications to that by susceptible strains. Mortality from pneumococcal meningitis caused by penicillin non-susceptible strains was also similar to that by susceptible strains. Conclusion : Data suggest that current situation of in vitro resistance to penicillin or macrolides may not affect the mortality from pneumococal pneumonia or meningitis caused by antibiotic-resistant strains.