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.

한국인 직무 스트레스 측정도구의 개발 및 표준화

장세진,고상백,강동묵,김성아,강명근,이철갑,정진주,조정진,손미아,채창호,김정원,김정일,김형수,노상철,박재범,우종민,김수영,김정연,하미나,박정선,이경용,김형렬,공정옥,김인아,김정수,박준호,현숙정,손동국 大韓産業醫學會 2005 대한직업환경의학회지 Vol.17 No.4

Background and Purposes: Over the past three decades, numerous studies performed in Korea have reported that job stress is a determinant risk factor for chronic diseases and work disability. Every society has its own culture and occupational climate particular to their organizations, and hence experiences different occupational stress. An occupational stress measurement tool therefore needs to be developed to estimate it objectively. The purpose of this study is to develop and standardize the Korean Occupational Stress Scale (KOSS) which is considered to be unique and specific occupational stressors in Korean employees. Subjects and Methods: Data were obtained from the National Study for Development and Standardization of Occupational Stress (NSDSOS Project: 2002-2004). A total of 12,631 employees from a nationwide sample proportional to the Korean Standard Industrial Classification and the Korean Standard Occupational Classification were administered. The KOSS was developed for 2 years (2002-2004). In the first year, we collected 255 items from the most popular job stress measurement tools such as JCQ, ERI, NIOSH and OSI, and 44 items derived from the a qualitative study (depth interview). Forty-three items of KOSS, in the second year, were retained for use in the final version of the KOSS by using Delphi and factor analysis. Items were scored using conventional 1-2-3-4 Likert scores for the response categories. Results: We developed eight subscales by using factor analysis and validation process: physical environment (3 items), job demand (8 items), insufficient job control (5 items), interpersonal conflict (4 items), job insecurity (6 items), organizational system (7 items), lack of reward (6 items), and occupational climate (4 items). Together they explained 50.0% of total variance. Internal consistency alpha scores were ranged from 0.51 to 0.82. Twenty-four items of the short form of the KOSS (KOSS-SF) were also developed to estimate job stress in the work setting. Because the levels of the subscales of occupational stress were gender dependent, gender-specific standard norms for both the 43-item full version and the 24-item short form using a quartile for the subscales of KOSS were presented. Conclusion: The results of this study suggest that KOSS might be an appropriate measurement scale to estimate occupational stress of Korean employees. Further and more detailed study needs to be conducted to improve the validity of this scale.

한열변증에 따른 중풍 환자의 제반특성 비교

김민경,이인환,신애숙,김나희,김혜미,심소라,나병조,조승연,박성욱,정우상,문상관,박정미,고창남,조기호,김영석,배형섭,Kim, Min-kyung,Lee, ln-whan,Shin, Ae-sook,Kim, Na-hee,Kim, Hye-mi,Shim, So-ra,Na, Byung-Jo,Cho, Seung-yeon,Park, Seong-uk,Jung, Woo Sang 대한중풍순환신경학회 2010 대한중풍.순환신경학회지 Vol.11 No.1

Object : This study was conducted as part of the national project to standardize stroke diagnosis in Korean medicine. In this study, we aimed to evaluate the characteristics of acute stroke between heat pattern group and cold pattern group. Methods : We recruited stroke patients from 5 universities(Kyung-Hee University oriental medical center, Kyung-Hee University East-West Neo medical center, Kyungwon university lncheon oriental medical center, Kyungwon university Songpa oriental medical center and DongGuk university llsan oriental medical center) from April, 2007 until February, 2010. We diagnosed them and selected 463 heat pattern patients and 182 cold pattern patients. Results : We find that the risk factor of smoking, alcohol, diet(prefer to meat) are more associated with the heat pattern group. On the other hand, inflammation history in recent 3 months and diet(prefer to sea food) are more associated with the cold pattern group. RBC, Hg, Hct, TG, CK and Cl are more related to the heat pattern group. CPT, total cholesterol and HDL are more related to the cold pattern group. Tae-eum type takes high distribution of the heat pattern group, and So-eum type takes high distribution of the cold pattern group. Conclusions : This study provides evidence that the heat pattern group have more risk factor than the cold pattern group.

Pseudomonas fluorescens의 Salicylate hydroxylase를 암호하는 유전자의 클로닝

정유선,민경희,이나리 숙명여자대학교 자연과학연구소 1997 자연과학논문집 Vol.- No.8

Pseudomonas fluorescens SME11로 부터 salicylate hydroxylase를 암호하는 nahG 유전자를 클로닝하기 위하여 NAH플라스미드를 주형으로 하여 PCR을 수행하였다. PCR방법으로 얻은 1.6kb DNA절편을 pT7Blue(R)벡터에 삽입시켜 재조합 플라스미드 pNY1을 제조하였으며 이것을 E. coli에 형질전환하였다. 재조합 DNA를 제한효소로 처리하여 EcoRⅤ, KpnⅠ, PvuⅡ, StuⅠ등이 존재함을 확인하였으며, 이것으로 간단한 제한효소지도를 작성하였고 재조합 DNA를 한 방향으로 deletion하여, nahG유전자를 포함한 DNA절편의 염기서열을 결정하였다. 재조합 플라스미드인 pNY1에는 1,305bp크기의 open reading frame이 존재하였으며, salicylate hydroxylase에 해당하는 434개의 아미노산을 암호하였다. 아미노산서열을 비교한 결과, P.putida KF715와 84.1%, P.putida PpG7과 71.4%, P.putida S-1 과 48.7%의 homology를 보였으며, 또한 Sphingmonas sp.와 26.8%의 homology를 보였다. Pseudomonas fluorescens SME11 carrying NAH plasmid was isolated from wastewater. To clone nahG gene encoding salicylate hydroxylase, 1.6kb DNA fragment of PCR product from NAH plasmid was inserted to pT7Blue(R) vertor and resulting recombinant DNA was named pNY1. The transformants, E.coli SMY1, clone containing the recombinant plasmid pNY1 were able to convert salicylate to catechol and produced dark brown color caused by accumulation and auto-oxidation of catechol. Restriction endonuclease mapping of 1.6kb size of the insert of the recombinant plasmid pNY1 was carried out with EcoRⅤ, KpnⅠ, PvuⅡ, StuⅠ. By means of unidirectional ExoⅢ deletion and dideoxynucleotide chain termination, we determined the nucleotide sequence of the DNA fragment containing nahG gene. One open reading frame of 1,305 bp corresponding to 434 amino acids was found in the insert DNA. Deduced amino acid sequences of the nahG gene showed 84.1%, 71.4%, 48.7%, and 26.8% homologies to those from P.putida KF715, P. putida PpG7, P. putida S-1, and Sphingmonas sp., respectively.

용량별 죽력 투여가 생쥐의 간과 신장의 조직 및 혈액학적 변화에 미치는 영향

정종길,나창수,김경수,홍광표,김정상 대한본초학회 2002 大韓本草學會誌 Vol.17 No.2

Objectives : Bambusae Caulis in Liquamen extracts (BE) has been used for various curative effect that remove intense heat from the heart, replenish deficiency Yin, nourish deficiency blood, resolve phlegm. This study was performed to investigate the toxicity of BE to mice according to the administered dosage. Methods : The experimental groups divided four. Control group treated saline, J1 group treated BE and distilled water in the ratio of 1:15(0.05ml/kg), F2 group treated BE and distilled water in the ratio of 1:7(0.05ml/kg), J3 group treated BE and distilled water in the ratio of 1:17(0.05ml/kg). We administered BE to the mice for 24 weeks at interval of 48 hours, and investigated the body weight, changes in hematological profile, activities of the transaminase(GOT, GPT) and two hepatic antioxidant enzyme(SOD, catalase), and histological changes of the liver and kidney. Results : Leukocytes of J3 group were increased in the administered for 12 weeks, but decreased in the administered for 24 weeks. Platelets were decreased about 36% in J3 group treated for 12 weeks, but increased about 50% in the same group treated for 24 weeks. Blood total proteins were decreased slightly in the all experimental groups compared with control group. The activities of the transaminase and superoxide dismutase(SOD) were increased, but decreased activities of catalase in the J2 and J3 groups administered for 12 or 24 weeks. In the light microscopical observation, ballooned and injured hepatocytes in portal vein area of J1 group occurred, and dilated hepatocytes and disoriented sinusoid observed in J2 group administered extracts to mice for 24 weeks. Apoptosis occured in the ballooned and injured hepatocytes of the portal vein area in J3 group. A agglutination of RBC in glomerular capsule of the kidney observed in the J2 group, and destructed convoluted tubule observed in the J3 group treated for 24 weeks. Conclusions : These results indicate that mice treated with high dose BE develop a hematological changes, dysfuncton of the liver and kidney.

만성신부전 환자에서 발생한 파종결핵

정가영,나선경,윤혜원,송하응,류정화,류동열 이화여자대학교 의과학연구소 2013 EMJ (Ewha medical journal) Vol.36 No.1

Patients with chronic renal failure (CRF) are known to be more susceptible to tuberculosis infection due to impairment of the host defense mechanism. Although extrapulmonary tuberculosis is more prevalent in those subjects and it may induce dismal outcome, its diagnosis has been challenging since there is no specific symptoms of the disease and the clinical course is usually atypical. Herein, We report a case of disseminated tuberculosis diagnosed by ultrasound-guided liver biopsy in a 31-year-old CRF patient presenting sustained fever despite broad-spectrum antimicrobial therapy and progressive cholestatic jaundice.

열린교육 이론에 근거한 멀티미디어 코스웨어의 개발 및 그 학습 효과 분석

나정흠,하경재 경남대학교 정보통신연구소 1999 연구논문집 Vol.1 No.-

본 논문은 열린교육이론에 근거한 멀티미디어 코스웨어의 설계전략을 제안한다. 이 코스웨어는 고등학교 공업과 '전동용 기계요소' 단원을 재구성하여 열린교육의 개념에 맞게 기본학습, 발전학습, 선택학습을 두어 학습자가 각기 자신의 학업능력에 따라 원하는 코스로 갈 수 있도록 설계 구현되었다. 또한 각 학습단계 마다 다양한 학습코스를 두어 각자의 개성과 취미에 맞게 적절한 학습코스 및 학습량을 조절할 수 있게 설계하였다. 본 논문에서 개발한 코스웨어를 실제의 교육현장에서 적용한 결과와 전통적인 수업방식의 결과를 통계적으로 분석하여 그 학습효과를 검증하였다. In this paper, a multimedia courseware design strategy based on the open education theory is proposed. This courseware is designed for studying the "Gearing machine element" part of high school's industry subject and to be fit for the open education concepts. It consists of the stepwise study courses such as the Basic study, the Progressive study and the Selective study courses according to the scholastic levels of students. Moreover, diverse study courses are embedded in each study step of the courseware. Therefore, using this courseware, students themselves can choose a proper study course and control their study quantity according to their individual character and interests. Through the application of the courseware to an actual education field, its study effects are statistically analyzed. Results of the analysis show that the courseware-applied groups show improvements on their study in all scholastic levels of students, especially in the lowest level in comparison with the groups educated by the traditional way of lecture.

Angiotensin 전환효소 유전자 다형성과 양극성 장애

김경나,김종우,정주호,이기철,정홍경,임성빈 대한생물치료정신의학회 2003 생물치료정신의학 Vol.9 No.2

연구목적 : 감정조절에 Renin-Angiotensin System이 관여하는 것으로 보고되어 왔다. 그 근거로 우울증의 새로운 약물치료로 주목받고 있는 Substance P의 대사에 angiotensin 전환효소(angiotensin-converting enzyme, ACE)가 관여한다는 것과 고혈압 환자에서 angiotensin 전환효소 억제제(ACE inhibitor)를 사용했을 때 다행감이나 우울감을 초래한다는 것 등이 있다. 본 연구에서는 ACE의 유전자 다형성을 분석하여 양극성장애와 ACE와의 연관성을 알아보고자 하였다. 방 법 : 양극성장애로 진단된 환자군 82명과 대조군 135명을 대상으로 16번째 intron의 다형성 부위를 가진 시발체 쌍(primer pair)을 사용하며 중합효소 연쇄반응(Polymerase Chain Reaction, PCR)을 시행하여 490bp 산물(I allele)과 190bp 산물(D allele)을 관찰함으로써 ACE 유전자의 유전자형(genotype)의 발현율과 대립유전자(allele)의 빈도를 비교 분석하였다. 결 과 : 양극성장애 환자군과 대조군 사이에서 유전자형의 발현율과 대립유전자적 빈도는 유의한 차이가 없었다. 결 론 : 양극성장애 환자군과 ACE 유전자 다형성 사이에 유의한 관련성은 없었다. 이 결과는 ACE가 양극성 장애의 원인으로 주요한 역할을 한다는 것을 시사하지 못했다. Objectives : A possible participation of the Renin-Angiotensin Systern(RAS) in regulating of the mood has been suggested by reports as follows : the angiotensrn converting enzyme(AGE1 is involved jn the metabolism of the neuropeptide substance P impficated with novel strategies for the pharmacotherapy of depression and the use of ACE inhibitors in hypertensive patients has been associated with euphoric or depressive stales. The aim of the present study was to analyze the role of the ACE gene I/D polymorphism for bipolar disorder. Methods : We examined the frequency of a polymorphism characterized by the insertion or deletion of a 287-bp Alu repeat sequence in intron 16 of the angiotensin converting enzyme gene(located on chromosome 37q233 in groups of patients with bipolar disorder(n=82) compared to healthy control subjects[n=135). ACE genotype was determined by size-analysis of polymerase chain reaction products. Results : The ACE ID polymorphism did not show any difference in allelic frequencies and genotypic distributions between bipolar disorder patients and control subjects. Conclusions : No significant association was found with bipolar disorder and the polymorphism of ACE gene. This finding does not support that ACE I/D polymorphism is a significant risk factor for bipolar disorder.

현훈증 감별에 있어 뇌간청각유발전위의 진단적 의의

조경원,정원영,나정균,임건한 조선대학교 1994 The Medical Journal of Chosun University Vol.19 No.1

Sudden onset vertigo is a common complaint in patients who are referred for neurological evaluation. But the entire physical examination and other diagnostic tests may be normal in these patients. Therefore we need more accurate diagnostic tools in the differential diagnosis between the peripheral and the contral vertigo. To evaluate diagnostic effectiveness, we performed Brainstem Auditory Evoked Potentials(BAEP) in the patients with 19 brainstem infarction, 23 peripheral vertigo, 20 vertebrobasilar transient ischemic attack(VB TIA) and analyzed the absolute latency of wave Ⅰ, Ⅲ, Ⅴ and interpeak latency of wave Ⅰ-Ⅲ, Ⅲ-Ⅴ,Ⅰ-Ⅴ compared to normal control data. The results were summerized as follows : 1. There was no significant differences in absolute and interpeak latencies of each BAEP waves between the group of normal control and the group of peripheral vertigo. 2. Among 19 VB TIA patients, prolonged absolute and interpeak latencies of BAEP waves were detected in eleven patients(57.9%) and in nine patients(47.3%), respectively. The abnormal findings were bilaterally in five patients(26.3%) 3. Among 20 brainstem infarction patients, ten patients(50%) showed abnormal BAEP findings, including prolonged interpeak latencies(in three, 15%) and absence of waveform(in seven, 35%). Therefore it is concluded that BAEP could be helpful in differential diagnosis of pathints with peripheral vertigo, V-B TlA, brainstem infarction and other disease of similiar symtomatology.

만화 과제를 이용한 정신분열병 환자의 사회인지 능력의 측정

오정은,나명현,하태현,신용욱,노규식,홍순범,이경진,신민섭,이영호,권준수 大韓神經精神醫學會 2005 신경정신의학 Vol.44 No.3

Objectives : This study is to investigate the hypothesis that schizophrenic patients have difficulty in inferring mental state of others. Methods : Twenty schizophrenic patients and twenty normal subjects were administered to the Cartoon Task required inferring the character's intention in a given context. Results : The schizophrenic patients showed a statistically significant impairment in the Cartoon Task. Both groups chose the card depicting a frequent everyday action significantly more rather than the similar card to the last picture in each story for wrong answers. Conclusion : These preliminary results suggest that schizophrenia is associated with a specific deficit of the cognitive ability referred to as social cognition, and this deficit can be detected not only in the acute phase as found in previous research studies, but also in remission. Also when subjects fail to appreciate what is going on in the minds of other people, they seem to rely on a socially familiar experience.