Clostridium difficile에 의한 설사의 예후인자

김준형,김희정,구남수,김영근,최준용,신소연,박윤선,김연아,김명수,정수진,최희경,송영구,이경원,김준명 대한감염학회 2007 감염과 화학요법 Vol.39 No.2

배경 : Clostridium difficile에 의한 설사(Clostridium difficile associated diarrhea; CDAD)는 임상 경과가 다양하다. 최근에 유럽과 북미에서 C. difficile 감염의 발생률이 증가하고 고전적 치료에 잘 반응하지 않으며 이환률이 증가하였고, 이러한 원인이 새로운 균주의 탄생에 기인한다고 보고되었다. CDAD의 예후에 영향을 미치는 세균성 요인과 숙주 요인을 확인하기 위해 본 연구를 진행하였다. 재료 및 방법 : 2002년 8월부터 2003년 12월까지 CDAD가 진단된 20세 이상인 환자들을 대상으로 후향적 Cohort 연구를 하였다. 세균성 요인을 확인하기 위해 cdt A, cdtB, tcd A, tcd A rep 그리고 tcd B 유전자(binary toxin)를 확인하였다. 설사가 치료 시작 후 11일 이상 지속되거나, 2달 이내에 재발하거나, 수술 혹은 다른 시술이 필요한 경우, 사망한 경우 예후가 좋지 않은 것으로 정의하였다. 결과 : 총 115예에서 toxin을 생성하는 C. difficile가 동정되었으며, Toxin A와 toxin B 모두 양성인 균이 91예, toxin B만 양성인 균이 24예였다. Toxin A 생성 여부가 예후에 영향을 미치지 않았지만, 제산제를 사용한 환자에서 그렇지 않은 환자에 비해 toxin B만 양성인 균이 많이 동정되었다(P<0.05). 예후가 좋지 않은 경우는 39예(33.9%)였고 76예(66.1%)에서 예후는 양호하였다. 단변량 분석에서 70세 이상의 고령, 남성, 증상 발현 후 사용한 항생제의 개수 사용, 증상 발현 후 carbapenem, aminoglycoside, glycopeptide 사용, 당뇨 및 뇌졸중 병력이 있는 경우, 그리고 높은 Charlson index가 불량한 예후 인자로 확인되었다. 그러나 독립적인 예후 인자를 조사했을 때에는70세 이상의 고령(odds ratio=3.378, P=0.009), 증상 발현후 carbapenem 사용(odds ratio 7.210, P<0.001)이 예후에 중요한 영향을 미치는 요소로 확인되었다. 결론 : 70세 이상의 고령과 증상 발현 후 carbapenem 사용이 CDAD 독립적인 불량한 예후인자이다. Background : Clostridium difficile associated diarrhea (CDAD) has a wide range of clinical manifestations. The prognostic factors of CDAD are not fully understood. Materialsand Methods : A retrospective cohort study of 115 patients with CDAD from Aug. 2002 to Dec. 2003 was conducted to evaluate prognostic factors of CDAD. Bacteriologic factors were determined by detecting the binary toxin gene, tcd A, tcd A rep and tcd B gene. Poor prognosis was defined as diarrhea more than 10 days even with classic treatment, recurrence, death, and moribund discharge. Results : Approximately 79% of isolated strains were toxin A+/B+ strains and 21% were toxin A-/B+ strains. There was no difference in prognosis between toxin A+ and toxin A- strains. 39 (33.9%) cases showed poor prognosis and 76 (66.1%) cases showed good prognosis. Univariate analyses revealed that the poor prognostic factors were old age over 70 years old, male, the number of antibiotics used after onset of symptom, the administration of carbapenems, aminoglycosides, glycopeptides after onset of symptom, history of DM and stroke, and high Charlson comorbidity index. Multiple logistic regression analysis identified old age over 70 years old (odds ratio=3.378, P=0.009) and the administration of carbapenems after onset of symptom (odds ratio 7.210, P<0.001) as the independent poor prognostic factors. Conclusion : Old age over 70 and the administration of carbapenems after onset of symptom were the poor prognostic factors for CDAD caused by none-binary toxin producing strains.

자궁 내 감염 관련 유전자 및 산화 스트레스 관련 유전자와 조기분만의 연관성

유시연 ( Si Yeon You ),김정명 ( Jung Myung Kim ),이경아 ( Kyung A Lee ),박미혜 ( Mi Hye Park ),김영주 ( Young Ju Kim ),전선희 ( Sun Hee Chun ) 대한산부인과학회 2010 Obstetrics & Gynecology Science Vol.53 No.7

목적: 조기 분만과 자궁 내 감염 관련 유전자 (IFN-γ, interleukin [IL]-10) 및 산화 스트레스 관련 유전자 (CYP1A1)와의 연관성을 알아보고자 한다. 연구 방법: 2007년 1월부터 2008년 12월까지 이대 목동병원 산부인과에서 산전 검사 및 분만을 시행한 산모 중 37주 이전에 분만한 조산군 164명과 37주 이후에 분만한 대조군 305명을 대상으로 하였으며, 임신 주수 24주 미만, 태아의 선천성 기형, 다태아 분만, 사산의 경우를 제외하였다. 참여자는 입원 시 키, 몸무게 측정 및 혈액 채취를 시행하였고 임신 주수는 최종 월경일 또는 초음파 측정을 통해 계산 되었다. 산모의 혈액에서 IFN-γ, IL-10, CYP1A1 유전자형을 PCR과 SNaPShot method를 사용하여 검사하였으며 카이제곱 검정과 다중 로지스틱 회귀분석을 사용하여 통계분석 하였다. 결과: 조기 분만군과 만삭 분만군 사이에 임신 주수, 태아 체중에 통계적으로 유의한 차이가 있었다(P<0.0001). IFN-γ, IL-10, CYP1A1 유전자형의 빈도와 조기 분만 사이에는 유의한 상관성이 없었다(P>0.05). 결론: 본 연구에서 IFN-γ (874A/T) 및 IL-10 (1082A/G), IL-10 (819C/T), IL-10 (592A/C)와 CYP1A1 (T6235C), CYP1A1 (Ile462val [A/G]) 유전자형의 빈도는 조산과 관련이 없었다. Objective: To investigate the association between preterm birth and cytokine genes (IFN-γ, interleukin (IL)-10) in intrauterine infection and enzyme gene (CYP1A1) in oxidative stress response. Methods: This study involved a case-control study conducted at Ewha Womans University Hospital in Seoul, Korea. Subjects with preterm deliveries (<37 weeks of gestation) and normal controls with term deliveries (≥37 weeks of gestation) were selected from gravidas who had undergone prenatal examinations in the hospital and were followed until infant delivery. The weight, height, and blood samples of each participants were obtained according to standard protocols. We included subjects who gave birth to a singleton infant and had a gestational age between 24 and 42 weeks. Mutiple births, stillbirths, and congenital anomalies were excluded. Finally, 164 gravidas with preterm births and 305 normal controls with term deliveries were enrolled in the present study. Results: Preterm delivery group and term delivery group had significant difference in gestational age and neonatal body weight (P<0.0001). There were no statistically significant association between preterm birth and IFN-γ, IL-10, CYP1A1 genes (P>0.05). Conclusion: In this study, IFN-γ (874A/T), IL-10 (1082A/G), IL-10 (819C/T), IL-10 (592A/C) and CYP1A1 (T6235C), CYP1A1 (Ile462val [A/G]) genes had no significant association with preterm birth.

흉부 방사선 치료후 완전방실차단증과 양측 관동맥구 협착증을 보인 1예

고경환,김정경,이수금,윤재형,조성제,이상훈,홍석근,현민수,황흥곤,김명아,박성훈 대한내과학회 1997 대한내과학회지 Vol.53 No.3S

We have experienced a case of radiation-induced coronary biostial stenosis presented with recurrent syncopal attack, which was confirmed by coronary angiography and pathologic findings. A 60 year-old woman was admitted with the symptoms of recurrent syncopal attack. She had a history of radiation therapy of the chest for lung neoplasm 15 years ago. Initial electrocardiogram showed transient high-degree A-V block followed by third-degree atrioventricular block which was associated with syncope. Echocardiography revealed mild aortic regurgitation without left ventricular dysfunction. The coronary angiogram revealed biostial stenosis of coronary arteries. Initial cardiac symptom subsided after temporary pacemaker implantation. She had a coronary bypass graft surgery on both coronary arteries using saphenous vein. Biopsy findings showed mild fibrosis with intimal thickening of coronary artery.

Guanylate cyclase activator YC-1 potentiates apoptotic effect of licochalcone A on human epithelial ovarian carcinoma cells via activation of death receptor and mitochondrial pathways

Lee, C.S.,Kwak, S.W.,Kim, Y.J.,Lee, S.A.,Park, E.S.,Myung, S.C.,Kim, W.,Lee, M.S.,Lee, J.J. North-Holland ; Elsevier Science Ltd 2012 european journal of pharmacology Vol.683 No.1

Natural phenol licorice compounds have been shown to induce apoptosis in cancer cells. 3-(5'-Hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1) may enhance the sensitivity of cancer cells to anticancer drugs. However, the combined effect of licochalcone A and YC-1 on cell death in ovarian cancer cells has not been studied. We assessed the combined effect of licochalcone A and YC-1 on apoptosis in human epithelial ovarian carcinoma cell lines in relation to the cell death process. In the OVCAR-3 and SK-OV-3 cell lines, licochalocone A induced a decrease in Bid, Bcl-2, Bcl-xL and survivin protein levels; an increase in Bax levels; loss of the mitochondrial transmembrane potential; cytochrome c release; activation of caspases (-8, -9 and -3); cleavage of PARP-1; and an increase in the tumor suppressor p53 levels. YC-1 enhanced licochalcone A-induced apoptosis-related protein activation, nuclear damage and cell death. These results suggest that YC-1 may potentiate the apoptotic effect of licochalcone A on ovarian carcinoma cell lines by increasing the activation of the caspase-8- and Bid-dependent pathway and the mitochondria-mediated apoptotic pathway, leading to caspase activation. The combination of licochalcone A and YC-1 may confer a benefit in the treatment of human epithelial ovarian adenocarcinoma.

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.

MOLECULAR EPIDEMIOLOGY OF AVIAN POXVIRUS IN THE ORIENTAL TURTLE DOVE (<i>STREPTOPELIA ORIENTALIS</i>) AND THE BITING MIDGE (<i>CULICOIDES ARAKAWAE</i>) IN THE REPUBLIC OF KOREA

Lee, Hae Rim,Koo, Bon-Sang,Kim, Jong-Taek,Kim, Heung-Chul,Kim, Myung-Soon,Klein, Terry A.,Shin, Man-Seok,Lee, Sanghun,Jeon, Eun-Ok,Min, Kyung-Cheol,Lee, Seung Baek,Bae, Yeonji,Mo, In-Pil Wildlife Disease Association 2017 JOURNAL OF WILDLIFE DISEASES Vol.53 No.4

<P>A total of 600 wild birds were analyzed for the causes of mortality in the Republic of Korea (ROK) from 2011 to 2013. Avian poxvirus (APV) infections were identified as the primary cause of mortality in 39% (29/74) Oriental Turtle Doves (Streptopelia orientalis). At necropsy, all 29 S. orientalis birds, of which, 76% (22/29) were juveniles, had severe diphtheritic lesions in their oral and nasal cavities and on their eyelids, which were the lesions of APV that resulted in mortality. We detected APV infection by chorioallantoic membrane inoculation and molecular study of the partial region of the P4b gene. All isolates belonged to the same APV strain and were identical to strains isolated from several different pigeon species in South Africa. Phylogenetically, the APV strain identified in S. orientalis belonged to subclade A2, which includes isolates from several species of pigeons from different parts of the world, including the United Kingdom, Germany, India, Egypt, Hawaii, Georgia, Hungary, South Africa, Tanzania, and the ROK. This identity indicated that this diphtheritic APV strain may be a potential pathogen of other pigeon species in the ROK and neighboring countries throughout the range of S. orientalis. However, reticuloendotheliosis virus insertion into the APV genome was not detected by PCR in any of the 29 APV infections. An identical strain of APV observed in S. orientalis was also detected in Culicoides arakawae (biting midge), with annual peak populations corresponding to the presence of APV in S. orientalis. Culicoides arakawae may be a primary vector of APV in S. orientalis. Active surveillance of APVs in wild birds and C. arakawae is needed to better understand the epidemiology of APVs, host-vector relationships, and its ecological effects on S. orientalis in the ROK.</P>

Small molecule and peptide-mediated inhibition of Epstein-Barr virus nuclear antigen 1 dimerization

Kim, Sun Young,Song, Kyung-A,Kieff, Elliott,Kang, Myung-Soo Elsevier 2012 Biochemical and biophysical research communication Vol.424 No.2

<P>Latent Epstein-Barr virus (EBV) infection is associated with human B cell lymphomas and certain carcinomas. EBV episome persistence, replication, and gene expression are dependent on EBV-encoded nuclear antigen 1 (EBNA1)'s DNA binding domain (DBD)/dimerization domain (DD)-mediated sequence-specific DNA binding activity. Homodimerization of EBNA1 is essential for EBNA1 DNA binding and transactivation. In this study, we characterized a novel small molecule EBNA1 inhibitor EiK1, screened from the previous high throughput screening (HTS). The EiK1 compound specifically inhibited the EBNA1-dependent, OriP-enhanced transcription, but not EBNA1-independent transcription. A Surface Plasmon Resonance Biacore assay revealed that EiK1 associates with EBNA1 amino acid 459-607 DBD/DD. Consistent with the SPR data, in vitro gel shift assays showed that EiK1 suppressed the activity of EBNA1 binding to the cognate familial repeats (FR) sequence, but not control RBP-Jκ binding to the Jκ site. Subsequently, a cross-linker-mediated in vitro multimerization assay and EBNA1 homodimerization-dependent yeast two-hybrid assay showed that EiK1 significantly inhibited EBNA1 dimerization. In an attempt to identify more highly specific peptide inhibitors, small peptides encompassing the EBNA1 DBD/DD were screened for inhibition of EBNA1 DBD-mediated DNA binding function. The small peptide P85, covering EBNA1 a.a. 560-574, significantly blocked EBNA1 DNA binding activity in vitro, prevented dimerization in vitro and in vivo, associated with EBNA1 in vitro, and repressed EBNA1-dependent transcription in vivo. Collectively, this study describes two novel inhibitors of EBNA1 dimerization. This study demonstrates that EBNA1 homodimerization can be effectively targeted by a small molecule or peptide.</P>

연령별 Antistreptolysin O 분포 및 정상치

김선주,정명아,정현주,김윤정,맹국영 대한감염학회 1998 감염 Vol.30 No.4

배 경 : ASO 검사는 S. pyogenes 감염과 류마티스열이나 급성 사구체신염 등 후유증을 진단하는데 매우 유용하다. ASO 정상치는 연령에 따라 달라지는 것으로 알려져 있으므로, 단회의 ASO 결과를 올바로 해석하기 위해서는 같은 지역의 동일한 연령의 정상치를 알고 있어야 한다. 방 법 : 저자들은 진주지역 학동기전 아동 (162명), 초등학생 (436명)과 성인 (231명) 세 군에서 ASO 정상치와 분포를 살펴보았다. 연쇄구균 감염 증상이나 징후가 없는 진주 지역 주민들을 대상으로 혈청내 ASO치를 자동화학분석기 (Cobas Mira, Roche)와 비탁기 (Behring Nephelometer 100 Analyzer)를 이용하여 정량 분석하였다. 결 과 : 학동기전 아동, 초등학생 및 성인에서의 평균 ASO치는 각각 71 IU/mL (표준편차 107), 285 IU/mL (표준편차 246) 및 80 IU/mL (표준편차 64) 이었고, 정상상한치는 각각 131 IU/mL, 433 IU/mL, 136 IU/mL 이었다. 결 론 : ASO 정상치 및 분포는 각 연령군에 따라 크게 다르므로, ASO 정상치는 연령에 따라 다르게 설정되어야 할 것이다. A군 연쇄구균 감염은 학동기전 아동이나 성인에서는 매우 드문 반면, 초등학생에서는 빈번함을 알 수 있었다. Background : Antistreptolysin O (ASO) is very useful as an indicator of recent streptococcal infection and its sequelae, such as rheumatic fever and acute glomerulonephritis. Becuase the upper limit of normal (ULN) value of ASO varies according to age, the ULN value of ASO in an area should be evaluated to accurately interpret single ASO levels of patients. Methods : The ULN value and distribution of ASO concentrations were investigated in three age groups of preschool children (N=162), elementary school children (N=436), and adults (N=231) in Chinju. ASO concentrations were measured quantitatively by autoanalyzer or nephelometer from sera of healthy population in Chinju who had no symptoms or signs of streptococcal infections. Results : The mean (±SD) ASO concentrations were 71 (±107) IU/mL, 285 (±246)IU/mL, and the UNL value of ASO concentratios were 131IU/mL, 433IU/mL, and 136 IU/mL in each group of preschool children, elementary school children, and adults, respectively. Conclusion : The distributio and ULN value of ASO concentrations varied according to age group. The ULN value of ASO concentrations should be set differently according to the patient's age. Group A streptococcal infections might be quite common in elementary school children, while very rare in preschool children or adults.

Long-Term Effects of ACE Inhibitors in Post-Tuberculosis Emphysema

Kim, Myung-A,Lee, Chang-Hoon,Kim, Deog-Kyeom,Chung, Hee-Soon The Korean Academy of Tuberculosis and Respiratory 2010 Tuberculosis and Respiratory Diseases Vol.69 No.6

Background: Little is known about the long-term effects of angiotensin-converting enzyme (ACE) treatment on post-tuberculosis emphysema. This study evaluated the effects of ACE inhibition on cardiac function and gas exchange in patients with post-tuberculosis emphysema. Methods: At baseline and at 6 months after initiation of ACE inhibition therapy, patients underwent pulmonary function testing, arterial blood gas analysis, and echocardiography, both at rest and post exercise. Cardiac output (CO) and right ventricular ejection fraction (RVEF) were measured at those time points as well. Results: After ACE inhibition; resting and post-exercise RVEF ($Mean{\pm}SEM,\;61.5{\pm}1.0,\;67.6{\pm}1.2%$, respectively) were higher than at baseline ($56.9{\pm}1.2,\;53.5{\pm}1.7%$). Resting and post-exercise CO ($6.37{\pm}0.24,\;8.27{\pm}0.34L/min$) were higher than at baseline ($5.42{\pm}0.22,\;6.72{\pm}0.24L/min$). Resting and post-exercise $PaO_2$ ($83.8{\pm}1.6,\;74.0{\pm}1.2mmHg$, respectively) were also higher than at baseline ($74.2{\pm}1.9,\;66.6{\pm}1.6mmHg$). Post-exercise $PaCO_2$($46.3{\pm}1.1mmHg$) was higher than at baseline ($44.9{\pm}1.1;\; Resting\;42.8{\pm}0.8\;vs.\;42.4{\pm}0.9mmHg$). Resting and post-exercise A-a $O_2$ gradient ($12.4{\pm}1.4,\;17.8{\pm}1.5 mmHg$) were lower than at baseline ($22.5{\pm}1.5,\;26.9{\pm}1.6mmHg$). Conclusion: In post-tuberculosis emphysema, RVEF and CO were augmented with a resultant increase in peripheral oxygen delivery after ACE inhibition. These findings suggest that an ACE inhibitor may have the potential to alleviate co-morbid cardiac conditions and benefit the patients with post-tuberculosis emphysema.

Functional Characterization of Pharmcogenetic Variants of Human Cytochrome P450 2C9 in Korean Populations

( Myung-a Cho ),( Jihoon G Yoon ),( Vitchan Kim ),( Harim Kim ),( Rowoon Lee ),( Min Goo Lee ),( Donghak Kim ) 한국응용약물학회 2019 Biomolecules & Therapeutics(구 응용약물학회지) Vol.27 No.6

Human cytochrome P450 2C9 is a highly polymorphic enzyme that is required for drug and xenobiotic metabolism. Here, we studied eleven P450 2C9 genetic variants―including three novel variants F69S, L310V, and Q324X―that were clinically identified in Korean patients. P450 2C9 variant enzymes were expressed in Escherichia coli and their bicistronic membrane fractions were prepared The CO-binding spectra were obtained for nine enzyme variants, indicating P450 holoenzymes, but not for the M02 (L90P) variant. The M11 (Q324X) variant could not be expressed due to an early nonsense mutation. LC-MS/MS analysis was performed to measure the catalytic activities of the P450 2C9 variants, using diclofenac as a substrate. Steady-state kinetic analysis revealed that the catalytic efficiency of all nine P450 2C9 variants was lower than that of the wild type P450 2C9 enzyme. The M05 (R150L) and M06 (P279T) variants showed high k_cat values; however, their K_m values were also high. As the M01 (F69S), M03 (R124Q), M04 (R125H), M08 (I359L), M09 (I359T), and M10 (A477T) variants exhibited higher K_m and lower k_cat values than that of the wild type enzyme, their catalytic efficiency decreased by approximately 50-fold compared to the wild type enzyme. Furthermore, the novel variant M07 (L310V) showed lower k_cat and K_m values than the wild type enzyme, which resulted in its decreased (80%) catalytic efficiency. The X-ray crystal structure of P450 2C9 revealed the presence of mutations in the residues surrounding the substrate-binding cavity. Functional characterization of these genetic variants can help understand the pharmacogenetic outcomes.