보행성 24 시간 식도 pH 및 내압검사를 이용한 만성기침 환자에서의 위식도역류에 관한 연구

지영구(Young Koo Jee),김윤섭(Yoon Seob Kim),임창영(Chang Young Lim),이계영(Kye Young Lee),김건열(Kun Yeol Kim) 대한내과학회 1997 대한내과학회지 Vol.53 No.5

N/A ficant GER among whom seven were confirmed to have true reflux related cough (cough induced by GER; 30.8±6.4%). Although the remained two have not only GER but cough, cough episodes were not directly related with GER events (cough induced by GER; 0%). Six among seven patients with reflux related cough showed good therapeutic response to anti-reflux medications but the other two patients with reflux not related cough did not. Conclusion: It is suggested that combined ambulatory 24hour esophageal pH and motility monitoring can provide an objective and good measurement for the discrimination of true reflux related cough episodes.

심포지움 : 점박이응애 알레르기: 유병현황 및 임상적 특성

지영구 ( Young Koo Jee ) 대한내과학회 1999 대한내과학회 추계학술대회 Vol.57 No.-

본태성 고혈압 및 동맥경화성 질환에서의 Prostacyclin 과 Thromboxane A₂ 혈장농도에 대한 고찰

지영구(Young Koo Jee),한형수(Hyung Soo Han),정문성(Moon Sung Jung),이봉휘(Bong Hwi Lee),김관우(Kwan Woo Kim),문언수(Un Soo Moon),한창순(Chang Soon Han),이홍순(Hong Soon Lee),이학중(Hak Joong Lee) 대한내과학회 1990 대한내과학회지 Vol.39 No.4

N/A The concentrations of the metabolites of prostacyclin and thromboxane A₂ (6-keto-PGF1α and 11-dehydro-TxB2) were measured in essential hypertension and artherosclerotic disease, and the concentrations of metabolites were compared after administration of 100 mg/日, 300 mg/日 and 900 mg/ 日of aspirin. The findings were as follows: 1) The concentrations of 6-keto-PGF1α and 11-dehydro-TxB₂ were significantly higher in the essential hypertension group and artherosclerotic disease group than in the control group (p<0.001). 2) The concentrations of 6-keto-PGF1α and 11-dehydro-TxB₂ were higher in the high cholesterol group (p<0.01, p<0.05, respectively). 3) With aspirin administration, the concenatrations of 6-keto-PGF1α and 11-dehydro-TxB₂ were significantly reduced (about 70% was reduced seven days after administration of aspirin). 4) There were no significant differences in reducing the concentrations of 6-keto-PGF1α and 11-dehydro-TxB₂ between three groups of different dosages of aspirin, 100 mg/日, 300 mg/日, and 900 mg/日 of aspirin. These findings suggest that thromboxane A₂ may contribute to the development or progression of hypertension and artherosclerotic disease. 100 mg/ 日 of aspirin may be used as effective as 300 mg/日 or 900 mg/日 of aspirin in preventing thrombotic events.

천안지역 알레르기 클리닉을 내원한 환자들에서 점박이응애 감작률

지영구(Young Koo Jee),최은경(Eun Kyung Choi),황영준(Young Joon Whang),김윤섭(Yun Seob Kim),박재석(Jae Suk Park),이계영(Kye Young Lee),김건열(Kun Yeol Kim) 대한천식알레르기학회 2000 천식 및 알레르기 Vol.20 No.2

N/A Background: Tetranychus urticae (two spotted spider mite, TSM) is considered to be an important outdoor allergen, especially among farmers as an occupational allergen. TSM may be an important allergen in Cheonan area because this area is surrounded by many pear orchards where TSM is commonly found. Objectives : To determine the sensitization rate to TSM in Cheonan area Material and methods : Rates of sensitization to common inhalant allergens were analyzed in the 456 patients who visited the allergy clinic in Dankook University Hospital, and skin prick tests were done with 55 common inhalent allergens and TSM extract, Results : The sensitization rate to Dermatophagoides farinae (37.7%) was highest followed by TSM (29.6%) and 25 (5.5%) patients were sensitized to TSM only. Sensitization rate to TSM was the highest in the third and fourth decades. Up to 50% of asthmatics aggravated during the summer season were sensitized to TSM. Conclusion TSM was the second most common sensitized allergen in patients visiting the allergy clinic in Cheonan area. These results suggest that TSM must be an important outdoor allergen in rural areas.

만성 기침으로 내원한 환자에서 원인 질환 및 빈도에 관한 전향적 연구

지영구,오형태,이계영,김건열,조상헌,민경업,김유영 (Young Koo Jee,Hyung Tae Oh,Kye Young Lee,Keun Yeol Kim,Sang Heon Cho,Kyung Up Min,You Young Kim) 대한천식알레르기학회 1998 천식 및 알레르기 Vol.18 No.2

Background: Chronic cough is commonly defined as a persistent or recurrent cough exceeding 3 weeks duration and the prevalence of chronic cough is reported to range from 14-23% among non-smoking adults. Irwin et al previously reported that common causes of chronic cough are postnasal drip syndrome asthma, and gastroesophageal reflux using the anatomic and diagnostic protocol. Objective: To determine the spectrum and frequency of chronic cough and to aid establishing algorithmic approach for chronic cough. Materials and metkod: We prospectively evaluated 105 consecutive and unselected immunocompetent patients complaining of chronic cough utilizing modified anatomic and diagnostic protocol proposed by Irwin et al. Initial diagnosis was made by history, physical examination and laboratory test including spirometry, methacholine provocation test, and 24 hour pH monitoring. Specific treatment was done based upon initial diagnosis and cough score was compared before and after treatment. Reassessment was done in case of treatment failure. Resalt: The causes of cough were determined in 100 of 105 patients(95% ). Cough was due to one condition in 94.8% and two in 15.2%. 121 causes of cough were identified and their spectrum and frequency were found to be postnasal drip syndrome (39.3% ), asthma (32.2% ), gasteroesophageal reflux (14.1%), chronic bronchitis (5.0%), others (4.1%: drug-induced, bronchiolitis, endobronchial tuberculosis, and lung cancer). History about nasal symptoms was useful, but history about gastroesophageal reflux were not useful for the diagnosis. Conclusion: The results suggest that anatomic and diagnostic approach for evaluating chronic cough is also useful in Korea and the most common causes of chronic cough are postnasal drip syndrome, asthma and gastroesophageal reflux.

폐상피세포에서 Triptolide에 의한 NF-${\kappa}B$ 의존성 IL-8 유전자 전사활성 억제기전

지영구,김윤섭,윤세영,김용호,최은경,박재석,김건열,채기남,곽상준,이계영,Jee, Young-Koo,Kim, Yoon-Seup,Yun, Se-Young,Kim, Yong-Ho,Choi, Eun-Kyoung,Park, Jae-Seuk,Kim, Keu-Youl,Chea, Gi-Nam,Kwak, Sahng-June,Lee, Kye-Young 대한결핵및호흡기학회 2001 Tuberculosis and Respiratory Diseases Vol.50 No.1

연구배경 : 폐상피세포가 능동적으로 IL-8을 분비한다는 것은 주지의 사실이다. NF-${\kappa}B$는 IL-8 발현 조절에 있어서 가장 중요한 역할을 담당하는 전사인자이다. Triptolide는 최근 밝혀진 NF-${\kappa}B$ 억제제로서 중국한약제인 뇌공등 (Tripterygium Wilfordii)에서 추출된약제이다. 연자들은 새로운 NF-${\kappa}B$ 억제제인 triptolide가 폐상피세포에서 NF-${\kappa}B$ 의존성 IL-8 유전자의triptolide가 염증성 폐질환에서 새로운 치료제로서의 가능성을 확인하기 위하여 본 연구를 시행하였다. 방법 : 폐상피세포로서 A549 사용하였고 triptolide는 미국의 Pharamagenesis(Palo Alto, CA)사로부터 제공받았다. NF-${\kappa}B$ 활성유도물질로는 IL-$1{\beta}$(R&D)와 PMA(Sigma)를 이용하였다. IL-8 유전자의 발현은 RT-PCR과 ELISA를 이용하여 측정 하였다. NF-${\kappa}B$의존성 IL-8 유전자의 전사활성을 평가하기 위하여는 IL-8 NF-${\kappa}B$ luciferase construct를 안정적으로 유전자주입한 A549 IL-8 NF-${\kappa}B$ luciferase 세포주를 제조해 사용하였고 NF-${\kappa}B$ DNA 결합은 electromobility shift assay(EMSA)를 이용하였다. p65 전사활성을 assay하기 위해서는 Gal4-p65 fusion protein expression system을 유전자주입과 luciferase assay를 통하여 시행하였다. Transcriptional coactivator의 역할을 규명 하가 위하여서는 CBP(CREB-binding protein)와 SRC-1(steroid receptor coactivator-1) 발현 벡터를 유전자 주입하고 luciferase assay를 이용하여 확인하였다. 결과 : Luciferase assay로 triptolide가 PMA와 IL-$1{\beta}$자극에 의한 IL-8 NF-${\kappa}B$ 활성을 의미있게 감소시킴을 확인하였다. IL-8 ELISA와 RT-PCR로 triptolide가 PMA와 IL-$1{\beta}$ 자극에 의해 유도되는 IL-8 발현을 각각 단백질과 mRNA 수준에서 억제함을 관찰하였다. Triptolide가 PMA와 IL-$1{\beta}$에 의한 IL-8 NF-${\kappa}B$의 전사활성을 억제시킨 반면 EMSA와 $I{\kappa}B{\alpha}$ Western blot을 이용한 실험에서는 triptolide가 NF-${\kappa}B$ DNA 결합과 $I{\kappa}B{\alpha}$의 분해에 전혀 영향을 미치지 못함을 확인하였다. 이러한 전사활성 억제와 DNA 결합 간의 불일치의 원인으로서는 DNA 결합 이후에 발생하는 핵내 에서의 transactivation에 triptolide가 영향을 미치리라고 생각되어 p65 transactivation study를 Gal4-p65T A(p65의 transactivation domain) fusion protein 발현 시스템과 luciferase assay를 이용하여 시행한 결과 triptolide가 p65 transactivation을 억제함으로써 NF-${\kappa}B$를 억제함을 확인하였다. 그러나 CBP나 SRC-1과 같은 coactivator의 역할을 규명하기 위한 유전자주입 실험에서 triptolide에 의한 p65 transactivation 억제에 대해 CBP나 SRC-1의 과발현이 별다른 영향을 미치지 못하였다. 결론 : Triptolide는 폐상피세포에서 NF-${\kappa}B$ 의존성 IL-8 유전자의 전사활성을 억제하고 그 기전은 $I{\kappa}B{\alpha}$ 경로가 아닌 핵내에서의 p65 transactivation 억제에 의해 발생하며 이에는 CBP나 SRC-1과 같은 coactivator가 관여하지 않음을 확인하였다. Background : NF-${\kappa}B$ is the most important transcriptional factor in IL-8 gene expression. Triptolide is a new compound that recently has been shown to inhibit NF-${\kappa}B$ activation. The purpose of this study is to investigate how triptolide inhibits NF-${\kappa}B$-dependent IL-8 gene transcription in lung epithelial cells and to pilot the potential for the clinical application of triptolide in inflammatory lung diseases. Methods : A549 cells were used and triptolide was provided from Pharmagenesis Company (Palo Alto, CA). In order to examine NF-${\kappa}B$-dependent IL-8 transcriptional activity, we established stable A549 IL-8-NF-${\kappa}B$-luc. cells and performed luciferase assays. IL-8 gene expression was measured by RT-PCR and ELISA. A Western blot was done for the study of $I{\kappa}B{\alpha}$ degradation and an electromobility shift assay was done to analyze NF-${\kappa}B$ DNA binding. p65 specific transactivation was analyzed by a cotransfection study using a Gal4-p65 fusion protein expression system. To investigate the involvement of transcriptional coactivators, we perfomed a transfection study with CBP and SRC-1 expression vectors. Results : We observed that triptolide significantly suppresses NF-${\kappa}B$-dependent IL-8 transcriptional activity induced by IL-$1{\beta}$ and PMA. RT-PCR showed that triptolide represses both IL-$1{\beta}$ and PMA-induced IL-8 mRNA expression and ELISA confirmed this triptolide-mediated IL-8 suppression at the protein level. However, triptolide did not affect $I{\kappa}B{\alpha}$ degradation and NF-$_{\kappa}B$ DNA binding. In a p65-specific transactivation study, triptolide significantly suppressed Gal4-p65T Al and Gal4-p65T A2 activity suggesting that triptolide inhibits NF-${\kappa}B$ activation by inhibiting p65 transactivation. However, this triptolide-mediated inhibition of p65 transactivation was not rescued by the overexpression of CBP or SRC-1, thereby excluding the role of transcriptional coactivators. Conclusions : Triptolide is a new compound that inhibits NF-${\kappa}B$-dependent IL-8 transcriptional activation by inhibiting p65 transactivation, but not by an $I{\kappa}B{\alpha}$-dependent mechanism. This suggests that triptolide may have a therapeutic potential for inflammatory lung diseases.

증례 : 파라핀 오일 흡인 후 발생한 급성 지방성 폐렴 1예

홍구현 ( Koo Hyun Hong ),임상수 ( Sang Soo Lim ),신재민 ( Jae Min Shin ),김도형 ( Doh Hyung Kim ),김윤섭 ( Youn Seup Kim ),지영구 ( Young Koo Jee ),박재석 ( Jae Seuk Park ) 대한내과학회 2007 대한내과학회지 Vol.73 No.1S

결핵균을 탐석한 말초혈액단핵구 배양상층액에 의해 유도되는 폐상피세포주에서의 NF-${\kappa}B$ 의존성 IL-8 분비기전

박재석,지영구,최은경,김건열,이계영,Park, Jae-Seuk,Jee, Young-Koo,Choi, Eun-Kyong,Kim, Keun-Youl,Lee, Kye-Young 대한결핵및호흡기학회 2001 Tuberculosis and Respiratory Diseases Vol.51 No.4

연구배경 : IL-8은 강력한 화학주성인자로서 결핵감염 부위로 염증세포들을 동원함으로서 결핵균에 대한 숙주의 방어기전에 있어서 중요한 역할을 한다. IL-8의 유전자의 발현에 있어서 NF-${\kappa}B$가 중요한 역할을 한다. 저자들은 결핵 감염시 폐상피세포가 NF-${\kappa}B$ 의존성으로 IL-8을 분비하는지 알아보고자 하였다. 방 법 : 말초혈액단핵구에 결핵균을 감염시키고 24시간 배양 후 배양상층액(CoMTB)을 얻었다. 결핵균, CoMTB로 자극한 A549 세포주의 IL-8 분비 정도를 ELISA 방법으로 측정하였다. CoMTB로 자극한 A549 세포주의 IL-8 mRNA 의 발현 정도를 RT-PCR로, $I{\kappa}B{\alpha}$의 분해를 western blot 분석으로, NF-${\kappa}B$의 핵이동과 DNA 결합은 electrophoretic mobility shift assay(EMSA)를 이용하여, 그리고 NF-${\kappa}B$ 의존성 IL-8 유전자의 전사활성은 luciferase reporter gene assay를 이용하여 측정하였다. 결 과 : A549 세포주를 CoMTB로 24시간 자극하여 얻은 배양액의 IL-8 농도는 $46.8{\pm}4.8\;ng/ml$로 분비하여 결핵균으로 직접 자극하였을 때의 $6.8{\pm}2.9\;ng/ml$보다 높았다. CoMTB로 A549 세포주를 자극하였을 때 IL-8 mRNA의 발현이 증가하였고, $I{\kappa}B{\alpha}$의 분해가 일어났으며, NF-${\kappa}B$의 핵이동과 DNA 결합이 일어났으며, NF-${\kappa}B$ 의존성 IL-8 유전자의 전사활성이 증가하였다. 결 론 : 결핵병변에서 폐상피세포는 결핵균을 탐식한 단핵식 세포와의 상호작용에 의해 NF-${\kappa}B$ 의존성으로 IL-8을 분비한다. Background : IL-8 is a potent chemotactic cytokine that plays an important role in the host defense mechanism against M. tuberculosis by recruiting inflammatory cells to the site of the infection. Lung epithelial cells, as well as alveolar macrophages are known to produce IL-8 in response to M. tuberculosis. IL-8 gene expression is mainly regulated on the level of transcription by NF-${\kappa}B$. This study investigated whether or not A549 cells produce IL-8 in NF-${\kappa}B$ dependent mechanism in response to macrophages phagocytosing M. tuberculosis. Methods : Peripheral blood monocytes that were obtained from healthy donors were cultured for 24 h with M. tuberculosis and a conditioned medium(CoMTB) was obtained. As a negative control, the conditioned medium without M. tuberculosis (CoMCont) was used. A549 cells were stimulated with M. tuberculosis, CoMCont and CoMTB and the IL-8 concentration in the culture media was measured by ELISA. The CoMTB induced IL-8 mRNA expression in the A549 cells was evaluated using RT-PCR, and CoMTB induced $I{\kappa}B{\alpha}$ degradation was measured using western blot analysis. CoMTB induced nuclear translocation and DNA binding of NF-${\kappa}B$ was also examined using an electrophoretic mobility shift assay(EMSA), and the CoMTB induced NF-${\kappa}B$ dependent IL-8 transcriptional activity was measured using a luciferase reporter gene assay. Results : CoMTB induced IL-8 production by A549 cells($46.8{\pm}4.8\;ng/ml$) was higher than with direct stimulation with M. tuberculosis ($6.8{\pm}2.9\;ng/ml$). CoMTB induced IL-8 mRNA expression increased after 2 h of stimulation and was sustained for 24 h. $I{\kappa}B{\alpha}$ was degraded after 10 min of CoMTB stimulation and reappeared by 60 min. CoMTB stimulated the nuclear translocation and DNA binding of NF-${\kappa}B$. The CoMTB induced NF-${\kappa}B$ dependent IL-8 transcriptional activity($13.6{\pm}4.3$ times control) was higher than either CoMCont($2.0{\pm}0.6$ times control) or M. tuberculosis ($1.4{\pm}0.6$ times control). Conclusion : A conditioned medium of peripheral blood monocytes phagocytosing M. tuberculosis stimulates NF-${\kappa}B$ dependent IL-8 production by the lung epithelial cells.

졸피뎀 유발 섬망의 발생률 및 위험요인

김영민 ( Young Min Kim ),이소라 ( So Ra Lee ),정지연 ( Ji Yun Jung ),신경황 ( Kyoung Hwang Shin ),김도형 ( Doh Hyung Kim ),김지현 ( Jee Hyun Kim ),지영구 ( Young Koo Jee ) 대한내과학회 2013 대한내과학회지 Vol.84 No.6

Background/Aims: Zolpidem is a safe and effective drug for the treatment of insomnia. However, there are some reports of adverse effects, such as delirium, after administration of zolpidem. The aim of this study was to evaluate the incidence of and risk factors for zolpidem-induced delirium. Methods: This retrospective study enrolled 481 patients who were admitted to hospital and received zolpidem between January and May 2011. We analyzed the incidence and risk factors associated with zolpidem-induced delirium. Results: Zolpidem-induced delirium occurred in 19 of 481 (4.0%) patients. Zolpidem-induced delirium was significantly associated with old age (≥ 65 years; odds ratio [OR] = 4.35, 95% confidence interval [CI] = 1.52-12.44, p = 0.006) and co-administration of benzodiazepine (OR = 4.30, 95% CI = 1.52-12.12, p = 0.006). When males > 65 years-old took both benzodiazepine and zolpidem simultaneously, the incidence of delirium was notably elevated (OR = 6.04, 95% CI = 1.80-20.20, p = 0.003). Other factors, including dosage, did not influence the occurrence of delirium. Conclusions: Old age and co-administration of benzodiazepine were independent risk factors for zolpidem-induced delirium. Therefore, a detailed medical history should be taken before prescribing zolpidem to an older person, and zolpidem should be used cautiously, with careful monitoring, in these patients. (Korean J Med 2013;84:804-809)

만성기도폐쇄를 보이는 환자에서 환기성역치 측정

이계영 ( Kye Young Lee ),지영구 ( Young Koo Jee ),김건열 ( Keun Yeol Kim ) 대한결핵 및 호흡기학회 1997 Tuberculosis and Respiratory Diseases Vol.44 No.2