비만증 환자에서 한약제에 의한 체중 감소효과

Oh, Seung-Joon,Jeong, In-Kyung,Kim, Young-Seol,Choi, Young-Kil,Paeng, Jeong-Ryung,Bae, Jung-Hwan,Shin, Hyun-Dae 경희대학교 동서의학연구소 1999 INTERNATIONAL SYMPOSIUM ON EAST-WEST MEDICINE Vol.1999 No.1

Seung-Joon Oh, In-Kyung Jeong, Young-Seol Kim, Young-Kil Choi, Jeong-Ryung Paeng¹, Jung-Hwan Bae and Hyun-Dae Shin²Department of internal Medicine, College Medicine, Endocrine Research Institute¹. Department of Rehabilitation, College of Oriental Medicine², Seoul, korea. Bady Fat Reduction Effects of Red Ginseng Compound Preparation on the Patients with Obesity. Proceedings of International Symposium on East-West Medicine, Seoul. 244-254, 1999.-Obesity can be defined as a metabolic disease due to an increased state of fat tissues caused by an imbalance of calorie intake and use. Recently, in Korea by improvement and westernization of food intake, along with decrease in exercise activities, the prevalence of obesity has increased greatly. Our objectives were to study stability and effects of decrease in body fat by administering red ginseng compound preparation (known to have body fat decreasing effects in laboratory animals) to obesity patients on low calorie diets. Changes in weight and body fat were measured while carrying out calorie-restricted diets on patients for 4 weeks, then administering red ginseng compound preparation for another 4 weeks. The patients were 20 people whose BMI were 25kg/㎡ or over and whose percent body fat was also 30% or over when tested by bioelectrical conductivity. 1. Changes in weight were from 70.04kg(base line) to 67.43kg(after taking red ginseng compound preparation). 2. In similar sense, BMI decreased from 27.12kg/㎡(base line) to 26.56kg/㎡(after dieting), and further to 26.01kg/㎡ (after taking red ginseng compound preparation). The BMI seemed to decrease significantly compared to the baseline after the use of red ginseng compound. 3. Waist hip ratio was changed from 0.8858(base line) to 0.8728, but it was statistically insignificant. 4. The percent body fat was 35,16%(base line), 33.87%(after dieting), and 31.68%(after taking red ginseng compound preparation). 5. Complete blood cell count and blood chemisrty remained unaffected by the administration. 6. In concern to endocrinologic studies, T3 decreased from 118.7 to 98.2ng/dL, and T4 increased from 8.8 to 9.2㎕/ dL. Epinephrine showed a tendency to decreased from 0.27 to 0.25 ng/mL, and norepinephrine increased from 0.39 to 0.44ng/mL. 7. Leptin was not changed. 8. Some patients complained adverse effects; constipation(5 patients, may be due to diet therapy), fatigue (2 patients), pruritus(2 patients), flushing(s patients), dizziness(3 patients) and epigastric discomfort(2 patients). However their symptoms were mild, so medication did not stopped. In conclusion, loss of weight without significant side effects was observed during low calorie diet and red ginseng compound preparation administration. This is thought to be in relation to sympathetic nerve system rather than adrenal gland. Also, further long0term studies should be required, since the observed results were based on short-term changes in weight.

Temporal trends and in-hospital outcomes of primary percutaneous coronary intervention in nonagenarians with ST-segment elevation myocardial infarction

( Joon Young Kim ),( Myung Ho Jeong ),( Yong Woo Choi ),( Yong Keun Ahn ),( Shung Chull Chae ),( Seung Ho Hur ),( Taek Jong Hong ),( Young Jo Kim ),( In Whan Seong ),( In Ho Chae ),( Myeong Chan Cho ) 대한내과학회 2015 The Korean Journal of Internal Medicine Vol.30 No.6

Background/Aims: Data regarding the outcomes of primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) in nonagenarians are very limited. The aim of the present study was to evaluate the temporal trends and in-hospital outcomes of primary PCI in nonagenarian STEMI patients. Methods: We retrospectively reviewed data from the Korea Acute Myocardial Infarction Registry (KAMIR) from November 2005 to January 2008, and from the Korea Working Group on Myocardial Infarction (KorMI) from February 2008 to May 2010. Results: During this period, the proportion of nonagenarians among STEMI patients more than doubled (0.59% in KAMIR vs. 1.35% in KorMI), and the rate of use of primary PCI also increased (from 62.5% in KAMIR to 81.0% in KorMI). We identified 84 eligible study patients for which the overall in-hospital mortality rate was 21.4% (25.0% in KAMIR vs. 20.3% in KorMI, p = 0.919). Multivariate analysis identified two independent predictors of in-hospital mortality, namely a final Thrombolysis in Myocardial Infarction (TIMI) flow < 3 (odds ratio [OR], 13.7; 95% confidence interval [CI], 3.2 to 59.0; p < 0.001) and cardiogenic shock during hospitalization (OR, 6.7; 95% CI, 1.5 to 30.3; p = 0.013). Conclusions: The number of nonagenarian STEMI patients who have undergone primary PCI has increased. Although a final TIMI flow < 3 and cardiogenic shock are independent predictors of in-hospital mortality, primary PCI can be performed with a high success rate and an acceptable in-hospital mortality rate.

Rat의 복강내에 투여한 5-fluorouracil-polyglycolic acid 제형이 장기에 미치는 영향에 관한 연구

강대영,송규상,최정목,노승무,정경수,오정연,김진향,양준묵,최선웅,이진호,조준식,민병무,김용백,김창식,박근성,김승영,김학용,인현빈 충남대학교 의과대학 지역사회의학연구소 1998 충남의대잡지 Vol.25 No.1

For more effective intraperitoneal chemotherapy, the authers made 5-fluorouracil-polyglycolic acid composite disks(FU-PGA disks) with 5-fluorouracil and polyglycolic acid, a biodegradable polymer. We inserted the FU-PGA disk into the peritoneal cavites of Sprague-Dawley male rats, the control and three experimental groups; one FU-PGA disk insert group(300mg/kg), two FU-PGA disk insert group(600mg/kg), and three FU-PGA disk insert group(900mg/kg). The control group received a similar number of PGA disk inserts. A pharmacokinetic study was performed to measure the 5-fluorouracil concentration in the peritoneal fluid, blood, and tissues(liver, kidney and heart) at 24 hours, 72hours and 168 hours after insertion of the FU-PGA disk. Light and electron microscopic studies were done. The results were as follows: 1) The number of white blood cells and platelets decreased after FU-PGA insertion. The degree was proportional to the duration and amounts inserted. The change in the number of red blood cells varied slightly. 2) Light microscopically, slight changes were noted at 168 hours in the 3 disk insert group (900mg/kg). Mild fatty change and hepatocyte degeneration around the central veins of the liver were noted, with vacuolar degeneration in the proximal convoluted tubules of the kidney. 3) Electron microscopically,the liver showed focal increases of lipid droplets in the hepatocytes, and irregular nuclear membrane with focal nucleolar segregation of the fibrillar and granular elements. Also the double membranous structure of the hepatocytes and Kupffer cells was widened with bleb formation. The kidney showed wide separation of the nuclear double membrane in the proximal convoluted tubular cells and mesangial cells, with vacuolation and myelin figure formation in the mitochondria of the proximal convoluted tubular cells, at 72 hours and 168 hours in the 2 to 3 FU-PGA insert groups. The heart showed focal loss of cristae,vacuolation and myelin figure formation in the mitochondria of the 2 to 3 FU-PGA insert groups. In conclusion, despite the large amont of FU-PGA inserted, the histopathological changes in the liver, kidney and heart were slight, and consonant with the very low amount of 5-fluorouracil concentrations detected in the liver, kidney and heart. The above results suggest that the FU-PGA composite can serve as a new device for releasing drugs in a controlled manner and easily targeted to intraperitoneal organs. This device can improve the efficacy of intraperitoneal chemotherapy for gastric cancer.

Adult invasive pneumococcal disease in the Republic of Korea: Risk medical conditions and mortality stratified by age group

Kim, Jong Hun,Baik, Seung Hee,Chun, Byung Chul,Song, Joon Young,Bae, In-Gyu,Kim, Hyo Youl,Kim, Dong-Min,Choi, Young Hwa,Choi, Won Suk,Jo, Yu Mi,Kwon, Hyun Hee,Jeong, Hye Won,Kim, Yeon-Sook,Kim, Jeong Elsevier 2018 INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES Vol.74 No.-

<P><B>Abstract</B></P> <P><B>Objectives</B></P> <P>This study aimed to characterize the risk factors for mortality in adult patients with invasive pneumococcal disease (IPD) stratified by age groups, after implementation of the national immunization program of 23-valent polysaccharide vaccine (PPSV23) for those aged ≥65 years in the Republic of Korea (ROK).</P> <P><B>Methods</B></P> <P>Clinical data and pneumococcal isolates from adult patients with IPD (≥18 years of age) were collected prospectively from 20 hospitals through the nationwide surveillance program from March 2013 to October 2015.</P> <P><B>Results</B></P> <P>A total of 319 patients with IPD were enrolled. Median age was 69 years. Overall in-hospital mortality was 34.2%: 17.1% in those aged 18–49 years, 23.7% in those aged 50–64 years, 33.0% in those aged 65–74 years, and 51.0% in those aged ≥75 years (<I>p<</I> 0.001). In particular, early death within 7days of hospitalization accounted for 60.6% (66/109). While old age (≥65 years), higher Pitt bacteremia score (≥4), and bacteremic pneumonia were independently associated with IPD mortality in all age groups, an additional mortality risk factor of immunocompromised status was identified for patients aged 50–64 years. PPSV23 serotypes accounted for 64.4% (122/189) of the pneumococcal isolates serotyped.</P> <P><B>Conclusions</B></P> <P>This study suggests that vaccine-type IPD continues to place a substantial burden on older adults in the ROK, necessitating an effective vaccination strategy for those at higher risk.</P> <P><B>Highlights</B></P> <P> <UL> <LI> National immunization of the elderly with the 23-valent polysaccharide vaccine (PPSV23) was implemented in Korea in 2013. </LI> <LI> Overall in-hospital mortality was 34.2% for adult invasive pneumococcal disease (IPD) and 51.0% for patients ≥75 years of age. </LI> <LI> Mortality risks were older age, higher bacteremia score, and immunocompromised status. </LI> <LI> An effective vaccination strategy for those at higher risk of IPD is needed. </LI> </UL> </P>

사람 성상세포종 세포주에서 사이토카인에 의한 Fas 및 FasL mRNA의 발현 조절

김옥준,임정희,최철희,최인홍,이병인,최일생 대한신경과학회 1999 대한신경과학회지 Vol.17 No.1

한국인 당뇨병 및 비당뇨병 환자에서의 뇌혈관 질환 유무에 따른 PAI-1 촉진자 유전자형과 인슐린저항성에 관한 연구

오승준,김영설,박철영,김덕윤,김성운,양인명,김진우,최영길,팽정령,정경천 대한비만학회 2000 The Korean journal of obesity Vol.9 No.2

연구배경 : 혈전현상을 특징으로 하는 질환에서는 Plasminogen activator inhibitor-1 (PAI-1) 이 높은 활성도를 보이는데, PAI-1 치는 당뇨병, 심근경색증, 비만 등에서 높다고 밝혀진 바 있다. 또한 당뇨병 환자들의 합병증의 주요한 병인은 죽상경화증으로 혈전현상이 특징인 질환에서 증가하는 PAI-1이 당뇨병 환자에서 높다. 목적 : 정상인에서의 PAI-1 유전자 촉진자의 유전자형의 분포 및 혈액농도를 관찰하고, 당뇨병 및 뇌혈관 질환 환자군에서의 PAI-1 유전자 촉진자 유전자형의 분포 및 혈액농도를 측정하여 정상인과 차이점을 알아본다. 당뇨병 환자군에서의 혈장 PAI-1 치와 인슐린 저항성, 전구 인슐린 등과의 상관관계를 살펴보고, 인슐린저항성과 대혈관질환의 지표로 사용될 수 있는지 알아보았다. 방법 : 대상으로는 정상인 76명, 제2형 당뇨병 환자 56명, 뇌혈관질환이 동반된 제2형 당뇨병 환자 48명, 뇌혈관질환 환자 51명을 선택하여, 환자의 혈액에서 인슐린, 공복시 혈당, 전구인슐린, 중성지방, 총콜레스테롤 및 기타 생화학 검사 및 이학적 검사를 시행하였다. 환자의 DNA를 채취하여 전사개시 -675bp를 포함하는 대립형질 특이 시발체를 사용하여 중합효소 연쇄 반응을 실시하여, 그 유전자형을 판독하였다. 결과 : 정상 대조군 76명 (46.4±11.1세), 2형 당뇨병 환자 56명 (58.3±12.6세), 뇌경색증 환자 51명 (63.1±13.2세) 대상으로 하였다. PAI-1 촉진자 유전자형의 (4G/4G, 4G/5G, 5G/5G)빈도는 정상 대조군이 각각 23.7%, 75.0%, 1.3%, 뇌경색 환자군이 19.6%, 66.7%, 13.7%, 뇌경색이 동반된 당뇨병 환자군이 33.3%, 58.3%, 8.3% 였다. (X2=12.6, p=0.05). 이러한 사실은 서구인에 비해 4G/4G, 5G/5G 동형 유전자형이 낮은 결과였다. 각 군별 혈장 PAI-1 농도는 정상 대조군 13.4, 1.8 ~ 65.2 ng/mL (중앙값 , 범위 ) 2형 당뇨병 환자군 14.4, 2.9 ~ 47.8 ng/mL, 뇌경색 환자군 21.9, 6.2 ~ 154.7 ng/mL , 뇌경색이 동반된 2형 당뇨병 환자군 28.8, 3.2 ~ 139.3 ng/mL 로 차이를 보였다 (p=0.000). 전체 대상에서 PAI-1 촉진자 부위의 유전자형에 따른 PAI-1 활성도와 항원 농도는 차이를 보이지 않았다. 그러나 PAI-1 활성도는 혈중 중성지방, 전구인슐린, 체질량지수와 독립적인 상관관계를 보였다 (p=0.000, p=0.000 and p=0.005). 결론 : 결론적으로 PAI-1 촉진자 부위의 유전자형은 뇌경색증의 지표는 아니며, PAI-1 활성도를 결정짓는 인자는 유전적 요인보다는 혈중 중성지방, 전구 인슐린, 체질량지수와 같은 대사적 요인으로 생각된다. Plasminogen activator inhibitor-1 (PAI-1) is known be related to insulin resistance and several components of the large vascular disease. Notably, the high frequencies of diseases such as coronary heart disease or stroke are related to type 2 diabetes complications. We studied to find out whether the PAI-1 promother genotype could be a marker for cerebral infarction in type 2 patients. Subject patients were; 56 type 2 diabetics (age 58.3±12.6), 51 patients with cerebral infarction (age 63.1±13.2), 48 type 2 diabetics with cerebral infarction (age 64.8±9.3) , and 76 healthy control (age 46.4±11.1). The 4G/5G genotype of PAI-1 promoter was evaluated by polymerase chain reaction and endonuclease digestion. PAI-1 promoter genotype frequency (4G/4G, 4G/5G, 5G/5G) was 23.7%, 75.0% and 1.3% in healthy control, 17.9%, 67.9% and 14.3% in type 2 diabetes patients, 19.6%, 66.7% and 13.7% in cerebral infarction patients, 33.3%, 58.3% and 8.3% in type 2 diabetics with cerebral infarction (X^2=12.6, p=0.05). This finding is lower in frequency of 5G/5G homozygote than that reported in Caucasians. The plasma PAI-1 concentrations according to the disease were 13.4, 1.8 ~ 65.2 ng/mL (median, range) for healthy control, 14.4, 2.9 ~ 47.8 ng/mL for type 2 diabetes, 21.9 6.2 ~ 154.7 ng/mL for cerebral infarction , and 28.8, 3.2 ~ 139.3 ng/mL, for cerebral infarction with type 2 diabetes (p=0.000). In the all subjects, PAI-1 concentration and activity of PAI-1 promoter genotype did not show any significant difference. However, the PAI-1 activity was independently associated with serum triglyceride level, plasma proinsulin and BMI (p=0.000, p=0.000 and p=0.005 respectively). We concluded that PAI-1 genotype is not a marker for the cerebral infarction ; however, the genotype is related to PAI-1 concentration , and therefore it seems to be that metabolic factors such as triglyceride level or plasma proinsulin or BMI are more in relations with determining the PAI-1 concentration than the genotype.

토끼에서 enrofloxacin과 enrofloxacin acetate의 比較藥物動態學

윤효인,박승춘,김창식,김민규,최기섭,신광순,박종일,조준형,조명행 충남대학교 수의과대학 동물의과학연구소 1996 動物醫科學硏究誌 Vol.4 No.-

This study was designed to examine the in vitro antibacterial activities and pharmacokinetics of enrofloxacin acetate (ENFXA) and enrofloxacin (ENFX). Two enrofloxacins had wide spectrum antibacterial activities against Gram positive and negative bacteria, and mycoplasma, showing potent antibacterial activities with low MICs (0.05-3.33 ㎍/㎖ for Gram positives, 0.002 ㎍/㎖ for Gram negatives and 0.02 ㎍/㎖ for mycoplasma). In order to investigate the profiles of two formulations of enrofloxacin we studied comparative pharmacokinetics of them in rabbits. Five rabbits were given 5 ㎎/㎏ body weight of each enrofloxacin formulation intravenously (i.v.) and orally (p.o.) in a cross-over study. Pharmacokinetic parameters of both formulations were calculated by the use of PCNONLIN, a computer program. Their bioavailibility in rabbits, the means of the area under the curve (AUC). After oral administration of each formulation in rabbits, the mean elimination half-lives (t_1/2,ke) were 3.25h (ENFX) and 4.32 h (ENFXA), and mean AUC 4.27 ㎍·h/㎖ (ENFX) and 6.21 ㎍·h/㎖ (ENFXA). Both enrofloxacin formulations seemed to have good tissue distribution and penetration as indicated by large volume of distribution: 4.76 1/㎏ for ENFX and 7.23 1/㎏ for ENFXA. With the results obtained in this study, ENFXA could be used in place of ENFX in rabbits.

나환자에 있어서 혈청내 면역복합체,백혈구 이동 억제인자 및 HLA-DR항원에 관한 연구

박주영,최인홍,김세종,유준,김주덕 大韓癩學會 1984 癩學 會誌 Vol.17 No.1

Poster Session : PS 1510 ; Rheumatology : Postoperative Infection Rates after Surgery with Prosthesis in Patients with Ankylosing Spondylitis Treated by TNF Alpha Blockade Compared to Conventional NSAIDs

( Ki Pyo Kim ),( Joon Young Hur ),( Ji Young Choi ),( Ran Song ),( Sang Wan Chung ),( Yeon Ah Lee ),( Seung Jae Hong ),( Hyung In Yang ),( Sang Hoon Lee ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: Some patients with severely advanced ankylosing spondylitis (AS) need to replace or correct destructed joints by surgical treatment. Among these patients, some patients who don’trespond sufficiently to conventional NSAIDs have to be treated by anti-TNF alpha blockades. We reviewed these patients to assess postoperative infection rate after surgery with prosthesis. Methods: We retrospectively reviewed the medical records of the patients with AS who experienced the surgery with prosthesis in Kyung Hee university hospital at Gangdong in Seoul, South Korea from Mar 2006 to May 2014. Results: Total 307 patients underwent the surgeries such as total hip replacement (THR) or corrective osteotomy of spine. Among them, 25 patients have been treated by TNF alpha blockades after surgery. 9 patients had been treated by TNF alpha blockade before the surgery. Total follow-up period was 4.3±2.3 years per person. Their average ages for surgeries are 35.6± 10.7 years. Among them, 13 patients had THR and the others had corrective osteotomy in spine. 11 patients have been treated by adalimumab, 9 patients have been treated by etanercept and 5 patients have been treated by in. iximab. There was no wound complication associated with infection after the surgery during follow-up period in the group of patients treated by TNF alpha blockade. But in the group of patients who had been treated by conventional NSAIDs, one patient had wound infection after spine surgery. His age was 62 and he had uncontrolled DM. Conclusions: There is no increased risk of infection after the surgeries using prosthesis in patients with AS treated by TNF alpha blockade compared to the patients treated by conventional NSAIDs.

제1형 탈요오드효소 유전자 갑상선호르몬 반응요소에서 T₃자극에 따른 갑상선호르몬 수용체 역동학 모델

이성진,박철영,정인경,홍은경,최철수,김현규,김두만,유재명,임성희,최문기,유형준,박성우,Larsen, P. Reed 대한내분비학회 2003 Endocrinology and metabolism Vol.18 No.3

연구배경: 제1형 탈요오드효소의 발현에 관여하는 hdiol 유전자는 5 flanking region 내 서로 다른 특성을 가진 두 종류의 갑상선호르몬 반응요소, 즉 TREI과 TRE2를 가지고 있음이 알려져 있다. 사람의 간암세포주인 HepG2 세포에서 T₃를 투여하였을 때 hdiol유전자의 전사작용이 급격하게 증가하는데 hdiol mRNA가 충분히 발현하기 위해서는 두 종류의 갑상선호르몬 반응요소가 모두 필요함이 보고 되어 있으나 T₃ 투여시 갑상선호르몬 반응요소와 결합하는 갑상선호르몬 수용체의 역동학에 대해서는 아직까지 연구된바 없다. 한편 현재까지 보고 된 연구 결과들은 갑상선호르몬 자극이 없더라도 갑상선호르몬 수용체와 갑상선호르몬 반응요소가 서로 지속적으로 상호작용 한다는 전제 조건을 바탕으로 하고 있는데 아직까지 이러한 가정은 간접적으로만 증명되어 있는 상태이다. 이에 저자들은 본 연구에서 사람의 간암세포주인 HepG2세포를 대상으로 염색체 면역침전법과 중합효소연쇄반응을 이용하여 갑상선호르몬 자극 전·후 hdiol 유전자의 갑상선호르몬 반응요소에 결합하는 갑상선호르몬 수용체의 결합양상 변화를 분석함과 동시에 갑상선호르몬 자극 전에도 갑상선호르몬 수용체와 갑상선호르몬 반응요소가 서로 결합된 상태로 존재함을 직접적으로 확인하고자 하였다. 방법: 사람의 간암세포주인 HepG2 세포를 대상으로 100 nM T₃를 투여하기 전과 투여한 후 12시간 뒤 TRα1, TR 1, TR 2 항체와 IREI, TRE2에 상보적인 시발체를 이용하여 염색체 면역침전법과 고식적 중합효소연쇄반응 및 정량적 중합효소연쇄반응을 시행하였다. 100nM T₃를 투여하기 전과 투여한 후 12시간 뒤 hdiol mRNA 발현량의 변화를 정량적으로 측정하기 위하여 역전사 중합효소연쇄반응을 시행하였다. 100 nM T₃를 투여하기 전과 투여한 후 12시간 뒤 TR4'1, TR 1, TR 2 단백질의 발현량을 알아보고자Western blot을 시행하였다. 결과: 100 nM T₃를 투여하기 전과 투여한 후 12시간 뒤 염색체 면역침전법과 TREI 시발체를 이용한 고식적 중합효소연쇄반응을 시행하였을 때 T₃ 투여 전후 TREI 부위에는 TRgl이 결합하였으며 T₃를 투여한 후 TRal 결합이 감소하였다. 정량적 중합효소연쇄반응으로 TR4'1 결합량을 측정하였을 때 T₃ 투여 전3.74에서 T₃ 투여 후 1.97로 감소하여 통계적으로 유의한 차이를 나타내었다(Δ=-47.3%, p<0.05). T₃ 투여 전 ·후 TRβl과 TRβ2의 결합은 관찰되지 않았다. 100 nM T₃를 투여하기 전과 투여한 후 12시간 뒤 염색체 면역침전법과 TRE2 시발체를 이용한 고식적 중합효소연쇄반응을 시god하였을 때 T₃ 투여 전ㆍ후 TRE2 부위에는 TRα1, TR 1, TR 2가 모두 결합하였으며 T₃를 투여한 후 TRα1과 TR 1의 결합은 감소하였으나 TR 2의 결합은 증가하였다. 정량적 중합효소연쇄반응으로 갑상선호르몬 수용체의 결합량을 측정하였을 때 TRαl은 T₃ 투여 전 10.41에서 T₃ 투여 후 3.01, TRβl은 T₃ 투여 전 12.56에서 T₃ 투여 후 2.93으로 유의하게 감소하였으며 TRβ2는 T₃ 투여 전 9.17에서 T₃ 투여 후 9.84로 증가하는 경향을 보였다(TRα1, Δ=-71.1%, p<0.05; TR 1, Δ=-76.7%, p<0.05; TR2, Δ=+7.3%). 정량적 중합효소연쇄반응으로 측정한 갑상선호르몬 수용체의 전체 결합량은 T₃ 투여 전 32.14에서 T₃ 투여 후 15.78로 감소하여 통계적으로 유의한 차이를 나타내었다(Δ=-50.9%, p.0.05). 갑상선호르몬 수용체 항체를 1.5μL와 4.5μL 첨가한 후TREI과 TRE2에 대하여 염색체 면역침전법 및 정량적 중합효소연쇄반응을 각각 시깡하였을 때 첨가한 갑상선호르몬 수용체 항체의 양에 따른 갑상선호르몬 수용체 결합량의 차이는 없었다. 100 nM T₃를 투여하기전과 투여란 후 12시간 뒤 역전사 중합효소연쇄반응 및 hdiol cDNA 시발체를 이용한 정량적 중합효소연쇄반응을 시행하였을 때 T₃를 투여한 후 hdiol mRNA발현량은 2.03배 증가하였다(p<0.001). 100 nM T₃를 투여하기 전과 투여한 후 12시간 뒤 Western blot을 시행하였을 때 갑상선호르몬 수용체 발현량은 유의한 차이가 없었다. 결론: 현재까지 갑상선호르몬 수용체의 역동학에 대한 연구가거의 이루어지지 않았던 실정을고려하여볼 때 본 연구는 제한적이나마 일정한 농도의 갑상선호르몬 자극 전 · 후 갑상선호르몬 수용체 결합양상의 변화, 특히 T₃ 자극 전 hdiol 유전자의 TREI 부위에서 TRal이 억제자 (silencer)로서 작용할 가능성 및 T₃자극 전 · 투 TRE2 부위에서 갑상선호르몬 수용체 교대현상을 처음으로 제시하였다는 점에서 의의가 있으며 향후 다른 종류의 세포주 및 체내에서 갑상선호르몬 자극 전 후 갑상선호르몬 수용체 결합양상의 변화 및 유전자 발현에 미치는 영향을 연구할 필요가 있으리라 생각된다. 한편 염색체 면역침전법을 통해 HepG2 세포에서 T₃ 자극이 없더라도 갑상선호르몬 수용체와 갑상선호르몬 반응요소 사이에 지속적인 상호작용이 존재할 뿐 아니라 갑상선호르몬 반응요소에 대한 갑상선호르몬 수용체의 결합이 교대로 이루어지고 있음을 직접적으로 확인할 수 있었으며 향후 T₃ 자극 전 · 후 갑상선호르몬 수용체를 통한 유전자 전사조절기전에 관여하는 전사인자와 역동학적 기전을 규명함에 있어서 염색체 면역침전법과 정량적 중합효소연쇄반응이 매우 유용하게 이용될 수 있을 것이다. Background: Type 1 iodothyronine deiodinase (Dl), the product of the hdiol gene, is involved in thyroid hormone activation by the deiodination of thyroxine (T4) to form 3,5,3'-triiodothyronine (T3). Recent studies have identified two thyroid hormone response elements (TREs) in the 5 ' flanking region of the hdiol gene. TRE1, proximal to TRE in the hdiol gene, consists of a direct repeat of thyroid hormone receptor (TR) binding octamers with 10 bp separating the two TR binding sites. The upstream TRE, TRE2, is a classical direct repeat of retinoid X receptor (RXR)/TR binding half-sites with a 4-bp separation. There are few studies clarifying the TR dynamics in the TRE of a specific gene with or without the exposure of activated thyroid hormone. We evaluated TR binding patterns in the proximal and distal TREs of the hdiol gene before and after T₃ stimulation. Methods: We employed chromatin immunoprecipitation (ChIP) technique to investigate the TR- TRE interaction before and after T₃ stimulation in human hepatocellular carcinoma HepG2 cell line. Following cross-linking and sonication of the cells, immunoprecipitation was performed overnight at 4℃ with TRαl, TRβ1 and TRβ2 antibodies. We analyzed the binding patterns and amounts of TRαl, TRβl and TRβ2 to TREl and TRE2 before and after 12 hours stimulation with 100 nM T3 by using conventional and quantitative real-time polymerase chain reactions (RQ-PCR). Reverse transcriptional PCR (RT-PCR) and Western blot with TR 1, TR 1 and TR 2 antibodies were performed to measure the levels of hdiol mRNA and TR 1, TR 1 and TR 2 proteins before and after 12 hours exposure to l00nM T3. Results: In TRE1, TRαl binding was significantly decreased after 12 hours stimulation with l00nM T3 (3.74→97, Δ=-47.3%, p<0.05), but TRβ1 and TRβ2 bindings were not detected by conventional PCR and RQ-PCR. Although all TR isoforms were bound to TRE2, the binding patterns were quite different. While TRα1 and TRβ1 bindings to TRE2 after 12 hours stimulation with 100 nM T3 were significantly decreased (10.41→3.01, Δ=-71.1%, p<0.05; 12.56 →2.93, Δ =-76.7%, p<0.05, respectively), TRβ2 binding was increased but not significantly (9.17 →9.84, Δ =+7.3%). Total TR bindings in TRE2 were significantly decreased after 12 hours stimulation with 1OOnM T₃ (32.14 →15.78, Δ=-50.9%, p<0.05). The TR bindings to TREl and TRE2 were not significantly different by the amounts of TR antibodies used during ChIP assays. The levels of hdiol mRNA were significantly increased, 2.03 times, after 12 hours exposure to l00nM T3 (p<O.001). Western blot showed no significant change of the level of each TR isoform protein before and after 12 hours exposure to 100nM T3. Conclusion: Our results demonstrate the dynamics of TRal at proximal TRE (TRE1) and the switching phenomenon of TR isoforms at distal TRE (TRE2) of the hdiol gene after T3 stimulation. Further investigation, however, is needed to clarify the mechanisms of these observations (J Kor SOC Endocrinol 18:283-295, 2003).