지속성 외래 복막투석 환자에서 복막염의 발병 양상 단일 임상 기관 연구

안규리(Cu Rie Ahn),한진석(Jin Suk Han),김성권(Suhng Gwon Kim),이정상(Jung Sang Lee),오윤규(Yoon Kyu Oh),김현리(Hyun Lee Kim),정우경(Woo Kyung Chung),오국환(Kwook Whan Oh),양재석(Jae Suk Yang),김세중(Se Jung Kim),이경이(Kyung Ey Lee) 대한신장학회 2001 Kidney Research and Clinical Practice Vol.20 No.4

Peritonitis remains the leading cause of the patient dropout in CAPD in many developing countries. In Korea, 71% of CAPD patients dropout is caused by peritonitis. To elucidate an adequate guideline for treating peritonitis in our country, we analyzed clinical and bacteriologic profiles of peritonitis(1995. l. 1- 1999. 12 31). Two hundred and twenty eight episodes of peritonitis were developed in 127/247 patients. The incidence of peritonitis was 0.41/patient-year in general, which was decreased to 0.24/patient-year in 1999. The incidence of causative organisms were as follows: 82(36.0%) by Gram positive organisms, 38 (16.2%) by gram negative organisms, 16 cases(7.0%) by mixed organsisms, and 5 cases(2.2%) by fungus. During study period, the incidence of peritonitis by gram positive organsism was decreased while the incidence of peritonitis by gram negative organism was not changed. Recurrent infection/relapse was noted in 58 patients(45%). Peritonitis were eradicated only in 66% of the cases by initial antibiotics(cefazolin+aminoglycoside); and another 17% responded by second line antibiotics. Peritoneal catheters were removed in 38 episodes(16.7%). Patients with exit infection were more frequent in removal of catheter. Risk factor analysis was performed in 146 patients, who were newly started CAPD. There were 60 initial episodes of peritonitis(mean duration of follow up was 16.7 patient months). Sixty-five percent were free of peritonitis at the end of first year, 54% at the end of second year and 45% at the end of third year (Kaplan-Meier). Factors such as age, sex, underlying DM, were not risk factor for CAPD peritonitis. In conclusion, we observed that the incidence of peritonitis decreased every year. It was revealed however that only 66% of peritonitis can be successfully treated by first line antibiotics. Second line antibiotics such as ceftazidime may need to be introduced in early phase of CAPD peritonitis. Up to one third of patients had recurrent infection/relapse, which raised the incidence of peritonitis. Continuing education as well as better exit care is needed to improve technical survival of CAPD patients in Korea.

상염색체 우성 다낭신에서의 신낭종 경화요법

김연수(Yon Su Kim),안규리(Cu Rie Ahn),한진석(Jin Suk Han),김성권(Shung Gwon Kim),이정상(Jung Sang Lee),이중건(Jung Geon Lee),윤성철(Sung Chul Yoon),박종훈(Jong Hoon Park),송은경(Eun Kyong Song),황대연(Dae Yeon Hwang),박정환(Jung Hwan 대한신장학회 2002 Kidney Research and Clinical Practice Vol.21 No.4

배 경 : 상염색체 우성 다낭신(ADPKD)은 성인에서 가장 흔한 유전성 신질환의 하나로서 낭종의 팽창으로 인한 복부 팽만이나 통증을 흔히 호소한다. 이의 치료를 위해 에탄올을 이용한 경화요법이나 복강경을 이용한 치료, 수술적 감압술 등이 사용되어지고 있다. 본 연구에서는 한국인 ADPKD 환자에서의 경화요법 후의 임상경과를 분석하고, 새로운 경화제인 n-butyl cyanoacrylate(NBCA)의 유용성을 검토하였다. 방 법: 저자들은 한국인 ADPKD 환자 24명을 대상으로 에탄올경화요법(n=9) 및 NBCALipiodol 혼합액을 이용한 경화요법(n=18)(3예는 두가지 치료법 병행 )을 시술하고 이들의 임상 경과를 추적 관찰하였다. 결 과: 대상 환자의 남녀비는 8 : 16이었고 치료 시 평균연령은 50±13세였다. 경화요법의 적응증으로는 동통이 14예, 복부 팽만이 7예였으며, 흡인된 낭종의 직경은 5 내지 16 ㎝으로 다양하였다. 동통이나 복부팽만은 2명을 제외한 전원에서 주관적인 개선을 보였다. 시술 전후의 평균동맥압은 시술 전 112±11.1, 시술 후 1개월 96±9.6, 시술 후 6개월에 98±9.7 ㎜Hg로 유의한 저하를 보였으나(p<0.05), 이러한 효과는 12개월째에 소실되었다. 혈중요소질소 농도는 기저치와 시술 후 6개월 측정치 사이에 유의한 차이가 없었다[24±12.1 대 22±14.6(㎎/dL)]. 출혈이나 감염과 같은 주요 합병증은 발생하지 않았으며, 시술과 관련된 사망례도 없었다. 에탄올과 NBCA 사용군 사이에 치료효과나 합병증에서 차이는 관찰되지 않았다. 결 론: ADPKD 환자에서의 신낭종 경화요법은 대부분에서 증상의 완화를 보였고, 일시적인 혈압강하 효과를 보였으며, NBCA는 신낭종 치료에 새롭게 사용된 경화제로서 단기관찰 결과 유용하고 안전한 것으로 생각된다. Background : Autosomal dominant polycystic kidney disease(ADPKD) is the most common hereditary renal disease in adults, and its major complaints include pain and abdominal fullness due to cyst expansion. So far, for the control of these symptoms, cyst ablation with ethanol or tetracycline, laparoscopic manipulations and surgical marsupialization have been used. Methods : We used conventional ethanol(n=9) or n-butyl cyanoacrylate(NBCA) plus lipiodol solution (n=18) or both(n=3) for separate cysts as the sclerosing agent in 24 adult Korean ADPKD patients. And their clinical courses after treatment were evaluated. Results : The male to female ratio was 8 : 16 and the mean age at the treatment was 50 yrs(S.D. 13.1). Causes for aspiration were pain in 14 and abdominal fullness in 7 patients and the range for the cyst diameters aspirated were 5-16 cm. Flank pain or discomfort were decreased subjectively in most cases except two. Mean arterial pressures(S.D.) (㎜Hg) before and after procedure were as follows 112(11.1)(basal), 96(9.6)(1 month) and 98(9.7)(6 month)(p<0.05, paired-t test). Blood urea nitrogen levels(㎎/dL) were not changed 6 month later[24 (12.1) vs. 22(14.6)]. There was no major complication such as bleeding or infection and no death and associated with procedure. There was no difference of therapeutic effect according to sclerosing agent. Conclusion : NBCA was as effective as conventional ethanol for sclerotherapy in ADPKD and cyst ablation therapy showed a BP-lowering effect in short-term period.

성인의 원발성 초점성 분절성 사구체 경화증 ( FSGS ) 의 예후 및 예후 인자

김연수(Yon Su Kim),안규리(Cu Rie Ahn),한진석(Jin Suk Han),김성권(Shung Gwon Kim),이정상(Jung Sang Lee),김성균(Seong Gyun Kim),김현리(Hyun Lee Kim),황영환(Young Hwan Hwang),이상구(Sang Goo Lee),이정은(Jung Eun Lee),오윤규(Yun Kyu Oh) 대한신장학회 2002 Kidney Research and Clinical Practice Vol.21 No.4

배 경: 성인에서 FSGS는 그 발생율이 증가하고 지속적인 스테로이드 치료로 예후가 향상됨이 제시되면서 질병에 대한 관심이 높아지고 있다. 그러나 우리나라 성인 FSGS의 임상상과 예후에 대한 보고는 많지 않다. 본 연구에서는 성인 FSGS의 임상상을 살펴보고 예후에 관계하는 임상 인자를 밝히고자 하였다. 방 법 : 1985년부터 1999년까지 서울대학교병원에서 조직검사로 확진된 성인 환자를 대상으로 연구를 진행하였고 이차적 원인이 있는 경우는 제외하였다. 조직검사 당시의 임상상을 분석하였고, 10주 이상 추적 관찰된 환자를 대상으로 신기능 악화여부를 후향적으로 분석하였다. 결 과: 대상 환자는 총 92명이였으며, 이 중 47명(51%)이 신증후군(NS) 범주에 속하였다. 남녀비는 1.7 : 1이였으며 조직검사시 신기능 저하가 51%에서 관찰되었고 고혈압은 45%에서 나타났다. NS군과 신증후군 이하의 단백뇨군(non-NS)간에 고혈압유무, 신기능 저하 등의 초기 임상상의 차이는 없었다. 이들 중, 10주 이상 추적 관찰된 환자는 88명이였고, 관찰 기간은 37.1개월(2.5-185)이였다. 관찰 기간동안 14명에서 신기능이 악화되었다. 신기능 악화군과 유지군간에 조직 진단시 임상상의 차이는 없었으며, 신기능 악화 여부에 대한 독립적 예후 인자는 단백 뇨량의 정도와 조직 검사시의 신기능, 스테로이드 치료 여부였다. 전체적으로 5년 신기능 유지율은 80%로 나타났다. NS군에서 스테로이드 치료를 한 환자는 77%(34/44명)이였으며 그 중 1명(3%)에서 신기능 악화소견을 보였다. NS군에서 스테로이드 치료를 하지 않은 10명 중 6명(60%)의 신기능이 악화되었다. 결 론 : 위의 결과에서 밝혀진 성인 FSGS 환자의 예후 인자에 대한 적극적인 조절이 필요하며 향후 스테로이드 치료법의 유용성을 확인하기 위한 전향적인 연구가 필요하다. N/A

위암환자에서 99mTc - MDP 스캔에 의한 골전이 평가

최창운,김상은,이동수,여정석,안규리,정준기,이명철,김노경,고창순 ( Chang Woon Choi,Sang Eun Kim,Dong Soo Lee,Jung Seok Lyeo,Cu Rie Ahn,Jung Key Chung,Myung Chul Lee,Noe Kyung Kim,Chang Soon Koh ) 대한핵의학회 1991 핵의학 분자영상 Vol.25 No.2

동종 및 이종 피부이식 거부반응에서의 cytokine mRNA 발현 및 면역세포 침윤 양상

김재영(Jae Young Kim),안규리(Cu Rie Ahn),김기원(Ki Won Kim),박준오(Joon Oh Park),김동희(Dong Hee Kim),이은미(Eun Mi Lee),오병희(Byung Hee Oh),이정상(Jung Sang Lee) 대한내과학회 2002 대한내과학회지 Vol.62 No.1

N/A Background: The immune response to xenogeneic organ transplants is stronger than that to allogeneic transplants and this extra strength results from the existence of preformed natural antibodies. However even in situation such as skin grafting, where antibody-mediated mechanisms are not thought to play a role, cell-mediated xenograft immunity is more potent than that to allograft. The mechanisms have not been well established yet. In the present study therefore we attempted to demonstrate the mechanism by the examination of the profiles of cytokine mRNA expression and immune cell infiltration in the Lewis rat-to-C57BL/6J mouse skin xenografts and the fully allogeneic BALB/c mouse-to-C57BL/6J mouse skin grafts. Methods: C57BL/6J mice were grafted with tail skins from Lewis rat and MHC class I/II different BALB/c mouse. The profiles of cytokine mRNA expression and infiltrated immune cells in both grafts harvested on days 3, 5, 7 and 9 after grafting were examined by quantitative RT-PCR and immunohistochemical analysis. Results: The mean survival time of xenogeneic skin grafts was 8.5±0.6 days, which was two days shorter than that of allogeneic skin grafts (10.3±0.5). The quantitative PCR analysis of intragraft cytokine expression revealed that the levels of IFN-γ, IL-6 and IL-1βin the xenografts were significantly up-regulated as compared to those in the allografts. The immunohistochemical analysis demonstrated that CD8+ T, CD11b+ and F4/80+ cells were more rapidly and severely infiltrated into the xenogeneic skin grafts as compared to those into the allogeneic grafts. Conclusion: Overall results indicate that the cell-mediated immune responses to allo- and xenogeneic skin grafts may be exerted by T lymphocytes, neutrophils, NK cells and macrophages in a complicated manner and rapid rejection of xenogeneic skin grafts may be due to more rapid and severe infiltration of CD8+ T, CD11b+ and F4/80+ cells as compared to that of allogeneic grafts. In addition up-regulated proinflammatory cytokines such as IFN-γ, IL-6 and IL-1βin xenografts may be involved in the development and proliferation of these cells. (Korean J Med 62:90-99, 2002)

복막투석 환자에서 항결핵제의 약물역동학

김기원(Ki Won Kim),안규리(Cu Rie Ahn),오국환(Kook Hwan Oh),이경이(Kyung Yi Lee),이중건(Jung Geon Lee),오명돈(Myung Don Oh),김연수(Yon Su Kim),한진석(Jin Suk Han),김성권(Suhng Gwon Kim),이정상(Jung Sang Lee),장인진(In Jin Jang),신상구(Sa 대한신장학회 2002 Kidney Research and Clinical Practice Vol.21 No.1

N/A Background : Tuberculosis is more prevalent in dialysis patients than in the general population, and more difficult to make a diagnosis, and often leads to death, Moreover, extra-caution is needed in prescribing anti-tuberculosis medications as dose modification is frequently needed in patients with renal insufficiency. Several pharmacokinetic studies have been performed for antimycobacterial regimens in patients with renal insufficiency, including under hemodialysis. However, the anti-mycobacterial regimens of patients on peritoneal dialysis have been made based on empirical methods because of few pharmacokinetic studies. Methods : To elucidate the pharmacokinetic profiles of anti-mycobacterial regimens for peritoneal dialysis, we measured both plasma and peritosol concentrations of anti- tuberculous drugs including isoniazide, rifampin and pyrazinamide in 9 patients maintained on chronic ambulatory peritoneal dialysis(CAPD). Results : After a conventional oral dose of anti-tuberculosis medication, their plasma concentrations were in the therapeutic range, but the peritosol concentration of rifampin was below the therapeutic range. Conclusion : No dose adjustments are required for isoniazid, rifampin and pyrazinamide for the treatment of systemic or peritoneal tuberculosis in CAPD patients. On the contrary, oral rifampin is not expected to be effective in the treatment of tuberculous peritonitis, because of its low peritosol concentration. (Korean J Nephrol 2002; 21(1):67-73)

말기 신부전으로 진행하는 한국인 상염색체우성 다낭신 환자의 임상적 특성

황영환(Young Hwan Hwang),안규리(Cu Rie Ahn),황대연(Dae Yeon Hwang),이은주(Eun Joo Lee),어현선(Hyun Seon Eo),채희진(Hee Jean Chae),이정은(Jung Eun Lee),김연수(Yon Su Kim),한진석(Jin Suk Han),김성권(Suhng Gwon Kim) 대한신장학회 2001 Kidney Research and Clinical Practice Vol.20 No.2

말기 신부전은 상염색체우성 다낭신 환자의 가장 중요한 합병증이다. 상염색체우성 다낭신에서 말기 신부전증의 위험인자로는 PKD1 가계, 남성, 안지오텐신 전환효소 유전자의 다형성 등의 유전인자와 함께 고혈압, 빠른 발병연령, 육안적 혈뇨, 단백뇨 등의 비유전인자가 알려져 있다. 그러나 동양인을 대상으로 한 연구는 거의 없는 실정이다. 방법 : 연구자들은 우리 나라 상염색체우성 다낭신 환자에서 말기 신부전증의 빈도, 신부전증의 진행속도 및 위험인자를 알아보기 위하여, 서울대학교병원 다낭신 클리닉에 등록된 다낭신 환자 148명 중 말기 신부전으로 진행한 32명 환자들의 임상적 특징을 파악하고, 이를 신기능이 50세 이후에도 정상으로 유지되는 군 14명과 비교하였다. 결과 : 말기 신부전 환자 32명의 남녀 14:18명이었고, 진단 당시 중앙연령은 43세(범위22-65세), 말기 신부전 도달연령은 52.5세(28-73세)이었으며 진단으로부터 신대체요법 시작까지의 기간은 6년(0-30년)이었다. 신기능 감소 속도를 알아보기 위해서 분석이 가능하였던 말기 신부전 환자 18명에서 혈청 크레아티닌의 역수를 취하여 시간에 따른 감소율을 보았을 때 고질소혈증이 시작된 후에는 진단 연령이나 성별에 관계없이 매년 -0.073dL/mg/year(-0.046- -0.114dL/mg/year)의 일정한 속도로 감소되어 8.2년(5.2-13년)에 말기 신부전에 도달하였다. 대상환자군에서 육안전 혈뇨, 하루 1g 이상의 단백뇨, 요석, 상부요로감염, 고혈압, 간 낭종의 빈도는 각각 69, 54, 16, 29, 85, 85%이었다. 한편 84%에서 가족력이 있었고 이들 중 10%는 말기 신부전의 가족력이 있었고, PKD1:PKD2의 비율은 8명 중 7:1이었다. 이를 대조군과 비교하였을 때, 육안적 혈뇨와 단백뇨의 빈도가 신기능유지군에 비해 말기신부전 군에서 유의하게 높았다(각각p=0.001,p=0.0008), 한편 연관분석을 실시한 유지군 2명 중 1명은 PKD1, 1명은 PKD2였다. 결론 : 마기 신부전 환자 34명에서 신기능은 어느 연령까지는 유지되다가 일단 고질소혈증이 발생하면 일정한 속도로 신기능의 감소가 진행하여 8.2년에 말기 신부전에 도달하였다. 말기 신부전증의 임상적 위험인자로 육안적 혈뇨와 단백뇨가 확인되었다. End stage renal disease(ESRD) is a well-known major complication of autosomal polycystic kidney disease(ADPKD). Several risk factors of renal progression in ADPKD were identified, such as PKD1 gene, male gender and earlier age of onset. In Korea, ADPKD is a cause of ESRD in 2Yo of hemodi- alysis patients. Until now, only a few detailed studies have been performed in regarding to evaluate the risk factor for ESRD especially in the Asian population. 148 ADPKD patients were registered to PKD clinic in our hospital(Mar. 1996-Dec. 1999). Among them, 34 patients(male : female 14: 20) who had started renal replacement therapy were studied to elucidate clinical characteristics including the nature of progression of renal failure. These data were compared with 14 patients(male : female 3: 11) who did not develop renal failure(serum creatinine ≤1.4 mg/dL) at the age of 50 years. Median age at the diagnosis of ADPKD was 43 years(range : 22-65 years), median age at initiation of renal replacement therapy(RRT) was 52.5 years(28-73) and median duration from the diagnosis to RRT were 6 years(0-30). The prevalence of gross hematuria, proteinuria (>1g/24h), urolithiasis, upper urinary tract infection, hypertension and liver cysts were 69, 54, 16, 29, 85 % and 85%, respectively. 84% of these patients had family members with ADPKD and 10% of them had ESRD family members. PKD1 vs. PKD2 was 7: 1 in 8 patients with ESRD and 1: 1 in 2 patients of control group. Gross hematuria and proteinuria were more prevalent in ESRD patients than the control group(p=0.001 and p=0.0008, respectively). In 18 patients with ESRD, rates of renal progression were traced using a reciprocal of serum creatinine(1/Cr) curve. Once azotemia(serum creatinine value ≥1.5 mg/dL) developed, the median rate of decline of 1/Cr was -0.073dL/mg/year(range : -0.046--0.114dL/mg/ year), which was constant irrespective of either the age of onset or sex. In summary, in 34 patients, the renal function seemed to be maintained to a certain age. But, once azotemia developed, the renal function was rapidly declining with similar rate, ended up ESRD in 8.2 years. Presence of gross hematuria and proteinuria were associated with poor prognosis.

IgA 신병증에서 신조직내 Cytokine 및 Chemokine 의 발현과 임상 및 병리학적 소견의 상관성

임춘수(Chun Soo Lim),정수환(Shou Huan Zheng),김연수(Yon Su Kim),안규리(Cu Rie Ahn),한진석(Jin Suk Han),김성권(Suhng Gwon Kim),이정상(Jung Sang Lee),이현순(Hyun Soon Lee),채동완(Dong Wan Chae) 대한신장학회 2001 Kidney Research and Clinical Practice Vol.20 No.4

IgA nephropathy is one of the most common forms of primary glomerulonephritis in adults, and the pathogenetic mechanisms seem to be diverse. Proinflammatory cytokines, Thl/Th2 cytokines, and chemokines would be involved in the pathogenetic pathways and would affect the functional and his- tologic consequences. To evaluate this hypothesis, we tried to quantify the magnitude of intrarenal gene expression of various cytokines(TNF- α, IL-1β, IL- 6, IL-15, IFN- r, IL-2, IL-10) and chemokines(IL-8, RANTES) in 61 renal core biopsy specimens con- firmed as IgA nephropathy by immunofluorescent microscopy. Semiquantitative reverse-transcriptase polymerase chain reactions(RT-PCR) using the internal competitors were done for the quantification of gene transcripts. And using the immunohistochemistry (IHC), we tried to determine the degree of expression and the location of various cytokines and chemokines in renal tissues in 29 patients among the above patients. The IFN- r /IL-10 ratio was higher in patients with renal dysfunction than that in patients with normal renal function(p=0.0483). Gene transcript levels of proinflammatory cytokines(TNF- α, IL-1 β ) were high in patients with significant proteinuria. In patients with severe glomerular sclerosis, the ratio of IFN- z /IL-10 gene transcripts was high(p=0.0363). IL-10 gene transcript level was related to the se- verity of tubulointerstitial damage. The levels of gene expression of TNF- α(p=0.0026), IL-10(p=0.0092) and IFN- r (p=0.0188) were related to the degree of mesangial matrix expansion, and the extent of intrarenal arteriolar lesions correlated with the expression of the IL-8 gene transcript(r=03828, p=0.0033). The cellular infiltration in glomeruli was related with chemokine(IL-8) gene expression, but the relation was not significant statistically. The degree of IgA deposition in glomeruli was related with the expression of IL-6 and IL-15. The expression of intrarenal gene transcripts of various cytokines and chemokines were closely interrelated. Thl or Th2 cytokine polarization was not present in IgA nephropathy. In IHC, TNF- α, IFN- r and IL-2 were immunostained dominantly in mesangial region, but not in tubulointerstitial region. In contrast, positive reactions for IL-10 were observed mainly in tubules. The significant reactions for IL-8 were noted in the periarteriolar and arteriolar areas. The results of RT- PCR and IHC showed positive relationships, but those were not significant statistically. This study suggests that proinflammatory, Thl/ Th2 cytokines and chemokines are involved in the specific processes of inflammation and immunologic injury, and their predominance and the level of expression could determine the pathogenetic processes and the severity of the clinical manifestations in IgA nephropathy.

Monocyte Chemoattractant Protein - 1 ( MCP-1 ) 조절부위에 따른 유전자다형성이 MCP-1 발현 및 낭창성 신염에 미치는 영향

오윤규(Yoon Kyu Oh),한진석(Jin Suk Han),안규리(Cu Rie Ahn),이정은(Joung Eun Lee),김연수(Yon Su Kim),김성권(Suhng Gwon Kim),이정상(Jung Sang Lee),김현리(Hyun Lee Kim),양승희(Seung Hee Yang),오지은(Ji Eun Oh),윤형진(Hyung Jin Yoon) 대한신장학회 2002 Kidney Research and Clinical Practice Vol.21 No.1

목 적 : MCP - 1 조절부위에 대한 유전자다형성이 MCP - 1 발현과 낭창성 신염의 발병, 진행에 대한 영향을 알아보고자 본 연구를 시행하였다. 방 법 : 전신성 홍반성 낭창(SLE) 환자 49명, 대조군 46명에서 유전자다형성을 결정 후, 각 유전자형에 따라 luciferase assay로 단백질 발현정도를 비교하였다. 정상 대조군 6명의 유전자형에 따라 말초혈액 단핵세포를 자극 후 배양 상청액의 MCP - 1 농도를 측정하였고 SLE 89명, 정상 대조군 21명의 혈중 MCP - 1 농도를 측정, 유전자형에 따라 신 침범과의 연관성을 조사하였다. 결 과 : SLE 환자에서 MCP- 1 조절부위(-2518 position :A- >G) 유전자다형성은 환자군(n=49)에서 각각 AA 10명(20%), GA 21명(42%), GG 18명(38%)으로 정상대조군(n=46)의 9명(20%), 27명(58%), 46명(22%)과 차이가 없었다. 말초혈액 단핵세포를 자극 후 배양 상청액의 MCP- 1 농도는 AA군이 현저히 증가되었다(p=0.01). 293 T 세포에 AA와 GG 유전자 이입 후 luciferase assay 시행시 GG 유전자 단백발현이 AA의 39%로 단백발현 감소(p=0.014), TNF-α를 처리 후 AA 유전자와 GG군의 construct 모두에서 activity가 증가되었고 특히 AA 유전자 단백발현이 GG 보다 3배 이상 증가되었다. SLE 환자군의 혈중 MCP- 1 농도는 418.17±935.30 pg/mL로 정상 대조군(127.78±114.53 pg/mL)에 비해 높았으나(p=0.047), 환자군의 혈중 MCP- 1 농도와 요단백량의 연관성은 없었다. 낭창성 신염으로 진단된 환자와 다른 대조군들 사이의 혈중 MCP- 1 농도를 비교하였을 때 의미있는 차이는 없었으나, AA homozygote군의 낭창성 신염 환자들에서 혈중 MCP- 1 농도가 신염이 없는 AA군에 비해 증가되었다(p=0.014). 결 론 : MCP - 1 유전자다형성이 단백발현의 차이를 낳고 낭창성 신염 진행에 중요한 역할을 하며 신질환 진행의 예측과 함께 적절한 치료방침을 세우는데 유전자다형성이 중요한 요소로 고려되어야 한다. Background : Monocyte chemoattractant protein-1(MCP-1) plays an important role in progression of lupus nephritis.(LN) The genetic polymorphism in the regulatory region would influence clinical manifestations by controlling serum levels of MCP-1. Methods : We determined the genotypes of the MCP-1 gene, the secretion of MCP-1 by pheripheral blood monocytes (PBMCs) and transcription activity according to polymorphism on ELISA and luciferase assay. We also correlated serum MCP-1 level with proteinuria according to the genotypes to evaluate the clinical implication of genetic polymorphism in LN. Results : 10 patients with SLE (20%) were AA homozygous, 21(42%) GA heterozygous, and 18(38%) GG homozygous, which w as similar with normal controls[AA 9(20%), GA 27(58%), GG 46(22%)](n=46). By in-vitro stimulation of PBMCs using Phytohemagglutinin, differential expression of MCP-1 appeared according to the genotypes at -2518 position; PBMCs from AA homozygotes 22.37±0.07 ng/ mL, GA 6.98±0.72 ng/ mL, GG 5.48±0.22 ng/ mL. In the luciferase assay, the gene construct with G at -2518 site showed decreased activity to 39% of that showed by A gene construct . In addition, After cells were treated with TNF-α (10 ng/mL), the transcription activity of A gene construct w as approximately 3 fold greater than that of G gene construct. Levels of serum MCP-1 were significantly higher in patients with SLE (n=89) than normal controls (n=21)(418.17±935.30 pg/mL vs. 127.78±114.53 pg/mL, respectively; p<0.05). In contrast, there were no significant differences in serum MCP-1 levels between patients with LN, patients without LN and normal controls. Also, correlation between serum MCP-1 levels and proteinuria was not found(r=0.191, p>0.05). But, in patients with LN, levels of serum MCP-1 were significant higher in patients with AA genotype than those of GA genotyes and GG genotypes (p<0.01). Conclusion : MCP-1 gene polymorphism at regulatory region may be a considerable marker for LN and may modulate the level of protein expression. Our study could make it possible to screen high risk individuals, thus help us to develop a practical application of the molecular findings in clinical practice.

신증후성 출혈열 환자로부터 한타바이러스의 분리

김근호(Gheun Ho Kim),진호준(Ho Joon Jin),정우경(Woo Kyung Chung),안규리(Cu Rie Ahn),김성권(Suhng Gwon Kim),이정상(Jung Sang Lee) 대한내과학회 1995 대한내과학회지 Vol.49 No.1

N/A Objectives: Past researches on the biochemical properties and pathogenicity of hantavirus have been mainly from rodent isolates, and we performed this study to obtain human isolates from patients with hemorrhagic fever with renal syndrome (HFRS) and to analyze the rate and source of viral isolation. Methods: Blood and urine specimens were collected from 48 patients with HFRS and inoculated onto subconfluent monolayers of Vero-E 6 cells, and human isolates of hantavirus were identified by direct and indirect immunofluorescent techniques, immunoblot analysis, and reverse transcriptase-directed polymerase chain reaction(RT-PCR). Results: Nineteen viral isolates(31 samples) were recovered from the blood and urine of 48 patients(90 samples) during days 3-11 following the onset of illness. Isolation rates of the virus from whole blood, serum, plasma, urine, and peripheral blood monuclear cells were 75%, 30%, 25%, 25%, and 18%, respectively. Viruses were more frequently isolated during days 3-9 of the illness(37%) than after day 9 (17%). Specific hantavirus antigens of isolates were identified by both indirect and direct immunofluorescent techniques and immunoblot analysis. The hantairus genomic sequences were detected in some of the isolates by RT-PCR. Conclusion: Nineteen hatavirus isolates were successfully recovered from 48 HFRS patients, mainly in the whole blood. Further investigations will be required to elucidate the differences in the pathogenicity of these human isolates using serologic and molecular biologic methods.