• 혜화의학회지
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• 제21권1호
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• pp.11-21
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• 2012

New onset diabetes is a major complication after kidney transplantation. However, the natural course of posttransplantation diabetes mellitus (PTDM) remains unclear. The aim of this study was to demonstrate the detailed natural courses of PTDM according to the onset and persistency of hyperglycemia, and to investigate risk factors for development of different courses of PTDM in renal allograft recipients. The purpose of this study is to develop novel immune suppressants for PTDM using of action mechanism of them. The use of immunosuppressive drugs in transplanted patients is associated with the development of diabetes, possibly due to ${\beta}$-cell toxicity. To better understand the mechanisms leading to post-transplant diabetes, we investigated the actions of prolonged exposure of ${\beta}$-cells to therapeutical levels of tacrolimus (FK506) or cyclosporin A(CsA). The immunosuppressive drug cyclosporine(CsA) is a potent agent widely used after organ transplantations and various autoimmune disorders. After using CsA, some patients suffer severe complications including renal and vascular toxicity. The renal or vascular toxicity is influenced by the degree of the endothelial damage. FK506(tacrolimus) is a widely used immunosuppressive agent in the treatment of various medical conditions, including autoimmune disease, bone marrow and organ transplantations. We found some interesting clusters and confirmed the feasibility of cDNA microarray in the study of Immunosuppressant. In this study, we investigated gene expression patterns induced by Immunosuppressant in RIN-m5F of rat insulinoma cell line. Gene expressions evaluated using cDNA microarry in two clusters were increased or decreased. this study provides comprehensive comparison of the patterns of gene expression changes induced by CsA and FK506 in ${\beta}$-cells. This study could establish that the mode of action mechanism by which currently used insulin inhibitors inducing PTDM could be elucidated at least in part, which raises the possibility that novel immune suppressive PTDM can be developed. The molecular biological study on PTDM will also contribute the progress in diabetes research field as well as in that of PTDM.

• 한국동물번식학회:학술대회논문집
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• 한국동물번식학회 2003년도 학술발표대회 발표논문초록집
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• pp.77-77
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• 2003

Chimeric animals are referred to as an organism composed of tissues derived from more than one species. In order to examine if a pluripotency of embryonic stem cells can cross the limitation of a species, we tried to establish human-mouse chimeric animals. Human embryonic stem cells were genetically modified to express eGFP using eukaryonic expression vector pcDNA 3.1 (In Vitrogene) for an easy identification. After selection with neomycin, approximately 15 cells were implanted into mouse blastocoele cavity. Ten chimeric blastocysts were transferred to one of the uterine horn of 2.5 days pesudopregnent ICR female. Out of 272 blastocysts transferred to pseudopregnant recipients 20 live newborn were obtained after 20 days. When newborn were obtained, pups were quickly removed immersed into 4% PFA. By histological examination using fluorescent microscope, green fluorescence was observed from the liver, heart, and spleen in newborn mice. Three weeks after born, presence of eGFP sequence within mouse genome (tail and kidney) was reconfirmed by PCR. eGFP sequence was amplified from the progenies of the animal suggesting a genetic transmission of the transgene. These chimeric mice having human cells at the beginning of development, are expected to recognize human cells as “self”, therefore, human cells or tissues will be able to escape the immunological surveillance of the host if grafted into the animal. These animals will serve as a good model system for studying the graft rejection in tissue transplantation and the potential of the cells to work well in many human disease.

• 대한이식학회지
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• 제32권4호
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• pp.92-103
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• 2018

Background: Currently, trimethoprim-sulfamethoxazole is used for Pneumocystis jirovecii pneumonia (PJP) prophylaxis, but it is associated with frequent adverse effects. This study evaluated the efficacy and safety of the current protocol and proposes an individualized risk-based prophylaxis protocol. Methods: The PJP incidence and risk factors during the first 6 months (early PJP) and afterwards (late PJP) was assessed in renal transplant recipients with (prophylaxis group) and without (no-prophylaxis group) 6-month PJP prophylaxis. Results: In 578 patients, there were 39 cases of PJP during a median follow-up of 51 months. Renal adverse events were encountered frequently during trimethoprim-sulfamethoxazole prophylaxis, leading to premature discontinuation. Patients without the prophylaxis had a significantly higher incidence of early PJP (n=27, 6.6%) compared to patients with the prophylaxis (n=0). The incidence of late PJP was 2.2%, without between-group differences. The factors associated with early PJP were preoperative desensitization and acute rejection within 1 month, whereas late PJP was associated with age, deceased donor transplant, and acute rejection requiring antithymocyte globulin treatment. Conclusions: Based on the simulation results of several risk-based scenarios, the authors recommend universal prophylaxis up to 6 months post-transplant and extended selective prophylaxis in patients aged ${\geq}57$ years and those with a transplant from deceased donors.

• 대한핵의학회지
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• 제29권1호
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• pp.79-83
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• 1995

정상기능 이식신장 50예와 비정상기능 이식신장 7예의 $^{99m}Tc-MAG_3$를 이용한 신장스캔에서 EI를 구하여 이식신장의 배설기능을 정량적으로 측정하였다. 이식신장의 $^{99m}Tc-MAG_3$ 신장기능곡선에서 정상기능 이식신장의 평균 EI는 $2.21{\pm}0.51$이었으며, 95% 신뢰구간은 2.01-2.87이었다. 비정상기능 이식신장에서는 평균 EI가 $0.74{\pm}0.18$로 1이하의 수치를 보여, 이식신장의 간질에 임파구의 침윤이나 세뇨관의 괴사등에 의해 관류와 배설기능의 장애를 초래하여 신실질과 수집관내에 방사능 동위원소의 저류가 나타났음을 뜻한다. 그리고 EI, $T_{max}$, $T_{1/2}$, BUN, 혈청 Creatinine의 정상기능 이식신장군과 비정상기능 이식신장군의 비교에서 통계학적으로 유의한 차이가 있었다(p<0.0001). 그러므로 이식 후 EI의 측정으로 이식신장의 기능상태를 알 수 있고 거부반응 및 신세뇨관 괴사 등의 합병증을 조기에 찾아내는 지표로 사용할 수 있을 것으로 사료된다.

• Journal of Chest Surgery
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• 제40권7호
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• pp.467-472
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• 2007

배경: 폐 이식이 호흡부전증 환자의 유일한 치료방법으로 인정받고 있으나 이는 역설적으로 많은 호흡부전증 환자의 이식 대기 기간 증가와 공급 장기 부족 현상을 초래하였다. 이에 동물에서 장기를 적출하는 이종 장기이식 수술이 대두되게 되었다. 그러나 이들 이종 장기이식 후 나타나는 초급성 거부반응을 아직 해결하지 못했으며 본 실험은 기초연구로써 이들 초급성 거부반응을 일으키는 주요 인자인 면역글로불린의 이식 전, 후 변화를 관찰하였다. 대상 및 방법: $20{\sim}30kg$의 잡종견과 돼지 각 6마리를 이용하여 돼지의 좌측 신장을 잡종견의 좌측 대퇴동정맥에 연결하여 30분간 관류하였고 다시 우측 신장을 교체 연결 후 30분간 관류하였다. 다시 돼지의 좌측 폐를 잡종견의 폐동맥과 좌심방에 연결 후 30분간 관류하였고 우측 폐를 교체 연결한 후 30분간 관류하였다. 실험과 실험 사이에 혈액을 채취하여 혈청을 분류하였고 절제한 신장과 폐의 IgM과 IgG 침착 정도를 관찰하였다. 결과: 관류 시간이 길어짐에 따라 혈액의 IgM은 감소하였으나 IgG의 감소는 확실하지 않았다. 신장과 폐의 면역형광염색 소견에서 IgM, IgG의 염색반응이 크게 줄어드는 것을 확인할 수 있었다. 결론: 이와 같은 연구결과로 이종 장기이식 전에 신장 및 폐를 이용하여 수혜자의 혈액을 관류함으로써 공급자의 자연 항체를 흡수 제거하는 방법은 이종 이식 후 발생하는 초급성 거부반응을 줄일 수 있으리라 생각한다.

• Journal of Chest Surgery
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• 제46권6호
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• pp.426-432
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• 2013

Background: Heart transplantation has become a widely accepted surgical option for end-stage heart failure in Korea since its first success in 1992. We reviewed early postoperative complications and mortality in 239 patients who underwent heart transplantation using bicaval technique in Asan Medical Center. Methods: Between January 1999 and December 2011, a total of 247 patients aged over 17 received heart transplantation using bicaval technique in Asan Medical Center. After excluding four patients with concomitant kidney transplantation and four with heart-lung transplantation, 239 patients were enrolled in this study. We evaluated their early postoperative complications and mortality. Postoperative complications included primary graft failure, cerebrovascular accident, mediastinal bleeding, renal failure, low cardiac output syndrome requiring intra-aortic balloon pump or extracorporeal membrane oxygenation insertion, pericardial effusion, and inguinal lymphocele. Follow-up was 100% complete with a mean follow-up duration of $58.4{\pm}43.6$ months. Results: Early death occurred in three patients (1.3%). The most common complications were pericardial effusion (61.5%) followed by arrhythmia (41.8%) and mediastinal bleeding (8.4%). Among the patients complicated with pericardial effusion, only 13 (5.4%) required window operation. The incidence of other significant complications was less than 5%: stroke (1.3%), low cardiac output syndrome (2.5%), renal failure requiring renal replacement (3.8%), sternal wound infection (2.0%), and inguinal lymphocele (4.6%). Most of complications did not result in the extended length of hospital stay except mediastinal bleeding (p=0.034). Conclusion: Heart transplantation is a widely accepted option of surgical treatment for end-stage heart failure with good early outcomes and relatively low catastrophic complications.

• Journal of Korean Medical Science
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• 제33권53호
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• pp.298.1-298.10
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• 2018

Background: The renal function of individuals is one of the reasons for the variations in therapeutic response to various drugs. Patients with renal impairment are often exposed to drug toxicity, even with drugs that are usually eliminated by hepatic metabolism. Previous study has reported an increased plasma concentration of indoxyl sulfate and decreased plasma concentration of $4{\beta}$-hydroxy (OH)-cholesterol in stable kidney transplant recipients, implicating indoxyl sulfate as a cytochrome P450 (CYP) inhibiting factor. In this study, we aimed to evaluate the impact of renal impairment severity-dependent accumulation of indoxyl sulfate on hepatic CYP3A activity using metabolic markers. Methods: Sixty-six subjects were enrolled in this study; based on estimated glomerular filtration rate (eGFR), they were classified as having mild, moderate, or severe renal impairment. The plasma concentration of indoxyl sulfate was quantified using liquid chromatography-mass spectrometry (LC-MS). Urinary and plasma markers ($6{\beta}$-OH-cortisol/cortisol, $6{\beta}$-OH-cortisone/cortisone, $4{\beta}$-OH-cholesterol) for hepatic CYP3A activity were quantified using gas chromatography-mass spectrometry (GC-MS). The total plasma concentration of cholesterol was measured using the enzymatic colorimetric assay to calculate the $4{\beta}$-OH-cholesterol/cholesterol ratio. The correlation between variables was assessed using Pearson's correlation test. Results: There was a significant negative correlation between MDRD eGFR and indoxyl sulfate levels. The levels of urinary $6{\beta}$-OH-cortisol/cortisol and $6{\beta}$-OH-cortisone/cortisone as well as plasma $4{\beta}$-OH-cholesterol and $4{\beta}$-OH-cholesterol/cholesterol were not correlated with MDRD eGFR and the plasma concentration of indoxyl sulfate. Conclusion: Hepatic CYP3A activity may not be affected by renal impairment-induced accumulation of plasma indoxyl sulfate.

• 대한핵의학회지
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• 제34권6호
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• pp.497-507
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• 2000

목적: 저자들은 이식 초기 이식신의 기능을 평가하기 위하여 시행한 $^{99m}Tc$-MAG3 신신티그라피에서 측정한 관류기 지표의 특성과 소견을 알아보고 신장 기능 이상을 초래하는 합병증의 진단에 이들 지표들이 얼마나 유용하게 이용될 수 있는 지를 규명하고자 하였다. 대상 및 방법: 신장 이식을 받은 환자 80명(남자: 48명, 여자: 32명, 평균 나이: 40.3세)을 대상으로 하였고, 조직검사, 검사실시험 소견 및 임상 경과 등을 종합하여 진단하였다. 신신티그라피는$^{99m}Tc$-MAG3, 100 MBq을 사용하여 이식 후 11일-23일 사이에 얻었다. 신전체 및 신피질 레노그람에서 측정한 신관류 지포는 Hilson관류지표(PI), 이식신 관류지표(TP)와 이식신 기능지표(TF)였고, 신기능 지표는 최대방사능 도달시간(Tmax)과 3분과 20분 방사능 비(K20/3)였다. 결과: 신신티그라피 시행 당시의 진단은 정상 신기능을 보인 경우가 44예, 급성거부가 14예, 급성 세뇨관괴사가 10예이었고 싸이클로스포린 A 신독성은 12예이었다. TP와 TF는 정상 신기능 군에 비해 합병증 군에서 통계적으로 유의하게 높았지만 PI는 유의한 차이가 없었다. 또한 정상 신기능 군에 비해 K20/3은 급성 거부와 급성세뇨관괴사에서, 신전체 Tmax은 급성거부에서 각각 유의하게 높았다. 합병증 군들 사이에서 유의한 차이를 보인 관류기 지표는 없었고 신기능 지표 중 K20/3은 싸이클로스포린 A 신독성에 비해 급성거부에서, 신피질 K20/3은 급성세뇨관괴사에서 각각 유의하게 증가하였다. 결론: $^{99m}Tc$-MAG3 신신티그라피를 이용한 이식 초기 이식신의 기능 평가에는 최초 동맥기 이후의 미세 관류와 초기 세뇨관 섭취를 나타내는 지표들인 TP와 TF가 중요한 역할을 하며, 신신티그라피 일 회 검사로 신장 기능의 이상을 초래하는 합병증의 감별은 쉽지 않지만 신 관류와 기능 지표를 연관시키고 검사 당시 질병의 진행 과정과 정도를 고려하면 진단에 도움이 되리라 생각한다.