• Biotechnology and Bioprocess Engineering:BBE
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• v.7 no.5
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• pp.303-310
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• 2002

Cell therapy applied to wound healing or tissue regeneration presents a revolutionary realm to which principles of gene engineering and delivery may be applied. One promising application is the transplantation of cells into the wounded tissue to help the tissue repair. However, when cells are transplanted from in vitro to in vivo, immune rejection occurs due to the immune response triggered by the activation of T-cell, and the transplanted cells are destroyed by the attack of activated T-cell and lose their function. Immune suppressant such as FK506 is commonly used to suppress immune rejection during transplantation. However, such kind of immune suppressants not only suppresses immune rejection in the periphery of transplanted cells but also suppresses whole immune response system against pathogenic infection. In order to solve this problem, we developed a method to protect the desired cells from immune rejection without impairing whole immune system during cell transplantation. Previously, we reported the success of constructing glomerular epithelial cells for removal of immune complex, in which complement receptor of type 1 (CR1) was over-expressed on the membrane of renal glomerular epithelial cells and could bind immune complex of DNA/anti-DNA-antibody to remove immune complex through phagocy-tosis [1]. Attempting to apply the CR1-expressing cells to cell therapy and evade immune rejection during cell transplantation, we constructed three plasmids containing genes encoding a soluble fusion protein of cytolytic T lymphocyte associated antigen-4 (CTLA4Ig) and an enhanced green fluorescent protein (EGFP). The plasmids were transfected to the above-mentioned glomerular epithelial cells to express both genes simultaneously. Using the clone cells for cell transplantation showed that mice with autoimmune disease prolonged their life significantly as compared with the control mice, and two injections of the cells at the beginning of two weeks resulted in remarkable survivability, whereas it requires half a year and 50 administrations of proteins purified from the same amount of cells to achieve the same effect.

• Journal of Chest Surgery
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• v.46 no.2
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• pp.111-116
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• 2013

Background: Heart transplantation in elderly patients has raised concerns because of co-morbidities and limited life expectancy in the era of donor shortage. We examined the outcomes after heart transplantation in elderly patients. Materials and Methods: From March 1994 to December 2011, 81 patients (male:female=64:17, $49.1{\pm}14.0$ years) underwent heart transplantation. The outcomes after heart transplantation in the younger patients (<60 years; group Y, n=60) were compared with those in the elderly patients (${\geq}60$ years; group O, n=21). The follow-up duration was $51.8{\pm}62.7$ months. Results: Early mortality (${\leq}30$ days) occurred in 5.0% (3/60) and 4.8% (1/21) of groups Y and O, respectively (p>0.999). There were no differences in overall survival between the two groups (p=0.201). Freedom from rejection was higher in group O than in group Y (p=0.026). Multivariable analysis revealed that age ${\geq}60$ years was not a significant risk factor for long-term survival; postoperative renal failure was the only significant risk factor for long-term survival (p=0.011). Conclusion: Early and mid-term results of heart transplantation in elderly patients were similar to those in younger patients.

• Childhood Kidney Diseases
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• v.21 no.2
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• pp.69-74
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• 2017

Purpose: Kidney transplantation (KT) is an ideal treatment for pediatric patients with end-stage renal disease (ESRD). We report the clinical outcomes of pediatric ESRD patients who underwent KT in a single regional center. Methods: We retrospectively investigated the medical records of 60 pediatric patients who were diagnosed with ESRD and underwent KT in our hospital between January 1985 and June 2016. Results: A total of 60 children and adolescents (40 male, 20 female; mean age, $13.86{\pm}4.26$ years) were included in this study. Six patients (10.0%) underwent KT immediately after receiving the diagnosis of ESRD, while the others underwent KT after dialysis treatment (mean period of dialysis, $368.7{\pm}4,41.8$ days). The mean donor age (50 living-related [83.3%], 10 deceased [16.7%]) was $40.0{\pm}12.85$ years and the male:female ratio was 1.07:1. The most common cause of ESRD was chronic glomerulonephritis. The overall survival rates at 1, 3, and 5 years after KT were 98%, 98%, and 96%, respectively, while the graft survival rates at 1, 3, and 5 years were 93%, 86%, and 68%, respectively. Children who underwent KT before 10 years of age had better monthly growth rates than those who underwent KT later than 10 years of age. Conclusions: KT is performed less frequently in children than in adults, but causes of ESRD vary and clinical outcomes after KT greatly affect the growth and development of pediatric patients. Therefore, further analysis and monitoring of clinical progression after KT in pediatric ESRD patients are necessary.

• Childhood Kidney Diseases
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• v.24 no.2
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• pp.75-82
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• 2020

Objectives: We aimed to investigate the incidence, manifestations, and outcomes of malignancy after pediatric kidney transplantation (KT) at our center over 30 years. Methods: We retrospectively reviewed the medical records of 155 patients under 18 years of age who underwent KT between January 1990 and February 2020 at Asan Medical Center. Results: Twelve patients (7.7%) were diagnosed with a malignancy after KT. Malignancy was diagnosed after a mean period of 6.4±5.9 years (median 4.6, range 0.5-20.6 years) after KT. Nine (75.0%) of the 12 cancer patients were diagnosed with post-transplant lymphoproliferative disease (PTLD), and the other three had papillary thyroid cancer, mucoepidermoid cancer of the hard palate, and T-cell acute lymphoblastic leukemia, respectively. PTLD was diagnosed within a mean of 3.7±3.4 years (median 3.7, range 0.5-9.8 years) after KT. Five patients diagnosed with PTLD were cured without recurrence. Three patients with PTLD died from the disease, and one patient with mucoepidermoid cancer from a non-PTLD malignancy died after progression, despite surgical resection and chemotherapy. Three (33.3%) of the nine survivors progressed to end-stage renal disease (ESRD) after completing cancer treatment. No patient with post-transplant malignancy (PTM) experienced critical renal deterioration during cancer treatment. Conclusion: PTLD was the most common PTM, occurring at 5.8% of the pediatric KT patients after KT in our center. Careful follow up is needed particularly considering the risk of PTLD after KT in children.

• Korean Journal of Transplantation
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• v.28 no.3
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• pp.165-168
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• 2014

The recipient candidate was a 51-year-old male with end-stage renal disease owing to diabetes mellitus. The initial immunosuppressive regimen included basiliximab for induction and tacrolimus, mycophenolate mofetil, and steroids. Urine output was 413 mL/day on the operative day and 100 mL/day on the postoperative day (POD) 1. There was no definite stenosis of the ureter or vessels. He had anuria on POD 2~4 and he had undergone hemodialysis. His serum creatinine level did not decrease. Therefore, a graft biopsy was performed on POD 4. The pathologic finding was consistent with acute calcineurin inhibitor (CNI) toxicity. There was no evidence of rejection or acute tubular necrosis. Anuria continued on POD 6; therefore, we started sirolimus instead of a CNI based regimen. Graft function was gradually recovered 1 day after reduction of CNI dose and hemodialysis was stopped. The serum creatinine level was normalized on POD 10. He was discharged on POD 21.

• BMB Reports
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• v.52 no.9
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• pp.554-559
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• 2019

Despite reports suggesting that tissue-resident natural killer (trNK) cells cause ischemic kidney injury, their contribution to the development of tubulointerstitial fibrosis has not been determined. This study hypothesized that the depletion of trNK cells may ameliorate renal fibrosis by affecting transglutaminase 2/syndecan-4 interactions. Aristolochic acid nephropathy (AAN) was induced in C57BL/6 mice as an experimental model of kidney fibrosis. The mice were treated with anti-asialo GM1 (ASGM1) or anti-NK1.1 antibodies to deplete NK cells. Although both ASGM1 and NK1.1 antibodies suppressed renal $NKp46^+DX5^+$ NK cells, renal $NKp46^+DX5^-$ cells were resistant to suppression by ASGM1 or NK1.1 antibodies during the development of tubulointerstitial fibrosis in the AAN-induced mouse model. Western blot analysis showed that both antibodies increased the expression of fibronectin, transglutaminase 2, and syndecan-4. These findings indicate that trNK cells played an exacerbating role in tubulointerstitial fibrosis by activating transglutaminase 2 and syndecan-4 in the AAN-induced mouse model.

• The Korean Journal of Nuclear Medicine
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• v.34 no.6
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• pp.497-507
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• 2000

Purpose: We have examined the utility of $^{99m}Tc$-MAG3 perfusion indices for assessing renal graft function in early post-transplantation period. Materials and Methods: Our study included 80 renal transplant recipients (48 men and 32 women, mean age: 40.3 years). Diagnosis was based on biopsy, laboratory data and clinical course. Renal scintigraphy (RS) was obtained using 100 MBq of $^{99m}Tc$-MAG3 from 11 days to 23 days of kidney transplantation. We measured 5 indices in whole-kidney (WK) and cortical (C) renograms; Hilson's perfusion index (PI), transplant perfusion index (TP) and transplant function index (TF) as perfusion parameter, and the time to peak activity (Tmax) and the ratio of renal counts at 20 min to that at 3 min (K20/3) as functional parameter. Results: The diagnoses at the day of RS were normal graft (NG) in 44, acute rejection (AR) in 14, acute tubular necrosis (ATN) in 10, and Cyclosporine A nephrotoxicity (CsA) in 12. TP and TF were significantly decreased in AR, ATN and CsA, compared to those in NG. K20/3 of AR and ATN wore significantly greater than that of NG. WK-Tmax of AR was significantly longer than that of NG. K20/3 of AR and C-K20/3 of ATN were significantly prolonged relative to those of CsA. There were no statistically significant perfusion indices among complication groups. Conclusion: TP and TF reflecting microperfusion and initial tubular extraction are reliable in assessing graft function. However, it is required to correlate perfusion indices with functional indices and clinical course in differentiating from one another among complication groups.

• Journal of Korean Foot and Ankle Society
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• v.4 no.2
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• pp.83-86
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• 2000

A vascular necrosis of the talus has frequently been reported following trauma because talus has no muscle insertions, sixty percent of the surface of the talus is covered by hyaline cartilage, takes only a small area for entrance of a blood supply. Osteonecrosis is also associated with a variety of nontraumatic disorders. There are many indications for steroid usage, patient with rheumatoid arthritis, systemic lupus erythematosus, chronic obstructive pulmonary disease, and status- post renal or cardiac transplantation may be on long- term steroid usage, osteonecrosis may develop. A vascular necrosis of the talus secondary to chronic steroid usage is an unusual case. Delay in detection of osteonecrosis may lead to fragmentation and collapse of the talar body. When pain on range of motion is present and conservative treatment have been exhausted, surgical treatment is indicated, that is, fusion of the ankle joint. However it is important that conservative treatment may prevent its various sequelae with early diagnosis because steroid - treated patients have a more operative risk and increased risk for postoperative infection. We report a rare case of corticosteroid induced avascular necrosis of talus after cardiac transplantation.

• Childhood Kidney Diseases
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• v.22 no.1
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• pp.7-11
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• 2018

Significant advances in the diagnosis and medical care of children with chronic kidney disease (CKD) are major reasons for the better survival rates of children and adolescents with CKD than the survival rates reported in previous decades. These patients are reaching adulthood, and therefore require a transition to adult medical care. This transition phase is well-recognized to be associated with considerably increased morbidities and medical problems, such as non-adherence, graft loss after transplantation, and loss to follow-up. Low adherence increases morbidity and medical complications and contributes to poorer qualities of life and an overuse of the health care system. However, these tragic outcomes may be avoidable through a structured and well-defined transition program. In the last decade, there has been increasing interest to resolve these medical and psychological problems that occur during the transfer of young adult patients from pediatric to adult renal units. The aims of a successful transition from pediatric to adult medical care include enhancing the individual development of better health-competence and stabilizing, or even improving, the state of health. This review will focus on various aspects of the transition phase of adolescents who have CKD or who underwent kidney transplantation from pediatric to adult nephrology care.

• Clinical and Experimental Pediatrics
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• v.62 no.11
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• pp.422-427
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• 2019

Background: Polyomavirus BK (BKV) infection is an important cause of graft loss in kidney transplant patients. Purpose: The purpose of this study was to evaluate clinical findings and risk factors for BKV in pediatric patients after kidney transplantation. Methods: This retrospective single-center study included 31 pediatric kidney transplant recipients from January 2002 to December 2017. Two patients received 2 transplantations during the study period, and each transplant was analyzed independently. Total number of cases is 33 cases with 31 patients. BKV infection was confirmed from blood samples via periodic quantitative polymerase chain reaction. Results: The mean age at kidney transplantation was 11.0±4.7 years, and the male-to-female ratio was 2.7:1. Three patients had a past medical history of high-dose chemotherapy and autologous stem-cell transplantation for solid tumors. Nine patients (27.3%) developed BKV infection. The median period from kidney transplantation to BKV detection in blood was 5.6 months. There was no statistically significant difference in estimated glomerular filtration rate between patients with and those without BKV infection. Among 9 patients with BKV viremia, 7 were treated by reducing their immunosuppressant dose, and BKV was cleared in 6 of these 7 patients. In the other 2 BKV-positive patients, viremia improved without immunosuppressant reduction. Conclusion: BKV infection is common in children with kidney transplantation and might not have affected short-term renal function in our patient sample due to early immunosuppressant reduction at the time of BKV detection.