Jaeseok Yang

Seoul National University Hospital, Sŏul, Seoul, South Korea

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Publications (64)165.08 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Polycystic liver disease (PLD) in autosomal dominant polycystic kidney disease (ADPKD) patients can induce massive hepatomegaly-related symptoms. Volume-reductive therapies for symptomatic PLD include transcatheter arterial embolization (TAE), liver resection and liver transplantation; however, consensus has not been reached regarding treatment selection. We compared three volume-reductive therapies for a better understanding of PLD treatment strategies. We retrospectively analyzed 28 ADPKD patients who underwent TAE, liver resection, or liver transplantation for PLD at a single center, and compared their outcomes. Of 18 TAE patients, five required repeat TAE, and five required rescue liver transplantation or liver resection because of refractory symptoms or hepatic failure. The treatment failure rate for TAE was high (69.6%). Nine underwent liver resection, and the degree of volume reduction in the liver resection group was greater than that in the TAE group (52.4% vs. 7.6%, P < 0.001). One liver resection patient required rescue liver transplantation because of hepatic failure. Seven patients underwent liver transplantations. All liver transplant patients successfully controlled symptoms or hepatic failure, and had good graft function. Three patients in the TAE group died of infections or hepatic failure, whereas no mortality occurred after surgical therapy. liver resection is a good first-line therapy in patients that have severe symptoms, cyst involvement in several segments with some spared segments, and preserved liver function. Liver transplantation is a preferred first-line therapy in patients with poor liver function or whole-liver involvement. Liver transplantation is also a good rescue therapy following TAE or liver resection. This article is protected by copyright. All rights reserved.
    Hepatology Research 07/2015; DOI:10.1111/hepr.12560 · 2.22 Impact Factor
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    ABSTRACT: With the introduction of the α1, 3-galactosyltransferase gene-knockout (GT-KO) pig and its pivotal role in preventing hyperacute rejection (HAR), coagulation remains a considerable obstacle yet to be overcome in order to provide long-term xenograft survival. Thrombomodulin (TBM) plays a critical anticoagulant and anti-inflammatory role in its part of the protein C pathway. Many studies have demonstrated the strong anticoagulant effects of TBM in xenotransplantation, but its complement regulatory effects have not been appropriately examined. Here, we investigate whether TBM can regulate complement activation as well as coagulation in response to xenogeneic stimuli. We transfected porcine endothelial cells (MPN-3) with adenovirus vectors containing the human TBM gene (ad-hTBM), or a control gene containing GFP (ad-GFP). The expression level of ad-hTBM was measured by flow cytometry. To confirm the anticoagulant effect of TBM, coagulation time was measured after treatment with recalcified human plasma in ad-hTBM-transfected MPN-3, and a thrombin activity assay was performed after treatment with 50% human serum in ad-hTBM-infected MPN-3. Thrombin generation was significantly decreased in a dose-dependent manner in ad-TBM group, and coagulation time was increased in the ad-hTBM group when compared to the ad-GFP group. Complement-dependent serum toxicity assays were performed after treatment with 20% human serum or heat-inactivated human serum by LDH assay. Complement-dependent toxicity was significantly attenuated in the ad-hTBM group, but complement-independent toxicity was not attenuated in the ad-hTBM group. These results suggest that human thrombomodulin (hTBM) has complement regulatory effects as well as anticoagulant effects. To further investigate the mechanisms of complement regulation by hTBM, we deleted the EGF5, 6 domains that are involved in thrombin generation or the lectin-like domain involved in inflammation of TBM and functional tests were performed using these modified forms. We showed that the EGF5, 6 domain of TBM principally inhibits complement activation rather than the lectin domain. The EGF5, 6 domains of TBM appear to be the major domains for down-regulating the complement system rather than the lectin-like domain during xenogenic stimuli. The role of EGF5, 6 domains of hTBM may be due to inhibition of thrombin as thrombin can cleave C3a and C5a directly and hTBM may also be involved in complement regulation. Clearly then human TBM has complement regulatory effects as well as anticoagulant effects in xeno-immune response, and it is a promising target for attenuating xenograft rejection. © 2015 The Authors Xenotransplantation Published by John Wiley & Sons Ltd.
    Xenotransplantation 07/2015; DOI:10.1111/xen.12173 · 1.78 Impact Factor
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    ABSTRACT: We investigated the effects of pregnancy and delivery on renal function in transplant recipients and the relationship between doses of immunosuppressants and blood drug levels during pregnancy in 75 women with 88 deliveries. Significant serum creatinine elevation (> 0.5 mg/dL) was found in eight deliveries. In the remaining 80 cases, serum creatinine was reduced by an average of 0.14 mg/dL and returned to pre-pregnant levels after delivery. Tacrolimus was used in 28 deliveries and cyclosporine in others. Tacrolimus blood trough level declined from 5.8 ± 2.8 ng/mL 12 months before delivery to 4.2 ± 1.8 ng/mL at second trimester; therefore, drug dose was increased from 4.1 ± 1.9 mg/d at first trimester to 5.5 ± 2.5 mg/d at delivery. Similarly, cyclosporine levels were 125.1 ± 65.1 ng/mL 12 months before delivery and 75.4 ± 35.0 ng/mL at second trimester resulting in dose elevation from 183.0 ± 71.8 mg/d at first trimester to 225.4 ± 85.1 mg/d at delivery. Renal function in female kidney transplant recipients improved slightly during pregnancy and returned to pre-pregnant level after delivery. The dose elevation of calcineurin inhibitor by approximately 20–25% should be considered during gestational period to maintain optimal blood drug level.
    Clinical Transplantation 01/2015; 29(2). DOI:10.1111/ctr.12494 · 1.49 Impact Factor
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    ABSTRACT: Background. Diagnosing acute rejection (AR) in kidney transplant recipients typically requires an invasive kidney biopsy. A previous study has suggested that expression of five genes in peripheral blood can indicate the presence of AR in American pediatric kidney transplant recipients. This study aims to validate if these five genes are also useful to diagnose AR in Korean adult kidney transplant patients. Methods. Blood samples were collected from 143 patients (39 biopsy-proven AR, 84 stable patients, and 20 other graft injuries) at an average of 9 months posttransplantation and performed real-time PCR for five-gene biomarkers (DUSP1, NKTR, MAPK9, PSEN1, and PBEF1). Results. Patients with acute cellular rejection (ACR) had a significantly decreased level of MAPK9 and a significantly increased level of PSEN1 when compared with controls and also with patients with other graft injury (OGI). In multivariate logistic regression analysis, for discrimination between ACR and OGI, an excellent diagnostic accuracy was observed in the gene sets but five-gene set generated a higher AUC than two-gene set. With clinical variables combined to these gene sets, the diagnostic accuracy increased in both five-gene set and two-gene set. Conclusions. These results support the validity of 5 gene-set for the prediction of AR in Asian adult kidney transplant recipients and suggest the promising role of the peripheral blood gene test in the diagnosis of AR in kidney transplantation.
    Transplantation 09/2014; 98(7). DOI:10.1097/TP.0000000000000138 · 3.78 Impact Factor
  • Peritoneal dialysis international: journal of the International Society for Peritoneal Dialysis 09/2014; DOI:10.3747/pdi.2013.00343 · 2.20 Impact Factor
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    ABSTRACT: A 44-year-old pregnant female patient gave stillbirth while being treated for pneumonia. She developed acute respiratory failure, which resulted in mechanical ventilator support. Diagnostic lung biopsy revealed a cryptogenic organizing pneumonia. The patient's condition deteriorated and a venous-venous extracorporeal membrane oxygenation was placed. She was listed for lung transplantation. Because of her worsening condition lung transplantation was performed despite positive cross matching result. She was treated with rituximab, intravenous immunoglobulin, and plasmapheresis and recovered without event. There is no sign of rejection at the time of last follow-up.
    08/2014; 47(4):420-2. DOI:10.5090/kjtcs.2014.47.4.420
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    ABSTRACT: Background Highly sensitized (HS) patients seldom have chance to receive kidney transplant. To increase transplantation rate among those population, previous IV immunoglobulin and rituximab desensitization protocol showed good transplant conversion rate, but also carried moderate rate of antibody mediated rejection. Bortezomib, a proteasome inhibitor can control the production of anti-HLA antibodies through plasma cell apoptosis. A single center waitlist desensitization program was employed to facilitate successful kidney transplantation in HS patients group. Methods We prospectively enrolled 23 patients from Jul 2010 to Dec 2013. Desensitization protocol included two doses of IVIG (2 g/kg), single dose of rituximab (375 mg/m2, max 500 mg), and 4 days of bortezomib (1.3 mg/m2 on days 1,3,7 and 9). Anti-HLA class I and II antibodies were determined by Luminex solid phase bead assay at baseline and M2, M3 and M6. We investigated the difference of transplant conversion rate between desensitized HS patients and non-desensitized HS waitlist patients. Also we analyzed the difference of PRA % values and mean fluorescence intensity (MFI) between pre- and post-desensitization serum. Results Mean age of treatment group was 48.7±11.2 years old. Male to female ratio was 12:11. O+ blood type patients were 34.8% of patients. Mean duration of previous renal replacement therapy were 153.5±65.5 months. Baseline mean class I and II PRA % values were 86±15.3 and 66±34. Baseline class I and II MFI values were 13,893±6,147 and 12,274±6,891. After desensitization, kidney transplant were successfully performed in 34.8% of patients, compared to 13.8% transplant conversion rate among non-desentized HS controls (p=0.001 by Log-Rank). Among KT recipients, median duration of waiting after desensitization was 3 months with interquartile range 2-8.1 months. Class I PRA % had showed decreased values until 3 months after desensitization. After 6 months, there were no differences between the class I PRA values between pre-desensitization samples and post-desensitization samples. There were no other differences except class I PRA % values. Desensitization protocol were generally well tolerated, with the completion rate of 92% patients. There were no serious adverse events, but moderate adverse event were in 46%, most commonly fever and diarrhea. Conclusion Highly sensitized waitlist patients are manageable by desensitization protocol including bortezomib.
    06/2014; 33(2):A2. DOI:10.1016/j.krcp.2014.05.018
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    ABSTRACT: Background Asian patients undergoing kidney transplantation (KT) generally have better renal allograft survival and a lower burden of cardiovascular disease than those of other racial groups. The KNOW-KT aims to explore allograft survival rate, cardiovascular events, and metabolic profiles and to elucidate the risk factors in Korean KT patients. Methods KNOW-KT is a multicenter, observational cohort study encompassing 8 transplant centers in the Republic of Korea. KNOW-KT will enroll 1,000 KT recipients between 2012 and 2015 and follow them up to 9 years. At the time of KT and at pre-specified intervals, clinical information, laboratory test results, and functional and imaging studies on cardiovascular disease and metabolic complications will be recorded. Comorbid status will be assessed by the age-adjusted Charlson co-morbidity index. Medication adherence and information on quality of life (QoL) will be monitored periodically. The QoL will be assessed by the Kidney Disease Quality of Life Short Form. Donors will include both living donors and deceased donors whose status will be assessed by the Kidney Donor Risk Index. Primary endpoints include graft loss and patient mortality. Secondary endpoints include renal functional deterioration (a decrease in eGFR to <30 mL/min/1.73 m2), acute rejection, cardiovascular event, albuminuria, new-onset diabetes after transplant, and QoL. Data on other adverse outcomes including episodes of infection, malignancy, recurrence of original renal disease, fracture, and hospitalization will also be collected. A bio-bank has been established for the acquisition of DNA, RNA, and protein from serum and urine samples of recipients at regular intervals. Bio-samples from donors will also be collected at the time of KT. KNOW-KT was registered in an international clinical trial registry (NCT02042963 at http://www.clinicaltrials.gov) on January 20th, 2014. Conclusion The KNOW-KT, the first large-scale cohort study in Asian KT patients, is expected to represent the Asian KT population and provide information on their natural course, complications, and risk factors for complications.
    BMC Nephrology 05/2014; 15(1):77. DOI:10.1186/1471-2369-15-77 · 1.52 Impact Factor
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    ABSTRACT: The role of hyperuricemia in disease progression of autosomal dominant polycystic kidney disease (ADPKD) has not been defined well. We investigated the association of serum uric acid (sUA) with renal function and the effect of hypouricemic treatment on the rate of renal function decline. This is a single-center, retrospective, observational cohort study. A total of 365 patients with ADPKD who had estimated glomerular filtration rate (eGFR) >= 15 mL/min/1.73 m2 and who were followed up for > 1 year were included in our analysis. Hyperuricemia was defined by a sUA level of >= 7.0 mg/dL in male and >= 6.0 mg/dL in female or when hypouricemic medications were prescribed. Hyperuricemia was associated with reduced initial eGFR, independent of age, sex, hypertension, albuminuria, and total kidney volume. During a median follow-up period of over 6 years, patients with hyperuricemia showed a faster annual decline in eGFR (-6.3% per year vs. -0.9% per year, p = 0.008). However, after adjusting for age, sex, hypertension and initial eGFR, sUA was no longer associated with either annual eGFR decline or the development of ESRD. Among 53 patients who received hypouricemic treatment, the annual eGFR decline appeared to be attenuated after hypouricemic treatment (pretreatment vs. posttreatment: -5.3 +/- 8. 2 vs. 0.2 +/- 6.2 mL/min/1.73 m2 per year, p = 0.001 by Wilcoxon signed-rank test). Although hyperuricemia was associated with reduced eGFR, it was not an independent factor for renal progression in ADPKD. However, the correction of hyperuricemia may attenuate renal function decline in some patients with mild renal insufficiency.
    BMC Nephrology 04/2014; 15(1):63. DOI:10.1186/1471-2369-15-63 · 1.52 Impact Factor
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    ABSTRACT: We performed a retrospective cohort study to determine the prognostic value of standard criteria donor/expanded criteria donor (SCD/ECD) designation, with regard to one-yr GFR and graft survival rate, in a region with short, cold ischemic time (CIT), and how this designation compares with the kidney donor risk index (KDRI) and zero-time kidney biopsies. We reviewed 362 cases of deceased donor kidney transplantation (DDKT). Donor kidneys were classified as SCD or ECD. They were also assessed by the KDRI. Zero-time kidney biopsy was performed in 196 patients, and histologic score was assessed. Median follow-up duration was 46 months. Forty-two cases (11.6%) used ECD kidneys. The mean CIT was only 4.9 ± 2.7 h. Graft survival rates were not significantly different between ECD and SCD groups. The KDRI showed the best correlation with one-yr estimations of glomerular filtration rate (eGFR) (R(2) = 0.230, p < 0.001), and higher KDRI was associated with a higher risk of graft failure (hazard ratio 2.63, 95% confidence interval 1.01-6.87). However, higher histologic score was not associated with a higher risk of graft failure. KDRI has greater predictive value for short-term outcomes in DDKT with short CIT than the SCD/ECD designation or pathology.
    Clinical Transplantation 02/2014; 28(3). DOI:10.1111/ctr.12318 · 1.49 Impact Factor
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    ABSTRACT: Generation of transgenic pigs for xenotransplantation is one of the most promising technologies for resolving organ shortages. Human heme oxygenase-1 (hHO-1/HMOX1) can protect transplanted organs by its strong anti-oxidative, anti-apoptotic, and anti-inflammatory effects. Soluble human TNFRI-Fc (shTNFRI-Fc) can inhibit the binding of human TNF-α (hTNF-α) to TNF receptors on porcine cells, and thereby, prevent hTNF-α-mediated inflammation and apoptosis. Herein, we successfully generated shTNFRI-Fc-F2A-HA-hHO-1 transgenic (TG) pigs expressing both shTNFRI-Fc and hemagglutinin-tagged-human heme oxygenase-1 (HA-hHO-1) by using an F2A self-cleaving peptide. shTNFRI-Fc and HA-hHO-1 transgenes containing the F2A peptide were constructed under the control of the CAG promoter. Transgene insertion and copy number in the genome of transgenic pigs was confirmed by polymerase chain reaction (PCR) and Southern blot analysis. Expressions of shTNFRI-Fc and HA-hHO-1 in TG pigs were confirmed using PCR, RT-PCR, western blot, ELISA, and immunohistochemistry. shTNFRI-Fc and HA-hHO-1 were expressed in various organs, including the heart, lung, and spleen. ELISA assays detected shTNFRI-Fc in the sera of TG pigs. For functional analysis, fibroblasts isolated from a shTNFRI-Fc-F2A-HA-hHO-1 TG pig (i.e., #14; 1 × 10(5) cells) were cultured with hTNF-α (20 ng/mL) and cycloheximide (10 μg/mL). The viability of shTNFRI-Fc-F2A-HA-hHO-1 TG pig fibroblasts was significantly higher than that of the wild type (wild type vs. shTNFRI-Fc-F2A-HA-hHO-1 TG at 24 h, 31.6 ± 3.2 vs. 60.4 ± 8.3 %, respectively; p < 0.05). Caspase-3/-7 activity of the shTNFRI-Fc-F2A-HA-hHO-1 TG pig fibroblasts was lower than that of the wild type pig fibroblasts (wild type vs. shTNFRI-Fc-F2A-HA-hHO-1 TG at 12 h, 812,452 ± 113,078 RLU vs. 88,240 ± 10,438 RLU, respectively; p < 0.05). These results show that shTNFRI-Fc and HA-hHO-1 TG pigs generated by the F2A self-cleaving peptide express both shTNFRI-Fc and HA-hHO-1 molecules, which provides protection against oxidative and inflammatory injury. Utilization of the F2A self-cleaving peptide is a promising tool for generating multiple TG pigs for xenotransplantation.
    Transgenic Research 02/2014; 23(3). DOI:10.1007/s11248-013-9780-x · 2.28 Impact Factor
  • Hee Jung Jeon, Jaeseok Yang
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    ABSTRACT: Current immunosuppressants have nonspecific immuosuppressive effects, and are not helpful for tolerance induction. Consequently, transplant patients cannot discontinue using them, and their nonspecific immunosuppressive effects result in many side effects, including infection and malignancy. However, most of cellular immunotherapy can have donor antigen-specific immunsuppressive effects. Therefore, cell therapy could be an alternative or adjunctive to nonspecific immunosuppressants. Polyclonal or antigen-specific Foxp3+ regulatory T cells have been actively tried for prevention of acute rejection, treatment of chronic rejection, or tolerance induction in clinical trials. Regulatory macrophages are also under clinical trials for kidney transplant patients. IL-10-secreting type 1 regulatory T cells and donor- or recipient-derived tolerogenic dendritic cells will also be used for immunoregulation in clinical trials of kidney transplantation. These cells have antigen-specific immunoregulatory effects. Mesenchymal stromal cells (MSCs) have good proliferative capacity and immunosuppressive actions independently of major histocompatibility complex; therefore, even third-party MSCs can be stored and used for many patients. Cell therapy using various immunoregulatory cells is now promising for not only reducing side effects of nonspecific immunosuppressants but also induction of immune tolerance, and is expected to contribute to better outcomes in transplant patients.
    01/2014; 28(3):121. DOI:10.4285/jkstn.2014.28.3.121
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    ABSTRACT: BK virus-associated nephropathy (BKVAN) is one of the major causes of allograft dysfunction in kidney transplant (KT) patients. We compared BKVAN combined with acute rejection (BKVAN/AR) with BKVAN alone in KT patients. We retrospectively analyzed biopsy-proven BKVAN in KT patients from 2000 to 2011 at Seoul National University Hospital. Among 414 biopsies from 951 patients, biopsy-proven BKVAN was found in 14 patients. Nine patients had BKVAN alone, while 5 patients had both BKVAN and acute cellular rejection. BKVAN in the BKVAN alone group was detected later than in BKVAN/AR group (21.77 vs 6.39 months after transplantation, P=0.03). Serum creatinine at diagnosis was similar (2.09 vs 2.00 mg/dL). Histological grade was more advanced in the BKVAN/AR group (P=0.034). Serum load of BKV, dose of immunosuppressants, and tacrolimus level showed a higher tendency in the BKVAN alone group; however it was not statistically significant. After anti-rejection therapy, immunosuppression was reduced in the BKVAN/AR group. Renal functional deterioration over 1 yr after BKVAN diagnosis was similar between the two groups (P=0.665). These findings suggest that the prognosis of BKVAN/AR after anti-rejection therapy followed by anti-BKV therapy might be similar to that of BKVAN alone after anti-BKV therapy.
    Journal of Korean medical science 12/2013; 28(12):1711-5. DOI:10.3346/jkms.2013.28.12.1711 · 1.25 Impact Factor
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    ABSTRACT: The organ shortage is as serious in Korea as in other parts of the world. As about one-third of the potential living donors are ABO incompatible (ABOi), transplantation across the blood group barrier can help overcome this shortage. One hundred and twenty-five ABOi kidney transplantations (KTs) were performed between 2007 and 2010 in Korea. We collected the perioperative and follow-up data for 118 of these patients until September 2011. The preconditioning and immunosuppressive protocols were almost identical across the different transplant centers, with rituximab but no splenectomy; pre-transplant plasmapheresis (PP) with target anti-A/B titer 8 or 16 on transplant day, on-demand, rather than routine, post-transplant PP, and tacrolimus-based immunosuppressants. The number of patients and participating centers showed a rapid increase over time, and in 2010, ABOi KT (n = 79) comprised 10% of all the living donor KTs in Korea. The mean follow-up period was 21 months (range, 1-56 months). Sixteen (14%) patients developed acute rejection, and three of these had antibody-mediated rejection (AMR). Two-yr patient and graft survival were 99.2% and 97.5%, respectively. No graft was lost due to AMR. ABOi KT is rapidly expanding in Korea with excellent medium-term outcome and will help mitigate the organ shortage.
    Clinical Transplantation 10/2013; 27(6). DOI:10.1111/ctr.12249 · 1.49 Impact Factor
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    ABSTRACT: Chronic antibody-mediated rejection (CAMR) in renal transplant patients has poor allograft outcomes. However, treatment strategy has not been established yet. Herein, we present short-term outcomes of combination therapy for CAMR. We identified 9 patients with CAMR or suspicious CAMR who were treated with antihumoral therapy from 2010 to 2011 and analyzed their medical records retrospectively. Five patients had CAMR, and 4 patients had suspicious CAMR. Severe transplant glomerulopathy (TG) was observed in 7 patients. The estimated glomerular filtration rate (eGFR) was decreased in all patients before treatment. We used 3 different treatment regimens: (1) high-dose intravenous immunoglobulin (IVIG) and rituximab; (2) high-dose IVIG, rituximab, and bortezomib; and (3) plasmapheresis with low-dose IVIG, rituximab and bortezomib. After treatment with 1 of these 3 regimens, graft function improved or stabilized in 6 patients, whereas 3 patients showed further deterioration of eGFR. The third regimen suppressed deterioration of renal function in all patients. Most patients showed no progression of proteinuria. Infectious complications due Pneumocystis jirovecii pneumonia and herpes zoster occurred in 2 patients. Combination therapy for CAMR might be effective, even in patients with relatively late-stage CAMR.
    Nephrology 09/2013; 18(12). DOI:10.1111/nep.12157 · 1.86 Impact Factor
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    ABSTRACT: In pig-to-primate xenotransplantation, multiple transgenic pigs are required to overcome a series of transplant rejections. The generation of multiple transgenic pigs either by breeding or the introduction of several mono-cistronic vectors has been hampered by the differential expression patterns of the target genes. To achieve simultaneous expression of multiple genes, a poly-cistronic expression system using the 2A peptide derived from the Thosea asigna virus (T2A) can be considered an alternative choice. Before applying T2A expression system to pig generation, the expression patterns of multiple genes in this system should be precisely evaluated. In this study, we constructed several bi-cistronic T2A expression vectors, which combine target genes that are frequently used in the xenotransplantation field, and introduced them into porcine fibroblasts. The proteins targeted to the same or different subcellular regions were efficiently expressed without affecting the localization or expression levels of the other protein. However, when a gene with low expression efficiency was inserted into the upstream region of the T2A sequences, the expression level of the downstream gene was significantly decreased compared with the expression efficiency without the insertion. A small interfering RNA targeting one gene in this system resulted in the significant downregulation of both the target gene and the other gene, indicating that multiple genes combined into a T2A expression vector can be considered as a single gene in terms of transcription and translation. In summary, the efficient expression of a downstream gene can be achieved if the expression of the upstream gene is efficient.
    PLoS ONE 07/2013; 8(7):e70486. DOI:10.1371/journal.pone.0070486 · 3.53 Impact Factor
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    ABSTRACT: Regulatory T cells (Tregs) can suppress immunologic damage in renal ischemia-reperfusion injury (IRI), but the isolation and ex vivo expansion of these cells for clinical application remains challenging. Here, we investigated whether the IL-2/anti-IL-2 complex (IL-2C), a mediator of Treg expansion, can attenuate renal IRI in mice. IL-2C administered before bilateral renal IRI induced Treg expansion in both spleen and kidney, improved renal function, and attenuated histologic renal injury and apoptosis after IRI. Furthermore, IL-2C administration reduced the expression of inflammatory cytokines and attenuated the infiltration of neutrophils and macrophages in renal tissue. Depletion of Tregs with anti-CD25 antibodies abrogated the beneficial effects of IL-2C. However, IL-2C-mediated renal protection was not dependent on either IL-10 or TGF-β. Notably, IL-2C administered after IRI also enhanced Treg expansion in spleen and kidney, increased tubular cell proliferation, improved renal function, and reduced renal fibrosis. In conclusion, these results indicate that IL-2C-induced Treg expansion attenuates acute renal damage and improves renal recovery in vivo, suggesting that IL-2C may be a therapeutic strategy for renal IRI.
    Journal of the American Society of Nephrology 07/2013; DOI:10.1681/ASN.2012080784 · 9.47 Impact Factor
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    ABSTRACT: Introduction Neural stem cells (NSCs) are among the most promising candidates for cell replacement therapy in neuronal injury and neurodegenerative diseases. One of the remaining obstacles for NSC therapy is to overcome the alloimmune response on NSCs by the host. Methods To investigate the mechanisms of immune modulatory function derived from the interaction of human NSCs with allogeneic T cells, we examined the immune regulatory effects of human NSCs on allogeneic T cells in vitro. Results Significantly, NSCs induced apoptosis of allogeneic T cells, in particular CD4+ T cells. Interaction of CD70 on NSCs and CD27 on CD4+ T cells mediated apoptosis of T cells. Thus, blocking CD70–CD27 interaction prevented NSC-mediated death of CD4+ T cells. Conclusions We present a rational explanation of NSC-induced immune escape in two consecutive stages. First, CD70 constitutively expressed on NSCs engaged CD27 on CD4+ T cells, which induced Fas ligand expression on CD4+ T cells. Second, CD4+ T-cell apoptosis was followed by Fas–Fas ligand interaction in the CD4+ T cells.
    Stem Cell Research & Therapy 05/2013; 4(3):56. DOI:10.1186/scrt206 · 4.63 Impact Factor
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    ABSTRACT: Retransplantation is common in allogeneic islet transplantation, and therefore, memory responses in previously sensitized recipients present a distinct obstacle for successful islet transplantation. Given the difficulties in controlling memory responses contributing to allograft rejection, it is worth investigating the effects of new immune-modulating agents against islet allograft rejection in the sensitized recipients. In this study, we investigated immune-modulating agents including 5-azacytidine and IL-2/anti-IL-2 complex to ascertain their suppressive effects on memory responses. In suppression assays, rapamycin effectively suppressed the proliferation of memory T cells, whereas 5-azacytidine, a methylation inhibitor suppressed the survival and proliferation of memory T cells. Combination therapy of anti-CD40L, anti-OX40L, and rapamycin slightly prolonged BALB/c islet allograft survival in sensitized C57BL6 mice, and reduced intragraft infiltration of macrophages, T cells, and B cells. However, the addition of IL-2/anti-IL-2 complex, an inducer of regulatory T cells, did not exhibit additional suppression against rejection in sensitized mice. Although a combination of 5-azacytidine and rapamycin markedly suppressed islet allograft rejection in naïve mice, it failed to achieve long-term graft survival even when combined with anti-CD40L and anti-OX40 in sensitized mice. In short, 5-azacytidine-based or IL-2/anti-IL-2 complex-based regimens can suppress islet allograft rejection in naïve recipients, but fail to control islet allograft rejection in sensitized recipients.
    Transplant Immunology 01/2013; DOI:10.1016/j.trim.2013.01.005 · 1.83 Impact Factor
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    ABSTRACT: Background Urinary tract infection (UTI) occurs in 30%-50% of individuals with autosomal dominant polycystic kidney disease (ADPKD). However, the clinical relevance of asymptomatic pyuria in ADPKD patients remains unknown. Methods We retrospectively reviewed medical records of 256 ADPKD patients who registered to the ADPKD clinic at Seoul National University Hospital from Aug 1999 to Aug 2010. We defined the asymptomatic pyuria as more than 5-9 white blood cells in high-power field with no related symptoms or signs of overt UTI. Patients were categorized into 2 groups depending on its duration and frequency: Group A included non-pyuria and transient pyuria patients; Group B included recurrent and persistent pyuria patients. The association between asymptomatic pyuria and both the development of overt UTI and the deterioration of renal function were examined. Results With a mean follow-up duration of 65.3 months, 176 (68.8%) out of 256 patients experienced 681 episodes of asymptomatic pyuria and 50 episodes of UTI. The annual incidence of asymptomatic pyuria was 0.492 episodes/patient/year. The patients in group B showed female predominance (58.5% vs. 42.0%, P=0.01) and experienced an upper UTI more frequently (hazard ratio: 4.612, 95% confidence interval: 1.735-12.258; P=0.002, adjusted for gender and hypertension). The annual change in estimated glomerular filtration rate (ΔeGFR) was significantly larger in magnitude in group B than in group A (-2.7±4.56 vs. -1.17±5.8, respectively; P=0.01). Age and Group B found to be the independent variables for ΔeGFR and developing end-stage renal disease (16.0% vs. 4.3%, respectively; P=0.001). Conclusions Chronic asymptomatic pyuria may increase the risk of developing overt UTI and may contribute to declining renal function in ADPKD.
    BMC Nephrology 01/2013; 14(1):1. DOI:10.1186/1471-2369-14-1 · 1.52 Impact Factor

Publication Stats

332 Citations
165.08 Total Impact Points

Institutions

  • 2003–2015
    • Seoul National University Hospital
      • Department of Internal Medicine
      Sŏul, Seoul, South Korea
  • 2003–2014
    • Seoul National University
      • • Law Research Institute
      • • Department of Internal Medicine
      • • Division of Nephrology
      Sŏul, Seoul, South Korea
  • 2013
    • Yonsei University Hospital
      Sŏul, Seoul, South Korea
  • 2007–2010
    • Gachon University
      • Department of Internal Medicine
      Seoul, Seoul, South Korea
    • University of Incheon
      Sŏul, Seoul, South Korea