• Journal of Chest Surgery
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• v.30 no.2
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• pp.164-171
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• 1997

Heart transplantation is now accepted as a definitive therapeutic modality in patients with terminal hear failure. The first successful heart transplantation in humans was done in 1967 and the first case in Korea was performed in november, 1992. Since the first case in 1992, more than 50 cases have been performed in Korea. A total of 20 patients underwent orthotopic heart transplantation since November, 1992 in Asan Medicla Center. The purpose of this study is to evaluate the early results and the follow-up course of 20 cases of heart transplantation done in Asan Medical Center. The average age of 20 patients was 39.9$\pm$11.8 years old(20~58). The mean follow-up duration was 14.4$\pm$11.2 months(1~41). All patients are alive till now. The blood type was identical in 14 and compatible in 6 patients. ihe original heart disease was dilated cardiomyopathy in 16, valvular heart disease in 2, ischemic cardiomyopathy in 1, and giant cell myocarditis in 1 patient. HLA cross matching for recipient and donor was done in 18 cases and the results were negative for T-cell and B-cell in 16 patients, pos tive for warm B-cell in 2 patients. Among 6 loci of A, B, and DR, one locus was matched in 8 cases, 2 loci in 5 cases, and 3 loci matched in 1 case. The number of acute allograft rejection averaged 2.8$\pm$0.5 (0~6) per case and the number of acute allograft rejection requiring treatment averaged 1.0$\pm$0.9 (1~3) per case. The time interval from operation to the first acute rejection requiring treatment was 35.5$\pm$20.4 days (5~60). Acute humoral rejection was suspected strongly in 1 case and was successfully treated. The left ventricular ejection fraction measured by echocardiography and/or MUGA scan was dramatically increased from 17.5$\pm$6.8 (9~32)% to 58.9$\pm$2.0 (55~62)% after heart transplantation. Temporary pacing was needed in 5 patients over 24 hours but normal sinus rhythm appeared within 7 days in all cases. One patient has been taken permanent pacemaker implantation due to complete AV block appearing 140 days after heart transplantaion. One patient had cyclosporine-associated n urotoxicity during the immediate postoperative period and was recovered after 27 hours. The heart transplantation of Asan Medical Center is on a developing stage but the early result is comparable to that of well established centers in other countries, even though the long-term follow-up result must be reevaluated. We can conclude that the heart transplantion is a promising therapeutic option in patients with terminal heart failure.

• IMMUNE NETWORK
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• v.2 no.3
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• pp.133-136
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• 2002

Background: The costimulatory molecule 4-1BB, a member of nerve growth factor receptor/tumor necrosis factor (NGFR/TNFR) super family, is involved in cell survival and death. Methods: In this study, female C57BL/6 ($H-2^b$) mice were used as a recipient, and DBA/2 ($H-2^d$) as a donor to assess a mixed lymphocyte reaction (MLR) and CTL response in vitro, and skin graft survival. IL-2, IFN level was measured by ELISA. Results: Mixed lymphocyte reaction (MLR) analysis showed that 4-1BB-deficient responder cells showed enhanced cellular proliferation over littermate controls. In contrast, IL-2 production was diminished only in 4-1BB knockout cultures. The IFN expression, on the other hand, was comparable between the groups. When female C57BL/6 ($H-2^b$) mice were grafted with the trunk skin of DBA/2 ($H-2^d$) mice, the in vivo tissue destruction of 4-1BB-deficient mice was not distinct from the normal littermates. Conclusion: These data suggest that 4-1BB is critical for the induction of alloreactive responses in vitro but 4-1BB alone could not change the course of skin rejection in vivo.

• IMMUNE NETWORK
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• v.7 no.1
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• pp.10-17
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• 2007

Autoimmune arthritis, such as rheumatoid arthritis (RA), is a chronic inflammatory disorder that primarily affects the joints and then results in their progressive destruction. Effector Th cells have been classified as Th1 and Th2 subsets based on their cytokine expression profiles and immune regulatory function. Another subset of T cells termed Th17 was recendy discovered and known to selectively produce IL-17. Also, Th17 was shown to be generated by TGF${\beta}$ and IL-6 and maintained by IL-23. IL-17 is a proinflammatory cytokine that is considered to involve the development of various inflammatory autoimmune diseases such as RA, asthma, lupus, and allograft rejection. IL-17 is present in the sera, synovial fluids and synovial biopsies of most RA patient. IL-17 activates RA synovial fibroblasts to synthesize IL-6, IL-8 and VEGF via PI3K/Akt and NF-${\kappa}B$ dependent pathway. IL-17 increases IL-6 production, collagen destruction and collagen synthesis. In addition, it not only causes bone resorption but also increases osteoclastogenesis and fetal cartilage destruction. Inhibition of the IL-17 production may contribute a novel therapeutic approach along with potent anti-inflammatory effect and with less immunosuppressive effect on host defenses.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.35 no.5
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• pp.342-351
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• 2013

Advances in immunosuppressive treatments and microsurgical techniques have rendered composite tissues allotransplantation (CTA), such as heteregeneous or non-organ tissues, possible in humans. CTA has evolved dramatically since the first successful rat hind limb allotransplantation. Numerous clinical applications including face, hand, trachea, larynx, and vascularized joint have been performed. Although composite tissue allografts are still in their infancy, they have opened a new era in the field of transplantation surgery and pathology, so that maxillofacial reconstructive surgeons may occasionally be faced with the challenge of diagnosing skin refection of a composite tissue allograft. Facial allotransplantation (FAT) is a new surgical technique that could be considered as a new paradigm in facial reconstruction. Since the first human FAT had been achieved in 2005, 17 cases have been reported in the world up to date. However, many problems such as life-long immunosuppression, immune rejection, ethical problems and psychological problems are remained, so facial CTA is new reconstructive option with no general acceptance. The authors reviewed the indications, the results of 17 cases and their complications, and additional consideration factors in this article, and intended to raise the awareness of oral and maxillofacial surgeons in this type of facial transplantation.

• Childhood Kidney Diseases
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• v.19 no.2
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• pp.176-179
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• 2015

Rituximab (RTX), a monoclonal antibody against the B-cell marker CD20, is commonly used as a treatment for antibody-mediated diseases or B-lymphocyte-mediated diseases. Destruction of B cells may reverse the disease course in many conditions; however, patients who are treated with RTX cannot respond appropriately to de novo infection due to lack of B lymphocytes. Here, we report one such case. A 7-year-old renal allograft recipient presented with severe anemia due to parvovirus infection after RTX treatment. The patient had focal segmental glomerulosclerosis and had received cadaveric kidney transplantation 6 months previously. She was treated with high-dose steroid for acute rejection and RTX for Epstein Barr Virus infection 3 months previously. At presentation, her hemoglobin level was 5.4 g/dL and leukocyte and platelet counts were normal. She had microcytic normochromic anemia and high viral load of parvovirus B19(70,578 copies/mL). Intravenous immunoglobulin ($200mg/kg{\cdot}d$) treatment controlled the progression of anemia and parvovirus infection. De novo parvovirus infection during the B lymphocyte-depletion period may have precipitated the severe anemia in this case. Close monitoring of infection is required after RTX therapy.

• Archives of Plastic Surgery
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• v.32 no.4
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• pp.533-538
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• 2005

Due to its safety and softness, autologous fat transplantation has been commonly performed for soft tissue correction. However, the injected fat is absorbed resulting in the reduction of volume of the graft by 40-60% within a few months. Thus, there was an attempt to use adipocytes differentiated from preadipocytes in vitro for transplantation. Differentiated adipocytes were biocompatible and matured with gradual volume increase at transplantation site in clinical study(unpublished data). In addition, they did not induce immune rejection in response to nonself lymphocytes in a mixed lymphocyte reaction(MLR)(unpublished data). The purpose of this study is to differentiate mouse preadipocytes following labeling into adipocytes to establish an animal model for allogenic transplantation. Preadipocytes isolated from inguinal and retroperitoneal fat pad of C57BL/6 mice were proliferated with growth medium by passage 3 and differentiated into adipocytes with different culture conditions after labeled with BrdU. At most suitable conditions, above 90% of preadipocytes were differentiated and BrdU labeling did not affect differentiation rate and function of differentiated adipocytes. These results demonstrate that BrdU-labeled adipocytes resulting from this in vitro differentiation protocol are useful for allogenic transplantation study.

• The Journal of Korean Obstetrics and Gynecology
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• v.23 no.2
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• pp.71-84
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• 2010

Purpose: In the theory of traditional medicine, Glenditsia spina(GS) can resolve carbuncle, relive swelling, dispel wind and destroy parasites. This study was designed to investigate the effects of GS on gene expression of ovarian tissue in polycystic ovary syndrome(PCOS) rats. Methods: In this experiment, female rats injected with a single dose of 2 mg estradiol valerate(EV) and GS was given for 5 weeks. The genetic profile for the effects on ovarian tissue in PCOS rats was measured using microarray technique, and the functional analysis on these genes was conducted. Results: 985 genes were increased in control and restored to normal level in GS group. (B), 733 genes were decreased in control group and restored to normal level in GS group. (F). Metabolic pathways related in B group genes were Graft-versus-host disease, Allograft rejection, Autoimmune thyroid disease, Cytokine-cytokine receptor interaction, Small cell lung cancer, Type I diabetes mellitus. Metabolic pathways related in F group genes were Antigen processing and present, Adipocytokine signalling pathway, Focal adhesion, ECM-receptor interaction, Pancreatic cancer, Notch signalling pathway, Tight junction. The network of total protein interactions was measured using cytoscape program, and some key molecules, such as c-Fos, c-Myc, ABL1 related in B group, MAPK8, RASA1, CALR related in F group that can be used for elucidation of therapeutical mechanism of medicine in future were identified. Conclusion: These results suggest possibility of GS as anti-cancer and anti-hyperplasia drug in PCOS. In addition, the present author also suggests that related mechanisms are involved in suppression of proto-oncogene such as c-Fos, c-Myc and ABL1, and in regulation of cell cycle such as RASA1.

• Biomolecules & Therapeutics
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• v.6 no.4
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• pp.389-394
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• 1998

Cyclosporine (CsA) is a major immunosuppressive drug used widely to prevent organ allograft rejection. fits potential organotoxicity by prolonged use is known to cause both direct tissue damage and indirect pharmacokinetic interactions with other drugs. This study was performed to determine the effect of nicardipine (NCP) on the pharmacokinetic parameters of CsA in Sprague-Dawley rats. Each rat was administered with CsA in saline-treated group or in NCP-treated group which was pretreated with NCP (5 mg/kg/12 hours, i.p.) for 6 days. The plasma CsA concentration were analyzed by reversed HPLC: UV system at 0.5, 1, 2, 4, 6, and 8 hours after bolus injection of CsA (10 mg/kg). Pharmacokinetic parameters (mean$\pm$ SD, n=7) such as initial plasma concentration (C(0)), mean residence time (MRT), steady-state volume of distribution (Vdss), terminal half-life (t$\frac{1}{2}$($\beta$)) and plasma clearance (CLp) of CsA in each groups (saline-group vs NCP-group) were determined as follows: C(0) (5.66$\pm$ 1.98 vs 17.98$\pm$2.36, p<0.01); Vdss (2.68$\pm$ 1.6 vs 0.94 $\pm$ 0.25, p<0.01); CLp (0.53 $\pm$0.18 vs 0.21 $\pm$0.06, p<0.01). Therefore, Our results indicate that nicardipine significantly affects the pharmacokinetic parameters of cyclosporme, especially C(0), Vdss, and CLp in NCP-treated group. We suggest that the significant pharmacokinetic interaction between cyclosporine and nicardipine should be considered and cyclosporine level should be closely monitored and dosage reduction made as necessary in clinical situation that was coadministered with CsA and NCP.

• Korean Journal of Transplantation
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• v.31 no.4
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• pp.170-176
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• 2017

We need to establish an informative guideline to increase inter-institutional and inter-observer reproducibility of renal transplant diagnosis, and to improve the diagnostic ability of pathologists in Korea. A first nation-wide survey for renal transplant pathology was conducted by Renal Pathology Study Group of the Korean Society of Pathologists in 2016, to provide the continued excellence in the transplantation pathology laboratory, and to improve the diagnostic ability for the best treatment of transplant patients. This survey revealed the significant variations in scale, work load and biopsy indications for the renal transplant pathology in various institutions in Korea. The Banff classification were used by all institutions for the diagnosis of renal transplant pathology, but different formats were used: most institutions (70%) used the "2013 Banff classification" while the others were using "2007 Banff classification" (20%) or even older formats. In daily diagnostic practice of the renal allografts, difficulties that pathologists encounter were quite diverse due to different environments they work in. Most respondents agreed that standardized diagnostic practice guidelines, regular education on renal transplant pathology and convenient ways of consultation are further needed. We are currently working toward the enhancement of the expertise of renal pathologists and to increase inter-institutional and inter-observer reproducibility by 1) development of a set of virtual slides of renal allograft biopsies for the training, 2) validation and gathering expert's consensus on the core variables of rejection diagnosis by using virtual slides, and 3) continued education by the developed virtual slide atlas.

• Asian-Australasian Journal of Animal Sciences
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• v.31 no.4
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• pp.595-606
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• 2018

Objective: The Fusarium mycotoxins of deoxynivalenol (DON) and zerolenone (ZEN) cause health hazards for both humans and farm animals. Therefore, the main intention of this study was to reveal DON and ZEN effects on the mRNA expression of pro-inflammatory cytokines and other immune related genes in the liver of piglets. Methods: In the present study, 15 six-week-old piglets were randomly assigned to the following three different dietary treatments for 4 weeks: control diet, diet containing 8 mg DON/kg feed, and diet containing 0.8 mg ZEN/kg feed. After 4 weeks, liver samples were collected and sequenced using RNA-Seq to investigate the effects of the mycotoxins on genes and gene networks associated with the immune systems of the piglets. Results: Our analysis identified a total of 249 differentially expressed genes (DEGs), which included 99 upregulated and 150 downregulated genes in both the DON and ZEN dietary treatment groups. After biological pathway analysis, the DEGs were determined to be significantly enriched in gene ontology terms associated with many biological pathways, including immune response and cellular and metabolic processes. Consistent with inflammatory stimulation due to the mycotoxin-contaminated diet, the following Kyoto encyclopedia of genes and genomes pathways, which were related to disease and immune responses, were found to be enriched in the DEGs: allograft rejection pathway, cell adhesion molecules, graft-versus-host disease, autoimmune thyroid disease (AITD), type I diabetes mellitus, human T-cell leukemia lymphoma virus infection, and viral carcinogenesis. Genome-wide expression analysis revealed that DON and ZEN treatments downregulated the expression of the majority of the DEGs that were associated with inflammatory cytokines (interleukin 10 receptor, beta, chemokine [C-X-C motif] ligand 9), proliferation (insulin-like growth factor 1, major facilitator superfamily domain containing 2A, insulin-like growth factor binding protein 2, lipase G, and salt inducible kinase 1), and other immune response networks (paired immunoglobulin-like type 2 receptor beta, Src-like-adaptor-1 [SLA1], SLA3, SLA5, SLA7, claudin 4, nicotinamide N-methyltransferase, thyrotropin-releasing hormone degrading enzyme, ubiquitin D, histone $H_2B$ type 1, and serum amyloid A). Conclusion: In summary, our results demonstrated that high concentrations DON and ZEN disrupt immune-related processes in the liver.