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New Immunosuppressive Agent: The Effects of an Antagonist IL-15/IgG Fusion Protein.

Yon Su KIM ; Dong Wan CHAE ; Terry B STROM

The Journal of the Korean Society for Transplantation.1998;12(2):173-182.

Owing to shared receptor components, the biological activities of IL-15 are similar to those of IL-2. However the patterns of tissue expression of IL-2/IL-2R alpha and IL-15/IL-15R differ. The development of agents targeting the receptor and signaling elements of IL-15 may provide a new perspective for treatment of diseases associated with expression of IL-15/IL-15R. We designed, genetically constructed and expressed a receptor site specific IL-15 antagonist by mutating glutamine residue within the C-terminus of IL-15 to aspartic acid and linked this mutant IL-15 to murine IgG2a. These IL-15 mutant/IgG fusion proteins specifically bound to the IL-15R, and competitively inhibited IL-15 triggered cell proliferation. We examined the immunosuppressive activity of this agent because of prolonged half-life and the potential for destruction of IL-15R+ leukocytes. The IL-15 mutant/IgG proteins markedly attenuated antigen specific DTH responses in Balb-c mice comparing with the responses in the mice treated with control IgG. Intraperitoneal injection of this mutant protein enhanced the acceptance of crude islet allograft from DBA/2J (H-2(d)) to B6AF1 (H-2(b/d),k) rendered diabetic by injection of streptozotocin (15 vs >65 days; control IgG vs IL-15 mutant/IgG treatment, mean survival time, 8 mice in each group). These findings suggest that i) IL-15/IL-15R+ cells are crucial to these T-cell dependent immune responses, and ii) treatment with IL-15 mutant/IgG protein may ameliorate T-cell dependent immune/inflammatory diseases.
Allografts ; Animals ; Aspartic Acid ; Cell Proliferation ; Glutamine ; Half-Life ; Immunoglobulin G ; Injections, Intraperitoneal ; Interleukin-15 ; Interleukin-2 ; Leukocytes ; Mice ; Mutant Proteins ; Streptozocin ; Survival Rate ; T-Lymphocytes

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24-hour Lung Preservation Study in a Canine Sequential Bilateral Lung Tranplant Model.

Chang Kwon PARK ; Kun Young KWON ; Suk Kil ZEON ; Jung Sik KIM ; Jae Hoon BAE

The Journal of the Korean Society for Transplantation.1998;12(2):161-172.

BACKGROUND: Numerous studies on safe, long term preservation for lung transplantation has been performed for the purpose of developing ideal preservation solution with extracellular type or intracellular type solutions and overcoming the shortage of donors. We prepared LPDG (low potassium dextran glucose)solution for lung preservation study. In this study we examined the efficacy of LPDG solution in 24-hour lung preservation by using of a sequential bilateral canine lung allotransplant model. METHOD: Seven bilateral lung transplant procedures were performed using weight-matched pairs (23 to 26 Kg) of adult mongrel dogs. The donor lungs were flushed with LPDG solution and maintained hyperinflated with 100% oxygen at 10oC for a planned ischemic time of 24 hours for the lung implanted first. After sequential bilateral lung transplantation, dogs were maintained on a ventilator for 3 hours: arterial oxygen tension, pulmonary artery pressure, and pulmonary vascular resistance were determined in the recipients hourly after bilateral reperfusion and compared with pretransplant-recipient values, which used as controls. After 2 hours of reperfusion, the chest X-ray, computed tomogram and lung perfusion scan were performed for assessment of early graft lung function. And pathological examinations for ultrastructural findings of alveolar structure and endothelial structure of pulmonary artery were performed. RESULTS: Five dogs of seven experiments had successfully finished the whole assessments after bilateral reperfusion for three hours. Arterial oxygen tension in the recipients was markedly decreased in immediate reperfusion period but gradually recovered after reperfusion for three hours. The pulmonary artery and pulmonary vascular resistance showed singificant elevation (p<0.05 versus control values) but also recovered after reperfusion for three hours (p<0.05 versus immediate period value). The ultrastructural findings of alveolar structure and endothelial structure of pulmonary artery showed reversible mild injury in 24 hours of lung preservation and reperfusion. CONCLUSIONS: The present study suggests that LPDG solution provide excellent preservation and transplanted lung function after 24 hours of preservation in a canine model in which the dog is completely dependent on the fuction of transplanted lung.
Adult ; Animals ; Dextrans ; Dogs ; Humans ; Lung Transplantation ; Lung* ; Oxygen ; Perfusion ; Potassium ; Pulmonary Artery ; Reperfusion ; Thorax ; Tissue Donors ; Transplants ; Vascular Resistance ; Ventilators, Mechanical

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Induction of Immune Tolerance after Transplantation.

Oh Jung KWON

The Journal of the Korean Society for Transplantation.1998;12(2):145-150.

No abstract available.
Immune Tolerance*

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Immunology of Acute Rejection.

Su Kil PARK

The Journal of the Korean Society for Transplantation.1998;12(2):135-144.

No abstract available.
Allergy and Immunology*

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Clinical Application of Renal Autotransplantation in Renovascular and Urologic Disease: 21 Cases.

Tae Hyun KIM ; Kwan Tae PACK ; Young Hoon KIM ; Song Chul KIM ; Duck Jong HAN ; Tae Won KWON

The Journal of the Korean Society for Transplantation.2008;22(2):214-219.

BACKGROUND: Renal autotransplantation is a kidney preserving procedure in various clinical situations otherwise requiring nephrectomy or renovascular disease that can not be treated by intervention. The purpose of this study is to report our experiences of renal autotransplantation. METHODS: A total 21 patients, 9 male and 12 females, underwent renal autotransplantation from May 1995 to July 2008 at our institution and were reviewed retrospectively by medical records. RESULTS: The mean age of the patients was 46.9 years (21~63). The indications for renal autotransplantation were 6 cases of renal artery aneurysms (28.5%) including 1 renal allograft aneurysm, 6 ureteral obstructions (28.5%), 4 renovascular hypertensions (19%), 2 renal cell carcinomas (9.5%), 2 ureteral cancers (9.5%) and others. The mean operative time was 409.2 minutes (145~689) and mean cold ischemic time was 85.4 min (11~215 min). Renal artery was anastomosed to internal iliac artery in 81% and to external iliac artery in 19%. All kidneys were preserved successfully after removal of lesions and renal artery reconstruction. There were no differences in pre- and post- operative creatinine levels and creatinine clearance. The mean follow up duration was 2.1 years (0.1~11.3) and 1 patient died from the recurrence of ureteral cancer 9 months after operation. CONCLUSIONS: With the advance of micro-surgical technique and standardization of kidney transplantation technique, possibility of renal preservation with renal autotransplantation has increased more than before. Therefore, renal autotransplantation should be considered as one of the treatment options and performed in appropriately selected patients.
Aneurysm ; Carcinoma, Renal Cell ; Cold Ischemia ; Creatinine ; Female ; Follow-Up Studies ; Humans ; Iliac Artery ; Kidney ; Kidney Transplantation ; Male ; Medical Records ; Microsurgery ; Nephrectomy ; Operative Time ; Recurrence ; Renal Artery ; Retrospective Studies ; Transplantation, Homologous ; Ureteral Neoplasms ; Ureteral Obstruction

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Factors Affecting the Result of Kidney Retransplantation.

Sung Hyung LEE ; Yung Min SEO ; Hyoung Tae KIM ; Won Hyun CHO ; Eun Ah HWANG ; Sung Yeop HAN ; Sung Bae PARK ; Hyun Cheol KIM ; Shin Huen JOO

The Journal of the Korean Society for Transplantation.2008;22(2):209-213.

BACKGROUND: As the result of renal transplantation improving, also increasing the number of graft failure which will be a candidate for second renal transplantation. The purpose of this study is to evaluate the factors that influence the survival of retransplanted kidney. METHODS: Among 775 renal transplantations that have been performed in Dongsan Medical Center until August 2007, 225 cases were failed their graft function and 59 of them were retransplanted during their follow up period. Graft survival of retransplanted kidney was compared with primary renal transplantation and factors that affecting the survival of kidney retransplantation were evaluated. RESULTS: Main causes of graft failure of first kidney transplantation were chronic rejection, followed by recurrence of original disease of recipient and acute vascular rejection. Mean survival time was 72.6 months (15 days~161 months). One and 5 years graft survivals were 94.6%, 90.7%, and patient survivals were 100.0%, 97.8%, respectively. Among the factors which showed significance in univariate analysis, short interval between failure of first transplantation and retransplantation, and graft failure due to chronic rejection were statistically significant unfavorable factors for survival of retransplanted kidney. CONCLUSIONS: Kidney retransplantation showed similar graft and patient survival compare to the first one. However, retransplantation should be performed after enough time after graft failure and should be cautious in a patient who lost their graft due to chronic rejection.
Follow-Up Studies ; Graft Survival ; Humans ; Kidney ; Kidney Transplantation ; Recurrence ; Rejection (Psychology) ; Survival Rate ; Transplants

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Epidemiological Data on Antibiotic-resistant Bacteria Isolated in Liver Transplant Recipients.

Youn Jeong KIM ; Sang Il KIM ; Sun Hee KO ; Yoon Hee JEON ; In Sung MOON ; Dong Goo KIM ; Myung Duk LEE ; Moon Won KANG

The Journal of the Korean Society for Transplantation.2008;22(2):203-208.

BACKGROUND: Post-transplant infections by antibiotic-resistant bacteria (ARB) are increasing in prevalence because of the wide use of broad-spectrum antibiotics. At our center, the perioperative prophylaxis for liver transplant recipients consistes of cefoperazone/sulbactam and ampicillin. When the recipient develops signs of infection, the initial antibiotics are empirically replaced with meropenem and vancomycin. We analyzed the epidemiology of ARB to assess the appropriateness of replacing empirical antibiotics during the first month after liver transplantation. METHODS: We reviewed 88 patients who had undergone living donor liver transplant between January 2006 and September 2007. RESULTS: Two hundred and seventy-six strains of bacteria were microbiologically documented in 75 liver transplant recipients. The most common bacteria was Staphylocococcus aureus (27%), followed by coagulase-negative staphylococci (CNS, 20%), Enterococcus species (18%) and Klebsiella species (7%). Our data on the resistance pattern showed that 87.8% and 71.4% of the S. aureus and CNS were resistant to methicillin, respectively; 88% of the Enterococcus species were resistant to ampicillin and 24% to vancomycin; and 62% of all enteric gram-negative bacilli (GNB) were resistant to 3rd generation cephalosporins. No strains of meropenem-resistant GNB were detected. Only one glucose non-fermentative GNB was resistant to all antibiotics except aminoglyco sides and colistin. CONCLUSIONS: Mainly methicillin-resistant gram- positive bacterial strains, including S. aureus and CNS, can colonize in early period after transplantation. According to the epidemiologic data on the high prevalence of antibiotic-resistant organisms, the empirical treatment regimen at our center is considered as appropriate. However, shifting down to less-broad-spectrum antibiotics after the pathogens are confirmed is essential to lowering the rate of ARB.
Ampicillin ; Anti-Bacterial Agents ; Bacteria ; Cephalosporins ; Colistin ; Colon ; Enterococcus ; Glucose ; Humans ; Klebsiella ; Liver ; Liver Transplantation ; Living Donors ; Methicillin ; Methicillin Resistance ; Prevalence ; Thienamycins ; Transplants ; Vancomycin

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Steroid Withdrawal in Renal Transplantation.

Joong Kyung KIM

The Journal of the Korean Society for Transplantation.2008;22(2):197-202.

Steroid is a critical component of immunosuppressive regimen. Unfortunately, steroid is associated with numerous adverse effects including diabetes, hypertension, hyperlipidemia, osteoporosis, sodium retention, and avascular necrosis. These adverse effects have prompted trials of steroid withdrawal with introduction of potent immunosuppressive agents in renal transplantation. Although late steroid withdrawal raised acute rejection rate compared with early steroid withdrawal, results of recent trials that used diverse steroid withdrawal protocols suggest good short and long term graft outcomes. But, in patients survival, patients with steroid withdrawal is similar to patients administered steroid. This review summarizes usefulness according to timing of steroid withdrawal and re-exams benefits of steroid withdrawal in renal transplantation.
Humans ; Hyperlipidemias ; Hypertension ; Immunosuppressive Agents ; Kidney Transplantation ; Necrosis ; Osteoporosis ; Rejection (Psychology) ; Retention (Psychology) ; Sodium ; Transplants

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Adipose Tissue Derived Mesenchymal Stem Cells.

Jin Sup JUNG

The Journal of the Korean Society for Transplantation.2008;22(2):183-196.

Mesenchymal stem cells (MSCs) are a heterogeneous population of cells that proliferate in vitro as plastic-adherent cells, have fibroblast-like morphology, form colonies in vitro and can differentiate into bone, cartilage and fat cells. Recent studies have shown that MSCs can be differentiated into nonmesordermal lineages. Although MSCs can be isolated from every type of connective tissues, the abundance, the easy and repeatable access to subcutaneous adipose tissue and the simple isolation procedures indicate that adipose tissue can be a preferable candidate in MSC isolation for clinical application. Therefore, in this review, the isolation, characterization, preclinical and clinical application, and the mechanisms and future roles of ADSC in cell therapy are discussed.
Adipocytes ; Adipose Tissue ; Cartilage ; Connective Tissue ; Mesenchymal Stromal Cells ; Subcutaneous Fat ; Tissue Therapy

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CMV Disease.

Dong Wan CHAE

The Journal of the Korean Society for Transplantation.2008;22(2):177-182.

Cytomegalovirus, one of beta human herpes virus, cause significant morbidity and mortality in the renal transplant patients via direct and indirect effects of viral infection, which is defined as the presence of CMV in the host. CMV disease in renal transplant recipients is the result of direct cytopathic effects of proliferating virus and manifest as CMV syndrome and/or tissue-invasive disease. Indirect effects of CMV infection are caused by the long-term immuological responses of host to existing CMV virus and manifest as increased occurrence of acute rejection, predisposition to opportunistic bacterial, viral or fungal infection, development of lymphoproliferative disease, atheroscrelosis and posttransplantation diabets mellitus and increase in all-cause mortality in renal transplant recipients. Because the development and severity of CMV disease depends on the amount of virus present in renal transplant recipients, the quantitative tests for viral load such as antigenemia assay and molecular amplification of CMV are useful for diagnosis of CMV disease and serve as a guidance in prophylaxis and treatment of CMV disease in renal transplant recipients. CMV prophylaxis is indicated in high-risk patients such as CMV negative recipients of CMV positive donor or CMV positive recipients who have received anti-lymphocyte antibodies as induction therapy or treatment of acute rejection. Universal prophylaxis and pre-emptive treatment using mainly ganciclovir are main strategies and have their own advantages and disadvantages. Recently long-term prophylaxis up to 24 weeks is favored to prevent the occurrence of CMV disease after discontinuation of prophylaxis. Although intravenous ganciclovir is effective standard treatment of tissue-invasive CMV disease in renal transplant recipients, emergence of ganciclovir-resistant CMV strain as a result of mutation of CMV genes involved in viral metabolism of CMV such as UL97 or UL54 is reported in renal transplant recipients.
Antibodies ; Collodion ; Cytomegalovirus ; Ganciclovir ; Humans ; Kidney Transplantation ; Rejection (Psychology) ; Sprains and Strains ; Tissue Donors ; Transplants ; Viral Load ; Viruses

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