• Journal of Chest Surgery
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• v.30 no.10
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• pp.949-960
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• 1997

Background. Limited ischemic tolerance of the lung has remained one of the factors that limits the expansion of pulmonary transplantation as a treatment for end-stage pulmonary disease. 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. In this. study, we examined the efficacy of L DG solution in lung preservation longer than 20 hours by comparison with modified Euro-Collins solution. Iwethods. Thirty-(our adult mongrel dogs were divided into two groups. Donor lungs were flushed with LPDG solution(n=9) or modified Euro-Collins(MEC) solution(n=8) and stored for 24 hours at 1$0^{\circ}C$. All donor lungs were perfused through the pulmonary arteries with solutions containing prostaglandin El and verapamil. Left canine lung allotransplantations wereperformed. Assessment(hemodynamic indices and arterial blood gas analysis) of left implanted lung was made by occluding the right pulmonary artery for ten minutes using pulmonary artery Cuff. Assessment was repeated at the interval of 30 minutes, one hour, and two hours later after reperfusion and then chest X-ray, computed tomogram and lung perfusion scan were obtained. In survival dogs follow-up studies were done with assessment with chest X-ray, computed tomogram of the chest and lung perfusion scan on 7th day postoperatively. After preservation above 20 hours, pathological examinations for ultrastructural findings on right lung were performed in each group. Results. With respect to arterial oxygen tension, LPDG group was superior to MEC but there was no statistical significance for 2 hours after reperfusion. Mean pulmonary artery pressure was less increased(p < 0.05) and cardiac output higher(p <0.05) than MEC group until 2 hours after reperfusion. After 2 hours of reperfusion, both groups showed transplanted lung function deteriorated gradually. Perfusion scan of the transplanted lung in LPDG group showed better perfusion rate in immediate post-reperfusion, 3 days and 7 days later respectively but there was no statistical significance and corelation with PaO2 and computed tomoRravhic views. In scanning electron microscopy of pulmonary artery after preservation, LPDG group relatively shows less irregular protrusion of the inner surface of endothelial cell of poulmonary artery than MEC group. Conclusions, e concluded that LPDG solution can offer safe lung preservation above 20 hours with adequate immunosuppressive therapy and prevention of the infection.

• Journal of Chest Surgery
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• v.31 no.12
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• pp.1119-1126
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• 1998

Background: In this study, we investigated the early time course of expression of the major histocompatibility(MHC) antigens, intercellular adhesion molecule-1(ICAM-1), vascular cell adhesion molecule-1(VCAM-1), interleukin-6 and the histopathological changes in the coronary arteries of cardiac allografts exchanged between inbred mice strains that differ in one loci of class I major histocompatibility antigen (B10.BR to B10.A). Material and Method: No immunosuppressive therapy was used. Both allografts and the hearts of the recipients were harvested at 7(group 1, n=6), 15(group 2, n=6), 21(group 3, n=6), and 30(group 4, n=6) days after transplantation. They were examined by immunohistochemistry, microscopy and morphometry. All allografts had contractions at the time of harvest. Result: A strong MHC class I antigen expression was present on the endothelial and medial cells of the coronary arteries in group 1 and remained unchanged in the rest of the groups. However, MHC class II reactivity was none or very little at any time. Mild to moderate ICAM-1 expression was observed on the endothelial cells, but not on the medial cells at any time by 30 days. VCAM-1 expression was strong both on the endothelial and medial cells at any time. Moderate degree expression of interleukin-6 was observed from 7 to 30 day specimens. Histopathologically, percentage of affected vessels(vessels with intimal thickening) was less than 10 % in 7 day group and increased up to 50 % at 30 days. Mean percent narrowing of the lumen of the affected vessels revealed less than 20 % at 7 days and 40 % at 30 days. The area occupied by tropomyosin positive cells in the intimal lesion, graded from 0 to 3, showed gradual increase but remained between grade 0 to 1 by 30 days. Medial integrity was also well preserved at any time. Moderate perivascular mononuclear cell infiltration was observed at 7 days and it was progressively increased upto 30 days. Recipients' heart revealed no positive immunopathologic findings. Conclusion: In this study, the early time course of progression of the transplantation vasculopathy was demonstrated in the murine heterotopic heart transplant model.

• Tuberculosis and Respiratory Diseases
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• v.66 no.4
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• pp.274-279
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• 2009

Background: Uteroglobin (UG) is a secretary protein that has strong immunomodulatory properties, and which is synthesized in most epithelia including lung tissue. Overexpression of UG is associated with decreased expression of cyclooxygenase (COX)-2 and suppression of cancer cell growth. Indoleamine 2,3-dioxygenase (IDO) catalyzes tryptophan along the kynurenine pathway, and both the reduction in local tryptophan and the production of tryptophan metabolites contribute to the immunosuppressive effects of IDO. Methods: In this study, we investigated the pattern of expression of COX-2 and IDO, and the effect of UG transduction in the expression of COX-2 and IDO in several non-small cell lung cancer cell lines, especially A549. Results: Both COX-2 and IDO were constitutionally expressed in A549 and H460 cells, and was reduced by UG transduction. In A549 cells, the slightly increased expression of COX-2 and IDO with the instillation of interferon-gamma (IFN-$\gamma$) was reduced by UG transduction. However, the reduced expression of COX-2 and IDO by UG transduction was not increased with IFN-$\gamma$ instillation in A549 cells. In both the A549 COX-2 sense and the A549 COX-2 anti-sense small interfering RNA (siRNA)-transfected cells, IDO was expressed; expression was reduced by UG transduction, irrespective of the expression of COX-2. Conclusion: The results suggest that the anti-proliferative function of UG may be associated with the immune tolerance pathway of IDO, which is independent of the COX-2 pathway.

• Clinical and Experimental Pediatrics
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• v.50 no.7
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• pp.686-693
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• 2007

Purpose : Mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil (MMF), is a potent inhibitor of inosine-monophosphate dehydrogenase (IMPDH), a new immunosuppressive drug used. It was reported that MPA protected neurons after excitotoxic injury, induced apoptosis in microglial cells. However, the effects of MPA on hypoxic-ischemic (HI) brain injury has not been yet evaluated. Therefore, we examined whether MPA could be neuroprotective in perinatal HI brain injury using Rice-Vannucci model (in vivo) and in rat brain cortical cell culture induced by hypoxia (in vitro). Methods : Cortical cells were cultured using a 18-day-pregnant Sprague-Dawley (SD) rats and incubated in 1% $O_2$ incubator for hypoxia. MPA ($10{\mu}g/mL$) before or after a HI insult was treated. Seven-day-old SD rat pups were subjected to left carotid occlusion followed by 2 hours of hypoxic exposure (8% $O_2$). MPA (10 mg/kg) before or after a HI insult were administrated intraperitoneally. Apoptosis was measured using western blot and real-time PCR for Bcl-2, Bax, caspase-3. Results : H&E stain revealed increased brain volume in the MPA-treated group in vivo animal model of neonatal HI brain injury. Western blot and real-time PCR showed the expression of caspase-3 and Bax/Bcl-2 were decreased in the MPA-treated group In in vitro and in vivo model of perinatal HI brain injury, Conclusion : These results may suggest that the administration of MPA before HI insult could significantly protect against perinatal HI brain injury via anti-apoptotic mechanisms, which offers the possibility of MPA application for the treatment of neonatal HI encephalopathy.

• The Journal of the Korean Society for Microbiology
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• v.21 no.1
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• pp.133-144
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• 1986

This study was undertaken to assess the effect of ginseng administration on T lymphocyte induced local xenogenic graft-versus-host(GVM) reactions which were induced with thymocyte, spleen cell and lymph node cell of ICR mice. Mice received daily 10mg of 70% alcohol ginseng extract oral1y for 100days and control mice remained untreated for the same period of time. The cells from donor mice were injected intradermally into the closely shaven abdominal skin of Sprague-Dawley rats for GVH tests. The thymocyte from control(ginseng-untreated) mice showed a negative local GVH reaction, whereas thymocyte from experimental(ginseng-treated) mice showed a positive reaction with the rate of 17.4%. When spleen cells were injected, the incidence of positive local GVH reaction was 66.7% among ginseng-treated mice, as opposed to incidence of 45.5% of positive local GVH reaction among control mice. The incidence of positive local GVH reaction of the lymph node cells when injected into a recipient was 71.4% among ginseng-treated mice as compared with that of 18.9% among control mice. The relationship between spleen cell inoculum and intensity of the local GVH reaction was assessed in ginseng-untreated mice. The intensity of GVH reaction clearly appears to be dose related. In ginseng-treated mice, a minimum of $1{\times}10^7$ spleen cell was required for production of positive local GVH reaction with almost linear relationship up to an inoculum of $5{\times}10^8$ cells. In control mice, however, a minimum of $1{\times}10^8$ spleen cells was required for positive GVH reaction. These results strongly suggest that the ginseng administration augments significantly the local xenogenic GVH reaction which was used to assess T lymphocyte function and immunocompetence of mice and in addition to this, these results appear to support previous suggestions that the local GVH reaction consitutes a qualitative test of the functional activity of T lymphocytes. These results may be the first to induce local GVH reaction, employing rats as recipient and mice as donor. This study was also desingned to investigate some of the effects of ginseng extract on lymphocyte-macrophage interactions. This was accomplished by in vitro quantification of 1) migratory inhibitory factor(MIF) synthetic capacity of splenic lymphocytes in mice previously primed with ginseng 2) MIF responsiveness of mouse peritoneal macrophages or chicken peripheral leucocytes under the presence of ginseng extract 3) migration ability of chicken peripheral leucocytes by direct stimulation of ginseng extract or ginseng saponin and 4) immunosuppressive effects of immunosuppressants such as cyclophosphamide, cyclosporin A or dexamethasone. Mice divided equally into the ginseng and the saline groups, which received intraperitoneally daily 0.2ml of ginseng absolute alcohol-extract(5mg/ml) and same amount of saline for 15 days, respectively. The cellular immune responsiveness of these mice was assayed 15 days after ginseng pretreatment. Splenic lymphocytes of mice treated with ginseng, when stimulated with sensitized specific-antigen such as sheep red blood cells or toxoplasmin, or with polyclonal activator concanavalin A, produced significantly more MIF than those of control saline group. MIF responsiveness of normal mouse macrophages was significantly augmented when assayed under the presence of ginseng extract (1mg/ml). The migratory ability of normal chicken leucocytes in the absence of MIF was significantly decreased by the stimulation of ginseng extract alone. MIF response was significantly decreased by immunosuppressants and this impaired response was not restored by ginseng pretreatment. This study was additionally performed to evaluate the effect of ginseng on the expulsion of adult Trichinella spiralis in mice. ICR mice were infected experimentally by esophageal incubation of 300 T. spiralis infective muscle larvae prepared by acid-pepsin digestion of infected mice. and received oral administration of 70% alcohol ginseng extract(10mg/mouse/day) for the indicated days plus 4 days before infection. At various times after infection, the number of adult T. spiralis worms in small intestines was determined. Interestingly, ginseng-treatment was accompanied by accelerated expulson of T. spiralis. These results led to the conclusion that Panax ginseng caused some enhancing effect on GVH reaction, macrophage migration inhibition reaction and expulsion of T. spiralis. In addition these results suggested that the mechanisms responsible for this enhancement of ginseng may be chiefly or partially due to nonspecific stimulation of cell-mediated immune response.

• Journal of Food Hygiene and Safety
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• v.13 no.2
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• pp.121-128
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• 1998

Ochratoxin A (OA) is a mycotoxin produced by Aspergillus ochraceus as well as other molds. It is a natural contaminant of mouldy food and feed. OA has a number of toxic effects, the most prominant being nephrotoxicity. Futhermore, OA is immunosuppressive, genotoxic, teratogenic and carcinogenic. OA inhibits protein synthesis by competition with phenylalanine in the phenylalanine-tRNA aminoacylation reaction. Recently, lipid peroxidation induced by OA has been reported, indicating that the lesion induced by this mycotoxin could be also related to oxidative pathway. Since it seems impossible to avoid contamination of foodstuffs by toxigenic fungi, detoxification and detoxication of OA are needed. In this study we investigated the protective effects of aspartame (Asp), phenylalanine (Phe), polyphenol 70S (PP) and aloe extract (AE) on the nephrotoxicity induced by subacute exposure to the OA. Asp and Phe are structural analogues of OA. PP, an ingredient of Green Tea and AE have been known as antioxidant and radical scavenger. Phe (40 mg/kg, i.p.) and Asp (25 mg/kg, p.o.) were administered to Sprague-Dawley rats simultaneously with OA (2.0 mg/kg, p.o.) for 2 weeks. PP (200 mg/kg, p.o.) and AE (50 mg/kg, i.v.) were pretreated before administration of OA, for 2 weeks and 3 days, respectively. Using enzymuria, BUN level, creatinemia and histophathologic examination as indices of renal damage, we observed that all of four compounds prevented the nephrotoxic effects induced by OA. It seems that structural analogues of OA such as Asp and Phe have better protective effect on the nephrotoxicity of OA than antioxidants. These results indicate that 1) formation of free radical and lipid peroxidation are likely to be involved in the nephrotoxicity of OA in vivo, 2) Asp, PP and AE might be used for prevention of renal lesions in cases of ochratoxicosis.

• Tuberculosis and Respiratory Diseases
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• v.53 no.3
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• pp.309-318
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• 2002

Background : Usual interstitial pneumonia (UIP) is a fatal progressive fibrotic disorder of the lung with unknown etiology and characterized by a poor response to conventional immunosuppressive therapy. The histologic hallmark of UIP is parchy distribution of subpleural fibrosis and fibroblastic foci(FBF) with interposed normal appearing lung. Because FBF is a collection of actively proliferating myofibroblasts, it can be a marker of activity and prognosis of UIP. However, there were contradictory reports about the correlation between the degree of FBF and survival. Therefore we performed this study to investigate the value of FBF as prognostic marker of UIP. Methods : This was a retrospective study on the 46 patients(M:F=33:13, mean age:$59{\pm}12$ years) with UIP diagnosed by the surgical lung biopsy at the Asan Medical Center, Seoul, Korea between 1990 and 2000 and had follow-up of more than a year. All the biopsy specimens were reevaluated and diagnosed as UIP according to the ATS/ERS classification. Semiquantitative grading of FBF(absent, 0; mild 1; moderate 2; marked 3) by the experienced pathologists who did not know the clinical findings were compared to the clinical data and the follow up course. Results : Thirteen patients(28.2%) died of UIP progression during the study period. The median survival time of all the subjects was 26 months after the biopsy. At the univariate analysis, FVC, $D_Lco$, smoking history and the grade of FBF were significantly related to the survial. The survival was longer in subjects with lesser degrees of FBF, higher DLco, higher FVC and history of smoking. However the multivariate analysis with Cox regression test showed the extent of FBF was the only independent prognostic marker of UIP. Conclusion : These data suggested that the extent of FBF on the surgical lung biopsy can be used as a prognostic marker of UIP.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.5 no.2
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• pp.150-157
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• 2002

Purpose: As the incidence of non-typhoidal salmonella strains resistant to antibiotics has been increased, we attempted to investigate clinical aspects of non-typhoidal salmonella gastroenteritis and antibiotics resistance. Methods: From January 2000 to June 2002, 99 children with positive stool culture of non-typhoidal salmonella were studied about clinical features, the incidence of antibiotics and multi-drug resistance and the difference of incidence of antibiotics resistance according to immune status. Results: There were 66 males and 33 females. The majority of them were under 5 years of age (71%). 25 children were immunocompromised due to chemotherapy, steroid or immunosuppressive treatment. Serogroup D was the most common isolates (65%) followed by B (16%), C (8%) and E (8%). Resistance rate of 30% to ampicillin, 12% to chloramphenicol, 20% to trimethoprim-sulfamethoxazole (TMP-SMX), 11% to cefotaxime and 8% to cefixime were obtained. All isolates were susceptible to ciprofloxacine. Resistance rate to cefotaxime and cefixime in immunocompromised patients was 24% and 14.3% respectively, which were significantly higher compared to that in immunocompetent patients (6.8%, 5.6%, p<0.05). 11 isolates were resistant to three or more antibiotics. The incidence of multi-drug resistant isolates was significantly higher in immunocompromised patients (24%) than that of immunocompetent patients (6.8%). Conclusion: Because of the high prevalence of non-typhoidal salmonella strains resistant to ampicillin, chloramphenicol and TMP-SMX, third-generation cephalosporin might be the treatment of choice in non-typhoidal salmonella gastroenteritis. In particular, antibiotics should be carefully selected in immunocompromised patients because non-typhoidal salmonellas from them showed the higher incidence of antibiotic resistance and multi-drug resistance.

• Childhood Kidney Diseases
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• v.7 no.2
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• pp.133-141
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• 2003

Purpose : Idiopathic Membranous Nephropathy(IMN) is a rare renal disease in children. To help better understanding of its clinical course and treatment strategies, we reviewed the clinical manifestations and pathological findings of children with IMN. Methods : Among 58 cases with MN, from 1977 to 2003, 42(72.4%) were hepatitis B virus (HBV) associated and 16(27.6%), 6 males and 10 females, were idiopathic. All cases diagnosed aster 2000 were IMN. Several clinicopathological findings(sex, onset age, proteinuria, serum albumin, cholesterol, creatinine clearance, tubulointerstitial changes, glomerular sclerosis, hypertension, renal vein thrombosis, the use of ACE inhibitor, and immunosuppressive therapy) were compared between the remission and the non-remission group of the patients with IMN. Results : The median onset age was 13.4 years. Clinical manifestations were nephrotic syn-drome(7 cases, 43.8%), gross hematuria(5 cases, 31.3%) and microscopic hematuria with proteinuria(3 cases, 18.8%). Hypertension, hypocalcemic tetany and renal vein thrombosis were accompanied in 2, 1 and 2 cases, respectively. In addition to the typical findings of MN, the kidney biopsies showed segmental sclerosis(5 cases, 31.3%) or global sclerosis(6 cases, 37.5 %), diffuse crescents(1 case), and mild(11 cases, 68.7%) or moderate tubulointerstitial changes(3 cases, 18.8%). Thirteen cases(86.7%) received oral steroid. Among them 2 cases received cyclophophamide and 1 received cyclosporin as well. Ten cases(62.5%) received ACE inhibitors. In the patients followed up, 7 cases(46.7%) became free from proteinuria (remission group) while 8(53.3%) presented continous proteinuria (non-remission group), two (13.3%) of which progressed to renal failure. Clinicopathological findings showed no significant differences between the two groups. Conclusion : With HBV vaccination, HBV associated MN decreased markedly and IMN has taken up most of MN in children. For better understanding of this rare disease, a prospective multicenter study of the clinical course and treatment strategies should be done.

• Journal of Life Science
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• v.33 no.2
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• pp.149-157
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• 2023

Transforming growth factor-β (TGF-β) is a multifunctional cytokine that affects not only the survival and growth of cancer cells but also the activity of immune cells. Although it has been generally accepted that cancer cell-derived TGF-β could promote the survival and growth of early cancer cells and have immunosuppressive roles, it has been known that TGF-β has differential effects according to the type or stage of cancer cells. Therefore, it is hard to clearly define its role in cancer progression and immune responses. This study investigated the effects of TGF-β signaling on the expression of five NKG2D ligands and the NK cell-mediated anticancer immune response in the primary colon cancer cell line KM12C and its two metastatic cell lines, KM12SM and KM12L4A. At the surface protein level, exogenous TGF-β decreased the expression of MICA, MICB, ULBP1, and ULBP2, and galunisertib increased the expression of MICA, MIAB, ULBP1, ULBP2, and ULBP3 in KM12C. However, KM12SM and KM12L4A showed no significant changes in the expression of NKG2DLs after treatment with TGF-β or galunisertib. TGF-β signaling inhibition via galunisertib improved the NK cell-mediated anticancer immune response against KM12C but did not show a significant response to KM12SM and KM12L4A. Therefore, the suppression of TGF-β signaling could improve the NK cell-mediated anticancer immune response against KM12C. However, an increase in NKG2DLs expression and an enhanced NK cell-mediated cancer immune response is hard to expect due to the alteration of TGF-β signaling in KM12SM and KM12L4A.