• Journal of Chest Surgery
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• v.32 no.3
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• pp.215-223
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• 1999

Background: The replacement of the narrowed long-segment trachea with various prosthetic materials or tissue grafts remains a difficult and unsolved surgical problem. Homologous cryopreserved tracheal transplantation has been considered to treat the irreversibly-damaged organs, such as in the lung or heart transplantation and also to overcome the limited supply of donor organs. We examined the morphological changes and the immunosuppressive effects of the cryopreserved trachea after the heterotopic transplantation in the rats. Material and Method: Sixty tracheal segments harvested from 30 donor Wistar rats were heterotopically implanted into the peritoneal cavity of 20 recipient Wistar rats and 40 Sprague Dawley rats. The 60 recipient rats were divided into 6 groups(10 rats/ group). In groups I, II, and III, 30 tracheal segments were implanted immediately after the harvesting and in groups IV, V, and VI, the segments were implanted 28 days after the cryopreservation. Groups I and IV were Wistar syngeneic controls. Groups II and V were Sprague Dawley recipients receiving no immunosuppression and Groups III and VI, were Sprague Dawley recipients receiving immunosuppressive agents. At 28 days all rats were sacrificed and the tracheal segments were evaluated grossly and histologically. Result: Immunosuppression of the tracheal segments had a significant influence on the changes of the tracheal lumen and tracheal epithelial cells, irrespective of the cryopreservation of the trachea(p<0.001). In groups III and VI receiving immunosuppressive agents, the tracheal lumen was patent and the normal epithelial cells were observed, however in the other groups not receiving the immunosuppressive agents, there were almost luminal obliteration by the proliferation of the fibrous tissues and a loss of the epithelial cells, the findings were similar to those in the case of obliterative bronchiolitis after a lung and a heart-lung transplantation. Conclusion: With the appropriate immunosuppressive agents, the lumen and the respiratory epithelium of the transplanted tracheal segment were well preserved, even after the cryopreservation of the tracheal segment, which shows the possibility of the long-term preservation and homologous transplantation of the trachea. But fibroproliferative obliteration of the tracheal lumen and the loss of the normal respiratory epithelial cells, characteristic findings of obliterative bronchiolitis, were observed in the groups without the immunosuppression. This experiment using the rat trachea may be useful in studying the pathogenesis, treatment, and prevention of obliterative bronchiolitis after a lung and a heart-lung transplantation.

• Korean Journal of Microbiology
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• v.39 no.4
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• pp.235-241
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• 2003

We have previously demonstrated that intracellular expression of an RNA aptamer termed RRE40, which was selected in vitro to bind HIV Rev 10-fold much tighter than wild-type RRE, efficiently protected human CD4+ T cell line, CEM, from HIV-1. In this study, to evaluate the efficacy of the RRE40 RNA in clinical settings, polyclonal CD4+ peripheral blood lymphocytes (PBLs) were transduced with retroviral vectors expressing RRE40 decoy RNA and then challenged with clinical isolates of HIV-1. In contrast to the control cells transduced with vectors expressing control tRNA, intracellular expression of RRE40 RNA more effectively inhibited HIV-1 replication in CD4+ PBLs. However, transient and diminished inhibition, rather than complete inhibition, of HIV-1 replication in PBLs expressing RRE40 decoys have been observed. These results suggest that RRE40 decoy RNA would be useful to inhibit HIV-1 replication in cells. However, development of more efficient gene transfer protocols and/or more effective decoy RNAs would be needed to apply RNA decoy to modulate HIV-1 patient.

• Journal of Life Science
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• v.24 no.12
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• pp.1356-1363
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• 2014

Ghrelin is a 28 amino acid orexigenic peptide hormone that is secreted predominantly by tX/A cells in the stomach, and it plays a major role in energy homeostasis. Activated ghrelin has an n-octanoyl group covalently linked to the hydroxyl group of the Ser3 residue, which is critical for its binding to the G-protein coupled growth hormone secretagogue receptor-1a (GHS-R1a). According to recent reports, both ghrelin and its receptor, GHS-R1a, are expressed by a variety of immune cells, including T- and B-lymphocytes, monocytes, and dendritic cells, and ghrelin stimulation of leukocytes provides a potent immunomodulatory signal controlling systemic and age-associated inflammation and thymic involution. Here, we report that ghrelin protected murine thymocytes from dexamethasone (DEX)-induced cell death both in vivo and in vitro. Subsequently, we explored the molecular mechanisms of the antiapoptotic effect of ghrelin. According to our experiments, ghrelin inhibited the expression of proapoptotic proteins via the regulation of glucocorticoid receptor (GR) phosphorylation. As a result, ghrelin inhibited the proapoptotic activation of proteins, such as Caspase-3, PARP, and Bim. These data suggest that ghrelin, through GHS-R, inhibits the pathway to apoptosis by regulation of the proapoptotic protein activation signal pathway. They provide evidence that blocking apoptosis is an essential function of ghrelin during the development of thymocytes.

• Childhood Kidney Diseases
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• v.9 no.2
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• pp.231-236
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• 2005

Juvenile rheumatoid arthritis(JRA) is the most common major connective tissue disease in children. Renal involvement in JRA is rare. Among the renal lesions that have been reported in JRA, amyloidosis and drug-induced nephropathy are the most common. Crescentic glomerulonephritis in JRA has rarely been reported. We report a case of ANCA-associated pauci-immune crescentic glomerulonephritis in JRA. The patient was a 15-year old boy with a 3-year history of JRA. He presented with gross hematuria, proteinuria, positive p-ANCA and elevation of BUN and creatinine. Pathologic findings revealed focal necrotizing and crescentic glomerulonephritis. There were no significant immunoglobulin or complement deposits. His renal function recovered after intravenous methylprednisolone pulse therapy and oral steroid use. In Korea, this is the first reported case of pauci-immune crescentic glomerulonephritis in JRA. (J Korean Soc Pediatr Nephrol 2005;9:231-236)

• Annals of Clinical Neurophysiology
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• v.14 no.2
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• pp.76-79
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• 2012

Statin is commonly used for lowering cholesterols and can be myotoxic to cause drug-induced necrotizing myopathy. Statin-induced myopathy ranges from asymptomatic hyperCKemia to lethal rhabdomyolysis but is usually reversed by withdrawal of causative drugs. The patient in this study presented with statin-induced necrotizing myopathy, which was finally improved with immunosuppressive therapy, but not just with drug withdrawal. Since statin can induce myopathy through autoimmune processes, we should consider using immunomodulating agents in cases with statin-induced myopathy, which is refractory to drug withdrawal.

• Journal of Chest Surgery
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• v.32 no.1
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• pp.1-4
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• 1999

Background: The transplantation of organs between phylogenetically disparate or harmonious species has invariably failed due to the occurrence of hyperacute rejection or accerelated acute rejection. But, concordant cardiac xenograft offer us an opportunity to study xenotransplantation in the absence of hyperacute rejection. Current therapeutics for the prolongation of survival of rodent concordant xenotransplantation are not ideal with many regimens having a high mortality rate. Cyclosporine A & Mycophenolate Mofetil are new immunosuppresive agent which has been shown to be effective at prolonging survival of allograft, as purine synthesis inhibitor. Material and Method: We used white mongrel rats as recipient and mice as donor, divided 4 groups(n=6), control group(Group 1) has no medication or pretreatment, Group 2 has splenectomy as pretreatment 7∼10 days before transplantation, Group 3 has Cyclosporine A treatment group, Group 4 has combined treatment of Cyclosporine A & Mycophenolate Mofetil(RS 61443). We compared survival time. Reuslt: We can't find significant difference of survival time between each groups. Conclusion: We concluded that rejection of cardiac xenograft was different from rejection of allograft, and new immunossuppresive Agent(Mycophenolate Mofetil, Cyclosporine A) was not effective for prolongation of survival time after cardiac xenograft.

• 한국유가공학회:학술대회논문집
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• 2007.09a
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• pp.49-58
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• 2007

Inflammatory process leads to the well-known mucosal damage and therefore a further disturbance of the epithelial barrier function, resulting abnormal intestinal wall function, even further accelerating the inflammatory process[1]. Despite of the records, etiology and pathogenesis of IBD remain rather unclear. There are many studies over the past couple of years have led to great advanced in understanding the inflammatory bowel disease(IBD) and their underlying pathophysiologic mechanisms. From the current understanding, it is likely that chronic inflammation in IBD is due to aggressive cellular immune responses including increased serum concentrations of different cytokines. Therefore, targeted molecules can be specifically eliminated in their expression directly on the transcriptional level. Interesting therapeutic trials are expected against adhesion molecules and pro-inflammatory cytokines such as TNF-${\alpha}$. The future development of immune therapies in IBD therefore holds great promises for better treatment modalities of IBD but will also open important new insights into a further understanding of inflammation pathophysiology. Treatment of cytokine inhibitors such as Immunex(Enbrel) and J&J/Centocor(Remicade) which are mouse-derived monoclonal antibodies have been shown in several studies to modulate the symptoms of patients, however, theses TNF inhibitors also have an adverse effect immune-related problems and also are costly and must be administered by injection. Because of the eventual development of unwanted side effects, these two products are used in only a select patient population. The present study was performed to elucidate the ability of TNF-${\alpha}$ antibodies produced in sheep colostrums to neutralize TNF-${\alpha}$ action in a cell-based bioassay and in a small animal model of intestinal inflammation. In vitro study, inhibitory effect of anti-TNF-${\alpha}$ antibody from the sheep was determined by cell bioassay. The antibody from the sheep at 1 in 10,000 dilution was able to completely inhibit TNF-${\alpha}$ activity in the cell bioassay. The antibodies from the same sheep, but different milkings, exhibited some variability in inhibition of TNF-${\alpha}$ activity, but were all greater than the control sample. In vivo study, the degree of inflammation was severe to experiment, despite of the initial pilot trial, main trial 1 was unable to figure out of any effect of antibody to reduce the impact of PAF and LPS. Main rat trial 2 resulted no significant symptoms like characteristic acute diarrhea and weight loss of colitis. This study suggested that colostrums from sheep immunized against TNF-${\alpha}$ significantly inhibited TNF-${\alpha}$ bioactivity in the cell based assay. And the higher than anticipated variability in the two animal models precluded assessment of the ability of antibody to prevent TNF-${\alpha}$ induced intestinal damage in the intact animal. Further study will require to find out an alternative animal model, which is more acceptable to test anti-TNF-${\alpha}$ IgA therapy for reducing the impact of inflammation on gut dysfunction. And subsequent pre-clinical and clinical testing also need generation of more antibody as current supplies are low.

• Journal of Life Science
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• v.28 no.6
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• pp.753-763
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• 2018

Cysteine cathepsins are lysosomal enzymes that belong to the papain family and can induce the degradation of damaged proteins through the endo-lysosomal pathway. It is highly upregulated in many cancers by regulating gene amplification and transcriptional, translational, and post-transcriptional modifications. Cathepsin S is part of the cysteine cathepsin family. Many studies have demonstrated that cathepsin S not only plays a specific role in MHC class II antigen presentation but also plays a crucial role in cancers. Cathepsin S is more stable at a neutral pH compared to other cysteine cathepsins, which supports the importance of cathepsin S in disease microenvironments. Therefore, the dysregulation of cathepsin S has participated in a variety of pathological processes, including cancer, arthritis, and cardiovascular disease. Furthermore, a decrease or depletion in the expression of cathepsin S has been implicated in the processes of tumor growth, invasion, metastasis, and angiogenesis. Taken together, cathepsin S has been suggested as an attractive therapeutic target for cancer therapy. In this review, the known involvement of cathepsin S in diseases, particularly with respect to recent work indicating its role in cancer therapy, is examined. An overview of current literature on the inhibitors of cathepsin S as a therapeutic target for cancer is also provided.

• Journal of Veterinary Clinics
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• v.24 no.2
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• pp.244-246
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• 2007

Clinical and histopathologic features of idopathic polymyositis in twenty-month-old Alaskan malamute dog are described. The clinical signs were progressive exercise intolerance with acute exacerbation of weakness, muscle atrophy, synchronous pelvic limb gait, short stiff steps and tip-toeing as like walking on eggshells. Physical and clinical examination revealed no evidence of neurologic, skeletal and secondary muscular disorders associated with other diseases. Therefore muscle biopsy was performed at the most severe muscle atrophy lesions to confirm by histopathology. Histopathologic findings documented mononuclear cell infiltration and necrosis of muscle fiber and it was diagnosed as idiopathic polymyositis. Initial treatment was focused on pain relief. Prednisone at immunosuppressive dose (2 mg/kg) was administered orally twice daily. After 3 weeks of starting treatment, the patient showed improvement of gait, appetite, exercise as well as gradually return to normal state of hematologic and serum chemistry profiles.

• Childhood Kidney Diseases
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• v.14 no.1
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• pp.10-21
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• 2010

The overall prognosis of Henoch-Schoenlein purpura (HSP) is favorable, but severe nephritis has a high risk of progression to end stage renal failure. Recent studies emphasize the importance of early treatment in children with severe HSP nephritis, but the treatment of severe HSP nephritis still remains controversial due to the rarity of randomized controlled studies in this field. Nevertheless, several intensive therapies, such as intravenous high-dose methylprednisolone pulse, immunosuppressive/cytotoxic drugs, fibrinolytic therapy, anticoagulants, antiplatelet agent and plasma exchange, have been used in children with severe HSP nephritis. In this review, we focus on the treatment of severe HSP nephritis in children.