• Korean Journal of Veterinary Research
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• 제52권3호
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• pp.183-191
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• 2012

The maintenance of peripheral immune tolerance and prevention of chronic inflammation and autoimmune disease require $CD4^{+}CD25^{+}$ T cells (regulatory T cells). The transcription factor Foxp3 is essential for the development of functional, regulatory T cells, which plays a prominent role in self-tolerance. Retroviral vectors can confer high level of gene transfer and transgene expression in a variety of cell types. Here we observed that following retroviral vector-mediated gene transfer of Foxp3, transductional Foxp3 expression was increased in the liver, lung, brain, heart, muscle, spinal cord, kidney and spleen. One day after vector administration, high levels of transgene and gene expression were observed in liver and lung. At 2 days after injection, transductional Foxp3 expression level was increased in brain, heart, muscle and spinal cord, but kidney and spleen exhibited a consistent low level. This finding was inconsistent with the increase in both $CD4^{+}CD25^{+}$ T cell and $CD4^{+}Foxp3^{+}$ T cell frequencies observed in peripheral immune cells by fluorescence-activated cell-sorting (FACS) analysis. Retroviral vector-mediated gene transfer of Foxp3 did not lead to increased numbers of $CD4^{+}CD25^{+}$ T cell and $CD4^{+}Foxp3^{+}$ T cell. These results demonstrate the level and duration of transductional Foxp3 gene expression in various tissues. A better understanding of Foxp3 regulation can be useful in dissecting the cause of regulatory T cells dysfunction in several autoimmune diseases and raise the possibility of enhancing suppressive functions of regulatory T cells for therapeutic purposes.

• Journal of Life Science
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• 제30권7호
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• pp.630-633
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• 2020

Renal failure syndrome in wild mammals is infrequently reported. Muskrat (Ondatra zibethicus) is a medium-sized rodent known to carry many diseases but rarely exhibiting renal failure. A six-month old female muskrat was submitted to our laboratory for pathological diagnosis, and necropsy revealed severe renal damage with sand-like lithiasis in the ureter, renal calculi, and hydronephrosis. All major organs, including the cerebrum, also showed systemic hemorrhage and calcification which may have been due to uremia induced by renal failure. Histopathologically, necrosis and microcalcification were detected in the renal cortex and the medulla, especially in the proximal convoluted tubules and collecting ducts of the kidney. Significant hyalinization of the glomeruli was also observed, and this suggested chronic nephritis. These findings would support mycotoxic effects, particularly on the kidney. Moreover, infiltration of neutrophils and mononuclear cells was observed in the lung and of plasma cells in the spleen. The definitive cause of the toxic effects in this case of muskrat renal failure could be attributed to contaminated food.

• Korean Journal of Clinical Pharmacy
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• 제21권4호
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• pp.364-375
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• 2011

Given that single blockade with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) can achieve only partial and undurable suppression of the Renin Angiotensin System (RAS), it has been hypothesized that dual blockage would be more beneficial in the management of blood pressure (BP) reduction and prevention of progressive chronic kidney disease (CKD) than either agent alone. Thus, it has been suggested that the combination of an ACEI and an ARB might provide renal benefits to hypertensive patients over and above BP reduction. However, this might also expose patients to additive or synergistic side effects. We attempted to conduct a systematic review to evaluate the benefits and harms of combination therapy in hypertensive patients with or without kidney diseases. MEDLINE and KoreaMed were searched for relevant randomized clinical trials in adult hypertensive patients with or without diabetes (restricted to 1997, limited to trials published in English). Results were summarized using the random-effects model, and between-studies heterogeneity was estimated with $I^2$. A final analysis of ten trials (23,928 patients) revealed that the combination of an ACEI and an ARB reduced blood pressure (SBP/DBP) by 3.95/2.02 mmHg (95% confidence interval [CI], -4.38 to -3.53/-2.33 to -1.71) compared with ACEI monotherapy, and 2.83/2.64 mmHg (95% CI, -3.25 to -2.41/-4.95 to -0.33) compared with ARB monotherapy. Eight trials (391 patients) demonstrated a significant reduction in 24h-proteinuria (weighted mean difference, 0.16 g/day, 95% CI, -0.26-0.05), but they did not translate into an improvement in GFR. Tests for heterogeneity showed no difference in effect among the studies. The combination therapy reduced proteinuria by 30% (95% CI, 23% to 37%) and 39% (95% CI, 31% to 48%) compared with ACEI monotherapy and ARB monotherapy, respectively. However, in patients who had proteinuria more than 0.5 g/day, the combination therapy failed to show significant reduction in urinary protein excretion. The current cumulative evidence suggests that diabetic patients with proteinuria on dual RAS blockade have an increase risk of adverse events such as hyperkalemia, hypotension, and so on, compared with ACEI or ARB alone. It is, therefore, proposed that the combination therapy should not be routinely used for the treatment of hypertension with or without compelling indications.

• Childhood Kidney Diseases
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• 제1권1호
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• pp.17-23
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• 1997

After the first description of IgA nephropathy by Berger in 1968, the prognosis of this disease was considered favourable. However recent studies have revealed that IgA nephropathy result in end stage renal desease in 25-30% by 20 years. Heavy proteinuria, hypertension, histological high class are regarded as poor prognostic factors. In 1996, Yagame et al reported the new histopathologic grading with a strong correlation between the grading, heavy proteinuria, high s-Cr level and renal survival. The aims of this study are to determine whether the pathological grading and other clinical parameters could contribute to predicting the outcome of this disease eventhough pediatric patients. Seventy nine patients (59 males, 20 females) with IgA nephropathy were examined. Patients were 2.08-15.17 years of age ($9.85{\pm}2.83$). The mean follow-up duration were $27{\pm}28$ months. Six of seventy nine patients progressed to chronic renal failure during the follow-up periods. High 24h urinary protein excretion at diagnosis were significantly higher in chronic renal failure patients (p<0.05). Hypertension at diagnosis were the significant associated factors in progression of chronic renal failure (p<0.05). Histological changes of IgA nephropathy in light microscopy were classified into five classes by WHO classification, four grades in Yagame's gradings. Among the seventy nine patients, 24 were as class 1, 30 as class 2, 23 as class 3; 4 as class 4, 0 as class 5 by WHO classification. 23 were classified grade 1, 31 as grade 2, 24 as grade 3, 1 as grade 4 by Yagame's grading. Among six patients who progressed to chronic renal failure, 1 clssified as class 1, 1 as class 2, 3 as class 3, 1 as class 4, 0 as class 5 by WHO Classification. 1 patients were classified as grade 1, 1 as grade 2, 3 as grade 3, 1 as grade 4 by Yagame's grading. (p>0.05) In conclusion, hypertension and heavy proteinuria at initial presentation were significantly associated with progression of chronic renal failure. The classification of WHO & Yagame's grading has no significant association with the progression of chronic renal failure in pediatric patients.

• Tuberculosis and Respiratory Diseases
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• 제42권1호
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• pp.1-10
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• 1995

Background: It has been well known that bronchial asthma is a chronic inflammatory disorder. The "activation" of lymphocytes has a significant role in the pathogenesis of bronchial asthma. Among these lymphocytes, TH2-like rather than TH1-like lymphoytes are activated in the bronchial tissues from patients with atopic bronchial asthma. However, the difference of cytokines expression is not well documented between the atopic normal subjects and atopic asthmatics. Methods: Bronchial tissues were obtained from the tweleve atopic and non-atpoic asthmatics and tweleve atopic and non-atopic healthy subjects for in stiu hybridizatin of IL-2, IL-4, IL-5, and INF-$\gamma$. The probe of cytokines were tagged with digoxigenin by random priming method. Results: The infiltration of many inflammatory cells on submucosa and denuded epithelium were observed in the bronchial tissue from patients with bronchial asthma. The RNase-treated bronchial tissues did not have the brown signal on the tissue, but, RNasc-untreated bronchial tissues had the positive brown signal on the inflammatory cells under the basement membrane. The IL-2 positive signals were detected in 2 cases, IFN-$\gamma$ in 1 casc, IL-4 in 2 cases, IL-5 in 2 cases among 6 non-atopic healthy subjects. The atopic healthy subjects showed 1 case of positive signal of IL-2 and IFN-$\gamma$, but did not show any signals of IL-4 and IL-5. The positive signals of IL-2 were detected in 4 cases among 6 atopic and 6 non-atopic asthmatics, 2 cases and 1 case of IFN-$\gamma$ respectively, 4 cases and 3 cases of IL-4 respectively, 4 cases and 3 cases of IL-5 respectively. Conclusion: The lymphocytes were activated in the bronchus of asthmatics. Among lymphocytes, TH2-like lymphocytes may be involved in the pathogenesis of bronchial asthma. However, futher study with immunohistochemical stain may be necessary for defining the source of cytokines, because of TH2-like lymphocytes were also activated in some atopic healthy subjects.

• Tuberculosis and Respiratory Diseases
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• 제45권4호
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• pp.846-860
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• 1998

Background: Endotoxin (LPS : lipopolysaccharide), a potent activator of immune system, can induce acute and chronic inflammation through the production of cytokines by a variety of cells, such as monocytes, endothelial cells, lymphocytes, eosinophils, neutrophils and fibroblasts. LPS stimulate the mononucelar cells by two different pathway, the CD14 dependent and independent way, of which the former has been well documented, but not the latter. LPS binds to the LPS-binding protein (LBP), in serum, to make the LPS-LBP complex which interacts with CD14 molecules on the mononuclear cell surface in peripheral blood or is transported to the tissues. In case of high concentration of LPS, LPS can stimulate directly the macrophages without LBP. We investigated to detect the generation of proinflammatory cytokines such as interleukin 1 (IL-1), IL-6 and TNF-$\alpha$ and fibrogenic cytokine, TGF-$\beta$, by peripheral blood mononuclear cells (PBMC) after LPS stimulation under serum-free conditions, which lacks LBPs. Methods : PBMC were obtained by centrifugation on Ficoll Hypaque solution of peripheral venous bloods from healthy normal subjects, then stimulated in the presence of LPS (0.1 ${\mu}g/mL$ to 100 ${\mu}g/mL$ ). The activities of IL-1, IL-6, TNF, and TGF-$\beta$ were measured by bioassaies using cytokines - dependent proliferating or inhibiting cell lines. The cellular sources producing the cytokines was investigated by immunohistochemical stains and in situ hybridization. Results : PBMC started to produce IL-6, TNF-$\alpha$ and TGF-$\beta$ in 1 hr, 4 hrs and 8hrs, respectively, after LPS stimulation. The production of IL-6, TNF-$\alpha$ and TGF-$\beta$ continuously increased 96 hrs after stimulation of LPS. The amount of production was 19.8 ng/ml of IL-6 by $10^5$ PBMC, 4.1 ng/mL of TNF by $10^6$ PBMC and 34.4 pg/mL of TGF-$\beta$ by $2{\times}10^6$ PBMC. The immunoreactivity to IL-6, TNF-$\alpha$ and TGF-$\beta$ were detected on monocytes in LPS-stimulated PBMC. Some of lymphocytes showed positive immunoreactivity to TGF-$\beta$. Double immunohistochemical stain showed that IL-1$\beta$, IL-6, TNF-$\alpha$ expression was not associated with CD14 postivity on monocytes. IL-1$\beta$, IL-6, TNF-$\alpha$ and TGF-$\beta$mRNA expression were same as observed in immunoreactivity for each cytokines. Conclusion: When monocytes are stimulated with LPS under serum-free conditions, IL-6 and TNF-$\alpha$ are secreted in early stage of inflammation. In contrast, the secretion of TGF-$\beta$ arise in the late stages and that is maintained after 96 hrs. The main cells releasing IL-1$\beta$, IL-6, TNF-$\alpha$ and TGF-$\beta$ are monocytes, but also lymphocytes can secret TGF-$\beta$.

• Tuberculosis and Respiratory Diseases
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• 제80권3호
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• pp.296-303
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• 2017

Background: Acute respiratory distress syndrome (ARDS) is related to high mortality and morbidity. There are no proven therapeutic measures however, to improve the clinical course of ARDS, except using low tidal volume ventilation. Metformin is known to have pleiotropic effects including anti-inflammatory activity. We hypothesized that pre-admission metformin might alter the progress of ARDS among intensive care unit (ICU) patients with diabetes mellitus (DM). Methods: We performed a retrospective cohort study from January 1, 2005, to April 30, 2005 of patients who were admitted to the medical ICU at Seoul National University Hospital because of ARDS, and reviewed ARDS patients with DM. Metformin use was defined as prescribed within 3-month pre-admission. Results: Of 558 patients diagnosed with ARDS, 128 (23.3%) patients had diabetes and 33 patients were treated with metformin monotherapy or in combination with other antidiabetic medications. Demographic characteristics, cause of ARDS, and comorbid conditions (except chronic kidney disease) were not different between metformin users and nonusers. Several severity indexes of ARDS were similar in both groups. The 30-day mortality was 42.42% in metformin users and 55.32% in metformin nonusers. On multivariable regression analysis, use of metformin was not significantly related to a reduced 30-day mortality (adjusted ${\beta}-coefficient$, -0.19; 95% confidence interval, -1.76 to 1.39; p=0.816). Propensity score-matched analyses showed similar results. Conclusion: Pre-admission metformin use was not associated with reduced 30-day mortality among ARDS patients with DM in our medical ICU.

• Tuberculosis and Respiratory Diseases
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• 제62권5호
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• pp.398-405
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• 2007

Background: There is little data on the 3 year prognosis and quality of life of patients on long-term (>72 hour) mechanical ventilation in a medical intensive care unit (MICU). Methods: Patients with long-term mechanical ventilation from May 2003 through July 2003 in MICU of Asan Medical Center, Seoul were enrolled in this studay. The survival rates were observed prospectively at 1, 3, 6, 12, 24, 36 months, and the quality of life of survivor was measured at 12 months by using Short Form 36 (SF-36). Results: The survival rate at 1, 3, 6, 12, 24 and 36 months was 54.8% (40/73), 39.7% (29/73), 30.1% (22/73), 20.5% (15/73), 18.3% (13/71) and 16.9% (12/71), respectively. There was a similar survival rate regardless of the diseases that required mechanical ventilation. A neoplasm or chronic liver disease had a worse survival rate than chronic lung or kidney disease (p<0.05). Each SF-36 domain except for the Role-emotional was inferior to the general population. Conclusions: The survival rate of patients with mechanical ventilation more than 72 hours is decreases continuously until 12 months but is relatively constant from 12 to 36 months. In these patients quality of life is also decrased.

• Childhood Kidney Diseases
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• 제4권1호
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• pp.17-24
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• 2000

Purpose: MCNS is found in approximately $85\%$ of the idiopathic nephrotic syndrome in children and shows good prognosis with initial steroid therapy. However in FSGS, there is poor prognosis with initial therapy and shows higher rate of progression to chronic renal failure and relapse after kindney transplantation. We have experienced 8 patients who were diagnosed as MCNS on initial renal biopsy and then progressed to FSGS on follow-up biopsy. So we have investigated their clinical course and risk factors for transition of MCNS to FSGS. Methods: We conducted a retrospective study with a review of histopathologic findings and clinical manifestations of 296 cases of MCNS and FSGS that were diagnosed from January 1988 to May 1999. We classified them into 3 groups according to the histopathologic finding; MCNS, FSGS, MCNS progressed to FSGS in follow-up biopsy. Results: The number of children was 296 cases comprising 241 cases($81.4\%$) showing MCNS, 8 cases($2.7\%$) transition group, 47 cases($15.9\%$) FSGS. The mean onset age was $6.0{\pm}2.6$years in MCNS, transition group $8.3{\pm}2.3$years, FSGS $7.2{\pm4.3$years, and the gender (M:F) ratio was 3.7:1 in MCNS, 3:1 in transition group, 1.8:1 in FSGS. Comparing the presence of initial hematuria, hypertension,24 hour urine protein, serum albumin, serum creatinine, there were significant difference between the transition group and the FSGS group in the following points; 24hour urine protein $684:342mg/m^2/hr$(P<0.05), serum albumin 1.92: 2.47g/dL(P<0.05), serum cholesterol 494:343mg/dL(P<0.05). Refractoriness to steroid therapy was 13.3$\%$ in MCNS. $12.5\%$ in transition group, $29.6\%$ in FSGS; significantly higher in FSGS(P<0.05). Immunosuppressant therapy was performed in $58.5\%$ of MCNS, $100\%$ in transition group, $80.8\%$ in FSGS; transition group showed significantly higher .ate(P<0.05) comparing with MCNS. Mean number of relapse and duration from onset to first relapse showed no significance difference between these groups. Conclusion: 249 patients with MCNS have been followed and $3.2\%$ (8 patients) of them has shown change in pathologic diagnosis from MCNS to FSCS. The risk factor for transition could not be found. Our results point to the need for a follow-up biopsy to certify the possibility of transition to FSCS in some MCNS cases with refractory cases to steroid therepy, frequent relapsing cases, or in case of no remission in spite of vigorous immunosuppressant therapy.

• Childhood Kidney Diseases
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• 제4권2호
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• pp.92-101
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• 2000

Purpose : We analyzed the demogaphic data md clinical course of Korean children with chronic renal failure (CRF) observed between 1990 and 1999. Patients and Methods : Questionnaires were mailed to all children's hospitals ail through the country. We asked for primary renal disease age and serum creatinine levels at first presentation with CRF and end-stage renal disease (ESRD), and modes of renal replacement therapy (RRT). Results : 401 children (254 boys, 147 girls) with CRF, defined as a permanent increase of serum creatinine above 1.2 mg/dl for at least 3 months or until death, were identified. This represents an incidence of 3.68 per million child population per year. Of these patients, 22$\%$ on younger than 5 years, 28$\%$ 5 to 10 years and 50$\%$ 10 to 15 year. Eight five $\%$ of the patients could be classified with a primary renal disease. The most frequent cause is glomerulonephritis (36$\%$), followed by chronic pyelonephritis (21$\%$), renal hrpo/dylplasia (9$\%$), and hereditary nephropathies (7$\%$). Reflux nephropathy (16$\%$) was the most common single cause of CRF. ESRD was reached in 70$\%$ of all patient. 99.3$\%$ of these started RRT. Hemodialysis (HD, 42$\%$), peritoneal dialysis (PD, 35$\%$) and transplantation (TP, 23$\%$) were performed as the initial mode of RRT. A total of 161 TPs were performed (159 first grafts, 2 second grafts). A total of 32 patients died. The main causes of death were dialysis related complication in HD patients and infections in PD patients. Survival rate on any form of RRT was 88.7$\%$ during the mean follow-up period of 37 months. Conclusion Major efforts should be directed toward earlier diagnosis and treatment of reflux nephropathy to prevent occurrence of Of. Dialysis and TP have now become well accepted forms of treatment in Korean children with ESRD.