• Tuberculosis and Respiratory Diseases
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• v.51 no.4
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• pp.354-363
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• 2001

Background : Although lung involvement has been reported in 5 to 46% of dermatomyositis/polymyositis(DM/PM) patients, reports of the condition in Korea are rare. This study evaluated the clinical features of lung involvement in DM/PM patients. Methods : The medical records, laboratory results and radiologic findings of 79 DM/pM patients, who attended the Seoul National University Hospital (SNUH) between 1989 and 1999, were reviewed retrospectively. Results : A total 79 patients of whom 24 patients(33%) showed lung involvement, were enrolled in this study. More patients with lung involvement were female(F:M=11:1), and older compared with those without lung involvement. Patients with lung involvement presented with dyspnea(79%), coughing(67%), an elevated ESR, and CK/LD. Anti-Jo 1 antibody test was positive in 30%, which is significantly higher in patients with lung involvement. A simple chest X-ray of the patients with lung involvement exhibited reticular opacity(50%), reticulonodular opacity(30%), patchy opacity(29%), nodular opacity(13%) and linear opacity(4%). HRCT(n=24) showed ground glass opacity(75%), linear or septal thickening(50%), patchy consolidation(42%), honey-combing(33%) and nodular opacity(17%). The pulmonary function test showed a restrictive ventilatory pattern(77%) and a lower diffusing capacity(62%). The patients were followed up during a mean duration of $30{\pm}28$ months. They were treated with steroid only(50%) or a combination of steroids and cytotoxic agents(46%). Muscle symptoms were improved in 89% with treatment, but an improvement in the respiratory symptoms or in the pulmonary function test was rare. Patients with lung involvement had a higher mortality rate(21%) than those without lung involvement(10%) during the follow-up periods. Conclusion : DM/PM patients with lung involvement were mostly female, older and had a higher positive rate Anti-Jo 1 antibodies, but there was no significant difference in prognosis.

• 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.

• 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.31 no.8
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• pp.710-718
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• 2021

Placenta-derived mesenchymal stem cells (PD-MSCs) are promising candidates for cell-based therapy in regenerative medicine. The migration and homing potential of PD-MSCs to injured sites is a critical property of MSC engraftment. MicroRNAs (miRNAs) have recently been shown to regulate the critical functions of MSCs, such as proliferation, survival, and migration. The objective of the present study was to identify the miRNA and target genes involved in PD-MSCs homing in a bile duct ligation (BDL) rat model. We selected candidate miRNAs targeting genes for PD-MSCs homing based on microarray analysis. PD-MSC engraftment in BDL-injured rat liver was identified by immunofluorescence assay and human-specific Alu gene expression by quantitative real-time polymerase chain reaction (qRT-PCR) one week after transplantation. Compared with migrated naïve PD-MSCs under hypoxic and normoxic conditions (Hyp/Nor), the transplanted group with PD-MSCs (Tx) showed distinct differences in miRNA expressions in BDL-injured rat liver. We also validated the miRNAs and their target genes for PD-MSCs homing. The expressions of integrin α4 (ITGA4) and integrin α5 (ITGA5) target genes for miR-199a-5p and miR-148a-3p were significantly upregulated in the Tx group (p<0.05). In addition, integrin β1 (ITGB1) and integrin β8 (ITGB8) were upregulated by suppressing miR-183-5p and miR-145-5p, respectively. These results demonstrated that PD-MSCs regulate miRNA expression related to the integrin family for their homing effects on the BDL-injured rat liver. The findings further suggest that miRNA-mediated regulation of the integrin family contributes to the therapeutic efficacy of PD-MSCs in the rat hepatic fibrosis model by BDL.

• Journal of Gastric Cancer
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• v.6 no.1
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• pp.36-42
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• 2006

Purpose: The $p21^{Waf1/Cip1}$ protein Inhibits the cell cycle by Inhibiting the phosphorylation at the $G1{\rightarrow}S$ check point, and the $p27^{kip1}$ protein similarly performs the suppressor function by controlling the p27-mediated G1 arrest. In this study, we analysed the clinical status and survival rates in correlations with p21 and p27 expression patterns in gastric cancer. Materials and Methods: Between 1993 and 1997, 192 patients who underwent surgeries in Catholic Medical Center were analysed retrospectively in this study. Immunohistochemical staining was performed and if the nuclei of the tumor cells were stained, we assumed those as positive results. Statistical analysis was based on clinicopathological findings and differences in survival rates. Results: The expression rate of p27 was 28.1% and 15.6% in p21 each. The ratio of T1-2(80.0%) was significantly high in p21 (+), but the ratio of T3-4 (50.6%) was slightly high in p21 (-). There was no statistical significance regarding other factors. The results in p27 was not much different from expression rate of p21 in T-stage. In addition, p27 expression in diffuse type (91.3%) was higher than in intestinal type (62.7%) by Lauren's classification (P<0.05). Also, there was no statistical significance in other factors. In the correlation of p21 and p27, p27 was positive when p21 was positive (53.5%). Conversely, p27 was negative when p21 was negative (76.5%, p<0.05). In the p21 and p27 combination test, there was higher rate of T1-2 (87.5%) in p21 (+)/p27 (+), and higher rate of T3-4 (58.1%) in p21 (-)/p27 (-) (P<0.05). Results showed higher rate of intestinal type (100%) in p21 (+)/p27 (+), and diffuse type (87.0%) was dominant in p21 (-)/p27 (-) (P<0.05) by Lauren's classification. Moreover, there was no statistical significance in the 5-year survival rate in the expression of p21 and p27, and the 5-year survival rate was highest in the case of p21 (+)/p27 (+) without statistical significance. Conclusion: In our study, $p21^{Waf1/Cip1}\;and\;p27^{kip1}$ expressed similar patterns. The expression of $p21^{Waf1/Cip1}\;and\;p27^{kip1}$ affected the degree of invasiveness of the tumor, and. Combined examination result revealed the correlation of $p21^{Waf1/Cip1}\;and\;p27^{kip1}$ with Lauren's classification and depth of invasion of the tumor. However, we assumed that little difference between the survival rates depending on expression of $p21^{Waf1/Cip1}\;and\;p27^{kip1}$ has limited their value as predictable prognostic indicators.

• Childhood Kidney Diseases
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• v.5 no.2
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• pp.78-86
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• 2001

Purpose: Rapidly progressive glomerulonephritis (RPGN) is characterized by the rapid increase in serum creatitnin and crescents formation involving more than $50\%$ of glomeruli. 10 patients who had been treated for RPGN were studied retrospectively for thier underlying diseases and clinical features Method: Cilinical review was performed on 10 children who were diagnosed with RPGN by clinical features and renal biopsy and followed up at department of pediatrics during tile last 10 years, from May 1990 to May 2000. Result: There were 6 males and 4 females between the ages of 2.1 and 14.3 years (mean $10.9{\pm}3.8$). 3 had Henoch-$Sch{\ddot{o}}nlein$ purpura nephritis; 2, idiopathic rapidly progressive glomerulonephritis; 2, lupus nephritis; 1, hemolytic uremic syndrome; 1, membranous glomerulonephritis and 1, microscopic polyangiitis. The most common chief complaints were gross hematuria and oliguria. Initial clinical features included proteinuria, edema, hypertension, nausea and arthralgia. Mean serum BUN was $74.2{\pm}39.1\;mg/dL$ mean serum creatinin, $3.2{\pm}1.8\;mg/dL$ and mean creatinin clearance, $26.5{\pm}13.2\;mL/min/1.73m^2$. Antineutrophil cytoplasmic antibody was positive only in microscopic polyangiitis. ANA and Anti-DNA antibody were positive in two lupus nephritis patients. Serum complements were decreased in 4 patients. All patients except Hemolytic uremic syndrome received steroid pulse therapy and immunosupressive agents. 3 patients were performed acute peritoneal dialysis and 2 patients were given plasmapheresis. At the last follow up, 1 patient was dead, 4 patients had elevated serum creatinin, 2 of these 4 patients were on chronic ambulatory peritoneal dialysis and 6 patients had normal renal function. Conclusion: Rapidly progressive glomerulonephritis is a medical emergency that requires very rapid diagnosis, classification, and therapy. Appropriate therapy selected on the basis of underlying disease mechanism can substantially improve renal survival. (J. Korean Soc Pediatr Nephrol 2001 ; 5 : 78-86)

• Journal of Radiation Protection and Research
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• v.32 no.4
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• pp.140-156
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• 2007

This research was performed to investigate the morphological changes of folliculus ovary according to the radiation dose. The whole body radiation of 200 cGy, 400 cGy, and 600 cGy was given to the each groups of 5 months-aged female mouse. Various staining methods used in this research are: Hematosylin-Eosin method, and immunohistochemistrical methods using BrdU, TUNEL, p53, p21, PCNA and inhibin. The minute structural changes of folliculus ovary were observed through an electron microscope with high magnification. The morphological changes of growing folliculus ovary became distinct as the dose of X-rays increased. Especially, the nuclei of granular cells showed manifest condensation and the changes of the transparent zone were distinct. As a result of histochemical reaction according to Masson's trichrome method and reticular fiber method, the changed granular cells, the deformed basilar membrane of folliculus ovary and the abnormal arrangement of the reticular fiber were observed. In the reaction of BrdU, the granular cells of normal folliculus ovary with positive reaction rapidly decreased according to the increase of the dose of X-rays. In TUNEL study, granular cells showing positive reaction in retarded folliculus ovary were expanded to growing folliculus ovary and primordial folliculus ovary according to the increase of the dose of X-rays. In case of 600 cGy of X-rays, oocyte underwent apoptosis. In p53 immunohistochemistry, p53 manifested to be stronger as the dose of X-rays increased. p53 reactivity was manifested distinctively in all cells comprising folliculus ovary following irradiation of 600 cGy. p21 was manifested in granular cells of folliculus ovary and showed very positive reaction around follicular antrum according to the increase of the dose of X-rays. In PCNA, positive reaction was manifested in growing folliculus ovary, mature folliculus ovary and primordial folliculus ovary, but the extent of the reaction decreased as the dose of the X-rays decreased. The finding that the reaction of granular cells around folliculus ovary was stronger than that near follicular membrane indicates that what was damaged first by X-ray was the cells near folliculus ovary and follicular antrum. The reactivity of $inhibin-{\alpha}$ showed difference according to the growing stage of folliculus ovary: $inhibin-{\alpha}$ showed the most strong reaction in mature folliculus ovary with follicular antrum. There was strong reaction in granular cells around follicular membrane but $inhibin-{\alpha}$ did not occur at all in theca cells comprising follicular membrane. $Inhibin-{\alpha}$ in ovary tissue exposed to 400 cGy of X-rays was manifested more strongly than in ovary tissue exposed to 600 cGy of X-rays, which was related to the phenomenon that granular cells of mature folliculus ovary underwent necrosis or apoptosis increasingly due to X-rays. In an electron microscope with high magnification, nuclei and protoplasm of granular cells in growing folliculus ovary abruptly underwent minute structural changes according to the increase of dose of X-rays. Cell residue, by-product of cell decease, neutrophil and macrophage around follicular antrum were observed. The minute structural changes in granular cells showed typical characteristics of apoptosis: the increase of electronic density due to nuclear condensation, fragmentation of nuclei and atrophy of protoplasm. Necrosis of cells was identified but it was not so remarkable. Macrophage with apoptotic bodies was scattered. Proportional to the radiation dose, we found that the generation of heterogeneous substance of normal ovary texture's follicular fluid, the emergence of dyeing characteristic in the basilar membrane of folicle, the generation of apoptosis, and the transformation of macrophages, etc. From this results, we can infer the possible radiation hazard on the ovary of cervix cancer patient with radiation therapy.

• Journal of Life Science
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• v.23 no.9
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• pp.1096-1103
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• 2013

Chronic traumatic encephalopathy (CTE), which is common in athletes, is a progressive neurodegenerative disease and a long-term consequence of repetitive closed head injuries. CTE is regarded as a chronic brain syndrome due to the effects of repetitive traumatic brain injury (TBI). Because neurotrophic factors are neuroprotective in models of brain and spinal cord injuries, we examined the effects of cerebrolysin, a mixture of various neurotrophic factors, on brain pathology in a mouse model of repetitive mild TBI (rmTBI), which is a good model of CTE. Five groups were created and treated as follows: groups 1 and 2: rmTBI for 4 weeks following cerebrolysin injection for 4 weeks; groups 3 and 4: rmTBI for 8 weeks with or without cerebrolysin injection for 4 weeks; group 5: control. We found that p-tau expression was increased in the pyramidal layer of the cortex and hippocampus, particularly the CA3 region, but not in the CA1 region and the dentate gyrus (DG). Intra-tail vein administration of cerebrolysin ($10{\mu}l$ of 1 mg/ml) after/during rmTBI treatment reduced p-tau expression in both the cortex and hippocampus. Histological analysis revealed mild astrocyte activation (increased expression of glial fibrillary acidic protein (GFAP)) but not microglia activation (ionized calcium binding adaptor molecule 1 (iba-1) expression) and peripheral macrophage infiltration (CD45). Additionally, administration of cerebrolysin after rmTBI resulted in reduced astrocyte activation. These observations in rmTBI demonstrated that cerebrolysin treatment reduces phosphorylation of tau and astrocyte activation, attenuates brain pathology, and mitigates function deficits in TBI. Taken together, our observations suggest that cerebrolysin has potential therapeutic value in CTE.

• Journal of Life Science
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• v.30 no.9
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• pp.804-812
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• 2020

The giant mealworm beetle, Zophobas atratus (Coleoptera: Tenebrionidae) has been used as a protein source for small pets and mammals. Recently, it was temporarily registered in the list of the Food Code. We previously performed an in silico analysis of the Zophobas atratus transcriptome to identify putative antimicrobial peptides and identified several antimicrobial peptide candidates. Among them, we assessed the antimicrobial and anti-inflammatory activities of zophobacin 1 that was selected bio-informatically based on its physicochemical properties against microorganisms and mouse macrophage Raw264.7 cells. Zophobacin 1 showed antimicrobial activities against microorganisms without inducing hemolysis and decreased the nitric oxide production of the lipopolysaccharide-induced Raw264.7 cells. Moreover, ELISA and Western blot analysis revealed that zophobacin 1 reduced expression levels of pro-inflammatory enzymes such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). We also investigated expression of pro-inflammatory cytokines (interleukin-6 and interleukin-1β) production through quantitative real time-PCR and ELISA. Zophobacin 1 markedly reduced the expression level of cytokines through the regulation of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) signaling. We confirmed that zophobacin 1 bound to bacterial cell membranes via a specific interaction with lipopolysaccharides. These data suggest that zophobacin 1 could be promising molecules for development as antimicrobial and anti-inflammatory therapeutic agents.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.6
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• pp.659-670
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• 2017

Oxidative stress and inflammation are key factors responsible for progression of liver injury. A variety of functions of oyster hydrolysate (OH) are affected by their antioxidant and anti-inflammatory activities. However, little is known regarding the effects of OH on a liver injury model. This study was performed to evaluate the effects of OH on acute liver injury induced by lipopolysaccharide/D-galactosamine (LPS/D-GalN) in mice. Experimental groups were divided into six groups as follows (each group, n=10): control (saline), LPS/D-GalN, LPS/D-GalN+OH (100 mg/kg), LPS/D-GalN+OH (200 mg/kg), LPS/D-GalN+OH (400 mg/kg), and LPS/D-GalN+silymarin (25 mg/kg, positive control). The experimental acute liver injury model was induced with LPS ($1{\mu}g/kg$) and D-GalN (400 mg/kg). We first analyzed antioxidant and anti-inflammatory activities in OH. OH showed high DPPH and ABTS radical scavenging activities and reduced ROS generation in Chang cells in a dose-dependent manner. In addition, OH showed anti-inflammatory activities, such as inhibition of cyclooxygenase-2 and 5-lipooxygenase. Treatment with OH down-regulated tumor necrosis factor $(TNF)-{\alpha}$, interleukin (IL)-6, and $IL-1{\alpha}$ expression levels in LPS-stimulated RAW264.7 cells. OH significantly reduced LPS/D-GalN-induced increases in the concentrations of alanine transaminase and aspartate aminotransferase in serum. In the LPS/D-GalN group, liver tissues exhibited apoptosis of hepatocytes with hemorrhages. These pathological alterations were ameliorated by OH treatment. Consistently, hepatic catalase activity was low in the LPS/D-GalN group compared to the control group, and catalase activity was significantly restored by OH treatment (P<0.05). Furthermore, OH markedly reduced the LPS/D-GalN-induced increase in $TNF-{\alpha}$, $IL-1{\beta}$, and IL-6 levels in liver tissue. Taken together, these results show that OH has hepatoprotective effects on LPS/D-GalN-induced acute liver injury via inhibition of oxidative stress and inflammation, suggesting that OH could be used as a health functional food and potential therapeutic agent for acute liver injury.