• Korean Journal of Poultry Science
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• v.46 no.1
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• pp.31-37
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• 2019

A chicken clathrin-associated adaptor protein $3-{\delta}$ subunit 2 (AP3S2) is a subunit of AP3, which is involved in cargo protein trafficking to target membrane with clathrin-coated vesicles. AP3S2 may play a role in virus entry into host cells through clathrin-dependent endocytosis. AP3S2 is also known to participate in metabolic disease developments of progressions, such as liver fibrosis with hepatitis C virus infection and type 2 diabetes mellitus. Chicken AP3S2 (chAP3S2) gene was originally identified as one of the differentially expressed genes (DEGs) in chicken kidney which was fed with different calcium doses. This study aims to characterize the molecular characteristics, gene expression patterns, and transcriptional regulation of chAP3S2 in response to the stimulation of Toll-like receptor 3 (TLR3) to understand the involvement of chAP3S2 in metabolic disease in chicken. As a result, the structure prediction of chAP3S2 gene revealed that the gene is highly conserved among AP3S2 orthologs from other species. Evolutionarily, it was suggested that chAP3S2 is relatively closely related to zebrafish, and fairly far from mammal AP3S2. The transcriptional profile revealed that chAP3S2 gene was highly expressed in chicken lung and spleen tissues, and under the stimulation of poly (I:C), the chAP3S2 expression was down-regulated in DF-1 cells (P<0.05). However, the presence of the transcriptional inhibitors, BAY 11-7085 (Bay) as an inhibitor for nuclear factor ${\kappa}B$ ($NF{\kappa}B$) or Tanshinone IIA (Tan-II) as an inhibitor for activated protein 1 (AP-1), did not affect the expressional level of chAP3S2, suggesting that these transcription factors might be dispensable for TLR3 mediated repression. These results suggest that chAP3S2 gene may play a significant role against viral infection and be involved in TLR3 signaling pathway. Further study about the transcriptional regulation of chAP3S2 in TLR3 pathways and the mechanism of chAP3S2 upon virus entry shall be needed.

• Tuberculosis and Respiratory Diseases
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• v.82 no.1
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• pp.42-52
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• 2019

Background: Transforming growth factor ${\beta}$ (TGF-${\beta}$), retinoic acid (RA), p38 mitogen-activated protein kinase (MAPK), and MEK signaling play critical roles in cell differentiation, proliferation, and apoptosis. We investigated the effect of RA and the role of these signaling molecules on the phosphorylation of Smad2/3 (p-Smad2/3) induced by TGF-${\beta}1$. Methods: A549 epithelial cells and CCD-11Lu fibroblasts were incubated and stimulated with or without all-trans RA (ATRA) and TGF-${\beta}1$ and with MAPK or MEK inhibitors. The levels of p-Smad2/3 were analyzed by western blotting. For animal models, we studied three experimental mouse groups: control, bleomycin, and bleomycin+ATRA group. Changes in histopathology, lung injury score, and levels of TGF-${\beta}1$ and Smad3 were evaluated at 1 and 3 weeks. Results: When A549 cells were pre-stimulated with TGF-${\beta}1$ prior to RA treatment, RA completely inhibited the p-Smad2/3. However, when A549 cells were pre-treated with RA prior to TGF-${\beta}1$ stimulation, RA did not completely suppress the p-Smad2/3. When A549 cells were pre-treated with MAPK inhibitor, TGF-${\beta}1$ failed to phosphorylate Smad2/3. In fibroblasts, p38 MAPK inhibitor suppressed TGF-${\beta}1$-induced p-Smad2. In a bleomycin-induced lung injury mouse model, RA decreased the expression of TGF-${\beta}1$ and Smad3 at 1 and 3 weeks. Conclusion: RA had inhibitory effects on the phosphorylation of Smad induced by TGF-${\beta}1$ in vitro, and RA also decreased the expression of TGF-${\beta}1$ at 1 and 3 weeks in vivo. Furthermore, pre-treatment with a MAPK inhibitor showed a preventative effect on TGF-${\beta}1$/Smad phosphorylation in epithelial cells. As a result, a combination of RA and MAPK inhibitors may suppress the TGF-${\beta}1$-induced lung injury and fibrosis.

• 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 the Korean Society of Radiology
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• v.82 no.3
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• pp.562-574
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• 2021

MRI has the advantages of having excellent soft-tissue contrast and providing functional information without any harmful ionizing radiation. Although previous technical limitations restricted the use of chest MRI, recent technological advances and expansion of insurance coverage are increasing the demand for chest MRI. Recognizing the need for guidelines on appropriate use of chest MRI in Korean clinical settings, the Korean Society of Radiology has composed a development committee, working committee, and advisory committee to develop Korean chest MRI justification guidelines. Five key questions were selected and recommendations have been made with the evidence-based clinical imaging guideline adaptation methodology. Recommendations are as follows. Chest MRI can be considered in the following circumstances: for patients with incidentally found anterior mediastinal masses to exclude non-neoplastic conditions, for pneumoconiosis patients with lung masses to differentiate progressive massive fibrosis from lung cancer, and when invasion of the chest wall, vertebrae, diaphragm, or major vessels by malignant pleural mesothelioma or non-small cell lung cancer is suspected. Chest MRI without contrast enhancement or with minimal dose low-risk contrast media can be considered for pregnant women with suspected pulmonary embolism. Lastly, chest MRI is recommended for patients with pancoast tumors planned for radical surgery.

• Korean Journal of Radiology
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• v.24 no.8
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• pp.807-820
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• 2023

Objective: To assess whether computed tomography (CT) conversion across different scan parameters and manufacturers using a routable generative adversarial network (RouteGAN) can improve the accuracy and variability in quantifying interstitial lung disease (ILD) using a deep learning-based automated software. Materials and Methods: This study included patients with ILD who underwent thin-section CT. Unmatched CT images obtained using scanners from four manufacturers (vendors A-D), standard- or low-radiation doses, and sharp or medium kernels were classified into groups 1-7 according to acquisition conditions. CT images in groups 2-7 were converted into the target CT style (Group 1: vendor A, standard dose, and sharp kernel) using a RouteGAN. ILD was quantified on original and converted CT images using a deep learning-based software (Aview, Coreline Soft). The accuracy of quantification was analyzed using the dice similarity coefficient (DSC) and pixel-wise overlap accuracy metrics against manual quantification by a radiologist. Five radiologists evaluated quantification accuracy using a 10-point visual scoring system. Results: Three hundred and fifty CT slices from 150 patients (mean age: 67.6 ± 10.7 years; 56 females) were included. The overlap accuracies for quantifying total abnormalities in groups 2-7 improved after CT conversion (original vs. converted: 0.63 vs. 0.68 for DSC, 0.66 vs. 0.70 for pixel-wise recall, and 0.68 vs. 0.73 for pixel-wise precision; P < 0.002 for all). The DSCs of fibrosis score, honeycombing, and reticulation significantly increased after CT conversion (0.32 vs. 0.64, 0.19 vs. 0.47, and 0.23 vs. 0.54, P < 0.002 for all), whereas those of ground-glass opacity, consolidation, and emphysema did not change significantly or decreased slightly. The radiologists' scores were significantly higher (P < 0.001) and less variable on converted CT. Conclusion: CT conversion using a RouteGAN can improve the accuracy and variability of CT images obtained using different scan parameters and manufacturers in deep learning-based quantification of ILD.

• IMMUNE NETWORK
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• v.24 no.2
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• pp.7.1-7.19
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• 2024

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019. In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×10⁵ plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×10² PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×10² PFU-virus-infected lungs from 2 dpi, but not in 1×10⁵ PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×10⁵ PFU; however, 1×1² PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

• Childhood Kidney Diseases
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• v.3 no.2
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• pp.130-144
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• 1999

Purpose : Long-term use of Cyclosporine(CsA) reduce renal blood flow by afferent arteriolar vasoconstriction and lead to chronic pathologic changes of CsA nephrotoxicity - 1) interstitial nephritis(IN); tubular atrophy (TA) and/or interstitial fibrosis(IF),2) arteriolopathy(AP). The Object of this study is to estimate the incidence of chronic pathologic CsA nephrotoxicity by duration of treatment and type of renal disease, relationship between histologic and clinical nephrotoxicity, and optimal duration of CsA therapy. Methods : 102 children with steroid resistant or dependent nephrotic syndrome confirmed by renal biopsy and treated with CsA from 1986 to 1997 were enrolled in this study(58 MCNS, 10 FSGS, 10 MGN, 15 $Henoch-Sch\"{o}nlein$ purpura nephritis with nephrotic syndrome (HSPN) and 9 IgA nephropathy with nephrotic syndrome(IgAN)). CsA was administered for 1yr, 1.5yr, 2yr in 24, 12, 22 MCNS patients and 2, 2, 6 FSGS patients respectively, 1yr, 2yr in MGN and 1yr in HSPN and IgAN. Sequential biopsies were done in all 102 patients after CsA treatment for evaluation of pathologic nephrotoxicity. Results : Complete remission rate was 92.2% (100% in MCNS and MGN, 80% in FSGS, 86.6% in HSPN and 55.5% in IgAN). Incidence of relapse during 6months after CsA treatment was significantly decreased compaed with relapsing spisodes during 6months before CsA treatment in MCNS(P<0.0001) and FSGS(P<0.0001). According to pathologic changes, 71 patients(69.6%) showed no pathological change, 24 patients(23.5%) showed IN and 7 patients(6.8%) showed AP. IN was 16.6%, 33.3%, 27.2% in 1, 1.5, 2 year of CsA treatment group in MCNS. AP was 0%, 16.6%, 9% in 1, 1.5, 2 year of CsA treatment group in MCNS. 14 out of 58 MCNS(24.1%) showed IN and 4 out of 58 MCNS(6.8%) showed AP. Incidence of pathologic change was significantly lower in CsA therapy of <1yr than >1yr(P=0.03). There were no significant difference of incidence of pathologic change in original renal disease, age and sex. Conclusion : Duration of CsA treatment was significant risk factor for nephrotoxicity and optimal duration seemed to be 1 year. Pathologic change due to nephrotoxicity did not correlate with deterioration of renal function and only detectable by renal biopsy.

• Journal of Chest Surgery
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• v.31 no.2
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• pp.118-124
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• 1998

Minimally invasive coronary artery bypass grafting without using cardiopulmonary bypass (CPB) is a recently accepted modality of myocardial revascularization prcedures which is particularly suitable to the patients with lesions in the left anterior descending(LAD) and the right coronary arteries. Of the consecutive 35 patients of coronary artery bypass grafting performed at Sejong General Hospital from March to August 1996, six patients underwent minimally invasive coronary artery bypass grafting without CPB. All had stenotic lesions of the LAD more than 90%. Bypass grafting of the LAD was approached through midline sternotomy in one, through ministernotomy in two, and through limited left anterior thoracotomy in three patients, respectively. The internal mammary arteries were prepared without the use of thoracoscope. The mobilized mammary arteries were connected directly to the LAD in 5 patients, and the anastomosis required interposition of a segment of the radial artery in the remaining one. The diagonal branch was revascularized with the saphenous vein graft at the same time in one patient. No blood transfusion was necessary in 2 patients, and average blood required during surgery was 800ml in 4 patients. All patients were extubated from 4 to 14 hours(mean 9 hours) after operation. Early postoperative coronary angiography in 5 patients between 7 and 10 days after surgery has proved full patency of the grafts. With these limited clinical experiences, the clinical results demonstrated that minimally invasive coronary artery bypass grafting without CPB is an useful procedure especially in patients with isolated lesion in the proximal LAD.

• Radiation Oncology Journal
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• v.19 no.1
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• pp.21-26
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• 2001

Purpose : This study was peformed to evaluate the cosmetic outcome of conservative treatment for early breast cancer and to analyze the factors influencing cosmetic outcome. Materials and Methods : From February 1992 through January 1997, 120 patients with early breast cancer were treated with conservative surgery and postoperative radiotherapy. The types of conservative surgery were quadrantectomy and axillary node dissection for 108 patients $(90\%)$ and lumpectomy or excisional biopsy for 10 patients $(8.3\%)$. Forty six patients $(38\%)$ received adjuvant chemotherapy (CMF or CAF). Cosmetic result evaluation was carried out between 16 and 74 months (median, 33 months) after surgery. The cosmetic results were classified into four categories, i.e., excellent, good, fair, and poor. The appearances of the patients' breasts were also analyzed for symmetry using the differences in distances from the sternal notch to right and left nipples. A logistic regression analysis was performed to identify independent variables influencing the cosmetic outcome. Results : Cosmetic score was excellent or good in $76\%$ (91/120), fair in $19\%$ (23/120) and poor in $5\%$ (6/120) of the patients. Univariate analysis showed that tumor size (T1 versus T2) (p=0.04), axillary node status (N0 versus N1) (p=0.0002), extent of surgery (quadrantectomy versus lumpectomy or excisional biopsy) (p=0.02), axillary node irradiation (p=0.0005) and chemotherapy (p=0.0001) affected cosmetic score. Multivariate analysis revealed that extent of surgery (p=0.04) and chemotherapy (p=0.0002) were significant factors. For breast symmetry, univariate analysis confirmed exactly the same factors as above. Multivariate analysis revealed that tumor size (p=0.003) and lymph node status (p=0.007) affected breast symmetry. Conclusion : Conservative surgery and postoperative radiotherapy resulted in excellent or good cosmetic outcome in a large portion of the patients. Better cosmetic results were achieved generally in the group of patients with smaller tumor size, without axillary node metastasis and treated with less extensive surgery without chemotherapy.

• Tuberculosis and Respiratory Diseases
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• v.48 no.4
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• pp.530-542
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• 2000

Background : Nonspecific interstitial pneumonia (NSIP) has been reported recently to have shown much better response to medical treatment and better prognosis compared with idiopathic UIP. However, clinical characteristics of idiopathic NSIP discriminating it from UIP have not been clearly defined. Method : Among 120 patients with biopsy-proven diffuse interstitial lung diseases admitted to the Samsung Medical Center between July 1996 and March 2000, 18 patients with idiopathic NSIP were included in this study. Retrospective chart review and radiographic analysis were performed. Results : 1) At diagnosis, 17 patients were female and the average age was $55.2{\pm}8.4$ years (44~73 years). The average duration from development of respiratory symptom to surgical lung biopsy was $9.9{\pm}17.1$ months. Increase in bronchoalveolar lavage fluid lymphocytes ($23.0{\pm}13.1%$) was noted. On HRCT, ground glass and irregular linear opacity were observed, but honeycombing was absent in all patients. 2) Corticosteroids were initially given to 13 patients, but the medication was stopped in 3 patients due to severe side effects. Further medical therapy was not possible in 1 patient who experienced streroid-induced psychosis. Herpes zoster (n=3), tuberculosis (n=1), avascular necrosis of the hip (n=1), cataract (n=2) and diabetes mellitus (n=1) developed during prolonged corticosteroid administration. Of the 7 patients receiving oral cyclophosphamide therapy, hemorrhagic cystitis hindered one patient from continuing with the medication. 3) After medical treatment, 14 of 17 patients improved, and 3 patients remained stable (mean follow-up ; $24.1{\pm}11.2$ months). FVC increased by $20.2{\pm}11.2%$ of predicted value and the extent of ground glass opacity on HRCT decreased significantly ($15.7{\pm}14.7%$). 4) Of the 14 patients who had stopped medication, 5 showed recurrence of NSIP and 2 became aggravated during steroid tapering. All patients with recurrence showed deterioration within one year after completion of initial treatment. Conclusion : Since idiopathic NSIP has unique clinical profiles and shows good prognosis, diagnosis different from UIP, and aggressive medical treatment are needed.