• Journal of The Korean Society of Inherited Metabolic disease
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• v.16 no.1
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• pp.24-33
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• 2016

Mucopolysaccharidosis type VI (MPS VI) is a rare disease caused by the mutation of ARSB with prevalence range from 1/5,000 in northeast Brazil to 1/2,057,529 births in Czech Republic. In Asia, there is only one published figure in Taiwan of about 1/833,000 births. The exact prevalence in the Korean population is unknown, but we estimated the incidence of MPS VI is about 0.03/100,000 live births. Enzyme replacement therapy (ERT) with recombinant human Arylsulfatase B (rhASB) is a modality for the treatment of MPS VI that reduces the excretion of urine glycosaminoglycan (GAG) and improves joint motion, pulmonary function, and endurance. We presented the clinical features, molecular analysis and outcome of ERT in three Korean MPS VI patients. All patients had the typical characteristic clinical features of MPS IV. Short stature, dysostosis multiplex, corneal opacity and valvular heart disease were found at first presentation, while restrictive lung disease and carpal tunnel syndrome developed later in all patients. Molecular analysis demonstrated novel missense and nonsense mutation in the patients, including p.Ile 67Ser, p.Gly328Arg, $p.Arg191^*$, p.Asp352Asn, and p.Gly17Asp. After ERT, urine GAG was decreased in all patients. Skeletal involvement, corneal opacity, heart valve abnormalities and pulmonary function were not improved with ERT, but it had a better outcome on regarding joint motion and endurance. One patient underwent allogeneic bone marrow transplantation (BMT) prior to ERT, but their clinical response was not improved much after BMT. This study demonstrates clinical phenotypes and molecular analysis of the severe form of MPS VI in Korean patients.

• Tuberculosis and Respiratory Diseases
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• v.64 no.4
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• pp.259-265
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• 2008

Background: Patients with diabetes mellitus are highly sensitive to infections, including tuberculosis, and the longer the duration of DM, the greater is the prevalance of tuberculosis. We studied the difference of the clinical manifestations, radiologic findings, resistance and others factors of patients with diabetic and non-diabetic pulmonary tuberculosis. Methods: The patients we enrolled in this study were newly diagnosed with pulmonary tuberculosis from January 2003 to December 2005. Results: 159 patients were enrolled in this study. There were 30 pulmonary tuberculosis patients with diabetic mellitus (DMTB) and 129 pulmonary tuberculosis patients without diabetic mellitus (non-DMTB). There was no difference in the basic characteristics and clinical manifestation between both the groups. For the chest X-ray findings, the moderately advanced tuberculosis patients were the most common (43.3% in the DMTB group and 49.6% in the non-DMTB group). There was no relation between the severity of tuberculosis activity on chest x-ray and the presence of diabetes. The prevalence of cavitory lesions in the DMTB group was significantly higher than that in the non-DMTB group, but the prevalence of atelectasis was higher in the non-DMTB group (p<0.05). There was no difference in the incidence of lower lung involvement, the number of involved lobes, the number of treatment days and the radiological sequelae in both groups. Conclusion: The DMTB patients had a higher incidence of cavitory lesions and a higher incidence of atelectasis than the non-DMTB patients.

• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.705-713
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• 1998

Background: An association between diabetes and tuberculosis has long been implied. The severity of diabetes appears to correlate with the degree of tuberculous activity. Methods: A retrospective chart review of 82 patients with active pulmonary tuberculosis in diabetics (DMTB) and 83 patients with active pulmonary tuberculosis in nondiabetics (Non-DMTB) admitted to the Kyung Hee Medical Center between January 1995 and December 1996 was underiaken. Results: The sex ratio of DMTB was 58 : 24, and that of Non-DMTB was 62 : 21. Male patients predominated in both groups. The highest incidence of DMTB was 6th and 7th decades and that of Non-DMTB was 3rd and 4th decades. In case which the tuberculosis developed after diagnosis of diabetes, the prevalence of pulmonary tuberculosis was the highest in diabetes for 5-10 years. On chest X-ray findings, the moderate advanced tuberculosis cases were the most common (60.9% in DMTTB and 50.6% in Non-DMTB). There was no relation between the degree of tuberculosis activity on chest x-ray(minimal, moderate, and far advanced tuberculosis) and presence of diabetes. The incidence of lower lung field tuberculosis in DMTB was significantly higher than Non-DMTB(p<0.05). The multiple lobe involvement was the predominant chest roentgenographic finding in both groups. There was no significant difference of treatment response between DMTB and Non-DMTB. There was no relationship between initial HbA1c and the severity of pulmonary tuberculosis on chest X-ray. During treatment of pulmonary tuberculosis in excellently and well controlled diabetes, the cure rate of pulmonary tuberculosis was significantly higher than the poorly controlled diabetes and the rate of treatment failure was significantly lower than poorly controlled diabetes. (p<0.05). Conclusion: Poor control of blood glucose is related with increased rate of treatment failure in pulmonary tuberculosis with diabetes mellitus. Further investigation will be needed to study the mechanisms of treatment failure in poorly controlled diabetics with pulmonary tuberculosis.

• Tuberculosis and Respiratory Diseases
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• v.49 no.5
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• pp.614-623
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• 2000

Background : Diffuse alveolar hemorrhage (DAH) is rare but often fatal. To determine the clinical manifestations of DAH, its etiology, clinical course and prognosis were studied. Method : A retrospective analysis was performed in 21 patients that were diagnosed as DAH. Diagnosis of DAH was based on the presence of the "classical triad" of hemoptysis, anemia, and rapidly progressive infiltrates on chest X-ray and a finding of bronchoalveolar lavage or lung biopsy. Results : Thirteen patients (61.9%) had collagen vascular diseases (CVDs) as underlying disease and 10 patients had systemic lupus erythematosus. Females were more prevalent in CVD than in non-collagen vascular disease (NCVD). Otherwise, there were no significant differences between the two groups in terms of clinical manifestations. Dyspnea (95.2%), cough (76.2%), hemoptysis (61.9%), and fever (33.0%) were frequent symptoms. The initial creatinine level was higher in CVD than in NCVD ($3.27{\pm}3.15$ mg/dl vs. $1.19{\pm}0.94$ mg/dl, p=0.030). The corresponding drop in hemoglobin level was $2.69{\pm}1.26$ g/dl. Maximal drop in hemoglobin preceded the progression of infiltrates on the chest radiograph by $1.38{\pm}4.22$ days. The mortality rate was higher in the patients with NCVD than in those with CVD (50.0% vs. 23.1%). Conclusion : The DAH can occur not only in patients with CVD but also in those with NCVD. Higher creatinine level CVD in patients is associated with renal involvement in conjunction with DAH. The maximal drop in hemoglobin preceeding the progression of infiltrates on the chest radiograph suggests that the drop in hemoglobin is important for diagnosing DAH.

• Tuberculosis and Respiratory Diseases
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• v.45 no.5
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• pp.1047-1057
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• 1998

Background : Sarcoidosis is a systemic granulomatous disorder of unknown origin and characterized by accumulation of T cells and macrophages. Various cytokines may play crucial roles in the activation of T cells and macrophages, and thereby in the formation of granulomas. However, little is known about the balance between proinflammatory cytokines and antiinflammatory cytokines in the development of sarcoid granulomas and disease activities. In the present study, we measured IL-6, IL-8 and IL-10 in the bronchoalveolar lavage fluid(BALF) from patients with pulmonary sarcoidosis to find out whether there is an imbalance between proinflammatory cytokines and antiinflammatory cytokines in the lung. Methods: Fourteen subjects with the diagnosis of sarcoidosis and six healthy volunteers were included. BALF was concentrated ten-fold by pressure ultrafiltration and each cytokine levels were measured by EUSA method. Active sarcoidosis was defined by major organ involvement or clinically progressive diseases. Results: The mean IL-6 levels in the BALF of the active sarcoidosis group were significantly increased than in controls or inactive sarcoidosis group(p<0.05). Meanwhile, the IL-8 levels were increased and IL-10 levels were decreased in the active sarcoidosis group than in controls or inactive sarcoidosis group without significance(p>0.05). In active pulmonary sarcoidosis patients, the IL-6 levels in BALF correlated with the BALF CD4/CD8 ratio(r=0.768, p<0.05) and IL-8 levels(r=0.564, p<0.05). Conclusions : The data presented showed that pro-inflammatory cytokine IL-6 is important in the pathogenesis of sarcoidosis and decreased tendency of anti-inflammatory cytokine IL-10 might also be involved in the development of granulomatous inflammation in sarcoidosis.

• 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.

• Radiation Oncology Journal
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• v.20 no.2
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• pp.139-146
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• 2002

Purpose : This study evaluated the treatment outcomes, patterns of failure, and treatment related complications of primary lymphoma patients who received definitive radiation therapy. Materials and Methods : A retrospective analysis was undertaken for 31 patients with primary orbital lymphoma at the Asan Medical Center between February 1991 and April 2001. There were 18 males and 13 females with ages ranging from 3 to 73 years (median, 44 years). The involved sites were 9 conjunctivae, 12 eyelids and 10 other orbits. The histological types were 28 MALT lymphomas (low-grade B-cell lymphoma of mucosa-associated lymphoid tissue type), 1 diffuse large B-cell lymphoma, 1 anaplastic large cell lymphoma and 1 lymphoblastic lymphoma. The Ann Arbor stages were all IE $(100\%)$. Ann Arbor stage III or IV patients were excluded from this study, Bilateral orbital involvement occurred in 6 cases. Radiation therapy was given with one anterior port of high energy electrons $(6\~16\;MeV)$ for the lesions located at the anterior structures like the conjunctivae or eyelids. Lesions with a posterior extension or other orbital lesions were treated with 4 or 6 MeV photons with appropriately arranged portals. In particular, lens blocks composed of lead alloy were used in conjunctival or eyelid lesions. Twelve patients received chemotherapy. The median follow-up period was 53 months. Results : The 5-year overall, cause-specific, and disease-free survival was $91\%,\;96\%,\;and\;80\%$, respectively. The complete response rate 6 months after radiation therapy was $100\%$. Local recurrences were observed in 2 patients at 16 and 18 months after completion of radiation treatment. They were salvaged with additional radiation therapy. Two patients developed distant metastases. A MALT lymphoma patient with a lung relapse was successfully salvaged with radiotherapy, but the other lymphoblastic lymphoma patient with bone marrow relapse expired. There were no severe complications but 5 patients developed radiation-induced cataracts and 2 patients developed dry eye. Conclusion : Most primary orbital lymphomas consisted of MALT lymphomas. Radiation therapy was a successful treatment modality for orbital lymphoma without any severe complications. In cases of local relapses, radiation therapy is also a very successful salvage treatment modality.