• IMMUNE NETWORK
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• v.22 no.5
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• pp.40.1-40.24
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• 2022

Mesenchymal stem cells (MSCs) are attractive alternatives to conventional anti-asthmatic drugs for severe asthma. Mechanisms underlying the anti-asthmatic effects of MSCs have not yet been elucidated. This study evaluated the anti-asthmatic effects of intravenously administered MSCs, focusing on macrophages and monocytes. Seven-week-old transgenic (Tg) mice with lung-specific overexpression of IL-13 were used to simulate chronic asthma. MSCs were intravenously administered four days before sampling. We examined changes in immune cell subpopulations, gene expression, and histological phenotypes. IL-13 Tg mice exhibited diverse features of chronic asthma, including severe type 2 inflammation, airway fibrosis, and mucus metaplasia. Intravenous administration of MSCs attenuated these asthmatic features just four days after a single treatment. MSC treatment significantly reduced SiglecF^-CD11c^-CD11b⁺ monocyte-derived macrophages (MoMs) and inhibited the polarization of MoMs into M2 macrophages, especially M2a and M2c. Furthermore, MSCs downregulated the excessive accumulation of Ly6c^- monocytes in the lungs. While an intravenous adoptive transfer of Ly6c^- monocytes promoted the infiltration of MoM and Th2 inflammation, that of MSC-exposed Ly6c^- monocytes did not. Ex vivo Ly6c^- MoMs upregulated M2-related genes, which were reduced by MSC treatment. Molecules secreted by Ly6c^- MoMs from IL-13 Tg mice lungs upregulated the expression of fibrosis-related genes in fibroblasts, which were also suppressed by MSC treatment. In conclusion, intravenously administered MSCs attenuate asthma phenotypes of chronic asthma by modulating macrophages. Identifying M2 macrophage subtypes revealed that exposure to MSCs transforms the phenotype and function of macrophages. We suggest that Ly6c^- monocytes could be a therapeutic target for asthma management.

• Tuberculosis and Respiratory Diseases
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• v.44 no.5
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• pp.1083-1093
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• 1997

Background : So far, there have been numerous reports on organ damage due to cryptococcosis, however, cases of lung localization have been infrequently reported. Recently pulmonary cryptococcosis has been reported more frequently than before due to enhanced diagnostic techniques and increased underlying diseases. Method : The author, therefore, analyzed the clinical manifestations of 5 cryptococcosis cases that we experienced at Hanyang University Hospital from 1985 to 1996 and 9 cases reported in Korea from 1984 and 1996 retrospectively. The following results were obtained. Results : Cryptococcosis occurred frequently over sixth decade and the male to female ratio was 3.6 : 1. Underlying diseases included acute rejection after kidney transplantation, rheumatoid arthritis, autoimmune hepatitis, diabetes mellitus and state of bilateral adrenalectomy. Remaining 8 cases had no evidence of an underlying disease. Because the symptoms were subacute & nonspecific, and not improved by conventional antibiotics, 6 patients of 14 pulmonary cryptococcosis patients were treated as pulmonary tuberculosis before correct diagnosis was made. There were three asymptomatic cases. According to the results of CXR, solitary alveolar consolidation was the most common finding(8 cases) followed by diffuse infiltration(5 cases). It also showed pleural effusion, hilar lymphadenopathy and cavity formation that was rarely reported in world literature. The diagnasis was made through fine needle aspiration biopsy in 10 cases, open thoracotomy in 2 cases, transbronchial lung biopsy in 1 case. and thoracentesis with pleural biopsy in 1 case. Only one case showed positive result in sputum stain and culture, serum latex agglutination test for cryptococcus neoformans. Treatment modalities were various such as fluconazole, amphotericin B, flucytosine, ketoconazole, surgery and it's combination. After 1990 year, there was a trend that fluconazole or ketoconazole are more used than other therapeutic modalities. Conclusion : Because the symptoms are subacute & nonspecific and not improved by conventional antibiotics, pulmonary cryptococcosis is likely to misdiagnosis as pulmonary tuberculosis in Korea. Because the diagnosic yield of sputum stain, culture and serologic test for pulmonary cryptococcosis is low, histologic diagnosis is need in most pulmonary cryptococcosis.

• Korean Journal of Poultry Science
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• v.35 no.4
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• pp.341-350
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• 2009

The research work was carried out to study the pathogenesis covering the clinical signs, gross and histopathological lesions in different organs, and reisolation and identification of the organisms after experimental infection with the local isolate of Salmonella enterica serovar. enterica subspecies (S.) Pullorum at different time interval of the experiment during the period February 2006 to December 2006. One hundred pullets (seronegative to S. Pullorum of 12 weeks age were purchased and divided into 5 (A, B, C, D and E) groups and each group consisted of 20 birds. Four groups (A, B, C and D) were infected orally with a dose of $10^6\;CFU$, $10^7\;CFU$, $2{\times}10^7\;CFU$, $10^8\;CFU$ of S. Pullorum, respectively, and one group (E) was treated as uninfected control. The used methods were necropsy and histopathology, culture of bacteria, staining and biochemical test of Salmonella. Five birds from each group were randomly selected and sacrificed $1^{st}$ week, $2^{nd}$, $3^{rd}$ and $4^{th}$ weeks of post infection (PI). From all the groups, the bacteriological samples (crop, liver, lung, heart, spleen, bile duodenum, ceca and blood) were collected with pre enriched in buffered peptone water in sterile poly bags. Liver, lungs, heart, spleen, intestine, etc. were collected in 10% buffered-formalin for histopathological examination. No clinical signs, gross and histopathological lesions were found in control group and no S. Pullorum was reisolated. Clinical sign of experimentally infected with S. Pullorum in pullets were loss of appetite (100%), slight depression (75%), ruffled feathers (85%), diarrhea (60%) and loss of weight (100%) in chickens. The feed intake and body weight at different weeks after PI differed significantly (p<0.01) among the groups. Grossly, the highest recorded lesion was button-like ulcer in the ceca (80%) and the lowest was white nodules in lungs (1.25%). S. Pullorum were reisolated from crop (91.25%), liver (91.25%), lung (83.75%), heart (71.25%), spleen (87.75%), bile (33.25%), duodenum (92.50%), ceca (97.50%) and from different group of infection (61.25%). The highest microscopic findings were intestinal and cecal mucosa and submucosa exhibited infiltration of mononuclear cells and congestion (96.25%), and the lowest finding was nodule formation in the lungs (3.75%). The pattern of the disease production by local isolate of S. Pullorum in Bangladesh is almost similar with other isolates in different countries.

• Tuberculosis and Respiratory Diseases
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• v.49 no.2
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• pp.169-178
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• 2000

Background : Usually fever subsides within one week in over 90% of pulmonary tuberculosis (TBp) patients after the start of short-course anti-tuberculosis therapy, but occasionally it persists over two weeks after treatment. When the fever persists, drug resistance, combined infection, or drug fever, and so on, are considered as an etiology and, in some cases, drugs are changed. But inadvertent discontinuation of a short-course regimen inevitably will extend the duration of treatment, and the treatment completion may be delayed. This study was performed to investigate the causes of prolonged fever (PF) and to identify the predictors of PF in drug-susceptible TBp patients in Korea. Method : Five hundred-ninety-eight patients, who were admitted to Asan Medical Center from January 1996 to March 1999, diagnosed with TBp and prescribed short-course, anti-tuberculosis treatment, were reviewed. PF was defined as having fever over two weeks despite treatment. The causes of PF were analyzed. Drug-sus-ceptible TBp patients who presented no causes for PF, except turberculosis itself, were selected(n=22), and they were compared with those who had no fever at diagnosis (n=22) and those who had fever at diagnosis, which had subsided within two weeks after treatment (n=22). Clinical, laboratory, and radiological parameters were compared among the three groups. Results : Twenty-eight (4.8%) of 598 patients showed PF over two weeks despite short-course treatment. The causes of PF were drug fever (n=2), multi-drug resistant tuberculosis (n=3), disseminated Mycobacterium kansasii infection (n=1), and drug-susceptible tuberculosis itself (n=22). The patients with PF had more risk factors for tuberculosis, long duration of symptoms before treatment, night sweats, weight long, numerous acid fast bacilli on sputum smear, anemia, hyponatremia, hypoalbuminemia, over three lung cavity numbers and extensive infiltration, indicating that they had prolonged and extensive lung diseases. Conclusion : The main cause of PF in TBp despite short-course regimen seems to be drug-susceptible but extensive disease in Korea. Any changes to the drug regiment provided for TBp patients with prolonged fever despite treatment should be carefully considered.

• Tuberculosis and Respiratory Diseases
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• v.52 no.1
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• pp.37-45
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• 2002

Background: Diffuse panbronchiolitis(DPB) is a chronic inflammatory lung disease that presents as coughing, copious sputum, exertional dyspnea, which progresses to bronchiectasis. The pathogenesis of bronchiectasis is controlled by inflammatory mediators, which are closely related to mucus hypersecretion, goblet cell dysplasia. In recent studies, the epidermal growth factor receptor(EGFR) system was reported to be associated with this process. It was hypothesized that a relationship exists between goblet cell dysplasia, EGFR expression, and inflammatory mediators produced by neutrophil. Method: Alcian blue/periodic acid -Schiff(AB/PAS) stain, MUC5AC, EGFR, CD16 immunohistochemical stain were examined to investigate a role for the EGFR system in a mucus hypersecretion in DPB using the lung biopsy specimens from 13 DPB patients and 6 controls. Results : In the DPB group, the AB/PAS and MUC5AC -stained areas were $8.31{\pm}3.36%$, $11.46{\pm}4.68%$, respectively. In the control group, the AB/PAS- and MUC5AC-stained areas were $50.5{\pm}5.77%$, $53.3%{\pm}6.67%$, which was significantly larger than in the DPB group (each comparison, p<0.05). The percentage of EGFR expression was $9.54{\pm}4.95%$ in the DPB group, but zero in of the control group. The extent of neutrophilic infiltration was $71.92{\pm}3.71$/5HPF in the DPB group and $45.0{\pm}5.73$/5HPF in the control group, which was statistically significant(p=0.002). Conclusion: The EGFR system is highly related to goblet cell dysplasia, mucus hypersecretion and neutrophilic inflammation in DPB.

• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.795-804
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• 1998

Background: Chronic eosinophilic pneumonia(CEP) is interstitial lung disease characterized by multiple infiltration on radiographic study, accumulation of eosinophils in the alveolar space and interstitium of the lung, chronic persistent symptoms and possible relapse. Acute eosinophilic pneumonia(AEP) is a recently described illness, characterized by rapid clinical course, acute respiratory insufficiency and no relapse. Method : To better characterize acute and chronic eosinophilic pneumonia, we studied the clinical and laboratory features of 16 patients(AEP : 7 patients, CEP : 9 patients), which were clinico-pathohistologically diagnosed and not to be associated with organic disorders producing peripheral blood eosinophilia. Results: The mean age was higher for patients with CEP than for patients with AEP ($55.4{\pm}15.1$ vs. $24.6{\pm}7.9$ years, p<0.05). High fever(above $38^{\circ}C$) was presented in all patients of AEP and in one patient(11%) of CEP. All patients of AEP and eight patients (89%) of CEP showed bilateral pulmonary infiltrates, and 6 patients(86%) of AEP and 2 patients(22%) of CEP showed pleural effusion in chest radiograph. The mean white blood cell count of AEP and CEP were $17,186/mm^3$ and $12,867/mm^3$, respectively. The mean peripheral blood eosinophil count of AEP and CEP were $939/mm^3$ and $2,104/mm^3$, respectively. The mean eosinophil fraction of BAL fluid of AEP and CEP were 32.4% (range: 18~47%) and 35.8% (range: 15.3~88.2%), respectively. The mean $PaO_2$ was lower for patients with AEP than for patients with CEP ($44.1{\pm}15.5$ vs. $62.7{\pm}6.9$mmHg, p<0.05). All patients of AEP and CEP were initially treated with antibiotics. All patients of CEP and one patients of AEP were finally required systemic steroid therapy. 6 patients of AEP were improved without steroid therapy. Relapse was observed in 3 patients(33%) of CEP. Conclusion : Compair with of chronic eosinophilic pneumonia, acute eosinophilic pneumonia was characterized by relatively young age, acute onset, high fever, severe hypoxemia, diffuse pulmonary infiltrates with pleural effusion, steroid therapy is effective but spontaneous improvement with conservative therapy was frequent.

• Tuberculosis and Respiratory Diseases
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• v.60 no.5
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• pp.532-539
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• 2006

Background : The incidence of pulmonary tuberculosis has been reducing, but endobronchial tuberculosis continues to be a signigicant heath problem. We performed prospectively bronchoscopy in patients diagnosed with pulmonary tuberculosis in order to evaluate the frequency of endobronchial tuberculosis and its related findings. Follow-up bronchoscopy was also performed after treatment to evaluate the incidence of endobronchial complications such as stenosis and remaining lesions. Methods : From January, 1999 to December, 2003, bronchoscopy was performed on patients newly diagnosed with pulmonary tuberculosis. Results : 458 patients were enrolled in this study, out of 699 patients with pulmonary tuberculosis from 1999 to 2003. 234(51%) had endobronchial tuberculosis. The frequency was 40.3% in males and 66.3% in females, The most common symptom was nonspecific cough and sputum, and the main radiologiy finding was patchy infiltration. The most common subtype of endobronchial tuberculosis was the edema-hyperemic form. The right lung was involved more frequently than the left, and the left upper lobe was the most commonly involved site. 58 patients underwent follow-up bronchoscopy and most of been cured without major sequels. However, 8 patients had a stenosis of trachea and main bronchus, and 6 patients had still had endobronchial lesions. Therefore the treatment was prolonged for 3 months. Conclusion : Endobronchial tuberculosis of pulmonary tuberculosis has been remained of high incidence. bronchoscopic and follow-up bronchoscopy examination needs to evaluate the incidence of endobronchial tuberculosis and its related findings and major complication despite of treatment.

• Clinical and Experimental Pediatrics
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• v.49 no.8
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• pp.889-894
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• 2006

Purpose : Asthma is characterized by the presence of airway hyperresponsiveness(AHR) and inflammation. The extensive eosinophil infiltration into the lung is the hallmark of asthma and contributes to the damage of respiratory epithelium during late phase airway responses. Eotaxin is the major eosinophil chemoattractant found in bronchoalveolar lavage(BAL) fluid of allergic inflammation. IL-13 has been known to induce the expression of exotaxin and eosinophilia. IL-13 also induces airway inflammation, mucus production and leads to marked fibrosis, airway remodeling and AHR. We investigated whether serum IL-13 levels can reflect the presence of airway hyperresponsiveness in children with asthma, and the relationship between serum IL-13 and eotaxin levels. Methods : Using sandwich enzyme-linked immunosorbent assay, the serum IL-13 and eotaxin levels were measured in 13 atopic asthmatics, 5 atopic non-asthmatics and 12 control subjects. Metacholine challenge tests were performed in all subjects. Airway hyperresponsiveness to metacholine was expressed as provocative concentration of metacholine causing a 20% fall in FEV1[$PC_{20}mg/mL$]. $PC_{20}$ value of 25 mg/mL was used as a cut-off for defining a AHR. Results : Serum IL-13 levels showed positive correlation with eotaxin levels. Serum IL-13 and eotaxin levels showed no differences among atopic asthmatics, atopic non-asthmatics and control subjects. And there were no differences serum IL-13 and eotaxin levels in children with and without AHR and atopy. Serum IL-13 and eotaxin levels did not correlate with $logPC_{20}$ levels. Conclusion : IL-13 is closely related to the eotaxin release. But serum IL-13 and eotaxin per se can't predict the severity of airway hyperresponsiveness. IL-13 and eotaxin may have local effect on respiratory epithelium or there can be some factors to induce airway hyperresponsiveness other than serum IL-13 in asthmatic airways.

• Journal of Life Science
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• v.17 no.8 s.88
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• pp.1090-1099
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• 2007

Myristicin, l-allyl-3,4-methylenedioxy-5-methoxybenzene, was one of the major essential oils of nutmeg. However, its anti-allergic effect in the Th1/Th2 immune response was poorly understood. Recently, it was shown that T-bet and GATA-3 was master Th1 and Th2 regulatory transcription factors. In this study, we have attempted to determine whether myristicin regulates Th1/Th2 cytokine production, T-bet and GATA-3 gene expression in ovalbumin (OVA)-induced asthma model mice. Myristicin reduced levels of IL-4, Th2 cytokine production in OVA-sensitized and challenged mice. In the other side, it increased $IFN-{\gamma}$, Th1 cytokine production in myristicin administrated mice. We also examined to ascertain whether myristicin could influence eosinophil peroxidase (EPO) activity. After being sensitized and challenged with ovalbumin (OVA) showed typical asthmatic reactions. These reactions included an increase in the number of eosinophils in bronchoalveolar lavage fluid, an increase in inflammatory cell infiltration into the lung tissue around blood vessels and airways, and the development of airway hyper-responsiveness (AHR). The administration of myristicin before the last airway OVA challenge resulted in a significant inhibition of all asthmatic reactions. Accordingly, these findings provide new insight into the immunopharmacological role of myristicin in terms of its effects in a murine model of asthma.

• Journal of Life Science
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• v.19 no.6
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• pp.735-743
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• 2009

The common word flavonoids is often used to classify a family of natural compounds, highly abundant in all higher plants, that have received significant therapeutic interest in recent years. Naringin is associated with a reduced risk of heart disease, neurodegenerative disease, cancer and other chronic diseases; however the molecular basis of this effect remains to be elucidated. Thus we attempted to elucidate the anti-allergic effect of Naringin in ovalbumin (OVA)-induced asthma model mice. The OVA-induced mice showed allergic reactions in the airways. These included an increase in the number of eosinophils in bronchoalveolar lavage (BAL) fluid, an increase in inflammatory cell infiltration into the lung around blood vessels and airways, airway luminal narrowing, and the development of airway hyper-responsiveness (AHR). The administration of Naringin before the last airway OVA challenge resulted in a significant inhibition of all asthmatic reactions. Accordingly, this study may provide evidence that Naringin plays a critical role in the amelioration of the pathogenetic process of asthma in mice. These findings provide new insight into the immunopharmacological role of Naringin in terms of its effects on asthma in mice.