• Tuberculosis and Respiratory Diseases
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• v.53 no.6
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• pp.619-634
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• 2002

Background : Many inflammatory mediators and collagenases are involved in the pathogenesis of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). The increase of matrix metalloproteinase-9 (MMP-9, gelatinase-B) produced mainly by inflammatory cells was reported in many ALI models and connective tissue cells. In this study, the expression of MMP-9 in ventilator-induced lung injury (VILI) model and the effects of matrix metalloproteinase inhibitor (MMPI) on VILI were investigated. Methods : Eighteen Sprague-Dawley rats were divided into three groups: low tidal Volume (LVT, 7mL/Kg tidal volume, 3 $cmH_2O$ PEEP, 40/min), high tidal volume (HVT, 30mL/Kg tidal volume, no PEEP, 40/min) and high tidal volume with MMPI (HVT+MMPI) groups. Mechanical ventilation was performed in room air for 2 hours. The 20 mg/Kg of CMT-3 (chemically modified tetracycline-3, 6-demethyl 6-deoxy 4-dedimethylamino tetracycline) was gavaged as MMPI from three days before mechanical ventilation. The degree of lung injury was measured with wet-to-dry weight ratio and acute lung injury score. Expression of MMP-9 was studied by immunohistochemical stain with a mouse monoclonal anti-rat MMP-9 $IgG_1$. Results : In the LVT, HVT and HVT+MMPI groups, the wet-to-dry weight ratio was $4.70{\pm}0.14$, $6.82{\pm}1.28$ and $4.92{\pm}0.98$, respectively. In the HVT group, the ratio was significantly higher than other groups (p<0.05). Acute lung injury score measured by five-point scale was $3.25{\pm}1.17$, $12.83{\pm}1.17$ and $4.67{\pm}0.52$, respectively. The HVT group was significantly damaged by VILI and MMPI protects injuries by mechanical ventilation (p<0.05). Expression of MMP-9 measured by four-point scale was $3.33{\pm}2.07$, $12.17{\pm}2.79$ and $3.60{\pm}1.95$, respectively, which were significantly higher in the HVT group (p<0.05). Conclusion : VILI increases significantly the expression of MMP-9 and MMPI prevents lung injury induced by mechanical ventilation through the inhibition of MMP-9.

• Clinical and Experimental Pediatrics
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• v.48 no.12
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• pp.1378-1384
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• 2005

Purpose : We hypothesized dexrazoxane(DXR) and pentoxifylline(PTX) may prevent myocardial damage in adriamycin(ADR)-induced cardiomyopathic rat model. We also investigated their effects on the myocardial apoptosis and fibrosis in ADR induced cardiomyopathy. Methods : The six-week old female Spregue-Dawley rats were divided into control group(CNT, n=4), ADR group(n=6), ADR+DXR group(DXR, n=5), ADR+PTX group(PTX, n=6), ADR+DXR+PTX group(DXPT, n=5). ADR(5 mg/week, twice) was administrated intravenously to rats except CNT group to induce cardiomyopathy. The PTX(50 mg/kg/day) was administered daily from day-0 to Day-21. The DXR(100 mg/kg) was administered 30 minutes before each ADR injection. On day 21, the rats were sacrificed and the degree of histopathologic changes of hypercontraction band necrosis, cytoplasmic vacuolar change and fibrosis were scored. Immunohistochemical staining for Bcl-2 expression and RT-PCR for $TNF-{\alpha}$ and CTGF were performed. Results : Histopathological scores of myocardial damage were significantly higher in ADR rats than CNT rats(P<0.05), and significantly lower in DXPT rats than ADR rats(P<0.01). Myocardial fibrosis was prevented in both PTX rats and DXPT rats. The expression of Bcl-2 was weaker in ADR rats than that in CNT rats(P<0.05), and stronger in both DXR and DXPT rats than that in ADR rats (P<0.05). $TNF-{\alpha}$ concentration of ADR rats was not different from that of treated groups. Conclusion : DXR prevented myocyte apoptosis with increased Bcl-2 expression, and PTX prevented myocardial fibrosis in ADR induced cardiomyopathic rats. The combination therapy of DXR and PTX showed prevention of cardiomyopathy in ADR induced cardiomyopathy rat model.

• Journal of Chest Surgery
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• v.40 no.8
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• pp.529-535
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• 2007

Background: An imbalance between oxidants and antioxidants leads to oxidative stress, and this has been proposed to play an important role in the pathogenesis of lung neoplasm. Apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE/ref-1) is a multifunctional protein involved in DNA base excision repair and the redox regulation of many transcription factors. However, the alteration of the expressed levels of APE/ref-1 in non-small cell lung cancer is unknown. Material and Method: Forty-nine patients with surgically resected non-small cell lung cancer (NSCLC) were included in this study. Immunohistochemical staining with APE/ref-1 antibodies was performed, and their expressions were analyzed via Western blotting for specific antibodies. Result: APE/ref-1 was localized at the nucleus and mainly in the non-tumor region of the NSCLC tissue specimens; it was expressed in the cytoplasm and nucleus of the NSCLC. The nuclear and cytoplasmic expressions of APE/ref-1 in lung cancers were markedly up-regulated in the NSCLC, and this was correlated with the clinical stage. Catalase, as first-line antioxidant defense, was dramatically decreased in the NSCLC. Conclusion: Taken together, our results suggest that APE/ref-1, and especially cytoplasmic APE/ref-1, was upregulated in the lung cancer regions, and this may contribute to the compensatory defense system against oxidative stress. A low expression of catalase might have fundamental effects on the extracellular redox state of lung tumors, along with the potential consequences for the tumors.

• Radiation Oncology Journal
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• v.25 no.3
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• pp.145-150
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• 2007

Purpose: To investigate the degree and effect of cyclooxygenase (COX)-2 expression on the survival of patients with glioblastoma multiforme (GM). Materials and Methods: Between 1997 and 2006, thirty consecutive GM patients treated with surgery and postoperative radiotherapy (dose range: $44{\sim}65.1$ Gy, median dose: 61.2 Gy) were included in the study. Three patients were excluded that discontinued radiotherapy before receiving a dose of 40 Gy due to mental deterioration. The expression of the COX-2 protein in surgical specimens was examined by immunohistochemical analysis. Survival analysis and verification were performed with respect to sex, age, performance status, resection extent, radiotherapy dose, and degree of COX-2 expression using the Kaplan-Meier method and the log rank test. Results: The median length of follow-up was 13.3 months (range:$6{\sim}83$ months). Staining for COX-2 was positive in all patient samples. Staining for COX-2 that was positive for over 75% of the tumor cells was found in 24 patients. Staining for COX-2 that was positive in less than 25% of tumor cells was found in 3 patients (10.0%), staining for COX-2 that was positive in 25 to 50% of tumor cells was found in 1 patient (3.3%), staining for COX-2 that was positive in 50 to 75% of tumor cells was found in 2 patients (6.7%) and staining for COX-2 that was positive in 75 to 100% of tumor cells was found in 24 patients (80.0%). The median survival and two-year survival rate were 13.5 months and 17.5%, respectively. The survival rate was influenced significantly by the degree of resection (tumor removal by 50% or more) and radiotherapy dose (59 Gy or greater) (p<0.05). The median survival of patients with staining for COX-2 that was positive in less than 75% of tumor cells and in at least 75% of tumor cells was 15.5 and 13.0 months, respectively (p>0.05), and the two-year survival for these groups was 33.3 and 13.3%, respectively (p>0.05). Conclusion: The absence of a statistical correlation between the degree of COX-2 expression and survival in GM patients, despite the high rate of COX-2 positive tumor cells in the GM patient samples, requires further studies with a larger series to ascertain the prognostic value of the degree of COX-2 expression in GM patients.

• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.835-845
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• 1998

Background: Silica-induced lung diseases is characterized by the accumulation of inflammatory cells at early stage and fibrosis in pulmonary parenchyma and interstitium at late stage. As a consequence of inflammation, silicosis is accompanied with the expansion of interstitial collagen and the formation of fibrotic nodule. In this process, several kinds of lung cells produce cytokines which can amplify and modulate pulmonary fibrosis. The alveolar macrophage is a potent source of proflammatory cytokines and growth factor. But in the process of silicotic inflammation and fibrosis, there are many changes of the kinetics in cytokine network. And the sources of cytokines in each phase are not well known. Method: 2.5 mg of silica was instillated into the lung of C57BL/6J mice. After intratracheal instillation of silica, the lungs were removed for imunohistochemical stain at 1, 2, 7 day, 2, 4, 8, 12 week, respectively. We investigated the expression of IL-1$\beta$, IL-6, TNF-$\alpha$ and TGF-$\beta$ in lung tissue. Results: 1) The expression of IL-6 increased from 1 day after exposure to 8 weeks in vascular endothelium. Also peribronchial area were stained for IL-6 from 7 days and reached the peak level for 4 weeks. 2) The IL-1 $\beta$ was expressed weakly at the alveolar and peribronchial area through 12 weeks. 3) The TNF-$\alpha$ expressed strongly at alveolar and bronchial epithelia during early stage and maintained for 12 weeks. 4) TGF-$\beta$ was expressed strongly at bronchial epithelia and peribronchial area after 1 week and the strongest at 8 weeks. Conclusion: The results above suggests IL-6, TNF-$\alpha$ appear to be a early inflammatory response in silica induced lung fibrosis and TGF-$\beta$ play a major role in the maintenance and modulation of fibrosis in lung tissue. And the regulation of TNF-$\alpha$ production will be a key role in modultion of silica-induced fibrosis.

• Journal of Yeungnam Medical Science
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• v.6 no.1
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• pp.47-57
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• 1989

T. verrucosum infection has been reported for the first time in 1986 in Korea and has been increasing progressively. To evaluate the progress of clinical and histopathological change of dermatophytosis caused by T. verrucosum, inoculation study, using T. verrucosum isolated from infected human(human strain) and from infected cattle(cattle strain), was done in 24 male albino Hartley guinea pig. Their clinical and histopathological changes were evaluated. In addition, comparison for the growth rate between human strain and cattle strain on Sabouraud's glucose agar was made. The results were as follows: 1. Growth rate on Sabouraud's glucose agar : Cattle strain showed significantly more rapid growth rate than human strain on Sabouraud's glucose rate at $25^{\circ}C$ and $37^{\circ}C$. And cattle strain showed more rapid growth rate at $37^{\circ}C$ than $25^{\circ}C$. But human strain showed no significant difference of growth rate at both temperature. 2. Clinical findings: Initial erythema, scale and crust were developed about 8th after inoculation. All three findings reached maximum severity about 12th to 16th day and disappeared about 30th to 34th day after inoculation. There was no significant difference in progress of erythema, scale and crust between cattle strain and human strain. 3. Histopathological findings: Although mild acanthosis was noticed on the 3rd day after inoculation, the other findings including parakeratosis, intraepidermal abscess, spongiosis and vascular change, cellular infiltration were found on 9th day after inoculation. They reached maximum severity on the 12th day and lasted to the 25th day after inoculation. After that, all three findings were decreased gradually between 29th day and 33th day. On the PAS stainings, hyphae and spores were found on the 6th day and disappeared on the 21th day after inoculation. 4. In trichophytin skin test, all of the 24 guinea pigs became positive within average $9.83{\pm}1.17$ lays. These findings suggested that dermatophytosis caused by T. verrucosum induced rapid cell mediated immunity and contributed to rapid resolution of the lesion.

• Korean Journal of Food Science and Technology
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• v.54 no.1
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• pp.43-51
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• 2022

Regulation of the hair follicle cycle in association with dermal papilla cells is one of the most interesting targets for promoting hair regrowth. In this study, we examined whether steam-dried Betula platyphylla extracts (BPE) promote hair growth by upregulating in vitro and in vivo responses of dermal papilla cells. The data showed that BPE3 contained high amounts of phenolic compounds with higher antioxidant effects and increased hair growth-related genes, including fibroblast growth factor7 and Wnt7b, in dermal papilla cells. Notably, BPE3 effectively enhanced the formation of hair follicles by increasing FGF7, Wnt7b, and vascular endothelial growth factor in C57BL/6N dorsal skins. Additionally, BPE3 significantly decreased the expression of inflammatory repertoires, inducible nitric oxide synthase, interleukin-6, and cyclooxygenase 2. Several small molecules, such as betulin and unsaturated fatty acids, support the pharmacological activity of BPE3. In conclusion, BPE3 effectively promoted hair growth by activating dermal papilla cells and enhancing hair follicle cycles by attenuating the inflammatory environment in the scalp.

• Radiation Oncology Journal
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• v.22 no.1
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• pp.40-54
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• 2004

Purpose : Captopril (angiotension converting enzyme inhibitor) is known to have a radioproptective effect in the lungs, intestines and skin, but its effect in the heart is unclear. To investigate the radioprotectlve efiect and mechanism of captopril on the heart, the histopathological changes and immunohistochemical stains were compared with radiation alone, and radiation combined with captopril, in the rats. Materials and Methods : The histopathological changes and immunohistochemical stains ($TNF{\alpha}$, $TGF{\beta}1$, PDGF and FGF2) were examined in the radiation alone and the combined captopril and radiation groups, 2 and 8 weeks after irradiation. Each group consisted of 8 to 10 rats (Sprague-Dawley). Irradiation (12.5 Gy) was given to the left hemithorax in a single fraction. Captopril (50 mg/Kg/d) mixed with water, was given orally and continuously from the first week prior to, up to the 8th week of the experiment. Results : In the radiation alone group, the ventricle at 2 weeks after irradiation showed prominent edema (p=0.082) and fibrin deposit (p=0.018) compared to the control group. At 8 weeks, the edema was decreased and fibrosis increased compared to those at 2 weeks. The histopathological changes of the combined group were similar to those of the control group, due to the reduced radiation toxicity at 2 and 8 weeks. The endocardial fibrin deposit (p=0.047) in the atrium, and the interstitial fibrin deposit (p=0.019) and edema (p=0.042) of the ventricle were reduced significantly in the combined group compared to those in the radiation alone group at 2 weeks. The expressions of $TNF-{\alpha}$, $TGF-{\beta}1$, PDGF and FGF-2 in the radiation alone group were more increased than in the control group, especially in the pericardium and endocardium of the atrium at 2 weeks. At 8 weeks, the pericardial $TNF-{\alpha}$ and $TGF-{\beta}1$ in the radiation alone group continuously increased. The expressions of $TNF-{\alpha}$, $TGF-{\beta}1$ and PDGF were decreased in the combined group at 2 weeks. At 8 weeks, the expressions of $TNF-{\alpha}$ in the atrial and ventricular pericardia were markedly reduced (p=0.049, p=0.009). Conclusion : This study revealed that the early heart damage induced by radiation can be reduced by the addition of captopril in a rat model. The expressions of $TNF-{\alpha}$, $TGF-{\beta}1$ and PDGF were further decreased in the combined compared to the radiation alone group at both 2 and 8 weeks. From these results, it may be concluded that these cytokines probably play roles in the radioprotective mechanism of captopril from the radiation-induced heart toxicity, similarly to in other organs.

• Journal of Chest Surgery
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• v.40 no.4 s.273
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• pp.264-272
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• 2007

Background: Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis, including stimulating the proliferation and migration of vascular smooth muscle cells (VSMCs). It has been known that diabetes is associated with accelerated cellular proliferation via VEGF, as compared to that under a normal glucose concentration. We investigated the effects of selective blockade of a VEGF receptor by using anti-Flt-1 peptide on the formation and hyperplasia of the neointima in balloon injured-carotid arteries of OLETF rats and also on the in vitro VSMCS' migration under high glucose conditions. Material and Method: The balloon-injury method was employed to induce neointima formation by VEGF. For f4 days beginning 2 days before the ballon injury, placebo or vascular endothelial growth factor receptor-1 (VEGFR-1) specific peptide (anti-Flt-1 peptide), was injected at a dose of 0.5mg/kg daily into the OLETF rats. At 14 days after balloon injury, the neointimal proliferation and vascular luminal stenosis were measured, and cellular proliferation was assessed by counting the proliferative cell nuclear antigen (PCNA) stained cells. To analyze the effect of VEGF and anti-Flt-1 peptide on the migration of VSMCs under a high glucose condition, transwell assay with a matrigel filter was performed. And finally, to determine the underlying mechanism of the effect of anti-Flt-1 peptide on the VEGF-induced VSMC migration in vitro, the expression of matrix metalloproteinase (MMP) was observed by performing reverse transcription-polymerase chain reaction (RT-PCR). Result: Both the neointimal area and luminal stenosis associated with neointimal proliferation were significantly decreased in the anti-Flt-1 peptide injected rats, ($0.15{\pm}0.04 mm^2$ and $ 36.03{\pm}3.78%$ compared to $0.24{\pm}0.03mm^2\;and\;61.85{\pm}5.11%$, respectively, in the placebo-injected rats (p<0.01, respectively). The ratio of PCNA(+) cells to the entire neointimal cells was also significantly decreased from $52.82{\pm}4.20%\;to\;38.11{\pm}6.89%$, by the injected anti-Flt-1 peptide (p<0.05). On the VSMC migration assay, anti-Flt-1 peptide significantly reduced the VEGF-induced VMSC migration by about 40% (p<0.01). Consistent with the effect of anti-Flt-1 peptide on VSMC migration, it also obviously attenuated the induction of the MMP-3 and MMP-9 mRNA expressions via VEGF in the VSMCS. Conclusion: Anti-Flt-1 peptide inhibits the formation and hyperplasia of the neointima in a balloon-injured carotid artery model of OLETF rats. Anti-Flt-1 peptide also inhibits the VSMCs' migration and the expressions of MMP-3 and MMP-9 mRNA induced by VEGF under a high glucose condition. Therefore, these results suggest that specific blockade of VEGFR-1 by anti-Flt-1 peptide may have therapeutic potential against the arterial stenosis of diabetes mellitus patients or that occurring under a high glucose condition.

• Journal of Chest Surgery
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• v.36 no.6
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• pp.397-403
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• 2003

Background: The research sought to identify the clinical features of pleomorphic carcinoma of the lung generally known as a rare subtype in accordance with the lung cancer classification done in 1999 by WHO. Material and Method: 250 cases of surgically resected lung cancers were collected in this hospital from January 1992 to December 2001. This study included 42 cases of pleomorphic carcinoma diagnosed through light microscope and immunohistochemistry. Result: Out of 42 cases, males represented 31, and females 11, the age ranged from 26 to 77. Main clinical symptoms included coughing, hemoptysis, sputum. Diagnoses disclosed the stage as stage la in 3 cases (7%), Ib in 16 (38%), IIa in 1 (2%), IIb in 8 (19%), IIIa in 15 (35%), and IIIb in 1 (2%). Out of these, no lymph node metastasis was represented in 23 cases (54%), while N1 and N2 involving lymph node metastasis was shown 19 cases (46%). A total of 19 patients developed metastasis, comprising the brain in 5 cases (26%), bone in 4 (21%), muscle in 4 (21%), Lymph node in 2 (10%), and 1 liver, ovary, contralateral lung, and adrenal gland, respectively. The size of the tumor ranged from 1 cm to 11 cm, averaging 5.85 cm. Out of the 42 patients, the total two-year and five-year survival rates in accordance with the Kaplan-Meier method represented 26% and 13%, respectively, These figures compared to the corresponding 44% and 34% in cases other than pleomorphic carcinoma from the survey target of 256 cases, proved to be significantly low (p<0.002). No significant difference was found in the survival rates compared between age and tumor size, between stage I and above stage II, and between N0 and above N1. Patients who developed postoperative metastasis all died, and showed significantly low survival rates (p<0.002) compared to those patients without metastasis. Conclusion: With the new diagnosis method of f999 WHO's lung cancer classification applied, pleomorphic carcinoma showed a higher prevalence rate than under previous classifications, their postoperative survival rate was significantly low compared to histologic type of non small cell lung carcinomas.