• Tuberculosis and Respiratory Diseases
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• v.51 no.4
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• pp.303-314
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• 2001

Background : Matrix metalioproteinase(MMP)-2 and MMP-9 have been known to play an important role in cell migration and the tissue remodeling process by type IV collagen lysis, a major component of the basement membrane. Intra-alveolar fibrosis, secondary to an injury to the basement membrane of the alveolar epithelial lining, is a major process in the pathogenesis of idiopathic pulmonary fibrosis(IPF). Therefore, MMP-2 and MMP-9 was hypothesized to play an important role in IPF pathogenesis. As a result, their level may reflect the activity or prognosis. Method : Forty one progressive IPF patients(age $59.82{\pm}1.73$ years, M:F=23:18), 16 patients with stable IPF for more than one year without therapy(age : $63.6{\pm}2.8$ years, M:F=13:3), and 7 normal controls were enrolled in this study. The MMP-2 and MMP-9 levels in the BAL fluid and alveolar macrophage conditioned media(AM-CM) were measured by zymography and the TIMP-1 level was measured by ELISA. Results : 1) The MMP-2 level in BALF was highest in the progressive IPF group ($1.36{\pm}0.28$) followed by the stable group ($0.46{\pm}0.13$) and the controls ($0.08{\pm}0.09$), which was statistically significant. The MMP-9 level of the IPF ($0.31{\pm}0.058$) and the stable group ($0.22{\pm}0.078$) were higher than that of the control group ($0.002{\pm}0.004$). In the AM-CM, only MMP-9 was detected, which was significantly higher in IPF group ($0.80{\pm}0.1O$) than in the control group($0.23{\pm}0.081$). The TIMP-1 level was also higher in both the IPF ($36.34{\pm}8.62\;{\mu}g/ml$) and stable group ($20.83{\pm}8.53\;{\mu}g/ml$) compared to the control group ($2.80{\pm}1.05\;{\mu}g/ml$) (p<0.05). 3) There was a correlation between the MMP-2 level in the BALF with the total cell number(r=0.298) and neutrophils(r=0.357) (p<0.05), and the MMP-9 level with the number of neutrophils (r=0.407) and lymphocytes (r=0.574)(p<0.05). The TIMP-1 level correlated with the total number of cell (r=0.338, p<0.05) and neutrophils(r=0.449, p=0.059). Conclusion : Both MMP and TIMP appear to play an important role in IPF pathogenesis, and their level may reflect the disease activity.

• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.846-860
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• 1998

Background: Endotoxin (LPS : lipopolysaccharide), a potent activator of immune system, can induce acute and chronic inflammation through the production of cytokines by a variety of cells, such as monocytes, endothelial cells, lymphocytes, eosinophils, neutrophils and fibroblasts. LPS stimulate the mononucelar cells by two different pathway, the CD14 dependent and independent way, of which the former has been well documented, but not the latter. LPS binds to the LPS-binding protein (LBP), in serum, to make the LPS-LBP complex which interacts with CD14 molecules on the mononuclear cell surface in peripheral blood or is transported to the tissues. In case of high concentration of LPS, LPS can stimulate directly the macrophages without LBP. We investigated to detect the generation of proinflammatory cytokines such as interleukin 1 (IL-1), IL-6 and TNF-$\alpha$ and fibrogenic cytokine, TGF-$\beta$, by peripheral blood mononuclear cells (PBMC) after LPS stimulation under serum-free conditions, which lacks LBPs. Methods : PBMC were obtained by centrifugation on Ficoll Hypaque solution of peripheral venous bloods from healthy normal subjects, then stimulated in the presence of LPS (0.1 ${\mu}g/mL$ to 100 ${\mu}g/mL$ ). The activities of IL-1, IL-6, TNF, and TGF-$\beta$ were measured by bioassaies using cytokines - dependent proliferating or inhibiting cell lines. The cellular sources producing the cytokines was investigated by immunohistochemical stains and in situ hybridization. Results : PBMC started to produce IL-6, TNF-$\alpha$ and TGF-$\beta$ in 1 hr, 4 hrs and 8hrs, respectively, after LPS stimulation. The production of IL-6, TNF-$\alpha$ and TGF-$\beta$ continuously increased 96 hrs after stimulation of LPS. The amount of production was 19.8 ng/ml of IL-6 by $10^5$ PBMC, 4.1 ng/mL of TNF by $10^6$ PBMC and 34.4 pg/mL of TGF-$\beta$ by $2{\times}10^6$ PBMC. The immunoreactivity to IL-6, TNF-$\alpha$ and TGF-$\beta$ were detected on monocytes in LPS-stimulated PBMC. Some of lymphocytes showed positive immunoreactivity to TGF-$\beta$. Double immunohistochemical stain showed that IL-1$\beta$, IL-6, TNF-$\alpha$ expression was not associated with CD14 postivity on monocytes. IL-1$\beta$, IL-6, TNF-$\alpha$ and TGF-$\beta$mRNA expression were same as observed in immunoreactivity for each cytokines. Conclusion: When monocytes are stimulated with LPS under serum-free conditions, IL-6 and TNF-$\alpha$ are secreted in early stage of inflammation. In contrast, the secretion of TGF-$\beta$ arise in the late stages and that is maintained after 96 hrs. The main cells releasing IL-1$\beta$, IL-6, TNF-$\alpha$ and TGF-$\beta$ are monocytes, but also lymphocytes can secret TGF-$\beta$.

• Journal of Animal Science and Technology
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• v.48 no.1
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• pp.9-14
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• 2006

Milk yield and its quality traits determine the dairy enterprise profitability and sustainability. Milk quality traits including somatic cell counts (SCC) is an upcoming economic challenge for dairy farming community in Korea. This study estimated the effect of parity, stage of lactation (early, mid and late lactation) on SCC, stress (blood cortisol) and immunity (blood IgG, lymphocyte and neutrophil) traits, their heritabilities and genetic correlations between them. SCS and blood neutrophil count were significantly affected by both parity and stage of lactation, however; IgG was affected by only stage of lactation, and blood cortisol and lymphocyte were not affected by both factors. The SCS has shown increasing trend with the parity, however; the difference between first and second parity, second and third parity were not significant. The SCS in early (≤90 days) and late lactation (181≤days) were higher than that of mid lactation (91～180 days). Cortisol concentration in blood was lowest in fourth parity, however; the differences among the first three parties were not significant. The IgG was higher in fourth parity compare with first parity however; all other comparisons were noted non-significant. The IgG concentration was significantly higher in early lactation than those of mid and late lactation. The blood lymphocytes were decreased with increasing parity however the differences beyond second parity were not significant. The neutrophils were increased with the increasing lactation stage however; the difference between early and mid lactation was not significant. Although heritability of SCS was still lower, but it was meaningful value (0.09) and may be considered to improve milk quality. The genetic correlations between SCS and cortisol (-0.96), and lymphocyte (-0.76) were highly negative. Heritability of cortisol was low, however genetic correlations between cortisol and lymphocyte (0.79) was highly positive. IgG with medium heritability was correlated negatively with lymphocyte (-0.88) and neutrophil (-0.98). Lymphocyte was lowly heritable and highly correlated with neutrophil concentration (0.87).This study suggested that cortisol, IgG, lymphocyte and neutrophil being positively genetically correlation with somatic cell score could be used as alternative traits to enhance milk quality in Holstein cattle. Further studies are warranted to estimate genetic relationships between immunological and production traits to increase the genetic merit of Holstein cows for milk yield, to improve animal health and economic viability under intensive management system.

• Journal of fish pathology
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• v.23 no.1
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• pp.69-83
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• 2010

This study was aimed to investigate the effects of injection of garlic, Allium sativum, extract and immersion in garlic juice on the nonspecific immunity and the resistance against the artificial infection of Streptococcus iniae and Edwardsiella tarda of the olive flounder, Paralichthys olivaceus. The nonspecific immune mechanisms were assessed in terms of lysozyme activity, nitroblue-tetrazolium (NBT) assay and superoxide dismutase (SOD) activity etc. Relative percent survival (RPS) was assessed by the challenge with S. iniae BS10 or E. tarda KE-1. Almost of the garlic extract injected groups showed the enhanced level of the tested nonspecific immune factors. In the challenge test with S. iniae and E. tarda, RPS of 5% garlic extract pre-injected group was much higher than that of any other tested groups, respectively. Almost of the garlic juice immersion tested groups exhibited strengthened nonspecific immune defence factors, lysozyme activity, the number of lymphocytes and neutrophils, NBT reduction and SOD activity in kidney. In the challenge with S. iniae and E. tarda, RPS in the 0.25 g/L of garlic juice immersed group was much higher than any other tested groups, respectively. The results suggest that the garlic extract and juice would be effective to enhance the nonspecific immunity and protective ability of olive flounder against fish disease such as S. iniae and E. tarda.

• Journal of fish pathology
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• v.6 no.1
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• pp.11-20
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• 1993

To study the immune responses of the japanese eel. Anguilla japonica, fish were injected intraperitoneally with several types of Edwardsiella tarda antigen, i. e., FKC(formalin killed cells), HKC(heat killed cells) or LPS(lipopolysaccharide), and the changes of immunocytes numbers, phagocytosis and agglutination titre in the peripheral blood of the fish were investigated. The number of lymphocytes in the peripheral blood of eels were decreased until 6 hours after injection, and then were turn to normal levels after 24 hours of injection. However, the level were slightly increased and were remained after 24 hours. The number of neutrophils of FKC, HKC or LPS injected fish were the highest at 12 hours after injection and were decreased slowly after that. Three weeks after the injections, the agglutination of antibody titre of all immunized groups were reached at 128 and were remained this level thereafter. However 6 weeks after the injections, that in HKC injected fish were dropped the level up to 4. Fish were injected with LPS and the blood from the fish were bled after 12 hours. Then the blood were incubated with E. tarda. Six hours after incubation, the phagocytic index was reached the highest level, 28.3. One week after the LPS injection, the blood were again bled and incubated with E. tarda. The phagocytic index at this time was 3.9. The phagocytic indexes of the fish injected with FKC and HKC, treted as same LPS injected fish as above, were 18.8 and 10.7, respectively. The phagocytic index of the control fish was 1.2. The antibacterial activities of normal antiserum against E. tarda were shown for both FKC and LPS injected fish, but not for HKC injected fish. The RPS(relative percentage of survival) of HKC, FKC and LPS injected fish in the challenge test were 10%, 20% and 30%, respectively. These results suggest that the effect of protection of the eel which were injected with antigen were varied with the method of preparation of the antigen.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.18 no.7
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• pp.130-139
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• 2017

This study investigated the effect of heat stress on the performance and blood characteristics in commercial pig farms. A total of 180 growing pigs and 180 finishing pigs were assigned to two treatments consisting of thermal-neutral period(TNP) and high-temperature period(HTP) with three replications in floor pen, respectively. Feeding trials in the TNP and HTP were individually performed in autumn and summer seasons, respectively. Temperature-humidity index(THI) was calculated by temperature and humidity. Performance and physiological responses were identified per growth stages and feeding trial. Average temperature and THI were $16.8^{\circ}C$ and 61.4 at the TNP, and $25^{\circ}C$ and 74.3 at the HTP, respectively. Growing pigs in HTP exhibited lower BW, ADG and ADFI than in TNP(p<0.01). Similarly, finishing pigs showed lower growth parameters in HTP than in TNP(p<0.01). Lymphocytes and neutrophils of growing pigs were lower in HTP than in TNP(p<0.05). The serum T-PRO and NEFA in finishing pigs were higher in HTP than in TNP(p<0.05). In HTP, finishing pigs had higher cortisol levels than in TNP. Therefore, HTP can negatively influence growth performance and nutritional metabolism in pigs. Our results may provide useful information for developing feeding programs and diets to control heat stress for swine farms.

• Korean Journal of Agricultural Science
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• v.6 no.2
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• pp.148-157
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• 1979

The followings are the results obtained from the investigation of blood pictures and serum components of rabbits according to gestation period. 1. The erythrocytes count and hematocrit values were insignificantly decreased with the progress of gestation period. The hemoglobin content was significantly decreased at 3- and 4-week after gestation. 2. The total leukocytes count was continuousely increased during the gestation period. This tendency was significantly recognized at 3- and 4- week after gestation, but the normal situation was restored after parturition. While the percentage of neutrophils was significantly increased, that of lymphocytes was decreased from 3 weeks after gestation. 3. The contents of total protein and non-protein nitrogen were continuously decreased with the process of gestation period, but the significant differences were recognized from 3 weeks. 4. The total lipids were not markedly changed until 3 weeks, but significantly increased at 4-week after gestation and on 5-day after parturition. 5. The serum cholesterol tended to be decreased until 3 weeks, but significantly increased at 4-week after gestation and on 5-day after parturition. 6. The serum calcium was continuousely decreased during the gestation period, but the significant differences were recognized at 3- and 4-week. The serum phosphorus was also significantly decreased at 4-week after gestation.

• Journal of Food Hygiene and Safety
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• v.27 no.1
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• pp.96-102
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• 2012

This study was designed to evaluate a repeated oral dose toxicity and immunomodulating activity of $Pulsatilla$ $koreana$ and $Artemisiae$ $annuae$ in Sprague-Dawley rats. The female rats were treated with $Pulsatilla$ $koreana$ and $Artemisiae$ $annuae$ of control group, low group (0.5 ml/kg), medium group (1 ml/kg), high group (2 ml/kg) for distilled water, intragastrically for 4 weeks, respectively. To ensure the safety of $Pulsatilla$ $koreana $ and $Artemisiae$ $annuae$ such as the following were observed and tested. We examined the body weight, the feed intake, the clinical signs, the ophthalmological test, the hematological and the serum biochemical analysis. We also observed the histopathological changes of liver and kidney in rats. Hematological results were the increase of neutrophils, lymphocytes and monocytes in the high dose group of $Pulsatilla$ $koreana$. The increase immune cells in the high dose group of $Pulsatilla$ $koreana$ might immunomodulating activity. No significant differences in body weight, feed intake, serum biochemical analysis and histopathological between control and fed group were found. In conclusion, $Pulsatilla$ $koreana$ and $Artemisiae$ $annuae$ is physiologically safe and improve immunomodulating activity.

• Tuberculosis and Respiratory Diseases
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• v.50 no.4
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• pp.450-461
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• 2001

Background : The underlying pathogenesis of radiation-induced lung fibrosis (RTLF) has not been very well defined. However, the role of TGF-$\beta$ in the generation of RTLF has been a major focus because there is an increase in the expression of both the TGF-${\beta}m$-RNA and its protein preceding RTLF lesions. The down stream signal after a TGF-$\beta$ stimulated lung fibrosis includes the activation of many mediators such as Smad and c-Jun N-terminal kinase (JNK) through TAK1. It is we hypothesized that JNK activation may play a pivotal role in RTLF pathogenesis through increased transcription of the fibrogenic cytokines. The present study evaluates JNK activity in alveolar macrophages after irradiation and the relationship between JNK activity and the amount of collagen in the lung tissues. Methods : C57BL/6 mice(20-25 gr, males) received chlorotetracycline(2g/L) in their drinking water 1 week prior to irradiation and continuously there after. The mice were irradiated once with 1400 cGy of $60CO{\gamma}$-ray over the whole chest. The cellular composition of the whole lung bronchoalveoalr lavage fluids(BALF), elastin expression in the lung tissues, the level of hydroxyproline in lung tissues, and an in vitro JNK assay was measured before irradiation and one, four, and eight weeks after irradiation (RT). Results : The volumes of BALF retrieved from instilled 4 mL of saline with 2% heparin were 3.7-3.8 mL for each group. The cell numbers were similar before($4.1{\times}10^4{\pm}0.5{\times}10^4/mL$) and 1 week($3.1{\times}10^4{\pm}0.5{\times}10^4/mL$) after RT. At four and eight weeks after RT, the cell number reached to $14.0{\times}10^4{\pm}1.5{\times}10^4mL$ and $10.0{\times}10^4{\pm}1.3{\times}10^4/mL$, respectively. There we no changes in the lymphocytes and neutrophils population observed in the BALF after RT. The H-E stain of the lung tissues did not show any structural and fibrotic change in the lung tissues at 4 and 8 weeks after RT. In addition, the amount of elastin and collagen were not different on Verhoeff staining of the lung tissues before RT to eight weeks after RT. The hydroxyproine content was measured with the left lung dissected from the left main bronchus. The lung were homogenized and hydrolyzed with 6 N Hel for 12 hours at $110^{\circ}C$ then measured as previously described. The content of hydroxyproline, standardized with a lung protein concentration, reached a peak 4 weeks after RT, and thereafter showed a plateau. AnIn vitro JNK assay using c-$Jun_{1-79}$-GST sepharose beads were performed with the alveolar macrophages obtained from the BAL. JNK activity was not detected prior to RT, However, the JNK activity increased from one week after RT and reached a peak four weeks after RT. Conclusion : JNK may be involved in the pathogenesis because the JNK activity showed similar pattern observed with the hydroxyproine content. However, it is necessary to clarify that the JNK increases the transcription of fibrogenic cyiokines through the transcription factor.

• Tuberculosis and Respiratory Diseases
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• v.43 no.6
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• pp.954-964
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• 1996

Background : The type of the infiltrating cells in al veolitis may be determined by the chemokines in the lesion. MIP-1 ${\alpha}$, a C-C type chemokine, stimulates proliferation and cytokine secretion from macrophages and induces early neutrophilic and later monocytic inflammation in vi vo. IL-8, a C-X-C type chemokine is known to attract neutrophils and T-lymphocytes. This study is performed to find out the relative role of two different chemokines in diffuse interstitial lung disease. Subject and Method : We measured the secretion of MIP- 1 ${\alpha}$ and IL-8 from alveolar macrophages(AM), and their level in BAL fluid of 26 patients with DILD (10 IPF, 4 collagen disease, 10 sarcoidosis, and 2 hypersensitivity pneumonitis) and 7 normal control. Result: IL-8 secretion was significantly increased in patients with DILD ($8.15{\pm}4.58$ ng/ml) than in normal ($1.10{\pm}0.93$ ng/ml, p=0.0003). Significant correlation was found between IL-8 secretion and total cell number in BAL fluid (r=0.484, p=0.0068), %(r=0.592, p=0.0004) and No. (r=0.516, p=0.0042) of lymphocyte, and % of AM (r=-0.505, 0.0032). MIP- 1 ${\alpha}$ secretion was also increased in DILD ($2.41{\pm}1.45$ ng/ml) compared to control ($0.63{\pm}0.30$ ng/ml, p=0.0031), and showed a tendency of correlation with total cell number (r=0.368, p=0.0456) and No. of alveolar macrophages (r=0.356, p=0.0579) in BAL fluid. The concentration of IL-8 in BAL fluid was significantly increased in the patients with DILD ($40.4{\pm}34.5$ pg/ml) compared to control ($3.90{\pm}2.47$ pg/ml, p=0.0094) and it showed a significant correlation with the total cell number (r=0.484, p=0.0068), %(r=-0.505, p=0.0032) of AM, and % (r=0.592, p=0.0004) and No. (r=0.516, p=0.0042) of lymphocyte in BAL fluid. But there was a no significant difference in MIP- 1 ${\alpha}$ concentration in BAL fluid between normal control group and the patients with DILD. Conclusion : From the above results, we concluded that AM of DILD releases increased amount of both IL-8 and MIP- 1 ${\alpha}$ but IL-8 has better correlation with the type of alveolitis.