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Soluble IL-2R, IFN-$\gamma$ and Neopterin as Immunologic Markers in Patients with Tuberculosis (결핵 환자에서 면역학적 지표로서의 sIL-2R, IFN-$\gamma$, Neopterin에 관한 연구)

  • Ryu, Yon-Ju;Ryu, Kum-Hei;Kim, Su-Hyun;Lee, Jong-Soo;Cheon, Seon-Hee;Seoh, Ju-Young
    • Tuberculosis and Respiratory Diseases
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    • v.53 no.3
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    • pp.294-308
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    • 2002
  • Background : The cell-mediated immune response plays an important role in tuberculosis. After being activated by mycobacterial antigens, T lymphocytes express a high affinity receptor (IL-2R) for interleukin-2 (IL-2) on their own surface and release a soluble fraction of the IL-2 receptor (sIL-2R) from the cell membrane into the circulation. Neopterin is a metabolite of guanosine-triphosphate, which is produced by stimulated macrophages under the influence of IFN-$\gamma$ with a T lymphocyte origin. Therefore, the utility of sIL-2R, IFN-$\gamma$ and the neopterin levels as immunologic indices of the cell-mediated immune response and severity of disease in patients with pulmonary tuberculosis was assessed. Methods : The serum sIL-2R, IFN-$\gamma$ and neopterin levels were measured in 39 patients with pulmonary tuberculosis, 6 patients with tuberculous lymphadenitis prior to treatment and 10 healthy subjects. The serum and pleural sIL-2R, neopterin and ADA levels were measured in 22 patients with tuberculous pleurisy. The patients with pulmonary tuberculosis were divided into a mild, moderate and severe group according to the severity by ATS guidelines. To compare the results from these patients with those of the pretreatment levels, the sIL-2R, IFN-$\gamma$ and neopterin levels were measured in 36 of the 39 patients(1 patient, expired; 2 patients were referred to a sanitarium) with pulmonary tuberculosis after 2 months of treatment. Results : 1) the serum sIL-2R and IFN-$\gamma$ levels were elevated in patients with tuberculosis when compared to those of healthy subjects (p>0.05). The neopterin concentration in the serum was significantly lower in patients with pulmonary tuberculosis($2967{\pm}2132.8$ pg/ml) than in healthy controls($4949{\pm}1242.1$ pg/ml)(p<0.05). 2) In the pulmonary tuberculosis group, the serum sIL-2R and IFN-$\gamma$ levels were higher in patients with severe disease than those in patients with mild and moderate disease. However, the neopterin levels declined as the pulmonary tuberculosis became more severe (p<0.01). 3) The mean serum sIL-2R and IFN-$\gamma$ levels declined from $1071{\pm}1139.4$ U/ml to $1023{\pm}1920.9$ U/ml(p>0.05), $41{\pm}52.8$ pg/ml to $22{\pm}23.9$ gm/ml(p<0.05), respectively, after 2 month of treatment. The mean serum neopterin levels increased from $3158{\pm}2272.6$ pg/ml to $3737{\pm}2307.5$ pg/ml(p>0.05) after a 2 month of treatment. These findings were remarkable in the severe group of pulmonary tuberculosis with a clinical correlation. 4) In the patients with tuberculous pleurisy, the serum sIL-2R and ADA were significantly higher than those in the pleural fluid, However, the neopterin levels in the sera and pleural effusion were similar. Conclusion : On the basis of this study, sIL-2R, IFN-$\gamma$ and neopterin measurements may not only provide an insight into the present state of the cell-mediated immune response, but also serve as parameters monitoring of the prognosis of the disease, particularly in patients with severe pulmonary tuberculosis. In addition, an assay of the pleural sIL-2R levels might signal a stimulated local immunity including T cell activation in the tuberculous pleural effusion.

Effects of Nitrogen , Phosphorus and Potassium Application Rates on Oversown Hilly Pasture under Different Levels of Inclination II. Changes on the properties, chemical composition, uptake and recovery of mineral nutrients in mixed grass/clover sward (경사도별 3요소시용 수준이 겉뿌림 산지초지에 미치는 영향 II. 토양특성 , 목초의 무기양분함량 및 3요소 이용율의 변화)

  • 정연규;이종열
    • Journal of The Korean Society of Grassland and Forage Science
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    • v.5 no.3
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    • pp.200-206
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    • 1985
  • This field experiment was undertaken to assess the effects of three levels of inclination ($10^{\circ},\;20^{\circ},\;and\;30^{\circ}$) and four rates of $N-P_2O_5-K_2O$ (0-0-0-, 14-10-10, 28-25-25, and 42-40-40kg/10a) on establishment, yield and quality, and botanical compositions of mixed grass-clover sward. This second part is concerned with the soil chemical properties, concentrations and uptake of mineral nutrients, and percent recovery and efficiency of NPK. The results obtained after a two-year experiment are summarized as follows: 1. The pH, exchangeable Mg and Na, and base saturation in the surface soils were decreased by increasing the grade of inclination, whereas organic matter and available $P_2O_5$ tended to be increased. However, the changes in the Ca content and equivalent ratio of $K\sqrt{Ca+Mg}$ were not significant. The pH, exchangeable Ca and Mg, and base saturation were reduced by increasing the NPK rate, whereas available $P_2O_5$, exchangeable K, and equivalent ratio of $K\sqrt{Ca+Mg}$ tended to be increased. 2. The concentrations of mineral nutrients in grasses and weeds were not significantly affected by increasing the grade of slope in hilly pasture, whereas the concentrations of N, K, and Mg in legume were the lowest with the steep slope, which seemed to be related to the low legume yield. The Mg concentrations of all forage species were below the critical level for good forage growth and likelihood of grass tetany. 3. The increase of NPK rate resulted in the increment of N, K and Na concentrations, and the decrease of Mg and Ca in grasses. The P concentration was increased with P application, but there were no differences in that among the P rates applied. It resulted also in a slight increase of K, and a decrease of Mg in legume, but the contents of N, Ca, and Na were not affected by that. On the other hand, it has not affected the mineral contents in weeds except a somewhat increase of N. The mixed forages showed a increase of N and K contents, a decrease of Ca and Mg, and a slight change in P and Na. 4. The percent recovery of N, P and K by mixed forages were greatly decreased by increasing the grade of inclination and NPK rate. They were high in the order; K>N>P. The efficiency of mixed NPK applications was decreased by that. The efficiency of mixed NPK fertilizers absorbed was slightly decreased by the increased rate of NPK, but it was not affected by the grade of inclination.

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Lipopolysaccharide-induced Synthesis of IL-1beta, IL-6, TNF-alpha and TGF-beta by Peripheral Blood Mononuclear Cells (내독소에 의한 말초혈액 단핵구의 IL-1beta, IL-6, TNF-alpha와 TGF-beta 생성에 관한 연구)

  • Jung, Sung-Hwan;Park, Choon-Sik;Kim, Mi-Ho;Kim, Eun-Young;Chang, Hun-Soo;Ki, Shin-Young;Uh, Soo-Taek;Moon, Seung-Hyuk;Kim, Yang-Hoon;Lee, Hi-Bal
    • 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-$\beta$.

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