• Title/Summary/Keyword: Lungs

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The Radioprotective Effect and Mechanism of Captopril on Radiation Induced-Heart Damage in Rats (방사선 조사 후 발생한 흰쥐 심장손상에서 Captopril의 방어역할과 기전)

  • Chang Seung-Hee;Lee Kyung-Ja;Koo Heasoo
    • 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.

Correlation between High-Resolution CT and Pulmonary Function Tests in Patients with Emphysema (폐기종환자에서 고해상도 CT와 폐기능검사와의 상관관계)

  • Ahn, Joong-Hyun;Park, Jeong-Mee;Ko, Seung-Hyeon;Yoon, Jong-Goo;Kwon, Soon-Seug;Kim, Young-Kyoon;Kim, Kwan-Hyoung;Moon, Hwa-Sik;Park, Sung-Hak;Song, Jeong-Sup
    • Tuberculosis and Respiratory Diseases
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    • v.43 no.3
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    • pp.367-376
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    • 1996
  • Background : The diagnosis of emphysema during life is based on a combination of clinical, functional, and radiographic findings, but this combination is relatively insensitive and nonspecific. The development of rapid, high-resolution third and fourth generation CT scanners has enabled us to resolve pulmonary parenchymal abnormalities with great precision. We compared the chest HRCT findings to the pulmonary function test and arterial blood gas analysis in pulmonary emphysema patients to test the ability of HRCT to quantify the degree of pulmonary emphysema. Methods : From october 1994 to october 1995, the study group consisted of 20 subjects in whom HRCT of the thorax and pulmonary function studies had been obtained at St. Mary's hospital. The analysis was from scans at preselected anatomic levels and incorporated both lungs. On each HRCT slice the lung parenchyma was assessed for two aspects of emphysema: severity and extent. The five levels were graded and scored separately for the left and right lung giving a total of 10 lung fields. A combination of severity and extent gave the degree of emphysema. We compared the HRCT quantitation of emphysema, pulmonary function tests, ABGA, CBC, and patients characteristics(age, sex, height, weight, smoking amounts etc.) in 20 patients. Results : 1) There was a significant inverse correlation between HRCT scores for emphysema and percentage predicted values of DLco(r = -0.68, p < 0.05), DLco/VA(r = -0.49, p < 0.05), FEV1(r = -0.53, p < 0.05), and FVC(r = -0.47, p < 0.05). 2) There was a significant correlation between the HRCT scores and percentage predicted values of TLC(r = 0.50, p < 0.05), RV(r = 0.64, p < 0.05). 3) There was a significant inverse correlation between the HRCT scores and PaO2(r = -0.48, p < 0.05) and significant correlation with D(A-a)O2(r = -0.48, p < 0.05) but no significant correlation between the HRCT scores and PaCO2. 4) There was no significant correlation between the HRCT scores and age, sex, height, weight, smoking amounts in patients, hemoglobin, hematocrit, and wbc counts. Conclusion : High-Resolution CT provides a useful method for early detection and quantitating emphysema in life and correlates significantly with pulmonary function tests and arterial blood gas analysis.

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Evaluation of Parameters of Gas Exchange During Partial Liquid Ventilation in Normal Rabbit Lung (토끼의 정상 폐 모델에서 부분액체환기 시 가스교환에 영향을 주는 인자들에 대한 연구)

  • An, Chang-Hyeok;Koh, Young-Min;Park, Chong-Wung;Suh, Gee-Young;Koh, Won-Jung;Lim, Sung-Yong;Kim, Cheol-Hong;Ahn, Young-Mee;Chung, Man-Pyo;Kim, Ho-Joong;Kwon, O-Jung
    • Tuberculosis and Respiratory Diseases
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    • v.52 no.1
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    • pp.14-23
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    • 2002
  • Background: The opitmal ventilator setting during partial liquid ventilation(PLV) is controversial. This study investigated the effects of various gas exchange parameters during PLV in normal rabbit lungs in order to aid in the development of an optimal ventilator setting during PLV. Methods: Seven New-Zealand white rabbits were ventilated in pressure-controlled mode with the following settings; tidal volume($V_T$) 8 mL/kg, positive end-expiratory pressure(PEEP) 4 $cmH_2O$, inspiratory-to-expiratory ratio(I:E ratio) 1:2, fraction of inspired oxygen($F_TO_2$) 1.0. The respiration rate(RR) was adjusted to keep $PaCO_2$ between 35~45 mmHg. The ventilator settings were changed every 30 min in the following sequence : (1) Baseline, as the basal ventilator setting, (2) Inverse ratio, I:E ratio 2:1, (3) high PEEP, adjust PEEP to achieve the same mean inspiratory pressure (MIP) as in the inverse ratio, (4) High $V_T$, $V_T$ 15 mL/kg, (5) high RR, the same minute ventilation (MV) as in the High $V_T$. Subsequently, the same protocol was repeated after instilling 18 mL/kg of perfluorodecalin for PLV. The parameters of gas exchange, lung mechanics, and hemodynamics were examined. Results: (1) The gas ventilation(GV) group showed no significant changes in the $PaO_2$ at all phases. The $PaCO_2$ was lower and the pH was higher at the high $V_T$ and high RR phases(p<0.05). No significant changes in the lung mechanics and hemodynamics parameters were observed. (2) The baseline $PaO_2$ for the PLV was $312{\pm}$ mmHg. This was significantly lower when decreased compared to the baseline $PaO_2$ for GV which was $504{\pm}81$ mmHg(p=0.001). During PLV, the $PaO_2$, was significantly higher at the high PEEP($452{\pm}38$ mmHg) and high $V_T$ ($461{\pm}53$ mmHg) phases compared with the baseline phase. However, it did not change significantly during the inverse I:E ratio or the high RR phases. (3) The $PaCO_2$ was significantly lower at high $V_T$ and RR phases for both the GV and PLV. During the PLV, $PaCO_2$ were significantly higher compared to the GV (p<0.05). (4) There were no important or significant changes in of baseline and high RR phases lung mechanics and hemodynamics parameters during the PLV. Conclusion: During PLV in the normal lung, adequate $V_T$ and PEEP are important for optimal oxygenation.

Correlation analysis of radiation therapy position and dose factors for left breast cancer (좌측 유방암의 방사선치료 자세와 선량인자의 상관관계 분석)

  • Jeon, Jaewan;Park, Cheolwoo;Hong, Jongsu;Jin, Seongjin;Kang, Junghun
    • The Journal of Korean Society for Radiation Therapy
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    • v.29 no.1
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    • pp.37-48
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    • 2017
  • Purpose: The most basic conditions of radiation therapy is to prevent unnecessary exposure of normal tissue. The risk factors that are important o evaluate the dose emitted to the lung and heart from radiation therapy for breast cancer. Therefore, comparing the dose factors of a normal tissue according to the radion treatment position and Seeking an effective radiation treatment for breast cancer through the analysis of the correlation relationship. Materials and Methods: Computed tomography was conducted among 30 patients with left breast cancer in supine and prone position. Eclipse Treatment Planning System (Ver.11) was established by computerized treatment planning. Using the DVH compared the incident dose to normal tissue by position. Based on the result, Using the SPSS (ver.18) analyzed the dose in each normal tissue factors and Through the correlation analysis between variables, independent sample test examined the association. Finally The HI, CI value were compared Using the MIRADA RTx (ver. ad 1.6) in the supine, prone position Results: The results of computerized treatment planning of breast cancer in the supine position were V20, $16.5{\pm}2.6%$ and V30, $13.8{\pm}2.2%$ and Mean dose, $779.1{\pm}135.9cGy$ (absolute value). In the prone position it showed in the order $3.1{\pm}2.2%$, $1.8{\pm}1.7%$, $241.4{\pm}138.3cGy$. The prone position showed overall a lower dose. The average radiation dose 537.7 cGy less was exposured. In the case of heart, it showed that V30, $8.1{\pm}2.6%$ and $5.1{\pm}2.5%$, Mean dose, $594.9{\pm}225.3$ and $408{\pm}183.6cGy$ in the order supine, prone position. Results of statistical analysis, Cronbach's Alpha value of reliability analysis index is 0.563. The results of the correlation analysis between variables, position and dose factors of lung is about 0.89 or more, Which means a high correlation. For the heart, on the other hand it is less correlated to V30 (0.488), mean dose (0.418). Finally The results of independent samples t-test, position and dose factors of lung and heart were significantly higher in both the confidence level of 99 %. Conclusion: Radiation therapy is currently being developed state-of-the-art linear accelerator and a variety of treatment plan technology. The basic premise of the development think normal tissue protection around PTV. Of course, if you treat a breast cancer patient is in the prone position it take a lot of time and reproducibility of set-up problems. Nevertheless, As shown in the experiment results it is possible to reduce the dose to enter the lungs and the heart from the prone position. In conclusion, if a sufficient treatment time in the prone position and place correct confirmation will be more effective when the radiation treatment to patient.

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Effects of Immunoactivity on Ascaris suum Infection in Mice (마우스에 있어서 멱역활성이 돼지회충의 감염에 미치는 영향)

  • Lee, Jae-Gu;Park, Bae-Geun;Seo, Yeong-Seok
    • Parasites, Hosts and Diseases
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    • v.29 no.3
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    • pp.279-292
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    • 1991
  • The immune response to sheep red blood cell (sRBC) was monitored in the mice infected with Ascaris strum or Trichinella spiralis. The effects of the infection with T. spiralis or the injection with cyclophosphamide (CY) as an immunosuppression agent prior to challenge infection with the embryonated eggs of A. suum were monitored in mice by means of the level of infection with A. strum and cellular and humoral immune response to sRBC. following the oral administration of 1, 000 eggs of A. suum to mice, delayed-type hypersensitivity (DTH) and rosette-forming rate were gradually decreased and reached to the lowest levels at the 5th week and 6th week postinfection, respectively, and then returned to normal at the loth week. The hemagglutinin (HA) and hemolysin (HE) titers were gradually elevated and reached to peak at the 3rd week postinfection, and then returned to normal level. The appearance ratios of the eosinophils and mast cells were in peak at the 4th week and the 2nd week postinfection, respectively. Meanwhile the harvest ratio of A. suum larvae from the liver and lungs was 21.97% at the 1st week postinfection. Following the oral administration of 300 T. spiralis infective larvae, DTH and rosette-forming rate were gradually decreased with the lapse of time and reached the lowest values in the 30th and 21st day of postinfection, and then slightly increased and transiently decreased in the 70th and 80th day of postinfection, respectively. HA and HE titers were the lowest in the 21st and 90th day, whereas the ratios of eosinophils and mast cells were the highest on the 40th and 14th day posti nfecti on, ruts petit i vela. Following the intraperitoneal injection of CY, the body weight, the spleen weight, DTH, rosette-orming ratio, HA and HE titers, the number of WBC and the ratio of the mast cell were predominantly decreased in the 5th day, and then returned to the same value of the 1st day postinjection. The ratio of eosinophils was gradually decreased following to advance of days. At the 1st, 5th and loth days after intraperitoneal injection of CY of 400 mg/kg, a dose with 1, 000 eggs of A. suum was administered orally to mice, and harvest rate of the larvae at the 7th day postadministration was 7.07% in the 1st day, 14.94% in the 5th day, 10.1% in the loth day, 8.02% in control group. The effect of prior infection with infective larvae of T. spiralis upon immunological sequelae of a challenge infection of mice with embryonated eggs of A. suum in 30 or 70 days interval was checked. On the 37th day of prior infection with T. spiralis, that was the 7th day with A. suum postinfection, DTH and rosette-forming rate were drastically decreased, but the ratio of mast cells was highly increased and the ratio of eosinophils, HA and HE titers were fairly increased. On the other hand, the rate of larvae harvest was 9.3% in experimental group in contrast with 22.18% in control group. Meanwhile the effect of immune response to sRBC was similar to that of the former, but DTH and rosettt-forming rate were greatly decreased in the 77th day after prior infection with the 7th day after challenge infection in compariton with control. At that time, Ascaris larvae were harvested 8.3% in experimental group in comparison with 10.5% in control group.

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Comparison and Evaluation of the Effectiveness between Respiratory Gating Method Applying The Flow Mode and Additional Gated Method in PET/CT Scanning. (PET/CT 검사에서 Flow mode를 적용한 Respiratory Gating Method 촬영과 추가 Gating 촬영의 비교 및 유용성 평가)

  • Jang, Donghoon;Kim, Kyunghun;Lee, Jinhyung;Cho, Hyunduk;Park, Sohyun;Park, Youngjae;Lee, Inwon
    • The Korean Journal of Nuclear Medicine Technology
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    • v.21 no.1
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    • pp.54-59
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    • 2017
  • Purpose The present study aimed at assessing the effectiveness of the respiratory gating method used in the flow mode and additional localized respiratory-gated imaging, which differs from the step and go method. Materials and Methods Respiratory gated imaging was performed in the flow mode to twenty patients with lung cancer (10 patients with stable signals and 10 patients with unstable signals), who underwent PET/CT scanning of the torso using Biograph mCT Flow PET/CT at Bundang Seoul University Hospital from June 2016 to September 2016. Additional images of the lungs were obtained by using the respiratory gating method. SUVmax, SUVmean, and Tumor Volume ($cm^3$) of non-gating images, gating images, and additional lung gating images were found with Syngo,bia (Siemens, Germany). A paired t-test was performed with GraphPad Prism6, and changes in the width of the amplitude range were compared between the two types of gating images. Results The following results were obtained from all patients when the respiratory gating method was applied: $SUV_{max}=9.43{\pm}3.93$, $SUV_{mean}=1.77{\pm}0.89$, and $Tumor\;Volume=4.17{\pm}2.41$ for the non-gating images, $SUV_{max}=10.08{\pm}4.07$, $SUV_{mean}=1.75{\pm}0.81$, and $Tumor\;Volume=3.56{\pm}2.11$ for the gating images, and $SUV_{max}=10.86{\pm}4.36$, $SUV_{mean}=1.77{\pm}0.85$, $Tumor\;Volume=3.36{\pm}1.98$ for the additional lung gating images. No statistically significant difference in the values of $SUV_{mean}$ was found between the non-gating and gating images, and between the gating and lung gating images (P>0.05). A significant difference in the values of $SUV_{max}$ and Tumor Volume were found between the aforementioned groups (P<0.05). The width of the amplitude range was smaller for lung gating images than gating images for 12 from 20 patients (3 patients with stable signals, 9 patients with unstable signals). Conclusion In PET/CT scanning using the respiratory gating method in the flow mode, any lesion movements caused by respiration were adjusted; therefore, more accurate measurements of $SUV_{max}$, and Tumor Volume could be obtained from the gating images than the non-gating images in this study. In addition, the width of the amplitude range decreased according to the stability of respiration to a more significant degree in the additional lung gating images than the gating images. We found that gating images provide information that is more useful for diagnosis than the one provided by non-gating images. For patients with irregular signals, it may be helpful to perform localized scanning additionally if time allows.

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A Study on the Treatment of Combine Electron Beam in the Treatment of Breast Cancer Tumor Bed (유방암 Tumor bed 치료 시 혼합 전자선 치료 방법에 대한 고찰)

  • Lee, Geon Ho;Kang, Hyo Seok;Choi, Byoung Joon;Park, Sang Jun;Jung, Da Ee;Lee, Du Sang;Ahn, Min Woo;Jeon, Myeong Soo
    • The Journal of Korean Society for Radiation Therapy
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    • v.31 no.1
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    • pp.51-56
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    • 2019
  • Purpose: The usefulness of using single-electron radiation for secondary radiotherapy of breast cancer patients after surgery is assessed and the use of a combine of different energy. Methods and materials : In this study, 40 patients (group A) using energy 6 MeV and 9 MeV, and 19 patients (group B) using a combine of 9 MeV and 12 MeV were studied among 59 patients who performed secondary care using combine electronic radiation. Each patient in each group, 6 MeV, 9 MeV, Combine(6 MeV / 9 MeV) and 9 MeV, 12 MeV, Combine (9 MeV / 12 MeV) were developed in different ways, and the maximum doses delivered to the original hospital, D95, D5, and $V_3$, $V_5$, $V_{10}$ were compared. Result: The D95 mean value of Group A treatment plan was $785.33{\pm}225.37cGy$, $1121.79{\pm}87.02cGy$ at 9 MeV, and $1010.98{\pm}111.17cGy$ at 6 MeV / 9 MeV, and the mean value at 6 MeV / 9 MeV was most appropriate for the dose. The mean values of the low dose area $V_3$ and $V_5$ in the lung of the breast direction being treated were $3.24{\pm}3.49%$ and $0.72{\pm}1.55%$ at 6 MeV, the highest 9 MeV at $7.25{\pm}4.59%$, $3.07{\pm}2.64%$, the lowest at 6 MeV. Maximum and average lung dose was $727.78{\pm}137.27cGy$ at 6 MeV / 9 MeV, $49.16{\pm}24.44cGy$, highest 9 MeV at $998.97{\pm}114.35cGy$, $85.33{\pm}41.18cGy$, and lowest 6 MeV at $387.78{\pm}208.88cGy$, $9.27{\pm}6.60cGy$. The value of $V_{10}$ was all close to zero. Group B appeared in the pattern of Group A. Conclusion: Relative differences in low-dose areas of the lungs $V_3$ and $V_5$ were seen and were most effective in the dose transfer of tumor bed in the application of combined energy. It is thought that the method of using electronic energy in further radiation treatments for breast cancer is a more effective way to use the energy effect of limiting energy resources, and that if you think about it again, it could be a little more beneficial radiation treatment for patients.

The Role of Tumor Necrosis Factor-$\alpha$ and Interleukin-$1{\beta}$ as Predictable Markers for Development of Adult Respiratory Distress Syndrome in Septic Syndrome (패혈증 증후군환자에서 성인성 호흡곤란 증후군 발생의 예측 지표서의 혈중 Tumor Necrosis Factor-$\alpha$와 Interleukin-$1{\beta}$에 관한 연구)

  • Koh, Youn-Suck;Jang, Yun-Hae;Kim, Woo-Sung;Lee, Jae-Dam;Oh, Soon-Hwan;Kim, Won-Dong
    • Tuberculosis and Respiratory Diseases
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    • v.41 no.5
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    • pp.452-461
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    • 1994
  • Background: Tumor necrosis factor(TNF)-$\alpha$ and Interleukin(lL)-$1{\beta}$ are thought to play a major role in the pathogenesis of the septic syndrome, which is frequently associated with adult respiratory distress syndrome(ARDS). In spite of many reports for the role of TNF-$\alpha$ in the pathogenesis of ARDS, including human studies, it has been reported that TNF-$\alpha$ is not sensitive and specific marker for impending ARDS. But there is a possibility that the results were affected by the diversity of pathogenetic mechanisms leading to the ARDS because of various underlying disorders of the study group in the previous reports. The purpose of the present study was to evaluate the roles of TNF-$\alpha$ and IL-$1{\beta}$ as a predictable marker for development of ARDS in the patients with septic syndrome, in which the pathogenesis is believed to be mainly cytokine-mediated. Methods: Thirty-six patients of the septic syndrome hospitalized in the intensive care units of the Asan Medical Center were studied. Sixteens suffered from ARDS, whereas the remaining 20 were at the risk of developing ARDS(acute hypoxemic respiratory failure, AHRF). In all patients venous blood samples were collected in heparin-coated tubes at the time of enrollment, at 24 and 72 h thereafter. TNF-$\alpha$ and IL-$1{\beta}$ was measured by an enzyme-linked immunosorbent assay (ELISA). All data are expressed as median with interquartile range. Results: 1) Plama TNF-$\alpha$ levels: Plasma TNF-$\beta$ levels were less than 10pg/mL, which is lowest detection value of the kit used in this study within the range of the $mean{\pm}2SD$, in all of the normal controls, 8 of 16 subjects of ARDS and in 8 in 20 subjects of AHRF. Plasma TNF-$\alpha$ levels from patients with ARDS were 10.26pg/mL(median; <10-16.99pg/mL, interquartile range) and not different from those of patients at AHRF(10.82, <10-20.38pg/mL). There was also no significant difference between pre-ARDS(<10, <10-15.32pg/mL) and ARDS(<10, <10-10.22pg/mL). TNF-$\alpha$ levels were significantly greater in the patients with shock than the patients without shock(12.53pg/mL vs. <10pg/mL) (p<0.01). There was no statistical significance between survivors(<10, <10-12.92pg/mL) and nonsurvivors(11.80, <10-20.8pg/mL) (P=0.28) in the plasma TNF-$\alpha$ levels. 2) Plasma IL-$1{\beta}$ levels: Plasma IL-$1{\beta}$ levels were less than 0.3ng/mL, which is the lowest detection value of the kit used in this study, in one of each patients group. There was no significant difference in IL-$1{\beta}$ levels of the ARDS(2.22, 1.37-8.01ng/mL) and of the AHRF(2.13, 0.83-5.29ng/mL). There was also no significant difference between pre-ARDS(2.53, <0.3-8.34ngfmL) and ARDS(5.35, 0.66-11.51ng/mL), and between patients with septic shock and patients without shock (2.51, 1.28-8.34 vs 1.46, 0.15-2.13ng/mL). Plasma IL-$1{\beta}$ levels were significantly different between survivors(1.37, 0.4-2.36ng/mL) and nonsurvivors(2.84, 1.46-8.34ng/mL). Conclusion: Plasma TNF-$\alpha$ and IL-$1{\beta}$ level are not a predictable marker for development of ARDS. But TNF-$\alpha$ is a marker for shock in septic syndrome. These result could not exclude a possibility of pathophysiologic roles of TNF-$\alpha$ and IL-$1{\beta}$ in acute lung injury because these cytokine could be locally produced and exert its effects within the lungs.

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The Effects of Proinflammatory Cytokines and TGF-beta, on The Fibroblast Proliferation (Proinflammatory Cytokines과 TGF-beta가 섬유모세포의 증식에 미치는 영향)

  • Kim, Chul;Park, Choon-Sik;Kim, Mi-Ho;Chang, Hun-Soo;Chung, Il-Yup;Ki, Shin-Young;Uh, Soo-Taek;Moon, Seung-Hyuk;Kim, Yong-Hoon;Lee, Hi-Bal
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.4
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    • pp.861-869
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    • 1998
  • Backgrounds: The injury of a tissue results in the infalmmation, and the imflammed tissue is replaced by the normal parenchymal cells during the process of repair. But, constitutional or repetitive damage of a tissue causes the deposition of collagen resulting in the loss of its function. These lesions are found in the lung of patients with idiopathic pulmonary fibrosis, complicated fibrosis after diffuse alveolar damage (DAD) and inorganic dust-induced lung fibrosis. The tissue from lungs of patients undergoing episodes of active and/or end-stage pulmonary fibrosis shows the accumulation of inflammatory cells, such as mononuclear cells, neutrophils, mast cells and eosinophils, and fibroblast hyperplasia. In this regard, it appears that the inflammation triggers fibroblast activation and proliferation with enhanced matrix synthesis, stimulated by inflammatory mediators such as interleukin-1 (IL-1) and/or tumor necrosis factor (TNF). It has been well known that TGF-$\beta$ enhance the proliferation of fibroblasts and the production of collagen and fibronectin, and inhibit the degradation of collagen. In this regard, It is likely that TGF-$\beta$ undergoes important roles in the pathogenesis of pulmonary fibrosis. Nevertheless, this single cytokine is not the sole regulator of the pulmonary fibrotic response. It is likely that the balance of many cytokines including TGF-$\beta$, IL-1, IL-6 and TNF-$\alpha$ regulates the pathogenesis of pulmonary fibrosis. In this study, we investigate the interaction of TGF-$\beta$, IL-1$\beta$, IL-6 and TNF-$\alpha$ and their effect on the proliferation of fibroblasts. Methods: We used a human fibroblast cell line, MRC-5 (ATCC). The culture of MRC-5 was confirmed by immunofluorecent staining. First, we determined the concentration of serum in cuture medium, in which the proliferation of MRC-5 is supressed but the survival of MRC-5 is retained. Second, we measured optical density after staining the cytokine-stimulated cells with 0.5% naphthol blue black in order to detect the effect of cytokines on the proliferation of MRC-5. Result: In the medium containing 0.5% fetal calf serum, the proliferation of MRC-5 increased by 50%, and it was maintained for 6 days. IL-1$\beta$, TNF-$\alpha$ and IL-6 induced the proliferation of MRC-5 by 45%, 160% and 120%, respectively. IL-1$\beta$ and TNF-$\alpha$ enhanced TGF-$\beta$-induced proliferation of MRC-5 by 64% and 159%, but IL-6 did not affect the TGF-$\beta$-induced proliferation. And lNF-$\alpha$-induced proliferation of MRC-5 was reduced by IL-1$\beta$ in 50%. TGF-$\beta$, TNF-$\alpha$ and both induced the proliferation of MRC-5 to 89%, 135% and 222%, respectively. Conclusions: TNF-$\alpha$, TGF-$\beta$ and IL-1$\beta$, in the order of the effectiveness, showed the induction of MRC-5 proliferation of MRC-5. TNF-$\alpha$ and IL-1$\beta$ enhance the TGF-$\beta$-induced proliferation of MRC-5, but IL-6 did not have any effect TNF-$\alpha$-induced proliferation of MRC-5 is diminished by IL-1, and TNF-$\alpha$ and TGF-$\beta$ showed a additive effect.

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Lung Injury Indices Depending on Tumor Necrosis Factor-$\alpha$ Level and Novel 35 kDa Protein Synthesis in Lipopolysaccharide-Treated Rat (내독소처치 흰쥐에서 Tumor Necrosis Factor-$\alpha$치 상승에 따른 폐손상 악화 및 35 kDa 단백질 합성)

  • Choi, Young-Mee;Kim, Young-Kyoon;Kwon, Soon-Seog;Kim, Kwan-Hyoung;Moon, Hwa-Sik;Song, Jeong-Sup;Park, Sung-Hak
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.6
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    • pp.1236-1251
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    • 1998
  • Background : TNF-$\alpha$ appears to be a central mediator of the host response to sepsis. While TNF-$\alpha$ is mainly considered a proinflammatory cytokine, it can also act as a direct cytotoxic cytokine. However, there are not so many studies about the relationship bet ween TNF-$\alpha$ level and lung injury severity in ALI, particularly regarding the case of ALI caused by direct lung injury such as diffuse pulmonary infection. Recently, a natural defense mechanism, known as the stress response or the heat shock response, has been reported in cellular or tissue injury reaction. There are a number of reports examining the protective role of pre-induced heat stress proteins on subsequent LPS-induced TNF-$\alpha$ release from monocyte or macrophage and also on subsequent LPS-induced ALI in animals. However it is not well established whether the stress protein synthesis such as HSP can be induced from rat alveolar macrophages by in vitro or in vivo LPS stimulation. Methods : We measured the level of TNF-$\alpha$, the percentage of inflammatory cells in bronchoalveolar lavage fluid, protein synthesis in alveolar macrophages isolated from rats at 1, 2, 3, 4, 6, 12, and 24 hours after intratracheal LPS instillation. We performed histologic examination and also obtained histologic lung injury index score in lungs from other rats at 1, 2, 3, 4, 6, 12, 24 h after intratracheal LPS instillation. Isolated non-stimulated macrophages were incubated for 2 h with different concentration of LPS (0, 1, 10, 100 ng/ml, 1, or 10 ${\mu}g/ml$). Other non-stimulated macrophages were exposed at $43^{\circ}C$ for 15 min, then returned to at $37^{\circ}C$ in 5% CO2-95% for 1 hour, and then incubated for 2 h with LPS (0, 1, 10, 100ng/ml, 1, or 10 ${\mu}g/ml$). Results : TNF-$\alpha$ levels began to increase significantly at 1 h, reached a peak at 3 h (P<0.0001), began to decrease at 6 h, and returned to control level at 12 h after LPS instillation. The percentage of inflammatory cells (neutrophils and alveolar macrophages) began to change significantly at 2 h, reached a peak at 6 h, began to recover but still showed significant change at 12 h, and showed insignificant change at 24 h after LPS instillation compared with the normal control. After LPS instillation, the score of histologic lung injury index reached a maximum value at 6 h and remained steady for 24 hours. 35 kDa protein band was newly synthesized in alveolar macrophage from 1 hour on for 24 hours after LPS instillation. Inducible heat stress protein 72 was not found in any alveolar macrophages obtained from rats after LPS instillation. TNF-$\alpha$ levels in supernatants of LPS-stimulated macro phages were significantly higher than those of non-stimulated macrophages(p<0.05). Following LPS stimulation, TNF-$\alpha$ levels in supernatants were significantly lower after heat treatment than in those without heat treatment (p<0.05). The inducible heat stress protein 72 was not found at any concentrations of LPS stimulation. Whereas the 35 kDa protein band was exclusively found at dose of LPS of 10 ${\mu}g/ml$. Conclusion : TNF-$\alpha$ has a direct or indirect close relationship with lung injury severity in acute lung injury or acute respiratory distress syndrome. In vivo and in vitro LPS stimulation dose not induce heat stress protein 72 in alveolar macrophages. It is likely that 35 kDa protein, synthesized by alveolar macrophage after LPS instillation, does not have a defense role in acute lung injury.

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