• Title/Summary/Keyword: 호흡기

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Muc5ac Gene Expression Induced by Cigarette Smoke is Mediated Via a Pathway Involving ERK1/2 and p38 MAPK (담배 연기에 의한 Muc5ac 유전자 발현에 관여하는 세포 내 신호 전달 경로로서의 ERK1/2와 p38 MAPK)

  • Kim, Yong Hyun;Yoon, Hyoung Kyu;Kim, Chi Hong;Ahn, Joong Hyun;Kwon, Soon Seog;Kim, Young Kyoon;Kim, Kwan Hyoung;Moon, Hwa Sik;Park, Sung Hak;Song, Jeong Sup;Cho, Kyung Sook
    • Tuberculosis and Respiratory Diseases
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    • v.58 no.6
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    • pp.590-599
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    • 2005
  • Object : Cigarette smoking is a major cause of mucus hypersecretion, which is a pathophysiological feature of many inflammatory airway diseases. Mucins, which are an important part of the airway mucus, are synthesized from the Muc gene in airway epithelial cells. However, the signaling pathways for cigarette smoke-induced mucin synthesis are unknown. The aim of this study was to determine the signal pathway for smoking induced Muc5ac gene expression. Methods : A549 cells were cultured and transiently transfected with the Muc5ac promoter fragment. These cells were stimulated with 5% cigarette smoke extract (CSE) alone or with CSE after a pretreatment with various signal transduction pathway inhibitors (AG1478, PD98059 and SB203580). The Muc5ac promoter activity was examined using the luciferase reporter system, and the level of phosphorylated EGFR, ERK1/2, p38 MAPK and JNK were all examined using Western blot analysis. Muc5ac mRNA expression was also examined using reverse transcriptase polymerase chain reactions (RT-PCR). Results : 1. The peak level of luciferase activity of the Muc5ac promoter was observed at 5% concentration and after 3 hours of incubation with the CSE. The level of EGFR phosphorylation and the luciferase activity of the transfected cells caused by the CSE were significantly suppressed by AG1478 or PD98059 (P<0.01). 2. CSE phosphorylated ERK1/2 or p38 MAPK but not JNK. The Muc5ac mRNA expression level was increased by the CSE but that was suppressed by PD98059 or AG1478. 3. The CSE-induced phosphorylation of ERK1/2 was blocked by PD98059 and that of p38 MAPK was blocked by either PD98059 or SB203580. Either PD98059 or SB203580 suppressed the luciferase activity of the transfected cells (P<0.0001). Conclusion : The Muc5ac mRNA expression level was increased by the CSE. The increased CSE-induced transcriptional activity was mediated via EGF receptor activation, which led to ERK1/2 and p38 MAPK phosphorylation.

Difference of Short Term Survival in Patients with ARDS According to Responsiveness to Alveolar Recruitment (급성호흡곤란증후군 환자에서 폐포모집술의 반응에 따른 초기 예후의 차이)

  • Kim, Ho Cheol;Cho, Dae Hyun;Kang, Gyoung Woo;Park, Dong Jun;Lee, Jong Deok;Hwang, Young Sil
    • Tuberculosis and Respiratory Diseases
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    • v.56 no.3
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    • pp.280-288
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    • 2004
  • Background : Lung protective strategies, using low tidal volume in ARDS, improve survival rate in ARDS. However, low tidal volume ventilation may promote alveolar de-recruitment. Therefore, alveolar recruitment is necessary to maintain arterial oxygenation and to prevent repetitive opening and closure of collapsed alveoli in lung protective strategies. There has been a recent report describing improvement in arterial oxygenation with use of recruitment maneuver. However, impact of recruitment on outcome of ARDS is unknown. We evaluated whether short-term survival difference existed in patients with ARDS, who were performed alveolar recruitment maneuver(ARM) and prone position, according to response of alveolar recruitment or not. Methods : All patients who were diagnosed with ADRS and received mechanical ventilation were included. ARM were sustained inflation($35-45cmH_2O$ CPAP for 30-40 sec.) or increasing level of PEEP. If these methods were ineffective, alveolar recruitment with prone position was done for at least 10 hours. $P_aO_2/FiO_2$(P/F) ratio was determined before and at 0.5 and 2 hours after ARM. We defined a responder if the P/F ratio was increased over 50% of baseline value. We compared 10-days and 30-days survival rate between responders and non-responders. Results : 20 patients(M:F=12:8, $63{\pm}14age$) were included. Among them, 12 patients were responders and 8 patients were non-responders. In responders, P/F ratio was increased from $92{\pm}25mmHg$ to $244{\pm}85mmHg$. In non-responders, P/F ratio increased from $138{\pm}37mmHg$ to $163{\pm}60mmHg$. Among non-responders, P/F ratio was improved over 50% in 2 patients after prone position. Overall, 14 patients were responders after ARM and prone position. The 10-days and 30-days survival rate in responders was significantly higher than in non-responders(86%, 57% in responders and 33%, 0% in non-responders)(p<0.05). There was no significant difference between responders and non-responders in age($71{\pm}11$, $60{\pm}14$), lung injury score($2.8{\pm}0.2$, $2.9{\pm}0.45$), simplified acute physiology score(SAPS) II ($35{\pm}4.6$, $34{\pm}5.7$), positive end-positive pressure level($15.6{\pm}1.9cmH_2O$, $14.5{\pm}2.1cmH_2O$). Conclusion : ARM may improve arterial oxygenation in some patients with ARDS. These responders in patients with ARDS showed significant higher 10-days and 30-days survival rate than non-responders patients with alveolar recruitment.

Diagnostic Value of ADA Multiplied by Lymphocyte to Neutrophil Ratio in Tuberculous Pleurisy (결핵성 흉막염에서 ADA 활성도와 림프구/중성구 비의 곱의 진단적 유용성)

  • Jeon, Eun Ju;Kwak, Hee Won;Song, Ju Han;Lee, Young Woo;Jeong, Jae Woo;Choi, Jae Cheol;Shin, Jong Wook;Kim, Jae Yeol;Park, In Won;Choi, Byoung Whui
    • Tuberculosis and Respiratory Diseases
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    • v.63 no.1
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    • pp.17-23
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    • 2007
  • Background: Many diagnostic approaches for defining the definitive cause of pleurisy should be included due to the large variety of diseases resulting in pleural effusion. Although ADA is a useful diagnostic tool for making a differential diagnosis of pleural effusion, particularly for tuberculous pleural effusion, a definitive diagnostic cut-off value remains problematic in Korea. It was hypothesized that ADA multiplied by the Lymphocyte/Neutrophil ratio(L/N ratio) might be more powerful for making a differential diagnosis of pleural effusion. Methods: One hundred and ninety patients, who underwent thoracentesis and treatment in Chung-Ang University Hospital from January, 2005 through to February 2006, were evaluated. The clinical characteristics, radiologic data and the examination of the pleural effusion were analyzed retrospectively. Results: 1. Among the 190 patients, 59 patients (31.1%) were diagnosed with tuberculous pleurisy, 45 patients(23.7%) with parapneumonic effusion, 42 patients(22.1%) with malignant effusions, 36 patients(18.9%) with transudate, and 8 patients(4.2%) with empyema. One hundred and twenty one patients were found to have an ADA activity of 1 to 39 IU/L(63.7%). Twenty-nine were found to have an ADA activity of 40 to 75 IU/L(15.3%) and 40 were found to have an ADA activity of 75 IU/L or greater(21.0%). 2. Among the patients with tuberculous pleurisy, 5(8%), 18(30%) and 36 patients(60%) had an ADA activity ranging from 1 to 39 IU/L, 40 to 75 IU/L, and 75 IU/L or greater, respectively. In those with an ADA activitiy 40 to 75 IU/L, 18 patients(62%) had tuberculous pleurisy, 9(31%) had parapneumonic effusion and empyema, and 1(3.4%) had a malignant effusion. 3. In those with an ADA activity of 40 to 75 IU/L, there was no significant difference between tuberculous pleurisy and non-tuberculous pleural effusion(tuberculous pleurisy : 61.3 ${\pm}$ 9.2 IU/L, non-tuberculous pleural effusion : 53.3${\pm}$10.5 IU/L). 4. The mean L/N ratio of those with tuberculous pleurisy was 39.1 ${\pm}$ 44.6, which was significantly higher than nontuberculous pleural effusion patients (p<0.05). The mean ADA x L/N ratio of the tuberculous pleurisy patients was 2,445.7 ${\pm}$ 2,818.5, which was significantly higher than the non-tuberculous pleural effusion patients (level p<0.05). 5. ROC analysis showed that the ADA x L/N ratio had a higher diagnostic value than the ADA alone in the group with an ADA between 40-75 IU/L. Conclusion: The ADA multiplied by the lymphocyte-to-neutrophil ratio might provide a more definitive diagnosis of tuberculous pleurisy.

Usefulness of Troponin-I, Lactate, C-reactive protein as a Prognostic Markers in Critically Ill Non-cardiac Patients (비 순환기계 중환자의 예후 인자로서의 Troponin-I, Lactate, C-reactive protein의 유용성)

  • Cho, Yu Ji;Ham, Hyeon Seok;Kim, Hwi Jong;Kim, Ho Cheol;Lee, Jong Deok;Hwang, Young Sil
    • Tuberculosis and Respiratory Diseases
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    • v.58 no.6
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    • pp.562-569
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    • 2005
  • Background : The severity scoring system is useful for predicting the outcome of critically ill patients. However, the system is quite complicated and cost-ineffective. Simple serologic markers have been proposed to predict the outcome, which include troponin-I, lactate and C-reactive protein(CRP). The aim of this study was to evaluate the prognostic values of troponin-I, lactate and CRP in critically ill non-cardiac patients. Methods : From September 2003 to June 2004, 139 patients(Age: $63.3{\pm}14.7$, M:F = 88:51), who were admitted to the MICU with non-cardiac critical illness at Gyeongsang National University Hospital, were enrolled in this study. This study evaluated the severity of the illness and the multi-organ failure score (Acute Physiologic and Chronic Health EvaluationII, Simplified Acute Physiologic ScoreII and Sequential Organ Failure Assessment) and measured the troponin-I, lactate and CRP within 24 hours after admission in the MICU. Each value in the survivors and non-survivors was compared at the 10th and 30th day after ICU admission. The mortality rate was compared at 10th and 30th day in normal and abnormal group. In addition, the correlations between each value and the severity score were assessed. Results : There were significantly higher troponin-I and CRP levels, not lactate, in the non-survivors than in the survivors at 10th day($1.018{\pm}2.58ng/ml$, $98.48{\pm}69.24mg/L$ vs. $4.208{\pm}10.23ng/ml$, $137.69{\pm}70.18mg/L$) (p<0.05). There were significantly higher troponin-I, lactate and CRP levels in the non-survivors than in the survivors on the 30th day ($0.99{\pm}2.66ng/ml$, $8.02{\pm}9.54ng/dl$, $96.87{\pm}68.83mg/L$ vs. $3.36{\pm}8.74ng/ml$, $15.42{\pm}20.57ng/dl$, $131.28{\pm}71.23mg/L$) (p<0.05). The mortality rate was significantly higher in the abnormal group of troponin-I, lactate and CRP than in the normal group of troponin-I, lactate and CRP at 10th day(28.1%, 31.6%, 18.9% vs. 11.0%, 15.8 %, 0%) and 30th day(38.6%, 47.4%, 25.8% vs. 15.9%, 21.7%, 14.3%) (p<0.05). Troponin-I and lactate were significantly correlated with the SAPS II score($r^2=0.254$, 0.365, p<0.05). Conclusion : Measuring the troponin-I, lactate and CRP levels upon admission may be useful for predicting the outcome of critically ill non-cardiac patients.

The Recovery of Left Ventricular Function after Coronary Artery Bypass Grafting in Patients with Severe Ischemic Left Ventricular Dysfunction: Off-pump Versus On-pump (심한 허혈성 좌심실 기능부전 환자에서 관상동맥우회술시 체외순환 여부에 따른 좌심실 기능 회복력 비교)

  • Kim Jae Hyun;Kim Gun Gyk;Baek Man Jong;Oh Sam Sae;Kim Chong Whan;Na Chan-Young
    • Journal of Chest Surgery
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    • v.38 no.2 s.247
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    • pp.116-122
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    • 2005
  • Background: Adverse effects of cardiopulmonary bypass can be avoided by 'Off-pump' coronary artery bypass (OPCAB) surgery. Recent studies have reported that OPCAB had the most beneficial impact on patients at highest risk by reducing bypass-related complications. The purpose of this study is to compare the outcome of OPCAB and conventional coronary artery bypass grafting (CCAB) in patients with poor left ventricular (LV) function. Material and Method: From March 1997 to February 2004, seventy five patients with left ventricular ejection fraction (LVEF) of $35\%$ or less underwent isolated coronary artery bypass grafting at our institute. Of these patients, 33 patients underwent OPCAB and 42 underwent CCAB. Preoperative risk factors, operative and postoperative outcomes, including LV functional change, were compared and analysed. Result: Patients undergoing CCAB were more likely to have unstable angina, three vessel disease and acute myocardial infarction among the preoperative factors. OPCAB group had significantly lower mean operation time, less numbers of total distal anastomoses per patient and less numbers of distal anastomoses per patient in the circumflex territory than the CCAB group. There was no difference between the groups in regard to in-hospital mortality $(OPCAB\; 9.1\%\;(n=3)\;Vs.\;CCAB\;9.5\%\;(n=4)),$ intubation time, the length of stay in intensive care unit and in hospital postoperatively. Postoperative complication occurred more in CCAB group but did not show statistical difference. On follow-up echocardiography, OPCAB group showed $9.1\%$ improvement in mean LVEF, 4.3 mm decrease in mean left ventricular end-diastolic dimension (LVEDD) and 4.2 mm decrease in mean left ventricular end-systolic dimension (LVESD). CCAB group showed $11.0\%$ improvement in mean LVEF, 5.1 mm decrease in mean LVEDD and 5.5 mm decrease in mean LVESD. But there was no statistically significant difference between the two groups. Conclusion: This study showed that LV function improves postoperatively in patients with severe ischemic LV dysfunction, but failed to show any difference in the degree of improvement between OPCAB and CCAB. In terms of operative mortality rate and LV functional recovery, the results of OPCAB were as good as those of CCAB in patients with poor LV function. But, OPCAB procedure was advantageous in shortening of operative time and in decrease of complications. We recommend OPCAB as the first surgical option for patients with severe LV dysfunction.

A study on the classification of research topics based on COVID-19 academic research using Topic modeling (토픽모델링을 활용한 COVID-19 학술 연구 기반 연구 주제 분류에 관한 연구)

  • Yoo, So-yeon;Lim, Gyoo-gun
    • Journal of Intelligence and Information Systems
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    • v.28 no.1
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    • pp.155-174
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    • 2022
  • From January 2020 to October 2021, more than 500,000 academic studies related to COVID-19 (Coronavirus-2, a fatal respiratory syndrome) have been published. The rapid increase in the number of papers related to COVID-19 is putting time and technical constraints on healthcare professionals and policy makers to quickly find important research. Therefore, in this study, we propose a method of extracting useful information from text data of extensive literature using LDA and Word2vec algorithm. Papers related to keywords to be searched were extracted from papers related to COVID-19, and detailed topics were identified. The data used the CORD-19 data set on Kaggle, a free academic resource prepared by major research groups and the White House to respond to the COVID-19 pandemic, updated weekly. The research methods are divided into two main categories. First, 41,062 articles were collected through data filtering and pre-processing of the abstracts of 47,110 academic papers including full text. For this purpose, the number of publications related to COVID-19 by year was analyzed through exploratory data analysis using a Python program, and the top 10 journals under active research were identified. LDA and Word2vec algorithm were used to derive research topics related to COVID-19, and after analyzing related words, similarity was measured. Second, papers containing 'vaccine' and 'treatment' were extracted from among the topics derived from all papers, and a total of 4,555 papers related to 'vaccine' and 5,971 papers related to 'treatment' were extracted. did For each collected paper, detailed topics were analyzed using LDA and Word2vec algorithms, and a clustering method through PCA dimension reduction was applied to visualize groups of papers with similar themes using the t-SNE algorithm. A noteworthy point from the results of this study is that the topics that were not derived from the topics derived for all papers being researched in relation to COVID-19 (

    ) were the topic modeling results for each research topic (
    ) was found to be derived from For example, as a result of topic modeling for papers related to 'vaccine', a new topic titled Topic 05 'neutralizing antibodies' was extracted. A neutralizing antibody is an antibody that protects cells from infection when a virus enters the body, and is said to play an important role in the production of therapeutic agents and vaccine development. In addition, as a result of extracting topics from papers related to 'treatment', a new topic called Topic 05 'cytokine' was discovered. A cytokine storm is when the immune cells of our body do not defend against attacks, but attack normal cells. Hidden topics that could not be found for the entire thesis were classified according to keywords, and topic modeling was performed to find detailed topics. In this study, we proposed a method of extracting topics from a large amount of literature using the LDA algorithm and extracting similar words using the Skip-gram method that predicts the similar words as the central word among the Word2vec models. The combination of the LDA model and the Word2vec model tried to show better performance by identifying the relationship between the document and the LDA subject and the relationship between the Word2vec document. In addition, as a clustering method through PCA dimension reduction, a method for intuitively classifying documents by using the t-SNE technique to classify documents with similar themes and forming groups into a structured organization of documents was presented. In a situation where the efforts of many researchers to overcome COVID-19 cannot keep up with the rapid publication of academic papers related to COVID-19, it will reduce the precious time and effort of healthcare professionals and policy makers, and rapidly gain new insights. We hope to help you get It is also expected to be used as basic data for researchers to explore new research directions.

  • The Effect of Pressure Support on Respiratory Mechanics in CPAP and SIMV (CPAP 및 SIMV Mode하에서 Pressure Support 사용이 호흡역학에 미치는 효과)

    • Lim, Chae-Man;Jang, Jae-Won;Choi, Kang-Hyun;Lee, Sang-Do;Koh, Youn-Suck;Kim, Woo-Sung;Kim, Dong-Soon;Kim, Won-Dong;Park, Pyung-Whan;Choi, Jong-Moo
      • Tuberculosis and Respiratory Diseases
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      • v.42 no.3
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      • pp.351-360
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      • 1995
    • Background: Pressure support(PS) is becomimg a widely accepted method of mechanical ventilation either for total unloading or for partial unloading of respiratory muscle. The aim of the study was to find out if PS exert different effects on respiratory mechanics in synchronized intermittent mandatory ventilation(SIMV) and continuous positive airway pressure (CPAP) modes. Methods: 5, 10 and 15 cm $H_2O$ of PS were sequentially applied in 14 patients($69{\pm}12$ yrs, M:F=9:5) and respiratory rate (RR), tidal volume($V_T$), work of breathing(WOB), pressure time product(PTP), $P_{0.1}$, and $T_1/T_{TOT}$ were measured using the CP-100 pulmonary monitor(Bicore, USA) in SIMV and CPAP modes respectively. Results: 1) Common effects of PS on respiratory mechanics in both CPAP and SIMV modes As the level of PS was increased(0, 5, 10, 15 cm $H_2O$), $V_T$ was increased in CPAP mode($0.28{\pm}0.09$, $0.29{\pm}0.09$, $0.31{\pm}0.11$, $0.34{\pm}0.12\;L$, respectively, p=0.001), and also in SIMV mode($0.31{\pm}0.15$, $0.32{\pm}0.09$, $0.34{\pm}0.16$, $0.36{\pm}0.15\;L$, respectively, p=0.0215). WOB was decreased in CPAP mode($1.40{\pm}1.02$, $1.01{\pm}0.80$, $0.80{\pm}0.85$, $0.68{\pm}0.76$ joule/L, respectively, p=0.0001), and in SIMV mode($0.97{\pm}0.77$, $0.76{\pm}0.64$, $0.57{\pm}0.55$, $0.49{\pm}0.49$ joule/L, respectively, p=0.0001). PTP was also decreased in CPAP mode($300{\pm}216$, $217{\pm}165$, $179{\pm}187$, $122{\pm}114cm$ $H_2O{\cdot}sec/min$, respectively, p=0.0001), and in SIMV mode($218{\pm}181$, $178{\pm}157$, $130{\pm}147$, $108{\pm}129cm$ $H_2O{\cdot}sec/min$, respectively, p=0.0017). 2) Different effects of PS on respiratory mechanics in CP AP and SIMV modes By application of PS (0, 5, 10, 15 cm $H_2O$), RR was not changed in CPAP mode($27.9{\pm}6.7$, $30.0{\pm}6.6$, $26.1{\pm}9.1$, $27.5{\pm}5.7/min$, respectively, p=0.505), but it was decreased in SIMV mode ($27.4{\pm}5.1$, $27.8{\pm}6.5$, $27.6{\pm}6.2$, $25.1{\pm}5.4/min$, respectively, p=0.0001). $P_{0.1}$ was reduced in CPAP mode($6.2{\pm}3.5$, $4.8{\pm}2.8$, $4.8{\pm}3.8$, $3.9{\pm}2.5\;cm$ $H_2O$, respectively, p=0.0061), but not in SIMV mode($4.3{\pm}2.1$, $4.0{\pm}1.8$, $3.5{\pm}1.6$, $3.5{\pm}1.9\;cm$ $H_2O$, respectively, p=0.054). $T_1/T_{TOT}$ was decreased in CPAP mode($0.40{\pm}0.05$, $0.39{\pm}0.04$, $0.37{\pm}0.04$, $0.35{\pm}0.04$, respectively, p=0.0004), but not in SIMV mode($0.40{\pm}0.08$, $0.35{\pm}0.07$, $0.38{\pm}0.10$, $0.37{\pm}0.10$, respectively, p=0.287). 3) Comparison of respiratory mechanics between CPAP+PS and SIMV alone at same tidal volume. The tidal volume in CPAP+PS 10 cm $H_2O$ was comparable to that of SIMV alone. Under this condition, the RR($26.1{\pm}9.1$, $27.4{\pm}5.1/min$, respectively, p=0.516), WOB($0.80{\pm}0.85$, 0.97+0.77 joule/L, respectively, p=0.485), $P_{0.1}$($3.9{\pm}2.5$, $4.3{\pm}2.1\;cm$ $H_2O$, respectively, p=0.481) were not different between the two methods, but PTP($179{\pm}187$, $218{\pm}181 cmH_2O{\cdot}sec/min$, respectively, p=0.042) and $T_1/T_{TOT}$($0.37{\pm}0.04$, $0.40{\pm}0.08$, respectively, p=0.026) were significantly lower in CPAP+PS than in SIMV alone. Conclusion: PS up to 15 cm $H_2O$ increased tidal volume, decreased work of breathing and pressure time product in both SIMV and CPAP modes. PS decreased respiration rate in SIMV mode but not in CPAP mode, while it reduced central respiratory drive($P_{0.1}$) and shortened duty cycle ($T_1/T_{TOT}$) in CPAP mode but not in SIMV mode. By 10 em $H_2O$ of PS in CPAP mode, same tidal volume was obtained as in SIMV mode, and both methods were comparable in respect to RR, WOB, $P_{0.1}$, but CPAP+PS was superior in respect to the efficiency of the respiratory muscle work (PTP) and duty cycle($T_1/T_{TOT}$).

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    The Difference in Chemokine Expression in Airway Epithelial Cells According to the Virulence of Tubercle Bacilli (결핵균 독성 여부에 따른 기도 상피세포의 Chemokine 발현에 관한 연구)

    • Kwon, O-Jung;Kim, Ho-Joong;Kim, Jung-Hee;Kim, Ho-Cheol;Suh, Gee-Young;Park, Jeong-Woong;Park, Sang-Joon;Chung, Man-Pyo;Choi, Dong-Chull;Rhee, Chong-H.
      • Tuberculosis and Respiratory Diseases
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      • v.44 no.4
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      • pp.729-741
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      • 1997
    • Background : We have recently reported that airway epithelial cells can produce RANTES and IL-8 in response to the stimulation of tubercle bacilli suggesting a certain role of airway epithelial cells in the pathogenesis of pulmonary tuberculosis. The pathogenesis of tuberculosis is determined by several factors including phagocytosis, immunological response of host, and virulence of tubercle bacilli. Interestingly, there have been reports suggesting that difference in immunological response of host according to the virulence of tubercle bacilli may be related with the pathogenesis of tuberculosis. We, therefore, studied the expressions and productions of RANTES and IL-8 in airway epithelial cells in response to tubercle bacilli(H37Rv, virulent strain and H37Ra, avirulent strain), in order to elucidate the possible pathophysiology of pulmonary tuberculosis. Methods : Peripheral blood monocytes were isolated from normal volunteers. Peripheral blood monocytes (PBM) were stimulated with LPS($10{\mu}g/ml$), H37Rv, or H37Ra($5{\times}10^5$ bacilli/well) along with normal control for 24 hours. A549 cells were stimulated with supernatants of cultured PBM for 24 hours. ELISA kit was used for the measurement of $TNF{\alpha}$ and IL-$1{\beta}$ production in supernatants of cultured PBM and for the measurement of RANTES and IL-8 in supernatants of cultured A549 cells. Northern blot analysis was used for the measurement of RANTES and IL-8 mRNA expression in cultured A549 cells. Results : $TNF{\alpha}$ and IL-$1{\beta}$ productions were increased in cultured PBM stimulated with LPS or tubercle bacilli(H37Rv or H37Ra) compared with the control. There was, however, no difference in $TNF{\alpha}$ and IL-$1{\beta}$ production between cultured PBM stimulated with H37Rv and H37Ra. RANTES and IL-8 expressions and productions were also increased in cultured A549 cells stimulated with LPS or tubercle bacilli compared with the control. RANTES and IL-8 mRNA expressions were significantly increased in cultured A549 cells stimulated with H37Ra-conditioned media(CM) compared with A549 cells stimulated with H37Rv-CM (p<0.05). However, there was no difference in RANTES and IL-8 productions between A549 cells stimulated with H37Rv-CM and H37Ra-CM. Conclusion : Airway epithelial cells can produce the potent chemokines such as RANTES and IL-8, in response to the stimulation of tubercle bacilli. These results suggest that airway epithelial cells may play a certain role in the pathogenesis of pulmonary tuberculosis. However, the role of airway epithelial cells in the pathogenesis of tuberculosis according to the virulence of tubercle bacilli was not clear in this study.

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    Clinical Application of Serum CEA, SCC, Cyfra21-1, and TPA in Lung Cancer (폐암환자에서 혈청 CEA, SCC, Cyfra21-1, TPA-M 측정의 의의)

    • Lee, Jun-Ho;Kim, Kyung-Chan;Lee, Sang-Jun;Lee, Jong-Kook;Jo, Sung-Jae;Kwon, Kun-Young;Han, Sung-Beom;Jeon, Young-June
      • Tuberculosis and Respiratory Diseases
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      • v.44 no.4
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      • pp.785-795
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      • 1997
    • Background : Tumor markers have been used in diagnosis, predicting the extent of disease, monitoring recurrence after therapy and prediction of prognosis. But the utility of markers in lung cancer has been limited by low sensitivity and specificity. TPA-M is recently developed marker using combined monoclonal antibody of Cytokeratin 8, 18, and 19. This study was conducted to evaluate the efficacy of new tumor marker, TPA-M by comparing the estabilished markers SCC, CEA, Cyfra21-1 in lung cancer. Method : An immunoradiometric assay of serum CEA, sec, Cyfra21-1, and TPA-M was performed in 49 pathologically confirmed lung cancer patients who visited Keimyung University Hospital from April 1996 to August 1996, and 29 benign lung diseases. Commercially available kits, Ab bead CEA (Eiken) to CEA, SCC RIA BEAD (DAINABOT) to SCC, CA2H (TFB) to Cyfra2H. and TPA-M (DAIICHI) to TPA-M were used for this study. Results : The mean serum values of lung cancer group and control group were $10.05{\pm}38.39{\mu}/L$, $1.59{\pm}0.94{\mu}/L$ in CEA, $3.04{\pm}5.79{\mu}/L$, $1.58{\pm}2.85{\mu}/L$ in SCC, $8.27{\pm}11.96{\mu}/L$, $1.77{\pm}2.72{\mu}/L$ in Cyfra21-1, and $132.02{\pm}209.35\;U/L$, $45.86{\pm}75.86\;U/L$ in TPA-M respectively. Serum values of Cyfra21-1 and TPA-M in lung cancer group were higher than control group (p<0.05). Using cutoff value recommended by the manufactures, that is $2.5{\mu}/L$ in CEA, $3.0{\mu}/L$ in Cyfra21-1, 70.0 U/L in TPA-M, and $2.0{\mu}/L$ in SCC, sensitivity and specificity of lung cancer were 33.3%, 78.6% in CEA, 50.0%, 89.7% in Cyfra21-1, 52.3%, 89.7% in TPA-M, 23.8%, 89.3% in SCC. Sensitivity and specificity of nonsmall cell lung cancer were 36.1%, 78.1% in CEA, 50.1%, 89.7% in Cyfra21-1, 53.1%, 89.7% in TPA-M, 33.8%, 89.3% in SCC. Sensitivity and specificity of small cell lung cancer were 25.0%, 78.5% in CEA, 50.0%, 89.6% in Cyfra21-1, 50.0%, 89.6% in TPA-M, 0%, 89.2% in SCC. Cutoff value according to ROC(Receiver operating characteristics) curve was $1.25{\mu}/L$ in CEA, $1.5{\mu}/L$ in Cyfra2-1, 35 U/L in TPA-M, $0.6{\mu}/L$ in SCC. With this cutoff value, sensitivity, specificity, accuracy and kappa index of Cyfra21-1 and TPA-M were better than CEA and SCC. SCC only was related with statistic significance to TNM stages, dividing to operable stages(TNM stage I to IIIA) and inoperable stages (IIIB and IV) (p<0.05). But no tumor markers showed any correlation with significance with tumor size(p>0.05). Conclusion : Serum TPA-M and Cyfra21-1 shows higher sensitivity and specificity than CEA and SCC in overall lung cancer and nonsmall cell lung cancer those were confirmed pathologically. SCC has higher specificity in nonsmall cell lung cancer. And the level of serum sec are signiticantly related with TNM staging.

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    Efficacy of Interferon-Gamma Treatment in Bronchial Asthma (기관지천식에서 Interferon-Gamma 치료의 효과)

    • Kim, Kwan-Hyoung;Kim, Seok-Chan;Kim, Young-Kyoon;Kwon, Soon-Seog;Kim, Chi-Hong;Moon, Hwa-Sik;Song, Jung-Sup;Park, Sung-Hak;Lee, Choong-Eon;Byun, Kwang-Ho
      • Tuberculosis and Respiratory Diseases
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      • v.44 no.4
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      • pp.822-835
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      • 1997
    • Background : There have been many in vitro evidences that interleukin-4(IL-4) might be the most important cytokine inducing IgE synthesis from B-cells, and interferon-gamma(IFN-$\gamma$) might be a main cytokine antagonizing IL-4-mediated IgE synthesis. Recently some reports demonstrated that IFN-$\gamma$ might be used as a new therapeutic modality in some allergic diseases with high serum IgE level, such as atopic dermatitis or bronchial asthma. To evaluate the in vivo effect of IFN-$\gamma$ in bronchial asthma we tried a clinical study. Methods : Fifty bronchial asthmatics(serum IgE level over 200 IU/ml) who did not respond to inhaled or systemic corticosteroid treatment, and 17 healthy nonsmoking volunteers were included in this study. The CD 23 expressions of peripheral B-cells, the IL-4 activities of peripheral T-cells, the serum soluble CD23(sCD23) levels, and the superoxide anion(${O_2}^-$) generations by peripheral PMN were compared between bronchial asthmatics and normal subjects. The IL-4 activities of peripheral T-cells were analyzed by T-cell supernatant (T-sup)-induced CD23 expression from tonsil B-cells. In bronchial asthmatics the serum IgE levels and histamine $PC_{20}$ in addition to the above parameters were also compared before and after IFN-$\gamma$ treatment. IFN-$\gamma$ was administered subcutaneously with a weekly dose of 30,000 IU per kilogram of body weight for 4 weeks. Results : The ${O_2}^-$ generations by peripheral PMNs in bronchial asthmatics were higher than normal subjects($8.23{\pm}0.94$ vs $5.00{\pm}0.68\;nmol/1{\times}10^6$ cells, P<0.05), and significantly decreased after IFN-$\gamma$ treatment compared to initial values($3.69{\pm}0.88$ vs $8.61{\pm}1.53\;nmol/1{\times}10^6$ cells, P<0.05). CD23 expression of peripheral B-cells in bronchial asthmatics was higher than normal subjects($47.47{\pm}2.96%$, vs $31.62{\pm}1.92%$, P<0.05), but showed no significant change after IFN-$\gamma$ treatment. The serum sCD23 levels in bronchial asthmatics were slightly higher than normal subjects($191.04{\pm}23.3\;U/ml$ vs $162.85{\pm}4.85\;U/ml$), and 11(64.7%) of 17 patients showed a decreasing pattern in their serum sCD23 levels after IFN-$\gamma$ treatment. However the means of serum sCD23 levels were not different before and after IFN-$\gamma$ treatment. The IL-4 activities of peripheral T-cells in bronchial asthmatics were slightly higher than normal subjects($22.48{\pm}6.81%$ vs $18.90{\pm}2.43%$), and slightly increased after IFN-$\gamma$ treatment($27.90{\pm}2.56%$). Nine(60%) of 15 patients showed a decreasing pattern in their serum IgE levels after IFN-$\gamma$ treatment. And the levels of serum IgE were significantly decreased after IFN-$\gamma$ treatment compared to initial values ($658.67{\pm}120.84\;IU/ml$ vs $1394.32{\pm}314.42\;IU/ml$, P<0.05). Ten(83.3%) of 12 patients showed an improving pattern in bronchial hyperresponsiveness after IFN-$\gamma$ treatment, and the means of histamine $PC_{20}$ were significantly increased after IFN-$\gamma$ treatment compared to initial values ($1.22{\pm}0.29mg/ml$ vs $0.69{\pm}0.17mg/ml$, P<0.05). Conclusion : Our results suggest that IFN-$\gamma$ may be useful as well as safety in the treatment of bronchial asthmatics with high serum IgE level and that in vivo effects of IFN-$\gamma$ may be different from its in vitro effects on the regulations of IgE synthesis or the respiratory burst of PMN.

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