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The Relationship between Expression of EGFR, MMP-9, and C-erbB-2 and Survival Time in Resected Non-Small Cell Lung Cancer (수술을 시행한 비소세포 폐암 환자에서 EGFR, MMP-9 및 C-erbB-2의 발현과 환자 생존율과의 관계)

  • Lee, Seung Heon;Jung, Jin Yong;Lee, Kyoung Ju;Lee, Seung Hyeun;Kim, Se Joong;Ha, Eun Sil;Kim, Jeong-Ha;Lee, Eun Joo;Hur, Gyu Young;Jung, Ki Hwan;Jung, Hye Cheol;Lee, Sung Yong;Lee, Sang Yeub;Kim, Je Hyeong;Shin, Chol;Shim, Jae Jeong;In, Kwang Ho;Kang, Kyung Ho;Yoo, Se Hwa;Kim, Chul Hwan
    • Tuberculosis and Respiratory Diseases
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    • v.59 no.3
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    • pp.286-297
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    • 2005
  • Background : Non-small cell lung cancer (NSCLC) is a common cause of cancer-related death in North America and Korea, with an overall 5-year survival rate of between 4 and 14%. The TNM staging system is the best prognostic index for operable NSCLC . However, epidermal growth factor receptor (EGFR), matrix metalloproteinase-9(MMP-9), and C-erbB-2 have all been implicated in the pathogenesis of NSCLC and might provide prognostic information. Methods : Immunohistochemical staining of 81 specimens from a resected primary non-small cell lung cancer was evaluated in order to determine the role of the biological markers on NSCLC . Immunohistochemical staining for EGFR, MMP-9, and C-erbB-2 was performed on paraffin-embedded tissue sections to observe the expression pattern according to the pathologic type and surgical staging. The correlations between the expression of each biological marker and the survival time was determined. Results : When positive immunohistochemical staining was defined as the extent area>20%(more than Grade 2), the positive rates for EGFR, MMP-9, and C-erbB-2 staining were 71.6%, 44.3%, and 24.1% of the 81 patients, respectively. The positive rates of EGFR and MMP-9 stain for NSCLC according to the surgical stages I, II, and IIIa were 75.0% and 41.7%, 66.7% and 47.6%, and 76.9% and 46.2%, respectively. The median survival time of the EGFR(-) group, 71.8 months, was significantly longer than that of the EGFR(+) group, 33.5 months.(p=0.018, Kaplan-Meier Method, log-rank test).. The MMP-9(+) group had a shorter median survival time than the MMP-9(-) group, 35.0 and 65.3 months, respectively (p=0.2). The co-expression of EGFR and MMP-9 was associated with a worse prognosis with a median survival time of 26.9 months, when compared with the 77 months for both negative-expression groups (p=0.0023). There were no significant differences between the C-erbB-2(+) and C-erbB-2 (-) groups. Conclusion : In NSCLC, the expression of EGFR might be a prognostic factor, and the co-expression of EGFR and MMP-9 was found to be associated with a poor prognosis. However, C-erbB-2 expression had no prognostic significance.

Development and Research into Functional Foods from Hydrolyzed Whey Protein Powder with Sialic Acid as Its Index Component - I. Repeated 90-day Oral Administration Toxicity Test using Rats Administered Hydrolyzed Whey Protein Powder containing Normal Concentration of Sialic Acid (7%) with Enzyme Separation Method - (Sialic Acid를 지표성분으로 하는 유청가수분해단백분말의 기능성식품 개발연구 - I. 효소분리로 7% Siailc Acid가 표준적으로 함유된 유청가수분해단백분말(7%)의 랫드를 이용한 90일 반복경구투여 독성시험 평가 연구 -)

  • Noh, Hye-Ji;Cho, Hyang-Hyun;Kim, Hee-Kyong
    • Journal of Dairy Science and Biotechnology
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    • v.34 no.2
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    • pp.99-116
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    • 2016
  • We herein performed animal safety assessment in accordance with Good Laboratory Practice (GLP) regulations with the aim of developing sialic acid from glycomacropeptide (hereafter referred to as "GMP") as an index ingredient and functional component in functional foods. GMP is a type of whey protein derived from milk and a safe food, with multiple functions, such as antiviral activity. A test substance was produced containing 7% (w/w) sialic acid and mostly-hydrolyzed whey protein (hereafter referred to as "7%-GNANA") by enzymatic treatment of substrate GMP. The maximum intake test dose level was selected based on 5,000 mg/kg/day dose set for male NOEL (no-observed-effect-level) and female NOAEL (no-observed-adverse-effect-level) determined by a dose-range finding (DRF) test (GLP Center of Catholic University of Daegu, Report No. 15-NREO-001) that was previously conducted with the same test substance. To evaluate the toxicity of a repeated oral dose of the test substance in connection with the previous DRF study, 1,250, 2,500, and 5,000 mg/kg of the substance were administered by a probe into the stomachs of 6-week-old SPF Sprague-Dawley male and female rats for 90 d. Each test group consisted of 10 male and 10 female rats. To determine the toxicity index, all parameters, such as observation of common signs; measurements of body weight and food consumption; ophthalmic examination; urinalysis, electrolyte, hematological, and serum biochemical examination; measurement of organ weights during autopsy; and visual and histopathological examinations were conducted according to GLP standards. After evaluating the results based on the test toxicity assessment criteria, it was determined that NOAEL of the test substance, 7%-GNANA, was 5,000 mg/kg/day, for both male and female rats. No animal death was noted in any of the test groups, including the control group, during the study period, and there was no significant difference associated with test substance, as compared with the control group, with respect to general symptoms, body weight changes, food consumption, ophthalmic examination, urinalysis, hematological and serum biochemical examination, and electrolyte and blood coagulation tests during the administration period (P<0.05). As assessed by the effects of the test substance on organ weights, food consumption, autopsy, and histopathological safety, change in kidney weight as an indicator of male NOAEL revealed up to 20% kidney weight increase in the high-dose group (5,000 mg/kg/day) compared with the change in the control group. However, it was concluded that this effect of the test substance was minor. In the case of female rats, reduction of food consumption, increase of kidney weight, and decrease of thymus weight were observed in the high-dose group. The kidney weight increased by 10.2% (left) and 8.9% (right) in the high-dose group, with a slight dose-dependency compared with that of the control group. It was observed that the thymus weight decreased by 25.3% in the high-dose group, but it was a minor test substance-associated effect. During the autopsy, botryoid tumor was detected on the ribs of one subject in the high-dose group, but we concluded that the tumor has been caused by a naturally occurring (non-test) substance. Histopathological examination revealed lesions on the kidney, liver, spleen, and other organs in the low-dose test group. Since these lesions were considered a separate phenomenon, or naturally occurring and associated with aging, it was checked whether any target organ showed clear symptoms caused by the test substance. In conclusion, different concentrations of the test substance were fed to rats and, consequently, it was verified that only a minor effect was associated with the test substance in the high-dose (5,000 mg/kg/day) group of both male and female rats, without any other significant effects associated with the test substance. Therefore, it was concluded that NOAEL of 7%-GNANA (product name: Helicobactrol) with male and female rats as test animals was 5,000 mg/kg/day, and it thus was determined that the substance is safe for the ultimate use as an ingredient of health functional foods.

Microbiological Studies of Korean Native Soy-sauce Fermentation -A Study on the Microflora Changes during Korean Native Soy-sauce Fermentation- (한국재래식(韓國在來式) 간장의 발효미생물(醱酵微生物)에 관(關)한 연구(硏究)(제2보(第二報)) -한국재래식(韓國在來式) 간장의 담금중(中)에 있어서의 발효미생물군(醱酵微生物群)의 소장(消長)에 관(關)한 연구(硏究)-)

  • Lee, Woo-Jin;Cho, Duck-Hiyon
    • Applied Biological Chemistry
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    • v.14 no.2
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    • pp.137-148
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    • 1971
  • Studies were carried out to investigate the main fermentation microorganisms and their flora changes during Korean native soy-sauce fermentation. Korean native Maeju loaves collected from 5 Do's were separated into surface and inner parts. Four different soy-sauces-the surface part Maeju fermented soy-sauce, the inner part, the surface and inner part combined Maeju fermented soy-sauce, and the semi-Japanese type soy-sauce were fermented and the changes of fermentation microorganism flora and the various chemical components during the period of their fermentations were studied. Besides, 14 home-made soy-sauces collected from 14 different places all over Korea were examined in comparison with the laboratory soy-sauces and to determine the characteristics of Korean native soy-sauce. The results were as follows: 1. The main microorganisms in Korean native soy-sauce fermentation were determined as; Aerobic bacteria: Bacillus subtilis, Bacillus pumilus Lactic acid bacteria: Pediococcus halophilus, Leuconostoc mesenteroides Yeasts: Torulopsis datila, Saccharomyces rouxii 2. Microflora changes during Korean native soy-sauce fermentation were as follows; Aerobic bacteria increased until the 2nd week of fermentation and then gradually decreased. The lactic acid bacteria increased until the 3rd week, after which decreased. When the lactic acid fermentation lowered the pH value to below the 5.4, yeasts were able to grow and participate the fermentation. As the production of organic acids amounted, to a certain height, the growth of all microorganisms lead to the period of decline or death at about the 2nd month of fermentation. After boiling of soy-sauce most microorganisms except a few of Bacillus sp. disappeared. Occosionally yeasts and lactic acid bacteria survived depending upon the composition of soy-sauce. 3. Changes of general chemical components influencing the microflora were investigated for the period of Korean native soy-sauce fermentation. Tetal acidity, salt concentration and total nitrogen were increasing steadily over the entire period of fermentation. pH values were dropping to a certain degree of about 4.5. Salt concentration and pH value seemed to be the important factors influencing the microflora. 4. The microflora were influenced by chemical components of soy-sauce. Aerobic bacteria were able to survive in all soy-sauce as they made spores. Growth of lactic acid bacteria was inhited at 23-26% of salt concentration and pH 4.8. Soy-sauce yeasts started to grow only at pH below 5.4 and seemed to be inhibited at around 26% of salt concentration under pH 4.5-4.7. 5. The open kettle boiling of soy-sauce, the characteristic process of Korean native soy-sauce manufacturing, was effective to sterilize microorganisms, increase the salt concentration, and coagulate proteins. 6. The average viable cell counts of microorganism found in collected samples of home-made Korean native soy-sauces were; Aerobic bacteria: $53{\times}10^2\;cell/ml$ Lactic acid bacteria: 34 cell/ml Yeasts: 14 cell/ml The average values of chemical compositions of samples of home-made Korean native soy-sauce were; Salt concentration: 28.9% pH value: 4.79 Total acidity(lactic acid): 0.91g/100ml Total nitrogen: 1.09g/100ml

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Long-term Survival Analysis of Bronchioloalveolar Cell Carcinoma (기관세지폐포암의 장기결과분석)

  • Lee Seung Hyun;Kim Yong Hee;Moon Hye Won;Kim Dong Kwan;Kim Jong Wook;Park Seung Il
    • Journal of Chest Surgery
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    • v.39 no.2 s.259
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    • pp.106-110
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    • 2006
  • Background: Bronchioloalveolar carcinoma (BAC) is an uncommon primary malignancy of the lung, and it accounts for $2{\~}14\%$ of all pulmonary malignancies. According to World Health Organization (WHO) categorisation, BAC is a subtype of adenocarcinoma. The current definition of BAC includes the following: malignant neoplasms of the lung that have no evidence of extrathoracic primary adenocarcinoma, an absence of a central bronchogenic source, a peripheral parenchymal location, and neoplastic cells growing along the alveolar septa. Previous reports had demonstrated a better prognosis following surgery for patients affected by BAC than those affected by other type of non-small cell lung cancer (NSCLC). We aim to analyse Asan Medical Center experiences of BAC. Material and Method: Between 1990 and 2002, 31 patients were received operations for BAC. We analyse retrosepectively sex, age, disease location, preoperative clinical stage, postoperative pathologic stage & complications, survival according to medical record. Result: There were 12 men and 19 women, the average age was 61.09$\pm$10.63 ($31{\~}79$) years. Tumor locations were 7 in RUL, 1 in RML, 4 in RLL, 8 in LUL, 11 in LLL. Operations were 28 lobectomies, 2 pneumonectomies. Postoperative pathologic stage were 12 T1N0M0, 15 T2N0M0, 1 T1N1M0, 1 T1N2M0, 1 T2N2M0, 1 T1N0M1. Mortality were 4 cases ($12.9\%$) and there were no early mortality. Cancer free death was 1 cases, other 3 were cancer related deaths. All of them were affected by distal metastasis and received chemotherapy and each metastatic locations were right rib, brain, and both lung field. The average follow up periods were 50.87$\pm$24.77 months. The overall 3, 5-year survival rate among all patients was $97.1\%,\;83.7\%$, stage I patients overall 2, 5year survival rate was $96.3\%$. The overall disease free 1, 2, 5-year survival rate among all patients was $100\%,\;90\%,\;76\%$ and 2, 5-year survival rate in cases of stage I was $96.4\%,\;90.6\%$. 7 cases ($22.58\%$) were chemotherapies, 1 case ($3.22\%$) was radiation therapy, and 2 cases ($6.45\%$) were chemoradiation therapies. Metastatic locations were 3 cases in lung, 1 case in bone, 1 cases in brain. Conclusion: BAC has a favourable survival and low recurrence rate compare with reported other NSCLC after operative resections.

On the Influence Each Other Between the Monks in the Buddhist Temples and the Society in Towns or Villages (중국(中國) 지방사회(地方社會)와 불교사원(佛敎寺院) 그리고 승인(僧人)의 상호(相互) 영향(影響)에 관한 일고(一考))

  • Yan, Yao zhong
    • Korean Journal of Heritage: History & Science
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    • v.45 no.3
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    • pp.60-79
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    • 2012
  • Environment of ancient Chinese Buddhist temple can be classified to three types such as regional society(鄕村), famous mountain(名山), and urban areas(都市). This made differences in environment where a temple existed and in turn, affected development of Buddhism. And this made another type in relationship between Buddhist temple and a society. This study explains influences which regional society gave on not only Buddhist temple and a monk but also existence and development of Buddhism. When temples are placed in different environmental position, that is, urban areas and regional society, among a social structure, they eventually should adapt to a different society externally and internally. As told in above, ancient Chinese Buddhist temple was located in regional society, famous mountain, and urban areas. Since Eastern Jin and Sixteen Kingdoms, as number of temple much increased, and temples and monks were concentrated on famous mountain, temples in famous mountains and urban areas had developed showing similar aspects each other. But because temples in regional society were influenced a little differently, this study focused on the point. There are four kinds of influences between temples and monks in regional areas. Monks in regional areas had a comparatively close relationship with a society because they came from same area or surrounding areas. Therefore,powers of regional areas restrict influences made by monk group in temple. Second, temples in regional areas shared their joys and sorrows depending on regional economy. Temples in regional areas became a public place for the society and often a market place. In fact, construction and existence of a temple originally became a driving force in regional economy. This is because construction of temple needs artisans and materials and some temples had visitors and included market economy like consumption of incense and candles, though the economic size was large or small. And when regional areas experienced natural disaster or man-made disaster or had poor harvest or economy was in depression, monks left temples and then, temples themselves could not exist. Third, the relationship between temples in regional areas and Buddhists was distinguished from the temples in urban areas and famous mountains. This is because temples in China were places where monks practiced and at the same time, places where general Buddhists worshipped. So there were always a number of Buddhists around the temples. Forth, Buddhism in resional areas was connected to regional Folk beliefs. As a result, Buddhism was spread across the nation, worship with local color often was changed to Buddhist belief or was tinged with Buddhism. While temples in regional areas maintained a close relationship with regional society.they were influenced by the region or gave influences. As a representative example, temples in regional areas showed model behaviors instead of roles of facilities related to various cultures with comparatively advanced level - for example, school, hospital etc. The temples highly affected funerary rites in regional areas. Chinese tombs were mainlymade in regional areas. After death,people living in urban areas were buried in hometown or at least, they were buried in suburbs not urban areas. Temples in regional areas generally participated in funerary rites. Above shows that though most of famous Buddhist temples were located in urban areas not in famous mountains,majority of temples were located in vast regional areas. Through mutual interaction between temples and regional society, the temples in the regional areas were related to Chinese people of over 90% and regional areas became the most important foundation for Buddhism in China. Mutual influences between temples in regional areas and the general public in regions were omnidirectional and spreaded to every aspects of social life in small or large degree. Thus Tombs in temple were widely spreaded across regional areas over time and space. This is enough to explain a close relationship between Buddhist temples and rural society in ancient China.

A Legal Study on liability for damages cause of the air carrier : With an emphasis upon liability of passenger (항공운송인의 손해배상책임 원인에 관한 법적 고찰 - 여객 손해배상책임을 중심으로 -)

  • So, Jae-Seon;Lee, Chang-Kyu
    • The Korean Journal of Air & Space Law and Policy
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    • v.28 no.2
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    • pp.3-35
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    • 2013
  • Air transport today is a means of transport that is optimized for exchanges between nations. Around the world, has experienced an increase in operating and the number of airline route expansion that has entered into the international aviation agreements in order to take advantage of the air transport efficient, but the possibility of the occurrence of air transport accidents increased. When compared to the accident of other means of transport, development of air transport accidents, not high, but it leads to catastrophe aviation accident occurs. Air Transport accident many international transportation accident than domestic transportation accident, in the event of an accident, the analysis of the legal responsibility of the shipper or the like is necessary or passenger air carrier. Judgment of the legal order of discipline of air transport accident is a classification of the type of air transport agreement. Depending on the object, air transport agreements are classified into the contract of carriage of aviation of the air passenger transportation contract. For casualties occurs, air passenger transportation accident is a need more discussion of legal discipline for this particular. Korean Commercial Code, it is possible to reflect in accordance with the actual situation of South Korea the contents of the treaty, which is utilized worldwide in international air transport, even on the system, to control land, sea, air transport and welcoming to international standards. However, Korean Commercial Code, the problem of the Montreal Convention has occurred as it is primarily reflecting the Montreal Convention. As a cause of liability for damages, under the Commercial Code of Korea and the contents of the treaty precedent is reflected, the concept of accident is necessary definition of the exact concept for damages of passengers in particular. Cause of personal injury or death of passengers, in the event of an accident to the "working for the elevation" or "aircraft" on, the Montreal Convention is the mother method of Korea Commercial Code, liability for damages of air carrier defines. The Montreal Convention such, continue to be a matter of debate so far in connection with the scope of "working for the lifting of" the concepts defined in the same way from Warsaw Convention "accident". In addition, it is discussed and put to see if you can be included mental damage passenger suffered in air transport in the "personal injury" in the damage of the passenger is in the range of damages. If the operation of aircraft, injury accident, in certain circumstances, compensation for mental damage is possible, in the same way as serious injury, mental damage caused by aviation accidents not be able to live a normal life for the victim it is damage to make. So it is necessary to interpret and what is included in the injury to the body in Korea Commercial Code and related conventions, non-economic damage of passengers, clearly demonstrated from the point of view of prevention of abuse of litigation and reasonable protection of air carrier it must compensate only psychological damage that can be. Since the compensation of delay damages, Warsaw Convention, the Montreal Convention, Korea Commercial Code, there are provisions of the liability of the air carrier due to the delayed arrival of passenger and baggage, but you do not have a reference to delayed arrival, the concept of delay arrangement is necessary. The strict interpretation of the concept of delayed arrival, because it may interfere with safe operation of the air carrier, within the time agreed to the airport of arrival that is described in the aviation contract of carriage of passenger baggage, or, these agreements I think the absence is to be defined as when it is possible to consider this situation, requests the carrier in good faith is not Indian or arrive within a reasonable time is correct. The loss of passenger, according to the international passenger Conditions of Carriage of Korean Air, in addition to the cases prescribed by law and other treaties, loss of airline contracts, resulting in passengers from a service that Korean Air and air transport in question do damage was is, that the fact that Korean Air does not bear the responsibility as a general rule, that was caused by the negligence or intentional negligence of Korean Air is proof, negligence of passengers of the damage has not been interposed bear responsibility only when it is found. It is a clause in the case of damage that is not mandated by law or treaty, and responsible only if the negligence of the airline side has been demonstrated, but of the term negligence "for" intentional or negligent "Korean Air's Terms" I considered judgment of compatibility is required, and that gross negligence is appropriate. The "Korean Air international passenger Conditions of Carriage", airlines about the damage such as electronic equipment that is included in the checked baggage of passengers does not bear the responsibility, but the loss of baggage, international to arrive or depart the U.S. it is not the case of transportation. Therefore, it is intended to discriminate unfairly passengers of international flights arriving or departure to another country passengers of international flights arriving or departure, the United States, airlines will bear the responsibility for the goods in the same way as the contents of the treaty it should be revised in the direction.

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The Value of Interleukin-12 as an Activity Marker of Pulmonary Sarcoidosis (폐유육종증의 활동성 지표로서 IL-12의 효용성에 관한 연구)

  • Kim, Tae-Hyung;Jeon, Yong-Gam;Shim, Tae-Sun;Lim, Chae-Man;Koh, Yun-Suck;Lee, Sang-Do;Kim, Woo-Sung;Kim, Won-Dong;Kim, Dong-Soon
    • Tuberculosis and Respiratory Diseases
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    • v.46 no.2
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    • pp.215-228
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    • 1999
  • Background: Sarcoidosis is a chronic granulomatous inflammatory disease of unknown etiology often involving the lungs and intrathoracic lymph nodes. The natural course of sarcoidosis is variable from spontaneous remission to significant morbidity or death. But, the mechanisms causing the variable clinical outcomes or any single parameter to predict the prognosis was not known. In sarcoidosis, the number and the activity of CD4 + lymphocytes are significantly increased at the loci of disease and their oligoclonality suggests that the CD4 + lymphocytes hyperreactivity may be caused by persistent antigenic stimulus. Recently, it has been known that CD4+ lymphocytes can be subdivided into 2 distinct population(Th1 and Th2) defined by the spectrum of cytokines produced by these cells. Th1 cells promote cellular immunity associated with delayed type hypersensitivity reactions by generating IL-2 and IFN-$\gamma$. Th2 cells playa role in allergic responses and immediate hypersensitivity reactions by secreting IL-4, IL-5, and IL-10. CD4+ lymphocytes in pulmonary sarcoidosis were reported to be mainly Th1 cells. IL-12 has been known to play an important role in differentiation of undifferentiated naive T cells to Th1 cells. And, Moller et al. observed increased IL-12 in bronchoalveolar lavage fluid(BALF) in patients with sarcoidosis. So it is possible that the elevated level of IL-12 is necessary for the continuous progression of the disease in active sarcoidosis. This study was performed to test the assumption that IL-12 can be a marker of active pulmonary sarcoidosis. Methods: We measured the concentration of IL-12 in BALF and in conditioned medium of alveolar macrophage(AM) using ELISA(enzyme-linked immunosorbent assay) method in 26 patients with pulmonary sarcoidosis(10 males, 16 females, mean age: $39.8{\pm}2.1$ years) and 11 normal control. Clinically, 14 patients had active sarcoidosis and 12 patients had inactive. Results: Total cells counts, percentage and number of lymhocytes, number of AM and CD4/CD8 lymphocyte ratio in BALF were significantly higher in patients with sarcoidosis than in control group. But none of these parameters could differentiate active sarcoidosis from inactive disease. The concentration of IL-12 in BALF was significantly increased in sarcoidosis patients ($49.3{\pm}9.2$ pg/ml) than in normal control ($2.5{\pm}0.4$ pg/ml) (p<0.001). Moreover it was significantly higher in patients with active sarcoidosis ($70.3{\pm}14.8$ pg/ml) than in inactive disease ($24.8{\pm}3.l$ pg/ml) (p=0.001). Also, the concentration of IL-12 in BALF showed significant correlation with the percentage of AM(p<0.001), percentage(p<0.001) and number of lymphocyte(p<0.001) in BALF, suggesting the close relationship between the level of IL-12 in BALF and the inflammatory cell infiltration in the lungs. Furthermore, we found a significant correlation between the level of IL-12 and the concentration of soluble ICAM-1 : in serum(p<0.001) and BALF (p=0.001), and also between IL-12 level and ICAM-1 expression of AM(p<0.001). The AM from patients with pulmonary sarcoidosis secreted significantly larger amount of IL-12 ($206.2{\pm}61.9$ pg/ml) than those of control ($68.3{\pm}43.7$ pg/ml) (p<0.008), but, there was no difference between inactive and active disease group. Conclusion : Our data suggest that the BALF IL-12 level can be used as a marker of the activity of pulmonary sarcoidosis.

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