The role of FGF-2 in smoke-induced emphysema and the therapeutic potential of recombinant FGF-2 in patients with COPD

Kim, You-Sun,Hong, Goohyeon,Kim, Doh Hyung,Kim, Young Min,Kim, Yoon-Keun,Oh, Yeon-Mok,Jee, Young-Koo Nature Publishing Group UK 2018 Experimental and molecular medicine Vol.50 No.11

<▼1><P>Although the positive effects of recombinant fibroblast growth factor-2 (rFGF-2) in chronic obstructive pulmonary disease (COPD) have been implicated in previous studies, knowledge of its role in COPD remains limited. The mechanism of FGF2 in a COPD mouse model and the therapeutic potential of rFGF-2 were investigated in COPD. The mechanism and protective effects of rFGF-2 were evaluated in cigarette smoke-exposed or elastase-induced COPD animal models. Inflammation was assessed in alveolar cells and lung tissues from mice. FGF-2 was decreased in the lungs of cigarette smoke-exposed mice. Intranasal use of rFGF-2 significantly reduced macrophage-dominant inflammation and alveolar destruction in the lungs. In the elastase-induced emphysema model, rFGF-2 improved regeneration of the lungs. In humans, plasma FGF-2 was decreased significantly in COPD compared with normal subjects (10 subjects, <I>P</I> <I>=</I> 0.037). The safety and efficacy of inhaled rFGF-2 use was examined in COPD patients, along with changes in respiratory symptoms and pulmonary function. A 2-week treatment with inhaled rFGF-2 in COPD (<I>n</I> = 6) resulted in significantly improved respiratory symptoms compared with baseline levels (<I>P</I> <I><</I> 0.05); however, the results were not significant compared with the placebo. The pulmonary function test results of COPD improved numerically compared with those in the placebo, but the difference was not statistically significant. No serious adverse events occurred during treatment with inhaled rFGF-2. The loss of FGF-2 production is an important mechanism in the development of COPD. Inhaling rFGF-2 may be a new therapeutic option for patients with COPD because rFGF-2 decreases inflammation in lungs exposed to cigarette smoke.</P></▼1><▼2><P><B>Lung disease: Inhaling a protein might help</B></P><P>Studies on the role of the protein ‘fibroblast growth factor-2’ (FGF-2) in chronic obstructive pulmonary disease (COPD) suggest that inhaled FGF-2 could help treat the emphysema linked to smoking. Researchers in South Korea led by Young-Koo Jee at Dankook University, Cheonan, and Yeon-Mok Oh at the University of Ulsan, Seoul, studied the role of the reduced FGF-2 levels found in mice with lung inflammation caused by exposure to cigarette smoke. They also uncovered details of a protective effect of inhaled FGF-2, identifying specific cellular and lung structure changes attributed to the administered FGF-2. Reduced FGF-2 levels were also found in patients with COPD. Initial trials revealed some improvement in patients treated with FGF-2, but not at a statistically significant level. Nevertheless, the authors suggest their results justify further investigation of the protein’s therapeutic potential.</P></▼2>

인천지역 TDI 노출 작업자에서 직업성천식 유병율

김형렬,김철우,홍윤철,전형준,김치년,김현수,이지나,신주연,고동희,노재훈 大韓産業醫學會 2004 대한직업환경의학회지 Vol.16 No.2

목적 : TDI는 직업성천식을 일으키는 대표적인 물질로 알려져 있다. 과거 TDI에 노출된 작업자들의 천식 발생률을 5~6%가량 보고하였고, 국내에서도 2-20%에 이르는 유병율을 보고한바 있다. 작업환경이 많이 개선되고, 노출량이 감소된 최근에도 TDI에 의한 직업성천식에 대한 보고가 많이 이루어지고 있어, 이에 대한 적극적인 조사와 진단과정을 통해 유병율을 구하고 질병발생의 변화양상을 파악해 보고자 하였다. 방법 : 인천지역에서 특수건강진단을 수행하는 2개 기관의 TDI 노출 근로자 400여명 중, 사업장의 규모가 50인 이상이며 사업주가 연구진행을 허락한 사업장에서 근무하는 근로자 중 직접적으로 TDI에 노출되는 작업에 종사하는 근로자 170명을 연구대상으로 하였다. 이들에 대해 설문지와 산업의학의사의 면담을 통한 작업관련성 평가를 근거로 정밀대상자를 선정하고 이들에 대해 메타콜린 유발시험, TDI 유발시험 등을 수행하여 직업성천식을 확인하였다. 결과 : 설문조사 결과 11명이 직업과 관련하여 천식증상을 보이는 것으로 나타났고(6.9%), 이중 7명에서 메타콜린 유발검사 양성소견을 보였다. TDI에 의한 특이유발시험 결과 1명에서 양성반응이 나타나, 이 집단에서 TDI에 의한 직업성천식의 유병율은 0.58%였다. 결론 : 과거 국내연구에서 TDI에 의한 직업성천식의 유병율이 2~20%에 이르렀던 데 비해, 본 연구에서는 0.58%로 나타났다. 이는 국외 논문에서도 나타나는 경향으로 작업장 노출량 감소로 점차 발생률이 감소하는 양상을 보이고 있다. 그러나 이미 증상이 나타난 근로자들이 부서를 옮기거나, 직장을 그만둠으로 인해 그 유병율이 과소평가되었을 가능성도 있다고 판단된다. Objecdives: This study was carried out to estimate the prevalence of isocyanate-induced occupational asthma in toluene diisocyanate (TDI) exposed workers. Methods: We examined 170 workers who had been directly exposed to TDI through a medical questionnaire, physical examination, and pulmonary function test. Based on screening examination, workers with suspected occupational asthma were selected for further evaluation such as methacholine and TDI challenge tests. Results: Eleven (6.9%) among 170 workers complained of symptoms of occupational asthma. and 7 among these 11 symptomatic workers showed positive responses to the methacholine challenge test (4.1 %). One spray painter was confirmed as having the TDI induced occupational asthma following a positive response to TDI challenge test. Conclusions: The prevalence of TDI-induced asthma was at 0.58% was lower than that for former studies (2-20%). Improved workplace environment, lower level of TDI exposure compared to the past, and the healthy workers effect may have contributed to this low rate of asthma prevalence in workers with TDI exposure.

Miss Kim 라일락(Syringa velutina ‘Miss Kim’)의 揷木時 發根에 미치는 NAA, IBA 및 IAA의 影響

李宗錫(Lee Jong Suk),金志娟(Kim Jee Yeon),李宅周(Lee Teak Joo) 한국원예학회 1999 Horticulture, Environment, and Biotechnology Vol.40 No.3

분편 인플루엔자백신(split influenza vaccine)의 임상효과 및 면역원성에 관한 연구

우흥정,김동림,정희진,천병철,이주연,안정배,김지희,박찬,신영규,김우주,김민자,박승철 대한화학요법학회 1999 대한화학요법학회지 Vol.17 No.1

목적 : 아단위 인플루엔자 백신 접종 후 백신의 인플루엔자 예방효과, 인플루엔자 방어 항체형성, 인플루엔자 백신의 안전성을 조사하고자 하였다. 방법 : 총 571명을 대상으로 인플루엔자 백신 접종을 하였고, 이들 접종자에서 인플루엔자 양질환의 이환을 조사하여 인플루엔자 백신의 인플루엔자예방효과를 알아보았고, 백신의 접종 전 및 접종 4주 후 혈청에서 혈구응집억제물(Hemagglutination Inhibition : HAI) 항체 검사를 실시하여 백신의 방어항체생성을 조사하였고, 백신의 안전성을 알아보기 위해 백신접종 후 1주일 이내의 부작용을 조사하였다. 결과 :백신 접종군과 백신 비접종군에서 인플루엔자 양 질환의 이환을 조사한 결과 접종군 28.35%, 비접종군 35.88%으로 나왔으며, p 값이 0.001로 통계적으로 접종군에서 유의하게 낮았고, 인플루엔자 양 질환의 예방 효과는 20.97%를 보였다. 백신의 방어항체 형성의 평가를 위해 유럽의 인플루엔자 백신 허가 기준을 조사하였는데 B/Guangdong/5/94균주의 백신접종 후 항체가 40이상의 비율을 제외한 다른 기준은 모두 만족 시켰다. 부작용은 전체 조사자 521명중 149명(29%)으로 주로 접종 부위의 국소 부작용을 호소했고, 전신 부작용은 2% 내외였으며 특별히 심각한 부작용은 발견되지 않았다. 결론 : 분편 인플루엔자 백신은 인플루엔자양질환의 예방과 방어항체생성에 효과 있으며 안전한 것으로 사료된다. Background : The safety and effectiveness of influenza vaccine are well known in developed country. The influenza vaccination has been recommended as one of the tentative immunization schedule for indicated persons since 1997 in Korea. But there are still no available data about them, even though nearly 5 million doses of influenza vaccine were used in 1997-1998 season. So it is immediately needed to investigate the safety. efficacy and immunogenicity of influenza vaccine among Korean. Methods : We studied the clinical efficacy of influenza vaccine by monitoring Occurrence of influenza-like illness in influenza risk group(vaccination ; 300, non-vaccination; 215) from December in 1997 to March in 1998. We used the split quadrivalent influenza vaccine containing 15 microgram of hemagglutinin of A/Beijing/262/95(HlNl), A/Wuhan/359/95(H3N2), B/Mie/1/93 and B/Guangdong/5/94. Hemagglutination inhibition(HA1) antibody titers were determined before immunization and 1 months after vaccination And we evaluated adverse effect of influenza vaccination at 7 days after vaccination. Results : Influenza vaccination was associated with si@icant reductions in influenza-like spptoms(vaccination group; 28.35%, non-vaccination group, 35.88%, p=0.001). The preventive effect of influenza-like i3lne.s among influenza risk goup was 20.97%. And immunogenicity of influenza A and B exceeded all of the European licensure criteria for immunogenicity except postvaccination proportion of titers 240 of B/Guangdong/5/94 strain. And the adverse effects were mainly local injection site problem and no serious adverse effect was noted. Conclusion : Split influenza vaccine is safe, inmunogenic and eff'tive in influenza risk group in Korea.

국가예방접종전산등록체계 개발을 위한 민간의료 기관 하부구조 및 환경 조사연구

이무식,김은영,이건세,이석구,홍지영,김건엽,김대경,신의철,이연경,기몽서,나백주,김영택 한국모자보건학회 2003 한국모자보건학회지 Vol.7 No.2

동아시아의 핵문제 : 북한과 일본의 사례분석 In the case of the North Korea and the Japan

김지연 현대일본학회 2003 日本硏究論叢 Vol.18 No.-

1990년대 초반 북한의 핵시설을 사찰한 국제원자력기구는 플루토늄 추출 사실을 확인했고 이 문제는 미북간 고위급 회담으로 논의되었다. 북한은 플루토늄의 보유여부를 애매하고 불확실하게 처리하여 국제제재를 피하면서 미국과의 협상의 주도권을 잡았고, 미국은 북한의 핵문제를 핵비확산원칙으로 해결하려 했으나, 북한이 과거 핵을 규명하지 못했다. 미북간 고위급 회담은 1994년 10월 제네바 미북핵합의로 일단락되는 양상을 띠었다. 이와 더불어 일본은 1990년대의 일본의 플루토늄 상용화로 상징되는 핵연료 리사이클을 추진했다. 1950년대 중반 에너지 안보적 필요에서 핵에너지 이용을 시작한 일본은 독자적인 재처리시설을 추진하여 1987년 미일원자력협상에서 30년간의 상대적으로 자유로운 재처리승인을 미국으로부터 얻어냈다. 일본은 재처리한 플루토늄을 에너지생산에 이용하는 핵연료 리사이클을 고속증식로와 프루서멀(플루토늄의 경수로 이용)을 통해 추진하고 있으나 1995년 고속증식로 몬주사고 이후 고속증식로의 개발이 불투명하고 프루서멀도 안전성의 문제가 제기되고 있다. 일본의 핵연료 리사이클은 전세계적인 핵에너지 이용경향과 상반되고 경제성과 안전성 모두가 검증되지 않았고 그에 따른 플루토늄의 증식이 예상된다. 북한의 핵개발 과정에서 나타난 플루토늄 보유와 일본의 핵연료 리사이클 과정에서 나타난 플루토늄의 증식은 동북아의 안보에 위협이 되고 안보딜레마 논리와 같이 주변국가의 적극적 대응을 유발할 수 있다. This paper aims at the analysis of the reality of the nuclear proliferation in the East Asia, especially in the case of the North Korea and Japan. In 1990 North Korea's nuclear development has emerged as serious security problem for the South Korea and the threat of peace of East Asia. Pyongyang's attempt to develop nuclear weapons was sufficient to rock the NPT system and become a major source of tension between North Korea and international community. Intending to use nuclear energy for both peaceful as well as military uses, North Korea began to develope the research in the nuclear energy. In 1994, by the Geneva accord North Korea promised to accommodation the IAEA safeguards, to freeze construction of graphite moderated reactors and to freeze operation of a controversial 5 MW reactor. In Fact, many Japanese leaders did want to keep a nuclear weapons options open and promoted a plutonium-based autonomous nuclear fuel recycle not only economic reasons, especially energy security but also because it can be readily converted to a military nuclear program. The continuance of the American nuclear umbrella over Japan will not, in itself, assure a non-nuclear Japan unless it is accompanied by meaningful U. S. and Russian leading to a global process of nuclear disarmament.

대장암의 침윤 깊이와 림프절 전이의 연관성

김상욱,이지연,오남건 부산대학교 병원 암연구소 2009 부산대병원학술지 Vol.- No.25

갑상샘 병변에서의 Galectin-3와 HBME-1의 진단적 유용성

김지연,최경운,설미영 부산대학교 병원 암연구소 2007 부산대병원학술지 Vol.- No.21

PURPOSE: Galectin-3 is a beta-galactoside-binding protein that has been reported to be expressed preferentially in thyroid malignancies. HBME-l is a monoclonal antibody that was raised to recognize an antigen on the surface of mesothelial cells. This preliminary study was designed to substantiate this finding further and to establish a presurgical diagnostic modality of differentiating between benign and malignant thyroid neoplasms by analyzing galectin-3 and HBME-l expression in fine-needle aspirates. SUBJECT AND METHODS: The expression of galectin-3 and HBME-1 were examined immunohistochemically in total of 34 specimens: 12 papillary carcinomas, 4 follicular carcinomas, 8 follicular adenomas and 10 goiters. RESULTS: The positive rate of galectin-3 and HBME-l were 100%(12/12) and 66.7%(8/12) in papillary carcinoma, 50%(2/4) and 75%(3/4) in follicular carcinoma, 50%(4/8) and 12.5%(1/8) in follicular adenoma, 30%(3/10) and 10%(1/10) in goiter, 39%(7/18) and 11.1%(2/18) in benign lesion, and 87.5%(14/16) and 68.8%(11/16) in malignant lesion, respectively. The sensitivity, specificity, positive predictive value and negative predictive value for galectin-3 were 87.5%, 61.1% ,66.7% and 84.6% and for HBME-1 were 68.8% ,88.9%,84.6% and 76.2%, respectively. CONCLUSIONS: Galectin-3 serves as an excellent sensitive marker of papillary carcinoma and HBME-1 as a specific marker of malignant thyroid tumor.

Graves 병과 혈청 면역글로불린-E의 연관성

김현영,박기룡,김성훈,김지연,송수근,최영식,박요한 대한내분비학회 2002 Endocrinology and metabolism Vol.17 No.5

연구배경: Graves 병은 미만성 갑상선종, 갑상선기능한진, 안구침법 등을 특징으로 하는 자가면역성 질환으로, 갑상선자극호르몬 수용체에 대한 자가항체(TRAb)가 갑상선을 자극하여 발생된다. TRAb는 Graves병 환자의 약 85%이상에서 검출되며 활성화된 TRAb는 대부분 IgE로 알려져 있다. 그러나 최근 Graves병 환자의 갑상선조직과 안구조직에 IgE의 침착과 꽃가루 등에 의한 알레르기성 비염으로 인해 Graves병이 발생하거나 재발된 견우가 보고되어 Graves병의 병인에 IgE의 연관성이 제기 되고 있으나, 국내에서는 이에 대한 연구가 드물다. 본 연구에서는 Graves병에서의 혈청 IgE농도와 Graves병의 병기와의 관계 및 TRAb와 IgE 농도와의 연관성을 살펴보고자 하였다. 대상 및 방법 : 2000년 4월 1일부터 7월 1일까지 고신의료원 내분비내과를 방문한 환자 중 Graves병 46예, 만성갑상선염 6예 및 고신의료원 건강증진센터를 방문한 환자 중 갑상선질환의 병력이나 가족력 및 알레르기성 비염의 병력이 없는 35예의 정상대조군을 대상으로 연구를 시행하였다. TRAb는 갑상선자극호르몬 결합 억제 면역글로불린(TBII)으로 측정하였으며, IgE는 효소면역분석법으로 측정하였다. 결과: IgG인 TBII는 Graves병에서 만성갑상선염과 대조군에 비해 높았으며, IgE 평균농도는 Graves병에서 598.1±1112.9U/mL로 만성갑상선염 환자의 98350±79.7U/mL, 대조군 161.72±194.4U/mL에 비해 높았다(p<0.05). Graves병에서 알레르기성 비염의 발병율은 10.9%(5/46)였으며, Graves 병에서의 혈청 IgE 농도는 알레르기성 비염의 병력이 있는 경우 903.1±1152.2U/mL로 없는 경우 560.8±1117.0U/mL보다 높은 경향을 보였다. Graves병의 병기에 따른 TBII와 IgE 농도의 변화를 항갑상선제로 치료하지 않은 군(비치료군)과 치료한 군(치료군) 및 재발군으로 나누어 비교하였을 때, TBII는 치료군(7.4±18.6%)에 비해 비치료군(49.9±23.9%)과 재발군(21.1±3.1%)에서 높았으며(p<0.05), 혈청 IgE치도 치료군(233.8±432.7U/mL)에 비해 비치료군(758.6±1250.0U/mL)과 재발군(1198.5±1952.1U/mL)에서 높은 경향을 보였다. 항갑상선제로 치료한 치료기간에 따른 TBII와 IgE 농도 변화에서, TBII는 비치료군(49.9±23.9%)과 1년 미만 치료군(24.8±3.8%)에서 1년 이상 치료군(2.22±1.97%)에 비해 높았으며(p<0.05), 혈청 IgE 농도는 비치료군(758.6±1250.2U/mL)에서 1년 미만 치료한 군(158.3±91.5U/mL)과 1년 이상 치료군(252.7±483.4U/mL)에 비해 높았으나 유의하지는 않았다. 결론: Graves 병에서 IgE 농도는 증가되어 있었으며, Graves 병의 각각 다른 병기에서의 혈청 IgE 농도의 변화는 Graves qudd의 경과에 영향을 미치는 IgG인 TBII치의 변화와 유사한 경향을 보였다. 그러나 혈청 IgE와 Graves 병과의 연관성을 알아보기 위해서 IgE와 더불어 CD23항원 등의 다른 검사도 병행하는 전향적 연구가 필요할 것으로 생각된다. Background: It is widely believed that Graves' disease is and autoimmune disorder characterized by the presence of the circulation TSH receptor antibody (TRAb). The majority of the activity of TRAb is of the immunoglobulin G(IgG) class. However, other immunoglobulin such as immunoglobulin E(IgE), may play a rloe in the activity. IgE accumulation has been reported to occur in the thyroid gland and ocular muscles of subjects with Graves' disease. Furthermore, it has been noted that recurrence of Graves' disease can be induced by and allergy to pollen. Because an allergy to pollen is commonly associated with IgE, IgE might play a role in the induction of Graves' disease. Therefore, investigated whether IgE was elevated in Graves' disease, and evaluated the potential relationship between the levels of TRAb and IgE Graves' disease. Methods: Forty-six patients with Graves' disease, and 6 with chronic thyroiditis, diagnosed at the Kosin Medical Center between April, 2000 and July, 2000 were included in this study. Thirty-five persons without thyroid disease or a history of allergic rhinitis were used as normal controls. The level or TRAb was measured using thyrotropin binding inhibitory immunoglobulin (TBII). Serum total IgE was measured using as enzymeimmunoassay method. Test for thyroid function, TBII and total IgE were performed in all cases, and the results statistically analyzed. Results: TBII, as IgG, and the serum IgE level were higher in the patients with Graves' disease, and the levels of the latter were 598.1±1112.9U/mL, 98.5±79.7U/mL and controls 161.7±194.4U/mL in the Graves' patients, those with thyroiditis and the controls, respectively (p<0.05). The prevalence of allergic rhinitis in Graves' disease was 10.9%. The serum IgE level in Graves' disease with, and without, allergic rhinitis were 903.1±1152.2U/mL and 560.8±1117.0U/mL, respectively, although there was no significancant difference between the two groups. According to the clinical stage, the serum TBII level was higher in the untreated Graves', and relapsed patients 49.9±23.9% and 21.1±3.1%, respectively, than in the treated group, 7.4±18.6% (p<0.05). The serum IgE level was higher in the untreated Graves' and relapsed patients 758.6±1250.2U/mL and 1198.5±1952.1U/mL, respectively, than in the treated group 233.8±432.7U/mL, although this was not significant. According to the duration of treatment, the serum TBII levels were higher in the untreated Graves' patients, and those treated for less than 1 year, than in those treated for more than 1 year, with values of 49.9±23.9, 24.8±3.8 and 2.22±1.97%, respectively (p<.05). The serum IgE level was higher in the untreated Graves' disease (758.6±1250.2U/mL) than in the groups treated for less than 12 months (158.3±91.5U/mL) and more than 12 months (252.7±483.4U/mL), but the differences were not significant. Conclusions: The concentration of IgE was high in Graves' patients, and although not statistically significant, the serum igE level in Graves' patients with allergic rhinitis was higher than those without. With regard to the clinical stage of Grave's disease, the change in the IgE level tended to follow that of the TBII. Further study will be required to define the possible role of IgE in the pathogenesis in Graves' disease (J Kor Soc Endocrinol 17:640∼648, 2002).

여대생의 영양섭취 실태 및 주요섭취음식의 1인 1회 분량에 관한 연구

김미경,이지연 이화여자대학교 생명과학연구소 1994 생명과학연구논문집 Vol.5 No.-

The use of food frequency questionnaire to estimate dietary intake has become widespread in epidemiologic studies. It has been suggested that knowledge about a person's usual serving size of each food, in addition to consumption frequency, will improve the accuracy of this method. This sutdy was performed to investigate the nutritional status and one serving sizes of commonly consumed dishes in Korean college women. Intakes of dish or food in 156 college women were measured by 7-day wiighed food records in May, 1992 and May, 1993. For each dish or food, variance in one serving size was partitioned into within-person(intraindividual) and between-person(interindividual) components. All nutrient intakes except vitimin A and vitamin C were less adequate. The jamor dish groups which contributed to the most daily nutrient intakes were boiled rice, bread, fruits, dairy product, and biscuit and snack groups. In more than 50% of dishes, the within-person variation was greater than between-person variation. And the variety and amount of food which was used in one dish were too variable to make standard recipe.