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>

FCL(5-FU, Carboplatin, Leucovorin) 항암 화학요법에서 Gm-CSF의 효과

최지영,김현수,김종숙,박상준,윤환중,조덕연,남상륜,김삼용 忠南大學校 癌共同硏究所 1998 癌共同硏究所 硏究誌 Vol.2 No.1

Background: One of the major side effects of cancer chemotherapy is myelosuppression. Neutropenia and/or thrombocytopenia are dose-limiting factors in chemotherapy. Colony-stimulating factor induces proliferation and functional maturation of hematopoietic progenitor cells. GM-CSF is primarily active on progenitor cells of granulocytic and monocytic lineage. Methods: Fifteen patients with histologically proven malignancy diagnosed at Chungnam National University Hospital from January 1993 to August 1995 were included in this study. We could evaluate the clinical efficacy of GM-CSF in 13 patients undergoing FCL(5-FU, Carboplatin and Leucovorin) chemotherapy; the first cycles involved no GM-CSF while the second cycles involved GM-CSF on day 6 through 15 of chemotherapy. Results: 1) The subjects were fifteen patients in all, there were five patients with head and neck cancer, which was the most common types of maligancy. There were four patients with colon cancer, two patients with stomach cancer, and one patient with breast cancer, gallbladder cancer, cervix cancer and cholangiocarcinoma respectively, two patients, who did not complete two cycles of chemotherapy were excluded. 2) Age distribution was from 38 years to 78 years with a median age of 57. 3) In FCL chemotherapy cycles with GM-CSF, the duration of neutropenia(<500/μL) was 0.5±0.3 day, while FCL chemotherapy cycles without GM-CSF, it was 2.9±0.7 day(P=0.008). 3) There was no significant difference in platelet count between the two chemotherapy cycles(P=0.133). 4) Febrile duration without GM-CSF was 4.9±2.1 day, but with GM-CSF the duration was 1.3±0.7 day, which was significantly different(P=0.003). The duration of antibiotics use with GM-CSF was 1.7±1.2 day and without GM-CSF was 6.8±3.2 day, also significantly different(P=0.002). But hospital stay between the two cycles were not significantly different(P=0.064). Conclusion: GM-CSF was effective in preventing or restoring bone marrow depression after FCL chemotherapy.

폐경전 여성에서 혈중 성호르몬결합글로불린 농도와 산화스트레스의 연관성

최영주,오지영,홍영선,성연아 대한내분비학회 2004 Endocrinology and metabolism Vol.19 No.1

연구배경: 여성에서 남성화의 간접적인 지표인 SHBG 농도는 인슐린저항성과 관련되며, 심혈관질환의 위험을 예측할 수 있는 지표로 보고되었다. 심혈관질환의 위험인자들이 산화스트레스의 증가와 관련되며, 최근 남성 호르몬의 증가와 인슐린저항성을 특징으로 하는 다낭성난소증후군 환자에서 성호르몬과 산화스트레스가 관련된다는 연구결과가 있다. 본 연구는 SHBG와 산화스트레스의 연관성을 규명하기 위하여 시행되었다. 방법: 당뇨병, 고혈압, 심혈관질환의 과거력 및 흡연력이 없는 폐경전 여성 46명을 대상으로 하여 방사 면역계수법으로 SHBG를 측정하였으며, ox-LDL은 효소면역측정법으로, TAS 및 MDA는 분광광도계로 측정하였고, SHBG와 산화스트레스를 나타내는 지표들간의 연관성을 관찰하였다. 결과: 1. 정상내당능군과 내당능장애군간에 SHBG와 MDA 농도는 유의한 차이가 없었으며, TAS는 내당능장애군에서 정상내당군에 비해 유의하게 높았다(1.41±0.15 mmol/L, 1.30±0.17 mmol/L, p=0.034). 2. SHBG 농도는 비만군에서 비비만군에 비해 유의하게 낮았다 (56.6±34.2 nmol/L, 76.0±23.8 nmol/L, p=0.036). 3. SHBG 농도는 체질량지수 (r=-0.394, p=0.007), 당부하후혈당(r=-0.326, p=0.027), 허리둘레(r=-0.323, p=0.029), 허리 대 허벅지둘레비 (r=-0.308, p=0.037), 공복인슐린 농도 (r=-0.387, p=0.008), 내장지방면적 (r=-0.339, p=0.021)과 유의한 음의 상관관계가 있었고, 인슐린 감수성지표와는 유의한 양의 상관관계(r=0.397, p=0.008)가 있었다. 4. SHBG 농도는 MDA 농도 (r=-0.357, p=0.015) 및 ox-LDL 농도 (r=-0.367, p=0.014)와 유의한 음의 상관관계가 있었다. 5. 다중회귀분석에서 연령, 체질량지수, 당부하후혈당, 허리둘레, 공복인슐린 농도, 수축기 혈압, 고밀도지 단백콜레스테롤, 중성지방을 보정한 후 SHBG 농도는 MDA 및 ox-LDL에 유의하게 독립적으로 영향을 주었다. TAS에 영항을 주는 인자로는 공복인슐린 농도와 당부하후 혈당이 통계학적으로 유의하였고, SHBG는 유의한 관련성이 없었다. 결론: 폐경전 여성에서 SHBG의 감소는 산화스트레스의 증가와 관련되어 심혈관질환의 위험을 예견할수 있는 지표로 생각된다. Background: Low levels of sex hormone-binding globulin (SHBG), an indirect index of androgenicity, are associated with insulin resistance and cardiovascular risk factors. The risk factors of the cardiovascular disease are known to be related to oxidative stress. In recent reports, sex hormones were associated with oxidative stress in women with polycystic ovarian syndrome (PCOS), which is characterized by increased androgenicity and insulin resistance. with NGT. Methods: To investigate the relationship between sex hormones and oxidative stress, we examined the association of malondialdehyde (MDA), total antioxidant status (TAS), oxidized low density lipoprotein cholesterol (ox-LDL), and SHBG in 46 Korean premenopausal women. Results: 1. SHBG and MDA levels were not significantly different among the women with NGT and IGT. But, TAS was significantly lower (p=0.034) in the subjects with IGT than in the subjects with NGT. 2. The SHBG level was significantly lower (p=0.036) in obese women than in non-obese women. 3. The SHBG level was significantly inversely correlated with BMI (r=-0.394, p=0.007), post challenge glucose (r=-0.326, p=0.027), waist size (r=-0.323, p=0.029), waist-to-thigh ratio (WTR) (r=-0.308, p=0.037), fasting insulin level (r=-0.387, p=0.008), visceral fat area (VFA)(r=-0.339, p=0.021), and was significantly positively correlated with SI (r=0.397, p=0.008). 4. The SHBG level was significantly inversely correlated with levels of MDA (r=-0.357, p=0.015) and ox-LDL (r=-0.367, p=0.014). 5. In a multiple linear regression analysis, the SHBG level was a significant and independent factor for both MDA and ox-LDL. For TAS, the fasting insulin level and post challenge glucose were significant and independent factors. Conclusion: Increased androgenicity assessed by the decrease in serum SHBG levels is associated with the increase in MDA and ox-LDL. These results suggest that increased androgenicity in premenopausal women can contribute to the development of cardiovascular diseases via increased oxidative stress (J Kor Soc Endocrinol 19:48∼57, 2004).

악성종양에서 혈청 Intercellular Adhesion Molecule-1의 혈청

조덕연,김현수,박상준,김종숙,최지영,윤환중,김삼용 충남대학교 의과대학 지역사회의학연구소 1995 충남의대잡지 Vol.22 No.1

Intercellular adhesion molecule-1 (ICAM-1) is a glycoprotein serving as ligands for leukocyte intergrin receptors, i.e. LFA-1, MAC-l. It has been suggested that the expression of ICAM-1 and the levels of circulating ICAM-1 were increased in several malignancies. We measured serum ICAM-1 by ELISA in patients with stomach cancer (n=25), acute lymphoblastic leukemia (n=7), non-Hodgkin's lymphoma (n=14), and metastasis of unknown origin (n=5). Serum levels of circulating ICAM-1 in all malignancies were significantly higer than in normal controls. And serum level of ICAM-1 in stomach cancer ptients having metastatic disease was higher than in patients with localized disease (p=0.027). These results suggest that elevated serum ICAM-1 is a rather common feature for malignancies, not unique for certain types of cancer such as malignant melanoma. It remains to be clalified whether marked increase of serum ICAM-1 in metastatic stomach cancers simply reflect tumor burden or this molecule plays a role in progression in stomach cancer.

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).

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.

일부 세탁소의 유기용제 관리실태 및 공기중 노출농도에 관한 조사

노영만,권기범,박승현,정지연 한국산업위생학회 2001 한국산업보건학회지 Vol.11 No.1

This study was conducted to identify the current status of occupational safety and health by checklist and to evaluate the airborne exposure to chemicals and to provide the appropriate recommendation for safety and health of laundries. A total of 20 laundries located in the Gyungi district area were surveyed from July 20 to September 15, 2000. The prevalence of laundries having a stove and gas range were found to be 25 % and 55 %, respectively. Smoking is not allowed in 60 % of the laundries. Only 10 % of dry-cleaners were isolated. Ventilation system in laundries had not been annually inspected. Most of the workers didn't put on respirators, MSDS were not available, and storage bottles did not contain warning labels. The bulk samples of dry cleaning agent include many chemicals that are not controlled by the MOL in Korea. The detected airborne organic solvents in the laundries were benzene, toluene, p-xylene, m-xylene, o-xylene, perchloroethylene, and 2-butoxy ethanol. The airborne concentrations of organic solvents were much less than the occupational exposure limits proposed by the Ministry of Labor(MOL) in Korea. But the concentrations of benzene exceeded the TLV of ACGIH. This study showed that the current status of occupational safety and health was not appropriate for workers in laundries. It is recommended that laundry workers should be educated for the treatment and storage of hazardous organic solvents to improve the occupational safety and health of the working environment as well as MSDS usage. Also, extended research and survey for the organic solvents that are not controlled by the MOL has to be conducted.

복수과 진료 환자의 중복 처방에 대한 분석 및 평가

이지은,장혜경,오지영,유윤경,김현지,임숙인,연숙희,강진숙,최귀령 한국병원약사회 2003 병원약사회지 Vol.20 No.1

In an aging society, there is an increasing possibility of the duplication of the drugs given to patients because they take many kinds of drugs. Among the prescriptions given to the patients who was treated at multiple ambulatory clinics in St. Mary's hospital for one month of September, 2002, in which drugs that has identical or similar effects are prescribed, we analysed and evaluated them by patients' characteristics, kinds of medication, severity of side effects on a case by case basis. More, we assessed the potential additional costs. As a result of this study, the duplication rate turned out to be 6.69% and it was shown that the proportion of the elderly patients over 60 was high. The gastro-intestinal medications took up a large part and most of the cases showed that the danger caused by double taking of medicine was slight, but there were some examples in which the serious side effects were predicted. Expected additional costs were the average 11.349 won and it ranges from the minimum of 56 won to the maximum of 135,720 won. In conclusion, the management of drug histories of the patients who need the plural treatments is very important and the necessity of the individual and professional guidance of taking medicines for the elderly patients is emerged, too.

전국 단위 감시체계의 현황과 전망

강성규,안연순,지영구,김형옥,하미나,권호장,백남종,김성아,홍윤철,김재용,강대희,정혜선,하은희 대한산업의학회 2001 대한직업환경의학회지 Vol.13 No.2

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