구연 : 내분비,대사 ; 효소법을 이용한 저밀도 콜레스테롤 측정의 임상적 유용성

남궁일성,송기호,김경수,고정민,전사일,민원기,김민선,박중열,이기업 대한내과학회 2002 대한내과학회 추계학술대회 Vol.63 No.-

갑상선 우연종에서 초음파 유도하의 세포검사: 병리 소견과의 비교

남궁일성,김하영,공경엽,이호규,홍석준,김원배,송영기 대한갑상선-내분비외과학회 2003 The Koreran journal of Endocrine Surgery Vol.3 No.2

Purpose: There are many reports that diagnostic accuracy of fine needle aspiration (FNA) of thyroid is improved with ultrasound guidance, especially for impalpable nodules. Despite its general acceptance, routine use of ultrasound guided fine needle aspiration (USGFNA) has been the source of much controversy due to the lack of large-scale studies and lack of data on the natural course of well- differentiated thyroid cancer of small size. Method: The aim of our study was to define the rate of malignancy in relatively large numbers of patients with incidentally detected impalpable thyroid nodules and to assess the extent of disease in patients with suspicious or malignant cytology on USGFNA of thyroid nodules by surgery. We retrospectively reviewed the medical records of the 267 patients who underwent USGFNA of incidental thyroid nodules from January 2000 through December 2001. Results: Three hundred and seventeen nodules from 267 patients were aspirated. The average size of nodules was 0.9⁑0.3 cm, a range of 0.2 cm to 1.5 cm. All 317 lesions were impalpable. Cytological diagnosis included 101 inadequate specimen (32%), 139 benign (44%), 29 indeterminate (9%), 4 suspicious of follicular or Hrthle cell neoplasm (1%), 42 papillary carcinoma (13%), and 2 others. The size of the nodule was not related to the probability of getting an adequate specimen for cytological diagnosis. Forty of 48 patients with suspicious or malignant cytology underwent surgery. All 35 patients with a cytological diagnosis of papillary carcinoma were confirmed to have papillary carcinoma on histological results. One of 3 patients with a cytological diagnosis of follicular neoplasm had a follicular carcinoma. In 36 patients with well-differentiated thyroid cancer, extrathyroidal extension was observed in 44% (16/36), regional lymph node metastasis was found in 50% (18/36), and multifocal tumors were found in 39% (14/36). Conclusion: The rate of malignancy in incidentally detected impalpable thyroid nodules was 12% in retrospective analysis of our patients. Among those, 69% (25/36) of patients had either extrathyroidal extension or regional node involvement and 39% had multifocal tumors at surgery. This suggests that the small size itself could not guarantee a good prognosis in incidentally found thyroid cancers. USGFNA is a useful diagnostic method in those patients. (Korean J Endocrine Surg 2003;3:127-135) 목적: 갑상선 결절의 세포검사시 초음파 유도는 진단적 정확도를 높혀주며 특히 촉진되지 않는 결절의 경우는 실제 검사를 할 수 있는 유일한 방법이다. 그러나 촉진되지 않는 작은 결절에서 실제 일상적으로 초음파 유도하에 세포검사를 할 필요가 있는지는 분명하지 않으며 이는 작은 크기의 갑상선암의 자연경과가 아직 분명하지 않는 것에도 원인이 있다. 방법: 본 연구의 목적은 촉진되지 않는 갑상선 우연종에서 갑상선암의 빈도를 알아보고 이를 수술하여 병리학적인 병변의 범위를 알아보는데 있다. 이를 위하여 2000년 1월부터 2001년 12월까지 서울아산병원에서 초음파유도하에 세포검사를 받은 갑상선 우연종 환자 267명의 기록을 확인하였다. 결과: 267명에서 317개의 촉진되지 않는 결절을 대상으로 초음파 유도하에 세포검사를 시행하였다. 결절의 평균 크기는 0.9 cm이었고 0.2 cm에서 1.5 cm 사이의 크기였으며 모든 317개의 결절이 촉진되지 않았다. 세포검사 결과로는 139명(44%)에서 양성, 29명(9%)에서 중간형, 4명(1%)에서 여포성 종양, 41명(13%)에서 유두선암, 2명에서 기타의 악성종양의 소견이었고 101명(32%)은 검체가 적절하지 못하였다. 결절의 크기는 세포검사에서 적절한 검체를 얻는 것과 관계없었다. 악성으로 진단되거나 의심스러운 48명 중 40명에서 수술이 시행되었으며 세포검사상 유두선암으로 진단되었던 35명은 전원 유두선암으로 확진되었고 세포검사상 여포성 종양으로 진단되었던 3명중 1명에 여포선암을 가지고 있었다. 분화된 갑상선암 36명중 갑상선 피막외로 침윤을 보인 경우는 16명(44%), 국소 림프절 전이를 동반한 경우는 18명(50%) 다발성 병소를 지는 경우는 14명(39%)이었다. 결론: 저자들의 후향적 연구결과 촉진되지 않는 갑상선 우연종에서 악성의 빈도는 12%였다. 이중 69% (25/36)는 수술결 과 갑상선 피막외 침윤, 국소 림프절 전이 또는 다발성 병소 등의 소견을 보였다. 이러한 결과는 우너발 병소의 크기가 작아도 우연히 발견된 갑상선암이 항상 좋은 예후를 보인다고 말하기 어렵게 한다. (Korean J Endocrine Surg 2003;3: 127-135)

스트렙토조토신으로 유발된 당뇨병 모델에서 과식증에 대한 시상하부 FoxO1의 역할

남궁일성 ( Il Seong Nam Goong ),김재근 ( Jae Geun Kim ),김세진 ( Se Jin Kim ),허성재 ( Seong Jae Hur ),이진우 ( Jin Woo Lee ),김은숙 ( Eun Sook Kim ),윤창호 ( Chang Ho Yun ),이병주 ( Byung Ju Lee ),김영일 ( Young Il Kim ) 대한당뇨병학회 2009 Diabetes and Metabolism Journal Vol.33 No.5

연구배경: 스트렙토조토신으로 유발된 당뇨병 실험동물은 혈중 인슐린과 렙틴의 결핍으로 인하여 과식증이 특징적으로 발생된다. 전사조절인자인 FoxO1은 인슐린 신호전달체계를 통하여 대사 및 세포의 분화를 조절한다. 본 연구에서는 인슐린과 렙틴이 결핍된 당뇨병 동물모델에서 시상하부의 FoxO1이 당뇨병성 과식증과 연관되어 있는지를 알아보고자 하였다. 방법: 생쥐(C57BL/6)의 복강으로 스트렙토조토신(200 mg/kg)을 투여하여 당뇨병을 유발하였으며 대조군은 50 mM의 sodium citrate buffer (pH4.0)을 복강으로 투여였다. 생쥐의 뇌실로 인슐린 및 렙틴을 주입하기 위하여 정위 뇌수술 장치를 이용하여 스테인리스 관을 삽관하고 3주 후 생리식염수(2 μL), 인슐린(500 nmoL), 렙틴(1 μg/2 μL)을 각각 주입하였다. FoxO1과 시상하부 신경펩타이드의 mRNA 발현을 확인하기 위하여 각각의 실험군 및 대조군 생쥐의 시상하부를 적출하여 RNA을 분리하고 cDNA를 합성하여 real time PCR을 수행하였다. 결과: 스트렙토조토신으로 유발된 당뇨병 생쥐에서는 대조군과 비교하여 유의한 혈당 증가(25.5±2.8 mmol/L vs. 6.8±0.8 mmol/L) 및 식사섭취의 증가(7.4±0.9 g/day vs. 4.2±0.4 g/day)가 나타났다. 또한 당뇨병이 유발된 생쥐는 정상 생쥐보다 혈중 인슐린(1,303.7±687.6 pmol/L vs. 240.3±26.8 pmol/L)과 렙틴(2,116.5±465.0 pg/mL vs. 86.5±41.5 pg/mL)은 현저하게 감소하였다. 시상하부 FoxO1의 mRNA 합성은 당뇨병이 유발된 생쥐(P<0.001)에서 대조군과 비교하여 유의한 증가를 관찰하였다(2.6배 증가, P<0.001). 당뇨병이 유발된 시험군은 시상하부의 NPY mRNA의 발현이 유의하게 증가(1.85배 증가, P<0.05)하였으며 POMC mRNA는 유의하게 감소(2.1배 감소, P<0.01)하였다. 생쥐의 뇌실로 인슐린 또는 렙틴을 투여하였을 때 증가된 시상하부 FoxO1이 유의하게 감소하였다(각각 1.5배, 1.8배 감소, P<0.05). 또한, 인슐린 또는 렙틴을 뇌실 내로 투여한 결과 NPY mRNA는 감소되고(인슐린 1.5배 감소, P<0.05, 렙틴 1.6배 감소, P<0.01) POMC mRNA는 증가되었다(각각 1.6배, 1.9배 증가, P<0.05). 결론: 본 연구에서는 인슐린과 렙틴의 결핍으로 과식증이 유발된 당뇨병 모델에서 시상하부 FoxO1의 합성이 증가하였으며 뇌실로 인슐린 또는 렙틴을 주입하였을 때 FoxO1합성의 증가가 상쇄됨을 확인하였다. 이러한 결과는 당뇨병에서 나타나는 과식증이 시상하부의 전사조절인자인 FoxO1과 연관되어 있음을 나타낸다. Background: Streptozotocin-induced diabetic animals are characterized by hyperphagia due to deficiencies of insulin and leptin. Forkhead box-containing protein of the O subfamily-1 (FoxO1) regulates energy homeostasis by regulating energy expenditure and food intake as well as mediating insulin and leptin signals in the hypothalamus. To identify the mediator of diabetic hyperphagia, we examined the effects of insulin or leptin on hypothalamic FoxO1 expression in a diabetic animal model. Methods: Diabetes was induced in mice (C57BL/6) by intraperitoneal administration of streptozotocin (200 mg/kg). Stainless steel cannula was implanted into the lateral ventricle of the brain in each mouse. After three weeks, the mice were administered saline, insulin or leptin via intracerebroventricular (ICV) route. The medial hypothalamus was isolated to evaluate the mRNA expressions of FoxO1 and neuropeptides. Results: Streptozotocin-induced diabetic mice exhibited significant elevations of blood glucose and food intake and significantly low levels of serum insulin and leptin. The levels of hypothalamic FoxO1 mRNA were significantly increased in diabetic mice. The hypothalamic expression of neuropeptide Y (NPY) mRNA was increased, but the expression of preproopiomelanocortin (POMC) mRNA was decreased in diabetic mice. ICV administration of insulin or leptin attenuated the upregulation of hypothalamic FoxO1 mRNA, and resulted in downregulation of NPY mRNA and upregulation of POMC mRNA in diabetic mice. Conclusion: We observed that the expression of hypothalamic FoxO1 mRNA was increased in streptozotocin-induced diabetic mice, and that it was significantly attenuated by central administration of insulin or leptin. These results suggest that hypothalamic FoxO1 is the direct mediator of diabetic hyperphagia. (Korean Diabetes J 33:375-381, 2009)

Effects of Rosiglitazone on Inflammation in Otsuka Long-Evans Tokushima Fatty Rats

이진우,남궁일성,김재근,윤창호,김세진,최정일,김영일,김은숙 대한당뇨병학회 2010 Diabetes and Metabolism Journal Vol.34 No.3

Background: Inflammation plays a role in the response to metabolic stress in type 2 diabetes. However, the effects of rosiglitazone on inflammation of skeletal muscle have not been fully examined in type 2 diabetes. Methods: We investigated the effects of the insulin-sensitizing anti-diabetic agent, rosiglitazone, on the progression of skeletal muscle inflammation in Otsuka Long-Evans Tokushima Fatty (OLETF) type 2 diabetic rats. We examined the expression of serologic markers (serum glucose, insulin and free fatty acid) and inflammatory cytokines (tumor-necrosis factor-α, interleukin [IL]-1β and IL-6) in OLETF rats from early to advanced diabetic stage (from 28 to 40 weeks of age). Results: Serum glucose and insulin concentrations were significantly decreased in rosiglitazone-treated OLETF rats compared to untreated OLETF rats. Rosiglitazone treatment significantly decreased the concentrations of serum inflammatory cytokines from 28 to 40 weeks of age. The mRNA expression of various cytokines in skeletal muscle was reduced in rosiglitazone-treated OLETF rats compared with untreated OLETF rats. Furthermore, rosiglitazone treatment resulted in the downregulation of ERK1/2 phosphorylation and NF-κB expression in the skeletal muscle of OLETF rats. Conclusion: These results suggest that rosiglitazone may improve insulin sensitivity with its anti-inflammatory effects on skeletal muscle.

갑상선절제술로 치료한 심각한 재발성 무통성 갑상선염 환자 1예

박소현,김은숙,남궁일성,김영일,김연선,김영민 대한갑상선학회 2015 International Journal of Thyroidology Vol.8 No.1

The course of painless thyroiditis is usually transient with a thyrotoxicosis phase that lasts for 2 months before recovery. Therefore, no treatment is required. This case is unusual because of the recurrence and severity of thyrotoxicosis, which required surgery of the thyroid gland to prevent a thyrotoxic crisis. A 43-year-old female who presented with severe thyrotoxicosis was found to have low radioactive iodine uptake, negative test results for TSH receptor antibodies, normal erythrocyte sedimentation rate and diffuse goiter without pain or tenderness; these findings suggested a diagnosis of painless thyroiditis. She was treated for relapsed painless thyroiditis for 10 years. However, in May 2014, she developed recurrent painless thyroiditis with severe thyrotoxicosis; free T4 41.5 ng/dL, TSH <0.005 mlU/mL. Owing to the severity and recurrence of thyrotoxicosis, total thyroidectomy was performed to prevent a thyrotoxic storm.

Combined Effects of Baicalein and Docetaxel on Apoptosis in 8505c Anaplastic Thyroid Cancer Cells via Downregulation of the ERK and Akt/mTOR Pathways

박찬호,한세은,남궁일성,김영일,김은숙 대한내분비학회 2018 Endocrinology and metabolism Vol.33 No.1

Background: Anaplastic thyroid cancer (ATC) is one of the most lethal human malignancies. Docetaxel, a microtubule stabilizer, isa common chemotherapeutic agent used to treat various metastatic cancers. However, prolonged use results in various side effectsand drug resistance. Flavonoids, such as baicalein, are accepted chemotherapeutic and dietary chemopreventive agents with manyadvantages, such as greater accessibility, affordability, and lower toxicity, compared with traditional chemotherapy agents. In thisstudy, we evaluated whether baicalein enhances the effects of docetaxel on apoptosis and metastasis in 8505c ATC cells. Methods: The 8505c cells were treated with baicalein or docetaxel individually and in combination. Cell viability was measured by MTT(thiazolyl blue tetrazolium bromide) assay, and apoptosis was detected by fluorescence microscopy of Hoechst-stained cells. The expressionof apoptotic (Bax and caspase-3), anti-apoptotic (Bcl-2), angiogenic (vascular endothelial growth factor [VEGF], transforminggrowth factor β [TGF-β], E-cadherin, and N-cadherin), and signaling (extracellular signal-regulated kinase [ERK] mitogen activated proteinkinase [MAPK], Akt, and mammalian target of rapamycin [mTOR]) proteins was determined by Western blot analysis. Results: The combination of baicalein (50 or 100 μM) and docetaxel (10 nM) significantly inhibited proliferation and induced apoptosiscompared with monotherapies. The combination treatment significantly inhibited the expression of Bax, caspase-3, VEGF,TGF-β1, E-cadherin, N-cadherin, and mTOR, but decreased the expression of Bcl-2 and significantly decreased the phosphorylationof ERK and Akt. Conclusion: The combination of baicalein and docetaxel effectively induced apoptosis and inhibited metastasis in 8505c cellsthrough downregulation of apoptotic and angiogenic protein expression and blocking of the ERK and Akt/mTOR pathways in 8505ccells. These results suggest that baicalein enhances the anticancer effects of docetaxel in ATC.

그레이브스병에서 공동자극분자인 4-1BB와 4-1BBL의 역할 연구

김은숙,정효원,남궁일성,우순주,최정일,김영일 대한내분비학회 2006 Endocrinology and metabolism Vol.21 No.2

Background: 4-1BB mediated costimulatory signal is a recently identified immunotherapeutic strategy for treating autoimmune diseases without depressing the immune response. In this study, we investigated the expression of 4-1BB and 4-1BBL on the peripheral blood mononuclear cells (PBMC) and we assessed whether the serum levels of soluble (s) 4-1BB and s4-1BBL in the patients with Graves' disease (GD) and compared them with normal subjects. Methods: Expression of 4-1BB and 4-1BBL on PBMC of GD patients was determined by flow cytometry. The concentrations of s4-1BB and s4-1BBL were assessed in the sera of GD patients by performing ELISA.Results: 4-1BB was constitutively expressed on naive CD4+ and CD8+ T cells of the GD patients and this was increased by stimulation. 4-1BBL was also expressed on the antigen-presenting cells such as CD19+ B cells, monocytes and dendritic cells in GD patients. The serum levels of s4-1BB and s4-1BBL were significantly higher in GD patients than those in controls, and these levels were significantly correlated with the serum levels of thyroid-binding inhibitory immunoglobulin and free T4. Conclusion: These results indicate that effector T cells of GD patients can be activated through the 4-1BB-mediated costimulatory signal. Elevated s4-1BB and s4-1BBL levels in the sera of GD patients may affect modulation of the clinical course in GD patients. (J Kor Soc Endocrinol 21:116~124, 2006) 연구배경: 4-1BB와 4-1BBL는 T 세포와 항원제시세포에서 발현되는 종양괴사인자 계열의 공동자극분자로서 T 세포 활성화와 생존에 중요한 역할을 한다. 본 연구에서는 그레이브스병에서 4-1BB와 4-1BBL의 발현특성을 조사하고 그 역할을 알아보고자 하였다.방법: 그레이브스병 환자와 정상인의 말초혈액로부터 단핵세포와 혈청을 분리한 다음 유세포 분석법과 ELISA 방법을 이용하여 4-1BB와 4-1BBL의 발현특성 및 임상증상과의 연관성을 비교하였다.결과: 정상인의 경우 4-1BB 발현은 활성화된 T 세포에서만 관찰되는 반면 그레이브스병 환자는 naive T 세포 및 활성화된 T 세포 모두에서 발현이 관찰되었으며 활성화 후 발현율이 더욱 증가하였다. 4-1BBL는 정상인과 그레이브스병 환자 모두 B 세포, 단핵구 및 수지상 세포와 같은 항원제시세포에서 주로 발현되었으며 활성화 후 발현율이 다소 증가하였다. 4-1BBL 발현율 역시 그레이브스병에서 높게 나타났다. 혈청 내 s4-1BB와 s4-1BBL 농도를 조사한 결과 그레이브스병 환자가 정상인에 비해 현저히 높게 측정되었으며, 이들의 농도는 TBII 및 유리 T4 농도와 서로 유의한 상관관계를 보였다.

Curcumin Enhances Docetaxel-Induced Apoptosis of 8505C Anaplastic Thyroid Carcinoma Cells

홍정민,박찬성,남궁일성,김연선,이종철,한명월,최정일,김영일,김은숙 대한내분비학회 2014 Endocrinology and metabolism Vol.29 No.1

Background: Anaplastic thyroid cancer (ATC) is one of the most aggressive malignancies in humans, and its progression is poorly controlled by existing therapeutic methods. Curcumin has been shown to suppress inflammation and angiogenesis. In this study, we evaluated whether curcumin could augment docetaxel-induced apoptosis of ATC cells. We also analyzed changes in nuclear factor κB (NF-κB) and cyclooxygenase-2 (COX-2) expression levels to delineate possible mechanisms of their combined action. Methods: ATC cells were cultured and treated with curcumin and docetaxel alone or in combination. The effects on cell viability were determined by MTS assay. Apoptosis was assessed by annexin V staining and confirmed by flow cytometric analysis. Caspase, COX-2, NF-κB levels were assayed by Western blotting. Results: Curcumin combined with docetaxel led to lower cell viability than treatment with docetaxel or curcumin alone. Annexin V staining followed by flow cytometric analysis demonstrated that curcumin treatment enhanced the docetaxel-induced apoptosis of ATC cells. Additionally, curcumin inhibited docetaxel-induced p65 activation and COX-2 expression. Conclusion: We conclude that curcumin may enhance docetaxel’s antitumor activity in ATC cells by interfering with NF-κB and COX-2. Our results suggest that curcumin may emerge as an attractive therapeutic candidate to enhance the antitumor activity of taxanes in ATC treatment.

포스터 전시 발표 : 호흡기,내분비-대사 ; 정읍 농촌지역 당뇨병 발생율과 당뇨병 위험인자; 6년 추적 조사

송기호,박중열,남궁일성,한성민,이은주,이영수,조민우,이무송,김민선,이기업 대한내과학회 2003 대한내과학회 추계학술대회 Vol.65 No.10

구연 : 내분비-대사 ; 정읍 농촌지역 당뇨병 유병율의 변화

송기호,박중열,남궁일성,한성민,이은주,이영수,조민우,이무송,김민선,이기업 대한내과학회 2003 대한내과학회 추계학술대회 Vol.65 No.10