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        당뇨병 환자에서 혈장 Thrombin-Antithrombin Ⅲ 및 Plasmin-α_2-Plasmin Inhibitor 복합체의 임상적 의의

        김경욱,김은숙,정상수,윤수지,박우일,이준희,남수연,안철우,문병수,김경래,차봉수,송영득,임승길,이현철,허갑범 대한당뇨병학회 2002 Diabetes and Metabolism Journal Vol.25 No.5

        연구배경:당뇨병 환자에서 혈액응고 및 섬유소용해 체계의 이상경향이 있어 그 결과로 여러 혈관합병증의 발생위험이 높다는 사실은 널리 알려져 있다. 그 기전은 아직 확실히 밝혀지지 않았으나, 고혈당으로 인한 혈장 단백질들의 비효소성 당화작용이나 산화성 스트레스로 인한 유리 라티칼 작용으로 응고항진이나 섬유소용해 활성의 저하를 유발하는 것으로 생각되고 있다. 최근 응고 및 용해인자와 그 억제자의 복합체들의 증가가 이 상태를 비교적 예민하게 반영한다고 알려져 있다. 방법:본 연구에서는 당뇨병 환자 101명과 정상 대조군 20명에서 혈장내 thrombin­antithrombin complex(TAT)와 plasmin­α₂­plasmin inhibitor complex(PIC)를 측정하여 비교하고, 당뇨병 환자에서 미세혈관 합병증과 대혈관합병증의 유무에 따른 차이와, 이미 혈관 질환의 위험인자로 알려져 있는 인자들간의 상관성을 알아보고자 하였다. 결과:1. 환자의 분포를 살펴보면 혈관합병증이 있는 군은 85명, 혈관합병증이 없는 군은 16명이었고, 평균연령은 각각 57.9±14.1세, 49.9±16.6세로 혈관 합병증이 있는 군에서 더 나이가 많았고, 체질량지수는 23.2±3.4㎏/㎡, 24.1±3.4㎏/㎡로 두 군간 유의한 차이는 없었다. 또 두 군간의 혈압 및 HbA1c, 공복혈당 및 인슐린과 C­peptide, 총 콜레스테롤, 중성지방, HDL­콜레스테롤, Lp⒜는 유의한 차이가 없었고, 미세혈관합병증이 있는 군에서 당뇨병의 유병기간이 길었다. 2. TAT 및 PIC의 농도는 정상 대조군에서는 2.8±1.2 ng/mL, 240.4±69.7 ng/mL이었고, 당뇨병 환자군에서는 9.5±22.6 ng/mL, 472.2±258.7 ng/mL이었다. TAT와 PIC 모두 당뇨병 환자군에서 정상 대조군에 비해 유의하게 증가되어 있었고(p<0.001), TAT/PIC ratio는 두 군간 차이가 없었다. 3. 당뇨병 환자의 혈관합병증에 따른 TAT 및 PIC, fibrinogen 농도는 합병증이 없는 군은 각각 4.1±2.4ng/mL, 362.2±272.0ng/mL, 322.7±102.4mg/mL으로 PIC와 fibrinogen의 증가를 보였으나, 연령을 보정한 후에는 통계학적 유의성은 없었다. 또 대혈관 합병증군에서는 각각 6.0±4.9 ng/mL, 507.4±321.6 ng/mL, 427.1±194.7 mg/dL이었으며 미세·대혈관 합병증군에서는 10.4±6.4 ng/mL, 484.8±269.7 ng/mL, 388.4±132.4 mg/dL으로 TAT의 증가를 보였으나 역시 연령을 보정한 후에는 통계학적 유의성은 없었다. 4. 미세혈관합병증군에서 HbA1c(>8%)가 높은 군의 PIC 농도가 유의하게 높았고(p=0.049), 대혈관합병증군에서 HbA1c(>8%)가 높은 군의 총 콜레스테롤 농도가 유의하게 높았다(p=0.042). 5. 총 당뇨병 환자군에서 PIC는 fibrinogen과 HbA1c와 양의 상관관계를, BMI와 음의 상관관계를 보였으며(r=0.47, 0.31,-0.25), 혈관 합병증이 없는 당뇨병 환자군에서만 TAT는 HbA1c와 양의 상관관계를 보였다(r=0.67). 결론:이상의 결과에서 혈장 TAT 및 PIC 농도는 당뇨병 환자에서 정상 대조군에 비해 의미있게 증가되어 있었고, 당뇨병 환자군에서는 연령의 증가와 유병기간이 혈액응고항진 및 용해의 장애에 큰 역할을 함을 알 수 있었으며, 총 당뇨병 환자군에 PIC와 HbA1c와 양의 상관관계를, BMI와 음의 상관관계를 보였으며 혈관 합병증이 없는 당뇨병 환자군에서만 TAT는 HbA1c와 양의 상관관계를 보였다. 따라서 당뇨병 환자에서 혈액응고 및 용해의 장애가 동반되어 있다고 볼 수 있으며, 혈장 TAT 및 PIC는 혈관합병증으로의 진행을 예측하는 지표로서 유용하리라 생각된다. 또 혈당조절정도와 상관성이 있으므로 혈당조절후에 추적검사를 시행하여 합병증의 예방이 가능한지 추후 연구가 필요하리라 생각된다. Background : Abnormality of coagulation and fibrinolystic system is known as a predisposing factor of vascular complication in diabetes. Although the pathogenesis is not well known, non-enzymatic glycation reaction and the increase in production of free radicals due to an increased oxidative stress may be linked to the hypercoagulibility and hypofibrinolytic activity. As indices of abnormality in coagulation and firinolysis in peripheral blood, plasma thrombin-antithrombin Ⅲ complex (TAT) and plasmin-α_2-plasmin inhibitor complex (PIC) were measured. The purpose of this study was to clarify whether hypercoagulability exists in diabetic patients with or without vascular complication. Methods : In our study, we measured plasma thrombin-antithrombin Ⅲ compelx (TAT) and plasmin-α_2-plasmin inhibit or complex (PIC) in 101 diabetic subjects and 20 controls. Comparing TAT and PIC levels in diabetic microvascular complication group, diabetic macrovascular complication group and controls, we examined correlation between risk factors associated with diabetic vascular complication. Results : 1. The group with diabetic vascular complication was older than group without complication. There was no significant difference in BMI, blood pressure, HbA_ic, blood sugar level, insulin, C-peptide, serum creatinine, total cholesterol, triglyceride, HDL-cholesterol, Lp (a) between two groups. The group with diabetic microvascular complication had longer duration of diabetes. 2. Concentration of TAT and PIC were 2.8±1.2 ng/ mL, 240.4±69.7 ng/ mL in controls and 9.5±22.6 ng/ mL, 472.2±258.7 ng/ mL in diabetic patients, respectively. TAT and PIC were significantly higher in diabetic patients than in control (p<0.001). But TAT/PIC ratio was no significant difference between two groups. 3. In diabetic patients, concentration of TAT and PIC and fibrinogen were respectively 4.1±2.4 ng/ mL, 362.2±272.0 ng/ mL, 322.7±102.4 mg/ dL in group without vascular complication and 5.3±4.1 ng/ mL, 529.5±258.7 ng/ mL, 374.9±106.2 mg/ dL in group with microvascular complication, which group had increase in PIC and Fibrinogen but no significance after correction of age. Concentration of TAT and PIC and Fibrinogen were 60.±4.9 ng/ mL, 507.4±321.6 ng/ mL, 427.1±194.7 mg/ dL in macrovascular complication, and 10.4±6.7 mg/ mL, 484.8±269.7 ng/ mL, 388.4±132.4 mg/ dL in combined vascular complication which group showed increase of TAT but also had no significant increase after correction of age. 4. In diabetic microvascular complication patients, group of high HbA_1c (>8%) (p=0.049) had significant high PIC concentration. In diabetic macrovascular complication patients, group of high HbA_1c (>8%) (p=0.042) had significant high total cholesterol concentration. 5. In all diabetic patients, PIC was positively correlated with fibrinogen and HbA_1c and negatively correlated BMI (r=0.47, 0.31, -0.25). Only in daibetic patients without angiopathy, TAT was positively correlated with HbA_1c (r=0.67). Conclusion : In this study, plasma TAT and PIC concentration significantly increased in diabetic patients compared with controls, and PIC was increased in group with microvascular complication, TAT were increased in group with combined micro macrovascular complication. However, there was no significance relationship existed when correctinf for age. PIC was correlated with HbA_1c. TAT was correlated with HbA_1c only in the group without angiopathy. Abnormality of coagulation and fibrinolysis were combined in diabetes, plasma TAT and PIC can be used as an index of vascular complication. Also we found the correlation with the degree of the blood glucose control. Therefore we need follow up study for the possibility of prevention of vascular complication after controlling the blood glucose to age-matched patients (J Kor Diaabetes Asso 25:354~363, 2001).

      • SCOPUSSCIEKCI등재

        Efficacy of Combining Proximal Balloon Guiding Catheter and Distal Access Catheter in Thrombectomy with Stent Retriever for Anterior Circulation Ischemic Stroke

        Kim, Sang Hwa,Choi, Jae Hyung,Kang, Myung Jin,Cha, Jae Kwan,Kim, Dae Hyun,Nah, Hyun Wook,Park, Hyun Seok,Kim, Sang Hyun,Huh, Jae Taeck The Korean Neurosurgical Society 2019 Journal of Korean neurosurgical society Vol.62 No.4

        Objective : We evaluated efficacy of combining proximal balloon guiding catheter (antegrade flow arrest) and distal access catheter (aspiration at the site of occlusion) in thrombectomy for anterior circulation ischemic stroke. Methods : We retrospectively analyzed 116 patients who underwent mechanical thrombectomy with stent retriever. The patients were divided by the techniques adopted, the combined technique (proximal balloon guiding catheter and large bore distal access catheter) group (n=57, 49.1%) and the conventional (guiding catheter with stent retriever) technique group (n=59, 50.9%). We evaluated baseline characteristics (epidemiologic data, clinical and imaging characteristics) and procedure details (the number of retrieval attempts, procedure time), as well as angiographic (thrombolysis in cerebral infarction (TICI) score, distal thrombus migration) and clinical outcome (National Institutes of Health Stroke Scale at discharge, modified Rankin Scale [mRS] at 3 months) of them. Results : The number of retrieval attempts was lower (p=0.002) and the first-pass successful reperfusion rate was higher (56.1% vs. 28.8%; p=0.003) in the combined technique group. And the rate of final result of TICI score 3 was higher (68.4% vs. 28.8%; p<0.01) and distal thrombus migration rate was also lower (15.8% vs. 40.7%; p=0.021) in the combined technique group. Early strong neurologic improvement (improvement of National Institutes of Health Stroke Scale ${\geq}11$ or National Institutes of Health Stroke Scale ${\leq}1$ at discharge) rate (57.9% vs. 36.2%; p=0.02) and favorable clinical outcome (mRS at 3 months ${\leq}2$) rate (59.6% vs. 33.9%; p=0.005) were also better in the combined technique group. Conclusion : The combined technique needs lesser attempts, decreases distal migration, increases TICI 3 reperfusion and achieves better clinical outcomes.

      • SCOPUSKCI등재

        체지방분포도가 당대사, 지질대사 및 성장호르몬 분비에 미치는 영향

        허갑범,이현철,임승길,김경래,송영득,남수연,김경욱,정대호,최병기,허애정 대한내분비학회 1999 Endocrinology and metabolism Vol.14 No.3

        Background: Body fat distribution, rather than the level of obesity per se, appears to be a strong predictor of abnormalities in metabolic complication. Visceral fat accumulation is significantly correlated with glucose intolerance and constitutes as an independent risk factor for the diabetes mellitus. Methods: We investigated the impact of body fat distribution on the glucose, lipid metabolism and growth hormone secretion in obese subjects with varying glucose tolerance and lean controls matched with sex and age. 69 obese Koreans (34 men, 35 women; 43.8 yrs) and 21 lean Koreans (10 men, 11 women; 40.8 yrs) were recruited. Anthropometric measurement and impedence for measurement of total body fat, and computed tomography for visceral and subcutaneous fat area at umbilicus level were performed. All subjects underwent a standard oral glucose tolerance test and GH stimulation test by L-dopa. Results: The results are summarized as follows. 1. Obese patients had greater ideal body weight (%, IBW) and lean body mass (LBM) than lean controls. But no significant differences were found in IBW and LBM between 3 obese groups. 2. The 25 obese NIDDM had the highest FFA-AUC during OGTI and the lowest GH-AUC to L-Dopa stimulation test. The insulin-AUC during OGTT was the highest in 24 obese subjects with normal glucose tolerance. 3. All male groups have VSR of more than 0.4, which has been designated visceral fat obesity. In contrast all female groups have VSR of lesser than 0.4 but obese DM subjects have the highest VSR. Visceral fat area per body weight ratio(VWR) showed increasing tendency in obese, IGT, and DM group. 4. Waist circumference and VWR showed strong correlation with metabolic parameters among anthropometric parameters. They were positively correlated with FFA-AUC during OGTT and negatively correlated with GH-AUC to L-dopa stimulation. Conclusion: Visceral fat accumulation are associated with insulin resistance, dyslipidemia and impairment of growth hormone secretion via increase of free fatty acid. The simple waist circumference may provide a more practical indicator that correlated with aMominal fat distribution and metabolic complications associated with obesity (J Kor Soc Endocrinol 14:541-552, 1999).

      • KCI등재

        Genetic Diversity and Population Structure of Glehnia littoralis (Umbelliferae) in Korea

        Huh Man Kyu,Choi Joo Soo,Huh Hong Wook,Choi Yung Hyun,Choi Byung Tae The Physiological Society of Korean Medicine and T 2003 동의생리병리학회지 Vol.17 No.6

        Glehnia littoralis Fr. Schmidt (Umbelliferae) is a short-lived herbaceous species that are mostly distributed throughout East Asia. Although G. littoralis has been regarded as ecologically important one, there is no report on population structure in Korea. Starch gel electrophoresis was used to investigate the allozyme variation and genetic structure of Korean populations of this species. A high level of genetic variation was found in G. littoral is populations. Nine enzymes revealed 18 loci, of which 12 were polymorphic (66.7%). Genetic diversity at the species and population levels were 0.159 and 0.129, respectively. The sexual and asexual reproduction, high fecundity, and colonization process are proposed as possible factors contributing to genetic diversity. An indirect estimate of the number of migrants per generation (Nm = 1.45) indicated that gene flow was not extensive among Korean populations of this species. It is suggested that the ability of vegetation and artificial selection may have played roles in shaping the population structure of this species. we recommend that a desirable conservation population should be included at least 30 plants per population and especially those with high variation.

      • SCOPUSKCI등재

        Treatment outcome of nasal natural killer/T-cell lymphoma

        Hyun Jin Lee,Sang-Wook Lee,Cheolwon Suh,Jooryung Huh,Sang Min Yoon,Young Seok Kim,Su San Kim,Jong Hoon Kim,Eun Kyung Choi,Seung Do Ahn 대한방사선종양학회 2011 Radiation Oncology Journal Vol.29 No.3

        Purpose: To evaluate the radiotherapy treatment outcome of patients in stage IE and IIE nasal natural killer/T-cell lymphoma. Materials and Methods: From August 1999 to August 2009, 46 patients with stage IE and IIE nasal natural killer/T-cell lymphoma were treated by definitive radiotherapy and chemotherapy. 33 patients were treated with chemotherapy followed by radiotherapy (CT + RT) and they received 50.4 Gy in 28 fractions. 13 patients were treated with concurrent chemoradiotherapy (CCRT) and they received 40 Gy in 20 fractions. Results: The median follow-up period was 4.6-137.6 months (median, 50.2 months) for all patients. The 4-year overall survival was 68.6% and 4-year disease free survival (DFS) was 61.9%. The 4-year locoregional recurrence free survival was 65.0%, and 4-year distant metastasis free survival (DMFS) was 66.2%. For patients treated with CT + RT, 15 patients (45.5%) achieved complete response after chemotherapy, and 13 patients (39.4%) achieved partial response. 13 patients (81.8%) achieved complete response after radiotherapy, and 6 patients (18.2%) achieved partial response. For patients treated with CCRT, 11 patients (84.6%) achieved complete response, and one patient (7.7%) achieved partial response. In univariate analysis, presence of cervical lymph node metastasis was only signifi cant prognostic factor for DFS and DMFS. Conclusion: This study did not show satisfactory overall survival rate and disease free survival rate of definitive radiotherapy and chemotherapy for stage IE and IIE nasal natural killer/T-cell lymphoma. For patients with cervical lymph node metastasis, further investigation of new chemotherapy regimens is necessary to reduce the distant metastasis.

      • SCIESCOPUSKCI등재

        Selective Depletion of SSEA-3- and TRA-1-60-Positive Undifferentiated Human Embryonic Stem Cells by Magnetic Activated Cell Sorter (MACS)

        ( Hyun Ok Kim ),( Yong Joon Huh ),( Jiho Jang ),( Youjung Choi ),( Dong Wook Kim ),( Han Soo Kim ) 한국조직공학·재생의학회 2011 조직공학과 재생의학 Vol.8 No.2

        The capacity of indefinite self-renewal and pluripotency make human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) an attractive source for potential regenerative medicine. However, teratoma formation is one of the major obstacles for implementing hESC-based therapeutics in a clinical setting. While this tumorigenic capacity is known to be lost upon lineage differentiation in vitro, there is a potential risk that any residual undifferentiated hESCs or progenitor cells may form tumors upon transplantation. To ensure the safety of hESCs in clinical application, we thus explored the magnetic activated cell sorter (MACS) as a tool for separating undifferentiated hESCs from a mixed population of hESCs and human blood mononuclear cells. Labeled with single or combinations of two fluorsecein-labeled monoclonal antibodies (SSEA-3 and TRA-1-60) and subsequently stained with anti-FITC and/or anti-PE magnetic microbeads, cells were subjected to MACS separation. While a reduction of hESCs by depletion with a single marker was observed, there was still a significant fraction of residual hESCs in the flow-through fraction. However, two consecutive MACS separations upon simultaneous staining of two different hESC markers, SSEA-3 and TRA-1-60, completely depleted hESCs, as validated by flow cytometer, real-time PCR and immunofluoresence microscopic analyses. The maximum efficacy of hESC removal using this protocol was higher than 99.9%. No teratoma formation was observed in hESC-depleted cell injection to NOD/SCID mice. These results indicate that the current MACS protocol with two antibodies can efficiently eliminate undifferentiated cells from differentiated cells and greatly alleviate concerns about tumor formation by hESC-derived cellular therapeutics.

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