• Nuclear Medicine and Molecular Imaging
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• 제41권4호
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• pp.299-308
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• 2007

본 연구의 목적은 의사결정트리를 생성하는 생물정보학 프로그램을 개발하고, 이를 갑상선유두암 혈청의 질량분석자료로 시험해 보는 것이다. 대상 및 방법: C4.5를 커스터마이징하여 의사결정트리 분석을 수행할 수 있는 'Protein analysis'라는 프로그램을 개발하였다 61개의 혈청시료(갑상선유두암 27, 자가면역성 갑상선염 17, 대조군 17)를 일정 기간 동안 순차적으로 냉동한 후 실온에서 일시에 해동하여 분석에 사용하였다. 모든 시료는 탈지질화 과정을 거쳐 준비한 후, 2종류의 단백질칩(CM10, IMAC3)에 각각 60개, 50개 시료를 적용하였다. 갑상선유두암의 특징적인 단백질 패턴을 찾기 위해 질량분석기를 이용하여 단백질칩을 분석했다. 'Protein analysis' 프로그램을 이용하여 단백질분포 자료로부터 의사결정트리를 작성하고, 생체표지자 후보물질을 검출하였다. CM10칩에서 발견된 생체표지자 후보물질을 무작위 표본추출 방법을 이용하여 검증하였다. 결과: 단백질분포 자료의 훈련과 검증이 가능한 의사결정트리 프로그램이 개발되었으며, 이 프로그램은 트리 구조와 노드 정보, 트리 구성 과정을 표시하는 3개의 창으로 구성되었다. CM10칩을 이용한 분석에서 총 113개의 단백질 피크 중 23개가 3그룹 간에 유의한 차이가 있었으며, IMAC3는 41개의 단백질 피크 중 8개가 3그룹 간에 유의한 차이가 있었다. 3그룹 분석에서 의사결정트리는 CM10칩과 IMAE3의 단백질분포 자료로부터 각각 60개와 50개의 시료를 높은 정확도로 분류하였으며(오차율 = 각각 3.3%, 2.0%), 각각 4개와 7개의 생체표지자 후보물질을 검출하였다. 암시료와 비암시료를 구분하는 2그룹 분석 에서, 의사결정트리는 모든 암시료를 정확히 구분하였으며(모두 오차율 = 0%), CM10칩을 이용한 분석에서는 단일 노드를 사용하고, IMAC3칩을 이용한 분석에서는 여러 개의 노드를 사용하였다. CM10칩의 단백질 분포자료를 5번의 무작위 추출에 의해 시행한 검증에서 암시료와 비암시료를 구분하는데 높은 정확도를 보였으나(정확도 = 98%, 54/55), 3그룹을 구분할 때는 중등도의 정확도를 보였다(정확도 = 65%, 36/55). 결론: 우리가 개발한 프로그램은 질량분석 자료로부터 성공적으로 의사결정트리를 생성하고, 생체표지자 후보물질을 검출할 수 있었다. 따라서 이 프로그램은 혈청 시료를 이용한 생체표지자 발굴 및 갑상선유두암의 추적관찰에 유용하게 사용될 수 있을 것이다.

• Clinical and Experimental Pediatrics
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• 제57권8호
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• pp.357-362
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• 2014

Purpose: The incidence of Kawasaki disease (KD) is rare in young infants (less than 3 months of age), who present with only a few symptoms that fulfill the clinical diagnostic criteria. The diagnosis for KD can therefore be delayed, leading to a high risk of cardiac complications. We examined the clinical characteristics and measured the serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) levels of these patients for assessing its value in the early detection of KD. Methods: We retrospectively reviewed the data of young infants diagnosed with KD from 2004 to 2012. The control group included 20 hospitalized febrile patients. Laboratory data, including NT-proBNP were obtained for each patient in both groups. Results: Incomplete KD was observed in 21/24 patients (87.5%). The mean fever duration on admission was $1.36{\pm}1.0$ days in the KD group. Common symptoms included erythema at the site of Bacille Calmette-Guerin inoculation (70.8%), skin rash (50.0%), changes of oropharyngeal mucosa (29.1%), and cervical lymphadenopathy (20.8%). The mean number of major diagnostic criteria fulfilled was $2.8{\pm}1.4$. Five KD patients (20.8%) had only one symptom matching these criteria. The incidence of coronary artery complications was 12.5%. The mean serum NT-proBNP level in the acute phase, in the KD and control groups, were $4,159{\pm}3,714pg/mL$ and $957{\pm}902pg/mL$, respectively, which decreased significantly in the convalescent phase. Conclusion: Incomplete KD was observed in 87.5% patients. Serum NT- proBNP might be a valuable biomarker for the early detection of KD in febrile infants aged <3 months.

• Safety and Health at Work
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• 제3권1호
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• pp.17-21
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• 2012

Objectives: Asbestos-related diseases (ARDs) have increased globally over the decades, causing an economic burden and increased health care costs. It is difficult to predict the risk of development of ARDs and of respiratory disability among workers with a history of asbestos exposure. Blood based biomarkers have been reported as promising tools for the early detection of malignant mesothelioma. This study investigated whether serum soluble mesothelin-related peptide (SMRP) would reflect severity of disablement in compensable ARDs. Methods: SMRP levels were measured in a cohort of 514 asbestos-exposed subjects. Severity of ARDs was assessed by a Medical Authority comprising four specially qualified respiratory physicians. Severity of ARDs and SMRP levels were compared. Results: Mean (standard deviation) serum SMRP level in the population with compensable ARDs (n = 150) was 0.95 (0.65) nmol/L, and was positively associated with disability assessment (p = 0.01). Mean SMRP level in healthy asbestos-exposed subjects was significantly lower than those with pleural plaques (p < 0.0001) and in subjects with ARDs who received compensation (p < 0.01). Conclusion: This study indicates that serum SMRP levels correlate with severity of compensable ARDs. Serum SMRP could potentially be applied to monitor progress of ARDs. Further prospective work is needed to confirm the relationship between SMRP and disability assessment in this population.

• Asian Pacific Journal of Cancer Prevention
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• 제15권22호
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• pp.9797-9800
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• 2014

Background: Nasopharyngeal carcinoma (NPC) is a common cancer in Southern China and Southeast Asia. Alu elements are among the most prevalent repetitive sequences and constitute 11% of the human genome. Although Alu methylation has been evaluated in many types of cancer, few studies have examined the levels of this modification in serum from NPC patients. Objective: To compare the Alu methylation levels and patterns between serum from NPC patients and normal controls. Materials and Methods: Sera from 50 NPC patients and 140 controls were examined. Quantitative combined bisulfite restriction analysis-Alu (qCOBRA-Alu) was applied to measure Alu methylation levels and characterize Alu methylation patterns. Amplified products were classified into four patterns according to the methylation status of 2 CpG sites: hypermethylated (methylation at both loci), partially methylated (methylation of either of the two loci), and hypomethylated (unmethylated at both loci). Results: A comparison of normal control sera with NPC sera revealed that the latter presented a significantly lower methylation level (p=0.0002) and a significantly higher percentage of hypomethylated loci (p=0.0002). The sensitivity of the higher percentage of Alu hypomethyted loci for distinguishing NPC patients from normal controls was 96%. Conclusions: Alu elements in the circulating DNA of NPC patients are hypomethylated. Moreover, Alu hypomethylated loci may represent a potential biomarker for NPC screening.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6533-6535
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• 2013

Background: The purpose of this study was to evaluate a new type of tumor biomarker, eukaryotic elongation factor 2 (eEF2), in serum for the early diagnosis, confirmative diagnosis as well as assessment of treatment of non-small cell lung cancer (NSCLC). Methods: 130 patients with NSCLC and 50 healthy individuals undergoing physical examination in our hospital provided the observation and healthy control groups. An enzyme linked immune sorbent assay (ELISA) method was applied to determine serum eEF2 levels. Serum neuron specific enolase (NSE) and squamous cell carcinoma antigen (SCC) levels in the observation group were assessed with an automatic biochemical analyzer. Results: The median levels of eEF2 in the serum of NSCLC patients was found to be significantly higher than the healthy control group (p < 0.01) and it was markedly higher in stages III, IV than stages I, II (p < 0.05). eEF2 was higher with tumor size ${\geq}2$ cm than <2 cm (P< 0.01). Furthermore, two weeks after surgery patients showed a significant trend for eEF2 decrease (p < 0.05). Conclusions: The eukaryotic elongation factor 2 (eEF2) has certain clinical values for early diagnosis, verification, and prognosis as well as classification of lung cancer patients.

• 한국어병학회지
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• 제29권1호
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• pp.25-33
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• 2016

In human medicine, circulating microRNAs have been successfully utilized as early biomarkers for various abnormalities and disease states. Vertebrate miR-122 is a liver-specific microRNA which is expressed almost solely in hepatocytes and plays an important role in the regulation of hepatocyte function. In this study, to evaluate the potential utility of circulating miR-122 as a biomarker for liver injury in olive flounder (Paralichthys olivaceus), fish were orally intubated with two doses of acetaminophen (500 mg/kg or 1.000 mg/kg of body weight), and the expression of miR-122 in serum was quantified using real time-PCR. Histological change in liver, and the enzymatic activity of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) were also analyzed. The results showed that miR-122 was higher in acetaminophen administered groups compared to control group. The histopathological effect of acetaminophen on olive flounder liver was not distinct. The serum level of GPT and GOT was increased within 2 folds compared to control group by acetaminophen administration. However, the serum miR-122 level was increased more than 3 or 4 folds compared to the control group by administration of 1000 mg/kg of acetaminophen. These results suggest the possible use of miR-122 as an indicator of liver injury in olive flounder, even when histopathological effects are not distinctive.

• Applied Biological Chemistry
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• 제49권3호
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• pp.196-201
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• 2006

Vitellogenin은 어류의 난황 단백질의 전구체 물질로서 암컷 혈청에서 발견되는 단백질이며, 외부에서 에스트로겐이나 내분비계장애물질에 노출된 경우에는 수컷이나 미성숙한 암컷에서도 이의 합성이 촉진되는 것으로 보고되었다. 따라서 수컷에서 유도되는 vitellogenin은 외인성 에스트로겐 물질에 노출되었음을 암시하는 중요한 지표로 인정되고 있다. Vitellogenin에 대한 항체를 생산하기 위하여 잉어의 vitellogenin 서열 중의 일부분에 대한 peptide를 합성한 후 그 합성 peptide에 대한 항체를 제작하였다. 그리고 $17{\beta}$-estradiol을 주입한 잉어의 혈청에서 DE-52 이온 교환 크로마토그래피를 사용하여 vitellogenin을 정제한 후 이에 대한 항체를 제작하였다. 본 연구에서는 상기의 합성 vitellogenin peptide에 대하여 제작한 다클론 항체와 vitellogenin 단백질에 대한 다클론 항체가 추후 에스트로겐의 지표로 사용될 수 있는 지를 조사하고자 항체의 반응성을 조사하였다. 정제하여 얻은 vitellogenin에 대한 다클론 항체는 Western blotting 시 $17{\beta}$-estradiol을 주입한 잉어의 혈청과 암컷 잉어의 혈청에 있는 vitellogenin과 반응한 반면에 vitellogenin peptide에 대한 다클론 항체는 이들과 반응하지 않았다. 이는 공유결합적으로 많은 변형이 일어난 vitellogenin 단백질은 vitellogenin 합성 펩타이드에 대한 항체로는 검출되지 않음을 나타낸다.

• 공업화학
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• 제32권4호
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• pp.461-466
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• 2021

본 논문에서는 이동성이 좋고 경제적이며, 간편하게 일회용 진단칩으로 제작 가능한 스크린 프린팅 한 탄소칩 전극[screen printed carbon electrode (SPCE)] 기반의 전압전류법 나노물질 융합형 바이오센서를 제작하여 폐암 조기진단에 활용 가능한 단백질 표지 인자 중에 하나인 heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) 단백질의 농도를 정량 분석하고자 하였다. 먼저 SPCE 표면에 금 나노입자를 전기적으로 증착한 후 크로스링커를 이용하여 hnRNP A1에 특이적으로 결합할 수 있는 바이오리셉터인 DNA 압타머를 고정하였다. Ethanolamine을 블로킹 시약으로 사용하여 압타머와 함께 센서 표면에 고정하여 그 표면을 처리함으로써 비특이적인 생물질의 흡착에 의한 방해 신호를 최소화하고자 하였다. DNA칩과 hnRNP A1 용액을 접촉하여 DNA와 hnRNP A1을 결합시킨 후 alkaline phosphatase (ALP) 효소로 접합한 hnRNP A1 항체(anti-hnRNP A1)을 센서칩 표면으로 주입하여 샌드위치 복합체를 형성하고, 이를 기질인 4-aminophenyl phosphate (APP)와 효소-기질 특이적 산화 반응에 의한 전류 변화를 순환 전압전류법과 시차 펄스전압전류법으로 측정하여 단백질의 농도를 정량적으로 분석하였다. 상기 산화 반응에 의한 피크 전류 변화는 순환전압전류법과 시차 펄스 전압전류법을 사용할 때 -0.05와 -0.17 V (vs. Ag/AgCl) 전위 값에서 각각 일어났다. 개발한 나노바이오센서를 실제 정상인 혈청 시료 분석에 적용 가능함을 보여줌으로써 혈청 한 방울로 폐암의 조기진단 가능성을 제시하고자 하였다.

• Tuberculosis and Respiratory Diseases
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• 제77권6호
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• pp.243-250
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• 2014

Background: Information regarding prognostic value of growth differentiation factor 15 (GDF-15) and heart-type fatty acid-binding protein (H-FABP) in patients with chronic obstructive pulmonary disease (COPD) exacerbation is limited. The aim of this study was to investigate whether serum levels of GDF-15 and H-FABP predict an adverse outcome for COPD exacerbation. Methods: Clinical variables, including serum GDF-15 and H-FABP levels were compared in prospectively enrolled patients with COPD exacerbation that did or did not experience an adverse outcome. An adverse outcome included 30-day mortality and need for endotracheal intubation or inotropic support. Results: Ninety-seven patients were included and allocated into an adverse outcome (n=10) or a control (n=87) group. Frequencies of mental change and $PaCO_2$>37 mm Hg were significantly higher in the adverse outcome group (mental change: 30% vs. 6%, p=0.034 and $PaCO_2$>37 mm Hg: 80% vs. 22%, p<0.001, respectively). Serum GDF-15 elevation (>1,600 pg/mL) was more common in the adverse outcome group (80% vs. 43%, p=0.041). However, serum H-FABP level and frequency of serum H-FABP elevation (>755 pg/mL) did not differ between the two groups. Multivariate analysis showed that an elevated serum GDF-15 and $PaCO_2$>37 mm Hg were significant predictors of an adverse outcome (odds ratio [OR], 25.8; 95% confidence interval [CI], 2.7-243.8; p=0.005 and OR, 11.8; 95% CI, 1.2-115.3; p=0.034, respectively). Conclusion: Elevated serum GDF-15 level and $PaCO_2$>37 mm Hg were found to predict an adverse outcome independently in patients with COPD exacerbation, suggesting the possibility that serum GDF-15 could be used as a prognostic biomarker of COPD exacerbation.

• Fisheries and Aquatic Sciences
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• 제2권2호
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• pp.167-171
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• 1999

This study was designed to develop biomarkers of coastal pollution using biochemical indices of flounder (Paralichthys olivaceus) by changes in lactate dehydrogenase (LDH) activity in the serum and cholinesterase activities in brain membranes. For this purpose acetylcholiesterase (AChE) activity, butyrylcholinesterase (BChE) activity, LDH/AChE ratio and LDH/BChE ratio of cultured flounders at 5 different sites on the southern coast of Korea were compared to those of wild flounders caught in the Pohang, eastern coast of Korea as a control group. Relatively high LDH activities were measured in the serum of flounders cultured on the southern coast of Korea (0.101-0.145 unit) than those in the Pohang control group (0.093 unit). AChE activities were significantly low $(about\;10-20\%)$ in brain membranes of cultured flounders compared to those in the Pohang control group. The ratios of LDH/AChE and LDH/BChE were consistently higher $(136-178\%,\; 155-214\%)$ in cultured flounders than those of Pohang control group. Thus, we propose that the ratios of LDH/AChE and LDH/BChE in flounders could be applicable for the diagnosis of marine pollution.