박테리아성 지역사회획득 폐렴과 2009 H1N1 바이러스성 감염의 감별에 있어 C-Reactive Protein, Procalcitonin, Lipopolysaccharide-Binding Protein의 역할

한선숙 ( Seon Sook Han ),김세현 ( Se Hyun Kim ),김우진 ( Woo Jin Kim ),이승준 ( Seung Joon Lee ),유숙원 ( Sook Won Ryu ),천명주 ( Myeong Ju Cheon ) 대한결핵 및 호흡기학회 2011 Tuberculosis and Respiratory Diseases Vol.70 No.6

Background: It is difficult but important to differentiate between bacterial and viral infections, especially for respiratory infections. Hence, there is an ongoing need for sensitive and specific markers of bacterial infections. We investigated novel biomarkers for discriminating community acquired bacterial pneumonia from 2009 H1N1 influenza A infections. Methods: This was a prospective, observational study of patients with community acquired bacterial pneumonia, 2009 H1N1 Influenza A infection, and healthy controls. Serum samples were obtained on the initial visit to the hospital and stored at -80˚C. We evaluated CRP (C-reactive protein), PCT (procalcitonin), LBP (lipopolysaccharide- binding protein) and copeptin. These analytes were all evaluated retrospectively except CRP. Receiver operating characteristic curve (ROC) analyses were performed on the resulting data. Results: Enrolled patients included 27 with community acquired bacterial pneumonia, 20 with 2009 H1N1 Influenza A infection, and 26 who were healthy controls. In an ROC analysis for discriminating community acquired bacterial pneumonia from 2009 H1N1 influenza A infection, areas under the curve (AUCs) were 0.799 for CRP (95% Confidence interval [CI], 0.664~0.934), 0.753 for PCT (95% CI, 0.613~0.892) and 0.684 for LBP (95% CI, 0.531~0.837). Copeptin was not different among the three groups. Conclusion: These findings suggest that serum CRP, PCT and LBP can assist physicians in discriminating community acquired bacterial pneumonia from 2009 H1N1 influenza A infection.

MUC5AC 프로모터의 유전자 다형성과 천식과의 연관성

한선숙 ( Seon Sook Han ),성지현 ( Ji Hyun Sung ),이미은 ( Mi Eun Lee ),이승준 ( Seung Joon Lee ),이성준 ( Sung Joon Lee ),김우진 ( Woo Jin Kim ) 대한결핵 및 호흡기학회 2007 Tuberculosis and Respiratory Diseases Vol.63 No.3

연구배경: 기관지 점액의 과분비는 천식의 중요한 기전중의 하나이며, 특히천식 환자에서는 MUC5AC가 중요한 역할을 하는 것으로 알려져 있다. MUC5AC는 다양한 유전자 다형성을 갖는 것으로 알려져 있으나 MUC5AC 유전자 다형성과 천식과의 관계를 본 연구는 거의 없는 실정이다. 따라서 본 연구는 MUC5AC 프로모터 부위의 유전자 다형성과 천식과의 관계를 조사하였다. 방법: 강원대학교 병원에서 78명의 천식환자와 이들과 성별, 나이가 일치하는 78명의 대조군을 선정하였다. 이들로부터 전혈을 채취하여 DNA를 분리하여 PCR과 RFLP를 이용하여 MUC5AC 프로모터의 -1274G>A 유전자 다형성을 분석하였다. 모든 대상환자는 의무기록지를 검토하여 주된 증상과 투여 약제를 확인하였으며, 이들에서의 폐기능, 총 호산구수, 혈청 IgE, 피부반응검사 결과를 조사하였다. 결과: 천식환자의 평균 나이는 47.7±16.1세, 남자가 38.5%이었으며, 평균 FEV1은 84.4±22.3%이었다. MUC5AC 프로모터의 -1274G>A 유전자 다형성은 두 군간에 차이가 없었다(p=0.752, Cod). 천식 증상의 심한 정도, FEV1, 총 호산구수, 혈청 IgE, PC20, 아토피의 유무에 따라서도 MUC5AC 프로모터의 -1274G>A 유전자 다형성은 차이가 없었다. 결론: MUC5AC 프로모터의 -1274G>A 유전자 다형성은 천식과는 무관하였으며, 여러 가지 임상적인 지표들과도 상관관계를 보이지 않았다. Background: Airway mucus hypersecretion plays an important role in the pathogenesis of asthma, and is associated with the induction of MUC5AC expression in airway secretion. The MUC5AC gene is highly polymorphic; however, there are few studies about the association between the polymorphisms of the MUC5AC gene and asthma susceptibility or asthma phenotypes. We have investigated the association of MUC5AC promoter polymorphisms with the risk of asthma and asthma phenotypes. Methods: We determined the genotypes of the MUC5AC promoter (-1274G>A) in 78 asthma patients and in 78 age, sex-matched control individuals in the Korean population. Genomic DNAs from blood were analyzed by PCR and RFLP (restriction fragment length polymorphism) determination. We examined FEV1, total eosinophil count, serum IgE level, PC20 and the presence of atopy (by a skin test) in asthma patients. Results: The mean age of the patients was 47.7 ± 16.1 years and 38.5% were men, and the mean FEV1 was 84.4 ± 22.3% of predicted in the asthma patients. The -1274G>A polymorphism of the MUC5AC promoter in asthma patients was not significantly different as compared with normal individuals (GG 57.7%, AG 34.6% and AA 7.7% in asthma patients vs. GG 56.4%, AG 38.5% and AA 5.1% in control subject, p = 0.752, Cod). Several clinical parameters in asthma patients such as FEV1, total eosinophil count, serum IgE level, PC20 and the presence of atopy, were not associated with the -1274G>A polymorphism of the MUC5AC promoter. Conclusion: The -1274G>A single nucleotide polymorphism (SNP) frequency of the MUC5AC promoter was not associated with asthma in a Korean population. (Tuberc Respir Dis 2007; 63: 235-241)

저산소증을 동반하지 않는 만성폐쇄성폐질환 환자에서의 인지기능장애

김우진 ( Woo Jin Kim ),한선숙 ( Seon Sook Han ),박명옥 ( Myoung Ok Park ),이승준 ( Seung Joon Lee ),김성재 ( Seong Jae Kim ),이정희 ( Jung Hie Lee ) 대한결핵 및 호흡기학회 2007 Tuberculosis and Respiratory Diseases Vol.62 No.5

연구배경: 저산소증을 동반한 COPD 환자에서 인지기능 장애를 보이는 것은 잘 알려져 있다. 그러나 저산소증이 없는 COPD 환자에서의 인지기능에 대해서는 논란의 여지가 있다. 또한, COPD 환자는 수면장애를 동반하는 것으로 알려져 있다. 저자들은 저산소증이 없는 COPD 환자들의 인지기능을 평가하고, 인지기능 장애를 가진 COPD 환자들에서 수면장애가 얼마나 나타나는지 알아보았다. 방법: 90% 이상의 동맥혈 산소 포화도를 가진 28명의 COPD 환자를 대상으로 연구를 시행하였으며, 환자의 평균 나이는 70.7세였다. 대조군은 건강검진을 위해 내원한 33명의 건강성인을 대상으로 하였고, 대조군의 평균 나이는 69.5세였다. 모든 환자 및 대조군은 the Korean version of the Consortium to Establish a Registry for Alzheimer``s Disease(CERAD- K)를 이용하여 신경인지기능을 평가하였다. 결과: COPD 환자군은 단어목록회상(p=0.03)과 단어목록재인(p=0.006) 항목에서 대조군과 비교하여 유의하게 낮은 점수를 보였다. 9명의 환자에서 유의미한 인지기능 장애를 가지고 있었으며, 이 중 7명의 환자에서 수면다원검사를 시행한 결과, 5명의 환자에서 시간당 5회 이상의 apnea-hypopnea index를 보였다. 7명의 환자에서 동맥혈 산소 포화도 감소 지수 및 평균 사지 운동 지수는 각각 3.6/시간과 38.6/시간이었다. 결론: 이 연구는 저산소증이 없는 COPD 환자에서 언어기억 장애를 가진다는 것을 시사하며, 이렇게 인지기능 장애를 가진 COPD 환자들이 수면장애를 동반하고 있어 이에 관한 추가연구의 필요성이 제시되었다. Background: The cognitive function is impaired in patients with hypoxemic chronic obstructive pulmonary disease (COPD). However, there are conflicting results regarding the cognitive function in patients with non-hypoxemic COPD. COPD patients also have sleep disorders. This study examined the cognitive function in non-hypoxemic COPD patients, and nocturnal sleep was assessed in COPD patients with a cognitive dysfunction. Methods: Twenty-eight COPD patients (mean age, 70.7 years) with an oxygen saturation > 90%, and 33 healthy control subjects (mean age, 69.5 years) who had visited for a routine check-up were selected. The neurocognitive tests were performed using the Korean version of the Consortium to Establish a Registry for Alzheimer`s Disease (CERAD-K) Neuropsychological Battery. Results: The scores of the word list recall test (p=0.03) and the word list recognition test (p=0.006) in the COPD group were significantly lower than those in the control group. Nine patients showed a significantly impaired cognitive function. Seven of these underwent polysomnography, which revealed apnea-hypopnea indices ≥ five per hour in five patients. The median oxygen desaturation index and median limb movement index were 3.6/h and 38.6/h, respectively. Conclusion: These results suggest that the verbal memory function is impaired in non-hypoxemic COPD patients. Six out of seven COPD patients with an impaired cognitive function had sleep disorders of sleep apnea and/or periodic limb movements during sleep. (Tuberc Respir Dis 2007; 62: 382-388)

건강성인에서 MDR1의 유전자 다형성에 따른 심바스타틴의 대사의 차이

성지현 ( Ji Hyun Sung ),한선숙 ( Seon Sook Han ),이미은 ( Mi Eun Lee ),하권수 ( Kwon Soo Ha ),김우진 ( Woo Jin Kim ) 대한내과학회 2009 대한내과학회지 Vol.77 No.2

Background/Aims: Simvastatin has dramatically reduced cardiovascular disease due to elevated cholesterol. The human multidrug resistance 1 gene (MDR1) encodes a 170-kDa transmembrane glycoprotein (P-glycoprotein), which plays an important role in regulating the absorption, distribution, and excretion of simvastatin. To clarify the effects of the MDR1 gene polymorphism on simvastatin pharmacokinetics, we investigated whether there is an association between genotype and the pharmacokinetic parameters for simvastatin. Methods: Thirty-one healthy unrelated Korean volunteers were genotyped for MDR1. Genomic DNA from blood was analyzed using the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Following an overnight fast, all of the subjects took a single 60-mg oral dose of simvastatin. Venous blood samples were taken for 12 hours after the oral drug intake. A statistical analysis of the MDR1 genotype and pharmacokinetic parameters of simvastatin was performed. Results: The mean Tmax of the 1236TT genotype was significantly higher than that of CT and CC (p=0.02). The mean AUC0-12h of 3435TT was also significantly higher, compared with CT and CC (p=0.01). No significant difference was observed between the MDR1 single nucleotide polymorphism (SNP) for G2677A/T and the pharmacokinetic parameters. Conclusions: These findings suggest that polymorphic MDR1 genes are important in the inter-individual variation of the disposition of simvastatin in humans. (Korean J 77:211-217, 2009)

피부근염 환자에서 발생한 미만성 폐포 출혈 1예

김세현 ( Se Hyun Kim ),김경현 ( Kyung Hyun Kim ),김태석 ( Tae Suk Kim ),한선숙 ( Seon Sook Han ),문기원 ( Ki Won Moon ) 대한류마티스학회 2011 대한류마티스학회지 Vol.18 No.2

Dermatomyositis is a inflammatory myopathy associated with interstitial lung disease in 5∼10% of cases. The occurrence of diffuse alveolar hemorrhage (DAH) is considered exceptional in the course of dermatomyositis. We experienced a case of DAH in a 58-year-old female with dermatomyositis. DAH was diagnosed by anemia, infiltration on chest X-ray and computed tomography, and a bloody aspirate on bronchoscopy. Combined Pneumocystis jiroveci (PJP) pneumonia was suspected, as the polymerase chain reaction for PJP was positive. After intravenous the administration of immunoglobulin and treatment for the PJP, she markedly improved but subsequently developed nosocomial pneumonia and died.

폐암 세포주에서 광역학 치료에 의한 유전자 발현 분석

성지현 ( Ji Hyun Sung ),이미은 ( Mi Eun Lee ),한선숙 ( Seon Sook Han ),이승준 ( Seung Joon Lee ),하권수 ( Kwon Soo Ha ),김우진 ( Woo Jin Kim ) 대한결핵 및 호흡기학회 2007 Tuberculosis and Respiratory Diseases Vol.63 No.1

연구배경: 광역학 치료는 폐암 치료에 실질적으로 이용 가능하며, 많은 연구들에서 폐암 세포에서 세포사멸을 일으킨다는 것이 이미 알려져 있다. 그러나 이 세포사멸의 기전은 아직 정확히 알려져 있지 않으며, 이에 암세포의 전사에서 초기 변화가 어떻게 일어나는 지를 알아보기 위하여 실험을 수행하였다. 방법: 광과민성 물질인 DH-I-180-3으로 A549 세포에 처리를 하고 광역학 치료를 한 후 관찰하였다. 광역학 치료 후 DEG kit를 이용하여 폐암 세포주에서의 유전자 발현을 보았으며, 유세포 분석기를 이용하여 세포 사멸을 측정하였다. 광역학 치료 후 의미있는 변화를 보인 유전자는 염기서열분석으로 확인하였다. 결과: 유세포분석 결과 폐암세포주는 대부분 세포괴사에 의하여 사멸되었다.광역학 치료 후, 9개의 유전자에서 명확한 변화가 있음을 발견했으며 이 중 8개의 유전자를 밝혀내었다. 3-phosphoglycerate dehydrogenase와 리보솜 단백질 S29의 유전자 발현이 증가되어 있었으며, carbonic anhydrase XII, clusterin, MRP3s1 protein, complement 3, membrane cofactor protein, β-1 integrin의 유전자 발현은 감소되어 있었다. 결론: 본 연구는 광과민성 물질인 DH-I-180-3을 이용한 광역학 치료에서 폐암 세포의 세포사멸의 주된 기전이 세포괴사에 의해 이루어 진 것임을 밝혀냈으며, 이와 관련된 유전자들 대부분이 막단백의 변화를 통해 이루어짐을 알 수 있었다. Background: Photodynamic therapy is a viable option for lung cancer treatment, and many studies have shown that it is capable of inducing cell death in lung cancer cells. However, the precise mechanism of this cell death has not been fully elucidated. To investigate the early changes in cancer cell transcription, we treated A549 cells with the photosensitizer DH-I-180-3 and then we illuminated the cells. Methods: We investigated the gene expression profiles of the the A549 lung cancer cell line, using a DEG kit, following photodynamic therapy and we evaluated the cell viability by performing flow cytometry. We identified the genes that were significantly changed following photodynamic therapy by performing DNA sequencing. Results: The FACS data showed that the cell death of the lung cancer cells was mainly caused by necrosis. We found nine genes that were significantly changed and we identified eight of these genes. We evaluated the expression of two genes, 3-phosphoglycerate dehydrogenase and ribosomal protein S29. The expressed level of carbonic anhydrase XII, clusterin, MRP3s1 protein, complement 3, membrane cofactor protein and integrin beta 1 were decreased. Conclusion: Many of the gene products are membrane-associated proteins. The main mechanism of photodynamic therapy with using the photosensitizing agent DH-I-180-3 appears to be necrosis and this may be associated with the altered production of membrane proteins. (Tuberc Respir Dis 2007; 63: 52-58)

정신지체환자에서 발생한 Streptococcus constellatus와 혐기성 균에 의한 거대농흉

김경현 ( Kyeong Hyun Kim ),김세현 ( Se Hyun Kim ),허정원 ( Jeong Won Heo ),이상훈 ( Sang Hoon Lee ),한선숙 ( Seon Sook Han ),이승준 ( Seoung Joon Lee ),김우진 ( Woo Jin Kim ) 대한결핵 및 호흡기학회 2011 Tuberculosis and Respiratory Diseases Vol.71 No.6

The Streptococcus milleri group, which also includes S. anginosus, S. intermedius and S. constellatus, is found in the oropharynx, upper respiratory tract, gastrointestinal tract, and urogenital tract mucosa. Bacteria in the Streptococcus milleri group are associated with bacteremia and abscess formation. Most of the reports of of Streptococcus milleri group (SMG) infection occur in patients with underlying medical conditions. Predisposing factors that have been associated with S. milleri group empyema include mucosal disturbances (sinusitis, periodontal disease, enteric disease), preceding to pneumonia, thoracic surgery, malignancy, neurological disease, alcohol abuse, and also diabetes mellitus. We report on a 42-year-old man with mental retardation. He who suffered from dyspnea and a fever that he had developed for over 14 days. S. constellatus and anaerobic bacterias ( Prevotella buccae and Micromonas micros) were cultured. The patient was treated with the drainage of pleural effusion and clindamycin and levofloxacin.

다기관성 대결절성 결핵

임경리 ( Kyoung Ree Kim ),강명호 ( Myung Ho Kang ),김태석 ( Tae Suk Kim ),문기원 ( Ki Won Moon ),류동열 ( Dong Ryeol Ryu ),이희영 ( Hui Young Lee ),한선숙 ( Seon Sook Han ) 대한결핵 및 호흡기학회 2012 Tuberculosis and Respiratory Diseases Vol.72 No.1

A 37 year old female presented with epigastric pain and weight loss over a period of 3 months. Her abdominal CT finding showed a 4.5 cm size hepatic mass and 4.3 cm size pancreatic head mass with multiple macronodules in the liver. At the same time, her chest CT revealed a 5 cm size necrotic mass in the left lower lobe of the lung with multiple bilateral pulmonary nodules. We diagnosed these lesions as tuberculosis through multiple biopsies. She was treated with anti-tuberculous medication. After taking the medications, her symptoms were improved. Twelve months later, imaging studies indicated an improvement in the patient`s health. Here we report a case report of multi-organ macronodular tuberculosis in lung, liver and pancreas.

들깨 기름 흡인에 의한 지질폐렴

김희정 ( Hee Jung Kim ),정대준 ( Dae Joon Jeong ),김경현 ( Kyeong Hyun Kim ),김세현 ( Se Hyun Kim ),이승준 ( Seung Joon Lee ),김우진 ( Woo Jin Kim ),한선숙 ( Seon Sook Han ) 대한결핵 및 호흡기학회 2010 Tuberculosis and Respiratory Diseases Vol.68 No.6

Exogenous lipid pneumonia is a rare disease resulting from the aspiration or inhalation of vegetable, animal, or mineral oils. In Korea, the most frequently implicated agent is squalen, which can be obtained from shark liver oil. Lipid pneumonia by aspiration of the vegetable oil is very rare. We experienced a 77-year-old man with a history of ingestion of green perilla oil. His clinical course was favorable; after exposure to the oil was stopped, the patient`s symptoms improved.