1.Lung Disease Diagnostic Model Through IgG Sensitization to Microbial Extracellular Vesicles
Jinho YANG ; Goohyeon HONG ; Youn-Seup KIM ; Hochan SEO ; Sungwon KIM ; Andrea MCDOWELL ; Won Hee LEE ; You-Sun KIM ; Yeon-Mok OH ; You-Sook CHO ; Young Woo CHOI ; You-Young KIM ; Young-Koo JEE ; Yoon-Keun KIM
Allergy, Asthma & Immunology Research 2020;12(4):669-683
Purpose:
Recently, there has been a rise in the interest to understand the composition of indoor dust due to its association with lung diseases such as asthma, chronic obstructive pulmonary disease (COPD) and lung cancer. Furthermore, it has been found that bacterial extracellular vesicles (EVs) within indoor dust particles can induce pulmonary inflammation, suggesting that these might play a role in lung disease.
Methods:
We performed microbiome analysis of indoor dust EVs isolated from mattresses in apartments and hospitals. We developed diagnostic models based on the bacterial EVs antibodies detected in serum samples via enzyme-linked immunosorbent assay (ELISA) in this analysis.
Results:
Proteobacteria was the most abundant bacterial EV taxa observed at the phylum level while Pseudomonas, Enterobacteriaceae (f) and Acinetobacter were the most prominent organisms at the genus level, followed by Staphylococcus. Based on the microbiome analysis, serum anti-bacterial EV immunoglobulin G (IgG), IgG1 and IgG4 were analyzed using ELISA with EV antibodies that targeted Staphylococcus aureus, Acinetobacter baumannii, Enterobacter cloacae and Pseudomonas aeruginosa. The levels of anti-bacterial EV antibodies were found to be significantly higher in patients with asthma, COPD and lung cancer compared to the healthy control group. We then developed a diagnostic model through logistic regression of antibodies that showed significant differences between groups with smoking history as a covariate. Four different variable selection methods were compared to construct an optimal diagnostic model with area under the curves ranging from 0.72 to 0.81.
Conclusions
The results of this study suggest that ELISA-based analysis of anti-bacterial EV antibodies titers can be used as a diagnostic tool for lung disease. The present findings provide insights into the pathogenesis of lung disease as well as a foundation for developing a novel diagnostic methodology that synergizes microbial EV metagenomics and immune assays.
2.Lung Disease Diagnostic Model Through IgG Sensitization to Microbial Extracellular Vesicles
Jinho YANG ; Goohyeon HONG ; Youn-Seup KIM ; Hochan SEO ; Sungwon KIM ; Andrea MCDOWELL ; Won Hee LEE ; You-Sun KIM ; Yeon-Mok OH ; You-Sook CHO ; Young Woo CHOI ; You-Young KIM ; Young-Koo JEE ; Yoon-Keun KIM
Allergy, Asthma & Immunology Research 2020;12(4):669-683
Purpose:
Recently, there has been a rise in the interest to understand the composition of indoor dust due to its association with lung diseases such as asthma, chronic obstructive pulmonary disease (COPD) and lung cancer. Furthermore, it has been found that bacterial extracellular vesicles (EVs) within indoor dust particles can induce pulmonary inflammation, suggesting that these might play a role in lung disease.
Methods:
We performed microbiome analysis of indoor dust EVs isolated from mattresses in apartments and hospitals. We developed diagnostic models based on the bacterial EVs antibodies detected in serum samples via enzyme-linked immunosorbent assay (ELISA) in this analysis.
Results:
Proteobacteria was the most abundant bacterial EV taxa observed at the phylum level while Pseudomonas, Enterobacteriaceae (f) and Acinetobacter were the most prominent organisms at the genus level, followed by Staphylococcus. Based on the microbiome analysis, serum anti-bacterial EV immunoglobulin G (IgG), IgG1 and IgG4 were analyzed using ELISA with EV antibodies that targeted Staphylococcus aureus, Acinetobacter baumannii, Enterobacter cloacae and Pseudomonas aeruginosa. The levels of anti-bacterial EV antibodies were found to be significantly higher in patients with asthma, COPD and lung cancer compared to the healthy control group. We then developed a diagnostic model through logistic regression of antibodies that showed significant differences between groups with smoking history as a covariate. Four different variable selection methods were compared to construct an optimal diagnostic model with area under the curves ranging from 0.72 to 0.81.
Conclusions
The results of this study suggest that ELISA-based analysis of anti-bacterial EV antibodies titers can be used as a diagnostic tool for lung disease. The present findings provide insights into the pathogenesis of lung disease as well as a foundation for developing a novel diagnostic methodology that synergizes microbial EV metagenomics and immune assays.
3.Clinical Usefulness of ¹â¸F-FC119S Positron-Emission Tomography as an Auxiliary Diagnostic Method for Dementia: An Open-Label, Single-Dose, Evaluator-Blind Clinical Trial
Inki LEE ; Hae Ri NA ; Byung Hyun BYUN ; Ilhan LIM ; Byung Il KIM ; Chang Woon CHOI ; In Ok KO ; Kyo Chul LEE ; Kyeong Min KIM ; Su Yeon PARK ; Yu Keong KIM ; Jun Young LEE ; Seon Hee BU ; Jung Hwa KIM ; Hee Seup KIL ; Chansoo PARK ; Dae Yoon CHI ; Jeong Ho HA ; Sang Moo LIM
Journal of Clinical Neurology 2020;16(1):131-139
BACKGROUND:
AND PURPOSE: The aim of this study was to determine the diagnostic performance and safety of a new ¹â¸F-labeled amyloid tracer, ¹â¸F-FC119S.
METHODS:
This study prospectively recruited 105 participants, comprising 53 with Alzheimer's disease (AD) patients, 16 patients with dementia other than AD (non-AD), and 36 healthy controls (HCs). In the first screening visit, the Seoul Neuropsychological Screening Battery cognitive function test was given to the dementia group, while HC subjects completed the Korean version of the Mini Mental State Examination. Individuals underwent ¹â¸F-FC119S PET, ¹â¸F-fluorodeoxyglucose (FDG) PET, and brain MRI. The diagnostic performance of ¹â¸F-FC119S PET for AD was compared to a historical control (comprising previously reported and currently used amyloid-beta PET agents), ¹â¸F-FDG PET, and MRI. The standardized uptake value (SUV) ratio (ratio of the cerebral cortical SUV to the cerebellar SUV) was measured for each PET data set to provide semiquantitative analysis. All adverse effects during the clinical trial periods were monitored.
RESULTS:
Visual assessments of the ¹â¸F-FC119S PET data revealed a sensitivity of 92% and a specificity of 84% in detecting AD. ¹â¸F-FC119S PET demonstrated equivalent or better diagnostic performance for AD detection than the historical control, ¹â¸F-FDG PET (sensitivity of 80.0% and specificity of 76.0%), and MRI (sensitivity of 98.0% and specificity of 50.0%). The SUV ratios differed significantly between AD patients and the other groups, at 1.44±0.17 (mean±SD) for AD, 1.24±0.09 for non-AD, and 1.21±0.08 for HC. No clinically significant adverse effects occurred during the trial periods.
CONCLUSIONS
¹â¸F-FC119S PET provides high sensitivity and specificity in detecting AD and therefore may be considered a useful diagnostic tool for AD.
4.IgG Sensitization to Extracellular Vesicles in Indoor Dust Is Closely Associated With the Prevalence of Non-Eosinophilic Asthma, COPD, and Lung Cancer.
You Sun KIM ; Jun Pyo CHOI ; Min Hye KIM ; Han Ki PARK ; Sejung YANG ; Youn Seup KIM ; Tae Bum KIM ; You Sook CHO ; Yeon Mok OH ; Young Koo JEE ; Sang Do LEE ; Yoon Keun KIM
Allergy, Asthma & Immunology Research 2016;8(3):198-205
PURPOSE: Recent experimental evidence shows that extracellular vesicles (EVs) in indoor dust induce neurtrophilic pulmonary inflammation, which is a characteristic pathology in patients with severe asthma and chronic obstructive pulmonary disease (COPD). In addition, COPD is known to be an important risk factor for lung cancer, irrespective of cigarette smoking. Here, we evaluated whether sensitization to indoor dust EVs is a risk for the development of asthma, COPD, or lung cancer. METHODS: Serum IgG antibodies against dust EVs were measured in 90 healthy control subjects, 294 asthmatics, 242 COPD patients, and 325 lung cancer patients. Serum anti-dust EV IgG titers were considered high if they exceeded a 95 percentile value of the control subjects. Age-, gender-, and cigarette smoke-adjusted multiple logistic regression analyses were performed to determine odds ratios (ORs) for asthma, COPD, and lung cancer patients vs the control subjects. RESULTS: In total, 4.4%, 13.6%, 29.3%, and 54.9% of the control, asthma, COPD, and lung cancer groups, respectively, had high serum anti-dust EV IgG titers. Adjusted multiple logistic regression revealed that sensitization to dust EVs (high serum anti-dust EV IgG titer) was an independent risk factor for asthma (adjusted OR, 3.3; 95% confidence interval [CI], 1.1-10.0), COPD (adjusted OR, 8.0; 95% CI, 2.0-32.5) and lung cancer (adjusted OR, 38.7; 95% CI, 10.4-144.3). CONCLUSIONS: IgG sensitization to indoor dust EVs appears to be a major risk for the development of asthma, COPD, and lung cancer.
Antibodies
;
Asthma*
;
Dust*
;
Humans
;
Immunoglobulin G*
;
Logistic Models
;
Lung Neoplasms*
;
Lung*
;
Odds Ratio
;
Pathology
;
Pneumonia
;
Prevalence*
;
Pulmonary Disease, Chronic Obstructive*
;
Risk Factors
;
Smoking
;
Tobacco Products
5.Management of endoscopic retrograde cholangiopancreatography-related perforations.
Byung Seup KIM ; In Gyu KIM ; Byoung Yoon RYU ; Jong Hyeok KIM ; Kyo Sang YOO ; Gwang Ho BAIK ; Jin Bong KIM ; Jang Yong JEON
Journal of the Korean Surgical Society 2011;81(3):195-204
PURPOSE: The purpose of this study is to analyze the treatment strategies of patients with endoscopic retrograde cholangiopancreatography (ERCP)-related perforations. This is a retrospective study. METHODS: We experienced 13 perforations associated with ERCP. We reviewed the medical recordsand classified ERCP-related perforations according to mechanism of injury in terms of perforating device. Injury by endoscopic tip or insertion tube was classified as type I, injury by cannulation catheter or sphincterotomy knife as type II, and injury by guidewire as type III. RESULTS: Of four type I injuries, one case was managed by conservative management after primary closure with a hemoclip during ERCP. The other three patients underwent surgical treatments such as primary closure orpancreatico-duodenectomy. Of five type II injuries, two patients underwent conservative management and the other three cases were managed by surgical treatment such as duodenojejunostomy, duodenal diverticulization and pancreatico-duodenectomy. Of four type III injuries, three patients were managed conservatively and the remaining patient was managed by T-tube choledochostomy. CONCLUSION: Type I injuries require immediate surgical management after EPCP or immediate endoscopic closure during ERCP whenever possible. Type II injuries require surgical or conservative treatment according to intra- and retro-peritoneal dirty fluid collection findings following radiologic evaluation. Type III injuries almost always improve after conservative treatment with endoscopic nasobilliary drainage.
Catheterization
;
Catheters
;
Cholangiopancreatography, Endoscopic Retrograde
;
Drainage
;
Humans
;
Retrospective Studies
6.Transcatheter Closure of Multiple Atrial Septal Defects With the Amplatzer Device.
Mi Jin CHO ; Jinyoung SONG ; Soo Jin KIM ; Eun Young CHOI ; Sang Yoon LEE ; Woo Seup SHIM
Korean Circulation Journal 2011;41(9):549-551
Percutaneous device occlusion of secundum atrial septal defect (ASD) has become an accepted alternative to surgical repair. A variety of devices have been used successfully. However, all of them have limitations. We report our experience with two devices used to close multiple ASDs.
Cardiac Catheterization
;
Heart Septal Defects
;
Heart Septal Defects, Atrial
7.Lymphocytic Interstitial Pneumonia in Primary Sjogren's Syndrome: A Case Report.
Ji Young KIM ; Sung Hoon PARK ; Seong Kyu KIM ; Dae Sung HYUN ; Yoon Seup KUM ; Kyung Jae JUNG ; Jung Yoon CHOE
The Korean Journal of Internal Medicine 2011;26(1):108-111
Sjogren's syndrome (SS) is an autoimmune disorder in which lymphocytes infiltrate the exocrine glands, resulting in the development of sicca symptoms. Lymphocytes may also invade various other organs and cause diverse symptoms. Interstitial pneumonia has been observed frequently in SS patients. Typically, the pneumonia responds well to systemic steroids, and fatal cases are rare. We experienced a case of lymphocytic pneumonia accompanied by SS and treated with cyclophosphamide pulse therapy, and we present details of the case herein.
Adult
;
Humans
;
Lung/*pathology
;
Lung Diseases, Interstitial/drug therapy/*pathology
;
Lymphocytes/*pathology
;
Male
;
Plasma Cells/pathology
;
Sjogren's Syndrome/*pathology
8.Visceral Pleural Invasion as a Prognostic Factor for Recurrence in Resected IB Non-small Cell Lung Cancer.
Seok KIM ; Ki Sung PARK ; Yoon Seup KUM ; Sub LEE ; Chi Hoon BAE ; Dae Sung HYUN
The Korean Journal of Thoracic and Cardiovascular Surgery 2009;42(5):610-614
BACKGROUND: Several trials have reported on whether adjuvant chemotherapy for resected stage IB non-small cell lung cancer is needed. The aim of our study was to investigate prognostic factors for recurrence to help identify patients who should receive adjuvant chemotherapy. MATERIAL AND METHOD: We reviewed the cases of 48 stage IB non-small cell lung cancer patients between 1997 and 2006. Disease-free survival and overall survival rates were calculated by the Kaplan-Meier method. Univariate analysis was performed with the log rank test and multivariate analysis was done using Cox's proportional hazard model. RESULT: The median follow-up time was 48 months. The overall survival rate was 55.9%, and the disease-free survival rate was 48.6%. Of 8 variables, two factors, visceral pleural invasion and lymphovascular invasion, were prognostic factors of disease-free survival (univariate analysis). Visceral pleural invasion was a significant prognostic factor in multivariate analysis, and overall survival in compared one or more variable such as visceral pleural invasion or, and lymphovascular invasion with the other variables. CONCLUSION: Visceral pleural invasion was identified as a poor prognostic factor and it may help select which patients will benefit from adjuvant chemotherapy in addition to more comprehensive follow-up.
Carcinoma, Non-Small-Cell Lung
;
Chemotherapy, Adjuvant
;
Disease-Free Survival
;
Follow-Up Studies
;
Humans
;
Multivariate Analysis
;
Proportional Hazards Models
;
Recurrence
;
Survival Rate
9.Clinical Significance of PTEN and Ki-67 Expression in Prostate Cancer.
Il KANG ; Yoon Seup KUM ; Kwan Kyu PARK ; Duk Yoon KIM ; Jae Shin PARK
Korean Journal of Urology 2009;50(6):560-566
PURPOSE: Phosphatase and tensin homolog (PTEN) is a novel tumor suppressor gene located at chromosome 10q23. Ki-67 antigen is a human nuclear protein that is expressed in all active parts of the cell cycle. We evaluated the significance of PTEN and Ki-67 expression in prostate cancer and investigated the relation of this expression with clinico-pathological factors in prostate cancer. MATERIALS AND METHODS: Initially, we did two kinds of immunohistochemical staining for PTEN and Ki-67. Immunohistochemical staining was performed on 75 formalin-fixed paraffin-embedded cancer specimens. Staining on paraffin blocks from prostate carcinomas was compared with that for adjacent normal prostate. Stainings were considered positive if nuclear staining was seen. Positive stainings were analyzed with the patient's clinico-pathological findings. Statistical analysis was performed by using chi-square test with p<0.05 considered significant. RESULTS: PTEN was expressed in 65 (86.6%) of 75 specimens. Ki-67 was expressed in 63 (84.0%) of 75 specimens. The staining scores of the tumor cells for PTEN and Ki-67 were higher than those of the adjacent normal cells (p<0.05). The staining scores for PTEN were negatively correlated with the serum prostate-specific antigen (PSA) level and Gleason score, but this was not statistically significant (p>0.05). PTEN expression was negatively correlated with lymph node or distant metastases (p<0.05). Ki-67 was positively correlated with the serum PSA level, the Gleason score, and metastases (p<0.05). CONCLUSIONS: PTEN and Ki-67 staining correlated well with Gleason score and PSA level in prostate cancer. These could be a possible predictor of prostatic neoplasms.
Cell Cycle
;
Genes, Tumor Suppressor
;
Humans
;
Ki-67 Antigen
;
Lymph Nodes
;
Microfilament Proteins
;
Neoplasm Grading
;
Neoplasm Metastasis
;
Nuclear Proteins
;
Paraffin
;
Prostate
;
Prostate-Specific Antigen
;
Prostatic Neoplasms
10.Extragastic Pedunculated Giant Gastrointestinal Stromal Tumor of the Stomach.
Min Soo KIM ; Young Seok HAN ; Dong Lak CHOI ; Yoon Seup KUM
Journal of the Korean Surgical Society 2008;75(4):268-271
Gastrointestinal stromal tumors (GISTs) are a mesenchymal tumor of the digestive tract and they have various clinical characteristics. We report here on the largest extragastric pedunculated GIST of the stomach that has been seen in Korea. The patient was a 67-year-old man with a giant abdominal mass occupying the whole abdomen, and both leg showed swelling for the previous several months. On computed tomography (CT) and magnetic resonance imaging (MRI), this appeared as a septated cystic tumor with a solid component. Laparotomy revealed a giant extragastric tumor arising from the lesser curvature of the stomach that measured 47x34x23 cm and it weighed about 40 kg. Surgical treatment was performed to remove both the giant mass and the gastric wall where the tumor was attached to a 3-cm pedicle. On immunohistochemistry, the tumor was positive for myeloid stem cell antigen (CD34) and c-kit (CD117). The final diagnosis was a pedunculated extragastric type GIST arising from the stomach. The postoperative course was uneventful and the swelling in both legs resolved.
Abdomen
;
Aged
;
Gastrointestinal Stromal Tumors
;
Gastrointestinal Tract
;
Humans
;
Immunohistochemistry
;
Korea
;
Laparotomy
;
Leg
;
Magnetic Resonance Imaging
;
Myeloid Progenitor Cells
;
Stomach

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