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1.  Effects of Transglutaminase 2 Inhibition on Ventilator-Induced Lung Injury 
Journal of Korean Medical Science  2014;29(4):556-563.
This study was performed to examine the role of transglutaminase 2 (TG2) in ventilator-induced lung injury (VILI). C57BL/6 mice were divided into six experimental groups: 1) control group; 2) lipopolysaccharide (LPS) group; 3) lung protective ventilation (LPV) group; 4) VILI group; 5) VILI with cystamine, a TG2 inhibitor, pretreatment (Cyst+VILI) group; and 6) LPV with cystamine pretreatment (Cyst+LPV) group. Acute lung injury (ALI) score, TG2 activity and gene expression, inflammatory cytokines, and nuclear factor-κB (NF-κB) activity were measured. TG2 activity and gene expression were significantly increased in the VILI group (P < 0.05). Cystamine pretreatment significantly decreased TG2 activity and gene expression in the Cyst+VILI group (P < 0.05). Inflammatory cytokines were higher in the VILI group than in the LPS and LPV groups (P < 0.05), and significantly lower in the Cyst+VILI group than the VILI group (P < 0.05). NF-κB activity was increased in the VILI group compared with the LPS and LPV groups (P < 0.05), and significantly decreased in the Cyst+VILI group compared to the VILI group (P = 0.029). The ALI score of the Cyst+VILI group was lower than the VILI group, but the difference was not statistically significant (P = 0.105). These results suggest potential roles of TG2 in the pathogenesis of VILI.
Graphical Abstract
PMCID: PMC3991800  PMID: 24753704
Acute Lung Injury; Respiratory Distress Syndrome, Adult; Respiration, Artificial; Ventilator-Induced Lung Injury; Inflammation; Transglutaminase 2
2.  A Case of IgG4-Related Disease Presenting as Massive Pleural Effusion and Thrombophlebitis 
Immunoglobulin (Ig) G4-related disease is a recently recognized systemic fibroinflammatory condition characterized by a lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells with elevated circulating levels of IgG4. The disease can either be localized to one or two organs, or present as diffuse multi-organ disease. Furthermore, lesions in different organs can present simultaneously or metachronously. In the pulmonary manefestations, lesions associated with IgG4-related disease have been described in the lung parenchyma, airways and pleura, as well as the mediastinum. We report a case of IgG4-related disease presenting as massive pleural effusion and thrombophlebitis.
PMCID: PMC4021266  PMID: 24851132
Immunoglobulin G; Pleural Effusion; Thrombophlebitis
3.  Personality Traits and Body Mass Index in a Korean Population 
PLoS ONE  2014;9(3):e90516.
Overweight and obesity is a serious problem worldwide related to cardiovascular and other diseases. Personality traits are associated with the abnormal body mass indices (BMIs) indicative of overweight and obesity. However, the links between personality traits and BMI have been little studied in Korea.
We evaluated the association between personality traits and BMI in men and women using the rural Ansung and urban Ansan cohort from the Korean Genome Epidemiology Study, and the Kangbuk Samsung Hospital Cohort Study datasets. A shorter version of the original Revised Neuroticism-Extroversion-Openness Personality Inventory (NEO-PI-R) was used to measure the five-factor model of personality (neuroticism, extraversion, openness to experience, agreeableness, and conscientiousness).
Data from a total of 1,495 men (mean age 60.0±9.8 years; mean BMI 24.3±3.0 kg/m2) and 2,547 women (mean age 47.0±15.5 years; mean BMI 22.8±3.4 kg/m2) were included in the analysis. Compared with the normal weight groups, overweight and obese men scored higher on openness to experience and lower on conscientiousness. Overweight and obese women scored lower on neuroticism and openness to experience and higher on agreeableness. Extraversion was positively associated with BMI in men (β = 0.032, P<0.05). BMI and waist circumference were significantly increased in individuals who were less dutiful. In women, neuroticism was inversely associated with BMI (β = −0.026, P<0.05). Openness to experience was negatively, and agreeableness was positively, associated with BMI (openness to experience: β = −0.072, agreeableness β = 0.068) and waist circumference (openness to experience: β = −0.202, agreeableness: β = 0.227) (P<0.05).
Personality traits were associated with underweight, overweight, and obesity in men and women. Increased understanding of the underlying factors contributing to this association will aid in the prevention and treatment of abnormal BMI.
PMCID: PMC3944006  PMID: 24598991
4.  Endometrial Stromal Sarcoma Presented as an Incidental Lung Mass with Multiple Pulmonary Nodules 
Low-grade endometrial stromal sarcoma (ESS) is an uncommon gynecologic malignancy of mesodermal origin. Pulmonary metastasis of low-grade ESS can occur years and decades after the treatment of the primary disease. Low-grade ESS is frequently mistaken as benign uterine neoplasm like uterine leiomyoma, which can potentially lead to a misdiagnosis. We present a case of a 42-year-old woman with low-grade ESS, that initially presented as an incidental lung mass with multiple pulmonary nodules, seven years after an uterine myomectomy. A 6.9×5.8 cm-sized intrapelvic mass suspected of uterine origin was discovered while searching for potential extrathoracic primary origin. A pelviscopy and simultaneous thoracoscopic lung biopsy were conducted for pathologic diagnosis. Finally, the diagnosis was confirmed as low-grade ESS with lung metastasis based on the histopathologic examination with immunohistochemical stain, which was showed positive for CD10 and hormone receptor markers (estrogen and progesterone receptors) in both pelvic and lung specimens.
PMCID: PMC3982240  PMID: 24734101
Sarcoma, Endometrial Stromal; Multiple Pulmonary Nodules; Neoplasm Metastasis
5.  Plasma Glucose Regulation and Mortality in Korea: A Pooled Analysis of Three Community-Based Cohort Studies 
Diabetes & Metabolism Journal  2014;38(1):44-50.
Although diabetes is a well-known risk factor for death, its impact on cancer death is not clearly understood. Furthermore, it remains controversial whether impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) are associated with increased risk of mortality. We investigated the impact of diabetes or glucose tolerance categories on all cause and cause-specific mortality.
Mortality analysis was conducted in three population-based cohort studies of 3,801 participants, divided according to fasting plasma glucose (FPG) (normal; stage 1 IFG [5.6≤FPG<6.1 mmol/L]; stage 2 IFG [6.1≤FPG<7.0 mmol/L]; diabetes mellitus [DM]-FPG); or 2-hour glucose after 75 g glucose loading (2hPG) (normal; IGT; DM-2hPG), or a combination of FPG and 2hPG criteria.
During a median follow-up of 11.0 years, 474 subjects died from all causes. Hazard ratios (HRs) for all cause death were higher in those with diabetes as defined by either FPG or 2hPG criteria than their normal counterparts (HR, 2.2, 95% confidence interval [CI], 1.6 to 2.9 for DM-FPG; HR, 2.0, 95% CI, 1.5 to 2.7 for DM-2hPG). Similarly, diabetes defined by either FPG or 2hPG was associated with cancer death (HR, 2.9, 95% CI, 1.7 to 5.0; and HR, 2.1, 95% CI, 1.2 to 3.9, respectively). Although neither IFG nor IGT conferred higher risk for death, when combining stage 2 IFG and/or IGT, the risk of all cause death was higher than in subjects with normal glucose regulation (HR, 1.3; 95% CI, 1.0 to 1.6).
Diabetes is associated with higher risk of death from all causes and cancer. In subjects without diabetes, stage 2 IFG and/or IGT confers increased risk for mortality.
PMCID: PMC3950194  PMID: 24627827
Diabetes mellitus; Glucose intolerance; Mortality
6.  Regional pulse wave velocities and their cardiovascular risk factors among healthy middle-aged men: a cross-sectional population-based study 
Both carotid-femoral (cf) pulse wave velocity (PWV) and brachial-ankle (ba) PWV employ arterial sites that are not consistent with the path of blood flow. Few previous studies have reported the differential characteristics between cfPWV and baPWV by simultaneously comparing these with measures of pure central (aorta) and peripheral (leg) arterial stiffness, i.e., heart-femoral (hf) PWV and femoral-ankle (fa) PWV in healthy populations. We aimed to identify the degree to which these commonly used measures of cfPWV and baPWV correlate with hfPWV and faPWV, respectively, and to evaluate whether both cfPWV and baPWV are consistent with either hfPWV or faPWV in their associations with cardiovascular (CV) risk factors.
A population-based sample of healthy 784 men aged 40–49 (202 white Americans, 68 African Americans, 202 Japanese-Americans, and 282 Koreans) was examined in this cross-sectional study. Four regional PWVs were simultaneously measured by an automated tonometry/plethysmography system.
cfPWV correlated strongly with hfPWV (r = .81, P < .001), but weakly with faPWV (r = .12, P = .001). baPWV correlated moderately with both hfPWV (r = .47, P < .001) and faPWV (r = .62, P < .001). After stepwise regression analyses with adjustments for race, cfPWV shared common significant correlates with both hfPWV and faPWV: systolic blood pressure (BP) and body mass index (BMI). However, BMI was positively associated with hfPWV and cfPWV, and negatively associated with faPWV. baPWV shared common significant correlates with hfPWV: age and systolic BP. baPWV also shared the following correlates with faPWV: systolic BP, triglycerides, and current smoking.
Among healthy men aged 40 – 49, cfPWV correlated strongly with central PWV, and baPWV correlated with both central and peripheral PWVs. Of the CV risk factors, systolic BP was uniformly associated with all the regional PWVs. In the associations with factors other than systolic BP, cfPWV was consistent with central PWV, while baPWV was consistent with both central and peripheral PWVs.
PMCID: PMC3893368  PMID: 24410766
Arterial stiffness; Aorta; Carotid arteries; Brachial artery; Femoral artery
7.  Correlation of a Self-Report and Direct Measure of Physical Activity Level in the Electron-Beam Tomography and Risk Assessment Among Japanese and US Men in the Post World War II Birth Cohort (ERA JUMP) Study 
Journal of Epidemiology  2013;23(6):411-417.
Physical activity (PA) is complex and a difficult behavior to assess as there is no ideal assessment tool(s) that can capture all contexts of PA. Therefore, it is important to understand how different assessment tools rank individuals. We examined the extent to which self-report and direct assessment PA tools yielded the same ranking of PA levels.
PA levels were measured by the Modifiable Activity Questionnaire (MAQ) and pedometer at baseline among 855 white (W), African-American (AA), Japanese-American (JA), and Korean (K) men (mean age 45.3 years) in 3 geographic locations in the ERA JUMP study.
Korean men were more active than W, AA, and JA men, according to both the MAQ and pedometer (MAQ total PA [mean ± SD]: 41.6 ± 17.8, 20.9 ± 9.9, 20.0 ± 9.1, and 29.4 ± 10.3 metabolic equivalent [MET] hours/week, respectively; pedometer: 9584.4 ± 449.4, 8363.8 ± 368.6, 8930.3 ± 285.6, 8335.7 ± 368.6 steps/day, respectively). Higher levels of total PA in Korean men, as shown by MAQ, were due to higher occupational PA. Spearman correlations between PA levels reported on the MAQ and pedometer indicated positive associations ranging from rho = 0.29 to 0.42 for total activity, rho = 0.13 to 0.35 for leisure activity, and rho = 0.10 to 0.26 for occupational activity.
The 2 assessment methods correlated and were complementary rather than interchangeable. The MAQ revealed why Korean men were more active. In some subpopulations it may be necessary to assess PA domains other than leisure and to use more than 1 assessment tool to obtain a more representative picture of PA levels.
PMCID: PMC3834277  PMID: 24064592
ethnic groups; exercise; pedometry; self-report; occupational activity
8.  Relationships of Coagulation Factor XIII Activity with Cell-Type and Stage of Non-Small Cell Lung Cancer 
Yonsei Medical Journal  2013;54(6):1394-1399.
Factor XIII (FXIII), a thrombin-activated plasma transglutaminase zymogen, is involved in cancer development and progression through a triggered coagulation pathway. The aim of this study was to examine whether FXIII activity levels differed in non-small cell lung cancer (NSCLC) patients according to histological types and TNM stage when compared with healthy subjects.
Materials and Methods
Twenty-eight NSCLC patients and 28 normal controls who had been individually age-, gender-, body mass index-, smoking status-, and smoking amount-matched were enrolled: 13 adenocarcinomas, 11 squamous cell carcinomas, and four undifferentiated NSCLCs; four stage I, two stage II, 12 stage III, and 10 stage IV NSCLCs. FXIII activity was measured using fluorescence-based protein arrays.
The median FXIII activity level of the NSCLC group [24.2 Loewy U/mL, interquartile range (IQR) 14.9-40.4 Loewy U/mL] was significantly higher than that of the healthy group (17.5 Loewy U/mL, IQR 12.6-26.4 Loewy U/mL) (p=0.01). There were no differences in FXIII activity between adenocarcinoma (median 18.6 Loewy U/mL) and squamous cell carcinoma (median 28.7 Loewy U/mL). NSCLC stage significantly influenced FXIII activity (p=0.02). The FXIII activity of patients with stage III NSCLC (median 27.3 Loewy U/mL, IQR 19.3-40.5 Loewy U/mL) was significantly higher than those of patients with stage I or II (median 14.0 Loewy U/mL, IQR 13.1-23.1 Loewy U/mL, p=0.04). FXIII activity was negatively correlated with aPTT in NSCLC patients (r=-0.38, p=0.04).
Patients with advanced-stage NSCLC exhibited higher coagulation FXIII activity than healthy controls and early-stage NSCLC patients.
PMCID: PMC3809885  PMID: 24142643
Factor XIII; histological type; neoplasm staging; non-small-cell lung carcinoma
9.  Low Vitamin D Status Is Associated with Nonalcoholic Fatty Liver Disease Independent of Visceral Obesity in Korean Adults 
PLoS ONE  2013;8(10):e75197.
To investigate the association between serum 25-hydroxyvitamin D [25(OH)D] levels and nonalcoholic fatty liver disease (NAFLD) independent of visceral obesity in Koreans and to examine whether the associations differ according to the presence of diabetes or insulin resistance.
Research Design and Methods
A total of 1081 adults were enrolled from a population-based cohort in Ansan city. Serum 25(OH)D concentrations were measured in all subjects. Insulin resistance was measured by homeostasis model assessment of insulin resistance (HOMA-IR). Using computed tomography, NAFLD was diagnosed if the liver attenuation index (LAI, the difference between the mean hepatic and splenic attenuation) was <5 Hounsfield Units.
In subjects with diabetes (n = 282), 25(OH)D levels were negatively associated with waist circumference, fasting insulin, HOMA-IR, triglyceride levels, and visceral abdominal fat, and were positively associated with LAI after adjusting for age, sex, season, exercise, and vitamin supplementation. In subjects without diabetes, only triglyceride level was negatively associated with 25(OH)D. The adjusted odds ratio (OR) for NAFLD increased sequentially across decreasing quartiles of 25(OH)D in subjects with diabetes even after adjusting for visceral fat [Q1 vs. Q4; OR for NAFLD 2.5 (95% CI:1.0–6.2)]. In contrast, no significant difference in OR was observed in subjects without diabetes. When we classified non-diabetic subjects by HOMA-IR, an increase in the OR for NAFLD across decreasing quartiles of 25(OH)D was observed in the high HOMA-IR (≥2.5) group [n = 207, Q1 vs. Q4; OR 3.8(1.4–10.3)], but not in the low HOMA-IR (<2.5) group [n = 592, OR 0.8 (0.3–1.9)].
Low vitamin D status is closely associated with NAFLD, independent of visceral obesity in subjects with diabetes or insulin resistance.
PMCID: PMC3793981  PMID: 24130687
10.  Serum levels of marine-derived n-3 fatty acids in Icelanders, Japanese, Koreans, and Americans - A descriptive epidemiologic study 
In the 1990’s Iceland and Japan were known as countries with high fish consumption whereas coronary heart disease (CHD) mortality in Iceland was high and that in Japan was low among developed countries. We described recent data fish consumption and CHD mortality from publicly available data. We also measured CHD risk factors and serum levels of marine-derived n-3 and other fatty acids from population-based samples of 1,324 men in Iceland, Japan, South Korea, and the US. CHD mortality in men in Iceland was almost 3 times as high as that in Japan and South Korea. Generally a profile of CHD risk factors in Icelanders compared to Japanese was more favorable. Serum marine-derived n-3 fatty acids in Iceland were significantly lower than in Japan and South Korea but significantly higher than in the US.
PMCID: PMC3404187  PMID: 22658580
n-3 fatty acids; eicosapentaenoic acid; docosaehexaenoic acid; coronary heart disease; descriptive epidemiologic study
11.  The start of chemotherapy until the end of radiotherapy in patients with limited-stage small cell lung cancer 
Chemotherapy combined with radiation therapy is the standard treatment for limited stage small cell lung cancer (LS-SCLC). Although numerous studies indicate that the overall duration of chemoradiotherapy is the most relevant predictor of outcome, the optimal chemotherapy and radiation schedule for LS-SCLC remains controversial. Therefore we analyzed the time from the start of any treatment until the end of radiotherapy (SER) in patients with LS-SCLC.
We retrospectively analyzed 29 patients diagnosed histologically with LS-SCLC and divided them into two groups: a short SER group (< 60 days) and a long SER (> 60 days) group. Patients were treated with irinotecan-based chemotherapy and thoracic radiotherapy.
Sixteen patients were in the short SER group and 13 patients were in the long SER group. Short SER significantly prolonged survival rate (p = 0.03) compared with that of long SER. However, no significant differences in side effects were observed.
Short SER should be considered to improve the outcome of concurrent chemoradiotherapy for LS-SCLC.
PMCID: PMC3712153  PMID: 23864803
Small cell lung carcinoma; Limited-stage; Chemoradiotherapy; Start of any treatment until the end of radiotherapy
12.  Aortic stiffness and calcification in men in a population-based international study 
Atherosclerosis  2012;222(2):473-477.
Aortic stiffness, a hallmark of vascular aging, is an independent risk factor of cardiovascular disease and all-cause mortality. The association of aortic stiffness with aortic calcification in middle-aged general population remains unknown although studies in patients with end-stage renal disease or elderly subjects suggest that aortic calcification is an important determinant of aortic stiffness. The goal of this study was to examine the association of aortic calcification and stiffness in multi-ethnic population-based samples of relatively young men.
We examined the association in 906 men aged 40–49 (81 Black Americans, 276 Japanese Americans, 258 White Americans and 291 Koreans). Aortic stiffness was measured as carotid-femoral pulse wave velocity (cfPWV) using an automated waveform analyzer. Aortic calcification from aortic arch to iliac bifurcation was evaluated using electron-beam computed tomography.
Aortic calcium score was calculated and was categorized into four groups: zero (n=303), 1–100 (n=411), 101–300 (n=110), and 401+ (n=82). Aortic calcification category had a significant positive association with cfPWV after adjusting for age, race, and mean arterial pressure (mean (standard error) of cfPWV (cm/second) from the lowest to highest categories: 836 (10), 850 (9), 877 (17) and 941 (19), p for trend <0.001). The significant positive association remained after further adjusting for other cardiovascular risk factors. The significant positive association was also observed in each race group.
The results suggest that aortic calcification can be one mechanism for aortic stiffness and that the association of aortic calcification with stiffness starts as early as the 40’s.
PMCID: PMC3361615  PMID: 22537531
aortic stiffness; aortic calcification; international multi-ethnic study
13.  A healthy dietary pattern consisting of a variety of food choices is inversely associated with the development of metabolic syndrome 
Nutrition Research and Practice  2013;7(3):233-241.
There are limited data on healthy dietary patterns protective against metabolic syndrome (MetSyn) development. We identified dietary patterns among middle-aged and older adults and investigated the associations with the incidence of MetSyn. A population-based prospective cohort study included 5,251 male and female Koreans aged 40-69 years. At baseline, all individuals were free of MetSyn, other major metabolic diseases, and known cardiovascular disease or cancer. Cases of MetSyn were ascertained over a 6-year of follow-up. Dietary patterns and their factor scores were generated by factor analysis using the data of a food frequency questionnaire. We performed pooled logistic regression analysis to estimate multivariable-adjusted relative risk (RR) and 95% confidence interval (CI) for associations between factor scores and MetSyn risk. Two dietary patterns were identified; (1) a healthy dietary pattern, which included a variety of foods such as fish, seafood, vegetables, seaweed, protein foods, fruits, dairy products, and grains; and (2) an unhealthy dietary pattern, which included a limited number of food items. After controlling for confounding factors, factor scores for the healthy dietary pattern were inversely associated with MetSyn risk (P-value for trend < 0.05) while those for the unhealthy dietary pattern had no association. Individuals in the top quintile of the healthy diet scores showed a multivariable-adjusted RR [95% CI] of 0.76 [0.60-0.97] for MetSyn risk compared with those in the bottom quintile. The beneficial effects were derived from inverse associations with abdominal obesity, low HDL-cholesterol levels, and high fasting glucose levels. Our findings suggest that a variety of healthy food choices is recommended to prevent MetSyn.
PMCID: PMC3679333  PMID: 23766885
Dietary pattern; food choices; metabolic syndrome incidence; prospective study
14.  Coronary Artery Calcification in Japanese Men in Japan and Hawaii 
American journal of epidemiology  2007;166(11):1280-1287.
Explanations for the low prevalence of atherosclerosis in Japan versus United States are often confounded with genetic variation. To help remove such confounding, coronary artery calcification (CAC), a marker of subclinical atherosclerosis, was compared between Japanese men in Japan and Japanese men in Hawaii. Findings are based on risk factor and CAC measurements that were made from 2001 to 2005 in 311 men in Japan and 300 men in Hawaii. Men were aged 40 to 50 years and without cardiovascular disease. After age-adjustment, there was a 3-fold excess in the odds of prevalent CAC scores ≥10 in Hawaii versus Japan (relative odds [RO] = 3.2; 95% confidence interval [CI] = 2.1,4.9). While men in Hawaii had a generally poorer risk factor profile, men in Japan were 4-times more likely to smoke cigarettes (49.5 vs. 12.7%, p<0.001). In spite of marked risk factor differences between the samples, none of the risk factors provided an explanation for the low amounts of CAC in Japan. After risk factor adjustment, the RO of CAC scores ≥10 in Hawaii versus Japan was 4.0 (95% CI = 2.2,7.4). Further studies are needed to identify factors that offer protection against atherosclerosis in Japanese men in Japan.
PMCID: PMC3660555  PMID: 17728270
Atherosclerosis; cohort studies; coronary disease; Japan; men; risk factors
15.  Diplotyper: diplotype-based association analysis 
BMC Medical Genomics  2013;6(Suppl 2):S5.
It was previously reported that an association analysis based on haplotype clusters increased power over single-locus tests, and that another association test based on diplotype trend regression analysis outperformed other, more common association approaches. We suggest a novel algorithm to combine haplotype cluster- and diplotype-based analyses.
Diplotyper combines a novel algorithm designed to cluster haplotypes of interest from a given set of haplotypes with two existing tools: Haploview, for analyses of linkage disequilibrium blocks and haplotypes, and PLINK, to generate all possible diplotypes from given genotypes of samples and calculate linear or logistic regression. In addition, procedures for generating all possible diplotypes from the haplotype clusters and transforming these diplotypes into PLINK formats were implemented.
Diplotyper is a fully automated tool for performing association analysis based on diplotypes in a population. Diplotyper was tested through association analysis of hepatic lipase (LIPC) gene polymorphisms or diplotypes and levels of high-density lipoprotein (HDL) cholesterol.
Diplotyper is useful for identifying more precise and distinct signals over single-locus tests.
PMCID: PMC3654869  PMID: 23819435
16.  Tae-Eum Type as an Independent Risk Factor for Obstructive Sleep Apnea 
Obstructive sleep apnea (OSA) is prevalent and associated with several kinds of chronic diseases. There has been evidence that a specific type of Sasang constitution is a risk factor for metabolic and cardiovascular diseases that can be found in patients with OSA, but there are no studies that address the association between the Sasang constitution type (SCT) and OSA. The purpose of this study was to investigate the association between the SCT and OSA. A total of 652 participants were included. All participants were examined for demographic information, medical history, and completed an interviewer-administered questionnaire on life style and sleep-related variables. Biochemical analyses were performed to determine the glucose and lipid profiles. An objective recording of OSA was done with an unattended home PSG using an Embla portable device. The apnea-hypopnea index (AHI) and oxygen desaturation index (ODI) were significantly higher in the Tae-eum (TE) type as compared to the So-eum (SE) and the So-yang (SY) types. Even after adjusting for confounding variables, the TE type still had a 2.34-fold (95% CI, 1.11–4.94; P = 0.0262) increased risk for OSA. This population-based cohort study found that the TE constitutional type is an independent risk factor for the development of OSA.
PMCID: PMC3608128  PMID: 23554836
17.  A case of secondary syphilis presenting as multiple pulmonary nodules 
Syphilis is a sexually transmitted disease caused by Treponema pallidum. The prevalence of this disease has recently increased worldwide. However, pulmonary involvement in secondary syphilis is extremely rare. A 51-year-old heterosexual male patient presented with multiple pulmonary nodules with reactive serology from the Venereal Disease Research Laboratory test and positive fluorescent treponemal antibody absorption testing. A hematogenous metastatic malignancy was suspected and an excisional lung biopsy was performed. Histopathological examination showed only central necrosis with abscess and plasma cell infiltration, but no malignant cells. The patient reported sexual contact with a prostitute 8 weeks previously and a penile lesion 6 weeks earlier. Physical examination revealed an erythematous papular rash on the trunk. Secondary syphilis with pulmonary nodules was suspected, and benzathine penicillin G, 2.4 million units, was administered. Subsequently, the clinical signs of syphilis improved and the pulmonary nodules resolved. The final diagnosis was secondary syphilis with pulmonary nodular involvement.
PMCID: PMC3604614  PMID: 23526483
Syphilis; Treponema pallidum; Multiple pulmonary nodules
18.  Influence of cigarette smoking on coronary artery and aortic calcium among random samples from populations of middle-age Japanese and Korean men 
Cigarette smoking is a risk factor of coronary heart disease (CHD). Vascular calcification such as coronary artery calcium (CAC) and aortic calcium (AC) is associated with CHD. We hypothesized that cigarette smoking is associated with coronary artery and aortic calcifications in Japanese and Koreans with high smoking prevalence.
Random samples from populations of 313 Japanese and 302 Korean men aged 40 to 49 were examined for calcification of the coronary artery and aorta using electron beam computed tomography. Coronary artery calcium (CAC) and aortic calcium (AC) were quantified using the Agatston score. We examined the associations of cigarette smoking with CAC and AC after adjusting for conventional risk factors and alcohol consumption. Current and past smokers were combined and categorized into two groups using median pack-years as a cutoff point in each of Japanese and Koreans. The never smoker group was used as a reference for the multiple logistic regression analyses.
The odds ratios of CAC (score ≥10) for smokers with higher pack-years were 2.9 in Japanese (P<0.05) and 1.3 in Koreans (non-significant) compared to never smokers. The odds ratios of AC (score ≥100) for smokers with higher pack-years were 10.4 in Japanese (P<0.05) and 3.6 in Koreans (P<0.05).
Cigarette smoking with higher pack-years is significantly associated with CAC and AC in Japanese men, while cigarette smoking with higher pack-years is significantly associated with AC but not significantly with CAC in Korean men.
PMCID: PMC3521870  PMID: 22844083
atherosclerosis; cigarette smoking; coronary calcium; aortic calcium; Japanese; Koreans
19.  Adiponectin, Systolic Blood Pressure, and Alcohol Consumption Are Associated with More Aortic Stiffness Progression among Apparently Healthy Men 
Atherosclerosis  2012;225(2):475-480.
We examined several risk factors as possible independent predictors of aortic stiffness progression among a population based sample of US men.
Methods and Results
A total of 240 men aged 40–49 from the Allegheny County site of the ERA JUMP Study, who were free of CVD at baseline were evaluated. Aortic stiffness was measured as carotid-femoral pulse wave velocity (cfPWV) at baseline and after 4.6±0.21(mean±SD) years of follow-up. Progression of cfPWV was evaluated as relative annual change in cfPWV (% change/year). Using linear regression, both baseline potential risk factors and their annual changes were evaluated as possible risk factors for cfPWV progression. Baseline age, follow-up time, race, heart rate, and medications use were forced in all models. During follow-up, relative to baseline level, cfPWV increased 0.3%±5.3% per year. In final models the independent predictors of degree of cfPWV progression were lower levels of adiponectin (β(SE): −1.8(0.8), P=0.03), higher levels of systolic blood pressure (SBP) (β(SE): 0.07(0.03), P=0.02), greater annual change in SBP (β(SE): 0.3(0.2), P=0.04), and alcohol consumption ≥ 2 times/week (β(SE): 1.6(0.7), P=0.02).
Lower levels of adiponectin, higher levels and annual changes of SBP, and alcohol consumption ≥2 times/week are associated with greater progression in aortic stiffness among relatively healthy middle-aged US men.
PMCID: PMC3502702  PMID: 23040831
arteriosclerosis; hypertension; risk factors; pulse wave velocity; stiffness
20.  A Case of Paraneoplastic Limbic Encephalitis Associated with Small Cell Lung Cancer 
Paraneoplastic limbic encephalitis (PLE) is a rare syndrome characterized by memory impairment, affective and behavioral disturbances and seizures. Among many different neoplasms known to cause PLE, small cell lung cancer (SCLC) is the most frequently reported. The pathogenesis is not fully understood but is believed to be autoimmune-related. We experienced a patient with typical clinical features of PLE. A 67-year-old man presented with seizure and disorientation. Brain magnetic resonance imaging demonstrated high signal intensity in the bilateral amygdala and hippocampus in flair and T2-weighted images suggestive of limbic encephalitis. Cerebrospinal fluid tapping revealed no evidence of malignant cells or infection. Positron emission tomography/computed tomography showed a lung mass with pleural effusion and a consequent biopsy confirmed the diagnosis of PLE associated with SCLC. The patient was subsequently treated with chemotherapy and neurologic symptoms gradually improved.
PMCID: PMC3517946  PMID: 23236319
Limbic Encephalitis; Paraneoplastic Syndromes; Lung Neoplasms
21.  Significant inverse association of marine n-3 fatty acids with plasma fibrinogen levels in Japanese in Japan but not in whites or Japanese Americans 
Numerous studies reported beneficial effects of marine n-3 fatty acids (n-3 FAs) on cardiovascular disease (CVD) and its risk factors. However, the association of marine n-3 FAs with plasma fibrinogen, a risk factor for CVD, remains uncertain.
In a population-based, cross-sectional study of 795 men aged 40-49 without CVD (262 whites in Allegheny County, Pennsylvania, US, 302 Japanese in Kusatsu, Japan, and 229 Japanese Americans in Honolulu, Hawaii, US), we examined the association of marine n-3 FAs with plasma fibrinogen. Serum FAs were measured by capillary gas-liquid chromatography. Marine n-3 FAs were defined as the sum of docosahexaenoic, eicosapentaenoic, and docosapentaenoic acids. Plasma fibrinogen was measured by an automated clot-rate assay. Multiple linear regression analyses were performed to assess the association.
White, Japanese, and Japanese American men had mean marine n-3 FAs levels of 3.47%, 8.78%, and 4.46%, respectively. Japanese men had a significant inverse association of marine n-3 FAs with fibrinogen (standardized regression coefficient of -0.11, p=0.049), after adjusting for age, body-mass index, and current smoking. The significant inverse association remained after further adjusting for diabetes, C-reactive protein, triglycerides and other variables. White or Japanese American men did not show a significant association.
We observed the significant inverse association of marine n-3 FAs with fibrinogen in Japanese, but not in whites or Japanese Americans. The observation suggests that marine n-3 FAs at very high levels, as seen in the Japanese, may decrease plasma fibrinogen levels.
PMCID: PMC3244567  PMID: 21897424
fibrinogen; marine n-3 fatty acids; epidemiology; Japanese
22.  Interaction Effects of Lipoprotein Lipase Polymorphisms with Lifestyle on Lipid Levels in a Korean Population: A Cross-sectional Study 
Genomics & Informatics  2012;10(2):88-98.
Lipoprotein lipase (LPL) plays an essential role in the regulation of high-density lipoprotein cholesterol (HDLC) and triglyceride levels, which have been closely associated with cardiovascular diseases. Genetic studies in European have shown that LPL single-nucleotide polymorphisms (SNPs) are strongly associated with lipid levels. However, studies about the influence of interactions between LPL SNPs and lifestyle factors have not been sufficiently performed. Here, we examine if LPL polymorphisms, as well as their interaction with lifestyle factors, influence lipid concentrations in a Korean population. A two-stage association study was performed using genotype data for SNPs on the LPL gene, including the 3' flanking region from 7,536 (stage 1) and 3,703 (stage 2) individuals. The association study showed that 15 SNPs and 4 haplotypes were strongly associated with HDLC (lowest p = 2.86 × 10-22) and triglyceride levels (lowest p = 3.0 × 10-15). Interactions between LPL polymorphisms and lifestyle factors (lowest p = 9.6 × 10-4) were also observed on lipid concentrations. These findings suggest that there are interaction effects of LPL polymorphisms with lifestyle variables, including energy intake, fat intake, smoking, and alcohol consumption, as well as effects of LPL polymorphisms themselves, on lipid concentrations in a Korean population.
PMCID: PMC3480683  PMID: 23105935
interaction; lipoprotein lipase; lipoproteins; lipids; single nucleotide polymorphism
23.  Coronary artery calcification by computed tomography in epidemiological research and cardiovascular disease prevention 
Journal of Epidemiology  2012;22(3):188-198.
Both American and European guidelines recommend coronary artery calcification (CAC) as a tool for screening asymptomatic individuals at intermediate risk. These recommendations are based on epidemiological studies mostly in the United States (U.S.). We review (1) the use of CAC in primary prevention of coronary heart disease (CHD) in the U.S., (2) epidemiological studies of CAC in asymptomatic adults outside of the U.S., and (3) international epidemiological studies of CAC. This review does not consider clinical studies of CAC among patients or symptomatic individuals. Studies in the U.S. have documented that CAC is a strong independent predictor of CHD for both sexes, middle- to old-age groups, various ethnic groups, and diabetics and non-diabetics and that CAC plays an important role in reclassifying individuals at intermediate into high risk. Studies in Europe support these conclusions. The Electron-Beam Tomography, Risk factor Assessment among Japanese and U.S. men in the post-World-War-II birth cohort (ERA JUMP) Study is the first international research comparing subclinical atherosclerosis including CAC in Japanese, Japanese Americans, Koreas, and Caucasians. The study has demonstrated that Japanese had lower levels of atherosclerosis compared to Caucasians whereas Japanese Americans compared to Caucasians had similar or higher levels. CAC is being established as a screening tool for asymptomatic individuals in Europe and the U.S. CAC is a powerful research tool, enabling us to describe the difference in atherosclerotic burden across populations. Such research could elucidate factors responsible for the population difference, which may lead to prevention of CHD.
PMCID: PMC3362675
24.  Coronary Artery Calcification by Computed Tomography in Epidemiologic Research and Cardiovascular Disease Prevention 
Journal of Epidemiology  2012;22(3):188-198.
Both American and European guidelines recommend coronary artery calcification (CAC) as a tool for screening asymptomatic individuals at intermediate risk for coronary heart disease (CHD). These recommendations are based on epidemiologic studies mostly in the United States. We review (1) the use of CAC in primary prevention of CHD in the United States, (2) epidemiologic studies of CAC in asymptomatic adults outside of the United States, and (3) international epidemiologic studies of CAC. This review will not consider clinical studies of CAC among patients or symptomatic individuals. US studies have shown that CAC is a strong independent predictor of CHD in both sexes among middle-aged and old age groups, various ethnic groups, and individuals with and without diabetes and that CAC plays an important role in reclassifying individuals from intermediate to high risk. Studies in Europe support these conclusions. The Electron-Beam Tomography, Risk Factor Assessment Among Japanese and US Men in the Post-World-War-II birth cohort (ERA JUMP) Study is the first international study to compare subclinical atherosclerosis, including CAC among Japanese, Japanese Americans, Koreans, and whites. It showed that as compared with whites, Japanese had lower levels of atherosclerosis, whereas Japanese Americans had similar or higher levels. CAC is being increasingly used as a screening tool for asymptomatic individuals in Europe and the United States. CAC is a powerful research tool, because it enables us to describe differences in atherosclerotic burden across populations. Such research could identify factors responsible for differences among populations, which may improve CHD prevention.
PMCID: PMC3798619  PMID: 22485011
coronary artery calcification; primary prevention; coronary calcium score; EBCT; MDCT
25.  A Prospective Population-based Study of Total Nasal Resistance in Korean Subjects 
Rhinomanometry is a widely accepted method for objective assessment of nasal patency. However, few studies have reported the values of otherwise healthy population for nasal resistance in East Asians. The purpose of this study was to measure normal total nasal resistance (TNR) values in a large sample of Korean adults and to reveal parameters contributing to TNR values.
Subjects were enrolled from a cohort of the Korean Genome and Epidemiology Study. They were evaluated by anthropometry, questionnaire, and active anterior rhinomanometry at transnasal pressures of 100 and 150 Pascal (Pa).
The study sample consisted of 2,538 healthy subjects (1,298 women and 1,240 men) aged 20 to 80 years. Normal reference TNR values were 0.19±0.08 Pa/cm3/second at 100 Pa and 0.22±0.09 Pa/cm3/second at 150 Pa. The TNR of women was significantly higher than that of men (P<0.0001). TNR decreased with increasing age in both genders (P<0.05). In women, lower body weight was related to increasing TNR. In men, current smokers had higher TNR than ex-smokers and never smokers.
The results of the present study provide information regarding the values of otherwise healthy population of TNR and parameters associated with TNR in Korean adults.
PMCID: PMC3314804  PMID: 22468201
Adult; Body weight; Nasal obstruction; Reference values; Rhinomanometry; Smoking

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