BACKGROUND AND OBJECTIVES: Diffuse long coronary artery disease (DLCAD) still has unfavorable clinical outcomes after successful percutaneous coronary intervention (PCI). Therefore, we aimed to evaluate the effectiveness and safety of Resolute™ zotarolimus-eluting stent (R-ZES; Resolute™ Integrity) for patients with DLCAD. METHODS: From December 2011 to December 2014, 1,011 patients who underwent PCI using R-ZES for CAD with longer than 25 mm lesion were prospectively enrolled from 21 hospitals in Korea. We assessed the clinical outcome of major adverse cardiac events (MACE) defined as the composite of cardiac death, non-fatal myocardial infarction (MI), and clinically-driven target vessel revascularization at 12 months. RESULTS: Mean age was 63.8±10.8 years, 701 (69.3%) patients were male, 572 (87.0%) patients had hypertension, 339 (33.8%) patients had diabetes, 549 (54.3%) patients diagnosed with acute MI and 545 (53.9%) patients had multi-vessel disease (MVD). A total of 1,697 stents were implanted into a total of 1,472 lesions. The mean diameter was 3.07±0.38 mm and the length was 28.27±6.97 mm. Multiple overlapping stents were performed in 205 (13.8%) lesions. A 12-month clinical follow-up was available in 1,004 patients (99.3%). The incidences of MACE and definite stent thrombosis at 12-month were 3.0% and 0.3% respectively. On multivariate Cox-regression analysis, multiple overlapping stents implantation, previous congestive heart failure, MVD, and age ≥75 years were independent predictors of one-year MACE. CONCLUSIONS: Our study shows that R-ZES has an excellent 1-year clinical outcome in Korean patients with DLCAD.
Coronary Artery Disease ; Coronary Vessels ; Death ; Drug-Eluting Stents ; Follow-Up Studies ; Heart Failure ; Humans ; Hypertension ; Incidence ; Korea ; Male ; Myocardial Infarction ; Percutaneous Coronary Intervention ; Prospective Studies ; Stents ; Thrombosis ; Treatment Outcome

Extracellular vesicles (EVs) not only eliminate unwanted molecular components, but also carry molecular cargo essential for specific intercellular communication mechanisms. As the molecular characteristics and biogenetical mechanisms of heterogeneous EVs are different, many studies have attempted to purify and characterize EVs. In particular, exosomal molecules, including proteins, lipids, and nucleic acids, have been suggested as disease biomarkers or therapeutic targets in various diseases. However, several unresolved issues and challenges remain despite these promising results, including source variability before the isolation of exosomes from body fluids, the contamination of proteins during isolation, and methodological issues related to the purification of exosomes. This paper reviews the general characteristics of EVs, particularly microvesicles and exosomes, along with their physiological roles and contribution to the pathogenesis of major diseases, several widely used methods to isolate exosomes, and challenges in the development of disease biomarkers using the molecular contents of EVs isolated from body fluids.
Biomarkers* ; Body Fluids ; Exosomes ; Extracellular Vesicles* ; Nucleic Acids

BACKGROUND: Airway epithelial cells are the first line of defense, against pathogens and environmental pollutants, in the lungs. Cellular stress by cadmium (Cd), resulting in airway inflammation, is assumed to be directly involved in tissue injury, linked to the development of lung cancer, and chronic obstructive pulmonary disease (COPD). We had earlier shown that ACN9 (chromosome 7q21), is a potential candidate gene for COPD, and identified significant interaction with smoking, based on genetic studies. However, the role of ACN9 in the inflammatory response, in the airway cells, has not yet been reported. METHODS: We first checked the anatomical distribution of ACN9 in lung tissues, using mRNA in situ hybridization, and immunohistochemistry. Gene expression profiling in bronchial epithelial cells (BEAS-2B), was performed, after silencing ACN9. We further tested the roles of ACN9, in the intracellular mechanism, leading to Cd-induced production, of proinflammatory cytokines in BEAS-2B. RESULTS: ACN9 was localized in lymphoid, and epithelial cells, of human lung tissues. ACN9 silencing, led to differential expression of 216 genes. Pathways of sensory perception to chemical stimuli, and cell surface receptor-linked signal transduction, were significantly enriched. ACN9 silencing, further increased the expression of proinflammatory cytokines, in BEAS-2B after Cd exposure. CONCLUSION: Our findings suggest, that ACN9 may have a role, in the inflammatory response in the airway.
Cadmium ; Cytokines ; Environmental Pollutants ; Epithelial Cells* ; Gene Expression ; Gene Expression Profiling ; Humans* ; Immunohistochemistry ; In Situ Hybridization ; Inflammation ; Lung ; Lung Neoplasms ; Pulmonary Disease, Chronic Obstructive ; RNA, Messenger ; Signal Transduction ; Smoke ; Smoking ; Succinate Dehydrogenase

Emerging evidence has emphasized the importance of cancer therapies targeting an abnormal metabolic state of tumor-initiating cells (TICs) in which they retain stem cell-like phenotypes and nicotinamide adenine dinucleotide (NAD⁺) metabolism. However, the functional role of NAD⁺ metabolism in regulating the characteristics of TICs is not known. In this study, we provide evidence that the mitochondrial NAD⁺ levels affect the characteristics of glioma-driven SSEA1⁺ TICs, including clonogenic growth potential. An increase in the mitochondrial NAD⁺ levels by the overexpression of the mitochondrial enzyme nicotinamide nucleotide transhydrogenase (NNT) significantly suppressed the sphere-forming ability and induced differentiation of TICs, suggesting a loss of the characteristics of TICs. In addition, increased SIRT3 activity and reduced lactate production, which are mainly observed in healthy and young cells, appeared following NNT-overexpressed TICs. Moreover, in vivo tumorigenic potential was substantially abolished by NNT overexpression. Conversely, the short interfering RNA-mediated knockdown of NNT facilitated the maintenance of TIC characteristics, as evidenced by the increased numbers of large tumor spheres and in vivo tumorigenic potential. Our results demonstrated that targeting the maintenance of healthy mitochondria with increased mitochondrial NAD⁺ levels and SIRT3 activity could be a promising strategy for abolishing the development of TICs as a new therapeutic approach to treating aging-associated tumors.
Glioblastoma* ; Lactic Acid ; Metabolism ; Mitochondria ; NAD ; NADP Transhydrogenases ; Phenotype ; Tics ; Up-Regulation*

In this article, a part of fund and grant supports was omitted unintentionally.

BACKGROUND AND OBJECTIVES: Carbon monoxide (CO) poisoning can cause tissue hypoxia and left ventricular systolic dysfunction (LVSD) requiring intensive medical management. Our objectives were to find incidence and clinical course of LVSD CO intoxicated patients and make a clinical scoring to predict LVSD. SUBJECTS AND METHODS: We included all consecutive patients with CO exposure in the emergency room. LVSD was defined by LVEF <50% assessed by echocardiography. We compared their clinical, chemical, radiological and electrocardiographic patterns according to the presence of LVSD. RESULTS: From May 2009 to June 2015, we included a total of 81 patients (48 men, 47±19 years old) with CO exposure in this cohort. LVSD was found in about 25 patients (31%). Nine had regional wall motion abnormality. Follow up echocardiographic examinations were available in 21 patients. Of them, 18 patients showed complete recovery in about 3 days (mean 2.8±1.7 days). Of 3 patients without recovery, 2 had significant coronary artery stenosis. LVSD was significantly associated with initial heart rate (>100/min), pulmonary edema on chest X-ray, serum NT pro-BNP (>100 pg/mL), troponin-I (>0.1 ng/mL) and lactic acid (>4.0 mg/dL) after a univariate analysis. Combining these into a clinical score, according to their beta score after a multivariate analysis (rage=0-16), allowed prediction of LVSD with a sensitivity of 84% and specificity of 91% (reference ≥8, area under the curve=0.952, p<0.001) CONCLUSION: About 31% showed LVSD in patients with CO poisoning, and most of them (86%, 18 of 21 patients) recovered within 3 days. Patients with a higher clinical score (≥8) might have LVSD.
Anoxia ; Carbon Monoxide Poisoning* ; Carbon Monoxide* ; Carbon* ; Cohort Studies ; Coronary Stenosis ; Echocardiography ; Electrocardiography ; Emergency Service, Hospital ; Follow-Up Studies ; Heart Rate ; Humans ; Incidence* ; Lactic Acid ; Male ; Multivariate Analysis ; Poisoning ; Pulmonary Edema ; Sensitivity and Specificity ; Thorax ; Troponin I ; Ventricular Dysfunction, Left

A-43-year-old man visited our clinic due to pain and swelling of his left first metatarsophalangeal (MTP) joint since 6-months ago. He was diagnosed as gouty arthritis at private clinic and took hypouricemic agent, but he had progressive pain and swelling. There was swelling, erythema and tenderness and ulceration at base of the left first MTP joint. His laboratory results showed elevated C-reactive protein and normal serum uric acid level. The plain radiograph of foot showed bone destruction of left first MTP joint. MRI revealed joint space narrowing, soft tissue swelling and subchondral cyst. He underwent excisional biopsy and histology demonstrated chronic granulomatous inflammation with caseation necrosis. Tissue polymerase chain reaction for mycobacterium tuberculosis was positive. He was diagnosed as tuberculous osteomyelitis. He started on quadruple anti-tuberculous therapy and his symptom was improved. Early diagnosis and anti-tuberculosis therapy could lead to improve outcomes.
Arthritis, Gouty* ; Biopsy ; Bone Cysts ; C-Reactive Protein ; Early Diagnosis ; Erythema ; Foot ; Gout ; Inflammation ; Joints ; Magnetic Resonance Imaging ; Metatarsophalangeal Joint* ; Mycobacterium tuberculosis ; Necrosis ; Osteomyelitis* ; Polymerase Chain Reaction ; Tuberculosis ; Ulcer ; Uric Acid

PURPOSE: Previously, we reported the presence of virus-encoded microRNAs (miRNAs) in the urine of prostate cancer (CaP) patients. In this study, we investigated the expression of two herpes virus-encoded miRNAs in prostate tissue. METHODS: A total of 175 tissue samples from noncancerous benign prostatic hyperplasia (BPH), 248 tissue samples from patients with CaP and BPH, and 50 samples from noncancerous surrounding tissues from these same patients were analyzed for the expression of two herpes virus-encoded miRNAs by real-time polymerase chain reaction (PCR) and immunocytochemistry using nanoparticles as molecular beacons. RESULTS: Real-time reverse transcription-PCR results revealed significantly higher expression of hsv1-miR-H18 and hsv2-miRH9- 5p in surrounding noncancerous and CaP tissues than that in BPH tissue (each comparison, P<0.001). Of note, these miRNA were expressed equivalently in the CaP tissues and surrounding noncancerous tissues. Moreover, immunocytochemistry clearly demonstrated a significant enrichment of both hsv1-miR-H18 and hsv2-miR-H9 beacon-labeled cells in CaP and surrounding noncancerous tissue compared to that in BPH tissue (each comparison, P<0.05 for hsv1-miR-H18 and hsv2- miR-H9). CONCLUSIONS: These results suggest that increased expression of hsv1-miR-H18 and hsv2-miR-H95p might be associated with tumorigenesis in the prostate. Further studies will be required to elucidate the role of these miRNAs with respect to CaP and herpes viral infections.
Carcinogenesis ; Herpesviridae ; Humans ; Hyperplasia* ; Immunohistochemistry ; MicroRNAs ; Nanoparticles ; Prostate* ; Prostatic Hyperplasia ; Prostatic Neoplasms ; Real-Time Polymerase Chain Reaction

BACKGROUND/AIMS: It remains unclear whether atrophic gastritis can affect dyspeptic symptoms. We aimed to investigate whether the extent of atrophic gastritis is associated with specific dyspeptic symptoms. METHODS: Consecutive adults in a routine health-checkup program were enrolled in the study. The extent of atrophic gastritis was classified into 3 groups based on the Kimura-Takemoto criteria; the gastritis with no or little atrophy (group A: C0), the gastritis with atrophy mainly in the antrum (group B: C1 and C2), and the gastritis with atrophy in the large area of the corpus (group C: C3 and O). Upper gastrointestinal symptoms were categorized into "typical reflux symptoms," "epigastric pain syndrome (EPS)-related symptoms," and "postprandial distress syndrome (PDS)-related symptoms." RESULTS: A total of 1827 patients (1009 males, mean age 45.1 years) were included in the analysis. The subgroups of atrophic gastritis were as follows: group A (n = 1218, 66.7%), group B (n = 392, 21.4%), and group C (n = 217, 11.9%). Typical reflux, EPS-related, and PDS-related symptoms were present in 10.5%, 19.8%, and 16.2% of the subjects, respectively. PDS-related and EPS-related symptoms were significantly more prevalent in the group C of male patients and the group B of female patients, respectively, compared with other groups. PDS-related and EPS-related symptoms were independently associated with the group C in males (OR, 2.123; 95% CI, 1.090-4.136) and the group B in females (OR, 2.571; 95% CI, 1.319-5.025), respectively. CONCLUSIONS: The extent of atrophic gastritis appears to affect the generation of specific dyspeptic symptoms in a gender-dependent manner.
Adult ; Atrophy ; Dyspepsia ; Female ; Gastritis ; Gastritis, Atrophic* ; Humans ; Male

PURPOSE: The purpose of this study was to evaluate the associated brain parenchymal abnormalities of developmental venous anomalies (DVA) with susceptibility-weighted image (SWI). MATERIALS AND METHODS: Between January 2012 and June 2013, 2356 patients underwent brain MR examinations with contrast enhancement. We retrospectively reviewed their MR examinations and data were collected as per the following criteria: incidence, locations, and associated parenchymal signal abnormalities of DVAs on T2-weighted image, fluid-attenuated inversion recovery (FLAIR), and SWI. Contrast enhanced T1-weighted image was used to diagnose DVA. RESULTS: Of the 2356 patients examined, 57 DVAs were detected in 57 patients (2.4%); 47 (82.4%) were in either lobe of the supratentorial brain, 9 (15.7%) were in the cerebellum, and 1 (1.7%) was in the pons. Of the 57 DVAs identified, 20 (35.1%) had associated parenchymal abnormalities in the drainage area. Among the 20 DVAs which had associated parenchymal abnormalities, 13 showed hemorrhagic foci on SWI, and 7 demonstrated only increased parenchymal signal abnormalities on T2-weighted and FLAIR images. In 5 of the 13 patients (38.5%) who had hemorrhagic foci, the hemorrhagic lesions were demonstrated only on SWI. CONCLUSION: The overall incidence of DVAs was 2.4%. Parenchymal abnormalities were associated with DVAs in 35.1% of the cases. On SWI, hemorrhage was detected in 22.8% of DVAs. Thus, we conclude that SWI might give a potential for understanding of the pathophysiology of parenchymal abnormalities in DVAs.
Brain* ; Cerebellum ; Drainage ; Hemorrhage ; Humans ; Incidence ; Magnetic Resonance Imaging* ; Pons ; Retrospective Studies