1.Increased Risk of Incident Chronic Obstructive Pulmonary Disease and Related Hospitalizations in Tuberculosis Survivors: A PopulationBased Matched Cohort Study
Taehee KIM ; Hayoung CHOI ; Sang Hyuk KIM ; Bumhee YANG ; Kyungdo HAN ; Jin-Hyung JUNG ; Bo-Guen KIM ; Dong Won PARK ; Ji Yong MOON ; Sang-Heon KIM ; Tae-Hyung KIM ; Ho Joo YOON ; Dong Wook SHIN ; Hyun LEE
Journal of Korean Medical Science 2024;39(11):e105-
Background:
Tuberculosis (TB) survivors have an increased risk of developing chronic obstructive pulmonary disease (COPD). This study assessed the risk of COPD development and COPD-related hospitalization in TB survivors compared to controls.
Methods:
We conducted a population-based cohort study of TB survivors and 1:1 age- and sex-matched controls using data from the Korean National Health Insurance Service database collected from 2010 to 2017. We compared the risk of COPD development and COPD-related hospitalization between TB survivors and controls.
Results:
Of the subjects, 9.6% developed COPD, and 2.8% experienced COPD-related hospitalization. TB survivors had significantly higher COPD incidence rates (36.7/1,000 vs. 18.8/1,000 person-years, P < 0.001) and COPD-related hospitalization (10.7/1,000 vs.4.3/1,000 person-years, P < 0.001) than controls. Multivariable Cox regression analyses revealed higher risks of COPD development (adjusted hazard ratio [aHR], 1.63; 95% confidence interval [CI], 1.54–1.73) and COPD-related hospitalization (aHR, 2.03; 95% CI, 1.81–2.27) in TB survivors. Among those who developed COPD, the hospitalization rate was higher in individuals with post-TB COPD compared to those with non-TB COPD (10.7/1,000 vs. 4.9/1,000 person-years, P < 0.001), showing an increased risk of COPD-related hospitalization (aHR, 1.84; 95% CI, 1.17–2.92).
Conclusion
TB survivors had higher risks of incident COPD and COPD-related hospitalization compared to controls. These results suggest that previous TB is an important COPD etiology associated with COPD-related hospitalization.
2.Nitrosylation of b2-Tubulin Promotes Microtubule Disassembly and Differentiated Cardiomyocyte Beating in Ischemic Mice
Da Hyeon CHOI ; Seong Ki KANG ; Kyeong Eun LEE ; Jongsun JUNG ; Eun Ju KIM ; Won-Ho KIM ; Young-Guen KWON ; Kwang Pyo KIM ; Inho JO ; Yoon Shin PARK ; Sang Ick PARK
Tissue Engineering and Regenerative Medicine 2023;20(6):921-937
BACKGROUND:
Beating cardiomyocyte regeneration therapies have revealed as alternative therapeutics for heart transplantation. Nonetheless, the importance of nitric oxide (NO) in cardiomyocyte regeneration has been widely suggested, little has been reported concerning endogenous NO during cardiomyocyte differentiation.
METHODS:
Here, we used P19CL6 cells and a Myocardiac infarction (MI) model to confirm NO-induced protein modification and its role in cardiac beating. Two tyrosine (Tyr) residues of b2-tubulin (Y106 and Y340) underwent nitrosylation (Tyr-NO) by endogenously generated NO during cardiomyocyte differentiation from pre-cardiomyocyte-like P19CL6 cells.
RESULTS:
Tyr-NO-b2-tubulin mediated the interaction with Stathmin, which promotes microtubule disassembly, and was prominently observed in spontaneously beating cell clusters and mouse embryonic heart (E11.5d). In myocardial infarction mice, Tyr-NO-b2-tubulin in transplanted cells was closely related with cardiac troponin-T expression with their functional recovery, reduced infarct size and thickened left ventricular wall.
CONCLUSION
This is the first discovery of a new target molecule of NO, b2-tubulin, that can promote normal cardiac beating and cardiomyocyte regeneration. Taken together, we suggest therapeutic potential of Tyr-NO-b2-tubulin, for ischemic cardiomyocyte, which can reduce unexpected side effect of stem cell transplantation, arrhythmogenesis.
3.Arg-Leu-Tyr-Glu Suppresses Retinal Endothelial Permeability and Choroidal Neovascularization by Inhibiting the VEGF Receptor 2 Signaling Pathway
Wonjin PARK ; Yi Yong BAEK ; Joohwan KIM ; Dong Hyun JO ; Seunghwan CHOI ; Jin Hyoung KIM ; Taesam KIM ; Suji KIM ; Minsik PARK ; Ji Yoon KIM ; Moo Ho WON ; Kwon Soo HA ; Jeong Hun KIM ; Young Guen KWON ; Young Myeong KIM
Biomolecules & Therapeutics 2019;27(5):474-483
Vascular endothelial growth factor (VEGF) plays a pivotal role in pathologic ocular neovascularization and vascular leakage via activation of VEGF receptor 2 (VEGFR2). This study was undertaken to evaluate the therapeutic mechanisms and effects of the tetrapeptide Arg-Leu-Tyr-Glu (RLYE), a VEGFR2 inhibitor, in the development of vascular permeability and choroidal neovascularization (CNV). In cultured human retinal microvascular endothelial cells (HRMECs), treatment with RLYE blocked VEGF-A-induced phosphorylation of VEGFR2, Akt, ERK, and endothelial nitric oxide synthase (eNOS), leading to suppression of VEGF-A-mediated hyper-production of NO. Treatment with RLYE also inhibited VEGF-A-stimulated angiogenic processes (migration, proliferation, and tube formation) and the hyperpermeability of HRMECs, in addition to attenuating VEGF-A-induced angiogenesis and vascular permeability in mice. The anti-vascular permeability activity of RLYE was correlated with enhanced stability and positioning of the junction proteins VE-cadherin, β-catenin, claudin-5, and ZO-1, critical components of the cortical actin ring structure and retinal endothelial barrier, at the boundary between HRMECs stimulated with VEGF-A. Furthermore, intravitreally injected RLYE bound to retinal microvascular endothelium and inhibited laser-induced CNV in mice. These findings suggest that RLYE has potential as a therapeutic drug for the treatment of CNV by preventing VEGFR2-mediated vascular leakage and angiogenesis.
Actins
;
Animals
;
Capillary Permeability
;
Choroid
;
Choroidal Neovascularization
;
Claudin-5
;
Endothelial Cells
;
Endothelium
;
Humans
;
Macular Degeneration
;
Mice
;
Nitric Oxide Synthase Type III
;
Permeability
;
Phosphorylation
;
Receptors, Vascular Endothelial Growth Factor
;
Retinaldehyde
;
Vascular Endothelial Growth Factor A
4.Health effects of environmental pollution in population living near industrial complex areas in Korea.
Sang Yong EOM ; Jonghyuk CHOI ; Sanghyuk BAE ; Ji Ae LIM ; Guen Bae KIM ; Seung Do YU ; Yangho KIM ; Hyun Sul LIM ; Bu Soon SON ; Domyung PAEK ; Yong Dae KIM ; Heon KIM ; Mina HA ; Ho Jang KWON
Environmental Health and Toxicology 2018;33(1):e2018004-
Several epidemiological studies have reported an association between environmental pollution and various health conditions in individuals residing in industrial complexes. To evaluate the effects of pollution from industrial complex on human health, we performed a pooled analysis of environmental epidemiologic monitoring data for residents living near national industrial complexes in Korea. The respiratory and allergic symptoms and the prevalence of acute and chronic diseases, including cancer, were used as the outcome variables for health effects. Multiple logistic regression analysis was used to analyze the relationship between exposure to pollution from industrial complexes and health conditions. After adjusting for age, sex, smoking status, occupational exposure, level of education, and body mass index, the residents near the industrial complexes were found to have more respiratory symptoms, such as cough (odds ratio [OR], 1.18; 95% confidence interval [CI], 1.06 to 1.31) and sputum production (OR, 1.13; 95% CI, 1.03 to 1.24), and symptoms of atopic dermatitis (OR, 1.10; 95% CI, 1.01 to 1.20). Among residents of the industrial complexes, the prevalence of acute eye disorders was approximately 40% higher (OR, 1.39; 95% CI, 1.04 to 1.84) and the prevalence of lung and uterine cancer was 3.45 times and 1.88 times higher, respectively, than those among residents of the control area. This study showed that residents living in the vicinity of industrial complexes have a high risk of acute and chronic diseases including respiratory and allergic conditions. These results can be used as basic objective data for developing health management measures for individuals residing near industrial complexes.
Body Mass Index
;
Chronic Disease
;
Cough
;
Dermatitis, Atopic
;
Education
;
Employment
;
Environmental Pollution*
;
Epidemiologic Studies
;
Epidemiological Monitoring
;
Humans
;
Korea*
;
Logistic Models
;
Lung
;
Prevalence
;
Smoke
;
Smoking
;
Sputum
;
Uterine Neoplasms
5.Health effects of environmental pollution in population living near industrial complex areas in Korea
Sang Yong EOM ; Jonghyuk CHOI ; Sanghyuk BAE ; Ji Ae LIM ; Guen Bae KIM ; Seung Do YU ; Yangho KIM ; Hyun Sul LIM ; Bu Soon SON ; Domyung PAEK ; Yong Dae KIM ; Heon KIM ; Mina HA ; Ho Jang KWON
Environmental Health and Toxicology 2018;33(1):2018004-
Several epidemiological studies have reported an association between environmental pollution and various health conditions in individuals residing in industrial complexes. To evaluate the effects of pollution from industrial complex on human health, we performed a pooled analysis of environmental epidemiologic monitoring data for residents living near national industrial complexes in Korea. The respiratory and allergic symptoms and the prevalence of acute and chronic diseases, including cancer, were used as the outcome variables for health effects. Multiple logistic regression analysis was used to analyze the relationship between exposure to pollution from industrial complexes and health conditions. After adjusting for age, sex, smoking status, occupational exposure, level of education, and body mass index, the residents near the industrial complexes were found to have more respiratory symptoms, such as cough (odds ratio [OR], 1.18; 95% confidence interval [CI], 1.06 to 1.31) and sputum production (OR, 1.13; 95% CI, 1.03 to 1.24), and symptoms of atopic dermatitis (OR, 1.10; 95% CI, 1.01 to 1.20). Among residents of the industrial complexes, the prevalence of acute eye disorders was approximately 40% higher (OR, 1.39; 95% CI, 1.04 to 1.84) and the prevalence of lung and uterine cancer was 3.45 times and 1.88 times higher, respectively, than those among residents of the control area. This study showed that residents living in the vicinity of industrial complexes have a high risk of acute and chronic diseases including respiratory and allergic conditions. These results can be used as basic objective data for developing health management measures for individuals residing near industrial complexes.
Body Mass Index
;
Chronic Disease
;
Cough
;
Dermatitis, Atopic
;
Education
;
Employment
;
Environmental Pollution
;
Epidemiologic Studies
;
Epidemiological Monitoring
;
Humans
;
Korea
;
Logistic Models
;
Lung
;
Prevalence
;
Smoke
;
Smoking
;
Sputum
;
Uterine Neoplasms
6.Decompressive Sacral Foraminotomy for Nerve Root Injury during Conservative Treatment of Sacral Fracture: A Case Report.
Jung Gil LEE ; Jae Hyuk SHIN ; Kwon KIM ; Sang Min CHOI ; Moon Soo PARK ; Ho Guen CHANG
Journal of the Korean Fracture Society 2017;30(1):24-28
A 35-year-old woman visited the emergency department for a pedestrian traffic accident. Severe tenderness was noted at the posterior sacrum area, without open wound or initial neurologic deficit. Fracture of the left sacral ala extended to the S1 foramen, anterior acetabulum, and pubic ramus. Two weeks after the injury, she presented aggravating radiculopathy with the weakness of the left great toe plantar flexion. The S1 nerve root was compressed by the fracture fragments in the left S1 foramen. Decompressive S1 foraminotomy was performed. The postoperative follow-up computed tomography scan showed successful decompression of the encroachment, and the patient recovered well from the radiculopathy with motor weakness. She was able to resume her daily routine activity. We suggest that early decompressive sacral foraminotomy could be a useful additional procedure in selective sacral zone II fractures that are accompanied by radiculopathy with a motor deficit.
Accidents, Traffic
;
Acetabulum
;
Adult
;
Decompression
;
Emergency Service, Hospital
;
Female
;
Follow-Up Studies
;
Foraminotomy*
;
Humans
;
Neurologic Manifestations
;
Radiculopathy
;
Sacrum
;
Toes
;
Wounds and Injuries
7.Decompressive Sacral Foraminotomy for Nerve Root Injury during Conservative Treatment of Sacral Fracture: A Case Report.
Jung Gil LEE ; Jae Hyuk SHIN ; Kwon KIM ; Sang Min CHOI ; Moon Soo PARK ; Ho Guen CHANG
Journal of the Korean Fracture Society 2017;30(1):24-28
A 35-year-old woman visited the emergency department for a pedestrian traffic accident. Severe tenderness was noted at the posterior sacrum area, without open wound or initial neurologic deficit. Fracture of the left sacral ala extended to the S1 foramen, anterior acetabulum, and pubic ramus. Two weeks after the injury, she presented aggravating radiculopathy with the weakness of the left great toe plantar flexion. The S1 nerve root was compressed by the fracture fragments in the left S1 foramen. Decompressive S1 foraminotomy was performed. The postoperative follow-up computed tomography scan showed successful decompression of the encroachment, and the patient recovered well from the radiculopathy with motor weakness. She was able to resume her daily routine activity. We suggest that early decompressive sacral foraminotomy could be a useful additional procedure in selective sacral zone II fractures that are accompanied by radiculopathy with a motor deficit.
Accidents, Traffic
;
Acetabulum
;
Adult
;
Decompression
;
Emergency Service, Hospital
;
Female
;
Follow-Up Studies
;
Foraminotomy*
;
Humans
;
Neurologic Manifestations
;
Radiculopathy
;
Sacrum
;
Toes
;
Wounds and Injuries
8.Carbon monoxide prevents TNF-α-induced eNOS downregulation by inhibiting NF-κB-responsive miR-155-5p biogenesis.
Seunghwan CHOI ; Joohwan KIM ; Ji Hee KIM ; Dong Keon LEE ; Wonjin PARK ; Minsik PARK ; Suji KIM ; Jong Yun HWANG ; Moo Ho WON ; Yoon Kyung CHOI ; Sungwoo RYOO ; Kwon Soo HA ; Young Guen KWON ; Young Myeong KIM
Experimental & Molecular Medicine 2017;49(11):e403-
Heme oxygenase-1-derived carbon monoxide prevents inflammatory vascular disorders. To date, there is no clear evidence that HO-1/CO prevents endothelial dysfunction associated with the downregulation of endothelial NO synthesis in human endothelial cells stimulated with TNF-α. Here, we found that the CO-releasing compound CORM-2 prevented TNF-α-mediated decreases in eNOS expression and NO/cGMP production, without affecting eNOS promoter activity, by maintaining the functional activity of the eNOS mRNA 3′-untranslated region. By contrast, CORM-2 inhibited MIR155HG expression and miR-155-5p biogenesis in TNF-α-stimulated endothelial cells, resulting in recovery of the 3′-UTR activity of eNOS mRNA, a target of miR-155-5p. The beneficial effect of CORM-2 was blocked by an NF-κB inhibitor, a miR-155-5p mimic, a HO-1 inhibitor and siRNA against HO-1, indicating that CO rescues TNF-α-induced eNOS downregulation through NF-κB-responsive miR-155-5p expression via HO-1 induction; similar protective effects of ectopic HO-1 expression and bilirubin were observed in endothelial cells treated with TNF-α. Moreover, heme degradation products, except iron and N-acetylcysteine prevented H₂O₂-mediated miR-155-5p biogenesis and eNOS downregulation. These data demonstrate that CO prevents TNF-α-mediated eNOS downregulation by inhibiting redox-sensitive miR-155-5p biogenesis through a positive forward circuit between CO and HO-1 induction. This circuit may play an important preventive role in inflammatory endothelial dysfunction associated with human vascular diseases.
Acetylcysteine
;
Bilirubin
;
Carbon Monoxide*
;
Carbon*
;
Down-Regulation*
;
Endothelial Cells
;
Heme
;
Humans
;
Iron
;
RNA, Messenger
;
RNA, Small Interfering
;
Vascular Diseases
9.A Case of Alpha-cell Nesidioblastosis and Hyperplasia with Multiple Glucagon-producing Endocrine Cell Tumor of the Pancreas.
Huapyong KANG ; Sewha KIM ; Tae Seop LIM ; Hye Won LEE ; Heun CHOI ; Chang Moo KANG ; Ho Guen KIM ; Seungmin BANG
The Korean Journal of Gastroenterology 2014;63(4):253-257
Nesidioblastosis is a term used to describe pathologic overgrowth of pancreatic islet cells. It also means maldistribution of islet cells within the ductules of exocrine pancreas. Generally, nesidioblastosis occurs in beta-cell and causes neonatal hyperinsulinemic hypoglycemia or adult noninsulinoma pancreatogenous hypoglycemia syndrome. Alpha-cell nesidioblastosis and hyperplasia is an extremely rare disorder. It often accompanies glucagon-producing marco- and mircoadenoma without typical glucagonoma syndrome. A 35-year-old female was referred to our hospital with recurrent acute pancreatitis. On radiologic studies, 1.5 cm sized mass was noted in pancreas tail. Cytological evaluation with EUS-fine-needle aspiration suggested serous cystadenoma. She received distal pancreatectomy. The histologic examination revealed a 1.7 cm sized neuroendocrine tumor positive for immunohistochemical staining with glucagon antibody. Multiple glucagon-producing micro endocrine cell tumors were scattered next to the main tumor. Additionally, diffuse hyperplasia of pancreatic islets and ectopic proliferation of islet cells in centroacinar area, findings compatible to nesidioblastosis, were seen. These hyperplasia and almost all nesidioblastic cells were positive for glucagon immunochemistry. Even though serum glucagon level still remained higher than the reference value, she has been followed-up without any evidence of recurrence or hormone related symptoms. Herein, we report a case of alpha-cell nesidioblastosis and hyperplasia combined with glucagon-producing neuroendocrine tumor with literature review.
Adult
;
Chromogranin A/blood
;
Female
;
Glucagon/*metabolism
;
Glucagon-Secreting Cells/metabolism
;
Humans
;
Hyperplasia/complications/*diagnosis
;
Islets of Langerhans/metabolism/ultrasonography
;
Nesidioblastosis/complications/*diagnosis
;
Neuroendocrine Tumors/complications/*diagnosis/pathology
;
Pancreas/*pathology
;
Tomography, X-Ray Computed
10.Goodness-of-Fits of the Spirometric Reference Values for Koreans and USA Caucasians to Spirometry Data from Residents of a Region within Chungbuk Province.
Sang Yong EOM ; Sun In MOON ; Dong Hyuk YIM ; Chul Ho LEE ; Guen Bae KIM ; Yong Dae KIM ; Jong Won KANG ; Kang Hyeon CHOE ; Sung Jin KIM ; Byung Sun CHOI ; Seung Do YU ; Soung Hoon CHANG ; Jung Duck PARK ; Heon KIM
Tuberculosis and Respiratory Diseases 2012;72(3):302-309
BACKGROUND: Korean regression models for spirometric reference values are different from those of Americans. Using spirometry results of Korean adults, goodness-of-fits of the Korean and the USA Caucasian regression models for forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were compared. METHODS: The number of study participants was 2,360 (1,124 males and 1,236 females). Spirometry was performed under the guidelines of the American Thoracic Society and the European Respiratory Society. After excluding unsuitable participants, spirometric data for 729 individuals (105 males and 624 females) was included in the statistical analysis. The estimated FVC and FEV1 values were compared with those measured. Goodness-of-fits for Korean and USA Caucasian models were compared using an F-test. RESULTS: In males, the expected values of FVC and FEV1 using the Korean model were 12.5% and 5.7% greater than those measured, respectively. The corresponding values for the USA Caucasian model were 3.5% and 0.6%. In females, the difference in FVC and FEV1 were 13.5% and 7.7% for the Korean model, and 6.3% and 0.4% for the USA model, respectively. Goodness-of-fit for the Korean model regarding FVC was not good to the study population, but the Korean regression model for FEV1, and the USA Caucasian models for FVC and FEV1 showed good fits to the measured data. CONCLUSION: These results suggest that the USA Caucasian model correlates better to the measured data than the Korean model. Using reference values derived from the Korean model can lead to an overestimation regarding the prevalence of abnormal lung function.
Adult
;
Female
;
Forced Expiratory Volume
;
Humans
;
Lung
;
Male
;
Prevalence
;
Reference Values
;
Spirometry
;
Vital Capacity

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