1.Telmisartan Inhibits TNFα-Induced Leukocyte Adhesion by Blocking ICAM-1 Expression in Astroglial Cells but Not in Endothelial Cells
Changhwan JANG ; Jungjin KIM ; Youngsun KWON ; Sangmee A. JO
Biomolecules & Therapeutics 2020;28(5):423-430
Telmisartan is an angiotensin-II receptor blocker and acts as a selective modulator of peroxisome proliferator-activated receptor gamma (PPARγ). Several studies have demonstrated that telmisartan ameliorates depression and memory dysfunction and reduces brain inflammation. We hypothesized that the beneficial effects of telmisartan on brain could be due to modulation of the blood-brain barrier (BBB) function. Here, we examined the effect of telmisartan on tumor necrosis factor alpha (TNF-α)-induced expression of intercellular adhesion molecule 1 (ICAM-1) which plays an important role in leukocyte transcytosis through the BBB. Telmisartan blocked TNF-α-induced ICAM-1 expression and leukocyte adhesion in U87MG human glioma cells but showed no effect on human brain microvascular endothelial cells. In U87MG cells, a PPAR antagonist, GW9662 did not block the effect of telmisartan on ICAM1 expression but rather potentiated. Moreover, GW9662 caused no change in TNF-α-induced ICAM-1 expression, suggesting no implication of PPARγ in the telmisartan effect. Further studies showed that telmisartan blocked TNF-α-induced activation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK1/2), p38, and nuclear factorkappa B (NF-κB). In contrast, inhibitors of JNK, ERK1/2 and NF-κB but not p38, blocked ICAM-1 expression induced by TNF-α.Thus, our findings suggest that the beneficial effect of telmisartan is likely due to the reduction of astrocytic ICAM1 expression and leukocytes adhesion to astrocytes, and that this response was mediated by the inhibition of JNK/ERK1/2/NF-κB activation and in the PPAR-independent manner. In conclusion, this study enhances our understanding of the mechanism by which telmisartan exerts the beneficial brain function.
2.Epithelial to Mesenchymal Transition of Mesothelial Cells in Tuberculous Pleurisy.
Changhwan KIM ; Dong Gyu KIM ; Sung Hoon PARK ; Yong Il HWANG ; Seung Hun JANG ; Cheol Hong KIM ; Ki Suck JUNG ; Kwangseon MIN ; Jae Woong LEE ; Young Sook JANG
Yonsei Medical Journal 2011;52(1):51-58
PURPOSE: Tuberculous pleurisy is the most frequent extrapulmonary manifestation of tuberculosis. In spite of adequate treatment, pleural fibrosis is a common complication, but the mechanism has not been elucidated. This study is to determine whether epithelial to mesenchymal transition (EMT) of mesothelial cells occurs in tuberculous pleurisy. MATERIALS AND METHODS: Normal pleural mesothelial cells, isolated from irrigation fluids during operations for primary spontaneous pneumothorax, were characterized by immunofluorescence and reverse transcription polymerase chain reaction (RT-PCR). These cells were treated in vitro with various cytokines, which were produced in the effluents of tuberculous pleurisy. The isolated cells from the effluents of tuberculous pleurisy were analyzed by immunofluorescence and RT-PCR analysis. RESULTS: The isolated cells from the irrigation fluid of primary spontaneous pneumothorax had epithelial characteristics. These cells, with transforming growth factor-beta1 and/or interleukin-1beta treatment, underwent phenotypic transition from epithelial to mesenchymal cells, with the loss of epithelial morphology and reduction in cytokeratin and E-cadherin expression. Effluent analysis from tuberculous pleurisy using immunofluorescence and RT-PCR demonstrated two phenotypes that showed mesenchymal characteristics and both epithelial & mesencymal characteristics. CONCLUSION: Our results suggest that pleural mesothelial cells in tuberculous pleurisy have been implicated in pleural fibrosis through EMT.
Cells, Cultured
;
Epithelial Cells/*pathology
;
Epithelial-Mesenchymal Transition/*physiology
;
Fluorescent Antibody Technique
;
Humans
;
Pleura/*pathology
;
Reverse Transcriptase Polymerase Chain Reaction
;
Tuberculosis, Pleural/*pathology
3.Laboratory-acquired dengue virus infection by needlestick injury: a case report, South Korea, 2014.
Changhwan LEE ; Eun Jung JANG ; Donghyok KWON ; Heun CHOI ; Jung Wan PARK ; Geun Ryang BAE
Annals of Occupational and Environmental Medicine 2016;28(1):16-
BACKGROUND: Dengue fever is one of the most dominant vector-borne diseases, putting approximately 3.9 billion people at risk worldwide. While it is generally vector-borne, other routes of transmission such as needlestick injury are possible. Laboratory workers can be exposed to dengue virus transcutaneously by needlestick injury. This is the first case, to our knowledge, of dengue virus infection by needlestick injury in a laboratory environment. This paper evaluates the risk and related health concerns of laboratory workers exposed to dengue virus. CASE PRESENTATION: We evaluated a 30-year-old female laboratory worker exposed to the dengue virus by needlestick injury while conducting virus filtering. During admission, she showed symptoms of fever, nausea, myalgia, and a characteristic maculopapular rash with elevated aspartate aminotransferase (AST) of 235 IU/L and alanine aminotransferase (ALT) of 269 IU/L. She had been diagnosed by a positive nonstructural protein 1 (NS1) antigen (Ag) rapid test one day prior to symptom onset along with positive immunoglobulin M (IgM) enzyme-linked immunosorbent assay (ELISA) on the ninth day of symptom onset. Reverse transcription polymerase chain reaction (RT-PCR), also conducted on the ninth day, was negative. After proper symptomatic treatment, she recovered without any sequelae. As a result of thorough epidemiologic investigation, it was determined that she had tried to recap the needle during the virus filtering procedure and a subsequent needlestick injury occurred. CONCLUSIONS: In the context of health promotion of laboratory workers, we suggest that the laboratory biosafety manual be revised and reinforced, and related prevention measures be implemented. Furthermore, health authorities and health care providers in Korea should be fully informed of proper dengue fever management.
Adult
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Alanine Transaminase
;
Aspartate Aminotransferases
;
Dengue Virus*
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Dengue*
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Enzyme-Linked Immunosorbent Assay
;
Exanthema
;
Female
;
Fever
;
Health Personnel
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Health Promotion
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Humans
;
Immunoglobulin M
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Korea*
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Myalgia
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Nausea
;
Needles
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Needlestick Injuries*
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Polymerase Chain Reaction
;
Reverse Transcription
4.One-year Prognosis and the Role of Brain Natriuretic Peptide Levels in Patients with Chronic Cor Pulmonale.
So Young PARK ; Chang Youl LEE ; Changhwan KIM ; Seung Hun JANG ; Yong Bum PARK ; Sunghoon PARK ; Yong Il HWANG ; Myung Goo LEE ; Ki Suck JUNG ; Dong Gyu KIM
Journal of Korean Medical Science 2015;30(4):442-449
Data on the clinical outcomes and role of brain natriuretic peptide (BNP) levels in patients with chronic cor pulmonale are limited. A total of 69 patients with chronic cor pulmonale, admitted for dyspnea (January 2007 to September 2011) to three university hospitals, were retrospectively reviewed. All of the patients had right ventricular (RV) dysfunction on echocardiography. The median age was 70.0 yr, and chronic obstructive pulmonary disease (40.6%) and tuberculosis-destroyed lung (TDL, 27.5%) were the leading causes of chronic cor pulmonale. At the 1-yr follow-up, the mortality rate was 15.9%, and the readmission rate was 53.7%; patients with TDL had higher mortality (31.6% vs. 10.0%; P = 0.059) and readmission rates (78.9% vs. 43.8%; P = 0.009) than those with non-TDL diseases. The area under the receiver operating characteristic curve for admission BNP levels to predict readmission was 0.788 (95% confidence interval [CI], 0.673-0.904), and the sensitivity and specificity of the cut-off value were 80.6% and 77.4%, respectively. In multivariate analysis, high admission BNP levels were a significant risk factor for subsequent readmission (hazard ratio, 1.049; 95% CI, 1.005-1.094). Additionally, admission BNP levels were well correlated with cardiac troponin I (r = 0.558), and delta BNP also correlated with delta RV systolic pressure (n = 25; r = 0.562). In conclusion, among hospitalized patients with chronic cor pulmonale, admission high BNP levels are a significant risk factor for subsequent readmission. Therefore, more intensive monitoring and treatment are needed in patients with higher BNP levels.
Aged
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Chronic Disease
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Female
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Humans
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Male
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Middle Aged
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Natriuretic Peptide, Brain/*blood
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Patient Readmission
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Prognosis
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Pulmonary Disease, Chronic Obstructive/complications
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Pulmonary Heart Disease/*blood/mortality
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ROC Curve
;
Retrospective Studies
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Tuberculosis, Pulmonary/complications
5.Catamenial Hemoptysis Treated by Video-assisted Thoracoscopic Surgery.
Chang Beom CHO ; Dong Gyu KIM ; Changhwan KIM ; Ji Young PARK ; Seok Won LEE ; Seung Hun JANG ; Ki Suck JUNG ; Sun Young JUN ; Jae Woong LEE
Tuberculosis and Respiratory Diseases 2008;65(1):29-33
Catamenial hemoptysis is a rare condition that's characterized by recurrent hemoptysis occurring in association with menstruation, and this is associated with the presence of intrapulmonary or endobronchial endometrial tissue. The diagnosis of pulmonary endometriosis can be made according to a typical clinical history and with exclusion of other causes of recurrent hemoptysis. Treatment of pulmonary endometriosis can be medical or surgical; however, the optimal management of this condition is still a matter of debate. Medical therapy may be problematic, due to recurrence of symptoms despite hormonal ablation, and adverse effects from long-term hormone therapy can also be a problem. We report here on a case of pulmonary endometriosis in a 23-year-old woman who presented with hemoptysis that occurred during the first 3 days of menstruation, and this happened over a 4 month period. She was successfully treated by video-assisted thoracoscopic surgery (VATS). No more hemoptysis was noted during 12 months of follow-up.
Endometriosis
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Female
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Follow-Up Studies
;
Hemoptysis
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Humans
;
Menstruation
;
Recurrence
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Thoracic Surgery, Video-Assisted
;
Young Adult
6.A Case of Thyroid Cancer Combined with Pulmonary Sarcoidosis.
Su Jin KIM ; Tae Kyung LIM ; Changhwan KIM ; Yong Il HWANG ; Sunghoon PARK ; Seung Hun JANG ; Kwangseon MIN ; In Jae LEE ; Hee Sung HWANG ; Jae Woong LEE ; Dong Gyu KIM
Tuberculosis and Respiratory Diseases 2008;65(1):52-56
Sarcoidosis is a systemic granulomatous disease that primarily affects the lung and lymphatic system of the body. Since Brincker first noted a statistically significant increase of malignant tumors among sarcoidosis patients, there have been several reports on simultaneously developed sarcoidosis and malignancy. A 30-year-old man was admitted to our hospital because of multiple enlarged mediastinal lymph nodes. The patient had been well until approximately 10 days before admission, when he developed a cough. Chest X-ray and computed tomography (CT) of the chest that were performed at the outpatient department revealed multiple enlarged mediastinal lymph nodes. Cervical lymph node biopsy revealed both non-caseating granuloma and metastatic papillary carcinoma, whereas the mediastinal lymph node showed only non-caseating granuloma. The thyroid gland surgical specimen showed papillary carcinoma. We report here on a case of a 30-year-old man who had sarcoidosis and thyroid cancer, and we include a review of the literature.
Adult
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Biopsy
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Carcinoma, Papillary
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Cough
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Granuloma
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Humans
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Lung
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Lymph Nodes
;
Lymphatic System
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Outpatients
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Sarcoidosis
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Sarcoidosis, Pulmonary
;
Thorax
;
Thyroid Gland
;
Thyroid Neoplasms
7.A Trial of Aerosolized Colistin for the Treatment of Nosocomial Pneumonia due to Multidrug-resistant Acinetobacter baumannii.
Changhwan KIM ; Dong Gyu KIM ; Hye Ryun KANG ; Jeong Hee CHOI ; Chang Youl LEE ; Yong Il HWANG ; Tae Rim SHIN ; Sang Myeon PARK ; Yong Bum PARK ; Jae Young LEE ; Seung Hun JANG ; Cheol Hong KIM ; Eun Kyung MO ; Myung Goo LEE ; In Gyu HYUN ; Ki Suck JUNG ; Young Jin CHOI ; Jae Woong LEE
Tuberculosis and Respiratory Diseases 2008;64(2):102-108
BACKGROUND: Recently, multidrug-resistant (MDR) A. baumannii has been implicated for a significant proportion of nosocominal pneumonia in many intensive care units (ICUs), and its acquisition may increase mortality and the length of stay in the ICU. Aerosolized colistin has been successfully used in patients with cystic fibrosis, but there is a lack of data regarding the use of aerosolized colistin in patients with nosocomial pneumonia. METHODS: We conducted the present study to assess the effectiveness of aerosolized colistin for the treatment of MDR A. baumannii nosocomial pneumonia. We retrospectively reviewed the medical records of 10 patients who had been hospitalized in the medical ICU and had received aerosolized colistin as a therapy for MDR A. baumannii pneumonia. RESULTS: The mean duration of aerosolized colistin therapy was 12.7+/-2.4 days. Nine (90%) of 10 patients showed a favorable response to the therapy. Follow-up cultures were available for all patients, and the responsible pathogen was completely eradicated. One patient suffered from bronchospasm, which resolved after treatment with nebulized salbutamol. CONCLUSION: Our results corroborate previous reports that aerosolized colistin may be an effective and safe choice for the treatment of nosocomial pneumonia caused by MDR A. baumannii. Larger prospective controlled clinical studies are warranted to validate further the effectiveness and safety of aerosolized colistin therapy.
Acinetobacter
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Acinetobacter baumannii
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Albuterol
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Bronchial Spasm
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Colistin
;
Cystic Fibrosis
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Follow-Up Studies
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Humans
;
Intensive Care Units
;
Length of Stay
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Medical Records
;
Pneumonia
;
Retrospective Studies
8.Immunoglobulin G Subclass Deficiencies in Adult Patients with Chronic Airway Diseases.
Joo Hee KIM ; Sunghoon PARK ; Yong Il HWANG ; Seung Hun JANG ; Ki Suck JUNG ; Yun Su SIM ; Cheol Hong KIM ; Changhwan KIM ; Dong Gyu KIM
Journal of Korean Medical Science 2016;31(10):1560-1565
Immunoglobulin G subclass deficiency (IgGSCD) is a relatively common primary immunodeficiency disease (PI) in adults. The biological significance of IgGSCD in patients with chronic airway diseases is controversial. We conducted a retrospective study to characterize the clinical features of IgGSCD in this population. This study examined the medical charts from 59 adult patients with IgGSCD who had bronchial asthma or chronic obstructive pulmonary disease (COPD) from January 2007 to December 2012. Subjects were classified according to the 10 warning signs developed by the Jeffrey Modell Foundation (JMF) and divided into two patient groups: group I (n = 17) met ≥ two JMF criteria, whereas group II (n = 42) met none. IgG3 deficiency was the most common subclass deficiency (88.1%), followed by IgG4 (15.3%). The most common infectious complication was pneumonia, followed by recurrent bronchitis, and rhinosinusitis. The numbers of infections, hospitalizations, and exacerbations of asthma or COPD per year were significantly higher in group I than in group II (P < 0.001, P = 0.012, and P < 0.001, respectively). The follow-up mean forced expiratory volume (FEV1) level in group I was significantly lower than it was at baseline despite treatment of asthma or COPD (P = 0.036). In conclusion, IgGSCD is an important PI in the subset of patients with chronic airway diseases who had recurrent upper and lower respiratory infections as they presented with exacerbation-prone phenotypes, decline in lung function, and subsequently poor prognosis.
Adult*
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Asthma
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Bronchitis
;
Follow-Up Studies
;
Forced Expiratory Volume
;
Hospitalization
;
Humans
;
Immunoglobulin G*
;
Immunoglobulins*
;
Lung
;
Phenotype
;
Pneumonia
;
Prognosis
;
Pulmonary Disease, Chronic Obstructive
;
Respiratory Tract Infections
;
Retrospective Studies
9.Microbiologic pattern and clinical outcome of non-ICU-acquired pneumonia: Korean HAP registry analysis
Jin Ho JANG ; Hye Ju YEO ; Taehwa KIM ; Woo Hyun CHO ; Kyung Hoon MIN ; Sang-Bum HONG ; Ae-Rin BAEK ; Hyun-Kyung LEE ; Changhwan KIM ; Youjin CHANG ; Hye Kyeong PARK ; Jee Youn OH ; Heung Bum LEE ; Soohyun BAE ; Jae Young MOON ; Kwang Ha YOO ; Hyun-Il GIL ; Kyeongman JEON ;
The Korean Journal of Internal Medicine 2023;38(3):450-450
10.Microbiologic pattern and clinical outcome of non-ICU-acquired pneumonia: Korean HAP registry analysis
Jin Ho JANG ; Hye Ju YEO ; Taehwa KIM ; Woo Hyun CHO ; Kyung Hoon MIN ; Sang-Bum HONG ; Ae-Rin BAEK ; Hyun-Kyung LEE ; Changhwan KIM ; Youjin CHANG ; Hye Kyeong PARK ; Jee Youn OH ; Heung Bum LEE ; Soohyun BAE ; Jae Young MOON ; Kwang Ha YOO ; Hyun-Il GIL ; Kyeongman JEON ;
The Korean Journal of Internal Medicine 2022;37(4):800-810
Background/Aims:
Most studies on hospital-acquired pneumonia (HAP) have been conducted in intensive care unit (ICU) settings. This study aimed to investigate the microbiological and clinical characteristics of non-ICU-acquired pneumonia (NIAP) and to identify the factors affecting clinical outcomes in Korea.
Methods:
This multicenter retrospective cohort study was conducted in patients admitted to 13 tertiary hospitals between July 1, 2019 and December 31, 2019. Patients diagnosed with NIAP were included in this study. To assess the prognostic factors of NIAP, the study population was classified into treatment success and failure groups.
Results:
Of 526 patients with HAP, 379 were diagnosed with NIAP. Overall, the identified causative pathogen rate was 34.6% in the study population. Among the isolated organisms (n = 113), gram-negative bacilli were common pathogens (n = 91), such as Pseudomonas aeruginosa (n = 25), Acinetobacter baumannii (n = 23), and Klebsiella pneumoniae (n = 21). The multidrug resistance rates of A. baumannii, P. aeruginosa, and K. pneumoniae were 91.3%, 76.0%, and 57.1%, respectively. Treatment failure was significantly associated with K. pneumoniae (odds ratio [OR], 3.50; 95% confidence interval [CI], 1.35 to 9.05; p = 0.010), respiratory viruses (OR, 3.81; 95% CI, 1.34 to 10.82; p = 0.012), hematological malignancies (OR, 3.54; 95% CI, 1.57 to 8.00; p = 0.002), and adjunctive corticosteroid treatment (OR, 2.40; 95% CI, 1.27 to 4.52; p = 0.007).
Conclusions
The causative pathogens of NIAP in Korea are predominantly gram-negative bacilli with a high rate of multidrug resistance. These were not different from the common pathogens of ICU-acquired pneumonia.