1.Altered Gene Expression Profile After Exposure to Transforming Growth Factor beta1 in the 253J Human Bladder Cancer Cell Line.
Changho LEE ; Sang Han LEE ; Doo Sang KIM ; Yun Soo JEON ; Nam Kyu LEE ; Sang Eun LEE
Korean Journal of Urology 2014;55(8):542-550
PURPOSE: Transforming growth factor beta1 (TGF-beta1) inhibits the growth of bladder cancer cells and this effect is prominent and constant in 253J bladder cancer cells. We performed a microarray analysis to search for genes that were altered after TGF-beta1 treatment to understand the growth inhibitory action of TGF-beta1. MATERIALS AND METHODS: 253J bladder cancer cells were exposed to TGF-beta1 and total RNA was extracted at 6, 24, and 48 hours after exposure. The RNA was hybridized onto a human 22K oligonucleotide microarray and the data were analyzed by using GeneSpring 7.1. RESULTS: In the microarray analysis, a total of 1,974 genes showing changes of more than 2.0 fold were selected. The selected genes were further subdivided into five highly cohesive clusters with high probability according to the time-dependent expression pattern. A total of 310 genes showing changes of more than 2.0 fold in repeated arrays were identified by use of simple t-tests. Of these genes, those having a known function were listed according to clusters. Microarray analysis showed increased expression of molecules known to be related to Smad-dependent signal transduction, such as SARA and Smad4, and also those known to be related to the mitogen-activated protein kinase (MAPK) pathway, such as MAPKK1 and MAPKK4. CONCLUSIONS: A list of genes showing significantly altered expression profiles after TGF-beta1 treatment was made according to five highly cohesive clusters. The data suggest that the growth inhibitory effect of TGF-beta1 in bladder cancer may occur through the Smad-dependent pathway, possibly via activation of the extracellular signal-related kinase 1 and Jun amino-terminal kinases Mitogen-activated protein kinase pathway.
Antineoplastic Agents/*pharmacology
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Cluster Analysis
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Gene Expression Profiling/methods
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Gene Expression Regulation, Neoplastic/*drug effects
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Genes, Neoplasm
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Humans
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MAP Kinase Signaling System/drug effects/genetics
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Neoplasm Proteins/genetics/metabolism
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Oligonucleotide Array Sequence Analysis/methods
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Reverse Transcriptase Polymerase Chain Reaction/methods
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Signal Transduction/drug effects/genetics
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Smad Proteins/genetics/metabolism
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Transforming Growth Factor beta1/*pharmacology
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Tumor Cells, Cultured/drug effects
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Urinary Bladder Neoplasms/*genetics/metabolism/pathology
2.Growth Inhibition After Exposure to Transforming Growth Factor-beta1 in Human Bladder Cancer Cell Lines.
Changho LEE ; Sang Han LEE ; Doo Sang KIM ; Yun Soo JEON ; Nam Kyu LEE ; Sang Eun LEE
Korean Journal of Urology 2014;55(7):487-492
PURPOSE: Transforming growth factor-beta1 (TGF-beta1) plays a dual role in apoptosis and in proapoptotic responses in the support of survival in a variety of cells. The aim of this study was to determine the function of TGF-beta1 in bladder cancer cells. MATERIALS AND METHODS: The role of TGF-beta1 in bladder cancer cells was examined by observing cell viability by using the tetrazolium dye (MTT) assay after treating the bladder cancer cell lines 253J, 5637, T24, J82, HT1197, and HT1376 with TGF-beta1. Among these cell lines, the 253J and T24 cell lines were coincubated with TGF-beta1 and the pan anti-TGF-beta antibody. Fluorescence-activated cell sorter (FACS) analysis was performed to determine the mechanism involved after TGF-beta1 treatment in 253J cells. RESULTS: All six cell lines showed inhibited cellular growth after TGF-beta1 treatment. Although the T24 and J82 cell lines also showed inhibited cellular growth, the growth inhibition was less than that observed in the other 4 cell lines. The addition of pan anti-TGF-beta antibodies to the culture media restored the growth properties that had been inhibited by TGF-beta1. FACS analysis was performed in the 253J cells and the 253J cells with TGF-beta1. There were no significant differences in the cell cycle between the two treatments. However, there were more apoptotic cells in the TGF-beta1-treated 253J cells. CONCLUSIONS: TGF-beta1 did not stimulate cellular proliferation but was a growth inhibitory factor in bladder cancer cells. However, the pattern of its effects depended on the cell line. TGF-beta1 achieved growth inhibition by enhancing the level of apoptosis.
Antineoplastic Agents/administration & dosage/*pharmacology
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Apoptosis/drug effects
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Cell Line, Tumor/drug effects/pathology
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Cell Proliferation/drug effects
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Cell Separation/methods
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Dose-Response Relationship, Drug
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Drug Screening Assays, Antitumor/methods
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Flow Cytometry/methods
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Humans
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Transforming Growth Factor beta1/administration & dosage/*pharmacology
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Urinary Bladder Neoplasms/*pathology
3.Human Norovirus Genogroups Detected from Acute Gastroenteritis Patients in Seoul from May 2013 to April 2015.
Heejin HAM ; Seah OH ; Hyunjung SEUNG ; Jungim JANG ; Changho HAN
Journal of Bacteriology and Virology 2015;45(4):376-381
Norovirus is an important cause of acute nonbacterial gastroenteritis in communities worldwide. It was evaluated the prevalence of norovirus infections in patients with acute gastroenteritis occurring in Seoul from May 2013 to April 2015, with regular surveillance. 7.3% (252/3,485) of the fecal specimens were determined to be positive for noroviruses by reverse transcription-polymerase chain reaction (RT-PCR). Norovirus genogroup distribution was 19.1% (48/252) genogroup GI, 71.4% (180/252) genogroup GII, and 9.5% (24/252) genogroup G1+GII respectively. It was most norovirus detection rates from November 2013 to March 2015. And it was rotavirus 0.2% (7/3,485), astrovirus 0.03% (1/3,485), sapovirus 0.03% (1/3,485) and, it was non-detective on adenovirus. Norovirus genotypes identified were nine kinds of genogroup GI (GI-1, GI-2, GI-3, GI-4, GI-6, GI-7, GI-8, GI-12, GI-14) and eight kinds of genogroup GII (GII-2, GII-3, GII-4, GII-5, GII-6, GII-7, GII-14, GII-16, GII-17). The genetic characteristics of norovirus and the epidemiological patterns of a viral pathogen from acute gastroenteritis patients may give potentially effective data for epidemiological studies in Seoul, Korea.
Adenoviridae
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Epidemiologic Studies
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Gastroenteritis*
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Genotype*
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Humans*
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Korea
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Norovirus*
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Prevalence
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Rotavirus
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Sapovirus
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Seoul*
4.Epidemiological Investigation of a Measles Outbreak in Seoul, 2013~2014.
Heejin HAM ; Jungim JANG ; Changho HAN
Journal of Bacteriology and Virology 2015;45(4):372-375
Korea declared in 2006 that measles had been eliminated; however, a measles outbreak occurred in the southeastern area of Korea in 2011. Active surveillance of measles patients was conducted in Seoul 3 cases were detected in 2013 and 103 cases in 2014. Of 106 confirmed measles patients, 32 cases were within one university in Seongbukgu, and 23 were within three schools in Yongsangu. Students 14~29 years old comprised 78.3% (83/106) of the cases, and 75.5% (80/106) of the measles viruses were of genotype B3. One foreign traveler played an important role in the measles outbreak in Seoul. This measles outbreak in Seoul may provide useful data for future epidemiological studies of measles.
Epidemiologic Studies
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Genotype
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Humans
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Korea
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Measles virus
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Measles*
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Seoul*
5.Changes in the Circadian Rhythm of High-Frequency Heart Rate Variability Associated With Depression
Deokjong LEE ; Changho HAN ; Hyungjun KIM ; Jae-Sun UHM ; Dukyong YOON ; Jin Young PARK
Journal of Korean Medical Science 2023;38(19):e142-
Background:
Heart rate variability (HRV) extracted from electrocardiogram measured for a short period during a resting state is clinically used as a bio-signal reflecting the emotional state. However, as interest in wearable devices increases, greater attention is being paid to HRV extracted from long-term electrocardiogram, which may contain additional clinical information. The purpose of this study was to examine the characteristics of HRV parameters extracted through long-term electrocardiogram and explore the differences between participants with and without depression and anxiety symptoms.
Methods:
Long-term electrocardiogram was acquired from 354 adults with no psychiatric history who underwent Holter monitoring. Evening and nighttime HRV and the ratio of nighttime-to-evening HRV were compared between 127 participants with depressive symptoms and 227 participants without depressive symptoms. Comparisons were also made between participants with and without anxiety symptoms.
Results:
Absolute values of HRV parameters did not differ between groups based on the presence of depressive or anxiety symptoms. Overall, HRV parameters increased at nighttime compared to evening. Participants with depressive symptoms showed a significantly higher nighttime-to-evening ratio of high-frequency HRV than participants without depressive symptoms. The nighttime-to-evening ratio of HRV parameters did not show a significant difference depending on the presence of anxiety symptoms.
Conclusion
HRV extracted through long-term electrocardiogram showed circadian rhythm. Depression may be associated with changes in the circadian rhythm of parasympathetic tone.
6.Comparison of the new and conventional injury severity scoring systems for predicting mortality in severe geriatric trauma
Ho Wan RYU ; Jae Yun AHN ; Kang Suk SEO ; Jung Bae PARK ; Jong Kun KIM ; Mi Jin LEE ; Hyun Wook RYOO ; Yun Jeong KIM ; Changho KIM ; Jae Young CHOE ; Dong Eun LEE ; In Hwan YEO ; Sungbae MOON ; Yeonjoo CHO ; Han Sol CHUNG ; Jae Wan CHO ; Haewon JUNG
Journal of the Korean Society of Emergency Medicine 2020;31(6):543-552
Objective:
This study compared the prognostic performance of the following five injury severity scores: the Geriatric Trauma Outcome Score (GTOS), the Injury Severity Score (ISS), the New Injury Severity Score (NISS), the Revised Trauma Score (RTS), and the Trauma and Injury Severity Score (TRISS) for in-hospital mortality in severe geriatric trauma patients.
Methods:
A retrospective, cross-sectional, observational study was conducted using a database of severe geriatric trauma patients (age ≥65 years and ISS ≥16) who presented to a single regional trauma center between November 2016 and October 2018. We compared the baseline characteristics between the survivor and mortality groups and the predictive ability of the five scoring systems.
Results:
A total of 402 patients were included in the analysis; the in-hospital mortality rate was 25.6% (n=103). The TRISS had the highest area under the curve of 0.953 (95% confidence interval [CI], 0.927-0.971); followed by RTS, 0.777 (95% CI, 0.733-0.817); NISS, 0.733 (95% CI, 0.687-0.776); ISS, 0.660 (95% CI, 0.612-0.707); and GTOS, 0.660 (95% CI, 0.611-0.706) in severe geriatric trauma. The TRISS also had the highest area under the curve of 0.961 (0.919-0.985) among the injury severity scoring systems in polytrauma. The predictive ability of TRISS was significantly higher than the other four scores with respect to overall trauma and polytrauma (P<0.001).
Conclusion
The TRISS showed the highest prognostic performance for predicting in-hospital mortality among all the injury severity scoring systems in severe geriatric trauma.
7.Comparison of the new and conventional injury severity scoring systems for predicting mortality in severe geriatric trauma
Ho Wan RYU ; Jae Yun AHN ; Kang Suk SEO ; Jung Bae PARK ; Jong Kun KIM ; Mi Jin LEE ; Hyun Wook RYOO ; Yun Jeong KIM ; Changho KIM ; Jae Young CHOE ; Dong Eun LEE ; In Hwan YEO ; Sungbae MOON ; Yeonjoo CHO ; Han Sol CHUNG ; Jae Wan CHO ; Haewon JUNG
Journal of the Korean Society of Emergency Medicine 2020;31(6):543-552
Objective:
This study compared the prognostic performance of the following five injury severity scores: the Geriatric Trauma Outcome Score (GTOS), the Injury Severity Score (ISS), the New Injury Severity Score (NISS), the Revised Trauma Score (RTS), and the Trauma and Injury Severity Score (TRISS) for in-hospital mortality in severe geriatric trauma patients.
Methods:
A retrospective, cross-sectional, observational study was conducted using a database of severe geriatric trauma patients (age ≥65 years and ISS ≥16) who presented to a single regional trauma center between November 2016 and October 2018. We compared the baseline characteristics between the survivor and mortality groups and the predictive ability of the five scoring systems.
Results:
A total of 402 patients were included in the analysis; the in-hospital mortality rate was 25.6% (n=103). The TRISS had the highest area under the curve of 0.953 (95% confidence interval [CI], 0.927-0.971); followed by RTS, 0.777 (95% CI, 0.733-0.817); NISS, 0.733 (95% CI, 0.687-0.776); ISS, 0.660 (95% CI, 0.612-0.707); and GTOS, 0.660 (95% CI, 0.611-0.706) in severe geriatric trauma. The TRISS also had the highest area under the curve of 0.961 (0.919-0.985) among the injury severity scoring systems in polytrauma. The predictive ability of TRISS was significantly higher than the other four scores with respect to overall trauma and polytrauma (P<0.001).
Conclusion
The TRISS showed the highest prognostic performance for predicting in-hospital mortality among all the injury severity scoring systems in severe geriatric trauma.
8.Confirmation of COVID-19 in Outof-Hospital Cardiac Arrest Patients and Postmortem Management in the Emergency Department during the COVID-19 Outbreak
Changho KIM ; In Hwan YEO ; Jong Kun KIM ; Yeonjoo CHO ; Mi Jin LEE ; Haewon JUNG ; Jae Wan CHO ; Ji Yeon HAM ; Suk Hee LEE ; Han Sol CHUNG ; You Ho MUN ; Sang Hun LEE ; Yang Hun KIM ;
Infection and Chemotherapy 2020;52(4):562-572
Background:
There is currently a lack of evidence-based postresuscitation or postmortem guidelines for patients with out-of-hospital cardiac arrest (OHCA) in the setting of an emerging infectious disease. This study aimed to develop and validate a multimodal screening tool that aids in predicting the disease confirmation in emergency situations and patients with OHCA during a coronavirus disease 2019 (COVID-19) outbreak.
Materials and Methods:
We conducted a retrospective, multicenter observational study of adult patients with OHCA in Daegu, Korea. To identify the potential predictors that could be used in screening tools in the emergency department, we applied logistic regression to data collected from March 1 to March 14. The prediction performance of the screening variables was then assessed and validated on the data of patients with OHCA who were treated between February 19 and March 31, 2020. General patient characteristics and hematological findings of the COVID-19-negative and COVID-19-positive groups were compared. We also evaluated confirmation test criteria as predictors for COVID-19 positivity in patients with OHCA.
Results:
Advanced age, body temperature, and abnormal chest X-ray (CXR) revealed significant predictive ability in the derivation cohort. Of the 184 adult patients with OHCA identified in the validation cohort, 80 patients were included in the analysis. Notably, 9 patients were positive and 71 were negative on the COVID-19 reverse transcription polymerase chain reaction test. Five patients (55.6%) in the COVID-19-positive group had a fever before OHCA, and 12 (16.9%) of the COVID-19-negative group had a fever before OHCA (P = 0.018).Eight patients (88.9%) in the COVID-19-positive group had a CXR indicating pneumonic infiltration. Of the criteria for predicting COVID-19, fever or an abnormal CXR had a sensitivity of 100% (95% confidence interval [CI]: 65.4 – 100) and a specificity of 22.5% (95% CI: 13.5 – 34.0).
Conclusion
The screening tools that combined fever or abnormal CXR had a good discriminatory ability for COVID-19 infection in adult patients with OHCA. Therefore, during the COVID-19 outbreak period, it is recommended to suspect COVID-19 infection and perform COVID-19 test if patients present with a history of fever or show abnormal findings in postmortem CXR
9.Confirmation of COVID-19 in Outof-Hospital Cardiac Arrest Patients and Postmortem Management in the Emergency Department during the COVID-19 Outbreak
Changho KIM ; In Hwan YEO ; Jong Kun KIM ; Yeonjoo CHO ; Mi Jin LEE ; Haewon JUNG ; Jae Wan CHO ; Ji Yeon HAM ; Suk Hee LEE ; Han Sol CHUNG ; You Ho MUN ; Sang Hun LEE ; Yang Hun KIM ;
Infection and Chemotherapy 2020;52(4):562-572
Background:
There is currently a lack of evidence-based postresuscitation or postmortem guidelines for patients with out-of-hospital cardiac arrest (OHCA) in the setting of an emerging infectious disease. This study aimed to develop and validate a multimodal screening tool that aids in predicting the disease confirmation in emergency situations and patients with OHCA during a coronavirus disease 2019 (COVID-19) outbreak.
Materials and Methods:
We conducted a retrospective, multicenter observational study of adult patients with OHCA in Daegu, Korea. To identify the potential predictors that could be used in screening tools in the emergency department, we applied logistic regression to data collected from March 1 to March 14. The prediction performance of the screening variables was then assessed and validated on the data of patients with OHCA who were treated between February 19 and March 31, 2020. General patient characteristics and hematological findings of the COVID-19-negative and COVID-19-positive groups were compared. We also evaluated confirmation test criteria as predictors for COVID-19 positivity in patients with OHCA.
Results:
Advanced age, body temperature, and abnormal chest X-ray (CXR) revealed significant predictive ability in the derivation cohort. Of the 184 adult patients with OHCA identified in the validation cohort, 80 patients were included in the analysis. Notably, 9 patients were positive and 71 were negative on the COVID-19 reverse transcription polymerase chain reaction test. Five patients (55.6%) in the COVID-19-positive group had a fever before OHCA, and 12 (16.9%) of the COVID-19-negative group had a fever before OHCA (P = 0.018).Eight patients (88.9%) in the COVID-19-positive group had a CXR indicating pneumonic infiltration. Of the criteria for predicting COVID-19, fever or an abnormal CXR had a sensitivity of 100% (95% confidence interval [CI]: 65.4 – 100) and a specificity of 22.5% (95% CI: 13.5 – 34.0).
Conclusion
The screening tools that combined fever or abnormal CXR had a good discriminatory ability for COVID-19 infection in adult patients with OHCA. Therefore, during the COVID-19 outbreak period, it is recommended to suspect COVID-19 infection and perform COVID-19 test if patients present with a history of fever or show abnormal findings in postmortem CXR
10.Revised Triage and Surveillance Protocols for Temporary Emergency Department Closures in Tertiary Hospitals as a Response to COVID-19 Crisis in Daegu Metropolitan City
Han Sol CHUNG ; Dong Eun LEE ; Jong Kun KIM ; In Hwan YEO ; Changho KIM ; Jungbae PARK ; Kang Suk SEO ; Sin-Yul PARK ; Jung Ho KIM ; Gyunmoo KIM ; Suk Hee LEE ; Jeon Jae CHEON ; Yang Hun KIM
Journal of Korean Medical Science 2020;35(19):e189-
Background:
When an emergency-care patient is diagnosed with an emerging infectious disease, hospitals in Korea may temporarily close their emergency departments (EDs) to prevent nosocomial transmission. Since February 2020, multiple, consecutive ED closures have occurred due to the coronavirus disease 2019 (COVID-19) crisis in Daegu. However, sudden ED closures are in contravention of laws for the provision of emergency medical care that enable the public to avail prompt, appropriate, and 24-hour emergency medical care. Therefore, this study ascertained the vulnerability of the ED at tertiary hospitals in Daegu with regard to the current standards. A revised triage and surveillance protocol has been proposed to tackle the current crisis.
Methods:
This study was retrospectively conducted at 6 level 1 or 2 EDs in a metropolitan city where ED closure due to COVID-19 occurred from February 18 to March 26, 2020. The present status of ED closure and patient characteristics and findings from chest radiography and laboratory investigations were assessed. Based on the experience from repeated ED closures and the modified systems that are currently used in EDs, revised triage and surveillance protocols have been developed and proposed.
Results:
During the study period, 6 level 1 or 2 emergency rooms included in the study were shut down 27 times for 769 hours. Thirty-one confirmed COVID-19 cases, of whom 7 died, were associated with the incidence of ED closure. Typical patient presentation with respiratory symptoms of COVID-19 was seen in less than 50% of patients, whereas abnormal findings on chest imaging investigations were detected in 93.5% of the study population. The chest radiography facility, resuscitation rooms, and triage area were moved to locations outside the ED, and a new surveillance protocol was applied to determine the factors warranting quarantine, including symptoms, chest radiographic findings, and exposure to a source of infection. The incidence of ED closures decreased after the implementation of the revised triage and surveillance protocols.
Conclusion
Triage screening by emergency physicians and surveillance protocols with an externally located chest imaging facility were effective in the early isolation of COVID-19 patients. In future outbreaks of emerging infectious diseases, efforts should be focused toward the provision of continued ED treatment with the implementation of revised triage and surveillance protocols.