1.Subchronic inhalation toxicity study of diethylbenzene in Wistar rats
Journal of Biomedical and Translational Research 2024;25(3):119-132
Diethylbenzene (DEB) is a colorless flammable liquid composed of a benzene ring and two ethyl substituents. DEBs mostly exist as a mixture of isomers and are mainly used as inter-mediates and solvents occupationally. Workers may be exposed to DEB inhalation during their occupational activities including manufacturing or processing of materials; however, limited data are available on the risk assessment of DEB mixtures. In this study, male and female Wistar rats were exposed to vapors of a DEB mixture for 13-weeks (6 hr/day, 5 days/ week) at concentrations of 0, 40, 80, and 160 ppm in a whole-body inhalation chamber. Clini-cal signs, mean body weight, food consumption, bronchoalveolar lavage fluid (BALF), hema-tology, blood biochemistry, gross findings, organ weights, and microscopic findings were ex-amined to determine the toxicity of DEB mixture. The exposure concentrations in chambers were 39.48 ± 1.13 ppm, 80.43 ± 2.06 ppm, and 160.20 ± 4.42 ppm for the low, medium, and high dose groups, respectively. No changes related to the test substance were observed, including changes in clinical observation, body weight, food consumption, BALF and blood analysis, necropsy findings, absolute and relative organ weights or histopathological analysis.Based on these results, the NOAEC (no-observed-adverse-effect-concentration) of DEB was defined as 160 ppm under the study conditions.
2.Subchronic inhalation toxicity study of diethylbenzene in Wistar rats
Journal of Biomedical and Translational Research 2024;25(3):119-132
Diethylbenzene (DEB) is a colorless flammable liquid composed of a benzene ring and two ethyl substituents. DEBs mostly exist as a mixture of isomers and are mainly used as inter-mediates and solvents occupationally. Workers may be exposed to DEB inhalation during their occupational activities including manufacturing or processing of materials; however, limited data are available on the risk assessment of DEB mixtures. In this study, male and female Wistar rats were exposed to vapors of a DEB mixture for 13-weeks (6 hr/day, 5 days/ week) at concentrations of 0, 40, 80, and 160 ppm in a whole-body inhalation chamber. Clini-cal signs, mean body weight, food consumption, bronchoalveolar lavage fluid (BALF), hema-tology, blood biochemistry, gross findings, organ weights, and microscopic findings were ex-amined to determine the toxicity of DEB mixture. The exposure concentrations in chambers were 39.48 ± 1.13 ppm, 80.43 ± 2.06 ppm, and 160.20 ± 4.42 ppm for the low, medium, and high dose groups, respectively. No changes related to the test substance were observed, including changes in clinical observation, body weight, food consumption, BALF and blood analysis, necropsy findings, absolute and relative organ weights or histopathological analysis.Based on these results, the NOAEC (no-observed-adverse-effect-concentration) of DEB was defined as 160 ppm under the study conditions.
3.Subchronic inhalation toxicity study of diethylbenzene in Wistar rats
Journal of Biomedical and Translational Research 2024;25(3):119-132
Diethylbenzene (DEB) is a colorless flammable liquid composed of a benzene ring and two ethyl substituents. DEBs mostly exist as a mixture of isomers and are mainly used as inter-mediates and solvents occupationally. Workers may be exposed to DEB inhalation during their occupational activities including manufacturing or processing of materials; however, limited data are available on the risk assessment of DEB mixtures. In this study, male and female Wistar rats were exposed to vapors of a DEB mixture for 13-weeks (6 hr/day, 5 days/ week) at concentrations of 0, 40, 80, and 160 ppm in a whole-body inhalation chamber. Clini-cal signs, mean body weight, food consumption, bronchoalveolar lavage fluid (BALF), hema-tology, blood biochemistry, gross findings, organ weights, and microscopic findings were ex-amined to determine the toxicity of DEB mixture. The exposure concentrations in chambers were 39.48 ± 1.13 ppm, 80.43 ± 2.06 ppm, and 160.20 ± 4.42 ppm for the low, medium, and high dose groups, respectively. No changes related to the test substance were observed, including changes in clinical observation, body weight, food consumption, BALF and blood analysis, necropsy findings, absolute and relative organ weights or histopathological analysis.Based on these results, the NOAEC (no-observed-adverse-effect-concentration) of DEB was defined as 160 ppm under the study conditions.
4.Aberrant Methylation of p16 Tumor Suppressor Gene and Death-Associated Protein Kinase in Non-Small Cell Lung Carcinoma.
Yun Seong KIM ; Min Ki LEE ; Kyung Sik JUNG ; Ki Uk KIM ; Young Dae KIM ; Hyung Ryul LEE ; Chang Hoon LEE ; Ju Won SEOK ; Yong Ki KIM ; Eun Sook JUN ; Young Min CHOI ; Seo Hee RHA ; Soon Kew PARK
Tuberculosis and Respiratory Diseases 2001;51(2):108-121
BACKGROUND: The p16INK4a (p16) tumor suppressor gene is frequently inactivated in human non-small cell lung cancers (NSCLCs), predominantly through homozygous deletion or in association with aberrant promotor hypermethylation. Death-associated protein kinase (DAPK) gene influences interferon γ-induced apoptotic cell death and has important role in metastasis of lung cancer in animal model. Hypermethylation of promoter region of DAP kinase gene may suppress the expression of this gene. METHODS: This study was performed to investigate the aberrant methylation of p16 or DAP kinase in 35 resected primary NSCLCs by methylation-specific PCR (MSP), and demonstrated frequency, diagnostic value and clinical implication of aberrant methylation of two genes. RESULTS: Thirty-two cases were male patients, and 3 cases were female patients with an average age was 57.8±10.5 years. The histologic types of lung cancer were 22 of squamous cell carcinoma, 12 of adenocarcinoma, 1 of large cell carcinoma. Pathologic stages were 11 cases of stage I(1 IA,10 IB), 13 cases of stage II (1 IIA, 12 IIB), and 11 cases of stage III(9 IIIA, 2 IIIB). Regarding for the cancer tissue, p16 aberrant methylation was noted in 13 case of 33 cases (39.4%), DAP kinase in 21 cases of 35 cases (60%). Age over 55 year was associated with p16 aberrant methylation significantly (p<0.05). Methylation status of two genes was not different by smoking history, histologic type, size of tumor, lymph node metastasis and disease progression of lung cancer. There was no correlation between p16 and DAP kinase hypermethylation. CONCLUSION: This investigation demonstrates that aberrant methylation of p16 tumor suppressor gene or DAP kinase showed relatively high frequency (74.3%) in NSCLCs, and that these genes could be a biologic marker for early detection of lung cancer.
Adenocarcinoma
;
Biomarkers
;
Carcinoma, Large Cell
;
Carcinoma, Squamous Cell
;
Cell Death
;
Death-Associated Protein Kinases
;
Disease Progression
;
DNA Methylation
;
Female
;
Genes, Tumor Suppressor*
;
Humans
;
Interferons
;
Lung Neoplasms
;
Lung*
;
Lymph Nodes
;
Male
;
Methylation*
;
Models, Animal
;
Neoplasm Metastasis
;
Polymerase Chain Reaction
;
Promoter Regions, Genetic
;
Protein Kinases*
;
Smoke
;
Smoking
5.Involvement of mitogen-activated protein kinases and p21Waf1 in hydroxyurea-induced G1 arrest and senescence of McA-RH7777 rat hepatoma cell line.
Seung Hee HONG ; Bum Sik HONG ; Dae Cheol KIM ; Mee Sook RHO ; Joo In PARK ; Soe Hee RHA ; Ho Sun JUN ; Jin Sook JEONG
Experimental & Molecular Medicine 2004;36(5):493-498
Hydroxyurea is commonly used to treat hematologic disorders and some type of solid tumors, but the mechanism for its therapeutic effect is not clearly known. In this study, we examined the effect of hydroxyurea on rat hepatoma McA-RH7777 cells, specifically, on the role of mitogen-activated protein (MAP) kinase signal transduction pathways and p21Waf1, p27Kip1 and p53. Rat hepatoma McA-RH7777 cells treated with hydroxyurea for 7 days, caused the inhibition of cell growth in a dose-dependent manner. But, this growth inhibition was not caused by necrosis or apoptosis but instead was associated with cell senescence-like change as evidenced by senescence associated-beta-galactosidase staining, and cells arrest at G1 phase of cell cycle. Phosphorylation of MAP kinases, such as ERK, JNK, and p38, was found to be decreased after treatment of cells with hydroxyurea. But, the expression of p21Waf1 was increased, while p27Kip1 and p53 were not detected in hydroxyurea treated rat hepatoma cells. Hydroxyurea treatment induced G1 arrest and a senescence-like changes in rat hepatoma McA-RH7777 cells may be the likely results of signal disruption of MAP kinases (ERK, JNK, and p38 MAP kinase) and p21Waf1 over-expression.
Animals
;
Antineoplastic Agents/*pharmacology
;
Cell Aging/drug effects
;
Cell Cycle Proteins/analysis/metabolism/*physiology
;
Cell Line, Tumor
;
Cell Proliferation/drug effects
;
G1 Phase/drug effects/physiology
;
Hydroxyurea/*pharmacology
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Liver Neoplasms, Experimental/enzymology/*metabolism
;
Mitogen-Activated Protein Kinases/analysis/*physiology
;
Phosphorylation/drug effects
;
Protein p53/analysis/metabolism
;
Rats
;
Research Support, Non-U.S. Gov't
;
Tumor Suppressor Proteins/analysis/metabolism
;
Up-Regulation
6.Guidelines for the Management of Unruptured Intracranial Aneurysm.
Dae Hee SEO ; Hyun Seung KANG ; Dae Won KIM ; Sukh Que PARK ; Young SONG ; Seung Hun SHEEN ; Seung Hoon YOU ; Sun Uk KWON ; Joung Ho RHA ; Hee Joon BAE ; Chang Wan OH ; Kyung Ho YU ; Byung Woo YOON ; Byung Chul LEE ; Ji Hoe HEO ; Keun Sik HONG ; Seung Chyul HONG ; In Sung PARK
Korean Journal of Cerebrovascular Surgery 2011;13(4):279-290
Intracranial aneurysmal rupture causes subarachnoid hemorrhage which usually leads to fatality or severe disability. Treatment of unruptured intracranial aneurysms (UIAs) can substantially reduce the risk of rupture and prevent the grave consequences, but the risk of prophylactic treatment cannot be ignored. UIAs have diverse characteristics and management strategy needs to be tailored according to their location, size and clinical status. In the absence of level I evidence, the treatment guidance often relied on expert's opinions and experience. Knowledge of the natural course and management risks of individual aneurysms can help to guide treatment decision, but the natural history is still controversial and risks are not clearly defined. The Korean Society of Cerebrovascular Surgeons (KSCVS) decided to issue a Korean version of UIA management guideline as a framework for the treatment decision and as a basis for future studies, following 'Guideline Development Manual' of the Clinical Research Center for Stroke (CRCS). The organized committee systematically reviewed relevant literature and major guidelines published between January 2000 and July 2010 and took a developmental strategy of adaptation rather than de novo methods. On the basis of interpretation of the published evidences, recommendations were synthesized, and the level of evidence and the grade of recommendation were determined using the methods adapted from those of the US Agency for Healthcare Policy and Research and CRCS. The current guideline focuses on three domains of natural history, diagnosis and treatment of UIAs. The hierarchy of evidence and the recommendation grading indicate the current level by the literature and do not indicate the necessity or the prohibition of a certain clinical practice. Accordingly, this guideline cannot provide the answer for every clinical situation and should not take precedence over the clinical judgment of responsible physicians for individual patients. The final judgment regarding the care of a particular patient must be made by the physician and patient in light of circumstances specific to that patient. This is the first version of the UIA management guideline in Korea and new evidences will be timely and continuously updated in the future guidelines.
Aneurysm
;
Calcium Hydroxide
;
Delivery of Health Care
;
Humans
;
Intracranial Aneurysm
;
Judgment
;
Korea
;
Light
;
Natural History
;
Risk Management
;
Rupture
;
Stroke
;
Subarachnoid Hemorrhage
;
Zinc Oxide
7.Scientific Statement for Screening of Coronary Artery Disease in Patients with Ischemic Stroke.
Dongbeom SONG ; Young Dae KIM ; Keun Sik HONG ; Byung Woo YOON ; Byung Chul LEE ; Joung Ho RHA ; Sun Uck KWON ; Hee Joon BAE ; Kyung Ho YU ; Jong Moo PARK ; Kwang Yeol PARK ; Sang Bae KO ; Chang Wan OH ; Jeong Eun KIM ; Ji Hoe HEO
Journal of the Korean Neurological Association 2016;34(2):91-98
Ischemic stroke and myocardial infarction share common risk factors and pathophysiologic mechanisms. Unrecognized coronary artery disease typically occurs in 20-30% of patients with ischemic stroke, and its presence helps to predict the outcome. Coronary artery disease is also an important cause of morbidity and mortality in patients with ischemic stroke. Therefore, applying a screening test for asymptomatic coronary artery disease may be considered in ischemic stroke patients who have a high cardiovascular risk profile. Coronary computed tomography (CT) angiography, myocardial perfusion imaging, or stress echocardiography can be used as a screening test. Coronary CT angiography is recommended in the absence of allergy to contrast media and renal insufficiency.
Angiography
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Contrast Media
;
Coronary Artery Disease*
;
Coronary Vessels*
;
Echocardiography, Stress
;
Humans
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Hypersensitivity
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Mass Screening*
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Mortality
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Myocardial Infarction
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Myocardial Perfusion Imaging
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Renal Insufficiency
;
Risk Factors
;
Stroke*
8.An unusual case of gastric carcinoma with synchronous non-Hodgkin's lymphoma.
Sung Ha PARK ; Sun Young RHA ; Dae Keun SHIM ; Hyun Jung RHO ; Nae Choon YOO ; Joo Hang KIM ; Jae Kyung ROH ; Woo Ick YANG ; Sung Hoon NOH ; Jin Sik MIN ; Byung Soo KIM ; Hyun Cheol CHUNG
Yonsei Medical Journal 1998;39(5):463-467
We report a case of synchronous gastric adenocarcinoma and abdominal non-Hodgkin's lymphoma in a 56-year-old man. An explo-laparotomy was performed for the purpose of palliative resection of the stomach and to evaluate the nature of splenic and peri-pancreatic mass lesions. The pathologic stage of the gastric carcinoma was stage IB (T2N0M0) and the clinical stage of the diffuse large cell type lymphoma was IIA2S. Following surgery and chemotherapy, the patient is now in a disease-free state.
Abdominal Neoplasms/pathology
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Abdominal Neoplasms/diagnosis*
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Adenocarcinoma/pathology
;
Adenocarcinoma/diagnosis*
;
Case Report
;
Human
;
Lymphoma, Non-Hodgkin/pathology
;
Lymphoma, Non-Hodgkin/diagnosis*
;
Male
;
Middle Age
;
Neoplasm Staging
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Neoplasms, Multiple Primary/pathology
;
Neoplasms, Multiple Primary/diagnosis*
;
Stomach Neoplasms/pathology
;
Stomach Neoplasms/diagnosis*
;
Tomography, X-Ray Computed
9.Review of Evidences and Updates of the Korean Clinical Practice Guidelines for Stroke in 2013.
Keun Sik HONG ; Kyung Ho YU ; Joung Ho RHA ; Hahn Young KIM ; Jaseong KOO ; Jong Moo PARK ; Dae Hee SEO ; In Sung PARK ; Kyung Hee CHO ; Keun Hwa JUNG ; Tai Hwan PARK ; Byung Chul LEE ; Byung Woo YOON
Journal of the Korean Neurological Association 2013;31(3):143-157
The first edition of Korean Clinical Practice Guidelines for Stroke, which was published in 2009, reflected evidence published prior to June 2007. Since then, many clinical trials and well-designed observational studies provided new evidence that may be pertinent to clinical practice. Accordingly, investigators of the Clinical Research Center for Stroke have timely updated the guidelines. This article summarizes the recent evidence and updated guidelines regarding the use of aspirin for primary stroke prevention, the management of asymptomatic carotid stenosis, the use of antithrombotics in atrial fibrillation for stroke prevention, the diagnosis and management of unruptured aneurysm, intravenous and intra-arterial thrombolysis in acute ischemic stroke, antiplatelet therapy for secondary stroke prevention in patients with non-cardioembolic stroke or transient ischemic attack, and the management of symptomatic carotid stenosis for secondary stroke prevention.
Aneurysm
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Aspirin
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Atrial Fibrillation
;
Carotid Stenosis
;
Humans
;
Ischemic Attack, Transient
;
Research Personnel
;
Stroke
10.Focused Update of Korean Clinical Practice Guidelines for the Thrombolysis in Acute Stroke Management.
Kyung Hee CHO ; Sang Bae KO ; Dae Hyun KIM ; Hee Kwon PARK ; A Hyun CHO ; Keun Sik HONG ; Kyung Ho YU ; Ji Hoe HEO ; Sun Uck KWON ; Hee Joon BAE ; Chang Wan OH ; O Ki KWON ; Byung Chul LEE ; Byung Woo YOON ; Joung Ho RHA
Korean Journal of Stroke 2012;14(3):95-105
Since the release of first Korean Clinical Practice Guideline of Stroke in 2009, many important new evidences have emerged in the field of thrombolytic therapy. Among the recent developments are the extended therapeutic time window of intravenous (IV) tissue plasminogen activator (tPA) up to 4.5 hours after onset, and the efforts for the wider application of IV thrombolysis to patients with minor stroke and elderly patients over 80 years old. Debates about the optimal dose of IV tPA according to the ethnic population is still ongoing. Further evidences for the efficacy of intra-arterial thrombolysis have also accumulated, including the application of various novel mechanical devices with promising results. Thus update of guideline became necessary and we revise the acute stroke management guideline, focusing on the thrombolytic therapy.
Aged
;
Humans
;
Stroke
;
Thrombolytic Therapy
;
Tissue Plasminogen Activator