Publications by authors named "Seon-Min Lee"

26 Publications

  • Page 1 of 1

Stereochemical Determination of Fistularins Isolated from the Marine Sponge and Their Regulatory Effect on Intestinal Inflammation.

Mar Drugs 2021 Mar 22;19(3). Epub 2021 Mar 22.

Department of Oceanography, Kunsan National University, Gunsan 54150, Korea.

By activity-guided fractionation based on inhibition of nitric oxide (NO) and prostaglandin E2 (PGE), six fistularin compounds (-) were isolated from the marine sponge (order Astrophorida). Based on stereochemical structure determination using Mosher's method, fistularin-3 was assigned as a new stereoisomer. On the basis of the stereochemistry of fistularin-3, the stereochemical homogeneity of all six compounds was established by comparing carbon and proton chemical shifts. For fistularin-1 () and -2 (), quantum calculations were performed to confirm their stereochemistry. In a co-culture system of human epithelial Caco-2 cells and THP-1 macrophages, all six isolated compounds showed potent anti-inflammatory activities. These bioactive fistularins inhibited the production of NO, PGE, TNF-α, IL-1β, and IL-6 induced by lipopolysaccharide and interferon gamma. Inducible NO synthase and cyclooxygenase-2 expression and MAPK phosphorylation were downregulated in response to the inhibition of NF-κB nuclear translocation. Among the compounds tested, fistularin-1 () and 19-deoxyfistularin-3 () showed the highest activity. These findings suggest the potential use of the marine sponge and its metabolites as pharmaceuticals for the treatment of inflammation-related diseases including inflammatory bowel disease.
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http://dx.doi.org/10.3390/md19030170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004254PMC
March 2021

Tolosa-Hunt Syndrome Misdiagnosed as Surgical Complication After Frontal Balloon Sinuplasty.

J Craniofac Surg 2021 Jan 28. Epub 2021 Jan 28.

Department of Otorhinolaryngology-Head and Neck Surgery, Konyang University College of Medicine Department of Neurology, Konyang University College of Medicine, Daejeon, Republic of Korea.

Abstract: Tolosa-Hunt syndrome (THS) is a rare benign disease caused by granulomatous inflammation in the craniofacial region. It is mostly idiopathic and generally presents with painful ophthalmoplegia, ipsilateral oculomotor paresis, and steroid responsiveness. There are few reports of THS after sinus surgery. Here, we present a case of THS in an adult immunocompetent patient with severe ophthalmic pain and diplopia after frontal balloon sinuplasty. The patient was initially misdiagnosed as having a surgical complication. The patient was treated with massive corticosteroid pulse therapy, and the symptoms resolved dramatically. There were no complications or recurrence in the 7-month follow-up period.
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http://dx.doi.org/10.1097/SCS.0000000000007483DOI Listing
January 2021

Standardized Fraction of Alleviates Dextran Sulfate Sodium-Induced Chronic Colitis in C57BL/6 Mice via Upregulation of FOXP3 Regulatory T Cells.

Biomolecules 2020 10 20;10(10). Epub 2020 Oct 20.

Department of Oceanography, Kunsan National University, Kunsan 54150, Korea.

is a tropical brown algae (seaweed) known to have anti-inflammatory properties. In this study, we analyzed extract (TOE) using liquid chromatography quadrupole time of flight mass spectrometry (LC-QTOF-MS) and nuclear magnetic resonance (NMR) and evaluated the in vivo efficacy of TOE against dextran sulfate sodium-induced chronic colitis in C57BL/6 mice. The bioactive fraction of TOE was administered orally daily for 6 weeks to mice under different treatments normal, colitis, and colitis + conventional drug (5-aminosalicylic acid, 5-ASA). Regarding clinical manifestation, the disease activity index and colon length of the colitis + TOE group were significantly reduced compared to those of the colitis group. The results of myeloperoxidase activity and histopathological examination showed similar results. Western blot analysis of colon tissues revealed that cyclooxygenase-2, tumor necrosis factor alpha (TNF-α), and phosphorylated signal transducer and activator of transcription-3 (p-STAT3) were significantly decreased in the colitis + 5-ASA group, whereas forkhead box P3 (FOXP3) was increased. qPCR results showed changes in T cell subsets; the administration of TOE upregulated regulatory T cell (Treg) expression, although T helper 17 cell (Th17) expression did not change significantly. Interestingly, the colitis + TOE group showed high levels of both Th1 and Th2 transcription factors, but the secreted cytokine interferon (IFN)-γ and interleukin (IL)-4 remained unchanged and somewhat reduced. Additionally, TNF-α gene expression was significantly reduced in the colitis + TOE group. IL-6 mRNA levels were also decreased, although not significantly. Four compounds were structurally elucidated using 1D- and 2D-NMR spectroscopy, and five compounds were fully identified or tentatively characterized using LC-QTOF-MS. In conclusion, TOE could alleviate chronic colitis via upregulation of Foxp3 Treg cells and production of the anti-inflammatory cytokine IL-10, which directly inhibits macrophages and pro-inflammatory cytokine synthesis, leading to reduced colitis.
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http://dx.doi.org/10.3390/biom10101463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590162PMC
October 2020

The Role of Negative Emotions Pre- and Post-Implementation of Graphic Health Warnings: Longitudinal Evidence from South Korea.

Int J Environ Res Public Health 2020 07 27;17(15). Epub 2020 Jul 27.

Dongguk Business School, Dongguk University, Seoul 04620, Korea.

This longitudinal study investigated the factors that determine the effectiveness of graphic health warnings (GHWs) by comparing 246 South Korean smoker's responses before and after the introduction of the country's new tobacco control policy wherein GHWs were placed on all cigarette packaging. Even though introducing GHWs did not cause immediate changes in smokers' intention to quit smoking or perception of smoking's health risk, GHWs eventually motivated smokers to quit smoking when they experienced negative emotional responses to the newly introduced graphic warnings on cigarette packaging. More importantly, this study found that positive changes in smokers' perceived risk associated with smoking due to the introduction of GHWs mediated a positive relationship between changes in smokers' negative emotions (NE) from text-only warnings to graphic warnings and changes in their intention to quit smoking during the same period. Based on these results, the authors suggest that, for GHW policy to be more effective in motivating smoking cessation, the warnings need to convey images sufficiently unpleasant to induce negative emotional responses among smokers.
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http://dx.doi.org/10.3390/ijerph17155393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432201PMC
July 2020

Integrated metabolomics and lipidomics reveals high accumulation of polyunsaturated lysoglycerophospholipids in human lung fibroblasts exposed to fine particulate matter.

Ecotoxicol Environ Saf 2020 Oct 1;202:110896. Epub 2020 Jul 1.

Environmental Chemistry Research Group, Korea Institute of Toxicology, Jinju, 52834, Republic of Korea. Electronic address:

Exposure to fine particulate matter (PM) comprising toxic compounds arising from air pollution is a major human health concern. It is linked to increased mortality and incidence of various lung diseases. However, the mechanisms underlying the toxic effects of PM on lung fibroblasts have not been fully explored. We used targeted quantitative metabolomics and lipidomics analysis along with cytotoxicity studies to comprehensively characterize the alterations in the metabolite profiles of human lung fibroblasts (HEL 299) upon exposure to PM and PM. This exposure at 50 μg/mL for 72 h induced an abnormally high apoptotic response via triggering intracellular reactive oxygen species (ROS) production and mitochondrial dysfunction through an imbalance between pro- and anti-apoptotic signaling pathways. The cytotoxic effects of PM were more severe than those of PM. Metabolomics and lipidomics analyses revealed that PM exposure triggered substantial changes in the cellular metabolite profile, which involved reduced mitochondria-related metabolites such as tricarboxylic acid (TCA) cycle intermediates, amino acids, and free fatty acids as well as increased lysoglycerophospholipids (LPLs) containing polyunsaturated fatty acids. The decrease in mitochondria-related metabolites suggested that PM exposure led to reduced TCA cycle capacity and energy production. Apoptotic and inflammatory responses as well as mitochondrial dysfunction were likely to be accelerated because of excessive accumulation of LPLs, contributing to the disruption of membrane rafts and Ca homeostasis and causing increased mitochondrial ROS formation. These results provide valuable insights regarding the toxic effects of PM exposure. Our study also provides a new direction for research on PM exposure-related health disorders using different cell lines.
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http://dx.doi.org/10.1016/j.ecoenv.2020.110896DOI Listing
October 2020

Cytotoxic 4-Hydroxyprorocentrolide and Prorocentrolide C from Cultured Dinoflagellate Induce Human Cancer Cell Death through Apoptosis and Cell Cycle Arrest.

Toxins (Basel) 2020 05 7;12(5). Epub 2020 May 7.

Department of Oceanography, Kunsan National University, Gunsan 54150, Korea.

Prorocentrolide and its analogs, the novel naturally derived antitumor agents, have recently been identified in the dinoflagellate . In the current study, the underlying inhibitory mechanisms of 4-hydroxyprorocentrolide () and prorocentrolide C () on the proliferation of human carcinoma cells were determined. and arrested the cell cycle at the S phase in A549 cells and G2/M phase in HT-29 cells, leading to apoptotic cell death, as determined using fluorescence-activated cell sorting analysis with Annexin V/PI double staining. Apoptosis induced by these compounds was associated with alterations in the expression of cell cycle-regulating proteins (cyclin D1, cyclin E1, CDK2, and CDK4), as well as alterations in the levels of apoptosis-related proteins (PPAR, Bcl-2, Bcl-xl, and survivin). These findings provide new insights into the antitumor mechanisms of 4-hydroxyprorocentrolide and prorocentrolide C and a basis for future investigations assessing prorocentrolide analogs as prospective therapeutic drugs.
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http://dx.doi.org/10.3390/toxins12050304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290926PMC
May 2020

Cadmium induces cytotoxicity in normal mouse renal MM55.K cells.

Int J Environ Health Res 2020 Mar 19:1-10. Epub 2020 Mar 19.

Biological Resources Research Group, Bioenvironmental Science & Toxicology Division, Gyeongnam Branch Institute, Korea Institute of Toxicology (KIT), Jinju, Republic of Korea.

The toxicity of cadmium (Cd) occurs through accumulation in the environment. The precise mechanism underlying Cd toxicity remains unclear. Therefore, in the present study, we studied the effects of Cd on MM55.K cells and investigated the mechanisms underlying Cd-induced cell death. CdCl2 significantly elevated apoptotic cell death, mitochondrial membrane potential (ΔΨ) loss, and caspase-dependent cell death. Moreover, immunoblotting results revealed that CdCl2 down-regulated the inhibitor of apoptotic protein such as survivin and Bcl-2 which led to the activation of caspase-3 and the cleavage of PARP in MM55.K cells. Besides, CdCl2 caused the up-regulation of ROS-related proteins such as HO-1 and ER stress-related proteins such as GRP78 and CHOP in MM55.K cells. CdCl2 toxicity resulted in the down-regulation of the AKT pathway that leads to the up-regulation of phosphorylated JNK and p38 in MM55.K cells. Thus, CdCl2 induce toxicity by AKT/MAPK regulation and causing ROS production, ER stress, ΔΨ loss, and apoptotic cell death in normal mouse renal cells.
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http://dx.doi.org/10.1080/09603123.2020.1739236DOI Listing
March 2020

Deacetylphylloketal, a New Phylloketal Derivative from a Marine Sponge, Genus , with Potent Anti-Inflammatory Activity in In Vitro Co-Culture Model of Intestine.

Mar Drugs 2019 Nov 8;17(11). Epub 2019 Nov 8.

Department of Oceanography, Kunsan National University, Kunsan 54150, Korea.

The inflammatory bowel diseases (IBD) cause chronic inflammation of the gastrointestinal tract and include ulcerative colitis (UC) and Crohn's disease (CD). The prevalence of IBD has been increasing worldwide, and has sometimes led to irreversible impairment of gastrointestinal structure and function. In the present study, we successfully isolated a new phylloketal derivative, deacetylphylloketal () along with four known compounds from the sponge genus The anti-inflammatory properties of deacetylphylloketal () and phyllohemiketal A () were evaluated using an in vitro co-culture system that resembles the intestinal epithelial environment. A co-culture system was established that consisted of human epithelial Caco-2 cells and phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 macrophage cells. The treatment of co-cultured THP-1 cells with compounds or significantly suppressed the production and/or gene expression of lipopolysaccharide (LPS)-induced nitric oxide (NO), prostaglandin E2 (PGE2), Interleukin-6 (IL-6), IL-1β and Tumor Necrosis Factor alpha (TNF-α). The expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 were down-regulated in response to inhibition of NF-kB translocation into the nucleus in cells. In addition, we observed that and markedly promoted the nuclear translocation of Nrf2 and subsequent increase in the expression of heme oxygernase (HO)-1. These findings suggest the potential use of sponge genus and its metabolites as a pharmaceutical aid in the treatment of inflammation-related diseases including IBD.
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http://dx.doi.org/10.3390/md17110634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6891596PMC
November 2019

Membrane-Free Stem Cell Components Inhibit Interleukin-1α-Stimulated Inflammation and Cartilage Degradation in vitro and in vivo: A Rat Model of Osteoarthritis.

Int J Mol Sci 2019 Sep 30;20(19). Epub 2019 Sep 30.

Biological Resources Research Group, Gyeongnam Department of Environment Toxicology and Chemistry, Korea Institute of Toxicology (KIT), 17 Jeigok-gil, Jinju 52834, Korea.

Membrane-free stem cell components (MFSCC) from basal adipose tissue-derived stem cells (ADSCs) are unknown for the treatment strategies in osteoarthritis (OA). OA has been considered to be associated with inflammatory damage and cartilage degradation. In this study, we intended to investigate the molecular mechanism of the anti-inflammation and cartilage protection effect of MFSCC in vitro (rat primary chondrocytes) and in vivo (rat OA model). The MFSCC treatment significantly inhibited interleukin-1α (IL-1α) stimulated inflammation and cartilage degradation. The MFSCC considerably reduced the levels of inflammatory factors such as iNOS, COX-2, NO, and PGE and was suppressed NF-κB and MAPKs signaling pathways in IL-1α-stimulated rat chondrocytes. Additionally, biomarkers of OA such as MMP-9, COMP, and CTX-II decreased in the monosodium iodoacetate (MIA)-induced rat OA model by MFSCC treatment. In conclusion, the MFSCC was established to suppress IL-1α induced inflammation and cartilage degradation in vitro and in vivo. These findings provide new insight for understanding OA therapy using membrane-free stem cell approaches.
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http://dx.doi.org/10.3390/ijms20194869DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801847PMC
September 2019

(10)-Debromohymenialdisine from Marine Sponge sp. Regulates Intestinal Inflammatory Responses in Co-Culture Model of Epithelial Caco-2 Cells and THP-1 Macrophage Cells.

Molecules 2019 Sep 18;24(18). Epub 2019 Sep 18.

Department of Agronomy and Medicinal Plant Resources, Gyeongnam National University of Science and Technology, Jinju 52725, Korea.

Crohn's disease (CD) and ulcerative colitis (UC), collectively referred to as inflammatory bowel disease (IBD), are autoimmune diseases characterized by chronic inflammation within the gastrointestinal tract. Debromohymenialdisine is an active pyrrole alkaloid that is well known to serve as a stable and effective inhibitor of Chk2. In the present study, we attempted to investigate the anti-inflammatory properties of (10)-debromohymenialdisine () isolated from marine sponge species using an intestinal in vitro model with a transwell co-culture system. The treatment with attenuated the production and gene expression of lipopolysaccharide (LPS)-induced Interleukin (IL)-6, IL-1β, prostaglandin E2 (PGE2), and tumor necrosis factor-α in co-cultured THP-1 macrophages at a concentration range of 1-5 μM. The protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 were down-regulated in response to the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) translocation into the nucleus in cells. In addition, we observed that markedly promoted the nuclear translocation of nuclear factor erythroid 2 related factor 2 (Nrf2) and subsequent increase of heme oxygenase-1 (HO-1) expression. These findings suggest the potential use of as a pharmaceutical lead in the treatment of inflammation-related diseases including IBD.
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http://dx.doi.org/10.3390/molecules24183394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6766964PMC
September 2019

Clinical Characteristics of Involuntary Movement in Hospitalized Patients.

J Mov Disord 2019 01 20;12(1):31-36. Epub 2018 Dec 20.

Department of Neurology and Parkinson's Disease Centre, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea.

Objective: Neurological symptoms in hospitalized patients are not rare, and neurological consultation for movement disorders is especially important in evaluating or managing those with various movement disorders. Therefore, we investigated a clinical pattern of in-hospital consultations for various movement disorders in a tertiary care university hospital.

Methods: Over two years, a total of 202 patients (70.7 ± 11.8 years of age) presenting with movement disorders referred to movement disorder specialists were investigated.

Results: The main symptoms referred by nonneurologists were tremor (56.9%), parkinsonism (16.8%), and gait disturbance (8.9%). The most frequent diagnostic category was toxic/metabolic-caused movement disorder (T/MCMD) (35%) with regard to medications, followed by Parkinson's disease (PD) (16%). Regarding the mode of onset, T/MCMD was the leading cause for acute (68%) and subacute onset (46%), while PD was the leading disorder (31%) for chronic onset.

Conclusion: The current study showed a characteristic pattern of inpatients presenting with movement disorders. Furthermore, our findings highlighted the clinical significance of drug use or metabolic problems for treating this patient population.
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http://dx.doi.org/10.14802/jmd.18040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369378PMC
January 2019

When sex doesn't sell to men: mortality salience, disgust and the appeal of products and advertisements featuring sexualized women.

Motiv Emot 2017 18;41(4):478-491. Epub 2017 May 18.

Dongkuk Business School, Dongguk University, Seoul, Republic of Korea.

Although men typically hold favorable views of advertisements featuring female sexuality, from a Terror Management Theory perspective, this should be less the case when thoughts of human mortality are salient. Two experiments conducted in South Korea supported this hypothesis across a variety of products (e.g., perfume and vodka). Men became more negative towards advertisements featuring female sexuality, and had reduced purchase intentions for those products, after thinking about their own mortality. Study 2 found that these effects were mediated by heightened disgust. Mortality thoughts did not impact women in either study. These findings uniquely demonstrate that thoughts of death interact with female sex-appeal to influence men's consumer choices, and that disgust mediates these processes. Implications for the role of emotion, and cultural differences, in terror management, for attitudes toward female sexuality, and for marketing strategies are discussed.
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http://dx.doi.org/10.1007/s11031-017-9615-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5509837PMC
May 2017

The Moderating Effects of Self-Esteem and Self-Efficacy on Responses to Graphic Health Warnings on Cigarette Packages: A Comparison of Smokers and Nonsmokers.

Health Commun 2018 08 16;33(8):1013-1019. Epub 2017 Jun 16.

d College of Pharmacy , Dongguk University.

Do graphic pictorial health warnings (GPHWs) on cigarette packaging work better for some people than others? According to the Extended Parallel Process Model (EPPM), fear appeals should heighten positive change only if a person believes he or she is capable of change (i.e., self-efficacy). We exposed 242 smokers and 241 nonsmokers (aged 18-29) in the Republic of Korea to either a GPHW or a text-only warning in a between-subjects experiment. Results indicated that the GPHW increased intentions and motivations to quit smoking (for smokers) and intentions and motivations to not start smoking (for nonsmokers). However, these effects were moderated by self-efficacy related to quitting or not starting smoking. For smokers, a GPHW was especially effective in increasing desires and intentions to quit for people high in self-efficacy and high in self-esteem. However, for nonsmokers, a GPHW was effective only when self-efficacy was high, regardless of self-esteem level. For smokers and nonsmokers, results were mediated by heightened perceived health estimation. Implications for understanding the effectiveness of warning labels on cigarettes, for the introduction of GPHWs in the Republic of Korea, and for the Extended Parallel Process Model, are discussed.
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http://dx.doi.org/10.1080/10410236.2017.1331186DOI Listing
August 2018

Comparison of motor and non-motor features between essential tremor and tremor dominant Parkinson's disease.

J Neurol Sci 2016 Feb 10;361:34-8. Epub 2015 Dec 10.

Department of Neurology and Parkinson's Disease Centre, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea. Electronic address:

Background: Differential diagnosis of tremor disorders, including essential tremor (ET) and Parkinson's disease-tremor dominant type (PD-TDT), requires further investigation. Therefore, the current study aimed to compare non-motor and tremor features in order to differentiate between ET and PD-TDT.

Methods: Twenty-eight patients with classic ET and 24 patients with typical PD-TDT were retrospectively enrolled in a multi-stage investigation process. Tremor features including surface electromyogram (EMG) were analyzed in detail. For non-motor symptom analyses, the global cognition test, frontal function test, and non-motor symptoms scale (NMSS) were administered, in addition to collecting patient history data.

Results: Patients with PD-TDT presented with more asymmetric tremor, whereas patients with ET presented with more symmetric tremor. Leg tremor was observed only in patients with PD-TDT. Surface EMG analyses of arm tremor demonstrated considerable overlaps in tremor type, tremor frequency, and contractive patterns. However, patients with PD-TDT were significantly more likely to exhibit resting tremor, and experienced alternative contraction patterns only for kinetic tremor, which was in contrast to patients with ET. For non-motor symptom analyses, patients with PD-TDT had more non-motor symptoms compared to patients with ET (mean=5.0 vs. 2.6; P=0.002). Specifically, patients with PD-TDT exhibited higher frequencies of hyposmia, REM sleep behavior disorder (RBD)-like symptom, urinary frequency, and memory disturbance. Age- and gender- matched analyses for the severity of NMSS scores did not indicate significant differences. However, patients with PD-TDT displayed slightly lower scores of frontal function test compared to patients with ET.

Conclusions: Careful and detailed evaluations of both tremor features and non-motor symptoms are required in order to distinguish between ET and PD-TDT.
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http://dx.doi.org/10.1016/j.jns.2015.12.016DOI Listing
February 2016

Nonmotor symptoms in essential tremor: Comparison with Parkinson's disease and normal control.

J Neurol Sci 2015 Feb 13;349(1-2):168-73. Epub 2015 Jan 13.

Department of Neurology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea. Electronic address:

Background: Recently, the definition of essential tremor (ET) has evolved to have two different meanings. One refers to classic ET, a benign mono-symptomatic disorder, and the other refers to a heterogeneous neurodegenerative disorder. The aim of this study was to categorize nonmotor symptoms according to ET phenotype, and compare them, along with autonomic function, in people with Parkinson's disease (PD) and normal controls.

Methods: We divided patients with ET into 3 subtypes according to their motor features: 23 Pure-ET, 25 Cerebellar-ET, and 12 Parkinsonism-ET. Comparisons were made between 30 PD subjects and 22 normal controls, and 60 subjects with ET. The following assessments were conducted: the Nonmotor Symptoms Scale, the Mini-Mental State Exam, Montreal Cognitive Assessment, the Montgomery-Asberg Depression Rating Scale, Neuropsychiatric Inventory Questionnaire, Beck Anxiety Inventory, the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and the Scales for Outcomes in Parkinson's Disease-Autonomic.

Results: There were significant differences in the Nonmotor Symptoms Scale total scores of the ET, PD, and control groups (ET: 25.500 ± 2.346; PD: 27.960 ± 3.267;

Control: 3.328 ± 3.796.). There were no significant differences in terms of each ET phenotype. ET patients had significant cognitive dysfunction, neuropsychiatric problems including depression and have complained about significant autonomic dysfunction and excessive daytime somnolence compared to normal controls.

Conclusions: Patients with ET have several nonmotor symptoms similar to those of patients with PD, which have a similar impact on their quality of life. Therefore, nonmotor symptoms should be considered in the clinical evaluation and management of ET.
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http://dx.doi.org/10.1016/j.jns.2015.01.012DOI Listing
February 2015

Nonmotor Symptoms and Cognitive Decline in de novo Parkinson's Disease.

Can J Neurol Sci 2014 Sep;41(5):597-602

1Department of Neurology and Parkinson's Disease Centre,Korea University Guro Hospital,Korea University College of Medicine,Seoul,Korea.

Background: Cognitive impairments are common in Parkinson's disease (PD). Despite its clinical importance, the development of dementia is still difficult to predict. In this study, we investigated the possible associations between non-motor symptoms and the risk of developing dementia within a 2-year observation period in PD.

Methods: A total of 80 patients with PD participated in this study. Nonmotor symptoms (the Nonmotor Symptoms Questionnaire), PD status (Unified Parkinson's Disease Rating Scale), depression (Geriatric d Depression Scale or Montgomery-Asberg Depression Scale), stereopsis and severity of nonmotor symptoms (Non-motor symptoms scale) were assessed. Global cognitive function (Mini-Mental State Examination) were evaluated at baseline and 2 years later.

Results: Presence of depression, vivid dreaming, REM sleep behavior disorders, hyposmia, abnormal stereopsis, non-smoking and postural instability/ gait disturbance phenotype were associated with a significantly more rapid decline of Mini-Mental State Examination. Logistic regression analyses demonstrated that depression (odds ratio=13.895), abnormal stereopsis (odds ratio=10.729), vivid dreaming (odds ratio=4.16), REM sleep behavior disorders (odds ratio=5.353) and hyposmia (odds ratio=4.911) were significant independent predictors of dementia risk within 2 years. Postural instability/ gait disturbance phenotype and age >62 years were also independent predictors of dementia risk (odd ratio=38.333, odds ratio=10.625).

Conclusions: We suggest that depression, vivid dreaming, REM sleep behavior disorders, hyposmia and abnormal stereopsis are closely associated with cognitive decline, and that presence of these nonmotor symptoms predict the subsequent development of Parkinson's disease dementia.
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http://dx.doi.org/10.1017/cjn.2014.3DOI Listing
September 2014

Histologic Findings and Inflammatory Reactions After Long-term Colonization of Helicobacter felis in C57BL/6 Mice.

J Cancer Prev 2014 Sep;19(3):224-30

Departments of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Korea.

Background: The Helicobacter felis (H. felis) mouse model has been developed for the research regarding pathogenesis of chronic gastritis and gastric cancer. The aim of this study was to investigate long-term H. felis colonization in the stomachs of C57BL/6 mice and subsequent histologic findings and inflammatory reactions including pro-inflammatory cytokines.

Methods: Twenty-three female C57BL/6 mice at 4 weeks of age were gavaged with H. felis, and 13 control mice served as vehicle only. The mice were sacrificed at 4, 24, and 52 weeks after inoculation. The infection status and degree of inflammation were determined by culture and histopathology. The level of gastric mucosal myeloperoxidase (MPO), tumor necrosis factor alpha (TNF-α), and interleukin-1beta (IL-1β) were measured by ELISA.

Results: The overall infection rate was 100%, as determined by the culture and histology. At 4, 24, and 52 weeks, the neutrophil and monocyte scores were significantly higher in infected mice than in control mice. At 24 weeks after inoculation, most of the infected mice showed mucosal atrophy with or without metaplasia, and a few showed focal dysplasia. Adenocarcinoma was observed in one mouse at 52 week post-infection. Gastric mucosal MPO and IL-1β levels were significantly higher in infected mice than those in control mice at 24 and 52 weeks. However, the expression of gastric mucosal TNF-α was not significantly different between the infected and control mice at any time-point.

Conclusions: Long-term H. felis-infection in C57BL/6 mice provoked a severe inflammatory reaction and it progressed into atrophy, metaplasia, dysplasia and cancer. IL-1β might play an important role in the inflammatory response of mice to Helicobacter species.
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http://dx.doi.org/10.15430/JCP.2014.19.3.224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4189513PMC
September 2014

A practical method for the detection of freezing of gait in patients with Parkinson's disease.

Clin Interv Aging 2014 8;9:1709-19. Epub 2014 Oct 8.

Department of Computer Engineering, Konkuk University, Chungju, Korea.

Purpose: Freezing of gait (FOG), increasing the fall risk and limiting the quality of life, is common at the advanced stage of Parkinson's disease, typically in old ages. A simple and unobtrusive FOG detection system with a small calculation load would make a fast presentation of on-demand cueing possible. The purpose of this study was to find a practical FOG detection system.

Patients And Methods: A sole-mounted sensor system was developed for an unobtrusive measurement of acceleration during gait. Twenty patients with Parkinson's disease participated in this study. A simple and fast time-domain method for the FOG detection was suggested and compared with the conventional frequency-domain method. The parameters used in the FOG detection were optimized for each patient.

Results: The calculation load was 1,154 times less in the time-domain method than the conventional method, and the FOG detection performance was comparable between the two domains (P=0.79) and depended on the window length (P<0.01) and dimension of sensor information (P=0.03).

Conclusion: A minimally constraining sole-mounted sensor system was developed, and the suggested time-domain method showed comparable FOG detection performance to that of the conventional frequency-domain method. Three-dimensional sensor information and 3-4-second window length were desirable. The suggested system is expected to have more practical clinical applications.
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http://dx.doi.org/10.2147/CIA.S69773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4199977PMC
April 2015

Is reduced arm and leg swing in Parkinson's disease associated with rigidity or bradykinesia?

J Neurol Sci 2014 Jun 27;341(1-2):32-5. Epub 2014 Mar 27.

Department of Neurology and Parkinson's Disease Centre, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea. Electronic address:

Background And Purpose: Arm and leg swings during gait are reduced and asymmetric in Parkinson's disease (PD). Although rigidity and bradykinesia are interconnected with each other, and related with gait hypokinesia including arm and leg swing alteration, it remains uncertain which factor is more responsible for the decrease of arm and leg swings. The study aimed to uncover which factor between rigidity and bradykinesia is more associated with the reduction of arm and leg swings during gait.

Methods: Patients with PD were selected and divided into a concordance group (21 patients) representing a match of both symptoms and a discordance group (nineteen patients) exhibiting a mismatch of pronounced rigidity and bradykinesia. Visual inspections of video clips for asymmetric features of gait and posture including arm swing, leg swing, shoulder position, external foot rotation were analyzed and accessed by two independent neurologists blindly.

Results: The side of more pronounced rigidity was significantly and moderately related with the side of more decreased arm and leg swings (p<0.001, κ=0.592 in arm swing; p=0.011, κ=0.432 in leg swing, respectively), but the side of more dominant bradykinesia was associated with neither arm nor leg swing asymmetry (p=1, κ=0.014 in arm swing; p=1, κ=-0.036 in leg swing). In addition, asymmetric posturing including shoulder position and a laterally rotated foot showed no relationship with rigidity or bradykinesia.

Conclusion: The reduction of arm and leg swings during gait in PD was associated with rigidity, but not with bradykinesia.
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http://dx.doi.org/10.1016/j.jns.2014.03.041DOI Listing
June 2014

Differential diagnosis of parkinsonism with visual inspection of posture and gait in the early stage.

Gait Posture 2014 Apr 15;39(4):1138-41. Epub 2014 Jan 15.

Department of Neurology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea. Electronic address:

Background: Parkinson's disease (PD) differs from atypical parkinsonism in many clinical aspects. Principally, posture and gait are distinct features in the early stages of the disease; thus, these differences can be helpful in differential diagnosis.

Methods: We analyzed videos of patients with PD or atypical parkinsonism. A total of 76 patients with early PD (n=56) or atypical parkinsonism (n=20) were included. Items related to posture and gait were classified into three categories (standing, gait and associated symptoms) and each sub-item was analyzed.

Results: Asymmetric arm-swing (p=0.004) and accompanying tremor (p=0.016) were significant indicators of early-stage PD. Staggering gait (p=0.007) and en-bloc turning (p=0.026) were more common in atypical parkinsonism. Characteristics with a high odds-ratio for atypical parkinsonism were en-bloc turning (β=8.475, p=0.032) and normal arm-swing (β=14.6084, p=0.036).

Conclusions: Visual inspection of gait and posture provides reliable clues in the differential diagnosis of parkinsonism.
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http://dx.doi.org/10.1016/j.gaitpost.2014.01.004DOI Listing
April 2014

The devil is in the specificity: the negative effect of prediction specificity on prediction accuracy.

Psychol Sci 2013 Jul 9;24(7):1164-70. Epub 2013 May 9.

Korea University Business School, Anam-dong 5-1, Seongbuk-Ku, Seoul 136-701, Republic of Korea.

In the research reported here, we proposed and demonstrated the prediction-specificity effect, which states that people's prediction of the general outcome of an event (e.g., the winner of a soccer match) is less accurate when the prediction question is framed in a more specific manner (e.g., guessing the score) rather than in a less specific manner (e.g., guessing the winner). We demonstrated this effect by examining people's predictions on actual sports games both in field and laboratory studies. In Study 1, the analysis of 19 billion bets from a commercial sports-betting business provided evidence for the effect of prediction specificity. This effect was replicated in three controlled laboratory studies, in which participants predicted the outcomes of a series of soccer matches. Furthermore, the negative effect of prediction specificity was mediated by participants' underweighting of important holistic information during decision making.
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http://dx.doi.org/10.1177/0956797612468760DOI Listing
July 2013

The interrelationship between non-motor symptoms in Atypical Parkinsonism.

J Neurol Sci 2013 Apr 18;327(1-2):15-21. Epub 2013 Feb 18.

Department of Neurology, Korea University College of Medicine, Seoul, Republic of Korea.

Background: Atypical Parkinsonism is less common and has more severe symptoms than Parkinson's disease (PD). Little is known about the non-motor symptom (NMS) characteristics of multiple systemic atrophy (MSA) or progressive supranuclear palsy (PSP). We report the interrelationship of NMS in MSA, PSP, and PD.

Methods: We studied 117 cases of PD and 57 of Atypical Parkinsonism. Out of the 57 patients, 31 had multiple systemic atrophy parkinsonian subtype (MSA-P), 14 had multiple systemic atrophy cerebellar dysfunction subtype (MSA-C), and 12 had PSP. We assessed the condition of the patients using the United Parkinson's Disease Rating Scale part III (UPDRS-III), the modified Hoehn & Yahr scale (H&Y), the non-motor symptom scale (NMSS), and the Parkinson's Disease Questionnaire (PDQ-39).

Results: In Atypical Parkinsonism, the NMSS scores significantly correlated with PDQ-39 scores, but not with UPDRS-III. In the MSA-P group, the mood/cognitive domain significantly correlated with both the urinary and sleep/fatigue domains. In the MSA-C group, the sleep/fatigue domain correlated with the mood/cognition and cardiovascular domains. Finally, in the PSP and PD groups, the attention/memory domain significantly correlated with the sleep/fatigue and mood/cognition domains.

Discussion: These results suggest that, with respect to cognitive function, dysautonomia and sleep/fatigue are detrimental factors in MSA and PSP, respectively.
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http://dx.doi.org/10.1016/j.jns.2013.01.034DOI Listing
April 2013

Fatty acid-binding protein 5 promotes cell proliferation and invasion in human intrahepatic cholangiocarcinoma.

Oncol Rep 2012 Oct 19;28(4):1283-92. Epub 2012 Jul 19.

Department of Surgery, Gyeongsang National University School of Medicine, Institute of Health Sciences, Gyeongsang National University Hospital, Jinju 660-751, Republic of Korea.

Intrahepatic cholangiocarcinoma (ICC) is a rare primary malignant liver tumor with an extremely poor prognosis. Recently its incidence has increased, however, little attention has been directed to factors related to its molecular carcinogenesis, including oncogenes, tumor suppressor genes and cell cycle-related proteins. ICC is generally characterized by strong proliferation, invasion and early metastasis. These biological behaviors of ICC, with respect to the genetic and molecular aspects, remain to be clarified. In this study, we performed a proteomic analysis to identify the proteomic alterations associated with carcinogenesis of ICC. Protein expression profiles of sixteen cases of ICC were compared with those of adjacent non-involved bile duct tissue. Among the 151 protein spots that showed a statistically significant expression difference (P<0.05), there were 50 spots with significantly increased intensity (3-fold increase) and 17 spots with decreased intensity (3-fold decrease) in cancerous tissues. Of these, increased expression of fatty acid-binding protein 5 (FABP5) was further confirmed by western blot analysis and immunohistochemical analysis. Immunohistochemical analysis of FABP5 expression in tumor specimens obtained from 43 patients with mass-forming (MF) type ICC showed a positive correlation of FABP5 immunoreactivity with tumor size (P=0.047), lymph node metastasis (P=0.013), angioinvasion (P=0.032) and staging (P=0.007). In addition, silencing FABP5 with short hairpin RNA (shRNA) suppressed cell proliferation and invasiveness in HuCCT1 cells, and conversely, overexpression of FABP5 in FABP5-negative Hep3B cells increased cell proliferation and invasiveness. Our study shows that FABP5 is significantly overexpressed in ICC combined lymph node metastasis and is involved in cell proliferation and invasion in vitro. Our data suggest that FABP5 may be associated with tumor progression in ICC.
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http://dx.doi.org/10.3892/or.2012.1922DOI Listing
October 2012

Biochemical characterization and preliminary X-ray crystallographic study of the domains of human ZBP1 bound to left-handed Z-DNA.

Biochim Biophys Acta 2006 Feb 18;1764(2):320-3. Epub 2006 Jan 18.

Department of Molecular Cell Biology, Center for Molecular Medicine, SBRI, Sungkyunkwan University School of Medicine, Suwon 440-746, Korea.

ZBP1 is involved in host responses against cellular stresses, including tumorigenesis and viral infection. Structurally, it harbors two copies of the Zalpha domain containing the Zalpha motif, at its N terminus. Here, we attempted to characterize the Z-DNA binding activities of two Zalpha domains in the human ZBP1, hZalpha(ZBP1) and hZbeta(ZBP1), using circular dichroism (CD). Our results indicated that both hZalpha(ZBP1) and hZbeta(ZBP1) are viable Z-DNA binders, and their binding activities are comparable to those of previously-established Zalpha domains. Additionally, we crystallized hZbeta(ZBP1) in a complex with Z-DNA, d(TCGCGCG)2. The crystal diffracted to 1.45 angstroms, and belongs to the P2(1)2(1)2(1) space group, with the unit-cell parameters: a = 29.53 angstroms, b = 58.25 angstroms, and c = 88.61 angstroms. The delineation of this structure will provide insight into the manner in which diverse Zalpha motifs recognize Z-DNA.
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http://dx.doi.org/10.1016/j.bbapap.2005.12.012DOI Listing
February 2006

Oxidation of thioredoxin reductase in HeLa cells stimulated with tumor necrosis factor-alpha.

FEBS Lett 2004 Jun;567(2-3):189-96

Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, Daegu 705-717, Republic of Korea.

Stimulation of cells with tumor necrosis factor-alpha (TNF-alpha) results in the increase in generation of H(2)O(2) in mitochondria that leads to apoptosis. The effect of H(2)O(2) produced by TNF-alpha on the redox status of selenocysteine (SeCys) residue essential for mitochondrial thioredoxin reductase (TrxR2) was investigated in HeLa cells. TNF-alpha caused accumulation of oxidized TrxR2 with a thioselenide bond. The conditional induction of SeCys-deficient TrxR2 resulted in the increased production of H(2)O(2) and apoptosis. These results suggest that the SeCys residue of TrxR2 plays a critical role in cell survival by serving as an electron donor for Trx-II and subsequent peroxiredoxin-III, which is a primary line of defense against H(2)O(2) in mitochondria.
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http://dx.doi.org/10.1016/j.febslet.2004.04.055DOI Listing
June 2004

The promoter of brain-specific angiogenesis inhibitor 1-associated protein 4 drives developmentally targeted transgene expression mainly in adult cerebral cortex and hippocampus.

FEBS Lett 2004 May;566(1-3):87-94

Medical Research Center for Gene Regulation, Chonnam National University Medical School, Hak-Dong 5, Dong-Ku, Kwangju 501-190, South Korea.

Restricting transgene expression to specific cell types and maintaining long-term expression are major goals for gene therapy. Previously, we cloned brain-specific angiogenesis inhibitor 1-associated protein 4 (BAI1-AP4), a novel brain-specific protein that interacts with BAI1, and found that it was developmentally upregulated in the adult brain. In this report, we isolated 5 kb of the 5' upstream sequence of the mouse BAI1-AP4 gene and analyzed its promoter activity. Functional analyses demonstrated that an Sp1 site was the enhancer, and the region containing the transcription initiation site and an AP2-binding site was the basal promoter. We examined the ability of the BAI1-AP4 promoter to drive adult brain-specific expression by using it to drive lacZ expression in transgenic (TG) mice. Northern blot analyses showed a unique pattern of beta-galactosidase expression in TG brain, peaking at 1 month after birth, like endogenous BAI1-AP4. Histological analyses demonstrated the same localization and developmental expression of beta-galactosidase and BAI1-AP4 in most neurons of the cerebral cortex and hippocampus. Our data indicate that TG mice carrying the BAI1-AP4 promoter could be a valuable model system for region-specific brain diseases.
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http://dx.doi.org/10.1016/j.febslet.2004.03.106DOI Listing
May 2004