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1.  Cochlear Implantation Using a Suprameatal Approach in a Case of Severely Contracted Mastoid Cavity 
Korean Journal of Audiology  2014;18(3):144-147.
Although cochlear implantation using posterior tympanotomy has been performed worldwide, other alternative approaches might be more beneficial and convenient in some selected cases. Of these, suprameatal approach was reported to be one of useful options in cases with narrow facial recess, anteriorly located facial nerve and an ossified cochlea. We describe a case of cochlear implantation using the modified suprameatal approach in a severely contracted mastoid cavity and suggest another indication of this approach.
PMCID: PMC4280758  PMID: 25558410
Cochlear implantation; Suprameatal approach; Mastoid
2.  A case of vulvar hematoma with rupture of pseudoaneurysm of pudendal artery 
Obstetrics & Gynecology Science  2014;57(2):168-171.
Vulvar hematomas are uncommon outside of the obstetric population and may be the result of trauma to the perineum. Vulvar hematomas most often present with low abdominal pain and urologic and neurologic symptoms. The vulva has rich vascularization that is supplied by the pudendal artery, a branch of the anterior division of the internal iliac artery. We describe a rare case of a 15-cm-sized vulvar hematoma with the suggested rupture of a pseudoaneurysm of the left pudendal artery without trauma injury. A 14-year-old girl presented with sudden pain and swelling in her left labium and was successfully treated with selective arterial embolization and surgical evacuation. We provide a literature review and discuss patient treatment and management strategies.
PMCID: PMC3965703  PMID: 24678493
Aneurysm, false; Hematoma; Vulvar
3.  Survey of controversial issues of end-of-life treatment decisions in Korea: similarities and discrepancies between healthcare professionals and the general public 
Critical Care  2013;17(5):R221.
End-of-life (EOL) treatment issues have recently gained societal attention after the Korean Supreme Court’s ruling that the presumed wishes of an elderly woman in a persistent vegetative state (PVS) should be honored. We tried to evaluate what Koreans thought about controversial issues regarding EOL treatments.
We surveyed Koreans with the following questions: 1) are ventilator-dependent PVS patients candidates for end-of life treatment decisions? 2) Is withholding and withdrawing EOL treatment the same thing? 3) In an unconscious, terminally ill patient, whose wishes are unknown, how should EOL decisions be made? 4) How should we settle disagreement amongst medical staff and the patient’s family on EOL decisions?
One thousand Koreans not working in healthcare and five hundred healthcare professionals responded to the survey. Fifty-seven percent of Koreans not working in healthcare and sixty seven percent of Korean healthcare professionals agreed that ventilator-dependent PVS patients are candidates for EOL treatment decisions. One quarter of all respondents regarded withholding and withdrawing EOL treatment as equal. Over 50% thought that EOL treatment decisions should be made through discussions between the physician and the patient’s family. For conflict resolution, 75% of Koreans not working in healthcare preferred direct settlement between the medical staff and the patient’s family while 55% of healthcare professionals preferred the hospital ethics committee.
Unsettled issues in Korea regarding EOL treatment decision include whether to include ventilator-dependent PVS patients as candidates of EOL treatment decision and how to sort out disagreements regarding EOL treatment decisions. Koreans viewed withholding and withdrawing EOL treatment issues differently.
PMCID: PMC4056664  PMID: 24093519
5.  Expression of keratin 20 and its clinicopathological significance in intrahepatic cholangiocarcinoma 
Oncology Letters  2012;4(3):534-540.
Although the expression of keratin 7 (K7) and K20 is considered to be a useful factor in the differential diagnosis of intrahepatic cholangiocarcinoma (ICC) and metastatic colorectal carcinoma (CRC) of the liver, a proportion of typical ICC retains K20 expression. The frequency and biological significance of K20 expression in ICC remains unclear. We analyzed the expression of K7, K19 and K20 in 66 surgically resected liver tumors consisting of 46 ICCs and 20 metastatic CRCs of the liver and 20 corresponding primary CRCs. In the 46 ICCs, K7, K19 and K20 were expressed in 40 (87%), 45 (98%) and 16 (35%) cases, respectively. K7, K19 and K20 were expressed in 1 (5%), 20 (100%) and 16 (80%) of the 20 primary CRCs and 2 (10%), 20 (100%) and 16 (80%) of the 20 metastatic CRCs, respectively. A combined K7/K20 profile was identified as a good predictor for differentiating ICC and metastatic CRC. K20 expression in ICC was significantly associated with male gender (P=0.034), hilar location (P=0.026), intraductal papillary type (P=0.006), intestinal phenotype (P<0.001) and MUC2 expression (P=0.008). Univariate analysis identified that poor patient survival was significantly associated with histological grade (P=0.020), invasion depth (P=0.005), lymph node metastasis (P=0.012), tumor stage (P=0.004) and vessel invasion (P=0.023). The tumor stage (P=0.002) was a poor independent prognostic indicator, while MUC6 expression (P=0.036) was a good independent prognostic indicator. The survival rate in patients with K20-positive ICC was lower compared to that of patients with K20-negative ICC, but was not statistically significant. Furthermore, the combined K7/K20 immunophenotype was identified to be useful for differentiating ICC and metastatic CRC. K20-positive ICC displays specific characteristics with regards to tumor location and histological subtype. Additionally, MUC6 expression in ICC is a good independent prognostic factor, while K20 expression is more often associated with aggressive biological behavior.
PMCID: PMC3439098  PMID: 22970052
keratin; cholangiocarcinoma; mucin; colorectal carcinoma
6.  Expression of peptidyl-prolyl isomerase PIN1 and its role in the pathogenesis of extrahepatic cholangiocarcinoma 
Oncology Letters  2013;6(5):1421-1426.
The phosphorylation of proteins on serine/threonine residues that immediately precede proline (pSer/Thr-Pro) is a key signaling mechanism by which cell cycle regulation and cell differentiation and proliferation occur. The peptidyl-prolyl isomerase PIN1-catalyzed conformational changes of the pSer/Thr-Pro motifs may have profound effects on the function of numerous oncogenic and cell signaling pathways. To date, no studies have examined the expression of PIN1 and its potential role in the pathogenesis of extrahepatic cholangiocarcinoma (ECC). Therefore, the present study performed an immunohistochemistry analysis of the expression of PIN1 in 67 cases of ECC and evaluated its association with clinicopathological factors. In addition, the role of PIN1 was examined using synthetic small interfering RNA (siRNA) to silence PIN1 gene expression in human CC RBE cells. Positive PIN1 expression was observed in 35 of the 67 (52.2%) ECC cases and was predominantly localized to the nucleus of the tumor cells. The immunoreactive score for PIN1 was significantly higher in the tumor cells (4.07±0.4) compared with the adjacent benign bile duct cells (1.19±0.4) (P<0.001). PIN1 expression was significantly correlated with tumor cell proliferation (Ki-67 labeling index; P=0.024). Silencing PIN1 expression using siRNA significantly decreased the proliferation, migration and invasion of the tumor cells. In conclusion, the results indicated that the expression of PIN1 may play a key role in the development and progression of ECC.
PMCID: PMC3813802  PMID: 24179535
extrahepatic cholangiocarcinoma; peptidyl-prolyl isomerase PIN1; phosphorylation
7.  Chaperone-like Activity of High-Mobility Group Box 1 Protein and Its Role in Reducing the Formation of Polyglutamine Aggregates 
High-mobility group box 1 protein (HMGB1), which mainly exists in the nucleus, has recently been shown to function as a sentinel molecule for viral nucleic acid sensing and an autophagy regulator in the cytoplasm. In this study, we studied the chaperone-like activity of HMGB1 and found that HMGB1 inhibited the chemically induced aggregation of insulin and lysozyme, as well as the heat-induced aggregation of citrate synthase. HMGB1 also restored the heat-induced suppression of cytoplasmic luciferase activity as a reporter protein in hamster lung fibroblast O23 cells with expression of HMGB1. Next, we demonstrated that HMGB1 inhibited the formation of aggregates and toxicity caused by expanded polyglutamine (polyQ), one of the main causes of Huntington disease. HMGB1 directly interacted with polyQ on immunofluorescence and coimmunoprecipitation assay, whereas the overexpression of HMGB1 or exogenous administration of recombinant HMGB1 protein remarkably reduced polyQ aggregates in SHSY5Y cells and hmgb1−/− mouse embryonic fibroblasts upon filter trap and immunofluorescence assay. Finally, overexpressed HMGB1 proteins in mouse embryonic primary striatal neurons also bound to polyQ and decreased the formation of polyQ aggregates. To this end, we have demonstrated that HMGB1 exhibits chaperone-like activity and a possible therapeutic candidate in polyQ disease.
PMCID: PMC3566580  PMID: 23303669
8.  Expression of Cortactin and Focal Adhesion Kinase in Colorectal Adenocarcinoma: Correlation with Clinicopathologic Parameters and Their Prognostic Implication 
Korean Journal of Pathology  2012;46(5):454-462.
Cortactin and focal adhesion kinase (FAK) are two important components among actin cross-linking proteins that play a central role in cell migration.
The aims of this study were to evaluate the expression of cortactin and FAK in normal colorectal mucosa and colorectal adenocarcinoma (CRC) using tissue microarray of 2 mm cores to correlate their expression with other clinicopathological factors and, investigate their prognostic significance.
Twenty (9%) and 24 cases (11%) of normal colorectal mucosa were immunoreactive for cortactin and FAK. In addition, 184 (84%) and 133 cases (61%) of CRCs were immunoreactive for cortactin and FAK, respectively. Cortactin expression was associated with histologic differentiation and FAK expression. Cortactin, but not FAK expression was also correlated with poor overall and relapse-free survival and served well as an independent prognostic factor for poor survival.
Cortactin expression, in association with FAK expression, may plays an important role in tumor progression. Furthermore, it may also be a satisfactory biomarker to predict tumor progression and survival in CRC patients.
PMCID: PMC3490120  PMID: 23136572
Colorectal neoplasms; Cortactin; Focal adhesion protein-tyrosine kinases; Immunohistochemistry
9.  Endovascular coiling versus neurosurgical clipping in patients with unruptured intracranial aneurysm: a systematic review 
BMC Neurology  2012;12:99.
To compare the effects of endovascular coiling and neurosurgical clipping in patients with unruptured intracranial aneurysm.
Sixteen electronic databases were searched for articles published between 1950 and July 2010 to compare clinical outcomes of clipping and coiling. Researchers reviewed all searched articles and extracted data independently. The quality of studies and evidence were evaluated using MINORS and GRADEprofiler, respectively. The odds ratio (OR) was calculated using the inverse variance meta-analysis method for each study outcome. To assess heterogeneity of ORs across cohorts, Cochran’s Q statistic and I2 were used.
Of 4160 studies, 24 were identified (n  =  31865). Clipping resulted in significantly higher disability using the Glasgow Outcome Scale (OR, 2.38; 95% CI, 1.33–4.26) and Modified Rankin Scale (OR, 2.83; 95% CI, 1.42–5.63) when compared with coiling. ORs for complications were also higher with clipping (ORs for neurological and cardiac complications were 1.94 with a 95% confidence interval [CI] of 1.09–3.47 and 2.51 with a 95% CI of 1.15–5.50). Clipping resulted in significantly greater disability in the short term (≤6 m)(OR on the Glasgow Outcome Scale, 2.72; 95% CI, 1.16–6.34), but not in the long term (>6 m)(OR for Glasgow Outcome Scale, 2.12; 95% CI, 0.93–4.84).
Coiling was a better procedure for treatment of unruptured intracranial aneurysm in terms of disability, complications, especially in the short term. Because of the limitations of the reviewed studies, further studies are required to support the present results.
PMCID: PMC3519507  PMID: 22998483
Unruptured intracranial aneurysm; Endovascular coiling; Neurosurgical clipping
10.  Polymorphisms in innate immunity genes and risk of childhood leukemia 
Human immunology  2010;71(7):727-730.
To evaluate whether candidate genes in innate immunity are associated with childhood leukemia, we conducted an association study with the 1,536 SNPs in 203 genes related to innate immunity.
Incident childhood leukemia cases (n=136) aged from 0 to 18 were recruited from three teaching hospitals in Seoul between 2003 and 2006. Non-cancer controls (n=140) were frequency-matched to cases by age and gender. The information on the characteristics of children and their parents were collected by trained interviewers using structured questionnaire. Candidate genes were selected based on SNP databases (CGAP and SNP500 database), and genotype assay was performed using GoldenGate (Illumina) oligonucleotide pool assay (OPA). False discovery rate (FDR), permutation test, and haplotype analyses were used to identify the SNP with significant association with childhood leukemia. Childhood leukemia risk was estimated as ORs and 95% CIs adjusted for age, gender and birth weight.
Fourteen SNPs in 13 genes (LMAN1, TLR4, STAT4, CCR9, MBP, ZP1, C8B, XDH, C7, C1QG, FGF2, LOC390183, and STAT6) were significantly associated with childhood leukemia risk (FDR p-values <0.05). In particular, LMAN1 rs1127220, TLR4 rs11536897, STAT4 rs13020076, CCR9 rs1471962, and MBP rs10514234 were significant in 5,000 permutation tests (Permutation p-value <0.05). The most significant association with childhood leukemia risk was for the LMAN1 rs1127220 that is in the protein-coding region, this finding was also supported by haplotype analysis.
A number of innate immunity related genes are associated with childhood leukemia, suggesting possible links between the innate immunity system and development of the childhood leukemia.
PMCID: PMC2967770  PMID: 20438785
Childhood Leukemia; Innate Immunity; Single Nucleotide Polymorphism
11.  Paternal smoking, genetic polymorphisms in CYP1A1 and childhood leukemia risk 
Leukemia research  2008;33(2):250-258.
We conducted a case–control study to evaluate the association between paternal smoking and childhood leukemia and to evaluate potential modification by polymorphisms in CYP1A1. Histologically confirmed childhood leukemia cases (n = 164) and non-cancer controls (n = 164) were recruited from three teaching hospitals in Seoul, Korea. Five single nucleotide polymorphisms in CYP1A1 (–17961T>C, –9893G>A, I462V, 1188C>T (*2A), and 11599C>G) were genotyped and haplotypes were estimated by the expectation-maximization method. We also conducted a meta-analysis of 12 studies that have reported the association between paternal smoking and childhood leukemia risk. Paternal smoking at home was associated with all leukemias (OR = 1.8, 95% CI = 1.1–2.8) and acute lymphoblastic leukemia (ALL) (2.0, 1.2–3.4). An increasing trend in risk was observed for pack-years smoked after birth (Ptrend = 0.06 and 0.02, respectively) and the number of smokers in the home during the child's life (Ptrend = 0.05 and 0.03, respectively). Among those without the CGACC haplotype, ALL risk was significantly increased by the father's smoking at home (2.8, 1.5–5.3) and the presence of at least one smoker in the home (2.3, 1.2–4.4), and the test for interaction was significant (Pinteraction = 0.03 and 0.02, respectively). The meta-analysis showed that overall paternal smoking (1.13, 1.04–1.24) and smoking before the pregnancy of the child (1.12, 1.04–1.21) were significantly associated with childhood leukemia risk. Our results suggest that paternal smoking is a risk factor for childhood leukemia and the effect may be modified by CYP1A1 genotype.
PMCID: PMC2787091  PMID: 18691756
Childhood leukemia; Paternal smoking; CYP1A1; Interaction; Haplotype
12.  Scabies in a 2-month-old Infant Successfully Treated with Lindane 
Annals of Dermatology  2009;21(2):200-202.
Diagnosis of scabies in young children can be challenging since the morphology and distribution of skin lesions may differ from adults. Therefore, clinicians should keep scabies in mind in their differential diagnosis in a child who presents with severe pruritic, polymorphic skin lesions. Regarding the treatment of scabies, the reported clinical experience with gamma benzene hexachloride (lindane) in young children is quite limited because of its neurotoxicity. However, a recent review suggests that lindane is an excellent alternative drug with minimal risk. We report the case of a 2-month-old male infant with pruritic, erythematous macules, papules, nodules, vesicles, and pustules from the top of the head to the tip of the toes. Initially, he was thought to have impetigo and antibiotics were prescribed. After obtaining a careful history and with the use of skin scraping, he was diagnosed with scabies. He was successfully treated with lindane with no adverse reactions.
PMCID: PMC2861204  PMID: 20523787
Infant; Lindane; Scabies
13.  Overdose Rate of Drugs Requiring Renal Dose Adjustment: Data Analysis of 4 Years Prescriptions at a Tertiary Teaching Hospital 
To determine the overdose rate of drugs that require renal dose adjustment and factors related with overdose.
Total of 23,635,210 records of prescriptions and laboratory data of inpatients at a tertiary teaching hospital for the period from January 2002 to December 2005.
A clinical data mart was constructed. A knowledge base containing dose adjusting information about 56 drugs was built. One day dose was compared to the reference dose adjusted to the patient’s renal function.
Considering the patient’s renal function, 5.3% of drug doses were excessive. The overdose rate in the patients with moderate to severe renal insufficiency was 28.2%. Only 25% of physicians were responsible for 50.6% of the overdoses. Of 56 drugs studied, 10 drugs, including ranitidine, amoxicillin, and piperacillin/tazobactam, were involved in 85.4% of the overdoses. The physicians with high overdose rate had patients with more impaired renal function (correlation coefficient = 0.192, P < .001). There were negative correlation between clinical experiences of physician and overdose rate (correlation coefficient = −0.221, P < .001) and workload of prescription (correlation coefficient = −0.446, P < .001), when excluding interns from the analyses. There was positive correlation between workload of prescription and overdose rate (correlation coefficient = 0.361, P < .001).
A clinical data mart was useful to analyze the vast amount of electronic hospital data. Drug overdose is quite common among inpatients with renal insufficiency. Only a few drugs are responsible for most of drug overdoses. The physicians’ clinical experience, workload of prescriptions, and patients’ renal function are correlated with drug overdose.
PMCID: PMC2359525  PMID: 18373140
adverse drug events; overdose; renal insufficiency; safety; knowledge base; data mart
14.  Development of Monoclonal Antibodies Against Human IRF-5 and Their Use in Identifying the Binding of IRF-5 to Nuclear Import Proteins Karyopherin-α1 and -β1 
Yonsei Medical Journal  2008;49(6):1023-1031.
IRF-5 is a direct transducer of virus-mediated and TLR-mediated signaling pathways for the expression of cytokines and chemokines which form homodimers or heterodimers with IRF-7. However, direct IRF-5-specific monoclonal antibodies (mAbs) are not available at present. These could be used to further evaluate the functions of IRF-5. In this study, we produced and characterized three mouse mAbs to human IRF-5. The binding of IRF-5 to nuclear import proteins was first identified using a mAb.
Materials and Methods
His-tagged human IRF-5 protein spanning amino acid residues 193-257 was used as an antigen and three mAbs were produced. The mAbs were tested with ELISA, Western blot analysis (WB), immunofluorescent staining (IF), and immunoprecipitation (IP). In addition, the nuclear import protein which carried phosphorylated IRF-5 was identified using one of these mAbs.
MAbs 5IRF8, 5IRF10 and 5IRF24 which reacted with the recombinant His-IRF-5193-257 protein were produced. All mAbs bound to human IRF-5, but not to IRF-3 or IRF-7. They could be used for WB, IF, and IP studies. The binding of phosphorylated IRF-5 to karyopherin-α1 and -β1 was also identified.
Human IRF-5-specific mAbs are produced for studying the immunologic roles related to IRF-5. Phosphorylated IRF-5 is transported to the nucleus by binding to nuclear import proteins karyopherin-α1 and -β1.
PMCID: PMC2628014  PMID: 19108028
Human IRF-5; monoclonal antibody; nuclear import protein; karyopherins
15.  Retrospective Evaluation of the Prescribing Behavior of Residents with respect to Nephrotoxic Drugs 
This study is a preliminary analysis of the prescription behavior of residents in a teaching hospital, with respect to nephrotoxic drugs during a 2-month period. The overdose rate was 3%. Only 5.1% of the doctors were responsible for 51% of the nephrotoxic drug overdoses.
PMCID: PMC1839520  PMID: 17249908
16.  An Architectural Framework for an Adverse Drug Event Surveillance System 
Much effort has focused on detecting as many adverse drug events (ADEs) as possible, as soon possible. An ADE surveillance system (ADESS) is a computerized surveillance system that detects ADEs automatically, by analyzing medication orders, laboratory results, and medical records. We propose a new ADESS architectural framework using the object-oriented component-based development (OOCBD) methodology to extract and analyze ADEs automatically, with a minimal server-side workload.
PMCID: PMC1839395  PMID: 17238619
17.  Identification of lipopolysaccharide-binding peptide regions within HMGB1 and their effects on subclinical endotoxemia in a mouse model 
European Journal of Immunology  2011;41(9):2753-2762.
Lipopolysaccharide (LPS) triggers deleterious systemic inflammatory responses when released into the circulation. LPS-binding protein (LBP) in the serum plays an important role in modifying LPS toxicity by facilitating its interaction with LPS signaling receptors, which are expressed on the surface of LPS-responsive cells. We have previously demonstrated that high mobility group box 1 (HMGB1) can bind to and transfer LPS, consequently increasing LPS-induced TNF-α production in human peripheral blood mononuclear cells (PBMCs). We report here on the identification of two LPS-binding domains within HMGB1. Furthermore, using 12 synthetic HMGB1 peptides, we define the LPS-binding regions within each domain. Among them, synthetic peptides HPep1 and HPep6, which are located in the A and B box domains of HMGB1, bind to the polysaccharide and lipid A moieties of LPS respectively. Both HPep1 and HPep6 peptides inhibited binding of LPS to LBP and HMGB1, LBP-mediated LPS transfer to CD14, and cellular uptake of LPS in RAW264.7 cells. These peptides also inhibited LPS-induced TNF-α release in human PBMCs and induced lower levels of TNF-α in the serum in a subclinical endotoxemia mouse model. These results indicate that HMGB1 has two LPS-binding peptide regions that can be utilized to design anti-sepsis or LPS-neutralizing therapeutics.
PMCID: PMC3193378  PMID: 21660935
Endotoxin shock; High mobility group box 1; Inflammation; Lipopolysaccharide

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