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1.  Prevalence of Anti-Ganglioside Antibodies and Their Clinical Correlates with Guillain-Barré Syndrome in Korea: A Nationwide Multicenter Study 
Background and Purpose
No previous studies have investigated the relationship between various anti-ganglioside antibodies and the clinical characteristics of Guillain-Barré syndrome (GBS) in Korea. The aim of this study was to determine the prevalence and types of anti-ganglioside antibodies in Korean GBS patients, and to identify their clinical significance.
Serum was collected from patients during the acute phase of GBS at 20 university-based hospitals in Korea. The clinical and laboratory findings were reviewed and compared with the detected types of anti-ganglioside antibody.
Among 119 patients, 60 were positive for immunoglobulin G (IgG) or immunoglobulin M antibodies against any type of ganglioside (50%). The most frequent type was IgG anti-GM1 antibody (47%), followed by IgG anti-GT1a (38%), IgG anti-GD1a (25%), and IgG anti-GQ1b (8%) antibodies. Anti-GM1-antibody positivity was strongly correlated with the presence of preceding gastrointestinal infection, absence of sensory symptoms or signs, and absence of cranial nerve involvement. Patients with anti-GD1a antibody were younger, predominantly male, and had more facial nerve involvement than the antibody-negative group. Anti-GT1a-antibody positivity was more frequently associated with bulbar weakness and was highly associated with ophthalmoplegia when coupled with the coexisting anti-GQ1b antibody. Despite the presence of clinical features of acute motor axonal neuropathy (AMAN), 68% of anti-GM1- or anti-GD1a-antibody-positive cases of GBS were diagnosed with acute inflammatory demyelinating polyradiculoneuropathy (AIDP) by a single electrophysiological study.
Anti-ganglioside antibodies were frequently found in the serum of Korean GBS patients, and each antibody was correlated strongly with the various clinical manifestations. Nevertheless, without an anti-ganglioside antibody assay, in Korea AMAN is frequently misdiagnosed as AIDP by single electrophysiological studies.
PMCID: PMC4017025  PMID: 24829594
Guillain-Barré syndrome; ganglioside; antibodies; Korea; acute motor axonal neuropathy
2.  Second Complete Remission of Relapsed Stage IV Non-Small Cell Lung Cancer Following Retreatment 
Non-small cell lung cancer (NSCLC) is the leading cause of cancer related deaths. Most patients were presented with advanced disease at the time of diagnosis. In advanced NSCLC, it is almost impossible to anticipate complete remission by using only cytotoxic chemotherapy or molecularly targeted agents. In our case, two patients were diagnosed as advanced NSCLC and received chemotherapy. They achieved complete response (CR). After finishing treatment, disease recurred. They were retreated with the same regimens and achieved second CR. Until now, they have received each regimen, continuously, and the CR state has been maintained.
PMCID: PMC3510290  PMID: 23227080
Carcinoma, Non-Small-Cell Lung; Remission Induction; Retreatment; Maintenance Chemotherapy
3.  Silver nanoparticles modify VEGF signaling pathway and mucus hypersecretion in allergic airway inflammation 
The anti-inflammatory action of silver nanoparticles (NPs) has been reported in a murine model of asthma in a previous study. But more specific mechanisms of silver NPs in an attenuation of allergic airway inflammation have not yet been established. Vascular and mucous changes are believed to contribute largely in pathophysiology in asthma. Among various factors related to vascular changes, vascular endothelial growth factor (VEGF) plays a pivotal role in vascular changes in asthma. Mucin proteins MUC5AC and MUC5B have been implicated as markers of goblet cell metaplasia in lung pathologies. The aim of this study was to investigate the effects of silver NPs on VEGF signaling pathways and mucus hypersecretion. Ovalbumin (OVA)-inhaled female BALBc mice were used to evaluate the role of silver NPs and the related molecular mechanisms in allergic airway disease. In this study, with an OVA-induced murine model of allergic airway disease, it was found that the increased levels of hypoxia-inducible factor (HIF)-1α, VEGF, phosphatidylinositol-3 kinase (PI3K) and phosphorylated-Akt levels, and mucous glycoprotein expression (Muc5ac) in lung tissues were substantially decreased by the administration of silver NPs. In summary, silver NPs substantially suppressed mucus hypersecretion and PI3K/HIF-1α/VEGF signaling pathway in an allergic airway inflammation.
PMCID: PMC3310409  PMID: 22457593
allergic airway disease; hypoxia inducible factor-1α; vascular endothelial growth factor
4.  Comparison on the Efficacy of Disinfectants Used in Automated Endoscope Reprocessors: PHMB-DBAC versus Orthophthalaldehyde 
Clinical Endoscopy  2011;44(2):109-115.
Since endoscopes are reusable apparatus classified as semicritical item, thorough reprocessing to achieve high-level disinfection is of utmost importance to prevent spread of infection. To improve disinfection efficacy and safety, disinfectants and endoscope reprocessors are continuously evolving. This study aimed to compare the efficacy of the combination of polyhexamethylenebiguanide hydrochloride-alkyldimethylbenzylammonium chloride (PHMB-DBAC) and orthophthalaldehyde (OPA) used respectively in ultrasonographic cleaning incorporated automated endoscope reprocessors: COOLENDO (APEX Korea) or OER-A (Olympus Optical).
A total of 86 flexible upper endoscopes were randomly reprocessed with either COOLENDO/PHMB-DBAC or OER-A/OPA. Culture samplings were done at two sites (endoscope tip and working channel) which were later incubated on blood agar plate. Bacterial colonies were counted and identified.
The culture-positive rate at the endoscope tip and working channel was 0% and 2.33% for COOLENDO/PHMB-DBAC and 4.65% and 0% for OER-A/OPA. Staphylococcus hominis was cultured from one endoscope reprocessed with COOLENDO/PHMB-DBAC and Pseudomonas putida was isolated from two endoscopes reprocessed with OER-A/OPA.
The reprocessing efficacy of COOLENDO/PHMB-DBAC was non-inferior to that of OER-A/OPA (p=0.032; confidence interval, -0.042 to 0.042). During the study period, significant side effect of PHMB-DBAC was not observed.
PMCID: PMC3363059  PMID: 22741121
Endoscope reprocessing; Disinfectants; High-level disinfection
6.  Progression-Free Survival: An Important Prognostic Marker for Long-Term Survival of Small Cell Lung Cancer 
Small cell lung cancer (SCLC) is an extremely aggressive tumor with a poor clinical course. Although many efforts have been made to improve patients' survival rates, patients who survive longer than 2 years after chemotherapy are still very rare. We examined the baseline characteristics of patients with long-term survival rates in order to identify the prognostic factors for overall survivals.
A total of 242 patients with cytologically or histologically diagnosed SCLC were enrolled into this study. The patients were categorized into long- and short-term survival groups by using a survival cut-off of 2 years after diagnosis. Cox's analyses were performed to identify the independent factors.
The mean patient age was 65.66 years, and 85.5% were males; among the patients, 61 of them (25.2%) survived longer than 2 years. In the multivariate analyses, CRP (hazard ratio [HR], 2.75; 95% confidence interval [CI], 1.25-6.06; p=0.012), TNM staging (HR, 3.29; 95% CI, 1.59-6.80; p=0.001), and progression-free survival (PFS) (HR, 11.14; 95% CI, 2.98-41.73; p<0.001) were independent prognostic markers for poor survival rates.
In addition to other well-known prognostic factors, this study discovered relationships between the long-term survival rates and serum CRP levels, TNM staging, and PFS. In situations with unfavorable conditions, the PFS would be particularly helpful for managing SCLC patients.
PMCID: PMC4050069  PMID: 24920948
Small Cell Lung Carcinoma; Prognosis; Disease-Free Survival
7.  Colonic lipoma covered by hyperplastic epithelium: Case report 
Colonic lipomas are submucosal nonepithelial tumors covered by intact or eroded mucosa. In rare cases, alterations in the mucosa covering a lipoma include hyperplasia, adenoma, atrophy, ulceration, and necrosis. Here, we report a case of a colonic lipoma covered by hyperplastic epithelium in a 68-year-old woman. Based on the colonoscopy findings, a snare polypectomy was performed for a presumptive diagnosis of an epithelial lesion; however, the histological examination revealed a colonic submucosal lipoma with overlying hyperplastic epithelium.
PMCID: PMC3845912  PMID: 24303482
Lipoma; Colonic lipomas; Hyperplastic; Colonoscopy
8.  The Appropriateness of the Length of Insulin Needles Based on Determination of Skin and Subcutaneous Fat Thickness in the Abdomen and Upper Arm in Patients with Type 2 Diabetes 
Diabetes & Metabolism Journal  2014;38(2):120-133.
Longer needle and complicated insulin injection technique such as injecting at a 45-degree angle and making skinfolds may decrease patient compliance to insulin injection therapy. In this light, shorter insulin needles have been recently developed. However, it is necessary to ascertain that such shorter needles are appropriate for Korean patients with diabetes as well.
First, the diverse demographic and diabetic features of 156 Korean adults with diabetes were collected by a questionnaire and a device unit of body fat measurement. The skin and subcutaneous fat thicknesses of each subject were measured by Ultrasound device with a 7- to 12-MHz probe. Data were analyzed using analysis of variance and multiple linear regression.
The mean skin thickness was 2.29±0.37 mm in the abdomen and 2.00±0.34 mm in the upper arms, and the mean subcutaneous fat thickness was to 10.15±6.54 mm in the abdomen and 5.50±2.68 mm in the upper arms. Our analysis showed that the factors affecting the skin thickness of the abdomen and upper arms were gender and body mass index (BMI), whereas the factors influencing the subcutaneous fat thickness in the abdomen were gender and BMI, and the factors influencing the subcutaneous fat thickness in the upper arms were gender, BMI, and age. Insulin fluids may not appear to be intradermally injected into the abdomen and upper arms at any needle lengths. The risk of intramuscular injection is likely to increase with longer insulin needles and lower BMI.
It is recommended to fully inform the patients about the lengths of needles for insulin injections. As for the recommended needle length, the findings of this study indicate that needles as short as 4 mm are sufficient to deliver insulin for Korean patients with diabetes.
PMCID: PMC4021299  PMID: 24851206
Diabetes mellitus; Insulin; Needles; Skin; Subcutaneous fat; Thickness
9.  Clinical Outcomes of Local Excision Following Preoperative Chemoradiotherapy for Locally Advanced Rectal Cancer 
To evaluate the treatment outcomes of local excision following preoperative chemoradiotherapy in patients with locally advanced rectal cancer who have not undergone radical surgery for any reason.
Materials and Methods
The data of 27 patients with locally advanced rectal cancer who underwent preoperative chemoradiotherapy followed by local excision were analyzed retrospectively. The primary endpoint was the 5-year relapse-free survival rate, and the secondary endpoint was the pattern of recurrence.
The median follow-up time was 81.8 months (range, 28.6 to 138.5 months). The 5-year local relapse-free survival (LRFS), distant metastasis-free survival (DMFS), relapse-free survival (RFS), and overall survival (OS) were 88.9%, 81.1%, 77.8%, and 85.0%, respectively. Six (22%) patients developed treatment failure; one (4%) patient had local recurrence only, three (11%) patients had distant recurrence only, and two (7%) patients had both. The 5-year LRFS, DMFS, RFS, and OS for patients with ypT0-1 compared with ypT2-3 were 94.1% vs. 77.8% (p=0.244), 94.1% vs. 55.6% (p=0.016), 88.2% vs. 55.6% (p=0.051), and 94.1% vs. 66.7% (p=0.073), respectively.
Local excision following preoperative chemoradiotherapy may be an alternative treatment for highly selected patients with locally advanced rectal cancer who have achieved ypT0-1 after preoperative chemoradiotherapy.
PMCID: PMC4022824  PMID: 24851107
Rectal neoplasms; Local excision; Preoperative chemoradiotherapy; Survival
10.  Boerhaave’s syndrome during bowel preparation with polyethylene glycol in a patient with postpolypectomy bleeding 
Boerhaave’s syndrome is spontaneous rupture of the esophagus, a rare condition with high mortality that occurs most often after forceful vomiting. Polyethylene glycol (PEG) solution is the most common preparation used for colonoscopy. Since large volumes have to be ingested, PEG may induce severe vomiting or retching. However, Boerhaave’s syndrome has rarely been reported as a potential problem related to PEG solution. We report a case of spontaneous esophageal rupture due to violent vomiting during bowel preparation with PEG solution in a patient with postpolypectomy bleeding.
PMCID: PMC3653029  PMID: 23678383
Esophageal perforation; Colonoscopy; Polyethylene glycols
11.  Interleukin-33 in the Human Placenta 
Interleukin-33 (IL-33) is the newest member of the IL-1 cytokine family, a group of key regulators of inflammation. The purpose of this study was to determine whether IL-33 is expressed in the human placenta and to investigate its expression in the context of acute and chronic chorioamnionitis.
Placental tissues were obtained from five groups of patients: (1) normal pregnancy at term without labor (n=10); (2) normal pregnancy at term in labor (n=10); (3) preterm labor without inflammation (n=10); (4) preterm labor with acute chorioamnionitis (n=10); and (5) preterm labor with chronic chorioamnionitis (n=10). Immunostaining was performed to determine IL-33 protein expression patterns in the placental disk, chorioamniotic membranes, and umbilical cord. mRNA expression of IL-33 and its receptor IL1RL1 (ST2) was measured in primary amnion epithelial and mesenchymal cells (AECs and AMCs, n=4) and human umbilical vein endothelial cells (HUVECs, n=4) treated with IL-1β (1ng/ml and 10ng/ml) and CXCL10 (0.5ng/ml and 1ng/ml or 5ng/ml).
1) Nuclear IL-33 expression was found in endothelial and smooth muscle cells in the placenta, chorioamniotic membranes, and umbilical cord; 2) IL-33 was detected in the nucleus of CD14+ macrophages in the chorioamniotic membranes, chorionic plate, and umbilical cord, and in the cytoplasm of myofibroblasts in the Wharton’s jelly; 3) acute (but not chronic) chorioamnionitis was associated with the presence of IL-33+ macrophages in the chorioamniotic membranes and umbilical cord; 4) expression of IL-33 or IL1RL1 (ST2) mRNA in AECs was undetectable; 5) IL-33 mRNA expression increased in AMCs and HUVECs after IL-1β treatment but did not change with CXCL10 treatment; and 6) IL1RL1 (ST2) expression decreased in AMCs and increased in HUVECs after IL-1β but not CXCL10 treatment.
IL-33 is expressed in the nucleus of placental endothelial cells, CD14+ macrophages, and myofibroblasts in the Wharton’s jelly. IL-1β can induce the expression of IL-33 and its receptor. Protein expression of IL-33 is detectable in macrophages of the chorioamniotic membranes in acute (but not chronic) chorioamnionitis.
PMCID: PMC3563729  PMID: 23039129
alarmin; chorioamnionitis; interleukin-1 family; pregnancy; preterm birth; preterm labor
12.  Association between Bone Mineral Density and Sleep Duration in the Korean Elderly Population 
An association between sleep duration and a wide spectrum of diseases has been reported, but little is known about its relationship with bone mineral density (BMD). Previously conducted studies in Korea and abroad have reported results that are controversial. The present study sought to assess whether sleep duration can be considered an independent risk factor of osteoporosis.
We included participants over the age of 60 years with data on self-reported habitual sleep duration and BMD measured with dual X-ray absorptiometry. Comprehensive data on the study sample was obtained from the Korea National Health and Nutritional Survey performed from 2008 to 2010. Sex-stratified multiple regression analyses were conducted with adjustments for possible confounding factors.
There was a significant inverse dose-dependent association between sleep duration and BMD measured at total hip, femur neck, and lumbar spine for women and total hip and femur neck for men. Sex-stratified regression analyses adjusted for age and body mass index revealed that sleep duration had a negative correlation with BMD at total hip and femoral neck for both women (β = -0.0048; P = 0.0172 for total hip, β = -0.0037; P = 0.0303 for femur neck) and men (β = -0.0057; P = 0.0218 for total hip, β = -0.0057; P = 0.0143 for femur neck). For women, the significance remained after further adjustment of confounding variables.
Prolonged sleep duration appears to have a significant association with lower total hip and femur neck BMD in elderly women but not in elderly men.
PMCID: PMC3978190  PMID: 24724004
Sleep Duration; Bone Density; Osteoporosis; Photon Absorptiometry; Koreans; Elderly
13.  Assessing the Diverse Functions of BAK1 and Its Homologs in Arabidopsis, beyond BR Signaling and PTI Responses 
Molecules and Cells  2012;35(1):7-16.
Plants possess a variety of extracellular leucine-rich repeats receptor-like kinases (LRR-RLKs) to coordinate developmental programs with responses to environmental changes. Out of sixteen families of LRR-RLKs in Arabidopsis, the LRR-RLKII family consists of fourteen individual members, including five Arabidopsis thaliana somatic embryogenesis receptor kinases (AtSERKs). BAK1/AtSERK3 was first identified as a dual co-receptor of BRI1 and FLS2, mediating BR signaling and pathogen-associated molecular pattern (PAMP) triggered immunity (PTI), respectively. Since its identification, many researchers have attempted to elucidate the phosphorylation mechanisms between receptor complexes and identify additional components that interact with receptor complexes to transduce the signaling downstream. Relatively detailed early events in complex formation, phosphorylation sites on the BRI1/BAK1 complex and BAK1-interacting proteins, such as BIK1 and PUB13, have been identified. Small receptor complexes consisting of BAK1 and BIR1 or BAK1 and AtSERK4 regulate cell death during steady state conditions. Moreover, the redundant and distinct functions of AtSERK proteins and other members of the LRR-RLKII family have been revealed. This review focuses on the integration of the information from the most recent studies concerning BAK1 and its homologs.
PMCID: PMC3887853  PMID: 23269431
AtSERK; BAK1; BAK1-interacting proteins; BR signaling; cell death; plant immunity
14.  Prognostic significance of gelsolin and MMP12 in Langerhans cell histiocytosis 
The Korean Journal of Hematology  2012;47(4):267-272.
Gelsolin and matrix metalloproteinase 12 (MMP12) expression has been reported in Langerhans cell histiocytosis (LCH), but the clinical significance of this expression is unknown. We investigated the associations of these proteins with clinical manifestations in patients diagnosed with LCH.
We performed a retrospective analysis of clinical data from patients diagnosed with LCH and followed up between 1998 and 2008. Available formalin-fixed, paraffin-embedded specimens were used for gelsolin and MMP12 immunohistochemical staining. We analyzed the expression levels of these proteins and their associations with LCH clinical features.
Specimens from 36 patients (20 males, 16 females) with a diagnosis of LCH based on CD1a positivity with clinical manifestations were available for immunohistochemical staining. Median patient age was 62 months (range, 5 to 207). The expression of gelsolin varied; it was high in 17 patients (47.2%), low in 11 patients (30.6%), and absent in 8 patients (22.2%). The high gelsolin expression group had a higher tendency for multi-organ and risk organ involvement, although the trend was not statistically significant. MMP12 was detected only in 7 patients (19.4%) who showed multi-system involvement (P=0.018) and lower event-free survival (P=0.002) in comparison to patients with negative MMP12 staining.
Gelsolin and MMP12 expression may be associated with the clinical course of LCH, and MMP12 expression may be particularly associated with severe LCH. Further studies of larger populations are needed to define the precise role and significance of gelsolin and MMP12 in the pathogenesis of LCH.
PMCID: PMC3538798  PMID: 23320005
Histiocytosis; Langerhans cells; Immunohistochemistry; Gelsolin; Matrix Metalloproteinase 12
15.  Genes Encoding Plant-Specific Class III Peroxidases Are Responsible for Increased Cold Tolerance of the brassinosteroid-insensitive 1 Mutant 
Molecules and Cells  2012;34(6):539-548.
We previously reported that one of the brassinosteroid-insensitive mutants, bri1-9, showed increased cold tolerance compared with both wild type and BRI1-overexpressing transgenic plants, despite its severe growth retardation. This increased tolerance in bri1-9 resulted from the constitutively high expression of stress-inducible genes under normal conditions. In this report, we focused on the genes encoding class III plant peroxidases (AtPrxs) because we found that, compared with wild type, bri1-9 plants contain higher levels of reactive oxygen species (ROS) that are not involved with the activation of NADPH oxidase and show an increased level of expression of a subset of genes encoding class III plant peroxidases. Treatment with a peroxidase inhibitor, salicylhydroxamic acid (SHAM), led to the reduction of cold resistance in bri1-9. Among 73 genes that encode AtPrxs in Arabidopsis, we selected four (AtPrx1, AtPrx22, AtPrx39, and AtPrx69) for further functional analyses in response to cold temperatures. T-DNA insertional knockout mutants showed increased sensitivity to cold stress as measured by leaf damage and ion leakage. In contrast, the overexpression of AtPrx22, AtPrx39, and AtPrx69 increased cold tolerance in the BRI1-GFP plants. Taken together, these results indicate that the appropriate expression of a particular subset of AtPrx genes and the resulting higher levels of ROS production are required for the cold tolerance.
PMCID: PMC3887832  PMID: 23180292
brassinosteroid-insensitive 1; cold stress; plant-specific class III peroxidases; stress response
16.  Quantitative PCR for Etiologic Diagnosis of Methicillin-Resistant Staphylococcus aureus Pneumonia in Intensive Care Unit 
Ventilator-associated pneumonia (VAP) requires prompt and appropriate treatment. Since methicillin-resistant Staphylococcus aureus (MRSA) is a frequent pathogen in VAP, rapid identification of it, is pivotal. Our aim was to evaluate the utility of quantitative polymerase chain reaction (qPCR) as a useful method for etiologic diagnoses of MRSA pneumonia.
We performed qPCR for mecA, S. aureus-specific femA-SA, and S. epidermidis-specific femA-SE genes from bronchoalveolar lavage or bronchial washing samples obtained from clinically-suspected VAP. Molecular identification of MRSA was based on the presence of the mecA and femA-SA gene, with the absence of the femA-SE gene. To compensate for the experimental and clinical conditions, we spiked an internal control in the course of DNA extraction. We estimated number of colony-forming units per mL (CFU/mL) of MRSA samples through a standard curve of a serially-diluted reference MRSA strain. We compared the threshold cycle (Ct) value with the microbiologic results of MRSA.
We obtained the mecA gene standard curve, which showed the detection limit of the mecA gene to be 100 fg, which corresponds to a copy number of 30. We chose cut-off Ct values of 27.94 (equivalent to 1×104 CFU/mL) and 21.78 (equivalent to 1×105 CFU/mL). The sensitivity and specificity of our assay were 88.9% and 88.9% respectively, when compared with quantitative cultures.
Our results were valuable for diagnosing and identifying pathogens involved in VAP. We believe our modified qPCR is an appropriate tool for the rapid diagnosis of clinical pathogens regarding patients in the intensive care unit.
PMCID: PMC3510279  PMID: 23227069
Methicillin-Resistant Staphylococcus aureus; Real-Time Polymerase Chain Reaction; Pneumonia, Ventilator-Associated
17.  Comparison of two preoperative chemoradiotherapy regimens for locally advanced rectal cancer: capecitabine alone versus capecitabine plus irinotecan 
To compare the short-term tumor response and long-term clinical outcome of two preoperative chemoradiotherapy (CRT) regimens for locally advanced rectal cancer.
This study included 231 patients scheduled for preoperative CRT using two chemotherapeutic protocols from April 2003–August 2006. Pelvic radiotherapy (50.4 Gy) was delivered concurrently with capecitabine (n = 148) or capecitabine/irinotecan (n = 83). Surgery was performed 4–8 weeks after CRT completion. Tumor responses to CRT were assessed using both radiologic and pathologic measurements. Radiologic responses were evaluated by magnetic resonance volumetry, which was performed at the initial work-up and after completion of preoperative CRT just before surgery. Pathologic responses were assessed with downstaging (ypStage 0-1) and grading tumor regression. Clinical outcomes were evaluated in terms of local control, relapse-free survival, and overall survival rates.
Radiologic examination demonstrated that tumor volume decreased by 65.6% in the capecitabine group and 66.8% capecitabine/irinotecan group (p = 0.731). Postoperative pathologic stage determination showed that tumor downstaging occurred in 44.1% of the capecitabine group and 48.6% of the capecitabine/irinotecan group (p = 0.538). The sum of tumor regression grade 3 (near complete response) and 4 (complete response) after CRT were 28.6% in the capecitabine group and 37.5% in the capecitabine/irinotecan group (p = 0.247). There were no significant differences between the two groups in 5-year local control (91.7% vs. 92.5%; p = 0.875), relapse-free survival (80.8% vs. 77.2%; p = 0.685), and overall survival (88.4% vs. 90.4%; p = 0.723).
This study revealed no differences in the short-term tumor response and long-term clinical outcome between preoperative capecitabine and capecitabine/irinotecan CRT regimens for locally advanced rectal cancer.
PMCID: PMC3827873  PMID: 24188746
Rectal cancer; Preoperative chemoradiotherapy; Capecitabine; Irinotecan
18.  Fermenting Red Ginseng Enhances Its Safety and Efficacy as a Novel Skin Care Anti-Aging Ingredient: In Vitro and Animal Study 
Journal of Medicinal Food  2012;15(11):1015-1023.
The objective of this study was to evaluate the anti-aging potential and skin safety of red ginseng (RG) and fermented red ginseng (FRG) using Lactobacillus brevis for use as cosmetic ingredients. Concentrations of uronic acid, polyphenols, and flavonoids, and antioxidant activities were greater in FRG compared to RG. The contents of total ginsenosides were not significantly different. However, the ginsenoside metabolite content was higher in FRG (14,914.3 μg/mL) compared to RG (5697.9 μg/mL). The tyrosinase inhibitory activity (IC50) of FRG was 27.63 μg/mL, and more potent compared with RG (34.14 μg/mL), (P<.05). The elastase inhibitory activity (IC50) of FRG was 117.07 μg/mL also higher compared with RG (157.90 μg/mL). In a primary skin irritation test, 10% RG and 10% FRG were classified as practically nonirritating materials. In a skin sensitization test, the RG group showed a sensitization rate of 100% and its mean evaluation score of irritation was 1.4, whereas the FRG group showed 20% and 0.2%, respectively. By fermentation of RG, FRG has increased contents of ginsenoside metabolites, such as Rg3, Rg5, Rk1, compound K, Rh1, F2, Rg2, and flavonoids content. Therefore, FRG offers increased anti-wrinkle efficacy, whitening efficacy, and reduced toxicological potency compared to RG.
PMCID: PMC3491619  PMID: 23126662
cosmeceutical; fermented red ginseng; red ginseng; skin safety
19.  Dipeptidyl Peptidase 10, a Novel Prognostic Marker in Colorectal Cancer 
Yonsei Medical Journal  2013;54(6):1362-1369.
The dipeptidyl peptidase IV (DPPIV) gene family exhibits multiple functions and is involved in the pathogenesis of various diseases. It has attracted pharmaceutical interest in the areas of metabolic disorders as well as cancer. However, clinicopathologic significance of DPPIV family in colorectal cancer is not fully understood.
Materials and Methods
The clinical relevance of DPPIV and DPP10 expression was determined by immunohistochemical staining, and by assessing its clinicopathologic correlation in 383 colorectal cancer patients with known clinical outcomes.
DPPIV was not expressed in normal colon mucosa, but it showed luminal expression in 52 of the 383 colorectal cancers (13.5%). DPPIV expression in tumors was associated with right-sided location of the colon (p=0.010) and more advanced tumor stage (p=0.045). DPP10 was expressed in normal colonic mucosa, but its expression varied in primary colorectal cancer tissues. Loss of DPP10 expression was found in 11 colorectal cancers (CRCs) (2.9%), and multivariate analysis showed that loss of DPP10 expression was an independent factor for poor patient prognosis (p=0.008).
DPP10 may play a role in disease progression of colorectal cancer and loss of DPP10 expression in primary CRC is significantly associated with poor survival outcomes.
PMCID: PMC3809881  PMID: 24142639
Colorectal cancer; dipeptidyl peptidase 10; progression; prognosis
20.  Improvements to the FIGO staging for ovarian cancer: reconsideration of lymphatic spread and intraoperative tumor rupture 
Journal of Gynecologic Oncology  2013;24(4):352-358.
To evaluate the improvement in prognosis prediction with reassignment of International Federation of Gynecology and Obstetrics (FIGO) stages for ovarian carcinoma.
This was a retrospective study of patients with epithelial ovarian, fallopian tube, and primary peritoneal cancers. Sub-staging criteria used in stage reassignment were defined as follows: surgical spillage (IC1), capsule rupture before surgery or tumor on the surface (IC2), and positive cytology results (IC3); microscopic (IIB1) and macroscopic (IIB2) pelvic spread; microscopic extrapelvic spread (IIIA1) and retroperitoneal lymph node (LN) metastasis without extrapelvic spread (IIIA2); and supraclavicular LN metastasis (IVA) and other distant metastasis (IVB). Survival outcomes associated with the current and reassigned stages were compared.
Overall, 870 patients were eligible for analysis. The median follow-up period was 45 months (range, 0 to 263 months). The 5-year overall survival rates (5YSRs) according to the current staging were 93.5% (IA), 82.5% (IC), 75.0% (IIB), 74.5% (IIC), 57.5% (IIIA), 54.0% (IIIB), 38.5% (IIIC), and 33.0% (IV). The 5YSRs of patients with IC1, IC2, and IC3 after sub-staging were 92.0%, 85.0%, and 71.0%, respectively (p=0.004). Patients who were reassigned to stage IIIA2 had a better 5YSR than those with extrapelvic tumors >2 cm (66.3% vs. 35.8%; p=0.005). Additionally, patients with newly assigned stage IVA disease had a significantly better 5YSR than those with stage IVB disease (52.0% vs. 28.0%; p=0.015).
The modified FIGO staging for ovarian carcinoma appears superior to the current staging for discriminating survival outcomes of patients with surgical spillage, retroperitoneal LN metastasis without extrapelvic peritoneal involvement, or distant metastasis to supraclavicular LNs.
PMCID: PMC3805916  PMID: 24167671
Lymph node metastasis; Ovarian cancer; Stage reassignment; Supraclavicular lymph node metastasis; Surgical spillage
21.  A National Prediction Model for PM2.5 Component Exposures and Measurement Error–Corrected Health Effect Inference 
Environmental Health Perspectives  2013;121(9):1017-1025.
Background: Studies estimating health effects of long-term air pollution exposure often use a two-stage approach: building exposure models to assign individual-level exposures, which are then used in regression analyses. This requires accurate exposure modeling and careful treatment of exposure measurement error.
Objective: To illustrate the importance of accounting for exposure model characteristics in two-stage air pollution studies, we considered a case study based on data from the Multi-Ethnic Study of Atherosclerosis (MESA).
Methods: We built national spatial exposure models that used partial least squares and universal kriging to estimate annual average concentrations of four PM2.5 components: elemental carbon (EC), organic carbon (OC), silicon (Si), and sulfur (S). We predicted PM2.5 component exposures for the MESA cohort and estimated cross-sectional associations with carotid intima-media thickness (CIMT), adjusting for subject-specific covariates. We corrected for measurement error using recently developed methods that account for the spatial structure of predicted exposures.
Results: Our models performed well, with cross-validated R2 values ranging from 0.62 to 0.95. Naïve analyses that did not account for measurement error indicated statistically significant associations between CIMT and exposure to OC, Si, and S. EC and OC exhibited little spatial correlation, and the corrected inference was unchanged from the naïve analysis. The Si and S exposure surfaces displayed notable spatial correlation, resulting in corrected confidence intervals (CIs) that were 50% wider than the naïve CIs, but that were still statistically significant.
Conclusion: The impact of correcting for measurement error on health effect inference is concordant with the degree of spatial correlation in the exposure surfaces. Exposure model characteristics must be considered when performing two-stage air pollution epidemiologic analyses because naïve health effect inference may be inappropriate.
Citation: Bergen S, Sheppard L, Sampson PD, Kim SY, Richards M, Vedal S, Kaufman JD, Szpiro AA. 2013. A national prediction model for PM2.5 component exposures and measurement error–corrected health effect inference. Environ Health Perspect 121:1017–1025;
PMCID: PMC3764074  PMID: 23757600
22.  Detection of EGFR mutations in circulating free DNA by PNA-mediated PCR clamping 
Epidermal growth factor receptor (EGFR)-activating mutations are major determinants in predicting the tumor response to EGFR tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC). Noninvasive test for the detection of EGFR mutations is required, especially in NSCLC patients from whom tissue is not available. In this study, we assessed the feasibility of detection of EGFR mutations in free DNA circulating in plasma.
Plasma samples of 60 patients with partial response to gefitinib were analyzed to detect EGFR-activating mutations in exons 19 and 21. Forty (66.7%) of patients had tumor EGFR mutation results. EGFR mutations in plasma were detected using the peptide nucleic acid (PNA)-mediated polymerase chain reaction (PCR) clamping method. All clinical data and plasma samples were obtained from 11 centers of the Korean Molecular Lung Cancer Group (KMLCG).
Of the 60 patients, 39 were female and the median age was 62.5 years. Forty-three patients never smoked, 53 had adenocarcinomas, and seven had other histologic types. EGFR-activating mutation was detected in plasma of 10 cases (exon 19 deletion in seven and exon 21 L858R point mutation in three). It could not be found in plasma after treatment for 2 months. When only patients with confirmed EGFR mutation in tumor were analyzed, 17% (6 of 35) of them showed positive plasma EGFR mutation and the mutation type was completely matched with that in tumor. There was no statistically significant difference in clinical parameters between patients with EGFR mutations in plasma and those without EGFR mutations.
The detection rate of EGFR mutations from plasma was not so high despite highly sensitive EGFR mutation test suggesting that more advances in detection methods and further exploration of characteristics of circulating free DNA are required.
PMCID: PMC3751150  PMID: 23927790
Plasma; EGFR mutation; PNA-mediated PCR clamping method; Non-small cell lung cancer
23.  Methylome of Fetal and Maternal Monocytes and Macrophages at the Feto-Maternal Interface 
Decidual macrophages (dMϕ) of the mother and placental macrophages (Hofbauer cells, HC) of the fetus are deployed at a critical location: the feto-maternal interface. This study was conducted to compare DNA methylome of maternal and fetal monocytes, dMϕ, and HC, and thereby to determine the immunobiological importance of DNA methylation in pregnancy.
Methods of Study
Paired samples were obtained from normal pregnant women at term not in labor and their own neonates. Maternal monocytes (MM) and fetal monocytes (FM) were isolated from peripheral blood of mothers and from fetal cord blood, respectively. dMϕ and HC were obtained from the decidua of fetal membranes and placenta, respectively. DNA methylation profiling was done using the Illumina Infinium Human Methylation27 BeadChip. Quantitative real-time PCR and western blot were performed for validation experiments.
1) Significant differences in DNA methylation were found in each comparison (MM vs. FM, 65 loci; dMϕ vs. HC, 266 loci; MM vs. dMϕ, 199 loci; FM vs. HC, 1,030 loci). 2) Many of the immune response-related genes were hypermethylated in fetal cells (FM and HC) compared to maternal cells (MM and dMϕ). 3) Genes encoding markers of classical macrophage activation were hypermethylated and genes encoding alternative macrophage activation were hypomethylated in dMϕ and HC compared to MM and FM, respectively. 4) mRNA expressions of DNMT1, DNMT3A, and DNMT3B were significantly lower in dMϕ than in HC. 5) 5-azacytidine treatment increased expression of INCA1 in dMϕ.
The findings herein indicate that DNA methylation patterns change during monocyte-macrophage differentiation at the feto-maternal interface. It is also suggested that DNA methylation is an important component of biological machinery conferring an anti-inflammatory phenotype to macrophages at the feto-maternal interface.
PMCID: PMC3479407  PMID: 22385097
Decidua; DNA methylation; DNA methyltransferase; Epigenetics; Epigenome; Hofbauer cell; Placenta; Pregnancy
24.  Clinical and radiologic evaluation of cytomegalovirus-induced thrombocytopenia in infants between 1 and 6 months of age 
Up to 90% of neonates with congenital or perinatal cytomegalovirus (CMV) infection are asymptomatic, and little is known about CMV-associated thrombocytopenia after the neonatal period. We investigated the clinical findings of a series of infants diagnosed with CMV infection and thrombocytopenia.
From July 2005 to July 2008, infants aged younger than 6 months with thrombocytopenia were screened for CMV infection, using CMV IgM. Those who were positive for CMV IgM were then tested for CMV IgG via polymerase chain reaction (PCR) for CMV and CMV pp65 Ag and urine culture. Brain magnetic resonance imaging (MRI) and otologic and ophthalmologic evaluations were also performed.
Twenty-one patients aged between 1 and 6 months (11 boys and 10 girls) were admitted and tested for CMV infection. Six patients (28.6%) were positive for CMV IgM; these were also positive for CMV IgG, CMV PCR, and urine culture, and 4 were also positive for CMV pp65 Ag. The median platelet count at admission was 6,500/µL (range, 2,000-105,000/µL). One patient (16.7%) was diagnosed with Evans syndrome and had calcifications on brain MRI. One patient had unilateral sensorineural hearing loss.
Thrombocytopenia can be the main clinical manifestation of otherwise asymptomatic CMV infection after the neonatal period, and close follow-up of neurodevelopmental sequelae is needed.
PMCID: PMC2983005  PMID: 21120160
Thrombocytopenia; Cytomegalovirus; Infant
25.  Association between Metabolic Syndrome and Gallbladder Polyps in Healthy Korean Adults 
Journal of Korean Medical Science  2013;28(6):876-880.
The goal of this study was to evaluate the association between gallbladder (GB) polyps and metabolic syndrome. A total of 5,685 healthy subjects were included, and 485 of these subjects had GB polyps and 744 had metabolic syndrome. In this study, metabolic syndrome was diagnosed according to standards suggested by the AHA/NHLBI ATP III 2005, and abdominal obesity (≥ 90 cm in men and ≥ 85 cm in women for Korean) was diagnosed according to standards set forth by the Korean Society for Study of Obesity. Biphasic logistic regression adjusted for age and gender was used to evaluate the association between metabolic syndrome and GB polyps. Subjects who were male (OR, 1.493; 95% CI, 1.11-2.00) and hepatitis B suface Ag (HBsAg) positive (OR, 1.591; 95% CI, 1.06-2.38) were significantly more likely to have GB polyps. The metabolic syndrome group had a higher risk of GB polyps (OR, 1.315; 95% CI, 1.01-1.69) than the group without metabolic syndrome. In conclusion, subjects who were HBsAg positive and male appear to be associated with the risk of GB polyps. The presence of metabolic syndrome also appears to be associated with the risk of GB polyps in Koreans.
PMCID: PMC3678004  PMID: 23772152
Metabolic Syndrome; GB Polyp; Risk Factors

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