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1.  Structure characterization of the 26S proteasome 
Biochimica et biophysica acta  2010;1809(2):67-79.
In all eukaryotic cells, 26S proteasome plays an essential role in the process of ATP-dependent protein degradation. In this review, we focus on structure characterization of the 26S proteasome. Although the progress towards a high-resolution structure of the 26S proteasome has been slow, the recently solved structures of various proteasomal subcomplexes have greatly enhanced our understanding of this large machinery. In addition to having an ATP-dependent proteolytic function, the 26S proteasome is also involved in many non-proteolytic cellular activities, which are often mediated by subunits in its 19S regulatory complex. Thus, we include a detailed discussion of the structures of 19S subunits, including proteasomal ATPases, ubiquitin receptors, deubiquitinating enzymes and subunits that contain PCI domain.
PMCID: PMC3010250  PMID: 20800708
26S proteasome; structure
2.  Trends in Body Mass Index and Associations With Physical Activity Among Career Soldiers in South Korea 
This study was designed to describe the trends in body mass index (BMI) during 6 years (2002 - 2008) and to identify associations between these trends and the amount of physical activity of South Korean career soldiers.
This study targeted the 40 993 (38 857 men and 2136 women) of the 58 657 career soldiers who had undergone four (2002, 2004, 2006, and 2008) biennial medical examinations conducted by the National Health Insurance Corporation; 17 664 soldiers with missing data on height, weight, and physical activity were excluded. A linear mixed-regression model was used to categorize changes in BMI due to age versus those due to amount of physical activity.
Career soldiers experienced significant increases in BMI compared with baseline data gathered in 2002. The increases in each age group were as follows: men aged 20- 29: 1.16, men aged 30 - 39: 0.61, men aged 40 - 49: 0.05, women aged 20- 29: 0.35, women aged 30- 39: 0.30, women aged 40-49: 0.26, and women aged 50- 59: 0.21. However, men aged 50 or older showed significant decreases (as high as 0.5) in BMI compared with baseline data obtained in 2002. They also experienced significant decreases in BMI compared with those who reported no physical activity. The differences between baseline and final BMIs were: 0.02 for men exercising 1- 2 times per week, -0.07 for men exercising 3-4 times per week, -0.19 for men exercising 5-6 times per week, -0.21 for men exercising seven times per week, -0.05 for women exercising 1- 2 times per week, -0.19 for women exercising 3- 4 times per week, -0.30 for women exercising 5-6 times per week, and -0.30 for women exercising seven times per week.
Obesity in South Korean career soldiers increased markedly between 2002 and 2008, and our data showed that the amount of physical activity was inversely related to increases in BMI. Policies to prevent obesity are needed to reduce this trend.
PMCID: PMC3249253  PMID: 21894065
Obesity; BMI; Trend; Career soldier; Physical activity; Exercise
3.  Myricetin suppresses UVB-induced wrinkle formation and MMP-9 expression by inhibiting Raf 
Biochemical pharmacology  2010;79(10):1455-1461.
Chronic exposure to solar ultraviolet (UV) light causes skin photoaging. Many studies have shown that naturally occurring phytochemicals have anti-photoaging effects, but their direct target molecule(s) and mechanism(s) remain unclear. We found that myricetin, a major flavonoid in berries and red wine, inhibited wrinkle formation in mouse skin induced by chronic UVB irradiation (0.18 J/cm2, 3 days/wk for 15 wk). Myricetin treatment reduced UVB-induced epidermal thickening of mouse skin and also suppressed UVB-induced matrix metalloproteinase-9 (MMP-9) protein expression and enzyme activity. Myricetin appeared to exert its anti-aging effects by suppressing UVB-induced Raf kinase activity and subsequent attenuation of UVB-induced phosphorylation of MEK and ERK in mouse skin. In vitro and in vivo pull-down assays revealed that myricetin bound with Raf in an ATP-noncompetitive manner. Overall, these results indicate that myricetin exerts potent anti-photoaging activity by regulating MMP-9 expression through the suppression of Raf kinase activity.
PMCID: PMC2864126  PMID: 20093107
myricetin; anti-wrinkle; Raf; photoaging; UVB
4.  Cloning-Independent Expression and Analysis of ω-Transaminases by Use of a Cell-Free Protein Synthesis System▿ †  
Applied and Environmental Microbiology  2010;76(18):6295-6298.
Herewith we report the expression and screening of microbial enzymes without involving cloning procedures. Computationally predicted putative ω-transaminase (ω-TA) genes were PCR amplified from the bacterial colonies and expressed in a cell-free protein synthesis system for subsequent analysis of their enzymatic activity and substrate specificity. Through the cell-free expression analysis of the putative ω-TA genes, a number of enzyme-substrate pairs were identified in a matter of hours. We expect that the proposed strategy will provide a universal platform for bridging the information gap between nucleotide sequence and protein function to accelerate the discovery of novel enzymes.
PMCID: PMC2937503  PMID: 20656866
5.  Changes in the Prevalence of Childhood Asthma in Seoul from 1995 to 2008 and Its Risk Factors 
To investigate the prevalence of asthma and determine its risk factors in elementary school students in Seoul.
A modified International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was used to survey 4,731 elementary school students from five areas in Seoul between April and October, 2008.
In elementary school children, the lifetime and recent 12-month prevalence of wheezing were 11.7% and 5.6%, respectively. The lifetime prevalence of asthma diagnosis was 7.9%, and the recent 12-month prevalence of asthma treatment was 2.7%. Male sex (adjusted odds ratio [aOR], 1.90; 95% confidence interval [CI], 1.36-2.66), history of atopic dermatitis (AD) (aOR, 2.76; 95% CI, 1.98-3.84), history of allergic rhinitis (AR) (aOR, 3.71; 95% CI, 2.61-5.26), history of bronchiolitis before 2 years of age (aOR, 2.06; 95% CI, 1.39-3.07), use of antibiotics during infancy for >3 days (aOR, 1.88; 95% CI, 1.35-2.62), parental history of asthma (aOR, 2.83; 95% CI, 1.52-5.27), exposure to household molds during infancy (aOR, 1.84; 95% CI, 1.18-2.89), and the development or aggravation of asthma symptoms within 6 months after moving to a new house (aOR, 11.76; 95% CI, 5.35-25.86) were the independent risk factors for wheezing within 12 months.
The prevalence of wheezing and asthma in elementary school students in 2008 was similar to that in the past decade. Male sex, history of AD, history of AR, history of bronchiolitis before 2 years of age, parental asthma, use of antibiotics during infancy, exposure to molds in the house during infancy, and development or aggravation of asthma symptoms within 6 months after moving to a new house, could be risk factors for wheezing within 12 months.
PMCID: PMC3005315  PMID: 21217922
Asthma; prevalence; risk factor; childhood
6.  Induction of the Intrinsic Apoptotic Pathway by 3-Deazaadenosine Is Mediated by BAX Activation in HL-60 Cells 
3-Deazaadenosine (DZA), a potent inhibitor of S-adenosylhomocysteine hydrolase, was previously proposed to induce intrinsic apoptosis in human leukemic cells. In the present study, we analyzed the mechanism underlying the DZA-induced intrinsic apoptotic pathway. DZA activated typical caspase-dependent apoptosis in HL-60 cells, as demonstrated by an accumulation of hypo-diploidic cells, the processing of multiple procaspases and an inhibitory effect of z-VAD-Fmk on this cell death. During DZA-induced apoptosis, cytochrome c (cyt c) was released into the cytosol. This was neither prevented by z-VAD-Fmk and nor was it associated with the dissipation of mitochondrial membrane potential (ΔΨm). Prior to the release of cyt c, BAX was translocated from the cytosol to mitochondria and underwent oligomerization. Finally, the overexpression of BCL-XL protected HL-60 cells from apoptosis by blocking both the cyt c release and BAX oligomerization. Collectively, these findings suggest that DZA may activate intrinsic apoptosis by stimulating BAX activation and thereby the release of cyt c.
PMCID: PMC3034121  PMID: 21311682
Apoptosis; BAX protein; BCL-XL protein; Cytochrome c; 3-Deazaadenosine
7.  Fusiform Aneurysm Presenting with Cervical Radiculopathy in Ehlers-Danlos Syndrome 
Ehlers-Danlos syndrome (EDS) type IV is characterized by its clinical manifestations, which are easy bruising, thin skin with visible veins, and rupture of arteries, uterus, or intestines. Arterial complications are the leading cause of death in vascular EDS because they are unpredictable and surgical repair is difficult due to tissue fragility. The authors report a case presented with cervical radiculopathy due to a segmental fusiform aneurysm of the cervical vertebral artery. Transfemoral cerebral angiography (TFCA) was done to verify the aneurysmal dilatation. However, during TFCA, bleeding at the puncture site was not controlled, skin and underlying muscle was disrupted and profound bleeding occurred during manual compression after femoral catheter removal. Accordingly, surgical repair of the injured femoral artery was performed. At this time it was possible to diagnose it as an EDS with fusiform aneurysm on cervical vertebral artery. Particularly, cervical fusiform aneurysm is rare condition, and therefore, connective tissue disorder must be considered in such cases. If connective tissue disorder is suspected, the authors suggest that a noninvasive imaging modality, such as, high quality computed tomography angiography, be used to evaluate the vascular lesion to avoid potential arterial complications.
PMCID: PMC3053548  PMID: 21430980
Ehlers-Danlos syndrome; Cervical radiculopathy; Fusiform aneurysm; Vascular reconstruction
8.  Delayed Spinal Epidural Hematoma after En Block Spondylectomy for Vertebral Ewing's Sarcoma 
Asian Spine Journal  2010;4(2):118-122.
We report here on a case of a 23-year-old male who received en block spondylectomy for a vertebral Ewing's sarcoma at our hospital. Nine days after surgery, he presented with severe back pain and motor weakness of the lower extremities. Based on the physical examination and the computed tomography scan, he was diagnosed with acute cauda equina syndrome that was caused by compression from an epidural hematoma. His neurological functions recovered after emergency evacuation of the hematoma. This case showed that extensive surgery for a malignant vertebral tumor has a potential risk of delayed epidural hematoma and acute cauda equina syndrome and this should be treated with emergency evacuation.
PMCID: PMC2996623  PMID: 21165315
Epidural hematoma; Ewing's sarcoma; Spine; En block spondylectomy
9.  Engagement of Toll-Like Receptor 3 Induces Vascular Endothelial Growth Factor and Interleukin-8 in Human Rheumatoid Synovial Fibroblasts 
Angiogenesis, which is a critical step in the initiation and progression of rheumatoid arthritis (RA), involves pro-angiogenic factors, including interleukin (IL)-8 and vascular endothelial growth factor (VEGF). We investigated the role of Toll-like receptor 3 (TLR3) in the regulation of pro-angiogenic factors in RA fibroblast-like synoviocytes (FLS).
FLS were isolated from RA synovial tissues and stimulated with the TLR3 ligand, poly (I:C). The levels of VEGF and IL-8 in the culture supernatants were measured using enzyme-linked immunosorbent assays, and the mRNA levels were assessed by semiquantitative reverse transcription-polymerase chain reaction. The expression patterns of VEGF and IL-8 in the RA synovium and osteoarthritis (OA) synovium were compared using immunohistochemistry.
The expression levels of TLR3, VEGF, and IL-8 were significantly higher in the RA synovium than in the OA synovium. VEGF and IL-8 production were increased in the culture supernatants of RA FLS stimulated with poly (I:C), and the genes for these proteins were up-regulated at the transcriptional level after poly (I:C) treatment. Treatment with inhibitors of nuclear factor-kappaB (NF-κB), i.e., pyrrolidine dithiocarbamate and parthenolide, abrogated the stimulatory effect of poly (I:C) on the production of VEGF and IL-8 in RA FLS.
Our results suggest that the activation of TLR3 in RA FLS promotes the production of proangiogenic factors, in a process that is mediated by the NF-κB signaling pathway. Therefore, targeting the TLR3 pathway may be a promising approach to preventing pathologic angiogenesis in RA.
PMCID: PMC2997973  PMID: 21179282
Toll-like receptor 3; Arthritis, rheumatoid; Vascular endothelial growth factor; Interleukin-8; Synovial fibroblast
10.  Thalidomide Induced Nonspecific Interstitial Pneumonia in Patient with Relapsed Multiple Myeloma 
A 63-year-old female diagnosed with relapsed multiple myeloma visited our hospital complaining of a persistent cough. Since July 2006, she had been taking 100 mg thalidomide daily and gradually developed shortness of breath and a persistent dry cough. A chest X-ray and computed tomography showed ground glass opacities in both lungs. An open lung biopsy of the right middle lobe under general anesthesia revealed chronic peribronchial inflammation, mild interstitial fibrosis, and intra-alveolar macrophage infiltration, with some hemosiderin features, compatible with non-specific interstitial pneumonia (NSIP). After discontinuing the thalidomide, the patient's symptoms did not deteriorate, although the radiographs did not improve. The patient is alive and well with regular outpatient follow-up without progression of the NSIP.
PMCID: PMC2997975  PMID: 21179284
Lung diseases, interstitial; Thalidomide; Multiple myeloma
11.  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
12.  Korean Guidelines for the Prevention of Venous Thromboembolism 
Journal of Korean Medical Science  2010;25(11):1553-1559.
This guideline focuses on the primary prevention of venous thromboembolism (VTE) in Korea. The guidelines should be individualized and aim at patients scheduled for major surgery, as well as patients with a history of trauma, high-risk pregnancy, cancer, or other severe medical illnesses. Currently, no nation-wide data on the incidence of VTE exist, and randomized controlled trials aiming at the prevention of VTE in Korea have yielded few results. Therefore, these guidelines were based on the second edition of the Japanese Guidelines for the Prevention of VTE and the eighth edition of the American College of Chest Physicians (ACCP) Evidenced-Based Clinical Practice Guidelines. These guidelines establish low-, moderate-, and high-risk groups, and recommend appropriate thromboprophylaxis for each group.
PMCID: PMC2966990  PMID: 21060742
Guideline; Prevention; Venous Thromboembolism
13.  Ethnic Coefficients for Glomerular Filtration Rate Estimation by the Modification of Diet in Renal Disease Study Equations in the Korean Population 
Journal of Korean Medical Science  2010;25(11):1616-1625.
Race and ethnicity are influential in estimating glomerular filtration rate (GFR). We aimed to find the Korean coefficients for the Modification of Diet in Renal Disease (MDRD) study equations and to obtain novel proper estimation equations. Reference GFR was measured by systemic inulin clearance. Serum creatinine (SCr) values were measured by the alkaline picrate Jaffé kinetic method, then, recalibrated to CX3 analyzer and to isotope dilution mass spectrometry (IDMS). The Korean coefficients for the 4 and 6 variable MDRD and IDMS MDRD study equations based on the SCr recalibrated to CX3 and to IDMS were 0.73989/0.74254 and 0.99096/0.9554, respectively. Coefficients for the 4 and 6 variable MDRD equations based on the SCr measured by Jaffé method were 1.09825 and 1.04334, respectively. The modified equations showed better performances than the original equations. The novel 4 variable equations for Korean based on the SCr measured and recalibrated to IDMS were 107.904×SCr-1.009×age-0.02 (×0.667, if woman) and 87.832×SCr-0.882×age0.01 (×0.653, if woman), respectively. Modified estimations of the MDRD and IDMS MDRD study equations with ethnic coefficients and the novel equations improve the performance of GFR estimation for the overall renal function.
PMCID: PMC2966999  PMID: 21060751
Coefficient; Glomerular Filtration Rate; Inulin Clearance; Modification of Diet in Renal Disease Study
14.  Variation of the Infrahyoid Muscle: Duplicated Omohyoid and Appearance of the Levator Glandulae Thyroideae Muscles 
Yonsei Medical Journal  2010;51(6):984-986.
The embryologic origin of the omohyoid muscle is different from that of the other neck muscles. A number of variations such as the absence of muscle, variable sites of origin and insertion, and multiple bellies have been reported. However, variations in the inferior belly of the omohyoid muscle are rare. There have been no reports of the combined occurrence of the omohyoid muscle variation with the appearance of the levator glandulase thyroideae muscle. Routine dissection of a 51-year-old female cadaver revealed a duplicated omohyoid muscle and the appearance of the levator glandulae thyroideae muscle. In this case, the two inferior bellies of the omohyoid muscle were found to originate inferiorly from the superior border of the scapula. One of the inferior bellies generally continued to the superior belly with the tendinous intersection. The other inferior belly continued into the sternohyoid muscle without the tendinous intersection. In this case, the levator glandulae thyroideae muscle appeared on the left side, which attached from the upper border of the thyroid gland to the inferior border of the thyroid cartilage. These variations are significant for clinicians during endoscopic diagnosis and surgery because of the arterial and nervous damage due to iatrogenic injuries. The embryologic origins of the omohyoid and levator glandulae thyroideae muscles may be similar based on the descriptions in the relevant literature.
PMCID: PMC2995959  PMID: 20879073
Variation; omohyoid muscle; levator glandulae thyroideae muscle; infrahyoid muscle
15.  Pulsed Electromagnetic Field Stimulates Cellular Proliferation in Human Intervertebral Disc Cells 
Yonsei Medical Journal  2010;51(6):954-959.
The purpose of this study is to investigate the mechanism of cellular proliferation of electromagnetic field (EMF) on human intervertebral disc (IVD) cells.
Materials and Methods
Human IVD cells were cultured three-dimensionally in alginate beads. EMF was exposed to IVD cells with 650Ω, 1.8 millitesla magnetic flux density, 60 Hz sinusoidal wave. Cultures were divided into a control and EMF group. Cytotoxicity, DNA synthesis and proteoglycan synthesis were measured by MTT assay, [3H]-thymidine, and [35S]-sulfate incorporation. To detect phenotypical expression, reverse transcription-polymerase chain reactions (RT-PCR) were performed for aggrecan, collagen type I, and type II mRNA expression. To assess action mechanism of EMF, IVD cells were exposed to EMF with NG-Monomethyl-L-arginine (NMMA) and acetylsalicylic acid (ASA).
There was no cytotoxicity in IVD cells with the EMF group in MTT assay. Cellular proliferation was observed in the EMF group (p < 0.05). There was no difference in newly synthesized proteoglycan normalized by DNA synthesis between the EMF group and the control. Cultures with EMF showed no significant change in the expression of aggrecan, type I, and type II collagen mRNA compared to the control group. Cultures with NMMA (blocker of nitric oxide) or ASA (blocker of prostaglandin E2) exposed to EMF demonstrated decreased DNA synthesis compared to control cultures without NMMA or ASA (p < 0.05).
EMF stimulated DNA synthesis in human IVD cells while no significant effect on proteoglycan synthesis and chondrogenic phenotype expressions. DNA synthesis was partially mediated by nitric oxide and prostaglandin E2. EMF can be utilized to stimulate proliferation of IVD cells, which may provide efficient cell amplification in cell therapy to degenerative disc disease.
PMCID: PMC2995961  PMID: 20879066
Electromagnetic fields; intervertebral disc; nitric oxide; prostaglandin E2
16.  Analysis of Hospital Disaster in South Korea from 1990 to 2008 
Yonsei Medical Journal  2010;51(6):965-970.
The purpose of this study is to systematically review and analyze disasters involving South Korean hospitals from 1990 and to introduce a newly developed implement to manage patients' evacuation.
Materials and Methods
We searched for studies reporting disaster preparedness and hospital injuries in South Korean hospitals from 1990 to 2008, by using the Korean Studies Information Service System (KISS, copyright Korean Studies Information Co, Ltd, Seoul, Korea) and, simultaneously, hospital injuries which were reported and regarded as a disaster. Then, each study and injury were analyzed.
Five studies (3 on prevention and structure, 1 on implement of new device, and 1 on basic supplement to current methods) and 8 injuries were found within this period. During the evacuations, the mean gait speed of walking patients was 0.82 m/s and the mean time of evacuation of individual patients was 38.39 seconds. Regarding structure evaluation, almost all hospitals had no balconies in patient rooms; hospital elevators were placed peripherally and were insufficient in number. As a new device, Savingsun (evacuation elevator) was introduced and had some merits as a fast and easy tool, regardless of patient status or the height of hospital.
In South Korea, preparation for hospital disasters was noted to be insufficient but has involved various departments such as architectural, clinical, and building operations. In addition, Savignsun has been shown to effectively evacuate and save patients in a hospital disaster.
PMCID: PMC2995976  PMID: 20879068
Injury; disaster; hospital; preparedness
17.  Induction of Macrophage Migration Inhibitory Factor in ConA-Stimulated Rheumatoid Arthritis Synovial Fibroblasts through the P38 MAP Kinase-Dependent Signaling Pathway 
This study was undertaken to identify the intracellular signaling pathway involved in induction of macrophage migration inhibitory factor (MIF) in human rheumatoid arthritis (RA) synovial fibroblasts.
Human RA synovial fibroblasts were treated with concanavalin A (ConA), various cytokines, and inhibitors of signal transduction molecules. The production of MIF by synovial fibroblasts was measured in culture supernatants by ELISA. The expression of MIF mRNA was determined using reverse transcriptase polymerase chain reaction (RT-PCR) and real-time PCR. Phosphorylation of p38 mitogen-activated protein (MAP) kinase in synovial fibroblasts was confirmed using Western blotting. The expression of MIF and p38 MAP kinase in RA synovium was determined using dual immunohistochemistry.
The production of MIF by RA synovial fibroblasts increased in a dose-dependent manner after ConA stimulation. MIF was also induced by interferon-γ, CD40 ligand, interleukin-15, interleukin-1β, tumor necrosis factor-α, and transforming growth factor-β. The production of MIF by RA synovial fibroblasts was significantly reduced after inhibition of p38 MAP kinase. The expression of MIF and p38 MAP kinase was upregulated in the RA synovium compared with the osteoarthritis synovium.
These results suggest that MIF production was induced through a p38 MAP-kinase-dependent pathway in RA synovial fibroblasts.
PMCID: PMC2932946  PMID: 20830230
Macrophage, migration-inhibitory factors; Arthritis rheumatoid; Synovial fibroblast; p38 mitogen-activated protein kinases
18.  Activation of CD147 with Cyclophilin A Induces the Expression of IFITM1 through ERK and PI3K in THP-1 Cells 
Mediators of Inflammation  2010;2010:821940.
CD147, as a receptor for Cyclophilins, is a multifunctional transmembrane glycoprotein. In order to identify genes that are induced by activation of CD147, THP-1 cells were stimulated with Cyclophilin A and differentially expressed genes were detected using PCR-based analysis. Interferon-induced transmembrane 1 (IFITM1) was detected to be induced and it was confirmed by RT-PCR and Western blot analysis. CD147-induced expression of IFITM1 was blocked by inhibitors of ERK, PI3K, or NF-κB, but not by inhibitors of p38, JNK, or PKC. IFITM1 appears to mediate inflammatory activation of THP-1 cells since cross-linking of IFITM1 with specific monoclonal antibody against it induced the expression of proinflammatory mediators such as IL-8 and MMP-9. These data indicate that IFITM1 is one of the pro-inflammatory mediators that are induced by signaling initiated by the activation of CD147 in macrophages and activation of ERK, PI3K, and NF-κB is required for the expression of IFITM1.
PMCID: PMC2935166  PMID: 20847954
19.  CD13 is a therapeutic target in human liver cancer stem cells 
The Journal of Clinical Investigation  2010;120(9):3326-3339.
Cancer stem cells (CSCs) are generally dormant or slowly cycling tumor cells that have the ability to reconstitute tumors. They are thought to be involved in tumor resistance to chemo/radiation therapy and tumor relapse and progression. However, neither their existence nor their identity within many cancers has been well defined. Here, we have demonstrated that CD13 is a marker for semiquiescent CSCs in human liver cancer cell lines and clinical samples and that targeting these cells might provide a way to treat this disease. CD13+ cells predominated in the G0 phase of the cell cycle and typically formed cellular clusters in cancer foci. Following treatment, these cells survived and were enriched along the fibrous capsule where liver cancers usually relapse. Mechanistically, CD13 reduced ROS-induced DNA damage after genotoxic chemo/radiation stress and protected cells from apoptosis. In mouse xenograft models, combination of a CD13 inhibitor and the genotoxic chemotherapeutic fluorouracil (5-FU) drastically reduced tumor volume compared with either agent alone. 5-FU inhibited CD90+ proliferating CSCs, some of which produce CD13+ semiquiescent CSCs, while CD13 inhibition suppressed the self-renewing and tumor-initiating ability of dormant CSCs. Therefore, combining a CD13 inhibitor with a ROS-inducing chemo/radiation therapy may improve the treatment of liver cancer.
PMCID: PMC2929722  PMID: 20697159
20.  Effects of Body Composition, Leptin, and Adiponectin on Bone Mineral Density in Prepubertal Girls 
Journal of Korean Medical Science  2010;25(8):1187-1190.
Body weight is positively associated with bone mineral density but the relationship between obesity and bone mineral density is unclear. Leptin and adiponectin are potential independent contributors to bone mineral density. We assessed the correlations of body composition, leptin and adiponectin with bone mineral density, and whether leptin, adiponectin and body composition determine bone mineral density independently in prepubertal girls. Forty-eight prepubertal girls were classified into obese and control groups by body mass index. Serum leptin and adiponectin levels were determined by enzyme immunoassay. Bone mineral density was measured using dual energy radiography absorptiometry and body composition was measured using bioelectrical impedance analysis. Lean and fat mass, and leptin were positively correlated with bone mineral density. Lean mass was a positive independent predictor of femoral and L-spine bone mineral density. Serum leptin was a postivie independent predictor of femoral bone mineral density. Fat mass was a negative independent predictor of femoral bone mineral density. In prepubertal girls, lean mass has a favorable effect on bone mineral density. Fat mass seems not to protect the bone structure against osteoporosis, despite increased mechanical loading. Serum leptin may play a biological role in regulating bone metabolism.
PMCID: PMC2908789  PMID: 20676331
Bone Density; Body Composition; Leptin; Adiponectin; Obesity
21.  A Case of Bilateral Endogenous Pantoea Agglomerans Endophthalmitis with Interstitial Lung Disease 
We here in report a case of bilateral endogenous endophthalmitis caused by Pantoea agglomerans (P. agglomerans) in a patient who had interstitial lung disease and was treated with oral corticosteroids. A 72-year-old man presented with decreased visual acuity in both eyes nine days after he received oral corticosteroids. He had marked uveitis, cataracts, and vitreous opacities. Cultures were taken of blood, aqueous humor, and vitreous. We initially suspected a fungal etiology and treated him with antifungal drugs; however, the intraocular disease progressed without improvement. Vitreous culture was positive for P. agglomerans. The patient underwent pars plana vitrectomy with cataract surgery bilaterally, followed by a 2-week course of antibiotics. The final visual acuity was 20/25 in the right eye and 20/200 in the left eye. This is the first report of bilateral endogenous endophthalmitis caused by P. agglomerans in Korea; it is also the first case reported outside of the United States.
PMCID: PMC2916109  PMID: 20714391
Endophthalmitis; Pantoea
22.  Comparison of different nutritional assessments in detecting malnutrition among gastric cancer patients 
AIM: To evaluate the prevalence of preoperative and postoperative malnutrition and the relationships between objective and subjective nutritional assessment of gastric cancer patients.
METHODS: From October 2005 to July 2006, we studied 80 patients with no evidence of recurrent disease and no loss to follow-up after curative surgery for gastric cancer. In this group, 9 patients underwent total gastrectomy and 71 patients subtotal gastrectomy. At admission, 6 and 12 mo after surgery, the patients were assessed on the subjective global assessment (SGA), nutritional risk screening (NRS-2002), nutritional risk index (NRI) and by anthropometric measurements and laboratory data. Differences between the independent groups were assessed with the Student’s t test and one-way analysis of variance. Spearman’s rank correlation coefficients were calculated to evaluate the association between the scores and variables.
RESULTS: The prevalence of malnutrition at admission was 31% by SGA and 43% by NRS-2002. At admission, the anthropometric data were lower in the malnourished groups defined by the SGA and NRS-2002 assessments, but did not differ between the groups using the NRI assessment. Body weight (BW), body mass index (BMI), triceps skin fold and midarm circumference were significantly reduced, but the total lymphocyte count, albumin, protein, cholesterol and serum iron levels did not decrease during the postoperative period. Six months after surgery, there was a good correlation between the nutritional assessment tools (SGA and NRS-2002) and the other nutritional measurement tools (BW, BMI, and anthropometric measurements). However, 12 mo after surgery, most patients who were assessed as malnourished by SGA and NRS-2002 had returned to their preoperative status, although their BW, BMI, and anthropometric measurements still indicated a malnourished status.
CONCLUSION: A combination of objective and subjective assessments is needed for the early detection of the nutritional status in case of gastric cancer patients after gastrectomy.
PMCID: PMC2900724  PMID: 20614488
Gastrectomy; Malnutrition; Nutritional assessment; Nutritional risk screening; Postoperative follow up; Subjective global assessment
24.  Lack of Association between PRNP M129V Polymorphism and Multiple Sclerosis, Mild Cognitive Impairment, Alcoholism and Schizophrenia in a Korean Population 
Disease markers  2010;28(5):315-321.
The genetic variant at codon 129 (M129V) of the prion protein gene (PRNP) is considered to be a major genetic risk factor for prion diseases. In this study, we examined the possible genetic association of PRNP*129Val with multiple sclerosis (MS, n = 681), mild cognitive impairment (MCI, n = 801), alcoholism (n = 761) and schizophrenia (n = 715) in a Korean population, and compared the data with previous genetic association studies of the variant. The minor allele frequency of PRNP*129Val (MAF = 0.025) was significantly lower in Korean population (n = 2,479) compared to Caucasian populations (P < 0.0001), suggestive of a weak influence of the variant in the previous population. Statistical analysis revealed no significant association between PRNP*129Val and MS (P = 0.76), MCI (P = 0.46), alcoholism (P = 0.84) and schizophrenia (P = 0.69). These findings were discussed in the context of prior inconsistent reports on the role of PRNP*129Val polymorphism in several diseases. Results from this study may provide further evidence that PRNP M129V is not a genetic susceptibility factor for MS, MCI, alcoholism and schizophrenia in a Korean population.
PMCID: PMC3833710  PMID: 20592456
Prion; PRNP M129V; multiple sclerosis; mild cognitive impairment; alcoholism; schizophrenia
25.  The Significance of p53 and K-ras Immunocytochemical Staining in the Diagnosis of Malignant Biliary Obstruction by Brush Cytology during ERCP 
Gut and Liver  2010;4(2):219-225.
Brush cytology during ERCP can provide a pathologic diagnosis in malignant biliary obstruction. K-ras and p53 mutations are commonly found in biliary and pancreatic cancers. We evaluated the diagnostic yield of brush cytology and the changes obtained by adding p53 and K-ras staining.
One hundred and forty patients with biliary obstruction who underwent ERCP with brush cytology during a 7-year period were included. The sensitivity and specificity of brush cytology only and with the addition of p53 and K-ras staining were obtained.
Malignant biliary obstruction was confirmed in 119 patients. The sensitivity and specificity of brush cytology were 78.2% and 90.5%, respectively. The sensitivity of cytology was 77.3% at the ampulla-distal common bile duct (CBD), 92.6% at the mid common hepatic duct (CHD), and 94.7% at the proximal CBD-CHD (p<0.05); these values did not differ with the degree or the length of the obstruction. In the 97 patients who received additional p53 and K-ras staining, the sensitivity of cytology plus p53 was 88.2%, cytology plus K-ras was 84.0%, and cytology plus p53 and K-ras was 88.2%. The sensitivity of cytology plus p53 was higher than that of brush cytology only (95% confidence interval: 83.69-92.78 vs 72.65-83.65) but not that of cytology plus K-ras.
Brush cytology for malignant biliary obstruction has a high diagnostic accuracy. Adding p53 staining can further improve the diagnostic yield, whereas K-ras staining does not.
PMCID: PMC2886932  PMID: 20559525
Malignant biliary obstruction; Brush cytology; ERCP; Immunocytochemical stain

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