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1.  Evaluation of the Contributions of Individual Viral Genes to Newcastle Disease Virus Virulence and Pathogenesis 
Journal of Virology  2014;88(15):8579-8596.
Naturally occurring Newcastle disease virus (NDV) strains vary greatly in virulence. The presence of multibasic residues at the proteolytic cleavage site of the fusion (F) protein has been shown to be a primary determinant differentiating virulent versus avirulent strains. However, there is wide variation in virulence among virulent strains. There also are examples of incongruity between cleavage site sequence and virulence. These observations suggest that additional viral factors contribute to virulence. In this study, we evaluated the contribution of each viral gene to virulence individually and in different combinations by exchanging genes between velogenic (highly virulent) strain GB Texas (GBT) and mesogenic (moderately virulent) strain Beaudette C (BC). These two strains are phylogenetically closely related, and their F proteins contain identical cleavage site sequences, 112RRQKR↓F117. A total of 20 chimeric viruses were constructed and evaluated in vitro, in 1-day-old chicks, and in 2-week-old chickens. The results showed that both the envelope-associated and polymerase-associated proteins contribute to the difference in virulence between rBC and rGBT, with the envelope-associated proteins playing the greater role. The F protein was the major individual contributor and was sometimes augmented by the homologous M and HN proteins. The dramatic effect of F was independent of its cleavage site sequence since that was identical in the two strains. The polymerase L protein was the next major individual contributor and was sometimes augmented by the homologous N and P proteins. The leader and trailer regions did not appear to contribute to the difference in virulence between BC and GBT.
IMPORTANCE This study is the first comprehensive and systematic study of NDV virulence and pathogenesis. Genetic exchanges between a mesogenic and a velogenic strain revealed that the fusion glycoprotein is the major virulence determinant regardless of the identical virulence protease cleavage site sequence present in both strains. The contribution of the large polymerase protein to NDV virulence is second only to that of the fusion glycoprotein. The identification of virulence determinants is of considerable importance, because of the potential to generate better live attenuated NDV vaccines. It may also be possible to apply these findings to other paramyxoviruses.
PMCID: PMC4135945  PMID: 24850737
2.  Electric-field-induced Shift in the Threshold Voltage in LaAlO3/SrTiO3 Heterostructures 
Scientific Reports  2015;5:8023.
The two-dimensional electron gas (2DEG) at the interface between insulating LaAlO3 and SrTiO3 is intriguing both as a fundamental science topic and for possible applications in electronics or sensors. For example, because the electrical conductance of the 2DEG at the LaAlO3/SrTiO3 interface can be tuned by applying an electric field, new electronic devices utilizing the 2DEG at the LaAlO3/SrTiO3 interface could be possible. For the implementation of field-effect devices utilizing the 2DEG, determining the on/off switching voltage for the devices and ensuring their stability are essential. However, the factors influencing the threshold voltage have not been extensively investigated. Here, we report the voltage-induced shift of the threshold voltage of Pt/LaAlO3/SrTiO3 heterostructures. A large negative voltage induces an irreversible positive shift in the threshold voltage. In fact, after the application of such a large negative voltage, the original threshold voltage cannot be recovered even by application of a large positive electric field. This irreversibility is attributed to the generation of deep traps near the LaAlO3/SrTiO3 interface under the negative voltage. This finding could contribute to the implementation of nanoelectronic devices using the 2DEG at the LaAlO3/SrTiO3 interface.
PMCID: PMC4306114  PMID: 25620684
3.  Improved application of the electrophoretic tissue clearing technology, CLARITY, to intact solid organs including brain, pancreas, liver, kidney, lung, and intestine 
BMC Developmental Biology  2014;14(1):781.
Mapping of tissue structure at the cellular, circuit, and organ-wide scale is important for understanding physiological and biological functions. A bio-electrochemical technique known as CLARITY used for three-dimensional anatomical and phenotypical mapping within transparent intact tissues has been recently developed. This method provided a major advance in understanding the structure-function relationships in circuits of the nervous system and organs by using whole-body clearing. Thus, in the present study, we aimed to improve the original CLARITY procedure and developed specific CLARITY protocols for various intact organs.
We determined the optimal conditions for reducing bubble formation, discoloration, and depositing of black particles on the surface of tissue, which allowed production of clearer organ images. We also determined the appropriate replacement cycles of clearing solution for each type of organ, and convincingly demonstrated that 250–280 mA is the ideal range of electrical current for tissue clearing. We then acquired each type of cleared organs including brain, pancreas, liver, lung, kidney, and intestine. Additionally, we determined the images of axon fibers of hippocampal region, the Purkinje layer of cerebellum, and vessels and cellular nuclei of pancreas.
CLARITY is an innovative biochemical technology for the structural and molecular analysis of various types of tissue. We developed improved CLARITY methods for clearing of the brain, pancreas, lung, intestine, liver, and kidney, and identified the appropriate experimental conditions for clearing of each specific tissue type. These optimized methods will be useful for the application of CLARITY to various types of organs.
Electronic supplementary material
The online version of this article (doi:10.1186/s12861-014-0048-3) contains supplementary material, which is available to authorized users.
PMCID: PMC4281481  PMID: 25528649
CLARITY; Brain; Nervous system; Electrophoretic tissue clearing; 3D Reconstruction; Purkinje layer
4.  18F-FDG PET in Patients with Primary Systemic Anaplastic Large Cell Lymphoma: Differential Features According to Expression of Anaplastic Lymphoma Kinase 
Primary systemic anaplastic large cell lymphoma (ALCL) is divided into two entities according to the expression of anaplastic lymphoma kinase (ALK). We investigated 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) findings in primary systemic ALCL according to ALK expression.
Thirty-seven patients who had baseline PET before CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone)-based chemotherapy were enrolled. Among them, patients who underwent interim and/or post-therapy PET were further investigated for the treatment response and survival analysis. Baseline PET was analyzed visually and semi-quantitatively using peakSUV, and interim and post-therapy PETs were visually analyzed.
All cases were 18F-FDG-avid on baseline PET. The peakSUV of ALK-positive ALCL (n = 16, 18.7 ± 10.5) was higher than that of ALK-negative ALCL (n = 21, 10.0 ± 4.9) (P = 0.006). In ALK-negative ALCL, complete response (CR) rate in negative-interim PET was higher than positive-interim PET (100 % vs 37.5 %, P = 0.02); however, there was no such difference in ALK-positive ALCL (100 % vs 75 %, P = 0.19). The 3-year progression-free survival (PFS) was not significantly different between ALK-positive and ALK-negative ALCL (72.7 % vs 47.6 %, P = 0.34). In ALK-negative ALCL, negative interim and post-therapy PET patients had better 3-year PFS than positive interim (83.3 % vs 25.0 %, P = 0.06) and post-therapy PET patients (70.0 % vs 20.0 %, P = 0.04). In contrast, ALK-positive ALCL had no such differences between PFS and PET results.
On baseline PET, all cases showed 18F-FDG-avidity, and ALK expression was related to higher 18F-FDG uptake. ALK-positive patients tend to have better PFS than ALK-negative patients. Negative-interim PET was a good indicator of CR, and interim or post-therapy PET was helpful for predicting the prognosis only in the ALK-negative group.
PMCID: PMC4035167  PMID: 24900120
Primary systemic anaplastic large cell lymphoma; Anaplastic lymphoma kinase; 18F-FDG PET
5.  The Expression of AGO2 and DGCR8 in Idiopathic Sudden Sensorineural Hearing Loss 
The microRNAs have been implicated in the development and function of the inner ear, especially in contribution to hearing. However, the impact of idiopathic sudden sensorineural hearing loss (SSNHL) on expression of miRNA biogenesis-related components has not been established. To investigate the regulations of microRNA (miRNA) biogenesis-related components, argonaute 2 (AGO2) and DiGeorge syndrome critical region gene 8 (DGCR8) mRNA expression in SSNHL and to evaluate the value of clinical parameters on their expression.
Thirty-seven patients diagnosed with SSNHL and fifty-one healthy volunteers were included in this study. We measured mRNA expression levels of AGO2 and DGCR8 in whole blood cells but erythrocytes of patients with SSNHL and controls, using reverse transcription and real-time polymerase chain reaction analysis.
The mRNA expression level of AGO2 is upregulated in SSNHL. The expression level of AGO2 was significantly correlated with that of DGCR8 in both patients with SSNHL and controls. Expression level of AGO2 in SSNHL was correlated with white blood cell counts.
This study demonstrated for the first time that the AGO2 mRNA expression level was upregulated in SSNHL, suggesting its important role in pathobiology of SSNHL development.
PMCID: PMC4240483  PMID: 25436045
MicroRNA biogenesis; Sudden hearing loss; DiGeorge syndrome critical region gene 8; Argonaute 2
6.  Relationship between adhering to dietary guidelines and the risk of obesity in Korean children 
Nutrition Research and Practice  2014;8(6):705-712.
Dietary guidelines for Korean children were released in 2009. The goal of the present study was to examine diet quality in terms of adherence to these dietary guidelines as well as explore the association between guideline adherence and risk of obesity in Korean children.
Children aged 5-11 years (mean age = 8.9 years old, n = 191, 80.6% girls) were recruited from a university hospital in Seoul, Korea. Adherence to dietary guidelines for Korean children was calculated using the Likert scale (1-5), and children were then categorized into low, moderate, and high groups based on adherence scores. Obesity or being overweight was determined based on an age- and gender- specific percentile for body mass index (BMI) of the 2007 Korean National Growth Charts. Diet quality was evaluated from 3 days of dietary intake data.
Children in the high adherence group were characterized by significantly lower BMI percentiles and paternal BMIs as well as higher percentages of fathers with a high level of education and higher household incomes compared to those in the low or moderate group. Children in the high adherence group consumed significantly higher amounts of milk and dairy products, were less likely to consume lower than the EAR of phosphorus and iron, and had higher NARs for calcium, phosphorus, iron, zinc, and MAR than those in low groups. The ORs for obesity (BMI ≥ 95th percentile) or being overweight including obesity (BMI ≥ 85th percentile) were significantly lower in the high adherence group compared to the low adherence group (OR: 0.33, 95% CI = 0.13-0.82, P for trend = 0.019; OR: 0.26, 95% CI: 0.11-0.61 P for trend = 0.002).
Korean children who adhered to dietary guidelines displayed better diet quality and a reduced risk of obesity.
PMCID: PMC4252531  PMID: 25489411
Children; obesity; adherence; dietary guidelines; Korean
7.  Clinical features and outcomes in patients with human immunodeficiency virus-negative, multicentric Castleman's disease: a single medical center experience 
Blood research  2014;49(4):253-258.
Multicentric Castleman's disease (CD) is commonly associated with poor prognosis, and well-known prognostic factors are scarce. We performed a retrospective analysis to define the clinical features and prognostic factors for patients with multicentric CD.
Between 1990 and 2013, 32 patients with multicentric CD were identified from the database of the Asan Medical Center, Seoul, Korea. Clinicopathologic data were collected by reviewing the medical records. With the exclusion of 4 patients because of unknown human immunodeficiency virus infection status, 28 human immunodeficiency virus-negative patients with multicentric CD were included in this analysis.
Most of the patients were male (76%) and had a median age of 54 years. Hyaline vascular variant was the most common subtype (N=11, 39%). Hepatosplenomegaly (61%), fever (39%), edema (29%), and ascites (18%) were the most frequently reported symptoms and signs at diagnosis. With a median follow-up of 67 months, the 5-year overall survival (OS) was 77%. Patients with extravascular fluid accumulation (i.e., peripheral edema, ascites, and/or pleural effusions) were significantly associated with a poor survival rate (5-year OS, 94% vs. 56%; P=0.04). The extent of disease involvement was also a significant prognostic factor (5-year OS, 91% for involvement on a single side vs. 73% on both sides of the diaphragm; P=0.03). Other clinicopathologic factors were not significantly associated with patient survival.
Our findings suggest that the hyaline vascular variant is not a rare subtype of multicentric CD. Extravascular fluid accumulation and disseminated disease involvement seem to be significant prognostic factors.
PMCID: PMC4278007  PMID: 25548759
Multicentric Castleman's disease; Giant lymph node hyperplasia; Angiofollicular lymphoid hyperplasia; Prognosis; HIV
8.  Serum lipid profiles and glycemic control in adolescents and young adults with type 1 diabetes mellitus 
We aimed to investigate serum lipid profiles and glycemic control in adolescents and young adults with type 1diabetes mellitus (T1DM).
This cross-sectional study included 29 Korean young adults and adolescents with T1DM. The median age was 17 years (range, 10-25 years) and 18 (62.1%) were female. We compared the lipid profiles of patients with dyslipidemia and those without dyslipidemia. Correlations between glycosylated hemoglobin (HbA1c) and lipid profiles (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglyceride [TG]) were determined by linear regression analysis.
Of the 29 patients with T1DM, 11 (37.9%) were classified as having dyslipidemia due to the following lipid abnormality: TC≥200 mg/dL in 8 patients, LDL-C≥130 mg/dL in 4 patients, TG≥150 mg/dL in 2 patients, and HDL-C≤35 mg/dL in 2 patients. Compared to patients without dyslipidemia, patients with dyslipidemia were more likely to have higher values of HbA1c (median, 10.6%; range, 7.5%-12.3% vs. median, 8.0%; range, 6.6%-10.0%; P=0.002) and a higher body mass index z score (median, 0.7; range, -0.57 to 2.6 vs. median, -0.4; range, -2.5 to 2.2; P=0.02). HbA1c levels were positively correlated with TC (P=0.03, R2=0.156) and TG (P=0.005, R2=0.261).
A substantial proportion of adolescents and young adults with T1DM had dyslipidemia. We found a correlation between poor glycemic control and poor lipid profiles in those patients.
PMCID: PMC4316412  PMID: 25654064
Diabetes mellitus; Dyslipidemia; Glycemic index; Prevalence; Young adult
9.  Varicella and Varicella Vaccination in South Korea 
With continuing occurrence of varicella despite increasing vaccine coverage for the past 20 years, a case-based study, a case-control study, and an immunogenicity and safety study were conducted to address the impact of varicella vaccination in South Korea. Varicella patients under the age of 16 years were enrolled for the case-based study. For the case-control study, varicella patients between 12 months and 15 years of age were enrolled with one control matched for each patient. For the immunogenicity and safety study, otherwise healthy children from 12 to 24 months old were immunized with Suduvax (Green Cross, South Korea). Fluorescent antibody to membrane antigen (FAMA) varicella-zoster virus (VZV) antibody was measured before and 6 weeks after immunization. In the case-based study, the median age of the patients was 4 years. Among 152 patients between 1 and 15 years of age, 139 children received varicella vaccine and all had breakthrough infections. Clinical courses were not ameliorated in vaccinated patients, but more vaccinated patients received outpatient rather than inpatient care. In the case-control study, the adjusted overall effectiveness of varicella vaccination was 54%. In the immunogenicity and safety study, the seroconversion rate and geometric mean titer for FAMA antibody were 76.67% and 5.31. Even with increasing varicella vaccine uptake, we illustrate no upward age shift in the peak incidence, a high proportion of breakthrough disease, almost no amelioration in disease presentation by vaccination, and insufficient immunogenicity of domestic varicella vaccine. There is need to improve the varicella vaccine used in South Korea.
PMCID: PMC4018876  PMID: 24671555
10.  Endothelial nitric oxide synthase gene polymorphisms and the risk of osteonecrosis of the femoral head in systemic lupus erythematosus 
International Orthopaedics  2013;37(11):2289-2296.
Nitric oxide (NO), a short-lived gaseous free radical, is a potent mediator of biological responses involved in the pathogenesis of autoimmune rheumatic diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Nitric oxide also serves as an important signal in physiological processes, including angiogenesis, thrombosis, and bone turnover, which are known to be related to the pathogenesis of osteonecrosis. We investigated whether NOS3 gene polymorphisms are associated with risk of osteonecrosis of the femoral head (ONFH).
Five polymorphisms in the NOS3 gene were genotyped using TaqMan assays in 306 controls, 150 SLE patients, and 50 SLE patients with ONFH (SLE_ONFH).
We found that Asp258Asp and Glu298Asp (G894T) polymorphisms in the NOS3 gene were significantly associated with risk of ONFH. Additionally, we calculated haplotype frequencies of a linkage disequilibrium (LD) block in NOS3 (rs1799983 − rs1800780) and tested for haplotype associations. The haplotypes G-A and T-A showed significant protective (P = 1.6 × 10-3; OR 0.39, 95 % confidence intervals (CI) 0.22–0.7) and increased risk (P = 2.0 x 10-5–6.0 x 10-4; OR 3.17−3.73) effects for ONFH, respectively.
These results suggest that exonic NOS3 polymorphisms may increase the risk of ONFH in Korean SLE patients
Electronic supplementary material
The online version of this article (doi:10.1007/s00264-013-1966-6) contains supplementary material, which is available to authorized users.
PMCID: PMC3824903  PMID: 23775455
11.  A Customized Bolus Produced Using a 3-Dimensional Printer for Radiotherapy 
PLoS ONE  2014;9(10):e110746.
Boluses are used in high-energy radiotherapy in order to overcome the skin sparing effect. In practice though, commonly used flat boluses fail to make a perfect contact with the irregular surface of the patient’s skin, resulting in air gaps. Hence, we fabricated a customized bolus using a 3-dimensional (3D) printer and evaluated its feasibility for radiotherapy.
We designed two kinds of bolus for production on a 3D printer, one of which was the 3D printed flat bolus for the Blue water phantom and the other was a 3D printed customized bolus for the RANDO phantom. The 3D printed flat bolus was fabricated to verify its physical quality. The resulting 3D printed flat bolus was evaluated by assessing dosimetric parameters such as D1.5 cm, D5 cm, and D10 cm. The 3D printed customized bolus was then fabricated, and its quality and clinical feasibility were evaluated by visual inspection and by assessing dosimetric parameters such as Dmax, Dmin, Dmean, D90%, and V90%.
The dosimetric parameters of the resulting 3D printed flat bolus showed that it was a useful dose escalating material, equivalent to a commercially available flat bolus. Analysis of the dosimetric parameters of the 3D printed customized bolus demonstrated that it is provided good dose escalation and good contact with the irregular surface of the RANDO phantom.
A customized bolus produced using a 3D printer could potentially replace commercially available flat boluses.
PMCID: PMC4206462  PMID: 25337700
12.  The Effectiveness of Cross-Tapering Switching to Ziprasidone in Patients with Schizophrenia or Schizoaffective Disorder 
Psychiatry Investigation  2014;11(4):459-466.
Switching antipsychotics is one useful therapeutic option when the treatment of schizophrenia encounters suboptimal efficacy and intolerability issues. This study aimed to investigate the efficacy and tolerability of cross-tapering switching to ziprasidone from other antipsychotics.
A total of 67 patients with schizophrenia or schizoaffective disorder were recruited in this 12-week, multicenter, non-comparative, open-label trial. Prior antipsychotics were allowed to be maintained for up to 4 weeks during the titration of ziprasidone. Efficacy was primarily measured using the 18-item Brief Psychotic Rating Scale (BPRS) at baseline, 4 weeks, 8 weeks, and 12 weeks. Efficacy was secondarily measured by the Clinical Global Impression-Severity (CGI-S) scale and the Global Assessment of Functioning (GAF) scale at each visit. Regarding the metabolic effects of switching to ziprasidone, weight, body mass index (BMI), waist-to-hip ratio (WHR), and lipid profile-including triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and total cholesterol levels-were measured at each follow-up visit.
The BPRS scores were significantly improved at 12 weeks after switching to ziprasidone (F=5.96, df=2.11, p=0.003), whereas the CGI-S and GAF scores were not significantly changed. BMIs, WHRs, and TG levels were significantly decreased, with no significant changes in other lipid profiles.
Cross-tapering switching to ziprasidone is effective for patients with schizophrenia spectrum disorders. Beyond the efficacy of the procedure, favorable metabolic profiles show that switching to ziprasidone may be helpful for maintenance therapy over an extended period.
PMCID: PMC4225211  PMID: 25395978
Ziprasidone; Schizophrenia; Switching; Pharmacotherapy; Triglyceride
13.  Fucoidan, a Sulfated Polysaccharide, Inhibits Osteoclast Differentiation and Function by Modulating RANKL Signaling 
Multinucleated osteoclasts differentiate from hematopoietic progenitors of the monocyte/macrophage lineage. Because of its pivotal role in bone resorption, regulation of osteoclast differentiation is a potential therapeutic approach to the treatment of erosive bone disease. In this study, we have found that fucoidan, a sulfated polysaccharide extracted from brown seaweed, inhibited osteoclast differentiation. In particular, addition of fucoidan into the early stage osteoclast cultures significantly inhibited receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL)-induced osteoclast formation, thus suggesting that fucoidan affects osteoclast progenitors. Furthermore, fucoidan significantly inhibited the activation of RANKL-dependent mitogen-activated protein kinases (MAPKs) such as JNK, ERK, and p38, and also c-Fos and NFATc1, which are crucial transcription factors for osteoclastogenesis. In addition, the activation of NF-κB, which is an upstream transcription factor modulating NFATc1 expression, was alleviated in the fucoidan-treated cells. These results collectively suggest that fucoidan inhibits osteoclastogenesis from bone marrow macrophages by inhibiting RANKL-induced p38, JNK, ERK and NF-κB activation, and by downregulating the expression of genes that partake in both osteoclast differentiation and resorption.
PMCID: PMC4227250  PMID: 25334060
fucoidan; osteoclastogenesis; sulfated polysaccharide; bone resorption; RANKL (receptor activator of nuclear factor kappa B (NF-κB) ligand)
14.  Meta-analysis identifies a MECOM gene as a novel predisposing factor of osteoporotic fracture 
Journal of medical genetics  2013;50(4):212-219.
Osteoporotic fracture (OF) as a clinical endpoint is a major complication of osteoporosis. To screen for OF susceptibility genes, we performed a genome-wide association study and carried out de novo replication analysis of an East Asian population.
Association was tested using a logistic regression analysis. A meta-analysis was performed on the combined results using effect size and standard errors estimated for each study.
In a combined meta-analysis of a discovery cohort (288 cases and 1139 controls), three hospital based sets in replication stage I (462 cases and 1745 controls), and an independent ethnic group in replication stage II (369 cases and 560 for controls), we identified a new locus associated with OF (rs784288 in the MECOM gene) that showed genome-wide significance (p=3.59×10−8; OR 1.39). RNA interference revealed that a MECOM knockdown suppresses osteoclastogenesis.
Our findings provide new insights into the genetic architecture underlying OF in East Asians.
PMCID: PMC4169276  PMID: 23349225
15.  Carboxypeptidase E Is a Novel Modulator of RANKL-Induced Osteoclast Differentiation 
Molecules and Cells  2014;37(9):685-690.
Osteoclasts are large polykaryons that have the unique capacity to degrade bone and are generated by the differentiation of myeloid lineage progenitors. To identify the genes involved in osteoclast development, we performed microarray analysis, and we found that carboxypeptidase E (CPE), a prohormone processing enzyme, was highly upregulated in osteoclasts compared with their precursors, bone marrow-derived macrophages (BMMs). Here, we demonstrate a novel role for CPE in receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation. The overexpression of CPE in BMMs increases the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinuclear osteoclasts and the expression of c-Fos and nuclear factor of activated T cells c1 (NFATc1), which are key regulators in osteoclastogenesis. Furthermore, employing CPE knockout mice, we show that CPE deficiency attenuates osteoclast formation. Together, our data suggest that CPE might be an important modulator of RANKL-induced osteoclast differentiation.
PMCID: PMC4179137  PMID: 25220258
c-Fos; CPE; NFATc1; osteoclast; RANKL
16.  The Study About Physical Activity for Subjects With Prevention of Benign Prostate Hyperplasia 
The number of benign prostatic hyperplasia (BPH) subjects has been increasing worldwide, and many studies have been conducted to determine the treatment that can delay drug therapy or surgery. Subsequently, most of these studies involved physical activity (PA) and associated factors. Therefore, we aimed to determine factors associated with BPH prevalence based on a review of past and present studies and to investigate the effect of a healthy lifestyle as a protective factor of BPH occurrence.
We selected 582 subjects aged ≥40 years from an initial 779 subjects recruited from Gyeonggi, Yangpyeong, South Korea, during August 2009 to August 2011. Trained investigators surveyed International Prostate Symptom Score and demographic information, including PA and lifestyle questionnaire during face-to-face interviews; further, they performed digital rectal examination, rectal ultrasonography, and measured prostate-specific antigen levels. The statistical association between PA and BPH was analyzed by logistic regression analysis using multivariable regression models which use categorical variables by the Cochran-Mantel-Haenszel test and continuous variables by the general linear model.
Seven statistically significant variables for PA were selected. Regular exercise, frequency of exercise, sedentary time, nonsedentary time, leisure time PA (metabolic equivalent, hr/wk) were not statistically associated with prostate volume but sedentary time (hr/day) was the only factor that showed a significant association in the multivariable model, including a linear effect relationship. Subjects with lower levels of sedentary time (4.5-7.0 hr/day) had a significantly lower risk of BPH (odds ratio [OR], 0.93; 95% confidence interval [CI], 0.52-1.67) than those with a higher sedentary time (>7 hr/day) (OR, 1.72; 95% CI, 0.96-3.09) (P for trend=0.05).
Our study showed that reducing sedentary time could have a protective effect and reduce the prevalence of BPH. Further prospective studies with a larger sample size are needed to assess the impact of reducing sedentary time on BPH risk.
PMCID: PMC4180167  PMID: 25279244
Prostatic hyperplasia; Leisure activities; Quality of life
17.  Treatment of primary testicular diffuse large B cell lymphoma without prophylactic intrathecal chemotherapy: a single center experience 
Blood research  2014;49(3):170-176.
Primary testicular diffuse large B-cell lymphoma (DLBCL) is a rare but aggressive extranodal lymphoma, and its relapse in the central nervous system (CNS) is a major concern during treatment. Despite this, the role of intrathecal prophylaxis in primary testicular DLBCL remains controversial.
We retrospectively reviewed the medical records of 14 patients with primary testicular DLBCL diagnosed between November 2000 and June 2012, and analyzed the CNS relapse rate in patients treated without intrathecal prophylaxis. Survival curves were estimated using the Kaplan-Meier method.
The median age at diagnosis was 57 years (range, 41-79 years). Unilateral testicular involvement was observed in 13 patients. Nine patients had stage I, 1 had stage II, and 4 had stage IV disease. The international prognostic index was low or low-intermediate risk in 12 patients and high-intermediate risk in 2 patients. Thirteen patients underwent orchiectomy. All the patients received systemic chemotherapy without intrathecal prophylaxis, and prophylactic radiotherapy was administered to the contralateral testis in 12 patients. The median follow-up period of surviving patients was 39 months (range, 10-139 months). Median overall survival was not reached and the median progression-free survival was 3.8 years. Four patients experienced relapse, but CNS relapse was observed in only one patient (7.1%) with stage IV disease, 27 months after a complete response.
Even without intrathecal prophylaxis, the rate of relapse in the CNS was lower in the Korean patients with primary testicular DLBCL compared to prior reports.
PMCID: PMC4188782  PMID: 25325036
Diffuse large B cell lymphoma; Intrathecal prophylaxis; Primary testicular lymphoma
18.  Oral Antimicrobial Therapy: Efficacy and Safety for Methicillin-Resistant Staphylococcus aureus Infections and Its Impact on the Length of Hospital Stay 
Infection & Chemotherapy  2014;46(3):172-181.
Carefully switching from intravenous to oral antibiotic therapy has shown to reduce treatment costs and lengths of hospital stay as well as increase safety and comfort in patients with infections. The aim of this study was to compare the clinical efficacy and safety between the patients treated with glycopeptides (case group), and the patients given oral antibiotics, as the initial or step-down therapy (control group), in the treatment of patients with methicillin-resistant Staphylococcus aureus (MRSA) infection.
Materials and Methods
A multicenter observational study was retrospectively performed in 7 teaching hospitals in Korea from January to December 2012. The study included adult patients (≥ 18 years) with infection caused by MRSA isolates, susceptible to clindamycin, erythromycin, and ciprofloxacin. The primary end point was treatment outcome, including all-cause mortality and switching of antibiotics. Drug-related adverse events and the lengths of hospital stay were also compared between the two treatment groups.
During the study period, 107 patients (43 cases and 64 controls) with MRSA infections were enrolled from the participating hospitals. The most common sites of MRSA infection were skin and soft tissue (n = 28) and bone and joint (n = 26). The median Charlson comorbidity index (P = 0. 560), the frequency of severe sepsis (P = 0.682) or thrombocytopenia (P = 1.000), and median level of serum C-reactive protein (P = 0.157) at the onset of MRSA infections were not significantly different between the case and control groups. The oral antibiotics most frequently prescribed in the case group, were fluoroquinolones (n = 29) and clindamycin (n = 8). The median duration of antibiotic treatment (P = 0.090) and the occurrence of drug-related adverse events (P = 0.460) did not reach statistically significant difference between the two groups, whereas the total length of hospital stay after the onset of MRSA infection was significantly shorter in the case group than the control group [median (interquartile range), 23 days (8-41) vs. 32 days (15-54), P = 0.017]. In multivariate analyses, the type of antibiotic used was not an independent risk factor for treatment failure. The statistically significant factors associated with treatment failure included underlying hepatic diseases, prior receipt of antibiotics, and foreign body retention.
This study indicates that oral antibiotic therapy with active agents against MRSA isolates can be considered as the initial or step-down therapy for the treatment of MRSA infections and also reduce the length of hospital stay.
PMCID: PMC4189139  PMID: 25298906
Methicillin-resistant Staphylococcus aureus; Administration; Oral; Length of stay
19.  Spontaneous Pneumomediastinum, Pneumopericardium, and Pneumothorax with Respiratory Failure in a Patient with AIDS and Pneumocystis jirovecii Pneumonia 
Infection & Chemotherapy  2014;46(3):204-208.
Spontaneous pneumothorax occurs in up to 35% of patients with Pneumocystis jirovecii pneumonia. However, spontaneous pneumomediastinum and pneumopericardium are uncommon complications in patients infected with human immunodeficiency virus, with no reported incidence rates, even among patients with acquired immunodeficiency syndrome (AIDS) and P. jirovecii pneumonia. We report a case of spontaneous pneumomediastinum, pneumopericardium, and pneumothorax with respiratory failure during treatment of P. jirovecii pneumonia in a patient with AIDS; the P. jirovecii infection was confirmed by performing methenamine silver staining of bronchoalveolar lavage specimens. This case suggests that spontaneous pneumomediastinum and pneumopericardium should be considered in patients with AIDS and P. jirovecii pneumonia.
PMCID: PMC4189138  PMID: 25298911
Pneumomediastinum; Pneumopericardium; Human immunodeficiency virus; Pneumocystis jirovecii
20.  Clinical and Radiological Outcomes of a New Cage for Direct Lateral Lumbar Interbody Fusion 
Korean Journal of Spine  2014;11(3):145-151.
In Korea, direct lateral interbody fusion (DLIF) was started since 2011, using standard cage (6° lordotic angle, 18mm width). Recently, a new wider cage with higher lordotic angle (12°, 22mm) was introduced. The aim of our study is to compare the clinical and radiologic outcomes of the two cage types.
We selected patients underwent DLIF, 125 cases used standard cages (standard group) and 38 cases used new cages (wide group). We followed them up for more than 6 months, and their radiological and clinical outcomes were analyzed retrospectively. For radiologic outcomes, lumbar lordotic angle (LLA), segmental lordoic angle (SLA), disc angle (DA), foraminal height change (FH), subsidence and intraoperative endplate destruction (iED) were checked. Clinical outcomes were compared using visual analog scale (VAS) score, Oswestry disability index (ODI) score and complications.
LLA and SLA showed no significant changes postoperatively in both groups. DA showed significant increase after surgery in the wide group (p<0.05), but not in the standard group. Subsidence was significantly lower in the wide group (p<0.05). There was no difference in clinical outcomes between the two groups. Additional posterior decompression was done more frequently in the wide group. Postoperative change of foraminal height was significantly lower in the wide group (p<0.05). The iED was observed more frequently in the wide group (p<0.05) especially at the anterior edge of cage.
The new type of cage seems to result in more DA and less subsidence. But indirect foraminal decompression seems to be less effective than standard cage. Intraoperative endplate destruction occurs more frequently due to a steeper lordotic angle of the new cage.
PMCID: PMC4206975  PMID: 25346760
DLIF; Cage; Type; Outcome
21.  AMD3100 improves ovariectomy-induced osteoporosis in mice by facilitating mobilization of hematopoietic stem/progenitor cells 
BMB Reports  2014;47(8):439-444.
Inhibition of an increase of osteoclasts has become the most important treatment for osteoporosis. The CXCR4 antagonist, AMD3100, plays an important role in the mobilization of osteoclast precursors within bone marrow (BM). However, the actual therapeutic impact of AMD3100 in osteoporosis has not yet been ascertained. Here we demonstrate the therapeutic effect of AMD3100 in the treatment of ovariectomy-induced osteoporosis in mice. We found that treatment with AMD3100 resulted in direct induction of release of SDF-1 from BM to blood and mobilization of hematopoietic stem/progenitor cells (HSPCs) in an osteoporosis model. AMD3100 prevented bone density loss after ovariectomy by mobilization of HSPCs, suggesting a therapeutic strategy to reduce the number of osteoclasts on bone surfaces. These findings support the hypothesis that treatment with AMD3100 can result in efficient mobilization of HSPCs into blood through direct blockade of the SDF-1/CXCR4 interaction in BM and can be considered as a potential new therapeutic intervention for osteoporosis. [BMB Reports 2014; 47(8): 439-444]
PMCID: PMC4206715  PMID: 24314140
AMD3100; Hematopoietic stem/Progenitor cell; Mobilization; Osteoclast; Osteoporosis
22.  A Medium-Chain Fatty Acid, Capric Acid, Inhibits RANKL-Induced Osteoclast Differentiation via the Suppression of NF-κB Signaling and Blocks Cytoskeletal Organization and Survival in Mature Osteoclasts 
Molecules and Cells  2014;37(8):598-604.
Fatty acids, important components of a normal diet, have been reported to play a role in bone metabolism. Osteoclasts are bone-resorbing cells that are responsible for many bone-destructive diseases such as osteoporosis. In this study, we investigated the impact of a medium-chain fatty acid, capric acid, on the osteoclast differentiation, function, and survival induced by receptor activator of NF-κB ligand (RANKL) and macrophage colony-stimulating factor (MCSF). Capric acid inhibited RANKL-mediated osteoclastogenesis in bone marrow-derived macrophages and suppressed RANKL-induced IκBα phosphorylation, p65 nuclear translocation, and NF-κB transcriptional activity. Capric acid further blocked the RANKL-stimulated activation of ERK without affecting JNK or p38. The induction of NFATc1 in response to RANKL was also attenuated by capric acid. In addition, capric acid abrogated M-CSF and RANKL-mediated cytoskeleton reorganization, which is crucial for the efficient bone resorption of osteoclasts. Capric acid also increased apoptosis in mature osteoclasts through the induction of Bim expression and the suppression of ERK activation by M-CSF. Together, our results reveal that capric acid has inhibitory effects on osteoclast development. We therefore suggest that capric acid may have potential therapeutic implications for the treatment of bone resorption-associated disorders.
PMCID: PMC4145371  PMID: 25134536
apoptosis; capric acid; cytoskeletal organization; NFATc1; NF-κB; osteoclast
23.  Effects of Naturally Occurring Six- and Twelve-Nucleotide Inserts on Newcastle Disease Virus Replication and Pathogenesis 
PLoS ONE  2014;9(8):e103951.
Newcastle disease virus (NDV) isolates contain genomes of 15,186, 15,192 or 15,198 nucleotides (nt). The length differences reflect a 6-nt insert in the 5′ (downstream) non-translated region (NTR) of the N gene (15,192-nt genome) or a 12-nt insert in the ORF encoding the P and V proteins (causing a 4-amino acid insert; 15,198-nt genome). We evaluated the role of these inserts in the N and P genes on viral replication and pathogenicity by inserting them into genomes of two NDV strains that have natural genome lengths of 15,186 nt and represent two different pathotypes, namely the mesogenic strain Beaudette C (BC) and the velogenic strain GB Texas (GBT). Our results showed that the 6-nt and 12-nt inserts did not detectably affect N gene expression or P protein function. The inserts had no effect on the replication or virulence of the highly virulent GBT strain but showed modest degree of attenuation in mesogenic strain BC. We also deleted a naturally-occurring 6-nt insertion in the N gene from a highly virulent 15,192-nt genome-length virus, strain Banjarmasin. This resulted in reduced replication in vitro and reduced virulence in vivo. Thus, although these inserts had no evident effect on gene expression, protein function, or replication in vivo, they did affect virulence in two of the three tested strains.
PMCID: PMC4122465  PMID: 25093330
24.  Multicenter Prospective Observational Study of the Comparative Efficacy and Safety of Vancomycin versus Teicoplanin in Patients with Health Care-Associated Methicillin-Resistant Staphylococcus aureus Bacteremia 
The purpose of this study was to compare the clinical efficacy and safety of vancomycin to those of teicoplanin for the treatment of adult patients with health care-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) bacteremia. A multicenter observational study was prospectively conducted in 15 teaching hospitals in Korea between February 2010 and July 2011. Adult patients (≥18 years old) with HA-MRSA bacteremia who were initially treated with vancomycin (VAN) (n = 134) or teicoplanin (TEC) (n = 56) were enrolled. Clinical and microbiological responses and drug-related adverse events were compared between the two treatment groups using univariate and multivariate logistic regression analyses. The vancomycin and teicoplanin MICs were determined by Etest. The MRSA-related mortality, duration of fever, and duration of MRSA bacteremia in the treatment groups were not significantly different. There was no significant difference in the occurrence of drug-related adverse events. Among the 190 MRSA isolates, the VAN MICs ranged from 0.5 to 2 μg/ml (MIC50 and MIC90, 1.5 μg/ml), and the TEC MIC ranged from 0.5 to 8 μg/ml (MIC50, 3 μg/ml; MIC90, 6 μg/ml). In multivariate analyses, the antibiotic type (vancomycin or teicoplanin) was not associated with treatment outcomes. This study indicates that teicoplanin is an effective and safe alternative to vancomycin for the treatment of HA-MRSA bacteremia.
PMCID: PMC3910721  PMID: 24165181
25.  Leptomeningeal Carcinomatosis of Gastric Cancer Misdiagnosed as Vestibular Schwannoma 
Gastric cancer is one of the most common causes of cancer-related death in Asian countries, including Korea. We experienced a case of leptomeningeal carcinomatosis (LC) from gastric cancer that was originally misdiagnosed as vestibular schwannoma based on the similar radiological characteristics. To our knowledge, LC from gastric cancer is very rare. In conclusion, our experience with this case suggests that clinicians should consider the possibility of delayed leptomeningeal metastasis when treating patients with gastric cancer.
PMCID: PMC4185321  PMID: 25289126
Meningeal carcinomatosis; Leptomeningeal carcinomatoses; Carcinomatous meningitis; Signet ring cell carcinoma; Vestibular schwannoma; Neurofibromatoses

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