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1.  Development of Safe and Effective RSV Vaccine by Modified CD4 Epitope in G Protein Core Fragment (Gcf) 
PLoS ONE  2014;9(4):e94269.
Respiratory syncytial virus (RSV) is a major cause of respiratory tract infection in infants and young children worldwide, but currently no safe and effective vaccine is available. The RSV G glycoprotein (RSVG), a major attachment protein, is an important target for the induction of protective immune responses during RSV infection. However, it has been thought that a CD4+ T cell epitope (a.a. 183–195) within RSVG is associated with pathogenic pulmonary eosinophilia. To develop safe and effective RSV vaccine using RSV G protein core fragment (Gcf), several Gcf variants resulting from modification to CD4+ T cell epitope were constructed. Mice were immunized with each variant Gcf, and the levels of RSV-specific serum IgG were measured. At day 4 post-challenge with RSV subtype A or B, lung viral titers and pulmonary eosinophilia were determined and changes in body weight were monitored. With wild type Gcf derived from RSV A2 (wtAGcf), although RSV A subtype-specific immune responses were induced, vaccine-enhanced disease characterized by excessive pulmonary eosinophil recruitment and body weight loss were evident, whereas wtGcf from RSV B1 (wtBGcf) induced RSV B subtype-specific immune responses without the signs of vaccine-enhanced disease. Mice immunized with Th-mGcf, a fusion protein consisting CD4+ T cell epitope from RSV F (F51–66) conjugated to mGcf that contains alanine substitutions at a.a. position 185 and 188, showed higher levels of RSV-specific IgG response than mice immunized with mGcf. Both wtAGcf and Th-mGcf provided complete protection against RSV A2 and partial protection against RSV B. Importantly, mice immunized with Th-mGcf did not develop vaccine-enhanced disease following RSV challenge. Immunization of Th-mGcf provided protection against RSV infection without the symptom of vaccine-enhanced disease. Our study provides a novel strategy to develop a safe and effective mucosal RSV vaccine by manipulating the CD4+ T cell epitope within RSV G protein.
doi:10.1371/journal.pone.0094269
PMCID: PMC3988050  PMID: 24736750
2.  Subclinical Ulnar Neuropathy at the Elbow in Diabetic Patients 
Objective
To demonstrate the prevalence and characteristics of subclinical ulnar neuropathy at the elbow in diabetic patients.
Methods
One hundred and five patients with diabetes mellitus were recruited for the study of ulnar nerve conduction analysis. Clinical and demographic characteristics were assessed. Electrodiagnosis of ulnar neuropathy at the elbow was based on the criteria of the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM1 and AANEM2). The inching test of the ulnar motor nerve was additionally performed to localize the lesion.
Results
The duration of diabetes, the existence of diabetic polyneuropathy (DPN) symptoms, the duration of symptoms, and HbA1C showed significantly larger values in the DPN group (p<0.05). Ulnar neuropathy at the elbow was more common in the DPN group. There was a statistically significant difference in the number of cases that met the three diagnostic criteria between the no DPN group and the DPN group. The most common location for ulnar mononeuropathy at the elbow was the retrocondylar groove.
Conclusion
Ulnar neuropathy at the elbow is more common in patients with DPN. If the conduction velocities of both the elbow and forearm segments are decreased to less than 50 m/s, it may be useful to apply the AANEM2 criteria and inching test to diagnose ulnar neuropathy.
doi:10.5535/arm.2014.38.1.64
PMCID: PMC3953366  PMID: 24639928
Diabetes mellitus; Diabetic polyneuropathy; Ulnar neuropathy; Elbow; Entrapment
3.  Osteogenic Differentiation of Bone Marrow Stem Cell in Poly(Lactic-co-Glycolic Acid) Scaffold Loaded Various Ratio of Hydroxyapatite 
Background and Objectives
Hydroxyapatite has biocompatibility and bioactivity and similar to bone of in human body. The purpose of this study is to evaluate osteogenic differentiation of bone marrow stem cell (BMSC) in PLGA Scaffold added various ratio of hydroxyapatite (HAp).
Methods and Results
PLGA and PLGA/HAp scaffold were prepared using solvent casting/salt-leaching method. BMSC was seeded on the PLGA and PLGA/HAp scaffold and the samples were cultured in 37℃ incubator with 5% CO2 for 28 days. Alkaline phosphatase (ALP) was carried out to evaluate alkaline phosphatase activity at 1, 3, 7, 10 and 14 days. Alizarin Red S stating was performed to identify calcium in scaffold at 1, 7, 14, 21 and 28 days. Compressive strength was measured to evaluate mechanical property of scaffold. To confirm cell viability, MTT was carried out at 1, 3, 7, 14 and 28 days. RT-PCR was performed to verify specific marker expression of osteoblast and stem cell at 7, 14, 21 and 28 days.
Conclusions
Osteogenic differentiation of BMSC was confirmed through ALP, RT-PCR, and alizarin red S staining in this study. These results suggest that HAp helps osteogenic differentiation of BMSC.
PMCID: PMC3841003  PMID: 24298375
Hydroxyapatite; Poly(lactic-co-glycolic acid); Scaffold; Bone marrow stem cell; Osteogenic differentiation
4.  Aurora A kinase expression is increased in leukemia stem cells, and a selective Aurora A kinase inhibitor enhances Ara-C-induced apoptosis in acute myeloid leukemia stem cells 
The Korean Journal of Hematology  2012;47(3):178-185.
Background
The overexpression of Aurora A kinase (AurA) has been reported in various malignancies, including acute myeloid leukemia (AML). However, the expression of AurA and the effects of AurA inhibition in cancer stem cells are not yet fully understood. We investigated the expression and inhibition of AurA in AML stem cells (CD34+/CD38-).
Methods
Expression of AurA was investigated in cell lines (NB4 and KG1) that express high levels of CD34 and low levels of CD38. Primary AML cells were harvested from 8 patients. The expression of AurA and cell death induced by inhibition of AurA were analyzed in CD34+/CD38- cells.
Results
AurA was shown to be overexpressed in both primary AML cells and leukemia stem cells (LSCs) compared to normal hematopoietic stem cells. Inhibition of AurA plus cytarabine treatment in LSCs resulted in increased cytotoxicity compared to cytarabine treatment alone. Additional stimulation with granulocyte-colony stimulating factor (G-CSF) increased the cell death caused by AurA inhibition plus cytarabine treatment.
Conclusion
To our knowledge, this is the first report describing increased expression of AurA in LSCs. Our results suggest that selective AurA inhibition may be used to reduce LSCs, and this reduction may be enhanced by stimulation with G-CSF. Further exploration of relationship between nuclear factor kappa-B and AurA inhibition and the potential of AurA inhibition for use in leukemia treatment is needed.
doi:10.5045/kjh.2012.47.3.178
PMCID: PMC3464334  PMID: 23071472
Acute myeloid leukemia; Leukemia stem cell; Aurora kinase
5.  Optimal Stimulation Site for Deep Peroneal Motor Nerve Conduction Study Around the Ankle: Cadaveric Study 
Annals of Rehabilitation Medicine  2012;36(2):182-186.
Objective
To identify the optimal distal stimulation point for conventional deep peroneal motor nerve (DPN) conduction studies by a cadaveric dissection study.
Method
DPN was examined in 30 ankles from 20 cadavers. The distance from the DPN to the tibialis anterior (TA) tendon was estimated at a point 8 cm proximal to the extensor digitorum brevis (EDB) muscle. Relationships between the DPN and tendons including TA, extensor hallucis longus (EHL), and extensor digitorum longus (EDL) tendons were established.
Results
The median distance from the DPN to the TA tendon in all 30 cadaver ankles was 10 mm (range, 1-21 mm) at a point 8 cm proximal to the EDB muscle. The DPN was situated between EHL and EDL tendons in 18 cases (60%), between TA and EHL tendons in nine cases (30%), and lateral to the EDL tendon in three cases (10%).
Conclusion
The optimal distal stimulation point for the DPN conduction study was approximately 1 cm lateral to the TA tendon at the level of 8 cm proximal to the active electrode. The distal stimulation site for the DPN should be reconsidered in cases with a weaker distal response but without an accessory peroneal nerve.
doi:10.5535/arm.2012.36.2.182
PMCID: PMC3358673  PMID: 22639741
Peroneal nerve; Cadaver; Nerve conduction; Stimulation
6.  Dual Role of Respiratory Syncytial Virus Glycoprotein Fragment as a Mucosal Immunogen and Chemotactic Adjuvant 
PLoS ONE  2012;7(2):e32226.
Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract disease in infancy and early childhood. Despite its importance as a pathogen, there is no licensed vaccine to prevent RSV infection. The G glycoprotein of RSV, a major attachment protein, is a potentially important target for protective antiviral immune responses and has been shown to exhibit chemotactic activity through CX3C mimicry. Here, we show that sublingual or intranasal immunization of a purified G protein fragment of amino acids from 131 to 230, designated Gcf, induces strong serum IgG and mucosal IgA responses. Interestingly, these antibody responses could be elicited by Gcf even in the absence of any adjuvant, indicating a novel self-adjuvanting property of our vaccine candidate. Gcf exhibited potent chemotactic activity in in vitro cell migration assay and cysteine residues are necessary for chemotactic activity and self-adjuvanticity of Gcf in vivo. Mucosal immunization with Gcf also provides protection against RSV challenge without any significant lung eosinophilia or vaccine-induced weight loss. Together, our data demonstrate that mucosal administration of Gcf vaccine elicits beneficial protective immunity and represents a promising vaccine regimen preventing RSV infection.
doi:10.1371/journal.pone.0032226
PMCID: PMC3288084  PMID: 22384186
7.  Evaluation of Protective Efficacy of Respiratory Syncytial Virus Vaccine against A and B Subgroup Human Isolates in Korea 
PLoS ONE  2011;6(9):e23797.
Human respiratory syncytial virus (HRSV) is a significant cause of upper and lower respiratory tract illness mainly in infants and young children worldwide. HRSV is divided into two subgroups, HRSV-A and HRSV-B, based on sequence variation within the G gene. Despite its importance as a respiratory pathogen, there is currently no safe and effective vaccine for HRSV. In this study, we have detected and identified the HRSV by RT-PCR from nasopharyngeal aspirates of Korean pediatric patients. Interestingly, all HRSV-B isolates exhibited unique deletion of 6 nucleotides and duplication of 60 nucleotides in the G gene. We successfully amplified two isolates (‘KR/A/09-8’ belonging to HRSV-A and ‘KR/B/10-12’ to HRSV-B) on large-scale, and evaluated the cross-protective efficacy of our recombinant adenovirus-based HRSV vaccine candidate, rAd/3xG, by challenging the immunized mice with these isolates. The single intranasal immunization with rAd/3xG protected the mice completely from KR/A/09-8 infection and partially from KR/B/10-12 infection. Our study contributes to the understanding of the genetic characteristics and distribution of subgroups in the seasonal HRSV epidemics in Korea and, for the first time, to the evaluation of the cross-protective efficacy of RSV vaccine against HRSV-A and -B field-isolates.
doi:10.1371/journal.pone.0023797
PMCID: PMC3168431  PMID: 21915262
8.  Intranasal Delivery of Cholera Toxin Induces Th17-Dominated T-Cell Response to Bystander Antigens 
PLoS ONE  2009;4(4):e5190.
Cholera toxin (CT) is a potent vaccine adjuvant, which promotes mucosal immunity to protein antigen given by nasal route. It has been suggested that CT promotes T helper type 2 (Th2) response and suppresses Th1 response. We here report the induction of Th17-dominated responses in mice by intranasal delivery of CT. This dramatic Th17-driving effect of CT, which was dependent on the B subunit, was observed even in Th1 or Th2-favored conditions of respiratory virus infection. These dominating Th17 responses resulted in the significant neutrophil accumulation in the lungs of mice given CT. Both in vitro and in vivo treatment of CT induced strongly augmented IL-6 production, and Th17-driving ability of CT was completely abolished in IL-6 knockout mice, indicating a role of this cytokine in the Th17-dominated T-cell responses by CT. These data demonstrate a novel Th17-driving activity of CT, and help understand the mechanisms of CT adjuvanticity to demarcate T helper responses.
doi:10.1371/journal.pone.0005190
PMCID: PMC2663811  PMID: 19360100

Results 1-8 (8)