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1.  Phylogenetic Analysis of Near Full-Length HIV Type 1 Genomic Sequences from 21 Korean Individuals 
The Korean subclade of subtype B (KSB) is the most prevalent HIV-1 strain found in Korea. To date, only two near full-length HIV-1 sequences from Korean patients have been reported. Here, we analyzed a total of 24 near full-length genomes of HIV-1 strains that were isolated from 17 antiretroviral therapy (ART)-naive patients and four ART-exposed patients. Proviral DNA from peripheral blood mononuclear cells was PCR amplified and directly sequenced. Phylogenetic analyses were used to classify viruses from 19 patients as KSB, from one patient as subtype B, from one patient as subtype D, and three viruses from one patient as CRF02_AG. All KSB viruses demonstrated TAAAA instead of TATAA at the TATA box in the LTR. Of the 19 KSB patients, their sequence identities at the nucleotide level ranged from 89.8% to 97.1% from the lowest env gene to the highest pol gene. Other than the CRF02_AG viruses, no recombination events were noted in any of the 19 KSB patients, which is consistent with our previous studies on the pol, vif, and nef genes. Except for one strain, all of the strains were classified as non-syncytium-inducing strains. This is the first report to describe near full-length KSB.
PMCID: PMC3607908  PMID: 23199052
2.  Endotracheal tube intubation with the aid of a laryngeal mask airway, a fiberoptic bronchoscope, and a tube exchanger in a difficult airway patient: a case report 
Korean Journal of Anesthesiology  2014;66(3):237-239.
A 28-year-old male patient with occipito-atlanto-axial instability underwent a cervical fusion with posterior technique. Post-operatively, the endotracheal tube (ETT) was removed, and the patient was transferred to the intensive care unit. After transfer, an upper airway obstruction developed and reintubations with a laryngoscope were attempted but failed. We inserted a #4 proseal laryngeal mask airway (LMA) and passed a 5.0 mm ETT through the LMA with the aid of a fiberoptic bronchoscope. We passed a tube exchanger through the 5.0 mm ETT and exchanged it with a 7.5 mm ETT. This method may be a useful alternative for difficult tracheal intubations.
PMCID: PMC3983421
Airway obstruction; Bronchoscopes; Cervical vertebrae; Laryngeal masks; Spinal fusion; Tube exchanger
4.  Role of calcium channels responsible for phenylephrine-induced contraction in rat aorta 3 days after acute myocardial infarction 
Korean Journal of Anesthesiology  2014;66(2):143-152.
Phenylephrine (PE) produces tonic contraction through involvement of various calcium channels such as store-operated calcium channels (SOCCs) and voltage-operated calcium channels (VOCCs). However, the relative contribution of each calcium channel to PE-induced contraction has not been investigated in isolated rat aorta of early acute myocardial infarction (AMI).
Endothelium-denuded rat aortic rings from rats 3 days after AMI or sham-operated (SHAM) rats were prepared in an organ chamber with Krebs-Ringer bicarbonate solution for isometric tension recording. We assessed the PE dose-response relationships in 2.5 mM calcium medium for both groups. The same procedure was repeated using rings pretreated with the SOCC inhibitor 2-aminoethoxydiphenyl borate, sarco/endoplasmic-reticulum calcium ATPase inhibitor thapsigargin (TG), diacyl glycerol lipase inhibitor RHC80267, and sodium-calcium exchanger inhibitor 3,4-dichlorobenzamil hydrochloride for 30 minutes before addition of calcium. When ongoing tonic contraction was sustained, dose-response curves to the VOCC inhibitor nifedipine were obtained to assess the relative contribution of each calcium channel under various conditions.
The effect of SOCC induction with TG pretreatment on PE-induced contraction was significantly lower in the AMI group compared to the SHAM group. In addition, there were significant decreases in the sensitivity and efficacy of the VOCC inhibitor nifedipine on PE-induced contraction in the AMI group.
Results suggest that the change of vascular reactivity of PE in rat aorta 3 days after AMI is characterized by a decreased contribution of L-type VOCCs. The enhanced VOCC-independent calcium entry mechanisms after AMI can be mediated by enhanced capacitative calcium entry through the activation of SOCCs.
PMCID: PMC3948442  PMID: 24624273
Calcium channels; Calcium influx; Myocardial infarction; Phenylephrine
5.  Diffusion-Weighted MRI in Recurrent Wernicke's Encephalopathy: a Remarkable Cerebellar Lesion 
We report unusual MRI findings (including those from diffusion-weighted imaging (DWI)) in a patient with recurrent Wernicke's encephalopathy with a remarkable cerebellar lesion. DWI showed high signal intensities in the superior portion of the cerebellar hemisphere and vermis area. After thiamine administration, clinical symptoms improved and the lesions with high signal intensities disappeared on follow-up DWI.
PMCID: PMC2854955  PMID: 20396499
Recurrent Wernicke's encephalopathy; Cerebellum; MRI; DWI
6.  Moderate and Deep Hypothermia Produces Hyporesposiveness to Phenylephrine in Isolated Rat Aorta 
Moderate and severe hypothermia with cardiopulmonary bypass during aortic surgery can cause some complications such as endothelial cell dysfunction or coagulation disorders. This study found out the difference of vascular reactivity by phenylephrine in moderate and severe hypothermia.
Preserved aortic endothelium by excised rat thoracic aorta was sectioned, and then down the temperature rapidly to 25℃ by 15 minutes at 38℃ and then the vascular tension was measured. The vascular tension was also measured in rewarming at 25℃ for temperatures up to 38℃. To investigate the mechanism of the changes in vascular tension on hypothermia, NG-nitro-L-arginine methyl esther (L-NAME) and indomethacin administered 30 minutes before the phenylephrine administration. And to find out the hypothermic effect can persist after rewarming, endothelium intact vessel and endothelium denuded vessel exposed to hypothermia. The bradykinin dose-response curve was obtained for ascertainment whether endothelium-dependent hyperpolarization factor involves decreasing the phenylnephrine vascular reactivity on hypothermia.
Fifteen minutes of the moderate hypothermia blocked the maximum contractile response of phenylephrine about 95%. The vasorelaxation induced by hypothermia was significantly reduced with L-NAME and indomethacin administration together. There was a significant decreasing in phenylephrine susceptibility and maximum contractility after 2 hours rewarming from moderate and severe hypothermia in the endothelium intact vessel compared with contrast group.
The vasoplegic syndrome after cardiac surgery might be caused by hypothermia when considering the vascular reactivity to phenylephrine was decreased in the endothelium-dependent mechanism.
PMCID: PMC3868687  PMID: 24368966
Hypothermia; Nitric oxide; Epoprostenol; Endothelium-dependent hyperpolarization factor; Phenylephrine
7.  Effects of Korean Red Ginseng and HAART on vif Gene in 10 Long-Term Slow Progressors over 20 Years: High Frequency of Deletions and G-to-A Hypermutation 
To investigate if Korean red ginseng (KRG) affects vif gene, we determined vif gene over 20 years in 10 long-term slowly progressing patients (LTSP) who were treated with KRG alone and then KRG plus HAART. We also compared these data with those of 21 control patients who did not receive KRG. Control patient group harbored only one premature stop codon (PSC) (0.9%), whereas the 10 LTSP revealed 78 defective genes (18.1%) (P < 0.001). The frequency of small in-frame deletions was found to be significantly higher in patients who received KRG alone (10.5%) than 0% in the pre-KRG or control patients (P < 0.01). Regarding HAART, vif genes containing PSCs were more frequently detected in patients receiving KRG plus HAART than patients receiving KRG alone or control patients (P < 0.01). In conclusion, our current data suggest that the high frequency of deletions and PSC in the vif gene is associated with KRG intake and HAART, respectively.
PMCID: PMC3844231  PMID: 24319487
8.  Modulation of experimental atopic dermatitis by topical application of Gami-Cheongyeul-Sodok-Eum 
Gami-Cheongyeul-Sodok-Eum (GCSE), an herbal formula of traditional Korean medicine, comprises nine herb components. GCSE has various biological activities such as anti-inflammatory, anti-bacterial and anti-viral activities. However, it is still unclear whether GCSE has any immunomodulatory effect on atopic dermatitis (AD).
GCSE was treated to primary B cells and CD4+ T cells isolated from atopic mice to compare its inhibitory effects on IgE secretion and cytokine expression. Experimental AD was established by alternative treatment of 2, 4-dinitrochlorobenzene (DNCB) and house dust mite extract to the ears of BALB/c mice. GCSE was topically applied to ears of atopic mice every day for 3 weeks. AD progression was analyzed by measuring ear thickness, serum IgE level, histological examination of ear tissue by H&E staining and cytokine profile of CD4+ T cells and CD19+ B cells by real time PCR and ELISA.
Treatment of GCSE significantly reduced IgE production and expression of AD associated pathogenic cytokines such as IL-4, IL-5, IL-10, IL-13, IL-17, TNF-α, and IFN-γ by lymphocytes isolated from AD-induced mice. Topical application of GCSE on the ears of AD-induced mice significantly reduced ear thickness, clinical score and lymphocytes infiltration to ears as compared to control group. GCSE treatment also reduced serum IgE level and the levels of major pathogenic cytokines such as IL-4, IL-5, IL-10, IL-13 and IL-17. In addition, GCSE treatment significantly increased Foxp3 expression level.
The protective effect of GCSE in experimental AD is mediated by inhibition of IgE production, by reduction in the levels of pathogenic cytokines and by induction of Foxp3, all of which are suggesting the beneficial effect of GCSE on modulating atopic dermatitis.
PMCID: PMC3832229  PMID: 24499290
Atopic dermatitis; Herbal medicine; GCSE (Gami-Cheongyeul-Sodok-Eum); Th1 & Th2 cells; B cells; IgE and Cytokines
9.  Intermittent PTH Administration Converts Quiescent Lining Cells to Active Osteoblasts 
Intermittent administration of parathyroid hormone (PTH) increases bone mass, at least in part, by increasing osteoblast number. One possible source of osteoblasts might be conversion of inactive lining cells to osteoblasts, and indirect evidence is consistent with this hypothesis. To better understand the possible effect of PTH on lining cell activation, a lineage tracing study was conducted using an inducible gene system. Dmp1-CreERt2 mice were crossed with ROSA26R reporter mice to render targeted mature osteoblasts and their descendents, lining cells and osteocytes, detectable by X-gal staining. Dmp1-CreERt2(+):ROSA26R mice were injected with 0.25 mg 4-OH-tamoxifen (4-OHTam) on postnatal day 3, 5, 7, 14, and 21. The animals were sacrificed on postnatal day 23, 33 or 43 (2, 12 or 22 days after the last 4-OHTam injection). On day 43, mice were challenged with a subcutaneous injection of human PTH (1–34, 80 μg/kg) or vehicle once daily for 3 days. By 22 days after the last 4-OHTam injection, most X-gal (+) cells on the periosteal surfaces of both the calvaria and tibia were flat. Moreover, bone formation rate and collagen I(α1) mRNA expression were decreased at day 43 compared to day 23. After 3 days of PTH injections, the thickness of X-gal (+) cells increased, as did their expression of osteocalcin and collagen I(α1) mRNA. Electron microscopy revealed X-gal-associated chromagen particles in both thin cells prior to PTH administration and cuboidal cells following PTH administration. These data support the hypothesis that intermittent PTH treatment can increase osteoblast number by converting lining cells to mature osteoblasts in vivo.
PMCID: PMC3529414  PMID: 22623172
osteoblasts; PTH; lining cells; lineage tracing study; inducible transgene system
10.  Auricular acupuncture for prehypertension and stage 1 hypertension: study protocol for a pilot multicentre randomised controlled trial 
Trials  2013;14:303.
Hypertension, a worldwide public health problem, is a major risk factor for cardiovascular and kidney disease, and the medical and economic burden of hypertension is increasing. Auricular acupuncture has been used to treat various diseases, including hypertension. Several studies have shown that auricular acupuncture treatment decreases blood pressure in patients with hypertension; however, the scientific evidence is still insufficient. Therefore, we aimed to perform a randomised controlled clinical trial in patients with prehypertension and stage 1 hypertension to evaluate the effect and safety of auricular acupuncture.
This on-going study is a two parallel arm, assessor-blinded, randomised controlled trial. Sixty participants with prehypertension and stage 1 hypertension will be recruited and randomly allocated into two groups in a 1:1 ratio. Participants in the auricular acupuncture group will receive auricular acupuncture treatment two times per week for 4 weeks. Participants in the usual care group will not receive any acupuncture treatment during the study period. All participants in both groups will be provided with verbal and written educational materials regarding the dietary and physical activity habits for controlling high blood pressure, and they will self-manage their lifestyle, including diet and exercise, during the study. The primary outcome is the 24-h average systolic and diastolic blood pressure, as measured with an ambulatory monitor. The secondary outcomes are the mean change in the average systolic and diastolic blood pressure during day- and night-time, the circadian rhythm of blood pressure, the mean arterial pressure, the change in blood pressure before and after auricular acupuncture treatment, the EuroQOL-5D (EQ-5D), heart rate variability (HRV), body mass index (BMI) and laboratory examination, including lipid profile and high sensitivity C-reactive protein (hs-CRP). Safety will be assessed at every visit.
This pilot multicentre randomised controlled trial will explore the feasibility of further auricular acupuncture research and provide important clinical evidence for the effect and safety of auricular acupuncture on blood pressure in patients with prehypertension and stage 1 hypertension compared with usual care.
Trial registration
Clinical Research Information Service: KCT0000169
PMCID: PMC3848952  PMID: 24053577
Hypertension; Auricular acupuncture; Effect; Safety; Clinical research protocol
13.  A New Disability-related Health Care Needs Assessment Tool for Persons With Brain Disorders 
This study aimed to develop a health needs assessment (HNA) tool for persons with brain disorders and to assess the unmet needs of persons with brain disorders using the developed tool.
The authors used consensus methods to develop a HNA tool. Using a randomized stratified systematic sampling method adjusted for sex, age, and districts, 57 registered persons (27 severe and 30 mild cases) with brain disorders dwelling in Seoul, South Korea were chosen and medical specialists investigated all of the subjects with the developed tools.
The HNA tool for brain disorders we developed included four categories: 1) medical interventions and operations, 2) assistive devices, 3) rehabilitation therapy, and 4) regular follow-up. This study also found that 71.9% of the subjects did not receive appropriate medical care, which implies that the severity of their disability is likely to be exacerbated and permanent, and the loss irrecoverable.
Our results showed that the HNA tool for persons with brain disorders based on unmet needs defined by physicians can be a useful method for evaluating the appropriateness and necessity of medical services offered to the disabled, and it can serve as the norm for providing health care services for disabled persons. Further studies should be undertaken to increase validity and reliability of the tool. Fundamental research investigating the factors generating or affecting the unmet needs is necessary; its results could serve as basis for developing policies to eliminate or alleviate these factors.
PMCID: PMC3796653  PMID: 24137530
Disabled persons; Brain disorders; Needs assessment; Unmet needs
14.  Electroacupuncture to treat painful diabetic neuropathy: study protocol for a three-armed, randomized, controlled pilot trial 
Trials  2013;14:225.
The purpose of this study is to conduct a basic analysis of the effectiveness and safety of electroacupuncture in the treatment of painful diabetic neuropathy (PDN) as compared to placebo and usual care and to evaluate the feasibility of large-scale clinical research.
This study is a protocol for a three-armed, randomized, patient-assessor-blinded (to the type of treatment), controlled pilot trial. Forty-five participants with a ≥ six month history of PDN and a mean weekly pain score of ≥ 4 on the 11-point Pain Intensity Numerical Rating Scale (PI-NRS) will be assigned to the electroacupuncture group (n = 15), sham group (n = 15) or usual care group (n = 15). The participants assigned to the electroacupuncture group will receive electroacupuncture (remaining for 30 minutes with a mixed current of 2 Hz/120 Hz and 80% of the bearable intensity) at 12 standard acupuncture points (bilateral ST36, GB39, SP9, SP6, LR3 and GB41) twice per week for eight weeks (a total of 16 sessions) as well as the usual care. The participants in the sham group will receive sham electroacupuncture (no electrical current will be passed to the needle, but the light will be seen, and the sound of the pulse generator will be heard by the participants) at non-acupuncture points as well as the usual care. The participants in the usual care group will not receive electroacupuncture treatment during the study period and will receive only the usual care. The follow-up will be in the 5th, 9th and 17th weeks after random allocation. The PI-NRS score assessed at the ninth week will be the primary outcome measurement used in this study. The Short-Form McGill Pain Questionnaire (SF-MPQ), a sleep disturbance score (11-point Likert scale), the Short-Form 36v2 Health Survey (SF-36), the Beck Depression Inventory (BDI) and the Patient Global Impression of Change (PGIC) will be used as outcome variables to evaluate the effectiveness of the acupuncture. Safety will be assessed at every visit.
The result of this trial will provide a basis for the effectiveness and safety of electroacupuncture for PDN.
Trial registration
Clinical Research information Service. Unique identifier: KCT0000466.
PMCID: PMC3720209  PMID: 23866906
Electroacupuncture; Painful diabetic neuropathy; Protocol
15.  Reflections of Two Parallel Pathways between the Hippocampus and Neocortex in Transient Global Amnesia: A Cross-Sectional Study Using DWI and SPECT 
PLoS ONE  2013;8(7):e67447.
Two parallel pathways have been proposed between the hippocampus and neocortex. Recently, the anterior and posterior hippocampus showed distinct connectivity with different cortical areas in an fMRI study. We investigated whether the two parallel pathways could be confirmed in patients with transient global amnesia (TGA) which is a natural lesion model of a perturbation of the hippocampus. In addition, we evaluated the relationship between the location of the hippocampal lesion and various clinical variables.
A consecutive series of 37 patients were identified from the TGA registry database of Seoul National University Bundang Hospital. Based on the location of the diffusion-weighted imaging (DWI) lesion along the anterior-posterior axis of the hippocampus, they were divided into the following three groups: head (n = 15), body (n = 15) or tail (n = 7). To evaluate which cortical regions showed hypoperfusion according to the location of the DWI lesion, their SPECT images were compared between two groups using statistical parametric mapping. We performed hierarchical cluster analysis to group demographic and clinical variables, including the location of the DWI lesion, into clusters.
Statistical parametric mapping analyses revealed that more anterior DWI lesions were associated with hypoperfusion of the anterior temporal and frontal areas, whereas more posterior lesions were associated with hypoperfusion of the posterior temporal, parietal, occipital and cerebellar areas. The difference was most prominent between the group of hippocampal lesions on the head and tail. Hierarchical cluster analysis demonstrated that vomiting was related to female gender and hippocampal head lesions, whereas vascular risk factors were related to male gender and hippocampal body lesions.
We confirmed the parallel pathways between the hippocampus and neocortex with DWI and SPECT images of patients with TGA. Patients with hippocampal head lesions and body lesions were clustered within different groups of clinical variables.
PMCID: PMC3702497  PMID: 23861765
16.  An open-label study of effects of acupuncture on chronic fatigue syndrome and idiopathic chronic fatigue: study protocol for a randomized controlled trial 
Trials  2013;14:147.
Even though chronic fatigue syndrome and idiopathic chronic fatigue are quite common, there are no clearly known causes. Most treatments are therefore symptomatic in nature, and chronic fatigue syndrome and idiopathic chronic fatigue patients are highly interested in using oriental medicine or complementary and alternative medicine treatment. Acupuncture, one of the major treatments used in oriental medicine, is effective in treating various diseases. This study will attempt to analyze the effectiveness and safety of acupuncture in the treatment of chronic fatigue by comparing the two treatment groups (body acupuncture, Sa-am acupuncture) and the control group (usual care).
This study consists of a four-center, three-arm, randomized, controlled, and open-label trial. One hundred and fifty participants are randomly divided into treatment groups A and B and a control group. The treatment groups will receive acupuncture treatments either two or three times per week for a total of 10 sessions over a period of 4 weeks. The control group will not receive acupuncture treatments and will continue their usual care during this period. The primary outcome variable is the Fatigue Severity Scale, which will be utilized 5 weeks after randomization. Secondary outcome variables are the Fatigue Severity Scale at 13 weeks, a short form of the Stress Response Inventory, the Beck Depression Inventory, the Numeric Rating Scale, and the EuroQol-5 Dimension at 5 and 13 weeks after randomization.
This study will provide evidence with high external validity on the effectiveness and safety of acupuncture as a treatment for chronic fatigue syndrome and idiopathic chronic fatigue.
Trial registration
Clinical Research Information Service KCT0000508
PMCID: PMC3663812  PMID: 23693129
Acupuncture; Chronic fatigue; Randomized controlled trial
18.  Insulin Like Growth Factor Binding Protein-5 Regulates Excessive Vascular Smooth Muscle Cell Proliferation in Spontaneously Hypertensive Rats via ERK 1/2 Phosphorylation 
Insulin-like growth factor binding proteins (IGFBPs) are important components of insulin growth factor (IGF) signaling pathways. One of the binding proteins, IGFBP-5, enhances the actions of IGF-1, which include the enhanced proliferation of smooth muscle cells. In the present study, we examined the expression and the biological effects of IGFBP-5 in vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). The levels of IGFBP-5 mRNA and protein were found to be higher in the VSMC from SHR than in those from WKY. Treatment with recombinant IGFBP-5-stimulated VSMC proliferation in WKY to the levels observed in SHR. In the VSMCs of WKY, incubation with angiotensin (Ang) II or IGF-1 dose dependently increased IGFBP-5 protein levels. Transfection with IGFBP-5 siRNA reduced VSMC proliferation in SHR to the levels exhibited in WKY. In addition, recombinant IGFBP-5 significantly up-regulated ERK1/2 phosphorylation in the VSMCs of WKY as much as those of SHR. Concurrent treatment with the MEK1/2 inhibitors, PD98059 or U0126 completely inhibited recombinant IGFBP-5-induced VSMC proliferation in WKY, while concurrent treatment with the phosphatidylinositol-3 kinase inhibitor, LY294002, had no effect. Furthermore, knockdown with IGFBP-5 siRNA inhibited ERK1/2 phosphorylation in VSMC of SHR. These results suggest that IGFBP-5 plays a role in the regulation of VSMC proliferation via ERK1/2 MAPK signaling in hypertensive rats.
PMCID: PMC3634093  PMID: 23626478
ERK1/2 MAPK; IGFBP-5; Insulin growth factor; Proliferation; Spontaneously hypertensive rats
19.  Moxibustion for treating knee osteoarthritis: study protocol of a multicentre randomised controlled trial 
The treatment of knee osteoarthritis, which is a major cause of disability among the elderly, is typically selected from multidisciplinary options, including complementary and alternative medicine. Moxibustion has been used in the treatment of knee osteoarthritis in Korea to reduce pain and improve physical activity. However, there is no sufficient evidence of its effectiveness, and it cannot therefore be widely recommended for treating knee osteoarthritis. We designed a randomised controlled clinical trial to evaluate the effectiveness, safety, cost-effectiveness, and qualitative characteristics of moxibustion treatment of knee osteoarthritis compared to usual care.
This is a protocol for a multicentre, pragmatic, randomised, assessor-blinded, controlled, parallel-group study. A total of 212 participants will be assigned to the moxibustion group (n = 106) and the usual care group (n = 106) at 4 clinical research centres. The participants assigned to the moxibustion group will receive moxibustion treatment of the affected knee(s) at 6 standard acupuncture points (ST36, ST35, ST34, SP9, Ex-LE04, and SP10) 3 times per week for 4 weeks (a total of 12 sessions). Participants in the usual care group will not receive moxibustion treatment during the study period. Follow-up will be performed on the 5th and 13th weeks after random allocation. Both groups will be allowed to use any type of treatment, including surgery, conventional medication, physical treatment, acupuncture, herbal medicine, over-the-counter drugs, and other active treatments. Educational material that explains knee osteoarthritis, the current management options, and self-exercise will be provided to each group. The global scale of the Korean Western Ontario and McMaster Osteoarthritis Index (K-WOMAC) will be the primary outcome measurement used in this study. Other subscales (pain, stiffness, and function) of the K-WOMAC, the Short-Form 36v2 Health Survey, the Beck Depression Inventory, the Physical Function test, Patient Global Assessment, and the Pain Numerical Rating Scale will be used as outcome variables to evaluate the effectiveness of moxibustion. Safety will be assessed at every visit. In addition, an economic evaluation and a qualitative study will be conducted as a mixed-methods approach.
This trial may contribute to developing evidence for the effectiveness and safety of moxibustion for treating knee osteoarthritis.
Trial registration
Trial registration number: KCT0000130
PMCID: PMC3605252  PMID: 23497032
20.  Osteoblast-Targeted Overexpression of TAZ Increases Bone Mass In Vivo 
PLoS ONE  2013;8(2):e56585.
Osteoblasts are derived from mesenchymal progenitors. Differentiation to osteoblasts and adipocytes is reciprocally regulated. Transcriptional coactivator with a PDZ-binding motif (TAZ) is a transcriptional coactivator that induces differentiation of mesenchymal cells into osteoblasts while blocking differentiation into adipocytes. To investigate the role of TAZ on bone metabolism in vivo, we generated transgenic mice that overexpress TAZ under the control of the procollagen type 1 promoter (Col1-TAZ). Whole body bone mineral density (BMD) of 6- to 19-week-old Col-TAZ mice was 4% to 7% higher than that of their wild-type (WT) littermates, whereas no difference was noticed in Col.1-TAZ female mice. Microcomputed tomography analyses of proximal tibiae at 16 weeks of age demonstrated a significant increase in trabecular bone volume (26.7%) and trabecular number (26.6%) with a reciprocal decrease in trabecular spacing (14.2%) in Col1-TAZ mice compared with their WT littermates. In addition, dynamic histomorphometric analysis of the lumbar spine revealed increased mineral apposition rate (42.8%) and the serum P1NP level was also significantly increased (53%) in Col.1-TAZ mice. When primary calvaria cells were cultured in osteogenic medium, alkaline phosphatase (ALP) activity was significantly increased and adipogenesis was significantly suppressed in Col1-TAZ mice compared with their WT littermates. Quantitative real-time polymerase chain reaction analyses showed that expression of collagen type 1, bone sialoprotein, osteocalcin, ALP, osterix, and Runx2 was significantly increased in calvaria cells from Col1-TAZ mice compared to their WT littermates. In vitro, TAZ enhanced Runx2-mediated transcriptional activity while suppressing the peroxisome proliferator-activated receptor gamma signaling pathway. TAZ also enhanced transcriptional activity from 3TP-Lux, which reflects transforming growth factor-beta (TGF-β)-mediated signaling. In addition, TAZ enhanced TGF-β-dependent nuclear translocation of Smad2/3 and Smad4. Taken together, these results suggest that TAZ positively regulates bone formation in vivo, which seems to be mediated by enhancing both Runx2 and TGF-β signaling.
PMCID: PMC3575506  PMID: 23441207
21.  Usefulness of the bispectral index during cardiopulmonary resuscitation -A case report- 
The usefulness of using the bispectral index (BIS) for monitoring during cardiopulmonary resuscitation (CPR) is not clearly understood. However, BIS has been a popular anesthetic monitoring device used during operations. The case presented is of a pregnant woman going into cardiac arrest due to an amniotic fluid embolism during a Cesarean section. CPR was performed, but neither the return of spontaneous circulation (ROSC) nor the return of consciousness was achieved, despite 50 min of effective CPR. However, CPR was continued based on BIS. ROSC was achieved, and an alert consciousness state was reached 1 day postoperation. This finding suggests that BIS be used as a basic monitoring device during CPR and that it may help in deciding to continue CPR.
PMCID: PMC3558654  PMID: 23372890
Bispectral index; Cardiopulmonary resuscitation; Consciousness
22.  Prophylactic Effect of Probiotics on the Development of Experimental Autoimmune Myasthenia Gravis 
PLoS ONE  2012;7(12):e52119.
Probiotics are live bacteria that confer health benefits to the host physiology. Although protective role of probiotics have been reported in diverse diseases, no information is available whether probiotics can modulate neuromuscular immune disorders. We have recently demonstrated that IRT5 probiotics, a mixture of 5 probiotics, could suppress diverse experimental disorders in mice model. In this study we further investigated whether IRT5 probiotics could modulate the progression of experimental autoimmune myasthenia gravis (EAMG). Myasthenia gravis (MG) is a T cell dependent antibody mediated autoimmune disorder in which acetylcholine receptor (AChR) at the neuromuscular junction is the major auto-antigen. Oral administration of IRT5 probiotics significantly reduced clinical symptoms of EAMG such as weight loss, body trembling and grip strength. Prophylactic effect of IRT5 probiotics on EMAG is mediated by down-regulation of effector function of AChR-reactive T cells and B cells. Administration of IRT5 probiotics decreased AChR-reactive lymphocyte proliferation, anti-AChR reactive IgG levels and inflammatory cytokine levels such as IFN-γ, TNF-α, IL-6 and IL-17. Down-regulation of inflammatory mediators in AChR-reactive lymphocytes by IRT5 probiotics is mediated by the generation of regulatory dendritic cells (rDCs) that express increased levels of IL-10, TGF-β, arginase 1 and aldh1a2. Furthermore, DCs isolated from IRT5 probiotics-fed group effectively converted CD4+ T cells into CD4+Foxp3+ regulatory T cells compared with control DCs. Our data suggest that IRT5 probiotics could be applicable to modulate antibody mediated autoimmune diseases including myasthenia gravis.
PMCID: PMC3527378  PMID: 23284891
23.  Immunomodulatory effect of water soluble extract separated from mycelium of Phellinus linteus on experimental atopic dermatitis 
Complementary and alternative medicine (CAM) is becoming a popular treatment for modulating diverse immune disorders. Phellinus linteus (P. linteus) as one of the CAMs has been used to modulate cancers, inflammation and allergic activities. However, little evidence has been shown about its underlying mechanism of action by which it exerts a beneficial role in dermatological disease in vivo. In this study, we examined the immunomodulatory effects of P. linteus on experimental atopic dermatitis (AD) and elucidated its action mechanism.
The immunomodulatory effect of total extract of P. linteus on IgE production by human myeloma U266B1 cells was measured by ELISA. To further identify the effective components, P. linteus was fractionated into methanol soluble, water soluble and boiling water soluble extracts. Each extract was treated to U266B1 cells and primary B cells to compare their inhibitory effects on IgE secretion. To test the in vivo efficacy, experimental atopic dermatitis (AD) was established by alternative treatment of DNCB and house dust mite extract into BALB/c mice. Water soluble extract of P. linteus (WA) or ceramide as a positive control were topically applied to ears of atopic mouse every day for 2 weeks and progression of the disease was estimated by the following criteria: (a) ear thickness, clinical score, (b) serum total IgE, IgG and mite specific IgE level by ELSIA, (c) histological examination of ear tissue by H&E staining and (d) cytokine profile of total ear cells and CD4+ T cells by real time PCR and ELSIA.
Treatment of total extracts of P. linteus to U266B1 inhibited IgE secretion. Among the diverse extracts of P. linteus, water soluble extract of P. linteus (WA) significantly reduced the IgE production in primary B cells and B cell line U266B1. Moreover, treatment of WA reduced AD symptoms such as ear swelling, erythema, and dryness and decreased recruitment of lymphocyte into the inflamed site. Interestingly WA treatment significantly reduced IgE level without affecting IgG levels and also down-regulated the levels of pathogenic cytokines (IL-4, IL-13, IL-12 and IFN-γ) and chemokines (CCL17 and CCL22) involved in AD development.
Our study indicates that protective effect of water soluble extract of P. linteus in atopic dermatitis is mediated by inhibiting IgE production and expression of AD associated pathogenic cytokines as well as chemokines, suggesting the beneficial effect of P. linteus to modulate allergic skin disease.
PMCID: PMC3479073  PMID: 22988890
24.  A Survey of the Awareness, Knowledge and Behavior of Hair Dye Use in a Korean Population with Gray Hair 
Annals of Dermatology  2012;24(3):274-279.
Gray hair naturally develops in the process of human aging. Many people with gray hair periodically dye their hair. Hair dyeing products are widely used and they can cause adverse effects. Therefore, the user's knowledge and recognition about hair dyeing and related side effects are important.
The goal of this study was to lay the foundation for understanding, preventing and treating side effects caused by hair coloring products.
We conducted a questionnaire survey for adult males and females aged over 20 who had gray hair. A total of 500 subjects were included in this study and statistical analysis was performed.
Large numbers of the people who had experience with hair dye (233 out of 319 people, 73.0%) did not know about the exact brand name of the hair dye product that they were using. Of 319 hair dye users, 23.8% (76 out of 319) people stated that they experienced side effects. Despite the occurrence of side effects from hair dyeing products, it seems they did not realize the seriousness of the side effects or the need for treatment.
It is advisable to introduce a system that enables users to become aware of the ingredients and side effects of hair coloring products and give opportunities for users to become aware of the side effects of hair coloring through education, publicity and publication of an informational booklet.
PMCID: PMC3412235  PMID: 22879710
Gray hair; Hair dyes; Side effects
25.  Clinical Features of Systemic Contact Dermatitis Due to the Ingestion of Lacquer in the Province of Chungcheongnam-do 
Annals of Dermatology  2012;24(3):319-323.
Lacquer contains an allergen, which can cause severe contact dermatitis. Systemic dermatitis resulting from the ingestion of lacquer is quite common in Korea, until now.
The purpose of this study is to elucidate the clinical features and laboratory findings of systemic contact dermatitis (SCD), due to the ingestion of lacquer in Chungcheongnam-do.
We retrospectively reviewed the medical records of 33 patients with SCD, after ingestion of lacquer from Soonchunhyang University Hospital in Cheonan, over a 6-month period.
In this study, 33.3% of patients ate lacquer, as a health food, and some (15.2%) by encouragement of friends or spouse. The most common way of ingestion was the lacquer-boiled chicken (48.5%), but many also ate lacquer tree sprouts (42.4%). The skin lesions developed as erythematous maculopapular eruptions, erythema multiforme, erythroderma, purpura, wheals and vesicles. On laboratory findings, 13 patients (52%) exhibited leukocytosis and 11 patients had elevated eosinophil counts.
The general public is becoming more aware of the toxic effects of lacquer ingestion, but still does not fully understand the dangers of lacquer tree sprouts, and this ignorance is frequently causing SCD in Chungcheongnam-do.
PMCID: PMC3412241  PMID: 22879716
Chungcheongnam-do; Lacquer tree sprout; Systemic contact dermatitis

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