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1.  Chordoma in the Tail of a Ferret 
Laboratory Animal Research  2011;27(1):53-57.
A chordoma is an uncommon tumor that originates from the remnants of the notochord and most commonly involves the cranial and caudal regions of the axial skeleton. Chordoma has been described in laboratory animals such as dogs, rats, minks, and ferrets. This report describes a case of a chordoma in the tail of a ferret. Grossly, a grayish-white, expansile, subcutaneous soft-tissue mass was observed in the tail. Histopathologically, the mass was a loosely placed, nodular, unencapsulated neoplasm within the dermis. In the mass, tumor lobules were intermingled with fibrous tissues. Fibrous tissues contained abundant extracellular basophilic material that was consistent with mucin. The tumor was composed of a close pack of adipocyte-like vacuolated cells (physaliferous cells). The cells were centrally or eccentrically located round nuclei and eosinophilic cytoplasm with large vacuoles. Immunohistologically, neoplastic cells were positive for vimentin and S-100 protein. Based on histopathologic findings and special staining characteristics, this case was diagnosed as chordoma.
PMCID: PMC3145987  PMID: 21826161
Chordoma; ferret; physaliferous cells; pathology
2.  A population-based case-crossover study of polyethylene glycol use and acute renal failure risk in the elderly 
AIM: To evaluate the possibility of an association between polyethylene glycol (PEG) and acute renal failure (ARF) in elderly patients using a health insurance claims database.
METHODS: We conducted a population-based case-crossover study using information obtained from Korean Health Insurance Review and Assessment Service (HIRA) claims from January 1, 2005 to December 31, 2005 (Seoul, Korea). The study population consisted of elderly patients who received PEG prior to experiencing their first ARF-related hospitalization from April 1, 2005 to December 31, 2005. For each patient, one case and two control periods were matched. PEG use in a 2- or 4-wk window period prior to hospitalization for ARF was compared with PEG use in two earlier 2- or 4-wk control window periods. Conditional logistic regression analysis was used to estimate odds ratios (ORs) and 95% CI, adjusting for concomitant uses of diuretics, angiotensin converting enzyme inhibitors, non-steroidal anti-inflammatory drugs, antibiotics, anti-cancer drugs, and contrast media.
RESULTS: Within the HIRA database which contained 1 093 262 elderly patients, 1156 hospitalized ARF cases were identified. Among these cases, PEG was prescribed to 17 (1.5%) patients before hospitalization. The adjusted ORs when applying the 2- and 4-wk window periods were 0.4 (95% CI: 0.03-5.24) and 2.1 (95% CI: 0.16-27.78), respectively.
CONCLUSION: No increased risk of ARF was found in elderly PEG users. However, based on the limited number of study subjects, further analysis should be performed to confirm these results.
PMCID: PMC3040338  PMID: 21350715
Polyethylene glycol; Acute renal failure; Adverse drug reaction; Health insurance claims database; Case-crossover
3.  Activation of CD147 with Cyclophilin A Induces the Expression of IFITM1 through ERK and PI3K in THP-1 Cells 
Mediators of Inflammation  2010;2010:821940.
CD147, as a receptor for Cyclophilins, is a multifunctional transmembrane glycoprotein. In order to identify genes that are induced by activation of CD147, THP-1 cells were stimulated with Cyclophilin A and differentially expressed genes were detected using PCR-based analysis. Interferon-induced transmembrane 1 (IFITM1) was detected to be induced and it was confirmed by RT-PCR and Western blot analysis. CD147-induced expression of IFITM1 was blocked by inhibitors of ERK, PI3K, or NF-κB, but not by inhibitors of p38, JNK, or PKC. IFITM1 appears to mediate inflammatory activation of THP-1 cells since cross-linking of IFITM1 with specific monoclonal antibody against it induced the expression of proinflammatory mediators such as IL-8 and MMP-9. These data indicate that IFITM1 is one of the pro-inflammatory mediators that are induced by signaling initiated by the activation of CD147 in macrophages and activation of ERK, PI3K, and NF-κB is required for the expression of IFITM1.
PMCID: PMC2935166  PMID: 20847954
4.  Relationships between Dietary Habits and Allostatic Load Index in Metabolic Syndrome Patients 
Korean Journal of Family Medicine  2013;34(5):334-346.
Allostatic load (AL) measures overall physiological wear and tear on one's body, as a preclinical marker of pathophysiologic processes that precede the onset of disease. We studied the association of dietary habits with AL.
Consecutive patients visiting a tertiary hospital Health Promotion Center from September 2009 to February 2010, older than 20 years with metabolic syndrome were selected for study (n = 204). By multivariable linear regression analysis, we investigated the association of various dietary habits evaluated by questionnaires.
In male, multivariable linear regression showed a significant negative association between fat preference and AL with BMI ≥ 30 (1st quartile [Q] vs. 2Q: β = -3.71; 95% confidence interval [CI], -6.26 to -1.16), a significant negative association between salt preference and AL with BMI 25-30 (β = -1.36; 95% CI, -2.46 to -0.26), a negative association between appetite control and AL with BMI < 25 (1Q vs. 3Q: β = -1.54; 95% CI, -3.00 to -0.096), a significant positive association between appetite control and AL with BMI 25-30 (1Q vs. 3Q: β = 1.30; 95% CI, 0.12 to 2.48), and a significant positive association between eating in response to food cues and AL in males with BMI 25-30 (1Q vs. 4Q: β = 1.09; 95% CI, 0.020 to 2.15).
Our results suggest that metabolic syndrome patients should be discouraged from eating fat and eating in response to food cues, and should be educated about nutrition and balanced diet.
PMCID: PMC3791341  PMID: 24106586
Allostasis; Metabolic Syndrome; Food Habits; Food Preferences
5.  Design and in vivo evaluation of oxycodone once-a-day controlled-release tablets 
The aim of present study was to design oxycodone once-a-day controlled-release (CR) tablets and to perform in vitro/in vivo characterizations. Release profiles to achieve desired plasma concentration versus time curves were established by using simulation software and reported pharmacokinetic parameters of the drug. Hydroxypropyl methylcellulose (HPMC) 100,000 mPa·s was used as a release modifier because the polymer was found to be resistant to changes in conditions of the release study, including rotation speed of paddle and ion strength. The burst release of the drug from the CR tablets could be suppressed by applying an additional HPMC layer as a physical barrier. Finally, the oxycodone once-a-day tablet was comprised of two layers, an inert HPMC layer and a CR layer containing drug and HPMC. Commercial products, either 10 mg bis in die (bid [twice a day]) or once-a-day CR tablets (20 mg) were administered to healthy volunteers, and calculated pharmacokinetic parameters indicated bioequivalence of the two different treatments. The findings of the present study emphasize the potential of oxycodone once-a-day CR tablets for improved patient compliance, safety, and efficacy, which could help researchers to develop new CR dosage forms of oxycodone.
PMCID: PMC4322610
pharmacokinetics; oral delivery; in vitro–in vivo correlation; double-layer tablet
6.  A review of deoxycorticosterone acetate-salt hypertension and its relevance for cardiovascular physiotherapy research 
[Purpose] The purpose of this review was to elucidate the deoxycorticosterone acetate (DOCA)-salt-related hypertensive mechanism and to contribute to future studies of cardiovascular physiotherapy. [Methods] This paper focuses on the signal transductions that control hypertension and its mechanisms. We include results reported by our laboratory in a literature review. [Results] Our results and the literature show the various mechanisms of DOCA-salt hypertension. [Conclusion] In this review paper, we carefully discuss the signal transduction in hypertension based on our studies and with reference to cardiovascular physiotherapy research.
PMCID: PMC4305587  PMID: 25642096
Deoxycorticosterone acetate-salt hypertension; Signal transduction; Cardiovascular physiotherapy
7.  Validation of the Korean version of the European Community Respiratory Health Survey screening questionnaire for use in epidemiologic studies for adult asthma 
Asia Pacific Allergy  2015;5(1):25-31.
Standardized questionnaire is one of key instruments for general population surveys.
The present study aimed to develop and validate the Korean version of the European Community Respiratory Health Survey (ECRHS) screening questionnaire for adult asthma surveys.
The ECRHS screening questionnaire was translated into Korean language according to the international criteria. Study participants were prospectively recruited from six referral hospitals and one health check-up center. Comprehensibility of the translation was tested in a pilot study of 10 patients. The reliability was evaluated by internal consistency and test-retest repeatability. Validity was assess with regard to physician-diagnosed asthma.
A total of 100 adult asthma patients and 134 volunteers were recruited. Reliability was examined for 10 items in 100 asthmatics; Cronbach α coefficients were 0.84, and test-retest repeatability was good (Cohen κ coefficient, 0.71-1.00). Validity was assessed for 8 items in 234 participants; in particular, 'recent wheeze' showed a high sensitivity (0.89) for physician-diagnosed asthma. 'Recent asthma attack' and 'current asthma medication' showed high specificity (0.96-0.98).
The present study demonstrated that the Korean version of the ECRHS screening questionnaire was comprehensible, reliable and valid. We suggest the questionnaire to be utilized in further epidemiological studies for asthma in Korean adult populations.
PMCID: PMC4313752  PMID: 25653917
Asthma; Epidemiology; Questionnaires
8.  Sociodemographic factors associated with the use of mental health services in depressed adults: results from the Korea National Health and Nutrition Examination Survey (KNHANES) 
The aims of this study were to determine the utilization of mental health services (MHSs) by adults with a depressive mood and to identify the influencing sociodemographic factors, using a nationwide representative Korean sample.
The study included 2735 subjects, aged 19 years or older, who had experienced a depressive mood continuously for over 2 weeks within the previous year, using the data from the KNHANES IV (Fourth Korea National Health and Nutrition Examination Survey), which was performed between 2007 and 2009, and involved a nationally representative sample of the Korean community population who were visited at home. A multivariate logistic regression analysis was used to estimate the adjusted odd ratios (ORs) and 95% confidence intervals (CIs) for the use of MHSs, which was defined as using healthcare institutions, consulting services, and inpatient or outpatient treatments due to mental health problems.
MHSs had been used by 9.6% of the subjects with a depressive mood. The use of the MHSs was significantly associated with age, education level, and employment status, after adjusting for sociodemographic and health-related factors. Specifically, the OR for the nonuse of MHSs by the elderly (≥65 years) relative to subjects aged 19–34 years was 2.55 (95% CI = 1.13–5.76), subjects with a lower education level were less likely to use MHSs compared to those with a higher education level (7–9 years, OR = 2.35, 95% CI = 1.19–4.64; 10–12 years, OR = 1.66, 95% CI = 1.07–2.56; ≥13 years, reference), and the OR of unemployed relative to employed was 0.47 (95% CI = 0.32–0.67).
Among Korean adults with a depressive mood, the elderly, those with a lower education level, and the employed are less likely to use MHSs. These findings suggest that mental health policies should be made based on the characteristics of the population in order to reduce untreated patients with depression. Greater resources and attention to identifying and treating depression in older, less educated, and employed adults are warranted.
PMCID: PMC4307909  PMID: 25527283
Mental health service; Use; Depressive mood; Sociodemographic factor; Age; Education
9.  Phosphorylation of Heat Shock Protein 27 is Increased by Cast Immobilization and by Serum-free Starvation in Skeletal Muscles 
Journal of Physical Therapy Science  2014;26(12):1975-1977.
[Purpose] Cast immobilization- and cell starvation-induced loss of muscle mass are closely associated with a dramatic reduction in the structural muscle proteins. Heat shock proteins are molecular chaperones that are constitutively expressed in several eukaryotic cells and have been shown to protect against various stressors. However, the changes in the phosphorylation of atrophy-related heat shock protein 27 (HSP27) are still poorly understood in skeletal muscles. In this study, we examine whether or not phosphorylation of HSP27 is changed in the skeletal muscles after cast immobilization and serum-free starvation with low glucose in a time-dependent manner. [Methods] We undertook a HSP27 expression and high-resolution differential proteomic analysis in skeletal muscles. Furthermore, we used western blotting to examine protein expression and phosphorylation of HSP27 in atrophied gastrocnemius muscle strips and L6 myoblasts. [Results] Cast immobilization and starvation significantly upregulated the phosphorylation of HSP27 in a time-dependent manner, respectively. [Conclusion] Our results suggest that cast immobilization- and serum-free starvation-induced atrophy may be in part related to changes in the phosphorylation of HSP27 in rat skeletal muscles.
PMCID: PMC4273071  PMID: 25540511
Heat shock protein 27; Cast immobilization and serum-free starvation; Muscle atrophy
10.  Decrease of PKB/Akt Phosphorylation is Partially Mediated by SAPK/JNK Activation in Serum-free L6 Myoblasts Starved with Low Glucose 
Journal of Physical Therapy Science  2014;26(11):1757-1760.
[Purpose] Studies have been using cell cultures of muscle cells to mimic atrophy in in vivo and in vitro tests. However, changes in the activation of atrophy-related PKB/Akt is not fully understood in serum-free starved skeletal muscle cells. The purpose of the present study was to determine the change of PKB/Akt phosphorylation in L6 myoblasts under serum-free starvation conditions. [Methods] We used western blotting to examine PKB/Akt expression and phosphorylation in atrophied L6 myoblasts. [Results] The phosphorylation of PKB/Akt was significantly lower in L6 myoblasts under serum-free starvation than that of the control group. Serum-free starvation for 6, 12, 24, 36, 48, 72, 96, and 120 hours significantly decreased the phosphorylation of PKB/Akt. Furthermore, the decrease of PKB/Akt phosphorylation under serum-free starvation was partially restored by SP600125, an inhibitor of SAPK/JNK. [Conclusion] These results suggest that decrease of PKB/Akt phosphorylation due to serum-free starvation with low glucose is partially related to the activity of SAPK/JNK in L6 myoblasts.
PMCID: PMC4242949  PMID: 25435694
PKB/Akt; Serum-free starvation; L6 myoblasts
11.  Dual Effect of Chrysanthemum indicum Extract to Stimulate Osteoblast Differentiation and Inhibit Osteoclast Formation and Resorption In Vitro 
The risk of bone-related diseases increases due to the imbalance between bone resorption and bone formation by osteoclasts and osteoblasts, respectively. The goal in the development of antiosteoporotic treatments is an agent that will improve bone through simultaneous osteoblast stimulation and osteoclast inhibition without undesirable side effects. To achieve this goal, numerous studies have been performed to identify novel approaches using natural oriental herbs to treat bone metabolic diseases. In the present study, we investigated the effect of Chrysanthemum indicum extract (CIE) on the differentiation of osteoclastic and osteoblastic cells. CIE inhibited the formation of TRAP-positive mature osteoclasts and of filamentous-actin rings and disrupted the bone-resorbing activity of mature osteoclasts in a dose-dependent manner. CIE strongly inhibited Akt, GSK3β, and IκB phosphorylation in RANKL-stimulated bone marrow macrophages and did not show any effects on MAP kinases, including p38, ERK, and JNK. Interestingly, CIE also enhanced primary osteoblast differentiation via upregulation of the expression of alkaline phosphatase and the level of extracellular calcium concentrations during the early and terminal stages of differentiation, respectively. Our results revealed that CIE could have a potential therapeutic role in bone-related disorders through its dual effects on osteoclast and osteoblast differentiation.
PMCID: PMC4228817  PMID: 25530776
12.  Cofilin Phosphorylation Decreased by Serum-free Starvation with Low Glucose in the L6 Myoblasts 
Journal of Physical Therapy Science  2014;26(10):1543-1545.
[Purpose] Many studies have been using cell culture models of muscle cells with exogenous cytokines or glucocorticoids to mimic atrophy in in vivo and in vitro tests. However, the changes in the phosphorylation of atrophy-related cofilin are still poorly understood in starved skeletal muscle cells. In this study, we first examined whether or not phosphorylation of cofilin is altered in L6 myoblasts after 3, 6, 12, 24, 48, and 72 hours of serum-free starvation with low glucose. [Methods] We used Western blotting to exam protein expression and phosphorylation in atrophied L6 myoblasts. [Results] L6 cell sizes and numbers were diminished as a result of serum-free starvation in a time-dependent manner. Serum-free starvation for 3, 6, 12, 24, 48, and 72 hours significantly decreased the phosphorylation of cofilin, respectively. [Conclusion] These results suggest that starvation-induced atrophy may be in part related to changes in the phosphorylation of cofilin in L6 myoblasts.
PMCID: PMC4210392  PMID: 25364107
Cofilin; Serum-free starvation; L6 myoblasts
13.  Capsaicin cough sensitivity is related to the older female predominant feature in chronic cough patients 
The present study aimed to examine the age and gender distributions among chronic cough patients referred to a tertiary cough clinic in Korea, and to investigate clinical factors related to the demographic findings.
Study participants were unselectively recruited from adult chronic cough patients who attended the cough clinic for the first time during one year. To validate their representativeness, their age and gender distributions were compared to the entire chronic cough population, or with those presenting with other chronic disease. Data from the baseline investigations were analyzed to identify clinical factors related to the demographic findings.
A total of 272 chronic cough patients were included. They had a middle-aged female predominant feature (mean age: 52.8±15.7 years and female 69.1%). Their age and gender distributions were almost identical to the entire chronic cough population, but were distinct from patients with hypertension. Among clinical factors, the older female predominance was associated with enhanced capsaicin cough sensitivity, and also with the presence of 'cough by cold air' symptom. Allotussia and laryngeal paresthesia were highly common in chronic cough patients, affecting 94.8% and 86.8% of them, respectively.
The present study demonstrated older female predominance among adult chronic cough patients attending a referral cough clinic in Korea. The demographic features were significantly associated with the capsaicin cough responses and also potentially with allotussia (particularly cold air as the trigger). These findings suggest a role of cough reflex sensitization in the pathophysiology of chronic cough in adults.
PMCID: PMC4161680  PMID: 25228996
Cough; respiratory hypersensitivity
14.  Parthenolide inhibits osteoclast differentiation and bone resorbing activity by down-regulation of NFATc1 induction and c-Fos stability, during RANKL-mediated osteoclastogenesis 
BMB Reports  2014;47(8):451-456.
Parthenolide, a natural product derived from Feverfew, prevents septic shock and inflammation. We aimed to identify the effects of parthenolide on the RANKL (receptor activator of NF-κB ligand)-induced differentiation and bone resorbing activity of osteoclasts. In this study, parthenolide dose-dependently inhibited RANKL-mediated osteoclast differentiation in BMMs, without any evidence of cytotoxicity and the phosphorylation of p38, ERK, and IκB, as well as IκB degradation by RANKL treatment. Parthenolide suppressed the expression of NFATc1, OSCAR, TRAP, DC-STAMP, and cathepsin K in RANKL-treated BMMs. Furthermore, parthenolide down-regulated the stability of c-Fos protein, but could not suppress the expression of c-Fos. Overexpression of NFATc1 and c-Fos in BMMs reversed the inhibitory effect of parthenolide on RANKL-mediated osteoclast differentiation. Parthenolide also inhibited the bone resorbing activity of mature osteoclasts. Parthenolide inhibits the differentiation and bone-resolving activity of osteoclast by RANKL, suggesting its potential therapeutic value for bone destructive disorders associated with osteoclast-mediated bone resorption. [BMB Reports 2014; 47(8): 451-456]
PMCID: PMC4206717  PMID: 24314143
Bone disorders; c-Fos; NFATc1; Osteoclase differentiation; Parthenolide
15.  A Case of Kawasaki Disease with Coronary Aneurysm Responding to the 4th IVIG Treatment 
Case Reports in Cardiology  2014;2014:821812.
Kawasaki disease is an acute febrile illness that usually occurs in children younger than 5 years of age. The use of intravenous immunoglobulin (IVIG) within the first 10 days of illness has been shown to reduce the incidence of coronary artery aneurysms significantly. The relative roles of repeated doses of intravenous immunoglobulin (IVIG) are controversial in refractory Kawasaki disease (KD). Most experts recommend the second retreatment with IVIG, 2 g/kg in refractory KD. However, the dose-response effect of the third or fourth IVIG was uncertain. Although there have been a significant number of reports on new therapeutic options for refractory KD, such as steroid, infliximab, methotrexate, and other immunosuppressants, their effectiveness in reducing the prevalence of coronary artery aneurysms was unproven. We present here KD patient with small coronary artery aneurysm who is resistant to the third IVIG and steroid pulse therapy but showed improvement immediately after the infusion of the 4th IVIG on fever day 18.
PMCID: PMC4137746  PMID: 25161773
16.  Somatotype Analysis of Elite Boxing Athletes Compared with Nonathletes for Sports Physiotherapy 
Journal of Physical Therapy Science  2014;26(8):1231-1235.
[Purpose] The purpose of this study was to show somatotype and physical characteristic differences between elite boxing athletes and non-athletes. [Methods] The somatotypes of 23 elite boxing athletes and 23 nonathletes were measured with the Heath-Carter method. The subjects were divided into four weight divisions as follows: lightweight, light middleweight, middleweight, and heavyweight class. [Results] The endomorphic component values of the boxing athletes were lower than those of the nonathletes. However, the mesomorphic component values of the boxing athletes were higher than those of the nonathletes. There was no significant difference in the ectomorphic component between the two groups. The higher weight divisions tended to have higher values of height, weight, and BMI than the lower weight divisions. The higher weight divisions also tended to have higher values for the endomorphic and mesomorphic components and a lower value for the ectomorphic component than the lower weight divisions. The group of nonathletes consisted of eight endomorphs, four mesomorphs, six ectomorphs, and five central types. Among the boxing athletes, there were 16 mesomorphic, four ectomorphic, and two central types and one endomorphic type. Subdividing the athletes into 13 somatotypes resulted in five balanced mesomorphs, five endomorphic mesomorphs, five mesomorph-ectomorphs, three mesomorph-endomorphs, two mesomorphic ectomorphs, two central types, and one ectomorphic mesomorph type. [Conclusion] The data from this study provides in part physical characteristics of elite boxing athletes that can be used to establish a reference for systemic study of sports physiotherapy.
PMCID: PMC4155226  PMID: 25202187
Somatotype analysis; Elite boxing athletes; Specialized sports physiotherapy
17.  Incidence and Risk Factors of Subsequent Hip Fractures in Korea: Multicenter Study 
Journal of Korean Medical Science  2014;29(7):992-994.
This study analyzes the incidence of subsequent hip fractures and its risk factors in the northwestern region of Korea. We analyzed hip fracture patients who visited any of the 5 teaching hospitals in the Bucheon and Incheon area from January 2000 to December 2010. Medical records were reviewed and presence of subsequent hip fractures, alcohol history, marital status, live in solitude, dementia, dizziness, American society of anesthesiologists score, osteoporosis treatment after fracture, body mass index (BMI) and initial bone mineral density were analyzed. The average follow-up period was 12 months (range 1-130 months). A total of 2,546 patients (women 1,770, men 776) who had experienced hip fractures were included. Of these, subsequent hip fractures were found in 233 patients (9.2%) (women 187, men 46). Mean age at the time of the first fracture was 79.2 yr old (range 50-100 yr). The average interval between the first fracture and the subsequent hip fractures was 30.2 months (range 4 days-154 months). In this large-scale, retrospective, multicenter study, overall incidence of subsequent hip fractures is 9.2%. Independent risk factors of subsequent fracture are women, BMI<22 kg/m2, and being unmarried.
PMCID: PMC4101789  PMID: 25045233
Subsequent Hip Fractures; Risk Factors; Incidence
18.  A Pilot Study on Pain and the Upregulation of Myoglobin through Low-frequency and High-amplitude Electrical Stimulation-induced Muscle Contraction 
[Purpose] It is well known that, in both in vivo and in vitro tests, muscle fatigue is produced by severe exercise, electrical stimulation, and so on. However, it is not clear whether or not low-frequency and high-amplitude modulation specifically affects serum myoglobin or urine myoglobin. The purpose of the present study was to determine the effect of low-frequency and high-amplitude modulation on serum myoglobin and urine myoglobin. [Methods] The study used whole blood samples and urine produced over 24 hours from the thirteen healthy subjects. [Results] There was a significant increase in serum myoglobin following electrical stimulation at a frequency of 10 Hz compared with the control group. Furthermore, within 24 hours, urine myoglobin also showed a significant increase for the test volunteers subjected to electrical stimulation at the 10 Hz frequency compared with the control group. However, there were no significant differences in the concentrations of hematologic results in subjects treated with electrical stimulation. [Conclusion] These results suggest that increased myoglobin related to muscle fatigue from electrical stimulation, particularly with a current of 10 Hz combined with a high-amplitude, may be partially related to increased muscle damage.
PMCID: PMC4135220  PMID: 25140079
Myoglobin; Pain; High-amplitude electrical stimulation
19.  Preclinical Efficacy and Mechanisms of Mesenchymal Stem Cells in Animal Models of Autoimmune Diseases 
Immune Network  2014;14(2):81-88.
Mesenchymal stem cells (MSCs) are present in diverse tissues and organs, including bone marrow, umbilical cord, adipose tissue, and placenta. MSCs can expand easily in vitro and have regenerative stem cell properties and potent immunoregulatory activity. They inhibit the functions of dendritic cells, B cells, and T cells, but enhance those of regulatory T cells by producing immunoregulatory molecules such as transforming growth factor-β, hepatic growth factors, prostaglandin E2, interleukin-10, indolamine 2,3-dioxygenase, nitric oxide, heme oxygenase-1, and human leukocyte antigen-G. These properties make MSCs promising therapeutic candidates for the treatment of autoimmune diseases. Here, we review the preclinical studies of MSCs in animal models for systemic lupus erythematosus, rheumatoid arthritis, Crohn's disease, and experimental autoimmune encephalomyelitis, and summarize the underlying immunoregulatory mechanisms.
PMCID: PMC4022782  PMID: 24851097
Mesenchymal stem cells; Immunoregulation; Autoimmune diseases
20.  mTOR Inhibition Ameliorates Cognitive and Affective Deficits Caused by Disc1 Knockdown in Adult-Born Dentate Granule Neurons 
Neuron  2013;77(4):647-654.
Abnormalities during brain development are thought to cause psychiatric illness and other neurodevelopmental disorders. However, developmental processes such as neurogenesis continue in restricted brain regions of adults, and disruptions of these processes could contribute to the phenotypes of neurodevelopmental disorders. As previously reported, we show that Disc1 knockdown specifically in adult-born dentate gyrus (DG) neurons results in increased mTOR signaling, hyper-excitability and neuronal structure deficits. Disc1 knockdown also resulted in pronounced cognitive and affective deficits, which could be reversed when the affected DG neurons were inactivated. Importantly, reversing increases in mTOR signaling with an FDA approved inhibitor, both prevented and treated these behavioral deficits, even when associated structural deficits were not reversed. Our findings suggest that a component of the affective and cognitive phenotypes in neurodevelopmental disorders may be caused by disruptions in adult-born neurons. Consequently, treatments directed at this cell population may have a significant impact on these phenotypes.
PMCID: PMC3586374  PMID: 23439118
21.  Secreted frizzled-related protein 3 regulates activity-dependent adult hippocampal neurogenesis 
Cell stem cell  2013;12(2):215-223.
Adult neurogenesis, a process of generating mature neurons from adult neural stem cells, proceeds concurrently with ongoing neuronal circuit activity and is modulated by various physiological and pathological stimuli. The niche mechanism underlying activity-dependent regulation of sequential steps of adult neurogenesis remains largely unknown. Here we report that neuronal activity decreases the expression of secreted frizzled-related protein 3 (sFRP3), a naturally secreted Wnt inhibitor highly expressed by adult dentate gyrus granule neurons. Sfrp3 deletion activates quiescent radial neural stem cells and promotes newborn neuron maturation, dendritic growth and spine formation in the adult mouse hippocampus. Furthermore, sfrp3 reduction is essential for activity-induced adult neural progenitor proliferation and acceleration of new neuron development. Our study identifies sFRP3 as an inhibitory niche factor from local mature dentate granule neurons that regulates multiple phases of adult hippocampal neurogenesis and suggests a novel activity-dependent mechanism governing adult neurogenesis via acute release of tonic inhibition.
PMCID: PMC3569732  PMID: 23395446
22.  Levothyroxine Dose and Fracture Risk According to the Osteoporosis Status in Elderly Women 
To evaluate the association between fracture risk and levothyroxine use in elderly women with hypothyroidism, according to previous osteoporosis history.
We conducted a cohort study from the Korean Health Insurance Review and Assessment Service claims database from January 2005 to June 2006. The study population comprised women aged ≥65 years who had been diagnosed with hypothyroidism and prescribed levothyroxine monotherapy. We excluded patients who met any of the following criteria: previous fracture history, hyperthyroidism, thyroid cancer, or pituitary disorder; low levothyroxine adherence; or a follow-up period <90 days. We categorized the daily levothyroxine doses into 4 groups: ≤50 µg/d, 51 to 100 µg/d, 101 to 150 µg/d, and >150 µg/d. The hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated with the Cox proportional hazard model, and subgroup analyses were performed according to the osteoporosis history and osteoporosis-specific drug prescription status.
Among 11 155 cohort participants, 35.6% had previous histories of osteoporosis. The adjusted HR of fracture for the >150 µg/d group, compared with the 51 to 100 µg/d group, was 1.56 (95% CI, 1.03 to 2.37) in osteoporosis subgroup. In the highly probable osteoporosis subgroup, restricted to patients who were concurrently prescribed osteoporosis-specific drugs, the adjusted HR of fracture for the >150 µg/d group, compared with the 51 to 100 µg/d group, was 1.93 (95% CI, 1.14 to 3.26).
While further studies are needed, physicians should be concerned about potential levothyroxine overtreatment in elderly osteoporosis patients.
PMCID: PMC3930806  PMID: 24570805
Thyroxine; Fractures; Cohort studies; Aged; Osteoporosis
23.  Comparison of the Safety of Seven Iodinated Contrast Media 
Journal of Korean Medical Science  2013;28(12):1703-1710.
We aimed to determine the characteristic adverse events (AEs) of iodinated contrast media (IOCM) and to compare the safety profiles of different IOCM. This study used the database of AEs reports submitted by healthcare professionals from 15 Regional Pharmacovigilance Centers between June 24, 2009 and December 31, 2010 in Korea. All reports of IOCM, including iopromide, iohexol, iopamidol, iomeprol, ioversol, iobitridol and iodixanol, were analyzed. Safety profiles were compared between different IOCM at the system organ level using the proportional reporting ratio (PRR) and 95% confidence interval (95% CI). Among a total of 48,261 reports, 6,524 (13.5%) reports were related to the use of IOCM. Iopromide (45.5%), iohexol (16.9%), iopamidol (14.3%) and iomeprol (10.3%) were identified as frequently reported media. 'Platelet, bleeding & clotting disorders' (PRR, 29.6; 95%CI, 1.9-472.6) and 'urinary system disorders' (PRR, 22.3; 95% CI, 17.1-29.1) were more frequently reported for iodixanol than the other IOCM. In conclusion, the frequency of AEs by organ class was significantly different between individual media. These differences among different IOCM should be considered when selecting a medium among various IOCM and when monitoring patients during and after its use to ensure optimum usage and patient safety.
PMCID: PMC3857363  PMID: 24339697
Contrast Media; Adverse Drug Reaction Reporting Systems; Patient Safety
24.  PPARγ modulates vascular smooth muscle cell phenotype via a protein kinase G-dependent pathway and reduces neointimal hyperplasia after vascular injury 
Vascular smooth muscle cells (VSMCs) undergo phenotypic changes in response to vascular injury such as angioplasty. Protein kinase G (PKG) has an important role in the process of VSMC phenotype switching. In this study, we examined whether rosiglitazone, a peroxisome proliferator-activated receptor (PPAR)-γ agonist, could modulate VSMC phenotype through the PKG pathway to reduce neointimal hyperplasia after angioplasty. In vitro experiments showed that rosiglitazone inhibited the phenotype change of VSMCs from a contractile to a synthetic form. The platelet-derived growth factor (PDGF)-induced reduction of PKG level was reversed by rosiglitazone treatment, resulting in increased PKG activity. This increased activity of PKG resulted in phosphorylation of vasodilator-stimulated phosphoprotein at serine 239, leading to inhibited proliferation of VSMCs. Interestingly, rosiglitazone did not change the level of nitric oxide (NO) or cyclic guanosine monophosphate (cGMP), which are upstream of PKG, suggesting that rosiglitazone influences PKG itself. Chromatin immunoprecipitation assays for the PKG promoter showed that the activation of PKG by rosiglitazone was mediated by the increased binding of Sp1 on the promoter region of PKG. In vivo experiments showed that rosiglitazone significantly inhibited neointimal formation after balloon injury. Immunohistochemistry staining for calponin and thrombospondin showed that this effect of rosiglitazone was mediated by modulating VSMC phenotype. Our findings demonstrate that rosiglitazone is a potent modulator of VSMC phenotype, which is regulated by PKG. This activation of PKG by rosiglitazone results in reduced neointimal hyperplasia after angioplasty. These results provide important mechanistic insight into the cardiovascular-protective effect of PPARγ.
PMCID: PMC3849568  PMID: 24287871
cGMP-dependent protein kinase; Rosiglitazone; Smooth muscle cells
25.  Satisfaction and Difficulties of Korean Family Medicine Resident Training Faculty 
Korean Journal of Family Medicine  2013;34(5):357-363.
Practitioners of family medicine are essential to primary care practices in Korea. Resident training staffs in Korean family medicine departments have a crucial role in producing well-trained family physicians. This study assesses the aspects of satisfaction and difficulties of Korean family medicine resident training staffs.
We surveyed the resident training staffs of various Korean family medicine departments using an online survey tool. The survey used in this study was modified from previously used questionnaires. Respondents rated items using a five-point Likert scale and a 0-10 visual analogue scale.
The response rate was 43.9% (122/278). The mean satisfaction score with regard to current family medicine residency programs was 7.59 out of 10. Resident training staffs found the administrative aspects of their role to be the most difficult. There were considerable differences in the reported difficulties of resident training according to the differing characteristics of each staff member, including age, sex, type of hospital, number of staff members, role as chief, and duration of staff. Most respondents (91.9%) cited a need for faculty development programs.
Korean family medicine resident training staffs need faculty development programs for the improvement of resident training. For the strengthening of core competencies among resident training staffs, faculty development programs or courses should be designed and implemented in Korea.
PMCID: PMC3791343  PMID: 24106588
Faculty Development; Survey; Family Medicine Teacher; Faculty Developmental Program

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