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2.  Immunophenotypic Characterization and Quantification of Neoplastic Bone Marrow Plasma Cells by Multiparametric Flow Cytometry and Its Clinical Significance in Korean Myeloma Patients 
Journal of Korean Medical Science  2013;28(4):542-549.
Multiparametric flow cytometry (MFC) allows discrimination between normal and neoplastic plasma cells (NeoPCs) within the bone marrow plasma cell (BMPC) compartment. This study sought to characterize immunophenotypes and quantitate the proportion of NeoPCs in BMPCs to diagnose plasma cell myeoma (PCM) and evaluate the prognostic impact of this method. We analyzed the MFC data of the bone marrow aspirates of 76 patients with PCM and 33 patients with reactive plasmacytosis. MFC analysis was performed using three combinations: CD38/CD138/-/CD45; CD56/CD20/CD138/CD19; and CD27/CD28/CD138/CD117. The plasma cells of patients with reactive plasmacytosis demonstrated normal immunophenotypic patterns. Aberrant marker expression was observed in NeoPCs, with negative CD19 expression observed in 100% of cases, CD56+ in 73.7%, CD117+ in 15.2%, CD27- in 10.5%, CD20+ in 9.2%, and CD28+ in 1.3%. In PCM patients, more than 20% of NeoPCs/BMPCs were significantly associated with factors suggestive of poor clinical outcomes. Patients who were CD27- or CD56+/CD27-, demonstrated shorter overall survival than patients of other CD56/CD27 combinations. Our results support the clinical value of immunophenotyping and quantifying NeoPCs in PCM patients. This strategy could help to reveal poor prognostic categories and delineate surrogate markers for risk stratification in PCM patients.
PMCID: PMC3617306  PMID: 23580331
Multiple Myeloma; Flow Cytometry; Immunophenotyping; Neoplastic Cells; Plasma Cells
3.  Tissue-Specific Expression of Human Calcineurin-Binding Protein 1 in Mouse Synovial Tissue Can Suppress Inflammatory Arthritis 
Calcineurin (CN) is a calcium- and calmodulin-dependent serine/threonine phosphatase. In immune cells, CN controls the activity of a wide range of transcription factors, including nuclear factor of activated T, nuclear factor-kappa B, c-fos, and Elk-1. CN plays an important role in synoviocyte activation and arthritis progression in vivo and this function is tightly linked to dysregulated intracellular Ca2+ store and Ca2+ response triggered by proinflammatory cytokines. In the present study, transgenic mice expressing human calcineurin-binding protein 1 (hCabin1) were generated, driven by type II collagen promoter, and the efficiency of these mice was investigated by experimental arthritis. These transgenic mice successfully expressed hCabin1 in joint tissue as well as other organs such as liver, heart, and brain. The overexpression of hCabin1 reduced the disease severity during collagen-induced arthritis. In fibroblast-like synoviocytes (FLSs) from hCabin1 transgenic mice, the productions of these cytokines, including interleukin (IL)-2, IL-4, and IFN-γ, were decreased and matrix metalloproteinases were also depressed in transgenic mice FLS. In addition, these effects were only found in the joint tissue, which is a major inflammation site. These findings will provide a better knowledge of the pathogenic mechanisms of rheumatoid arthritis and a potential animal model of the chronic inflammatory conditions, including atherosclerosis and transplantation.
PMCID: PMC3255519  PMID: 22175542
4.  Relationship between Irritable Bowel Syndrome, Worry and Stress in Adolescent Girls 
Journal of Korean Medical Science  2012;27(11):1398-1404.
The aim of this study is to investigate prevalence of irritable bowel syndrome (IBS) among adolescents and difference in worry and stress between normal and IBS groups. Questionnaire survey was conducted at a girl's middle and high school. Students from seventh to eleventh grade participated in the examination on Rome II criteria, lifestyle and dietary habits. Worry and stress were measured with the Korean version Penn State Worry Questionnaire-Children and the Korean version Brief Encounter Psychosocial Instrument. Worry score was significantly higher in the IBS group (22.07 ± 9.38, P < 0.001) than in the normal group (18.65 ± 8.99) and was higher in high school students than in middle school students (P = 0.02). Stress score also was higher in the IBS group than in the normal group (P < 0.001) and was higher in the high school girls than in the middle school ones (P = 0.04). Of all the lifestyle factors influencing IBS preference for fatty foods, preference for salty foods, drinking alcohol and sleeping for less than six hours a day were found to be significant. Worry and stress seem to be associated with IBS symptoms. The findings of this study draw a clue that less worry and stress will help decrease IBS symptoms.
PMCID: PMC3492677  PMID: 23166424
Irritable Bowel Syndrome; Worry; Stress
5.  Over-expression of extracellular superoxide dismutase in mouse synovial tissue attenuates the inflammatory arthritis 
Experimental & Molecular Medicine  2012;44(9):529-535.
Oxidative stress such as reactive oxygen species (ROS) within the inflamed joint have been indicated as being involved as inflammatory mediators in the induction of arthritis. Correlations between extracellular-superoxide dismutase (EC-SOD) and inflammatory arthritis have been shown in several animal models of RA. However, there is a question whether the over-expression of EC-SOD on arthritic joint also could suppress the progression of disease or not. In the present study, the effect on the synovial tissue of experimental arthritis was investigated using EC-SOD over-expressing transgenic mice. The over-expression of EC-SOD in joint tissue was confirmed by RT-PCR and immunohistochemistry. The degree of the inflammation in EC-SOD transgenic mice was suppressed in the collagen-induced arthritis model. In a cytokine assay, the production of pro-inflammatory cytokines such as, IL-1β, TNFα, and matrix metalloproteinases (MMPs) was decreased in fibroblast-like synoviocyte (FLS) but not in peripheral blood. Histological examination also showed repressed cartilage destruction and bone in EC-SOD transgenic mice. In conclusion, these data suggest that the over-expression of EC-SOD in FLS contributes to the activation of FLS and protection from joint destruction by depressing the production of the pro-inflammatory cytokines and MMPs. These results provide EC-SOD transgenic mice with a useful animal model for inflammatory arthritis research.
PMCID: PMC3465746  PMID: 22718219
arthritis, experimental; reactive oxygen species; rheumatoid arthritis; superoxide dismutase; synovial membrane
6.  Assessment of Lifestyle Effects on the Levels of Free Oxygen Radicals in the Korean Population 
Korean Journal of Family Medicine  2012;33(5):296-304.
As many studies revealed that oxidative stress due to the imbalance of reactive oxygen species (ROS) and antioxidant capacity is related with pathologic processes such as cardiovascular diseases, diabetes, as well as aging and obesity, the relationship between lifestyle and oxidative stress has recently gained much medical attention. However, little information exists on the effects of lifestyle on ROS in Korea. In this study, we investigated the effects of lifestyle on free oxygen radical levels in men and women in Korea.
A total of 138 adults participated in this study from September 2007 to June 2010 at a health promotion center and department of family medicine. Information on the lifestyle of each participant was obtained by questionnaire. Biochemical markers and a free oxygen radical test (FORT) were also measured.
The average age was 47.28 ± 10.85 years and 79.7% were male. High sensitivity C-reactive protein (hs-CRP; r = 0.418, P = 0.012), triglycerides (r = -0.243, P = 0.008), hemoglobin (r = -0.445, P < 0.001), total protein (r = 0.210, P = 0.036), creatinine (r = -0.294, P = 0.001), fruit intake per day (P = 0.047), and smoking (P = 0.003) were related to the FORT levels in univariate analysis. Multiple linear regression analysis showed that hs-CRP (P = 0.039) was an independent predictor of serum FORT values. This statistical model can explain 78% of the variance in FORT values.
This result suggests that hs-CRP showed a statistically significant positive association with FORT values. Further studies on the relationship between lifestyle and antioxidant capacity as well as ROS seem to be warranted to evaluate the overall effect of oxidative stress.
PMCID: PMC3481029  PMID: 23115704
Free Oxygen Radical Test; High Sensitivity C-reactive Protein; Life Style
7.  CD5-negative Blastoid Variant Mantle Cell Lymphoma with Complex CCND1/IGH and MYC Aberrations 
Annals of Laboratory Medicine  2011;32(1):95-98.
The coexistence of CCND1/IGH and MYC rearrangements in mantle cell lymphoma (MCL) is a rare finding associated with a very poor prognosis. In this study, a patient with blastoid variant (MCL) is reported. The disease was clinically aggressive and refractory to chemotherapy, and the patient only survived for 1 month following diagnosis. Conventional cytogenetic study, FISH, and multicolor FISH (mFISH) demonstrated the involvement of the BCL1/CCND1 locus in a complex translocation, t(3;11)(q25;p15)t(11;14)(q13;q32). In addition, subclonal abnormalities in the 8q24 region, manifested as a t(8;14)(q24;q32)/MYC rearrangement, were identified. To the best of our knowledge, this is the first MCL case in Korea bearing these complex genomic aberrations.
PMCID: PMC3255497  PMID: 22259787
Mantle cell lymphoma; CCND1; MYC
8.  Effect of Dance Exercise on Cognitive Function in Elderly Patients with Metabolic Syndrome: A Pilot Study 
Metabolic syndrome is associated with an increased risk of cognitive impairment. The purpose of this prospective pilot study was to examine the effects of dance exercise on cognitive function in elderly patients with metabolic syndrome. The participants included 38 elderly metabolic syndrome patients with normal cognitive function (26 exercise group and 12 control group). The exercise group performed dance exercise twice a week for 6 months. Cognitive function was assessed in all participants using the Korean version of the Consortium to Establish a Registry for Alzheimer’s disease (CERAD-K). Repeated-measures ANCOVA was used to assess the effect of dance exercise on cognitive function and cardiometabolic risk factors. Compared with the control group, the exercise group significantly improved in verbal fluency (p = 0.048), word list delayed recall (p = 0.038), word list recognition (p = 0.007), and total CERAD-K score (p = 0.037). However, no significance difference was found in body mass index, blood pressure, waist circumference, fasting plasma glucose, triglyceride, and HDL cholesterol between groups over the 6-month period. In the present study, six months of dance exercise improved cognitive function in older adults with metabolic syndrome. Thus, dance exercise may reduce the risk for cognitive disorders in elderly people with metabolic syndrome.
Key pointsMetabolic syndrome (MS) is associated with an increased risk of cognitive impairment.Aerobic exercise improves cognitive function in elderly people and contributes to the prevention of degenerative neurological disease and brain damage. Dance sport is a form of aerobic exercise that has the additional benefits of stimulating the emotions, promoting social interaction, and exposing subjects to acoustic stimulation and music.In the present study, dance exercise for a 6-month period improved cognitive function in older adults with MS. In particular, positive effects were observed in verbal fluency, word list delayed recall, word list recognition, and the total CERAD-K score.Our data suggest that the implementation of dance exercise programs may be an effective means of prevention and treatment of cognitive disorders.
PMCID: PMC3761497  PMID: 24149557
Dance exercise; cognitive function; metabolic syndrome; elderly; CERAD-K
9.  The Relationship between Metabolic Syndrome and Cognitive Function 
Korean Journal of Family Medicine  2011;32(6):358-366.
Metabolic syndrome has been reported to have adverse effects on cognitive function, although the results are conflicting. The purpose of this study was to examine the relationship between metabolic syndrome and cognitive function in elderly Korean participants older than 60 years.
We examined elderly participants who visited the health promotion center in Gyeonggi-do province. We categorized the participants into two groups based on the presence of metabolic syndrome (48 participants in the metabolic syndrome group and 45 in the control group). Cognitive function was assessed in all participants using the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD-K).
Compared with those without metabolic syndrome, participants with metabolic syndrome had lower mean total CERAD-K scores (64.2 ± 11.1 vs. 69.8 ± 9.2, P = 0.010). In the comparison of CERAD-K items, significantly lower scores were observed in the verbal fluency test, the construction recall test, the word list learning test, and trail making B in the group with metabolic syndrome. After controlling age, sex, education, smoking, alcohol, physical activity and the Korean version of the Short Geriatric Depression Scale of Korean, multiple regression analysis showed that metabolic syndrome was independently associated with cognitive function (P = 0.014). Alcohol intake (P = 0.002) and education years (P = 0.001) were also contributing factors to cognitive function.
This study found a significant relationship between cognitive function and metabolic syndrome. It will be necessary to perform a prospective study to determine whether metabolic syndrome causes cognitive dysfunction or if the correction of metabolic syndrome can improve cognitive function.
PMCID: PMC3383144  PMID: 22745874
Metabolic Syndrome; Cognitive Function; CERAD-K
10.  The Relationship between Menopausal Symptoms and Heart Rate Variability in Middle Aged Women 
Korean Journal of Family Medicine  2011;32(5):299-305.
The study of the correlation of menopausal symptoms with heart rate variability (HRV) has not been adequate. The aim of this study was to investigate the relationship between postmenopausal symptoms measured by the menopause rating scale (MRS) and HRV.
We assessed postmenopausal symptoms (using MRS) with age, BMI, educational status, occupation, marital status, alcohol and caffeine consumption, smoking history, exercise, duration of sleep and amenorrhea, degree of anxiety and depression, menarcheal age, and heart rate variability. For evaluation of HRV, the record of electrocardiogram for 5 minutes in the resting state was divided into temporal categories and frequency categories, and analyzed.
No significant differences in age, BMI, duration of amenorrhea, heart rate, systolic blood pressure, diastolic blood pressure, fasting blood sugar, triglyceride, and high-density lipoprotein were observed between two groups, which were divided according to menopausal symptoms. Low frequency/high frequency (LF/HF) ratio was significantly higher in symptomatic women, compared with asymptomatic women (P < 0.05). No significant differences of HRV index by the severity of postmenopausal symptoms were observed. LF/HF ratio of HRV parameters showed a significant increase in moderate or severe degree of "hot flashes" and "sleep problem" score (P < 0.05). Anxiety scale in symptomatic women was significantly higher than in asymptomatic women (P < 0.05).
The above data suggest that postmenopausal symptoms are associated with altered autonomic control of heart rate. In particular, hot flashes and sleep problems in moderate or severe degree are related to increase of sympathetic nerve activity.
PMCID: PMC3383141  PMID: 22745867
Postmenopausal Symptoms; Menopause Rating Scale; Heart Rate Variability
11.  The First Korean Case of Camurati-Engelmann Disease (Progressive Diaphyseal Dysplasia) Confirmed by TGFB1 Gene Mutation Analysis 
Journal of Korean Medical Science  2009;24(4):737-740.
Camurati-Engelmann disease (CED) is an autosomal dominant progressive diaphyseal dysplasia caused by mutations in the transforming growth factor-β1 (TGFB1) gene. We report the first Korean family with an affected mother and son who were diagnosed with CED. The proband is a 19-yr-old male with a history of abnormal gait since the age of 2. He also suffered from proximal muscle weakness, pain in the extremities, and easy fatigability. Skeletal radiographs of the long bones revealed cortical, periosteal, and endosteal thickenings, predominantly affecting the diaphyses of the upper and lower extremities. No other bony abnormalities were noted in the skull and spine and no remarkable findings were seen on laboratory tests. The patient's mother had a long-standing history of mild limb pain. Under the impression of CED on radiographic studies, we performed mutation analysis. A heterozygous G to A transition at cDNA position +653 in exon 4 of the TGFB1 gene (R218H) was detected in the patient and his mother.
PMCID: PMC2719210  PMID: 19654961
Camurati-Engelmann Syndrome; Transforming Growth Factor β1 Gene; Skeletal Dysplasia; Mutation Analysis

Results 1-11 (11)