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1.  Role of CD4+CD25high+FOXP3+ Regulatory T Cells in Psoriasis 
Annals of Dermatology  2010;22(4):397-403.
Background
CD4+CD25high+regulatory T cells (Tregs) are considered to be of vital importance for maintaining immunologic self-tolerance and preventing autoimmune diseases. These cells have been found to be deficient in skin lesions and in the peripheral blood of patients with psoriasis.
Objective
To investigate the role of Tregs in the pathogenesis of psoriasis and to evaluate the changes in Tregs in relation to the severity and the clinical course of psoriasis.
Methods
Immunohistochemistry (CD3, 4, 8, 79 and FOXP3) was performed in 22 psoriatic patients compared to 5 normal controls. Flow cytometry (CD3, 4, 8, 25 and FOXP3) was performed in 18 psoriatic patients and 8 normal volunteers and reverse transcriptase polymerase chain reaction (foxp3 mRNA) was performed in 8 psoriasis patients.
Results
An increase in the FOXP3+ cell fraction was detected in the lesional psoriatic skin irrespective of the severity of psoriasis as compared with the normal skin. However, a decrease in FOXP3+ cells was observed in the samples obtained from psoriasis of 'acute course'. FOXP3+ Treg populations in the blood of the 'acute course' psoriasis was not different compared to that of 'chronic course' psoriasis and normal controls.
Conclusion
The deficiency of FOXP3+ Tregs in the lesional psoriatic skin might be responsible for the exacerbation of psoriasis.
doi:10.5021/ad.2010.22.4.397
PMCID: PMC2991715  PMID: 21165208
CD4+CD25high+regulatory T cells; FOXP3; Psoriasis
2.  Neuroprotective effects of bovine colostrum on intracerebral hemorrhage-induced apoptotic neuronal cell death in rats☆ 
Neural Regeneration Research  2012;7(22):1715-1721.
Brain cell death after intracerebral hemorrhage may be mediated in part by an apoptotic mechanism. Colostrum is the first milk produced by mammals for their young. It plays an important role in protection and development by providing various antibodies, growth factors and nutrients, and has been used for various diseases in many countries. In the present study, we investigated the anti-apoptotic effects of bovine colostrum using organotypic hippocampal slice cultures and an intracerebral hemorrhage animal model. We performed densitometric measurements of propidium iodide uptake, a step-down avoidance task, Nissl staining, and caspase-3 immunohistochemistry. The present results revealed that colostrum treatment significantly suppressed N-methyl-D-aspartic acid-induced neuronal cell death in the rat hippocampus. Moreover, colostrum treatment improved short-term memory by suppressing hemorrhage-induced apoptotic neuronal cell death and decreasing the volume of the lesion induced by intracerebral hemorrhage in the rat hippocampus. These results suggest that colostrum may have a beneficial role in recovering brain function following hemorrhagic stroke by suppressing apoptotic cell death.
doi:10.3969/j.issn.1673-5374.2012.22.006
PMCID: PMC4302452  PMID: 25624793
intracerebral hemorrhage; organotypic hippocampal slice culture; bovine colostrum; apoptotic cell death; N-methyl-D-aspartic acid; caspase-3; hippocampus; memory
3.  Signet-ring cell carcinoma arising from a fundic gland polyp in the stomach 
World Journal of Gastroenterology : WJG  2014;20(47):18044-18047.
Fundic gland polyps (FGPs) are currently the most common type of gastric polyps and are usually benign. However, although rare, gastric adenocarcinoma of FGP has been recently proposed as a new variant of gastric adenocarcinoma. Here we report the first case of a 49-year-old woman with focal signet ring cell carcinoma that arose from an FGP of the stomach. The tumor was completely excised by endoscopic snare polypectomy. FGPs should therefore be evaluated for malignant changes although they occur rarely, if the FGP has an erosive or irregular surface.
doi:10.3748/wjg.v20.i47.18044
PMCID: PMC4273157  PMID: 25548505
Fundic gland polyp; Signet ring cell
4.  Is DBM Beneficial for the Enhancement of Bony Consolidation in Distraction Osteogenesis? A Randomized Controlled Trial 
BioMed Research International  2015;2015:281738.
The aim of the present study was to compare the radiographic and clinical outcomes of DBM injection and conventional treatment during tibial lengthening over an intramedullary nail in adult patients with short stature. Twenty-nine patients were randomized to receive DBM injection (n = 14) or conventional treatment without any injection (n = 15) and evaluated. The outcome was measured on the basis of the pixel value ratio (PVR) in the digital radiographs during the consolidation period; healing index; clinical assessment; and the rate of complications. In the DBM group, the mean PVR of 1 (mineral density of the callus is comparable to the adjacent bone) was reached by 40 weeks in anterior and medial cortices which was significantly different than that in the control group (P = 0.03 for anterior cortex; P = 0.04 for medial cortex). The average healing index in the DBM group was 39.8 ± 5.3 days/cm compared to 44.3 ± 5.8 days/cm in the control group (P = 0.05). There were no significant differences in clinical outcomes (P = 0.23) and functional status (P = 0.47) including complications (P = 0.72) between two groups. In this randomized clinical trial, injection of DBM at the time of initial operation enhanced consolidation of regenerate callus without interfering with clinical outcomes compared to that with conventional treatment.
doi:10.1155/2015/281738
PMCID: PMC4326219
5.  Predictive Factors of Response to Proton Pump Inhibitors in Korean Patients With Gastroesophageal Reflux Disease 
Background/Aims
Proton pump inhibitors (PPIs) are widely used in the treatment of gastroesophageal reflux disease (GERD). However, some patients fail to respond to PPI therapy. We investigated the efficacy of response to PPI therapy in patients with GERD symptoms.
Methods
A total of 179 subjects with GERD symptoms were prospectively enrolled and diagnosed with non-erosive reflux disease (NERD, n = 100) and erosive reflux disease (n = 79) by gastroscopy and Bernstein test and/or 24-hour esophageal pH testing. Subjects then received a standard dose of daily PPI therapy for at least 4 weeks. PPI therapy response was evaluated using questionnaires including questions about demographics, GERD symptoms, GERD impact scale, Epworth sleepiness scale, Pittsburgh sleep quality index (PSQI), hospital anxiety and depression scale, and abbreviated version of the World Health Organization quality of life scale.
Results
The rates of complete (≥ 80%), satisfactory (≥ 50%), partial (< 50%), and refractory response in the 179 participants were 41.3%, 30.2%, 18.4%, and 10.1%, respectively. Thus, overall response rate (complete and satisfactory responses) was 71.5%. Multivariate analysis showed body mass index < 23 kg/m2 (OR, 2.20; 95% CI, 1.12–4.34), higher total PSQI score (OR, 1.20; 95% CI, 1.05–1.35), history of psychotherapy or neuropsychiatric medication (OR, 2.44; 95% CI, 1.23–4.85), and NERD (OR, 3.30; 95% CI, 1.54–7.11) were associated with poor response to PPI therapy.
Conclusions
Psychological factors, sleep dysfunction, body mass index < 23 kg/m2, and NERD seem to be the major factors that lead to a poor response to PPI treatment in patients with GERD symptoms.
doi:10.5056/jnm14078
PMCID: PMC4288103  PMID: 25537676
Esophagitis; Gastroesophageal reflux; Proton pump inhibitors; Psychology; Sleep disorders
6.  What can be the criteria of outpatient-based endoscopic resection for colon polyp? 
AIM: To investigate whether out-patient based endoscopic mucosal resection (EMR) for colon polyps ≤ 10 mm is safe.
METHODS: Between January 2004 and December 2012, a total of 3015 EMR cases conducted in 1320 patients were retrospectively reviewed. The factors contributing delayed hemorrhage were analyzed. We calculated the probability of delayed bleeding after stratifying conditions of specific risk factors.
RESULTS: The size of the polyp (95%CI: 1.096-1.164, P < 0.001) and patients with chronic renal failure (95%CI: 1.856-45.106, P = 0.007) were identified as independent risk factors for delayed bleeding in multivariate analysis. 95%CI for percent of delayed bleeding according to polyp size was determined for the following conditions: size ≤ 10 mm, 0.05%-0.43%; 20 mm ≥ size > 10 mm, 0.54%-2.08%; size > 20 mm, 4.22%-11.41%. 95%CI was determined for the risk of serious immediate bleeding for a polyp ≤ 10 mm was 0.10%-0.56%. Finally, 95%CI for percent of incomplete resection was 0.07%-0.49% in polyps ≤ 10 mm.
CONCLUSION: It seems acceptable to perform outpatient-based EMR for colon polyps ≤ 10 mm.
doi:10.4253/wjge.v6.i10.493
PMCID: PMC4198395  PMID: 25324921
Colon; Polyp; Endoscopic mucosal resection; Bleeding
7.  The Significance of Serum Phosphate Level on Healing Index and Its Relative Effects in Skeletally Immature and Mature Patients with Hypophosphatemic Rickets 
BioMed Research International  2014;2014:569530.
The aim of this study was to find out the ideal cut-off level of phosphate for safe healing when deformity correction and concomitant lengthening are indicated in the two different skeletal maturity groups of patients with rickets. Thirty-nine hypophosphatemic rickets patients were selected for the study and were divided into two groups: 27 skeletally immature (group IM) and 12 skeletally mature (group M). The outcomes were evaluated with respect to the healing index (HI), laboratory findings, and complications with the mean follow-up of 5.1 years (range, 3.1–7.9). The healing index (HI) of group IM was 1.44 month/cm and HI of group M was 1.68 month/cm. The negative correlation between the level of serum phosphate and HI in group M (coefficient = −0.94) was evaluated to be less than the correlation in group IM (coefficient = −0.50), indicating that the HI is more likely to be affected by serum phosphate in group M than in group IM. Preoperative serum phosphate levels of 2.3 mg/dL and 2.6 mg/dL were analyzed to be the cut-off values of group IM and group M, respectively, in which the cut-off points divided the series into two groups having the most significantly different HI.
doi:10.1155/2014/569530
PMCID: PMC4017876  PMID: 24868530
8.  Bone Formation in a Rat Tibial Defect Model Using Carboxymethyl Cellulose/BioC/Bone Morphogenic Protein-2 Hybrid Materials 
BioMed Research International  2014;2014:230152.
The objective of this study was to assess whether carboxymethyl cellulose- (CMC-) based hydrogel containing BioC (biphasic calcium phosphate (BCP); tricalcium phosphate (TCP) : hydroxyapatite (Hap) = 70 : 30) and bone morphogenic protein-2 (BMP-2) led to greater bone formation than CMC-based hydrogel containing BioC without BMP-2. In order to demonstrate bone formation at 4 and 8 weeks, plain radiographs, microcomputed tomography (micro-CT) evaluation, and histological studies were performed after implantation of all hybrid materials on an 8 mm defect of the right tibia in rats. The plain radiographs and micro-CT analyses revealed that CMC/BioC/BMP-2 (0.5 mg) led to much greater mineralization at 4 and 8 weeks than did CMC/BioC or CMC/Bio/BMP-2 (0.1 mg). Likewise, bone formation and bone remodeling studies revealed that CMC/BioC/BMP-2 (0.5 mg) led to a significantly greater amount of bone formation and bone remodeling at 4 and 8 weeks than did CMC/BioC or CMC/BioC/BMP-2 (0.1 mg). Histological studies revealed that mineralized bone tissue was present around the whole circumference of the defect site with CMC/BioC/BMP-2 (0.5 mg) but not with CMC/BioC or CMC/BioC/BMP-2 (0.1 mg) at 4 and 8 weeks. These results suggest that CMC/BioC/BMP-2 hybrid materials induced greater bone formation than CMC/BioC hybrid materials. Thus, CMC/BioC/BMP-2 hybrid materials may be used as an injectable substrate to regenerate bone defects.
doi:10.1155/2014/230152
PMCID: PMC3997084  PMID: 24804202
9.  Reversible dilated cardiomyopathy caused by idiopathic hypoparathyroidism 
Dilated cardiomyopathy (DCM) is usually an idiopathic disease with a poor prognosis. Hypocalcemia is a rare and reversible cause of DCM. Here, we report a 50-year-old female with DCM, induced by idiopathic hypoparathyroidism, that improved after treatment with calcium.
doi:10.3904/kjim.2013.28.5.605
PMCID: PMC3759768  PMID: 24009458
Cardiomyopathy, dilated; Hypocalcemia; Hypoparathyroidism
10.  Early-stage primary signet ring cell carcinoma of the colon 
Primary signet ring cell carcinoma of the colorectum detected at an early stage is very rare; most cases are detected at an advanced stage. Therefore, its prognosis is poorer than that of ordinary colorectal cancer. A 56-year-old Korean man was seen at this hospital for management of signet ring cell carcinoma of the colon. Colonoscopic examination revealed a IIa-like, ill-defined and flatly elevated 9-mm residual tumor in the cecum. Endoscopic mucosal resection was preformed. Pathological examination of the resected specimen revealed signet ring cell carcinoma that had invaded the lamina propria without venous or perineural invasion. Abdominal computed tomography (CT) and positron CT showed no evidence of primary lesions or distant metastasis. An additional laparoscopic right-hemicolectomy was performed; no residual tumor or lymph node metastasis was found. We report a case of primary signet ring cell carcinoma of the colon detected at an early stage and provide a review of the literature.
doi:10.3748/wjg.v19.i24.3895
PMCID: PMC3699035  PMID: 23840131
Colon carcinoma; Signet ring cell carcinoma; Primary carcinoma; Early stage; Endoscopic mucosal resection
11.  Acquired Long QT Syndrome Manifesting with Torsades de Pointes in a Patient with Panhypopituitarism due to Radiotherapy 
Korean Circulation Journal  2013;43(5):340-342.
We describe a 64-year-old male patient with panhypopituitarism who experienced polymorphic ventricular tachycardia (VT) associated with long QT intervals. The panhypopituitarism developed as a sequelae of radiation therapy administered 20 years prior to his current presentation and was recently aggravated by urinary tract infection with sepsis. In this case, polymorphic VT was resistant to conventional therapy (including magnesium infusion), and QT prolongation and T wave inversion were normalized after the administration of steroid and thyroid hormones. Thyroid hormone is generally known to be associated with torsades de pointes (TdP), but steroid or other hormones may also provoke TdP. Hormonal disorders should be considered as a cause of polymorphic VT with long QT intervals. Some arrhythmias can be life-threatening, and they can be prevented with supplementation of the insufficient hormone.
doi:10.4070/kcj.2013.43.5.340
PMCID: PMC3675309  PMID: 23755081
Tachycardia, ventricular; Torsades de pointes; Hypopituitarism; Radiotherapy
12.  Effect of Helicobacter pylori Eradication on Functional Dyspepsia 
Background/Aims
This study evaluated the effect of Helicobacter pylori eradication on functional dyspepsia (FD), and the relationship between the changes of histological gastritis and FD symptom responses.
Methods
A total of 213 FD patients diagnosed by Rome III criteria were consecutively enrolled. H. pylori tests and gastritis grade by the Sydney system were performed before and 1 year after the proton pump based-eradication therapy for 7 days. Serum levels of pepsinogen, and genetic polymorphisms IL-6, IL-8 and IL-10 were investigated.
Results
Total of 91 patients completed the 1 year follow-up. When the response rate of dyspepsia was compared at 1 year between the non-eradicated group (n = 24) and eradicated group (n = 67), each group showed complete response of 62.5% and 62.7%; satisfactory response (≥ 50%) of 0.0% and 19.4%; partial response (< 50%) of 12.5% and 11.9%; and refractory response of 25.0% and 6.0%, respectively (P = 0.015). In addition, the responder group (complete + satisfactory response) at 1 year showed improvement of activity and chronic inflammation in both the antrum and corpus (all P < 0.001). Multivariate analysis showed that H. pylori eradication (OR, 5.81; 95% CI, 1.07-31.59) and symptom improvement at 3 month (OR, 28.90; 95% CI, 5.29-157.82) were associated with the improvement of dyspepsia at 1 year. Among the successfully eradicated FD patients (n = 67), male (P = 0.013) and higher initial BMI (P = 0.016) were associated with the improvement of dyspepsia at 1 year.
Conclusions
H. pylori eradication improved FD symptoms, as well as gastritis at 1 year, suggesting that inflammation mediates FD.
doi:10.5056/jnm.2013.19.2.233
PMCID: PMC3644660  PMID: 23667755
Eradication; Functional dyspepsia; Helicobacter pylori
13.  Primary Mucinous Cystadenocarcinoma of the Breast: Cytologic Finding and Expression of MUC5 Are Different from Mucinous Carcinoma 
Korean Journal of Pathology  2012;46(6):611-616.
Mucinous cystadenocarcinoma (MCA) in the breast is a rare neoplasm. There have been 13 cases of primary breast MCA reported. The MCA presents as a large, partially cystic mass in postmenopausal woman with a good prognosis. The microscopic findings resemble those of ovarian, pancreatic, or appendiceal MCA. The aspiration findings showed mucin-containing cell clusters in the background of mucin and necrotic material. The cell clusters had intracytoplasmic mucin displacing atypical nuclei to the periphery. Histologically, the tumor revealed an abundant mucin pool with small floating clusters of mucin-containing tumor cells. There were also small cysts lined by a single layer of tall columnar mucinous cells, resembling those of the uterine endocervix. The cancer cells were positive for mucin (MUC) 5 and negative for MUC2 and MUC6. This mucin profile is different from ordinary mucinous carcinoma and may be a unique characteristic of breast MCA.
doi:10.4132/KoreanJPathol.2012.46.6.611
PMCID: PMC3540343  PMID: 23323116
Mucinous cystadenocarcinoma; Breast; MUC5; MUC2
14.  Effects of vagus nerve preservation and vagotomy on peptide YY and body weight after subtotal gastrectomy 
AIM: To investigate the relationship between the function of vagus nerve and peptide YY3-36 and ghrelin levels after subtotal gastrectomy.
METHODS: We enrolled a total of 16 patients who underwent subtotal gastrectomy due to gastric cancer. All surgeries were performed by a single skilled surgeon. We measured peptide YY3-36, ghrelin, leptin, insulin, growth hormone levels, and body weight immediately before and one month after surgery.
RESULTS: Vagus nerve preservation group showed less body weight loss and less increase of peptide YY3-36 compared with vagotomy group (-5.56 ± 2.24 kg vs -7.85 ± 1.57 kg, P = 0.037 and 0.06 ± 0.08 ng/mL vs 0.19 ± 0.12 ng/mL, P = 0.021, respectively). Moreover, patients with body weight loss of less than 10% exhibited reduced elevation of peptide YY3-36 level, typically less than 20% [6 (66.7%) vs 0 (0.0%), P = 0.011, odd ratio = 3.333, 95% confidence interval (1.293, 8.591)].
CONCLUSION: Vagus nerve preservation contributes to the maintenance of body weight after gastrectomy, and this phenomenon may be related to the suppressed activity of peptide YY3-36.
doi:10.3748/wjg.v18.i30.4044
PMCID: PMC3420002  PMID: 22912556
Anal cushion; Anal incontinence; Liquids continence test; Wexner score; Hemorrhoidectomy
15.  An Elderly Case of Acute Cerebellitis after Alleged Vaccination 
Journal of Movement Disorders  2012;5(1):21-23.
Acute cerebellitis (AC) is a benign and self-limiting inflammatory disease. It typically occurs as a primary infectious or postinfectious disorder. Although AC mostly presents in early childhood, it can appear in adult. A 66-year-old man admitted to our hospital because of limb and gait ataxia. Three weeks ago, he took an influenza vaccination. There was no abnormality on brain MRI with contrast enhancement, but Technetium-99m hexamethyl propylene amine oxime-single photon emission computed tomography (HMPAO-SPECT) showed markedly cerebellar asymmetry, suggesting hypoperfusion in the right cerebellum. Influenza vaccination can cause AC in the elderly and brain HMPAO-SPECT imaging is more useful than MRI in identifying patients with AC.
doi:10.14802/jmd.12006
PMCID: PMC4027673  PMID: 24868409
Cerebellitis; Influenza; Vaccination
16.  Transparent-cap-fitted colonoscopy shows higher performance with cecal intubation time in difficult cases 
AIM: To investigate the efficacy of cap-fitted colonoscopy (CFC) with regard to cecal intubation time.
METHODS: Two hundred and ninety-five patients undergoing screening colonoscopy at Gospel Hospital, Kosin University College of Medicine were enrolled in this randomized controlled trial between January and December 2010. Colonoscopies were conducted by a single endoscopist. Patient characteristics including age, sex, body mass index, history of abdominal surgery, quality of preparation, and the presence of diverticulosis were recorded.
RESULTS: One hundred and fifty patients were allocated into a CFC group and 145 into a non-CFC (NCF) group. Cecal intubations were achieved in all patients. Cecal intubation time in the CFC group was significantly shorter than in the NCF group for specific conditions: age ≥ 60 years, prior abdominal surgery, and poor bowel preparation. The number of detected adenomas was higher in the CFC group than in the NCF group (P = 0.040).
CONCLUSION: CFC facilitated shortening of the cecal intubation time in difficult cases, and was more sensitive for detecting adenomas than was NCF.
doi:10.3748/wjg.v18.i16.1953
PMCID: PMC3337572  PMID: 22563177
Colonoscopy; Cap-fitted colonoscopy; Cecal intubation
17.  Isolated cricoid fracture associated with blunt neck trauma 
Emergency Medicine Journal : EMJ  2007;24(7):505-506.
A 32‐year‐old woman without a remarkable history presented at the emergency department with strangulation of the neck. CT scans of the neck revealed a displaced cricoid fracture. Six days after admission to hospital, hoarseness and dyspnoea disappeared. On the 10th day, the patient was discharged without complications. The traditional treatment guidelines for laryngeal trauma have recommended an early surgical intervention after immediate tracheotomy in cases of displaced fractures of the cricoid cartilage. The patient could be treated successfully through continuous monitoring of airway obstruction without surgical management.
doi:10.1136/emj.2007.048355
PMCID: PMC2658407  PMID: 17582051
19.  Distinct serum metabolomics profiles associated with malignant progression in the KrasG12D mouse model of pancreatic ductal adenocarcinoma 
BMC Genomics  2015;16(Suppl 1):S1.
Background
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer deaths worldwide with less than a 6% 5-year survival rate. PDAC is associated with poor prognosis based on the late stage diagnosis of the disease. Current diagnostic tests lack the sensitivity and specificity to identify markers of early staging. Metabolomics has provided biomarkers for various diseases, stressors, and environmental exposures. In this study we utilized the p48-Cre/LSL-KrasG12D mouse model with age-matched wild type mice. This model shows malignant progression to PDAC analogous to the human disease stages via early and late pancreatic intra-epithelial neoplasia (PanIN) lesions.
Results
Serum was collected from mice with early PanIN lesions (at 3-5 months) and with late PanIN or invasive PDAC lesions (13-16 months), as determined by histopathology. Metabolomics analysis of the serum samples was conducted through UPLC-TOFMS (Ultra Performance Liquid Chromatography coupled to Time-of-flight Mass Spectrometry). Multivariate data analysis revealed distinct metabolic patterns in serum samples collected during malignant progression towards invasive PDAC. Animals with early or late stage lesions were distinguished from their respective controls with 82.1% and 81.5% accuracy, respectively. This also held up for randomly selected subgroups in the late stage lesion group that showed less variability between animals. One of the metabolites, citrate, was validated through tandem mass spectrometry and showed increased levels in serum with disease progression. Furthermore, serum metabolite signatures from animals with early stage lesions identified controls and animals with late stage lesions with 81.5% accuracy (p<0.01) and vice-versa with 73.2% accuracy (p<0.01).
Conclusions
We conclude that metabolomics analysis of serum samples can identify the presence of early and late stage pancreatic cancer.
doi:10.1186/1471-2164-16-S1-S1
PMCID: PMC4315147
20.  γ-Glutamyl hydrolase modulation significantly influences global and gene-specific DNA methylation and gene expression in human colon and breast cancer cells 
Genes & Nutrition  2014;10(1):444.
γ-Glutamyl hydrolase (GGH) plays an important role in folate homeostasis by catalyzing hydrolysis of polyglutamylated folate into monoglutamates. Polyglutamylated folates are better substrates for several enzymes involved in the generation of S-adenosylmethionine, the primary methyl group donor, and hence, GGH modulation may affect DNA methylation. DNA methylation is an important epigenetic determinant in gene expression, in the maintenance of DNA integrity and stability, and in chromatin modifications, and aberrant or dysregulation of DNA methylation has been mechanistically linked to the development of human diseases including cancer. Using a recently developed in vitro model of GGH modulation in HCT116 colon and MDA-MB-435 breast cancer cells, we investigated whether GGH modulation would affect global and gene-specific DNA methylation and whether these alterations were associated with significant gene expression changes. In both cell lines, GGH overexpression decreased global DNA methylation and DNA methyltransferase (DNMT) activity, while GGH inhibition increased global DNA methylation and DNMT activity. Epigenomic and gene expression analyses revealed that GGH modulation influenced CpG promoter DNA methylation and gene expression involved in important biological pathways including cell cycle, cellular development, and cellular growth and proliferation. Some of the observed altered gene expression appeared to be regulated by changes in CpG promoter DNA methylation. Our data suggest that the GGH modulation-induced changes in total intracellular folate concentrations and content of long-chain folylpolyglutamates are associated with functionally significant DNA methylation alterations in several important biological pathways.
Electronic supplementary material
The online version of this article (doi:10.1007/s12263-014-0444-0) contains supplementary material, which is available to authorized users.
doi:10.1007/s12263-014-0444-0
PMCID: PMC4265218  PMID: 25502219
Folate; γ-Glutamyl hydrolase (GGH); DNA methylation; Gene expression; Colon cancer; Breast cancer
21.  In Vivo Effects of Adipose-Derived Stem Cells in Inducing Neuronal Regeneration in Sprague-Dawley Rats Undergoing Nerve Defect Bridged with Polycaprolactone Nanotubes 
Journal of Korean Medical Science  2014;29(Suppl 3):S183-S192.
There have been many attempts for regeneration of peripheral nerve injury. In this study, we examined the in vivo effects of non-differentiated and neuronal differentiated adipose-derived stem cells (ADSCs) in inducing the neuronal regeneration in the Sprague-Dawley (SD) rats undergoing nerve defect bridged with the PCL nanotubes. Then, we performed immunohistochemical and histopathologic examinations, as well as the electromyography, in three groups: the control group (14 sciatic nerves transplanted with the PCL nanotube scaffold), the experimental group I (14 sciatic nerves with the non-differentiated ADSCs at a density of 7×105 cells/0.1 mL) and the experimental group II (14 sciatic nerves with the neuronal differentiated ADSCs at 7×105 cells/0.1 mL). Six weeks postoperatively, the degree of the neuronal induction and that of immunoreactivity to nestin, MAP-2 and GFAP was significantly higher in the experimental group I and II as compared with the control group. In addition, the nerve conduction velocity (NCV) was significantly higher in the experimental group I and II as compared with the control group (P=0.021 and P=0.020, respectively). On the other hand, there was no significant difference in the NCV between the two experimental groups (P>0.05). Thus, our results will contribute to treating patients with peripheral nerve defects using PCL nanotubes with ADSCs.
doi:10.3346/jkms.2014.29.S3.S183
PMCID: PMC4248004  PMID: 25473208
Stem Cells; Adipose Tissue; Nanotubes; Matrix Attachment Regions; Peripheral Nerves; Regeneration; Polycaprolactone
22.  Autophagy proteins regulate cell engulfment mechanisms that participate in cancer 
Seminars in cancer biology  2013;23(5):329-336.
Recent evidence has uncovered cross-regulation of mechanisms of cell engulfment by proteins of the autophagy pathway, in what is called LC3-Associated Phagocytosis, or LAP. By LAP, lysosome fusion to phagosomes and the degradation of engulfed extracellular cargo are facilitated by autophagy proteins that lipidate LC3 onto phagosome membranes. Here we discuss the contexts where LAP is known to occur by focusing on potential roles in tumorigenesis, including predicted consequences of LAP inhibition.
doi:10.1016/j.semcancer.2013.05.004
PMCID: PMC3791149  PMID: 23726896
autophagy; entosis; phagocytosis; cell death; macrophage; tumor; immune
23.  Immediate Direct-To-Implant Breast Reconstruction Using Anatomical Implants 
Archives of Plastic Surgery  2014;41(5):529-534.
Background
In 2012, a new anatomic breast implant of form-stable silicone gel was introduced onto the Korean market. The intended use of this implant is in the area of aesthetic breast surgery, and many reports are promising. Thus far, however, there have been no reports on the use of this implant for breast reconstruction in Korea. We used this breast implant in breast reconstruction surgery and report our early experience.
Methods
From November 2012 to April 2013, the Natrelle Style 410 form-stable anatomically shaped cohesive silicone gel-filled breast implant was used in 31 breasts of 30 patients for implant breast reconstruction with an acellular dermal matrix. Patients were treated with skin-sparing mastectomies followed by immediate breast reconstruction.
Results
The mean breast resection volume was 240 mL (range, 83-540 mL). The mean size of the breast implants was 217 mL (range, 125-395 mL). Breast shape outcomes were considered acceptable. Infection and skin thinning occurred in one patient each, and hematoma and seroma did not occur. Three cases of wound dehiscence occurred, one requiring surgical intervention, while the others healed with conservative treatment in one month. Rippling did not occur. So far, complications such as capsular contracture and malrotation of breast implant have not yet arisen.
Conclusions
By using anatomic breast implants in breast reconstruction, we achieved satisfactory results with aesthetics better than those obtained with round breast implants. Therefore, we concluded that the anatomical implant is suitable for breast reconstruction.
doi:10.5999/aps.2014.41.5.529
PMCID: PMC4179357  PMID: 25276645
Breast implants; Breast implantation; Mammoplasty; Mastectomy; Breast neoplasms
24.  Myocardial Contrast Echocardiography for the Detection of Coronary Artery Disease in Patients with Global Hypokinesis Admitted for First-Onset Acute Heart Failure: Pilot Study 
Background
The non-invasive differentiation of ischemic and nonischemic acute heart failure (AHF) not resulting from acute myocardial infarction is difficult and has therapeutic and prognostic implications. The aim of this study was to assess whether resting myocardial contrast echocardiography (MCE) can detect coronary artery disease (CAD) in patients with decreased left ventricular (LV) systolic function and global hypokinesis presenting with AHF.
Methods
Twenty-one consecutive patients underwent low-power real-time MCE based on color-coded pulse inversion Doppler. Standard apical LV views were acquired during contrast IV infusion of Definity®. Following transient microbubbles destruction, the contrast replenishment rate (β), reflecting myocardial blood flow velocity, was derived by plotting signal intensity vs. time and fitting data to the exponential function: y (t) = A (1 - e-β(t-t0)) + C.
Results
Of the 21 (mean age 56.6 ± 13.6 years) patients, 5 (23.8%) demonstrated flow-limiting CAD (> 70% of luminal diameter narrowing). The mean ± standard deviation of LV ejection fraction was 29.6 ± 8.6%. Quantitative MCE analysis was feasible in 258 of 378 segments (68.3%). There were no significant difference in "β" and "Aβ" in patients without and with CAD (0.48 ± 0.27 vs. 0.45 ± 0.25, p = 0.453 for β and 2.99 ± 2.23 vs. 3.68 ± 3.13, p = 0.059 for Aβ, respectively). No contrast-related side effects were reported.
Conclusion
Resting quantitative MCE analysis in patients with AHF was feasible, however, the parameters did not aid in detecting of CAD.
doi:10.4250/jcu.2014.22.3.121
PMCID: PMC4192409  PMID: 25309688
Coronary disease; Diagnosis; Echocardiography; Heart failure
25.  Postnatal treadmill exercise alleviates short-term memory impairment by enhancing cell proliferation and suppressing apoptosis in the hippocampus of rat pups born to diabetic rats 
During pregnancy, diabetes mellitus exerts detrimental effects on the development of the fetus, especially the central nervous system. In the current study, we evaluated the effects of postnatal treadmill exercise on short-term memory in relation with cell proliferation and apoptosis in the hippocampus of rat pups born to streptozotocin (STZ)-induced diabetic maternal rats. Adult female rats were mated with male rats for 24 h. Two weeks after mating, the pregnant female rats were divided into two groups: control group and STZ injection group. The pregnant rats in the STZ injection group were administered 40 mg/kg of STZ intraperitoneally. After birth, the rat pups were divided into the following four groups: control group, control with postnatal exercise group, maternal STZ-injection group, and maternal STZ-injection with postnatal exercise group. The rat pups in the postnatal exercise groups were made to run on a treadmill for 30 min once a day, 5 times per week for 2 weeks beginning 4 weeks after birth. The rat pups born to diabetic rats were shown to have short-term memory impairment with suppressed cell proliferation and increased apoptosis in the hippocampal dentate gyrus. Postnatal treadmill exercise alleviated short-term memory impairment by increased cell proliferation and suppressed apoptosis in the rat pups born to diabetic rats. These findings indicate that postnatal treadmill exercise may be used as a valuable strategy to ameliorate neurodevelopmental problems in children born to diabetics.
doi:10.12965/jer.140145
PMCID: PMC4157927  PMID: 25210695
Diabetic rats; Treadmill exercise; Cell proliferation; Apoptosis; Rat pups; Hippocampal dentate gyrus

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