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1.  Laparoscopic repair of indirect inguinal hernia containing endometriosis, ovary, and fallopian tube in adult woman without genital anomalies 
Obstetrics & Gynecology Science  2014;57(6):557-559.
Indirect inguinal hernia containing an ovary is a rare condition, especially in adult women who do not have any other genital tract anomalies. In addition, inguinal hernia containing an ovary and endometriosis is exceedingly rare. In the present report, we describe a case of indirect inguinal hernia containing an ovary, fallopian tube, and endometriosis. Laparoscopic repair was performed successfully using polypropylene mesh for the treatment of the inguinal hernia.
PMCID: PMC4245355  PMID: 25469350
Endometriosis; Hernia, inguinal; Laparoscopic repair; Ovary
2.  Hypomania Induced by Subthalamic Nucleus Stimulation in a Parkinson’s Disease Patient: Does It Suggest a Dysfunction of the Limbic Circuit? 
Journal of Movement Disorders  2012;5(1):14-17.
The aim of this report was to describe a case of hypomania after deep brain stimulation of the subthalamic nucleus (STN DBS) in a Parkinson’s disease (PD) patient. 59-year-old man with a 15-year history of PD underwent bilateral implantation of electrodes to the STN. Immediately after surgery, his motor function was markedly improved and his mood was elevated to hypomania. Fusion images of the preoperative MRI and postoperative CT scan showed that the electrodes were located in the medial portion of the STN. In this case, behavioral mood change was related to the deep brain stimulation. Moreover, the anatomical location and the functional alteration of the STN after the DBS surgery might be related to the regulatory system of the associative and limbic cortico-subcortical circuits.
PMCID: PMC4027680  PMID: 24868407
Deep brain stimulation; Subthalamic stimulation; Non motor symptom; Hypomania; Mood
3.  Effects of Long-Term Supplementation of Blue-Green Algae on Lipid Metabolism in C57BL/6J mice 
Dyslipidemia is a primary risk factor for cardiovascular disease. In this study, we investigated the effect of long-term supplementation of two blue-green algae (BGA) species, i.e., Nostoc commune var. sphaeroides Kützing (NO) and Spirulina platensis (SP), on lipid metabolism in vivo. Male C57BL/6J mice were fed an AIN-93G/M diet supplemented with 2.5 or 5% (wt/wt) NO or SP for 6 months. Mice fed NO and SP showed lower plasma total cholesterol (TC) and triglyceride (TG) concentrations than control at certain months during 6 month experimental period. Both BGA supplementation for 6 months significantly increased hepatic TC contents whereas SP-fed groups had significantly less TG levels in the liver compared with control and NO groups. None of BGA-fed animals showed significantly different mRNA levels of sterol regulatory element binding protein 2, while 3-hydroxy-3-methylglutaryl coenzyme A reductase and low-density lipoprotein receptor (LDLR) expression was higher in NO groups than the other groups in the liver. Furthermore, NO supplementation increased the hepatic expression of acetyl-CoA carboxylase 1, stearoyl CoA desaturase 1, carnitine palmitoyltransferase 1α, and acyl-CoA oxidase 1 but SP did not elicit any significant changes in mRNA levels of the genes compared with control. LDLR protein level was significantly higher in NO 2.5% and SP 5%, as compared to the control and NO 5% groups; while the level of fatty acid synthase protein in the liver was significantly higher in NO 5% and SP 5%, than that in the control group. In conclusion, our results suggest that long-term supplementation of NO and SP decreased plasma TC and TG concentrations. Therefore, supplementation of NO and SP may be potentially beneficial for preventing dyslipidemia-associated chronic diseases.
PMCID: PMC4299668  PMID: 25614902
Blue-green algae; Cholesterol; Nostoc commune var. sphaeroides Kützing; Spirulina platensis; Triglyceride
4.  Retreatment with peginterferon and ribavirin in chronic hepatitis C 
The development of boceprevir and telaprevir was a major step forward in the treatment of chronic hepatitis C. In addition, the treatment of these infections has been recently revolutionized by the approval of sofosbuvir and simeprevir. However, there are several challenges associated with the application of novel drugs, such as new and more frequent adverse events, new drug interactions, and excessively high treatment costs. An additional concern is viral resistance. These considerations highlight the fact that direct-acting antiviral agents are not a panacea and may not be the best option for all patients who are in need of therapy. This retrospective study revealed that the sustained virologic response was not significantly reduced following peginterferon and ribavirin retreatment compared with the new therapy. We suggest that patients who experience relapse shortly after completing treatment with peginterferon and ribavirin have a reasonable chance of achieving a sustained virologic response when retreated with these drugs alone.
PMCID: PMC4323480
Chronic hepatitis C; Direct-acting antiviral agents; Peginterferon; Ribavirin; Retreatment
5.  Egg Intake during Carbohydrate Restriction Alters Peripheral Blood Mononuclear Cell Inflammation and Cholesterol Homeostasis in Metabolic Syndrome 
Nutrients  2014;6(7):2650-2667.
Egg yolk contains bioactive components that improve plasma inflammatory markers and HDL profiles in metabolic syndrome (MetS) under carbohydrate restriction. We further sought to determine whether egg yolk intake affects peripheral blood mononuclear cell (PBMC) inflammation and cholesterol homeostasis in MetS, as HDL and its associated lipid transporter ATP-binding cassette transporter A1 (ABCA1) reduce the inflammatory potential of leukocytes through modulation of cellular cholesterol content and distribution. Thirty-seven men and women classified with MetS consumed a moderate carbohydrate-restricted diet (25%–30% of energy) for 12 weeks, in addition to consuming either three whole eggs per day (EGG) or the equivalent amount of yolk-free egg substitute (SUB). Interestingly, lipopolysaccharide-induced PBMC IL-1β and TNFα secretion increased from baseline to week 12 in the SUB group only, despite increases in PBMC toll-like receptor 4 (TLR4) mRNA expression in the EGG group. Compared to baseline, ABCA1 and 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase mRNA expression increased by week 12 in the EGG group only, whereas changes in PBMC total cholesterol positively correlated with changes in lipid raft content. Together, these findings suggest that intake of whole eggs during carbohydrate restriction alters PBMC inflammation and cholesterol homeostasis in MetS.
PMCID: PMC4113762  PMID: 25045936
inflammation; cholesterol; peripheral blood mononuclear cells; ABCA1; eggs; metabolic syndrome
6.  Epstein-Barr virus-associated lymphoepithelioma-like early gastric carcinomas and endoscopic submucosal dissection: Case series 
Epstein-Barr virus (EBV)-associated lymphoepithelioma-like gastric carcinoma (LELC) is characterized by a lower lymph node (LN) metastasis rate and a higher survival rate than other forms of gastric cancer. Although current prognosis for LELC is favorable, the most common approach is radical gastrectomy involving an extensive D2 lymph node dissection. Here, we report four cases of EBV-associated early LELC that were treated by an alternative approach, endoscopic submucosal dissection (ESD). The long-term outcome of this procedure is discussed. All patients were treated by ESD en bloc, and all ESD specimens showed tumor-free lateral resection margins. None of the lesions showed lymphovascular invasion. A pathological examination of ESD specimens revealed submucosal invasion of more than 500 μm in all four cases. One patient underwent additional radical surgery post-ESD; no residual tumor or LN metastasis was noted in the surgical specimen. The other three patients did not undergo additional surgery, either because of severe comorbidity or their refusal to undergo operation, but were subjected to medical follow-up. None of the ESD-treated patients reported local recurrence or distant metastases during the 27-32 mo of follow-up after ESD.
PMCID: PMC3921521  PMID: 24574813
Endoscopic submucosal dissection; Epstein-Barr virus; Lymph node; Lymphoepithelioma-like gastric carcinoma; Prognosis
7.  Anesthesia for cesarean section in a patient with respiratory failure -A case report- 
Korean Journal of Anesthesiology  2013;64(5):460-463.
We present successful epidural anesthesia and assisted mechanical ventilation in a parturient woman with respiratory failure. A 41-year-old woman at 35 weeks' of gestation was entering labor. She was pneumonectomized on the left, had bronchiectasis on the remnant lung, and was under assisted mechanical ventilation by continuous positive airway pressure (CPAP) because of severely restricted lung function and superimposed pneumonia. We administered continuous epidural analgesia for vaginal delivery, and extended it for cesarean section after failure of vaginal delivery. During the procedure, her ventilation was continuously assisted by CPAP. The maternal and fetal outcomes were successful.
PMCID: PMC3668111  PMID: 23741572
Cesarean section; Continuous positive airway pressure; Epidural anesthesia; Respiratory failure
8.  Anesthetic management of a neonate with congenital laryngeal cyst 
Korean Journal of Anesthesiology  2012;63(3):282-283.
PMCID: PMC3460163  PMID: 23060991
9.  Balsamic Vinegar Improves High Fat-Induced Beta Cell Dysfunction via Beta Cell ABCA1 
Diabetes & Metabolism Journal  2012;36(4):275-279.
The aim of this study was to investigate the effects of balsamic vinegar on β-cell dysfunction.
In this study, 28-week-old Otsuka Long-Evans Tokushima Fatty (OLETF) rats were fed a normal chow diet or a high-fat diet (HFD) and were provided with tap water or dilute balsamic vinegar for 4 weeks. Oral glucose tolerance tests and histopathological analyses were performed thereafter.
In rats fed both the both chow diet and the HFD, the rats given balsamic vinegar showed increased insulin staining in islets compared with tap water administered rats. Balsamic vinegar administration also increased β-cell ATP-binding cassette transporter subfamily A member 1 (ABCA1) expression in islets and decreased cholesterol levels.
These findings provide the first evidence for an anti-diabetic effect of balsamic vinegar through improvement of β-cell function via increasing β-cell ABCA1 expression.
PMCID: PMC3428415  PMID: 22950058
Balsamic vinegar; Islets; Insulin; ABCA1; Diet, high-fat
10.  Dietary Oleate Has Beneficial Effects on Every Step of Non-Alcoholic Fatty Liver Disease Progression in a Methionine- and Choline-Deficient Diet-Fed Animal Model 
Diabetes & Metabolism Journal  2011;35(5):489-496.
Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized as a major cause of liver-related morbidity and mortality. The underlying mechanisms of disease progression remain poorly understood, and primary therapy of NAFLD is not yet established. We investigated the effects of dietary oleate on the development and progression of NAFLD in a methionine- and choline-deficient (MCD) diet-fed animal model.
A total of 30 C57BL/6J mice were randomly divided into three groups (n=10 in each group) and fed various experimental diets for four weeks: chow, MCD diet, or OMCD (MCD diet with oleate, 0.5 mg/g/day). Liver samples were examined for steatohepatitis and fibrosis parameters and associated genes.
Additional dietary oleate dramatically reduced MCD diet-induced hepatic steatosis. Hepatic carbohydrate responsive element-binding protein was overexpressed in MCD diet-fed mice, and dietary oleate prevented this overexpression (P<0.001). Dietary oleate partially prevented MCD diet-induced serum level increases in aspartate aminotransferase and alanine aminotransferase (P<0.001, respectively). The mRNA expressions of hepatic monocyte chemoattractant protein 1, tumor necrosis factor-α and matrix metalloproteinase-9 were increased in MCD diet-fed mice, and this overexpression of inflammatory molecules was prevented by dietary oleate (P<0.001). Hepatic pericellular fibrosis was observed in MCD diet-fed mice, and dietary oleate prevented this fibrosis. Altogether, dietary oleate prevented MCD diet-induced hepatic steatosis, inflammation and fibrosis.
Dietary oleate has beneficial effects in every step of NAFLD development and progression and could be a nutritional option for NAFLD prevention and treatment.
PMCID: PMC3221024  PMID: 22111040
ChREBP; Fatty acids, monounsaturated; Non-alcoholic steatohepatitis
11.  Spinal Cord Injury Markedly Altered Protein Expression Patterns in the Affected Rat Urinary Bladder during Healing Stages 
Journal of Korean Medical Science  2011;26(6):814-823.
The influence of spinal cord injury (SCI) on protein expression in the rat urinary bladder was assessed by proteomic analysis at different time intervals post-injury. After contusion SCI between T9 and T10, bladder tissues were processed by 2-DE and MALDI-TOF/MS at 6 hr to 28 days after SCI to identify proteins involved in the healing process of SCI-induced neurogenic bladder. Approximately 1,000 spots from the bladder of SCI and sham groups were visualized and identified. At one day after SCI, the expression levels of three protein were increased, and seven spots were down-regulated, including heat shock protein 27 (Hsp27) and heat shock protein 20 (Hsp20). Fifteen spots such as S100-A11 were differentially expressed seven days post-injury, and seven proteins including transgelin had altered expression patterns 28 days after injury. Of the proteins with altered expression levels, transgelin, S100-A11, Hsp27 and Hsp20 were continuously and variably expressed throughout the entire post-SCI recovery of the bladder. The identified proteins at each time point belong to eight functional categories. The altered expression patterns identified by 2-DE of transgelin and S100-A11 were verified by Western blot. Transgelin and protein S100-A11 may be candidates for protein biomarkers in the bladder healing process after SCI.
PMCID: PMC3102878  PMID: 21655070
Spinal Cord Injuries; Urinary Bladder, Neurogenic; Proteomic Analysis; Biological Markers; S100-A11; Transgelin
12.  Aspiration pneumonia in the child with DiGeorge syndrome -A case report- 
Korean Journal of Anesthesiology  2011;60(6):449-452.
DiGeorge syndrome is associated with a chromosome 22q11.2 deletion and manifests with variable clinical findings. Aspiration pneumonia can be a perioperative complication of great concern in this syndrome. In this report, we present a case of a 16-month old child with DiGeorge syndrome undergoing cranioplasty. He developed perioperative aspiration pneumonia but was managed successfully.
PMCID: PMC3121095  PMID: 21738851
Aspiration pneumonia; DiGeorge syndrome
13.  In vitro Evaluation of Antibiotic Lock Technique for the Treatment of Candida albicans, C. glabrata, and C. tropicalis Biofilms 
Journal of Korean Medical Science  2010;25(12):1722-1726.
Candidaemia associated with intravascular catheter-associated infections is of great concern due to the resulting high morbidity and mortality. The antibiotic lock technique (ALT) was previously introduced to treat catheter-associated bacterial infections without removal of catheter. So far, the efficacy of ALT against Candida infections has not been rigorously evaluated. We investigated in vitro activity of ALT against Candida biofilms formed by C. albicans, C. glabrata, and C. tropicalis using five antifungal agents (caspofungin, amphotericin B, itraconazole, fluconazole, and voriconazole). The effectiveness of antifungal treatment was assayed by monitoring viable cell counts after exposure to 1 mg/mL solutions of each antibiotic. Fluconazole, itraconazole, and voriconazole eliminated detectable viability in the biofilms of all Candida species within 7, 10, and 14 days, respectively, while caspofungin and amphotericin B did not completely kill fungi in C. albicans and C. glabrata biofilms within 14 days. For C. tropicalis biofilm, caspofungin lock achieved eradication more rapidly than amphotericin B and three azoles. Our study suggests that azoles may be useful ALT agents in the treatment of catheter-related candidemia.
PMCID: PMC2995224  PMID: 21165285
Candida; Biofilms; Antibiotic Lock Technique
14.  Mesothelial Cyst of the Round Ligament Mimicking a Metastasis: a Case Report 
Korean Journal of Radiology  2010;11(3):364-367.
A mesothelial cyst of the round ligament is a rare cause of an inguinal mass. Clinically, it is frequently misdiagnosed as one of commoner diseases such as an inguinal hernia, femoral hernia, lipoma, and lymphadenopathy upon physical examination. Some previous reports elaborated the sonographic features of a mesothelial cyst of the round ligament. However, to our knowledge, few reports have described the CT features of a mesothelial cyst. We illustrated here the sonographic and multidetector CT features of a case of a mesothelial cyst of the round ligament that presented as an inguinal palpable mass and mimicked a metastasis in a patient with a Sertoli-Leydig cell tumor of the ovary.
PMCID: PMC2864865  PMID: 20461192
Mesothelial cyst; Round ligament; Inguinal area; Ultrasonography; Multi-detector row CT
15.  Factors Influencing the Increasing Disparity in LDL Cholesterol Control between White and Black Patients with Diabetes in a Context of Active Quality Improvement 
After implementing a multifaceted physician-directed quality improvement (QI) initiative, we observed an increased disparity in LDL cholesterol control between white and black diabetes patients. To examine possible causes, we performed a retrospective analysis of 962 black and white patients treated continuously between 2008 and 2010. At baseline, 55.0% of whites and 49.8% of blacks were controlled (5.2% disparity). The disparity increased, with 61.8% of whites and 44.6% of blacks having control in 2010 (17.2% disparity). Among patients uncontrolled at baseline, blacks were less likely to become controlled. Among patients controlled at baseline, blacks were less likely to remain controlled. Accounting for patient characteristics and changes in lipid-lowering drug prescription regimens did not attenuate these relationships. Physician-facing, general QI interventions may be insufficient to produce equity in LDL cholesterol control. Helping patients maintain prior success controlling cholesterol appears as important in addressing this disparity as is helping uncontrolled patients achieve control.
PMCID: PMC3951676  PMID: 23939486
16.  Identification of HNRNPK as Regulator of Hepatitis C Virus Particle Production 
PLoS Pathogens  2015;11(1):e1004573.
Hepatitis C virus (HCV) is a major cause of chronic liver disease affecting around 130 million people worldwide. While great progress has been made to define the principle steps of the viral life cycle, detailed knowledge how HCV interacts with its host cells is still limited. To overcome this limitation we conducted a comprehensive whole-virus RNA interference-based screen and identified 40 host dependency and 16 host restriction factors involved in HCV entry/replication or assembly/release. Of these factors, heterogeneous nuclear ribonucleoprotein K (HNRNPK) was found to suppress HCV particle production without affecting viral RNA replication. This suppression of virus production was specific to HCV, independent from assembly competence and genotype, and not found with the related Dengue virus. By using a knock-down rescue approach we identified the domains within HNRNPK required for suppression of HCV particle production. Importantly, HNRNPK was found to interact specifically with HCV RNA and this interaction was impaired by mutations that also reduced the ability to suppress HCV particle production. Finally, we found that in HCV-infected cells, subcellular distribution of HNRNPK was altered; the protein was recruited to sites in close proximity of lipid droplets and colocalized with core protein as well as HCV plus-strand RNA, which was not the case with HNRNPK variants unable to suppress HCV virion formation. These results suggest that HNRNPK might determine efficiency of HCV particle production by limiting the availability of viral RNA for incorporation into virions. This study adds a new function to HNRNPK that acts as central hub in the replication cycle of multiple other viruses.
Author Summary
As obligate intracellular parasites with limited gene coding capacity viruses exploit host cell machineries for the sake of efficient replication and spread. Thus, identification of these cellular machineries and factors is necessary to understand how a given virus achieves efficient replication and eventually causes host cell damage. Hepatitis C virus (HCV) is an RNA virus replicating in the cytoplasm of hepatocytes. While viral proteins have been studied in great detail, our knowledge about how host cell factors are used by HCV for efficient replication and spread is still scarce. In the present study we conducted a comprehensive RNA-interference-based screen and identified 40 genes that promote the HCV lifecycle and 16 genes that suppress it. Follow-up studies revealed that one of these genes, the heterogeneous nuclear ribonucleoprotein K (HNRNPK), selectively suppresses production of infectious HCV particles. We mapped the domains of HNRNPK required for this suppression and demonstrate that this protein selectively binds to the HCV RNA genome. Based on the correlation between suppression of virus production, HCV RNA binding and recruitment to lipid droplets, we propose that HNRNPK might limit the amount of viral RNA genomes available for incorporation into virus particles. This study provides novel insights into the complexity of reactions that are involved in the formation of HCV virions.
PMCID: PMC4287573  PMID: 25569684
17.  Changes in Bone Density after Cancer Treatment in Patients with Cervical and Endometrial Cancer 
Journal of Cancer  2015;6(1):82-89.
OBJECTIVE: This study aimed to evaluate the impact of cancer treatment on bone mineral density (BMD) in the lumbar spine (LS) and femur in the postmenopausal women with cervical or endometrial cancer without bone metastasis compared to normal control postmenopausal women.
METHODS: We retrospectively evaluated the BMD data in the LS, femur neck (FN) and trochanter (FT) by dual-energy X-ray absorptiometry and laboratory data of bone turnover markers at baseline and after one year in 130 patients with cervical cancer, 68 patients with endometrial cancer, and 225 healthy controls.
RESULTS: There were no significant differences in the T-scores of basal BMD in LS and femur between patients with endometrial cancer and controls, and only T-score of basal BMD at the fourth lumbar vertebra (L4) was significantly lower in patients with cervical cancer compared to controls. One year later, T-scores of BMD at all LS sites and FN in patients with cervical cancer and T-scores of BMD at L3, L4, FN, and FT in those with endometrial cancer after cancer treatment were significantly lower compared to controls. Lower proportions of normal BMD at all skeletal sites except L2 in patients with endometrial cancer and those at L1, L4, and FN in patients with cervical cancer were observed compared to controls after cancer treatment.
CONCLUSIONS: Our results suggest that cancer treatment increase bone loss in postmenopausal women with cervical and endometrial cancer.
PMCID: PMC4278918  PMID: 25553092
Bone mineral density; Cervical cancer; Endometrial cancer; Osteoporosis.
18.  Spectral domain optical coherence tomography cross-sectional image of optic nerve head during intraocular pressure elevation 
To analyze changes of the optic nerve head (ONH) and peripapillary region during intraocular pressure (IOP) elevation in patients using spectral domain optical coherence tomography (SD-OCT).
Both an optic disc 200×200 cube scan and a high-definition 5-line raster scan were obtained from open angle glaucoma patients presented with monocular elevation of IOP (≥30 mm Hg) using SD-OCT. Additional baseline characteristics included age, gender, diagnosis, best-corrected visual acuity, refractive error, findings of slit lamp biomicroscopy, findings of dilated stereoscopic examination of the ONH and fundus, IOP, pachymetry findings, and the results of visual field.
The 24 patients were selected and divided into two groups: group 1 patients had no history of IOP elevation or glaucoma (n=14), and group 2 patients did have history of IOP elevation or glaucoma (n=10). In each patient, the study eye with elevated IOP was classified into group H (high), and the fellow eye was classified into group L (low). The mean deviation (MD) differed significantly between groups H and L when all eyes were considered (P=0.047) and in group 2 (P=0.042), not in group 1 (P=0.893). Retinal nerve fiber layer (RNFL) average thickness (P=0.050), rim area (P=0.015), vertical cup/disc ratio (P=0.011), cup volume (P=0.028), inferior quadrant RNFL thickness (P=0.017), and clock-hour (1, 5, and 6) RNFL thicknesses (P=0.050, 0.012, and 0.018, respectively), cup depth (P=0.008), central prelaminar layer thickness (P=0.023), mid-inferior prelaminar layer thickness (P=0.023), and nasal retinal slope (P=0.034) were significantly different between the eyes with groups H and L.
RNFL average thickness, rim area, vertical cup/disc ratio, cup volume, inferior quadrant RNFL thickness, and clock-hour (1, 5, and 6) RNFL thicknesses significantly changed during acute IOP elevation.
PMCID: PMC4270970  PMID: 25540759
spectral domain optical coherence tomography; optic nerve head; elevated intraocular pressure; open angle glaucoma; retinal nerve fiver layer
19.  Protective Effect of Metformin on Gentamicin-Induced Vestibulotoxicity in Rat Primary Cell Culture 
One of the antidiabetic drugs, metformin, have shown that it prevented oxidative stress-induced death in several cell types through a mechanism involving the opening of the permeability transition pore and cytochrome c release. Thus, it is possible that the antioxidative effect of metformin can also serve as protection against gentamicin-induced cytotoxicity related to reactive oxygen species (ROS). The aim of this study was to examine the protective effect of metformin on gentamicin-induced vestibulotoxicity in primary cell culture derived from rat utricle.
For vestibular primary cell culture, rat utricles were dissected and incubated. Gentamicin-induced cytotoxicity was measured in both the auditory and vestibular cells. To examine the effects of metformin on gentamicin-induced cytotoxicity in the primary cell culture, the cells were pretreated with metformin at a concentration of 1 mM for 24 hours, and then exposed to 2.5 mM gentamicin for 48 hours. The intracellular ROS level was measured using a fluorescent dye, and also measured using a FACScan flow cytometer. Intracellular calcium levels in the vestibular cells were measured with calcium imaging using Fura-2 AM.
Vestibular cells were more sensitive to gentamicin-induced cytotoxicity than auditory hair cells. Metformin protects against gentamicin-induced cytotoxicity in vestibular cells. Metformin significantly reduced a gentamicin-induced increase in ROS, and also reduced an increase in intracellular calcium concentrations in gentamicin-induced cytotoxicity.
Metformin significantly reduced a gentamicin-induced increase in ROS, stabilized the intracellular calcium concentration, and inhibited gentamicin-induced apoptosis. Thus, Metformin showed protective effect on gentamicin-induced cytotoxicity in vestibular primary cell culture.
PMCID: PMC4240486  PMID: 25436048
Labyrinth vestibule; Gentamicins; Metformin; Reactive oxygen species; Calcium
20.  Effects of different target sites on antisense RNA-mediated regulation of gene expression 
BMB Reports  2014;47(11):619-624.
Antisense RNA is a type of noncoding RNA (ncRNA) that binds to complementary mRNA sequences and induces gene repression by inhibiting translation or degrading mRNA. Recently, several small ncRNAs (sRNAs) have been identified in Escherichia coli that act as antisense RNA mainly via base pairing with mRNA. The base pairing predominantly leads to gene repression, and in some cases, gene activation. In the current study, we examined how the location of target sites affects sRNA-mediated gene regulation. An efficient antisense RNA expression system was developed, and the effects of antisense RNAs on various target sites in a model mRNA were examined. The target sites of antisense RNAs suppressing gene expression were identified, not only in the translation initiation region (TIR) of mRNA, but also at the junction between the coding region and 3' untranslated region. Surprisingly, an antisense RNA recognizing the upstream region of TIR enhanced gene expression through increasing mRNA stability. [BMB Reports 2014; 47(11): 619-624]
PMCID: PMC4281340  PMID: 24411463
Artificial RNA; Antisense RNA; Double stem-loop; Enhancer; Up-regulation
21.  Regulation of Transcription from Two ssrS Promoters in 6S RNA Biogenesis 
Molecules and Cells  2013;36(3):227-234.
ssrS-encoded 6S RNA is an abundant noncoding RNA that binds σ70-RNA polymerase and regulates expression at a subset of promoters in Escherichia coli. It is transcribed from two tandem promoters, ssrS P1 and ssrS P2. Regulation of transcription from two ssrS promoters in 6S RNA biogenesis was examined. Both P1 and P2 were growth phase-dependently regulated. Depletion of 6S RNA had no effect on growth-phase-dependent transcription from either promoter, whereas overexpression of 6S RNA increased P1 transcription and decreased P2 transcription, suggesting that transcription from P1 and P2 is subject to feedback activation and feedback inhibition, respectively. This feedback regulation disappeared in Δfis strains, supporting involvement of Fis in this process. The differential feedback regulation may provide a means for maintaining appropriate cellular concentrations of 6S RNA.
PMCID: PMC3887979  PMID: 23864284
6S RNA; feedback regulation; Fis; promoter; sigma factor
22.  Usefulness of the Simplified Cough Test in Evaluating Cough Reflex Sensitivity as a Screening Test for Silent Aspiration 
Annals of Rehabilitation Medicine  2014;38(4):476-484.
To assess cough reflex sensitivity using the simplified cough test (SCT) and to evaluate the usefulness of SCT to screen for silent aspiration.
The healthy control group was divided into two subgroups: the young (n=29, 33.44±9.99 years) and the elderly (n=30, 63.66±4.37 years). The dysphagic elderly group (n=101, 72.95±9.19 years) consisted of patients with dysphagia, who suffered from a disease involving central nervous system (ischemic stroke 47, intracerebral hemorrhage 27, traumatic brain injury 11, encephalitis 5, hypoxic brain damage 3, and Parkinson disease 8). The SCT was performed using the mist of a 1% citric acid from a portable nebulizer. The time from the start of the inhalation to the first cough was measured as the cough latency. All the dysphagic patients underwent the videofluoroscopic swallowing study.
The cough latency was more significantly prolonged in the healthy elderly group than in the healthy young group (p<0.001), and in the dysphagic elderly group than in the healthy elderly group (p<0.001). The sensitivity and specificity of SCT were 73.8% and 72.5% for detecting aspiration in the dysphagic patients, and 87.1% and 66.7% for detecting silent aspiration in the aspirated patients.
Cough latency measured with the SCT reflects the impairment of cough reflex in healthy elderly and dysphasic subjects. The results of this study show that the SCT test can be a valuable method of screening aspiration with or without cough in dysphasic patients.
PMCID: PMC4163587  PMID: 25229026
Deglutition disorders; Cough; Respiratory aspiration of gastric contents; Diagnosis; Citric acid
23.  The Associations between Immunity-Related Genes and Breast Cancer Prognosis in Korean Women 
PLoS ONE  2014;9(7):e103593.
We investigated the role of common genetic variation in immune-related genes on breast cancer disease-free survival (DFS) in Korean women. 107 breast cancer patients of the Seoul Breast Cancer Study (SEBCS) were selected for this study. A total of 2,432 tag single nucleotide polymorphisms (SNPs) in 283 immune-related genes were genotyped with the GoldenGate Oligonucleotide pool assay (OPA). A multivariate Cox-proportional hazard model and polygenic risk score model were used to estimate the effects of SNPs on breast cancer prognosis. Harrell’s C index was calculated to estimate the predictive accuracy of polygenic risk score model. Subsequently, an extended gene set enrichment analysis (GSEA-SNP) was conducted to approximate the biological pathway. In addition, to confirm our results with current evidence, previous studies were systematically reviewed. Sixty-two SNPs were statistically significant at p-value less than 0.05. The most significant SNPs were rs1952438 in SOCS4 gene (hazard ratio (HR) = 11.99, 95% CI = 3.62–39.72, P = 4.84E-05), rs2289278 in TSLP gene (HR = 4.25, 95% CI = 2.10–8.62, P = 5.99E-05) and rs2074724 in HGF gene (HR = 4.63, 95% CI = 2.18–9.87, P = 7.04E-05). In the polygenic risk score model, the HR of women in the 3rd tertile was 6.78 (95% CI = 1.48–31.06) compared to patients in the 1st tertile of polygenic risk score. Harrell’s C index was 0.813 with total patients and 0.924 in 4-fold cross validation. In the pathway analysis, 18 pathways were significantly associated with breast cancer prognosis (P<0.1). The IL-6R, IL-8, IL-10RB, IL-12A, and IL-12B was associated with the prognosis of cancer in data of both our study and a previous study. Therefore, our results suggest that genetic polymorphisms in immune-related genes have relevance to breast cancer prognosis among Korean women.
PMCID: PMC4116221  PMID: 25075970
24.  Prevalence of renal dysfunction in patients with cirrhosis according to ADQI-IAC working party proposal 
Clinical and Molecular Hepatology  2014;20(2):185-191.
A revised classification system for renal dysfunction in patients with cirrhosis was proposed by the Acute Dialysis Quality Initiative and the International Ascites Club Working Group in 2011. The aim of this study was to determine the prevalence of renal dysfunction according to the criteria in this proposal.
The medical records of cirrhotic patients who were admitted to Konkuk University Hospital between 2006 and 2010 were reviewed retrospectively. The data obtained at first admission were collected. Acute kidney injury (AKI) and chronic kidney disease (CKD) were defined using the proposed diagnostic criteria of kidney dysfunction in cirrhosis.
Six hundred and forty-three patients were admitted, of whom 190 (29.5%), 273 (42.5%), and 180 (28.0%) were Child-Pugh class A, B, and C, respectively. Eighty-three patients (12.9%) were diagnosed with AKI, the most common cause for which was dehydration (30 patients). Three patients had hepatorenal syndrome type 1 and 26 patients had prerenal-type AKI caused by volume deficiency after variceal bleeding. In addition, 22 patients (3.4%) were diagnosed with CKD, 1 patient with hepatorenal syndrome type 2, and 3 patients (0.5%) with AKI on CKD.
Both AKI and CKD are common among hospitalized cirrhotic patients, and often occur simultaneously (16.8%). The most common type of renal dysfunction was AKI (12.9%). Diagnosis of type 2 hepatorenal syndrome remains difficult. A prospective cohort study is warranted to evaluate the clinical course in cirrhotic patients with renal dysfunction.
PMCID: PMC4099334  PMID: 25032185
Hepatorenal syndrome; Cirrhosis; Acute kidney injury; Chronic kidney disease

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