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1.  Can Mitochondrial Dysfunction Be a Predictive Factor for Oxidative Stress in Patients with Obstructive Sleep Apnea? 
Antioxidants & Redox Signaling  2014;21(9):1285-1288.
Mitochondrial dysfunction reflects a lifelong cumulative burden of cellular damage, and a decrease in mitochondrial DNA (mtDNA) copy number is associated with oxidative stress and chronic inflammation. The goal of this study was to assess whether mitochondrial dysfunction and a decrease in mtDNA copy number are common features of patients with obstructive sleep apnea syndrome (OSA). We compared mtDNA copy number between 20 healthy volunteers and 20 patients with OSA and investigated whether a significant attenuation of mtDNA copy number was observed in genomic DNA isolated from whole blood of OSA patients. Our observations lead to the hypothesis that mtDNA copy number is lower in whole blood DNA of OSA subjects and might be related to OSA severity, reflecting excessive oxidative stress in patients with OSA. Antioxid. Redox Signal. 21, 1285–1288.
PMCID: PMC4158965  PMID: 24926527
2.  Clinical Effect of Surgical Correction for Nasal Pathology on the Treatment of Obstructive Sleep Apnea Syndrome 
PLoS ONE  2014;9(6):e98765.
This study aimed to evaluate the hypothesis that relief of nasal obstruction in subjects with obstructive sleep apnea (OSA) would lead to reduce OSA severity and to discuss the available evidence on the clinical efficacy of nasal surgery as a treatment modality for OSA.
Study Design
Twenty-five subjects who had reduced patency of nasal cavity and narrowing of retroglossal or retropalatal airways were diagnosed with OSA and underwent nasal surgery, such as septoplasty or turbinoplasty to correct nasal pathologies. The effect of the surgery on nasal patency was quantified by measuring minimal cross-sectional area (MCA) using acoustic rhinometry. The watch-PAT-derived respiratory disturbance index (RDI), apnea and hypopnea index (AHI), lowest oxygen saturation, and valid sleep time were measured before and after nasal surgery.
The present study shows that the AHI and RDI decreased significantly and the lowest oxygen saturation and valid sleep time rose after nasal surgery in 25 OSA subjects. In addition, a reduction in subjective symptoms was observed in subjects and mean MCA increased after nasal surgery. Fourteen subjects were classified as responders and 11 subjects as non-responders. Responders showed considerable improvement of their subjective symptoms and the AHI and RDI were significantly lower after surgery. We found that the changes between pre- and post-operative AHI and RDI values were minimal in 11 non-responders. However, daytime somnolence and REM sleep time improved after nasal surgery in non-responders.
Our study provides evidence that the surgical treatment of nasal pathology improves nasal airway patency and reduces OSA severity in 56% subjects. Furthermore, correction of nasal pathology appears to result in improved sleep quality in both responder and non-responders OSA subjects.
PMCID: PMC4045850  PMID: 24896824
3.  Effects of Nicotine on the Neurophysiological and Behavioral Effects of Ketamine in Humans 
Background: N-methyl-d-aspartate (NMDA) receptor hypofunction has been implicated in the pathophysiology of schizophrenia and its associated neurocognitive impairments. The high rate of cigarette smoking in schizophrenia raises questions about how nicotine modulates putative NMDA receptor hypofunction in the illness. Accordingly, we examined the modulatory effects of brain nicotinic acetylcholine receptor (nAChR) stimulation on NMDA receptor hypofunction by examining the interactive effects of nicotine, a nAChR agonist, and ketamine, a non-competitive NMDA receptor antagonist, on behavioral and neurophysiological measures in healthy human volunteers.
Methods: From an initial sample of 17 subjects (age range 18–55 years), 8 subjects successfully completed 4 test sessions, each separated by at least 3 days, during which they received ketamine or placebo and two injections of nicotine or placebo in a double-blind, counterbalanced manner. Schizophrenia-like effects Positive and Negative Syndrome Scale, perceptual alterations Clinician Administered Dissociative Symptoms Scale, subjective effects Visual Analog Scale and auditory event-related brain potentials (mismatch negativity, MMN; P300) were assessed during each test session.
Results: Consistent with existing studies, ketamine induced transient schizophrenia-like behavioral effects. P300 was reduced and delayed by ketamine regardless of whether it was elicited by a target (P3b) or novel (P3a) stimulus, while nicotine only reduced the amplitude of P3a. Nicotine did not rescue P300 from the effects of ketamine; the interactions of ketamine and nicotine were not significant. While nicotine significantly reduced MMN amplitude, ketamine did not.
Conclusion: Nicotine failed to modulate ketamine-induced neurophysiological and behavioral effects in this preliminary study. Interestingly, ketamine reduced P3b amplitude and nicotine reduced P3a amplitude, suggesting independent roles of NMDA receptor and nAChR in the generation of P3b and P3a, respectively.
PMCID: PMC3900858  PMID: 24478731
schizophrenia; nicotine; ketamine; N-methyl-d-aspartate receptor; nicotinic acetylcholine receptor; event-related potential; mismatch negativity; P300
4.  Verbal and Visual Memory Impairments in Bipolar I and II Disorder 
Psychiatry Investigation  2012;9(4):339-346.
To compare verbal and visual memory performances between patients with bipolar I disorder (BD I) and patients with bipolar II disorder (BD II) and to determine whether memory deficits were mediated by impaired organizational strategies.
Performances on the Korean-California Verbal Learning Test (K-CVLT) and the Rey-Osterrieth Complex Figure Test (ROCF) in 37 patients with BD I, 46 patients with BD II and 42 healthy subjects were compared. Mediating effects of impaired organization strategies on poor delayed recall was tested by comparing direct and mediated models using multiple regression analysis.
Both patients groups recalled fewer words and figure components and showed lower Semantic Clustering compared to controls. Verbal memory impairment was partly mediated by difficulties in Semantic Clustering in both subtypes, whereas the mediating effect of Organization deficit on the visual memory impairment was present only in BD I. In all mediated models, group differences in delayed recall remained significant.
Our findings suggest that memory impairment may be one of the fundamental cognitive deficits in bipolar disorders and that executive dysfunctions can exert an additional influence on memory impairments.
PMCID: PMC3521109  PMID: 23251197
Bipolar I disorder; Bipolar II disorder; Memory; Organization; Executive function; Path analysis
5.  Association of the Brain-derived Neurotrophic Factor Gene and Clinical Features of Bipolar Disorder in Korea 
Brain-derived neurotrophic factor (BDNF) plays an important role in cell survival, differentiation, and cell death as well as in neural plasticity. Recent studies have suggested that BDNF is involved in the pathogenesis of bipolar disorder. The aim of this study was to investigate the association of the genetic variations of the BDNF gene with bipolar disorder in Korea. We also studied the possible association of these genetic variants with clinical features.
The allelic and genotypic distributions of Val66Met polymorphism of the BDNF gene were analyzed using a polymerase chain reaction-based method in 184 bipolar patients and 214 controls. Analysis was performed to investigate an association of the Val66Met polymorphism of the BDNF gene and the clinical features in bipolar patients.
No significant difference was found between bipolar patients and controls in the genotype and allele frequencies for the investigated BDNF polymorphism. However, the age of onset of bipolar disorder among the Val/Val (25.57), Val/Met (30.42) and Met/Met (32.45) genotype groups were significantly different (p=0.037).
This study suggests that Val66Met polymorphisms are unlikely to contribution to the genetic predisposition to bipolar disorder as a whole. But Val66Met polymorphism may be associated with age of onset of the disorder, further studies designed to investigate the relationship in a larger population may be warranted.
PMCID: PMC3569161  PMID: 23430274
Bipolar disorder; Brain-derived neurotrophic factor; Polymorphism; Age of onset
6.  A Case of Bilateral Postauricular Sinuses 
Korean Journal of Audiology  2012;16(2):99-101.
Preauricular sinuses are common congenital malformations that usually occur at the anterior margin of the ascending limb of the helix. There are rare cases in which the location of the preauricular sinus is posterior to the tragus, and the direction of the sinus tract is toward the posterior. This variant type of preauricular sinus is called, 'postauricular sinus'. Postauricular sinus is uncommon. Thus, diagnosis and treatment may be delayed due to its location of its opening and atypical clinical symptoms. Typical treatment is a single stage operation through bidirectional skin incision. However, we found out that according to the length and invasion depth of the sinus tract, there was an option between unidirectional and bidirectional skin incisions that we may choose from.
PMCID: PMC3936561  PMID: 24653881
Preauricular sinus; Variant; Excision
7.  Initial Depressive Episodes Affect the Risk of Suicide Attempts in Korean Patients with Bipolar Disorder 
Yonsei Medical Journal  2010;51(5):641-647.
Suicide is a major concern for increasing mortality in bipolar patients, but risk factors for suicide in bipolar disorder remain complex, including Korean patients. Medical records of bipolar patients were retrospectively reviewed to detect significant clinical characteristics associated with suicide attempts.
Materials and Methods
A total of 579 medical records were retrospectively reviewed. Bipolar patients were divided into two groups with the presence of a history of suicide attempts. We compared demographic characteristics and clinical features between the two groups using an analysis of covariance and chi-square tests. Finally, logistic regression was performed to evaluate significant risk factors associated with suicide attempts in bipolar disorder.
The prevalence of suicide attempt was 13.1% in our patient group. The presence of a depressive first episode was significantly different between attempters and nonattempters. Logistic regression analysis revealed that depressive first episodes and bipolar II disorder were significantly associated with suicide attempts in those patients.
Clinicians should consider the polarity of the first mood episode when evaluating suicide risk in bipolar patients. This study has some limitations as a retrospective study and further studies with a prospective design are needed to replicate and evaluate risk factors for suicide in patients with bipolar disorder.
PMCID: PMC2908881  PMID: 20635436
Suicide attempt; bipolar disorder; depressive episode
8.  Bystander-Mediated Regression of Murine Neuroblastoma via Retroviral Transfer of the HSV-TK Gene 
Journal of Korean Medical Science  2004;19(1):107-112.
Selective introduction of genes conferring chemosensitivity into proliferating tumor cells may be used to treat cancer. We investigated the bystander effect of retrovirusmediated gene transfer of herpes simplex virus thymidine kinase (HSV-TK) gene to murine neuroblastoma cell line (neuro-2a) in vitro and in vivo, and we examined whether the mechanism of bystander effect in neuroblastoma would also depend on connexin-dependent gap junction and/or immune response. A strong bystander effect was observed in vitro, whereby nontransduced tumor cells in proximity to transduced cells acquired susceptibility to ganciclovir (GCV) killing. Implanted mixtures of wildtype cells and HSV-TK transduced cells showed a potent bystander effect upon administration of GCV in A/J mice. HSV-TK/GCV system in murine neuroblastoma induced systemic immunity. Immunohistochemical staining showed many CD4+ and CD8+ cell infiltration but did not show anti-connexin 43+ cells. In conclusion, a strong bystander effect was observed in vitro and in vivo. The bystander effect in murine neuroblastoma might be dependent on immune response and/or on other mechanism such as protein phosphorylation or transfer of apoptotic vesicle, rather than connexin-dependent gap junction.
PMCID: PMC2822245  PMID: 14966351
Bystander Effect; Neuroblastoma; Gene Therapy
9.  Autologous stem cell transplantation for the treatment of neuroblastoma in Korea. 
Journal of Korean Medical Science  2003;18(2):242-247.
Autologous stem cell transplantation (ASCT) for the treatment of high-risk neuroblastoma (NBL) is an accepted method for restoring bone marrow depression after high dose chemotherapy. We retrospectively analyzed eighty eight cases of NBL that underwent ASCT following marrow ablative therapy at 12 transplant centers of the Korean Society of Pediatric Hematology-Oncology between January 1996 and September 2000. Seventy nine children were of stage IV NBL and 9 were of stage III with N-myc amplification. Various cytoreductive regimens were used. However, the main regimen was 'CEM' consisting of carboplatin, etoposide and melphalan, and this was used in 66 patients. Total body irradiation was also added in 36 patients for myeloablation. To reduce tumor cell contamination, stem cell infusions after CD34+ cell selection were performed in 16 patients. Post-transplantation therapies included the second transplantation in 18 patients, interleukin2 therapy in 45, 13-cis retinoic acid in 40, 131-meta-iodobenzylguanidine in 4, conventional chemotherapy in 11, and local radiotherapy in 8. Twenty two patients died, sixty six patients are surviving 1 to 46 months after ASCT (median followup duration, 14.5 months). Although the follow-up period was short and the number of patients small, we believe that ASCT might improve the survival rate in high-risk NBL.
PMCID: PMC3055035  PMID: 12692423

Results 1-9 (9)