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1.  Integrating Traditional Medicine into Modern Inflammatory Diseases Care: Multitargeting by Rhus verniciflua Stokes 
Mediators of Inflammation  2014;2014:154561.
Despite the fact that numerous researches were performed on prevention and treatment of inflammation related diseases, the overall incidence has not changed remarkably. This requires new approaches to overcome inflammation mediated diseases, and thus traditional medicine could be an efficacious source for prevention and treatment of these diseases. In this review, we discuss the contribution of traditional medicine, especially Rhus verniciflua Stokes, to modern medicine against diverse inflammation mediated diseases. Traditionally, this remedy has been used in Eastern Asia for the treatment of gastric problems, hepatic disorders, infectious diseases, and blood disorders. Modern science has provided the scientific basis for the use of Rhus verniciflua Stokes against such disorders and diseases. Various chemical constituents have been identified from this plant, including phenolic acid, and flavonoids. Cell-based studies have exhibited the potential of this as antibacterial, antioxidant, neuroprotective, anti-inflammatory, growth inhibitory, and anticancer activities. Enormous animal studies have shown the potential of this against proinflammatory diseases, neurodegenerative diseases, diabetes, liver diseases, and chemical insults. At the molecular level, this medicinal plant has been shown to modulate diverse cell-signaling pathways. In clinical studies, Rhus verniciflua Stokes has shown efficacy against various cancer patients such as colorectal, gastric, hepatic, renal, pancreatic, and pulmonary cancers. Thus, this remedy is now exhibiting activities in the clinic.
PMCID: PMC4082934  PMID: 25024508
2.  Magnifying endoscopy for the diagnosis of specialized intestinal metaplasia in short-segment Barrett’s esophagus 
AIM: To determine whether magnified observation of short-segment Barrett’s esophagus (BE) is useful for the detection of specialized intestinal metaplasia (SIM).
METHODS: Thirty patients with suspected short-segment BE underwent magnifying endoscopy up to × 80. The magnified images were analyzed with respect to their pit-patterns, which were simultaneously classified into five epithelial types [I (small round), II (straight), III (long oval), IV (tubular), V (villous)] by Endo’s classification. Then, a 0.5% solution of methylene blue (MB) was sprayed over columnar mucosa. The patterns of the magnified image and MB staining were analyzed. Biopsies were obtained from the regions previously observed by magnifying endoscopy and MB chromoendoscopy.
RESULTS: Three of five patients with a type V (villous) epithelial pattern had SIM, whereas 21 patients with a non-type V epithelial patterns did not have SIM. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of pit-patterns in detecting SIM were 100%, 91.3%, 92.3%, 60% and 100%, respectively (P = 0.004). Three of the 12 patients with positive MB staining had SIM, whereas 14 patients with negative MB staining did not have SIM. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of MB staining in detecting SIM were 100%, 60.9%, 65.4%, 25% and 100%, respectively (P = 0.085). The specificity and accuracy of pit-pattern evaluation were significantly superior compared with MB staining for detecting SIM by comparison with the exact McNemar’s test (P = 0.0391).
CONCLUSION: The magnified observation of a short-segment BE according to the mucosal pattern and its classification can be predictive of SIM.
PMCID: PMC3819544  PMID: 24222952
Short-segment; Barrett’s esophagus; Magnifying endoscopy; Methylene blue chromoendoscopy; Specialized intestinal metaplasia; Dysplasia; Esophageal adenocarcinoma; Diagnosis
3.  Comparison of Clinico-Radiological Features between Congenital Cystic Neuroblastoma and Neonatal Adrenal Hemorrhagic Pseudocyst 
Korean Journal of Radiology  2011;12(1):52-58.
To evaluate the radiological and clinical findings of congenital cystic neuroblastomas as compared with those of the cystic presentation of neonatal adrenal hemorrhage.
Materials and Methods
We analyzed the US (n = 52), CT (n = 24), and MR (n = 4) images as well as the medical records of 28 patients harboring congenital cystic neuroblastomas (n = 16) and neonatal adrenal hemorrhagic pseudocysts (n = 14). The history of prenatal detection, location, size, presence of outer wall enhancement, internal septations, solid portion, calcification, turbidity, vascular flow on a Doppler examination, and evolution patterns were compared in two groups of cystic lesions, by Fischer's exact test.
All (100%) neuroblastomas and three (21%) of the 14 hemorrhagic pseudocysts were detected prenatally. Both groups of cystic lesions occurred more frequently on the right side; 11 of 16 (69%) for neuroblastomas and 11 of 14 (79%) for hemorrhagic pseudocysts. The size, presence of solid portion, septum, enhancement, and turbidity did not differ significantly (p > 0.05) between the two groups of cystic lesions. However, tiny calcifications (n = 3) and vascular flow on color Doppler US (n = 3) were noted in only neuroblastomas. The cystic neuroblastomas became complex solid and cystic masses, and did not disappear for up to 90 days in the three following cases, whereas 11 of the 14 (79%) hemorrhagic pseudocysts disappeared completely and the three remaining (27%) evolved to calcifications only.
Although the imaging findings of two groups of cystic lesions were similar, prenatal detection, the presence of calcification on initial images, vascularity on color Doppler US, and evolution to a more complex mass may all favor neuroblastomas.
PMCID: PMC3017884  PMID: 21228940
Neonate; Adrenal hemorrhage; Neuroblastoma
4.  Pulmonary Venous Malformation in a 4-Year-Old Boy: a Case Report 
Korean Journal of Radiology  2009;10(4):420-423.
We report a case of a pulmonary venous malformation in a 4-year-old boy who presented with recurrent pneumonia. A radiograph revealed a right infrahilar mass and a hyperlucent right lung. Computed tomography (CT) demonstrated a mass containing intensely enhancing areas and multiple phleboliths located in the right lower lobe and encasing the right bronchus and right inferior pulmonary vein. Magnetic resonance imaging (MRI) precisely revealed the mass demarcation. A right lower lobectomy was performed and a pathological examination confirmed the diagnosis of a venous malformation. To the best of our knowledge, a venous malformation in pulmonary tissue has not been reported in the English literature. Herein, we report a case of a pulmonary venous malformation, with the radiograph, CT, MRI, and blood pool scan findings, along with its pathologic correlation.
PMCID: PMC2702055  PMID: 19568474
Congenital vascular malformation; Venous malformation; Lung, CT; Magnetic resonance (MR)
5.  Congenital Cerebellar Mixed Germ Cell Tumor Presenting with Hemorrhage in a Newborn 
Korean Journal of Radiology  2008;9(Suppl):S26-S29.
We report here on a neonate with congenital cerebellar mixed germ cell tumor, and this initially presented as cerebellar hemorrhage. Postnatal cranial ultrasonography revealed an echogenic cerebellar mass that exhibited the signal characteristics of hemorrhage rather than tumor on MR images. The short-term follow-up images also suggested a resolving cerebellar hemorrhage. One month later, the neonate developed vomiting. A second set of MR images demonstrated an enlarged mass that exhibited changed signal intensity at the same site, which suggested a neoplasm. Histological examination after the surgical resection revealed a mixed germ cell tumor.
PMCID: PMC2627202  PMID: 18607121
Congenital cerebellar tumor; Mixed germ cell tumor; Posterior fossa tumor; Neonatal cerebellar hemorrhage
6.  US Features of Transient Small Bowel Intussusception in Pediatric Patients 
Korean Journal of Radiology  2004;5(3):178-184.
To describe the sonographic (US) and clinical features of spontaneously reduced small bowel intussusception, and to discuss the management options for small bowel intussusception based on US findings with clinical correlation.
Materials and Methods
During a five years of period, 34 small bowel intussusceptions were diagnosed on US in 32 infants and children. The clinical presentations and imaging findings of the patients were reviewed.
The clinical presentations included abdominal pain or irritability (n = 25), vomiting (n = 5), diarrhea (n = 3), bloody stool (n = 1), and abdominal distension (n = 1), in combination or alone. US showed multi-layered round masses of small (mean, 1.5±0.3 cm) diameters and with thin (mean, 3.5±1 mm) outer rims along the course of the small bowel. The mean length was 1.8±0.5 cm and peristalsis was seen on the video records. There were no visible lead points. The vascular flow signal appeared on color Doppler images in all 21 patients examined. Spontaneous reduction was confirmed by combinations of US (n = 28), small bowel series (n = 6), CT scan (n = 3), and surgical exploration (n = 2). All patients discharged with improved condition.
Typical US findings of the transient small bowel intussusception included 1) small size without wall swelling, 2) short segment, 3) preserved wall motion, and 4) absence of the lead point. Conservative management with US monitoring rather than an immediate operation is recommended for those patient with typical transient small bowel intussusceptions. Atypical US findings or clinical deterioration of the patient with persistent intussusception warrant surgical exploration.
PMCID: PMC2698160  PMID: 15467415
Children, gastrointestinal tract; Intussusception; Intestine, US
7.  Acute Necrotizing Encephalopathy in Korean Infants and Children: Imaging Findings and Diverse Clinical Outcome 
Korean Journal of Radiology  2004;5(3):171-177.
The purpose of our study was to describe acute necrotizing encephalopathy in Korean infants and children, and we sought to evaluate the prognostic factors.
Materials and Methods
Acute necrotizing encephalopathy was diagnosed in 14 Korean infants and children. We retrospectively analyzed the neuroimaging findings including the follow-up changes. The clinical course of the disease was graded, and we evaluated prognostic factors including age, serum level of the aminotransferase, hemorrhage, and localized atrophy of the brain.
This encephalopathy predominantly affected the bilateral thalami (n=14), pons (n=12), and midbrain (n=10) in a symmetrical pattern. Hemorrhage was observed in eight patients (57%). On the follow-up images (n=12), the brain lesions were reduced in extent for all patients, and generalized atrophy was seen in six patients. Localized tissue loss was observed in five patients and a complete resolution occurred for one patient. All the patients survived and two recovered completely; mild (n=6) to severe (n=6) neurological deficits persisted in the remaining 12 patients. The significant prognostic factors identified in this study were the presence of hemorrhage (p = 0.009) and localized atrophy (p = 0.015).
Acute necrotizing encephalopathy in Korean patients showed the characteristic patterns of the post-infectious encephalopathy as described in the literature. The high survival rate and the relatively favorable clinical course observed for the present study suggest a more diverse spectrum of disease severity than was previously described. The presence of hemorrhage and localized tissue loss on MR images may suggest a poor prognosis.
PMCID: PMC2698159  PMID: 15467414
Brain, encephalopathy; Infants and children, disease; Brain, MR
8.  Role of Neuronal NADPH Oxidase 1 in the Peri-Infarct Regions after Stroke 
PLoS ONE  2015;10(1):e0116814.
The molecular mechanism underlying the selective vulnerability of neurons to oxidative damage caused by ischemia—reperfusion (I/R) injury remains unknown. We sought to determine the role of NADPH oxidase 1 (Nox1) in cerebral I/R-induced brain injury and survival of newborn cells in the ischemic injured region. Male Wistar rats were subjected to 90 min middle cerebral artery occlusion (MCAO) followed by reperfusion. After reperfusion, infarction size, level of superoxide and 8-hydroxy-2′-deoxyguanosine (8-oxo-2dG), and Nox1 immunoreactivity were determined. RNAi-mediated knockdown of Nox1 was used to investigate the role of Nox1 in I/R-induced oxidative damage, neuronal death, motor function recovery, and ischemic neurogenesis. After I/R, Nox1 expression and 8-oxo-2dG immunoreactivity was increased in cortical neurons of the peri-infarct regions. Both infarction size and neuronal death in I/R injury were significantly reduced by adeno-associated virus (AAV)-mediated transduction of Nox1 short hairpin RNA (shRNA). AAV-mediated Nox1 knockdown enhanced functional recovery after MCAO. The level of survival and differentiation of newborn cells in the peri-infarct regions were increased by Nox1 inhibition. Our data suggest that Nox-1 may be responsible for oxidative damage to DNA, subsequent cortical neuronal degeneration, functional recovery, and regulation of ischemic neurogenesis in the peri-infarct regions after stroke.
PMCID: PMC4305324  PMID: 25617620
9.  Matrix Metalloproteinase-3 Causes Dopaminergic Neuronal Death through Nox1-Regenerated Oxidative Stress 
PLoS ONE  2014;9(12):e115954.
In the present study we investigated the interplay between matrix metalloproteinase 3 (MMP3) and NADPH oxidase 1 (Nox1) in the process of dopamine (DA) neuronal death. We found that MMP3 activation causes the induction of Nox1 via mitochondrial reactive oxygen species (ROS) production and subsequently Rac1 activation, eventually leading to Nox1-derived superoxide generation in a rat DA neuronal N27 cells exposed to 6-OHDA. While a MMP3 inhibitor, NNGH, largely attenuated mitochondrial ROS and subsequent Nox1 induction, both apocynin, a putative Nox inhibitor and GKT137831, a Nox1 selective inhibitor failed to reduce 6-OHDA-induced mitochondrial ROS. However, both inhibitors for MMP3 and Nox1 similarly attenuated 6-OHDA-induced N27 cell death. RNAi-mediated selective inhibition of MMP3 or Nox1 showed that knockdown of either MMP3 or Nox1 significantly reduced 6-OHDA-induced ROS generation in N27 cells. While 6-OHDA-induced Nox1 was abolished by MMP3 knockdown, Nox1 knockdown did not alter MMP3 expression. Direct overexpression of autoactivated MMP3 (actMMP3) in N27 cells or in rat substantia nigra (SN) increased expression of Nox1. Selective knockdown of Nox1 in the SN achieved by adeno-associated virus-mediated overexpression of Nox1-specific shRNA largely attenuated the actMMP3-mediated dopaminergic neuronal loss. Furthermore, Nox1 expression was significantly attenuated in Mmp3 null mice treated with N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Together we established novel molecular mechanisms underlying oxidative stress-mediated dopaminergic neuronal death in which MMP3 activation is a key upstream event that leads to mitochondrial ROS, Nox1 induction and eventual dopaminergic neuronal death. Our findings may lead to the development of novel therapeutic approach.
PMCID: PMC4275264  PMID: 25536219
10.  A Case of Organizing Pneumonia Associated with FOLFIRI Chemotherapy 
The combination chemotherapy of irinotecan with 5-fluorouracil and leucovorin (FOLFIRI regimen) was recently proven to be beneficial in patients with advanced colorectal cancer. Pulmonary toxicity is very rare in adverse effects of irinotecan. No case of organizing pneumonia (also known as bronchiolitis obliterans organizing pneumonia) associated with FOLFIRI chemotherapy has been reported. We experienced a case of a 62-year-old man who presented persistent dry cough and progressive dyspnea after receiving chemotherapy with FOLFIRI regimen. After surgical lung biopsy, the patient was diagnosed with FOLFIRI chemotherapy-induced organizing pneumonia which was successfully treated with steroid therapy.
PMCID: PMC4286784  PMID: 25580143
Irinotecan; IFL Protocol; Cryptogenic Organizing Pneumonia; Colorectal Neoplasmsoxaliplatin
11.  21-O-Angeloyltheasapogenol E3, a Novel Triterpenoid Saponin from the Seeds of Tea Plants, Inhibits Macrophage-Mediated Inflammatory Responses in a NF-κB-Dependent Manner 
Mediators of Inflammation  2014;2014:658351.
21-O-Angeloyltheasapogenol E3 (ATS-E3) is a triterpenoid saponin recently isolated from the seeds of the tea tree Camellia sinensis (L.) O. Kuntze. ATS-E3 has several beneficial properties including anti-inflammatory, antidiabetic, antiatherosclerotic, and anticancer effects. Unlike other phenolic compounds isolated from tea plants, there are no studies reporting the pharmacological action of ATS-E3. In this study, we therefore aimed to explore the cellular and molecular inhibitory activities of ATS-E3 in macrophage-mediated inflammatory responses. ATS-E3 remarkably diminished cellular responses of macrophages such as FITC-dextran-induced phagocytic uptake, sodium nitroprusside- (SNP-) induced radical generation, and LPS-induced nitric oxide (NO) production. Analysis of its molecular activity showed that this compound significantly suppressed the expression of inducible NO synthase (iNOS), nuclear translocation of nuclear factor- (NF-) κB subunits (p50 and p65), phosphorylation of inhibitor of κB kinase (IKK), and the enzyme activity of AKT1. Taken together, the novel triterpenoid saponin compound ATS-E3 contributes to the beneficial effects of tea plants by exerting anti-inflammatory and antioxidative activities in an AKT/IKK/NF-κB-dependent manner.
PMCID: PMC4245502  PMID: 25477714
12.  Blood lead levels of Korean lead workers in 2003–2011 
This study aimed to document the trend in blood lead levels in Korean lead workers from 2003 until 2011 and blood lead levels within each of the main industries.
Nine years (2003–2011) of blood lead level data measured during a special health examination of Korean lead workers and collected by the Korea Occupational Safety and Health Agency were analyzed. Blood lead levels were determined by year, and a geometric mean (GM) was calculated for each industry division.
The overall GM blood lead level for all years combined (n = 365,331) was 4.35 μg/dL. The GM blood lead level decreased from 5.89 μg/dL in 2003 to 3.53 μg/dL in 2011. The proportion of the results ≥30 μg/dL decreased from 4.3% in 2003 to 0.8% in 2011. In the “Manufacture of Electrical Equipment” division, the GM blood lead level was 7.80 μg/dL, which was the highest among the industry divisions. The GM blood lead levels were 7.35 μg/dL and 6.77 μg/dL in the “Manufacturers of Rubber and Plastic Products” and the “Manufacture of Basic Metal Products” division, respectively.
The blood lead levels in Korean lead workers decreased from 2003 to 2011 and were similar to those in the US and UK. Moreover, workers in industries conventionally considered to have a high risk of lead exposure also tended to have relatively high blood lead levels compared to those in other industries.
PMCID: PMC4209518  PMID: 25379187
Blood lead level; Lead worker; Special health examination; Korean
13.  NADPH Oxidase 1, a Novel Molecular Source of ROS in Hippocampal Neuronal Death in Vascular Dementia 
Antioxidants & Redox Signaling  2014;21(4):533-550.
Aims: Chronic cerebral hypoperfusion (CCH) is a common pathological factor that contributes to neurodegenerative diseases such as vascular dementia (VaD). Although oxidative stress has been strongly implicated in the pathogenesis of VaD, the molecular mechanism underlying the selective vulnerability of hippocampal neurons to oxidative damage remains unknown. We assessed whether the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) complex, a specialized superoxide generation system, plays a role in VaD by permanent ligation of bilateral common carotid arteries in rats. Results: Male Wistar rats (10 weeks of age) were subjected to bilateral occlusion of the common carotid arteries (two-vessel occlusion [2VO]). Nox1 expression gradually increased in hippocampal neurons, starting at 1 week after 2VO and for approximately 15 weeks after 2VO. The levels of superoxide, DNA oxidation, and neuronal death in the CA1 subfield of the hippocampus, as well as consequential cognitive impairment, were increased in 2VO rats. Both inhibition of Nox by apocynin, a putative Nox inhibitor, and adeno-associated virus-mediated Nox1 knockdown significantly reduced 2VO-induced reactive oxygen species generation, oxidative DNA damage, hippocampal neuronal degeneration, and cognitive impairment. Innovation and Conclusion: We provided evidence that neuronal Nox1 is activated in the hippocampus under CCH, causing oxidative stress and consequential hippocampal neuronal death and cognitive impairment. This evidence implies that Nox1-mediated oxidative stress plays an important role in neuronal cell death and cognitive dysfunction in VaD. Nox1 may serve as a potential therapeutic target for VaD. Antioxid. Redox Signal. 21, 533–550.
PMCID: PMC4086030  PMID: 24294978
14.  Chordoid Meningioma in a Pediatric Patient with Tuberous Sclerosis Complex 
Korean Journal of Pathology  2014;48(4):302-306.
PMCID: PMC4160594  PMID: 25214863
15.  Establishment of Hertwig’s Epithelial Root Sheath/Epithelial Rests of Malassez Cell Line from Human Periodontium 
Molecules and Cells  2014;37(7):562-567.
Human Hertwig’s epithelial root sheath/epithelial rests of Malassez (HERS/ERM) cells are epithelial remnants of teeth residing in the periodontium. Although the functional roles of HERS/ERM cells have yet to be elucidated, they are a unique epithelial cell population in adult teeth and are reported to have stem cell characteristics. Therefore, HERS/ERM cells might play a role as an epithelial component for the repair or regeneration of dental hard tissues; however, they are very rare population in periodontium and the primary isolation of them is considered to be difficult. To overcome these problems, we immortalized primary HERS/ERM cells isolated from human periodontium using SV40 large T antigen (SV40 LT) and performed a characterization of the immortalized cell line. Primary HERS/ERM cells could not be maintained for more than 6 passages; however, immortalized HERS/ERM cells were maintained for more than 20 passages. There were no differences in the morphological and immunophenotypic characteristics of HERS/ERM cells and immortalized HERS/ERM cells. The expression of epithelial stem cell and embryonic stem cell markers was maintained in immortalized HERS/ERM cells. Moreover, immortalized HERS/ERM cells could acquire mesenchymal phenotypes through the epithelial-mesenchymal transition via TGF-β1. In conclusion, we established an immortalized human HERS/ERM cell line with SV40 LT and expect this cell line to contribute to the understanding of the functional roles of HERS/ERM cells and the tissue engineering of teeth.
PMCID: PMC4132309  PMID: 25081036
epithelial-mesenchymal transition; Hertwig’s epithelial root sheath/epithelial rests of Malassez cells; immortalization; stemness; SV40 large T antigen
16.  IKKβ-Targeted Anti-Inflammatory Activities of a Butanol Fraction of Artificially Cultivated Cordyceps pruinosa Fruit Bodies 
The inhibitory activities of the Cordyceps pruinosa butanol fraction (Cp-BF) were investigated by determining inflammatory responses of lipopolysaccharide (LPS)-treated RAW264.7 macrophage cells and by evaluating HCl/ethanol (EtOH)-triggered gastric ulcers in mice. The molecular mechanisms of the inhibitory effects of Cp-BF were investigated by identifying target enzymes using biochemical and molecular biological approaches. Cp-BF strongly inhibited the production of NO and TNF-α, release of reactive oxygen species (ROS), phagocytic uptake of FITC-dextran, and mRNA expression levels of interleukin (IL)-6, inducible NO synthase (iNOS), and tumour necrosis factor-alpha (TNF)-α in activated RAW264.7 cells. Cp-BF also strongly downregulated the NF-κB pathway by suppressing IKKβ according to luciferase reporter assays and immunoblot analysis. Furthermore, Cp-BF blocked both increased levels of NF-κB-mediated luciferase activities and phosphorylation of p65/p50 observed by IKKβ overexpression. Finally, orally administered Cp-BF was found to attenuate gastric ulcer and block the phosphorylation of IκBα induced by HCl/EtOH. Therefore, these results suggest that the anti-inflammatory activity of Cp-BF may be mediated by suppression of IKKα and its downstream NF-κB activation. Since our group has established the mass cultivation conditions by developing culture conditions for Cordyceps pruinosa, the information presented in this study may be useful for developing new anti-inflammatory agents.
PMCID: PMC4123572  PMID: 25132860
17.  Genome wide association scan for chronic periodontitis implicates novel locus 
BMC Oral Health  2014;14:84.
There is evidence for a genetic contribution to chronic periodontitis. In this study, we conducted a genome wide association study among 866 participants of the University of Pittsburgh Dental Registry and DNA Repository, whose periodontal diagnosis ranged from healthy (N = 767) to severe chronic periodontitis (N = 99).
Genotypingi of over half-million single nucleotide polymorphisms was determined. Analyses were done twice, first in the complete dataset of all ethnicities, and second including only samples defined as self-reported Whites. From the top 100 results, twenty single nucleotide polymorphisms had consistent results in both analyses (borderline p-values ranging from 1E-05 to 1E-6) and were selected to be tested in two independent datasets derived from 1,460 individuals from Porto Alegre, and 359 from Rio de Janeiro, Brazil. Meta-analyses of the Single nucleotide polymorphisms showing a trend for association in the independent dataset were performed.
The rs1477403 marker located on 16q22.3 showed suggestive association in the discovery phase and in the Porto Alegre dataset (p = 0.05). The meta-analysis suggested the less common allele decreases the risk of chronic periodontitis.
Our data offer a clear hypothesis to be independently tested regarding the contribution of the 16q22.3 locus to chronic periodontitis.
PMCID: PMC4096424  PMID: 25008200
Periodontitis; Chronic periodontitis; Aggressive periodontitis; Genetics; Medical genetics; Genetic polymorphism
18.  Molecular mechanism of protopanaxadiol saponin fraction-mediated anti-inflammatory actions 
Journal of Ginseng Research  2014;39(1):61-68.
Korean Red Ginseng (KRG) is a representative traditional herbal medicine with many different pharmacological properties including anticancer, anti-atherosclerosis, anti-diabetes, and anti-inflammatory activities. Only a few studies have explored the molecular mechanism of KRG-mediated anti-inflammatory activity.
We investigated the anti-inflammatory mechanisms of the protopanaxadiol saponin fraction (PPD-SF) of KRG using in vitro and in vivo inflammatory models.
PPD-SF dose-dependently diminished the release of inflammatory mediators [nitric oxide (NO), tumor necrosis factor-α, and prostaglandin E2], and downregulated the mRNA expression of their corresponding genes (inducible NO synthase, tumor necrosis factor-α, and cyclooxygenase-2), without altering cell viability. The PPD-SF-mediated suppression of these events appeared to be regulated by a blockade of p38, c-Jun N-terminal kinase (JNK), and TANK (TRAF family member-associated NF-kappa-B activator)-binding kinase 1 (TBK1), which are linked to the activation of activating transcription factor 2 (ATF2) and interferon regulatory transcription factor 3 (IRF3). Moreover, this fraction also ameliorated HCl/ethanol/-induced gastritis via suppression of phospho-JNK2 levels.
These results strongly suggest that the anti-inflammatory action of PPD-SF could be mediated by a reduction in the activation of p38-, JNK2-, and TANK-binding-kinase-1-linked pathways and their corresponding transcription factors (ATF2 and IRF3).
PMCID: PMC4268567  PMID: 25535478
activating transcription factor 2; anti-inflammatory activity; interferon regulatory transcription factor 3; Korean red ginseng; protopanaxadiol saponin fraction
19.  The Reverse Nasolabial Flap with a Cartilage Graft for the Repair of a Full-Thickness Alar Defect: A Single-Stage Procedure 
Annals of Dermatology  2014;26(3):377-380.
A 65-year-old woman with a deeply infiltrating basal cell carcinoma in the right ala underwent full-thickness excision of most of the ala, including the alar rim, crease, and the adjacent cheek, leaving a 'through-and-through' defect. Reconstruction was performed by using the reverse nasolabial flap and a cartilage graft across the alar defect, harvested from the concha, to prevent nostril collapse and to maintain the alar shape. The reverse or turnover nasolabial flap is a variant of the conventional nasolabial flap; however, it may be more suited for the repair of a full-thickness, lateral alar defect. The reverse nasolabial flap functions both as an inner liner and an outer cover and the repair is performed as a single-stage procedure. Furthermore, this flap can provide both excellent function and excellent cosmetic outcome.
PMCID: PMC4069650  PMID: 24966639
Nasal cartilages; Surgical flaps
20.  Clinical outcome of acute necrotizing encephalopathy in related to involving the brain stem of single institution in Korea 
Korean Journal of Pediatrics  2014;57(6):264-270.
Acute necrotizing encephalopathy (ANE) is a fulminant disease of the brain characterized by bilateral thalamic lesions, and is prevalent among children in East Asia. The prognosis of ANE is usually poor with a high mortality rate and neurological sequelae. This study aimed to delineate the clinical characteristics and prognostic factors of ANE.
We retrospectively analyzed clinical data of 399 pediatric patients with encephalitis who were admitted to Samsung Medical Center from December 1998 to March 2011. We enrolled ten patients (11 cases) with ANE and analyzed their demographic, clinical, and neuroimaging data. The location and extent of the brain regions were checked based on fluid-attenuated inversion recovery, T1-, and T2-weighted imaging findings; the presence of contrast enhancement, restricted diffusion, and hemorrhage.
Ten patients were identified, including one patient with two episodes. The median age of onset was 1.5 years (0.4-8.4 years). The mortality rate was 40%, and only 30% of patients survived without neurological sequelae. The definite involvement of the brainstem on brain magnetic resonance imaging was significantly correlated with mortality (P=0.04).
Broad and extensive brainstem involvement suggested the fulminant course of ANE. Early diagnosis of ANE before brainstem involvement, through careful identification of symptoms of brain dysfunction, may be the best way to achieve better neurological outcomes.
PMCID: PMC4115067  PMID: 25076971
Acute necrotizing encephalopathy; Pediatrics
21.  Clinically Useful Diagnostic Tool of Contrast Enhanced Ultrasonography for Focal Liver Masses: Comparison to Computed Tomography and Magnetic Resonance Imaging 
Gut and Liver  2014;8(3):292-297.
To evaluate the diagnostic value of contrast (SonoVue®) enhancement ultrasonography (CEUS) and to compare this method with computed tomography (CT) and magnetic resonance imaging (MRI) in evaluating liver masses.
CEUS (n=50), CT (n=47), and MRI (n=43) were performed on 50 liver masses in 48 patients for baseline mass characterization. The most likely impression for each modality and the final diagnosis, based on the combined biopsy results (n=14), angiography findings (n=36), and clinical course, were determined. The diagnostic value of CEUS was compared to those of CT and MRI.
The final diagnosis of the masses was hepatocellular carcinoma (n=43), hemangioma (n=3), benign adenoma (n=2), eosinophilic abscess (n=1), and liver metastasis (n=1). The overall diagnostic agreement with the final diagnosis was substantial for CEUS, CT, and MRI, with κ values of 0.621, 0.763, and 0.784, respectively. The sensitivity, specificity, and accuracy were 83.3%, 87.5%, and 84.0%, respectively, for CEUS; 95.0%, 87.5%, and 93.8%, respectively, for CT; and 94.6%, 83.3%, and 93.0%, respectively for MRI. After excluding the lesions with poor acoustic sonographic windows, the sensitivity, specificity, and accuracy for CEUS were 94.6%, 87.5%, and 93.3%, respectively, with a κ value of 0.765.
If an appropriate acoustic window is available, CEUS is comparable to CT and MRI for the diagnosis of liver masses.
PMCID: PMC4026647  PMID: 24827626
Contrast enhanced ultrasonography; Liver masses
22.  Gallstones are Associated with Intima-Media Thickness of Common Carotid Arteries in Men 
Korean Journal of Family Medicine  2014;35(3):136-142.
The prevalence of gallstone disease is increasing in Korea. Gallstone disease and atherosclerosis share common risk factors. Ultrasonographic carotid intima-media thickness is an independent predictor of atherosclerosis. We measured the carotid intima-media thickness among men who had gallstones to establish the association between atherosclerosis and gallstones.
A total of 330 men who visited the health promotion center of the IS Hallym Hospital from January 2011 to July 2012 were recruited. Both abdomen and carotid ultrasonographies were performed. Demographic, anthropometric, and biochemical data were collected.
The prevalence of gallstones was 6.6%. The carotid intima-media thickness, age, and body mass index were higher in subjects with gallstones (P < 0.05 for all). After Pearson correlation analysis, gallstone, age, body mass index, and fasting blood sugar were significantly associated with carotid intima-media thickness. A statistically positive association between gallstone and carotid intima-media thickness was demonstrated in a multivariate analysis adjusted for age, body mass index, and fasting blood sugar.
Carotid intima-media thickness is higher in male subjects with gallstones, indicating that they are at greater risk for atherosclerosis.
PMCID: PMC4040431  PMID: 24921032
Gallstones; Carotid Intima-Media Thickness; Atherosclerosis; Men
24.  Lancemaside A from Codonopsis lanceolata Modulates the Inflammatory Responses Mediated by Monocytes and Macrophages 
Mediators of Inflammation  2014;2014:405158.
In this study, we aimed to examine the cellular and molecular mechanisms of lancemaside A from Codonopsis lanceolata (Campanulaceae) in the inflammatory responses of monocytes (U937 cells) and macrophages (RAW264.7 cells). Lancemaside A significantly suppressed the inflammatory functions of lipopolysaccharide- (LPS-) treated RAW264.7 cells by suppressing the production of nitric oxide (NO), the expression of the NO-producing enzyme inducible NO synthase (iNOS), the upregulation of the costimulatory molecule CD80, and the morphological changes induced by LPS exposure. In addition, lancemaside A diminished the phagocytic activity of RAW264.7 cells and boosted the neutralizing capacity of these cells when treated with the radical generator sodium nitroprusside (SNP). Interestingly, lancemaside A strongly blocked the adhesion activity of RAW264.7 cells to plastic culture plates, inhibited the cell-cell and cell-fibronectin (FN) adhesion of U937 cells that was triggered by treatment with an anti-β1-integrin (CD29) antibody and immobilized FN, respectively. By evaluating the activation of various intracellular signaling pathways and the levels of related nuclear transcription factors, lancemaside A was found to block the activation of inhibitor of κB kinase (IKK) and p65/nuclear factor- (NF-) κB. Taken together, our findings strongly suggest that the anti-inflammatory function of lancemaside A is the result of its strong antioxidative and IKK/NF-κB inhibitory activities.
PMCID: PMC3981472  PMID: 24782593
25.  Reduced-dose craniospinal radiotherapy followed by tandem high-dose chemotherapy and autologous stem cell transplantation in patients with high-risk medulloblastoma 
Neuro-Oncology  2012;15(3):352-359.
We assessed the feasibility and effectiveness of reduced-dose craniospinal (CS) radiotherapy (RT) followed by tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT) in reducing late adverse effects without jeopardizing survival among children with high-risk medulloblastoma (MB).
From October 2005 through September 2010, twenty consecutive children aged >3 years with high-risk MB (presence of metastasis and/or postoperative residual tumor >1.5 cm2) were assigned to receive 2 cycles of pre-RT chemotherapy, CSRT (23.4 or 30.6 Gy) combined with local RT to the primary site (total 54.0 Gy), and 4 cycles of post-RT chemotherapy followed by tandem HDCT/autoSCT. Carboplatin-thiotepa-etoposide and cyclophosphamide-melphalan regimens were used for the first and second HDCT, respectively.
Of 20 patients with high-risk MB, 17 had metastatic disease and 3 had a postoperative residual tumor >1.5 cm2 without metastasis. The tumor relapsed/progressed in 4 patients, and 2 patients died of toxicities during the second HDCT/autoSCT. Therefore, 14 patients remained event-free at a median follow-up of 46 months (range, 23−82) from diagnosis. The probability of 5-year event-free survival was 70.0% ± 10.3% for all patients and 70.6% ± 11.1% for patients with metastases. Late adverse effects evaluated at a median of 36 months (range, 12−68) after tandem HDCT/autoSCT were acceptable.
In children with high-risk MB, CSRT dose might be reduced when accompanied by tandem HDCT/autoSCT without jeopardizing survival. However, longer follow-up is needed to evaluate whether the benefits of reduced-dose CSRT outweigh the long-term risks of tandem HDCT/autoSCT.
PMCID: PMC3578484  PMID: 23258845
autologous stem cell transplantation; high-dose chemotherapy; late effect; medulloblastoma; radiotherapy

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