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1.  Significance of an endoscopically injected nodule detected on ultrasound as a predictive factor for the resolution of vesicoureteral reflux 
Endoscopic treatment of vesicoureteral reflux (VUR) is feasible in pediatric patients. As endoscopic injection has a lower success rate than ureteral reimplantation, a postoperative voiding cystourethrogram (VCUG) is usually performed. The present study evaluated whether the presence of a nodule on noninvasive ultrasound could predict the resolution of VUR and replace invasive VCUG. Patients who received an injection of endoscopic bulking agent for VUR from January 2005 to December 2010 were evaluated retrospectively. It was evaluated whether a nodule, an echogenic mass lesion distinguished from the bladder at the ureteral orifice, was present on the ultrasound one month postoperatively. The success of the injection in the group with nodules was compared with that of the group without nodules by VCUG 3 months postoperatively. A total of 149 patients (220 ureters) met the inclusion criteria. The mean age at surgery was 3.5 years (range, 0.6–18 years). The overall success rate was 73.2%. A nodule was present in 152 cases (69.1%). The group with nodules had a higher success rate than the group without nodules (84.2%, 128/152 vs. 48.5%, 33/68, respectively; P<0.001). According to multivariate analysis, injection nodules were a predictive factor for the success of the endoscopic injection (odds ratio, 6.050; P<0.001). The failure rate increased with increasing injection volume. The sensitivity of sonographic injection nodules for predicting success was 79.5% and the specificity was 59.3%. To conclude, the presence of a postoperative nodule can predict the resolution of VUR.
PMCID: PMC4316906  PMID: 25667678
vesico-ureteral reflux; dextranomer-hyaluronic acid copolymer; ultrasonography
2.  Acute ileofemoral artery thromboembolism due to left ventricle thrombi with spontaneous coronary artery dissection 
Spontaneous coronary artery dissection (SCAD) is a very rare cause of peripheral artery thromboembolism. It is especially rare to show symptoms of acute limb ischemia without chest symptoms during a hospital visit. In this case, a rare case of SCAD led to left heart failure and caused left ventricle thrombi, which in turn caused peripheral thromboembolism.
PMCID: PMC4279993  PMID: 25553326
Spontaneous coronary artery dissection; Thromboembolism; Limb; Ischemia
3.  Reaction Kinetics of Substrate Transglycosylation Catalyzed by TreX of Sulfolobus solfataricus and Effects on Glycogen Breakdown 
Journal of Bacteriology  2014;196(11):1941-1949.
We studied the activity of a debranching enzyme (TreX) from Sulfolobus solfataricus on glycogen-mimic substrates, branched maltotetraosyl-β-cyclodextrin (Glc4-β-CD), and natural glycogen to better understand substrate transglycosylation and the effect thereof on glycogen debranching in microorganisms. The validation test of Glc4-β-CD as a glycogen mimic substrate showed that it followed the breakdown process of the well-known yeast and rat liver extract. TreX catalyzed both hydrolysis of α-1,6-glycosidic linkages and transglycosylation at relatively high (>0.5 mM) substrate concentrations. TreX transferred maltotetraosyl moieties from the donor substrate to acceptor molecules, resulting in the formation of two positional isomers of dimaltotetraosyl-α-1,6-β-cyclodextrin [(Glc4)2-β-CD]; these were 61,63- and 61,64-dimaltotetraosyl-α-1,6-β-CD. Use of a modified Michaelis-Menten equation to study substrate transglycosylation revealed that the kcat and Km values for transglycosylation were 1.78 × 103 s−1 and 3.30 mM, respectively, whereas the values for hydrolysis were 2.57 × 103 s−1 and 0.206 mM, respectively. Also, enzyme catalytic efficiency (the kcat/Km ratio) increased as the degree of polymerization of branch chains rose. In the model reaction system of Escherichia coli, glucose-1-phosphate production from glycogen by the glycogen phosphorylase was elevated ∼1.45-fold in the presence of TreX compared to that produced in the absence of TreX. The results suggest that outward shifting of glycogen branch chains via transglycosylation increases the number of exposed chains susceptible to phosphorylase action. We developed a model of the glycogen breakdown process featuring both hydrolysis and transglycosylation catalyzed by the debranching enzyme.
PMCID: PMC4010986  PMID: 24610710
4.  Risk factors for contralateral patent processus vaginalis determined by transinguinal laparoscopic examination 
Concurrent contralateral inguinal exploration in children with unilateral hernia or hydrocele is a subject of debate. The aim of the present study was to investigate the incidence of contralateral patent processus vaginalis (CPPV) using transinguinal laparoscopy (inguinoscopy). In addition, the risk factors of CPPV were evaluated in order to facilitate the selection of appropriate candidates for contralateral examination. A total of 119 patients who presented with unilateral hydrocele, inguinal hernia or cryptorchidism between 2001 and 2008 underwent inguinoscopy during the ipsilateral surgery. All data were collected prospectively. The incidence of CPPV was investigated and the risk factors affecting the presence of CPPV were analyzed. Among these patients, 29 individuals (24.4%) had CPPV confirmed by inguinoscopy. No surgical complications were observed during the inguinoscopy. Cases with suspicious ultrasound findings were at a higher risk of CPPV than cases with normal findings (odds ratio, 13.800; P=0.004). A history of contralateral disease was also found to be a significant risk factor (odds ratio, 4.008; P=0.019). The present study identified that the significant risk factors for CPPV were suspicious findings on ultrasound examination and a history of contralateral disease. Therefore, it is concluded that performing inguinoscopy in children with these risk factors is beneficial.
PMCID: PMC4280956  PMID: 25574209
hydrocele; inguinal hernia; contralateral; laparoscopy
5.  Spinal Paraganglioma Adherent to the Cauda Equina 
Korean Journal of Spine  2014;11(4):252-254.
Paragangliomas are rare among intradural spinal tumors. Most of them are benign, but aggressive behavior and local recurrence can occur. Cases of paraganglioma are, difficult to diagnose radiologically; hence, diagnosis is confirmed histopathologically. Radiologically, paragangliomas are similar to ependymomas, and, histopathologically, they are similar to neuroendocrine tumors. We evaluated the case of a 76-year-old woman with a spinal paraganglioma that was associated with back pain and radiating pain in both the lower extremities. She underwent an operation, and her symptoms were relieved. Here, we describe a rare case of paraganglioma that was adherent to the cauda equina.
PMCID: PMC4303282  PMID: 25620989
Paraganglioma; Cauda equina; Operation
6.  Quantitative assessment of Azumiobodo hoyamushi distribution in the tunic of soft tunic syndrome–affected ascidian Halocynthia roretzi using real-time polymerase chain reaction 
Parasites & Vectors  2014;7(1):539.
The kinetoplastid parasite, Azumiobodo hoyamushi, is the causative agent of soft tunic syndrome (STS) in ascidians and leads to their mass mortality in Korean waters. This study was conducted to quantify A. hoyamushi density during the development of STS in the tunics of ascidians (Halocynthia roretzi) using real-time polymerase chain reaction (qPCR).
The infection intensity of A. hoyamushi, as measured by qPCR, varied depending on the part of the tunic analyzed, as well as the stage of STS development. The highest infection intensity was recorded in the tunics of the siphons. The infection intensity of A. hoyamushi in the siphons was only 2.9 cell/tunic (area, 0.25 cm2) or 106.0 cell/gram tunic (GT) in the early phase of STS, but this value increased dramatically to 16,066 cells/tunic (0.25 cm2) or 617,004 cell/GT at the time of death. The number of A. hoyamushi parasites increased gradually and their distribution spread from the siphons to the other parts of the tunics.
qPCR enabled the quantitation of A. hoyamushi and the results revealed that parasite density increased as STS progressed. In addition, our results suggested that the siphons might function as the portal of entry for A. hoyamushi during infection.
PMCID: PMC4253000  PMID: 25425505
Halocynthia roretzi; Azumiobodo hoyamushi; Real-time PCR; Soft tunic syndrome
7.  Small RNA- and DNA-based gene therapy for the treatment of liver cirrhosis, where we are? 
World Journal of Gastroenterology : WJG  2014;20(40):14696-14705.
Chronic liver diseases with different aetiologies rely on the chronic activation of liver injuries which result in a fibrogenesis progression to the end stage of cirrhosis and liver failure. Based on the underlying cellular and molecular mechanisms of a liver fibrosis, there has been proposed several kinds of approaches for the treatment of liver fibrosis. Recently, liver gene therapy has been developed as an alternative way to liver transplantation, which is the only effective therapy for chronic liver diseases. The activation of hepatic stellate cells, a subsequent release of inflammatory cytokines and an accumulation of extracellular matrix during the liver fibrogenesis are the major obstacles to the treatment of liver fibrosis. Several targeted strategies have been developed, such as antisense oligodeoxynucleotides, RNA interference and decoy oligodeoxynucleotides to overcome this barriers. With this report an overview will be provided of targeted strategies for the treatment of liver cirrhosis, and particularly, of the targeted gene therapy using short RNA and DNA segments.
PMCID: PMC4209535  PMID: 25356032
Liver cirrhosis; Gene therapy; Oligodeoxynucleotides; Antisense; Small interfering RNA; Micro RNA; Decoy
8.  Ovarian angioleiomyoma: a case report 
Angioleiomyoma (ALM) is a rare and painful, benign neoplasm that is referred to an uncommon type of leiomyoma originating from smooth muscle cells of arterial and venous walls. ALM is very rarely found in the female genital organs such as uterus or ovary. Herein, we present the case of a huge primary ovarian ALM in a 35 year-old woman, clinically and radiologically mimicking an ovarian fibroma, which histologically has diffuse myxoid degeneration. This is the third case of ovarian ALM and the first case of ovarian ALM with diffuse degeneration reported in English literatures, to the best of our knowledge.
PMCID: PMC4270608  PMID: 25550878
Angioleiomyoma; ovary; degeneration
9.  Fractionated Gamma Knife Radiosurgery for Benign Perioptic Tumors: Outcomes of 38 Patients in a Single Institute 
This study was performed to evaluate the efficacy and safety of fractionated Gamma Knife radiosurgery (GKRS) for perioptic lesions.
Thirty-eight patients with perioptic tumors were treated at our institute from May 2004 to December 2008. All patients had a lesion in close contact with the optic apparatus. Twenty-four of these patients had undergone surgical resection before fractionated GKRS. Radiation was delivered in four sessions with 12 hours intervals between sessions. The mean target volume was 3,851 mm3 and the median cumulative marginal dose was 20 Gy. The median follow-up was 38.2 months. Visual acuity and visual fields were analyzed according to visual impairment score using the German Ophthalmological Society guidelines.
Tumor control was achieved in 35 (94.6%) of the 37 patients with available follow-up images. Progressive tumor growth was observed in two craniopharyngioma patients (5.4%). Favorable visual outcomes in the postoperative period were achieved in 94.7% of cases (36/38). Sixteen patients showed visual function after fractionated GKRS, twenty cases were stationary, and two patients showed visual function deterioration after GKRS.
GKRS is a safe and effective alternative to either surgery or fractionated radiotherapy for selected benign lesions that are adjacent to the optic apparatus.
PMCID: PMC4231616  PMID: 25408926
Gamma Knife radiosurgery; Fractionated radiosurgery; Stereotactic radiosurgery; Tumor control; Visual outcome
10.  Evaluation of Seismic Performance and Effectiveness of Multiple Slim-Type Damper System for Seismic Response Control of Building Structures 
The Scientific World Journal  2014;2014:189106.
This paper presents the evaluation of seismic performance and cost-effectiveness of a multiple slim-type damper system developed for the vibration control of earthquake excited buildings. The multiple slim-type damper (MSD) that consists of several small slim-type dampers and linkage units can control damping capacity easily by changing the number of small dampers. To evaluate the performance of the MSD, dynamic loading tests are performed with three slim-type dampers manufactured at a real scale. Numerical simulations are also carried out by nonlinear time history analysis with a ten-story earthquake excited building structure. The seismic performance and cost-effectiveness of the MSD system are investigated according to the various installation configurations of the MSD system. From the results of numerical simulation and cost-effectiveness evaluation, it is shown that combinations of the MSD systems can effectively improve the seismic performance of earthquake excited building structures.
PMCID: PMC4180896  PMID: 25301387
11.  Neuroprotective effects of melittin on hydrogen peroxide-induced apoptotic cell death in neuroblastoma SH-SY5Y cells 
Free radicals are involved in neuronal cell death in human neurodegenerative diseases. Since ancient times, honeybee venom has been used in a complementary medicine to treat various diseases and neurologic disorders. Melittin, the main component of honeybee venom, has various biologic effects, including anti-bacterial, anti-viral, and anti-inflammatory activities.
We investigated the neuroprotective effects of melittin against H2O2-induced apoptosis in the human neuroblastoma cell line SH-SY5Y. The neuroprotective effects of melittin on H2O2-induced apoptosis were investigated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylterazolium bromide assay, caspase 3 activity, 4,6-diamidino-2-phenylindole staining, a lactate dehydrogenase release assay, Western blots, and reverse transcription-polymerase chain reaction.
The H2O2-treated cells had decreased cell viability with apoptotic features and increased production of caspase-3. On the other hand, melittin treatment increased cell viability and decreased apoptotic DNA fragmentation. Melittin attenuated the H2O2-induced decrease in mRNA and protein production of the anti-apoptotic factor Bcl-2. In addition, melittin inhibited both the H2O2-induced mRNA and protein expression of Bax-associated pro-apoptotic factor and caspase-3.
These findings suggest that melittin has potential therapeutic effects as an agent for the prevention of neurodegenerative diseases.
PMCID: PMC4246557  PMID: 25091565
12.  Isoniazid Could Be Used for Antibiotic-loaded Bone Cement for Musculoskeletal Tuberculosis: An In Vitro Study 
Antibiotic-loaded bone cement (ALBC) has been used in serious cases of musculoskeletal tuberculosis, but the type and amount of antibiotic that should be used in ALBC have not been determined.
We therefore determined the (1) elution characteristics and (2) antimycobacterial activity of isoniazid- and rifampicin-loaded bone cement.
A total of 240 elution samples of each of three discs from 40 g bone cement mixed with one of eight dosages: 1 g, 2 g, and 4 g isoniazid, 1 g, 2 g, and 4 g rifampicin, and a combination of 1 + 1 g or 2 + 2 g of isoniazid and rifampicin. The polymerization of rifampicin-loaded bone cement was delayed to mean 122.5 ± 31.1 minutes. We measured the quantity of isoniazid and rifampicin and the antimycobacterial activity on Days 1, 3, 7, 14, and 30.
Isoniazid eluted in almost all the samples while rifampicin was detected only on Day 1 with 2 g (0.7 ± 0.4 ug/mL/day), and until Day 14 with 4 g (0.1 ± 0.0u g/mL/day). Most of the samples containing isoniazid showed antimycobacterial activity while the samples containing rifampicin showed antimycobacterial activity only on Day 1 with 1 g (0.52 ± 0.18 ug/mL), until Day 14 with 2 g (0.03 ± 0.00 ug/mL), and until Day 30 with 4 g (1.84 ± 1.90 ug/mL).
Rifampicin was unsuitable for ALBC because of its delayed polymerization. Isoniazid eluted and showed antimycobacterial activity for 30 days.
Clinical Relevance
The data suggest isoniazid could be considered for use in ALBC for musculoskeletal tuberculosis if used with systemic treatment. For preventing resistance and systemic toxicity, a combination with a second-line drug and an in vivo study would be needed.
PMCID: PMC3676586  PMID: 23504536
13.  Immunohistochemical study for the origin of ductular reaction in chronic liver disease 
The appearance of proliferating bile ductular structures, which is called the “atypical ductular reaction” is frequently observed in various chronic liver diseases associated. However, the origin of these increased bile ductules has been a matter of controversy. In this study, we investigated the origin of ductular cells as an aspect of relation between epithelial to mesenchymal transition (EMT) and epithelial members of liver parenchyme, such as hepatocyte and cholangiocyte by immunohistochemical staining of human liver. Thirteen specimens of surgically resected liver with biliary cirrhosis were selected. Three sets of double immunohistochemical stains were done; Hep-Par 1 - cytokeratin 19 (CK19), Hep-Par 1 - α-sm ooth mus cle actin (α-SMA) and CK19 - α-SMA. As a result, we investigated the dual expression of the markers of hepatocyte and cholangiocyte in the same cell; in ductular cell and surrounding hepatocyte. However, there seems to be no dual expression of markers for EMT with epithelial markers. This study suggests a possibility of phenotypic change of mature hepatocyte into cholangiocyte. Future studies will be necessary to determine the role that proliferating cholangiocytes play in the pathogenesis of biliary fibrosis and how cholangiocytes interact with other cell types of the liver such as hepatic stellate cells or Kupffer cells.
PMCID: PMC4129021  PMID: 25120786
Liver; hepatocyte; bile duct cell; ductular reaction; transdifferentiation; immunohistochemistry
14.  Transcription factors related to epithelial mesenchymal transition in tumor center and margin in invasive lung adenocarcinoma 
The tumor microenvironment has many roles involving tumor progression, invasion and metastasis. The tumor cells at the tumor border loose epithelial properties and acquire mesenchymal features. This, epithelial-to-mesenchymal transition (EMT) has been suggested to be an important process for tissue and lymphovascular invasion. Pulmonary tissue samples from 15 patients with primary adenocarcinoma were evaluated with using immunofluorescence multi-staining the EMT-associated markers including E-cadherin and alpha-smooth muscle actin (α-SMA), and transcription factors including E-SNAIL and SLUG, and ZEB1. The data were analyzed in specific area, such as tumor center and tumor border. In this study we show that the invasive adenocarcinoma differentially expressed SNAIL and SLUG, and Zeb1 and it was associated with the loss of epithelial marker (E-cadherin) and gaining of mesenchymal marker (α-SMA) at the invasive border of lung carcinoma. The positive rates of SNAIL and ZEB1 were 26.7% and 0% in the tumor center and 40% and 20% in tumor margin, respectively. In addition, the expression of both SNAIL and ZEB1 at the border of tumor was observed in two cases (2/10). These two cases were associated with lymph node metastasis and advanced stage. The process of EMT has been suggested to be of prime importance for tissue and lymphovascular invasion. The process of EMT may be activated in the tumor border of lung adenocarcinoma. Related transcription factors, such as SNAIL and SLUG, and ZEB1, might be induced by paracrine effects of surrounded inflammatory cells and fibroblasts.
PMCID: PMC4129023  PMID: 25120788
Epithelial mesenchymal transition; lung adenocarcinoma; SNAIL; SLUG; ZEB1
15.  Urothelial Tumors of the Urinary Bladder in Two Adolescent Patients: Emphasis on Follow-up Methods 
Korean Journal of Urology  2014;55(6):430-433.
Here we describe two cases of papillary urothelial neoplasm of low malignant potential in adolescent boys. One case was a 16-year-old boy with a polypoid mass beside the right ureteral orifice and the other case was a 13-year-old boy with a papillary mass beside the left ureteral orifice. The initial presentation was hematuria in both cases and the bladder mass was detected by ultrasonography. Complete resection of the bladder tumor was performed by using an 11-Fr pediatric resectoscope. Follow-up has been performed with urine analysis, urine cytology, and bladder ultrasonography or cystoscopy every 3 months with no evidence of recurrence.
PMCID: PMC4064054  PMID: 24955230
Adolescent; Urinary bladder neoplasms
16.  Treatment of extensive comminuted mandibular fracture between both mandibular angles with bilateral condylar fractures using a reconstruction plate: a case report 
This following case report describes the open reduction, internal fixation and the reconstruction of an extensive comminuted mandibular fracture with bilateral condylar fractures in a 19-year-old male patient with an intellectual disability and autistic disorder. He suffered fall trauma, resulting in shattered bony fragments of the alveolus and mandibular body between both mandibular rami, the fracture of both condyles and the avulsion or dislocation of every posterior tooth of the mandible. The patient underwent open reduction and internal fixation between both mandibular rami using a reconstruction plate, open reduction and internal fixation of the shattered fragments using miniplates and screws, and the closed reduction of the bilateral condylar fractures.
PMCID: PMC4095810  PMID: 25045641
Fractures; Comminuted; Mandibular fractures; Fracture fixation
17.  Mechanisms of fibrogenesis in liver cirrhosis: The molecular aspects of epithelial-mesenchymal transition 
World Journal of Hepatology  2014;6(4):207-216.
Liver injuries are repaired by fibrosis and regeneration. The cause of fibrosis and diminished regeneration, especially in liver cirrhosis, is still unknown. Epithelial-mesenchymal transition (EMT) has been found to be associated with liver fibrosis. The possibility that EMT could contribute to hepatic fibrogenesis reinforced the concept that activated hepatic stellate cells are not the only key players in the hepatic fibrogenic process and that other cell types, either hepatic or bone marrow-derived cells could contribute to this process. Following an initial enthusiasm for the discovery of this novel pathway in fibrogenesis, more recent research has started to cast serious doubts upon the real relevance of this phenomenon in human fibrogenetic disorders. The debate on the authenticity of EMT or on its contribution to the fibrogenic process has become very animated. The overall result is a general confusion on the meaning and on the definition of several key aspects. The aim of this article is to describe how EMT participates to hepatic fibrosis and discuss the evidence of supporting this possibility in order to reach reasonable and useful conclusions.
PMCID: PMC4009476  PMID: 24799989
Epithelial-mesenchymal transition; Liver; Fibrosis; Transforming growth factor-beta1; Biological markers
18.  Bee venom ameliorates compound 48/80-induced atopic dermatitis-related symptoms 
Honeybee (Apis mellifera L.) venom (BV) has been traditionally used for the treatment of pain and inflammatory diseases such as itchy skin problems. However, the precise mechanism of BV in ameliorating the scratching behavior is not fully understood. Objective: In order to evaluate the effect of BV on atopic dermatitis-related symptoms in mice, we used a mouse skin scratching model induced by compound 48/80. The anti-itch effect of BV was investigated in a compound 48/80-induced mouse scratching behavior model. BALB/c mice were injected intraperitoneally with vehicle (saline 0.9%) or BV (0.01 and 0.1 mg/kg). One hour after treatment, the animals received a subcutaneous injection of compound 48/80. Intraperitoneal administration of BV (0.01 and 0.1 mg/kg) attenuated compound 48/80-induced scratching behaviors. The anti-scratching behavior effect of BV was in proportional to its vascular permeability effects. Treatment with BV also inhibited the degranulation of mast cells and the production of pro-inflammatory cytokines in compound 48/80-treated skin tissues. According to these results, BV may improve atopic dermatitis-related symptoms by inhibiting the mast cell degranulation and pro-inflammatory cytokine expression.
PMCID: PMC3843270  PMID: 24294376
Bee venom; scratching behavior; mast cell degranulation; compound 48/80; inflammation
19.  A Trend Analysis of the Prevalence, Awareness, Treatment, and Control of Hypertension by Age Group 
We examined the trends in prevalence, awareness, treatment, and control of hypertension in Korea as a basis for improving hypertension control programs.
12 598 participants of the Korean National Health and Nutrition Examination Survey were included in this study. Weighted linear regression to test time trends from 2007 to 2011 was performed.
The prevalence of hypertension was 20.7% in 2007, 29.4% in 2009, and 26.2% in 2011. Awareness of hypertension was 64.8% in 2007 and 61.1% in 2011. Awareness in those aged 65 and over was greater than in younger groups (age 19 to 44 and 45 to 64; p<0.001). The treatment rates were 58.4% in 2007 and 56.8% in 2011. The treatment rate was greater for those 65 and over than for younger age groups (p<0.001). The percentage of controlled hypertension was 37.6% in 2011. The percentage of controlled hypertension in those 65 and over was higher than in younger age groups (p<0.001). The treatment-control rates were 65.9% in 2007 and 67.7% in 2011. The prevalence of hypertension was higher in the males (p<0.001), while the awareness (p<0.001), treatment (p<0.001), and control (p<0.001) rates were higher in the females.
The prevalence of hypertension was increasing and the hypertension awareness, treatment, and control rates were low in younger age groups and males.
PMCID: PMC3859857  PMID: 24349657
Prevalence; Awareness; Therapeutics; Prevention & control; Hypertension; Korean National Health and Nutrition Examination Survey
20.  Pathogenesis and significance of glomerular C4d deposition in lupus nephritis: activation of classical and lectin pathways 
Immune complex-mediated complement activation through the classic pathway plays a key role in the pathogenesis of lupus nephritis (LN). C4d deposition in renal tissue reflects the prognosis of systemic lupus erythematosus (SLE). The aim of the current study is to investigate the pathogenesis and clinicopathologic significance of glomerular C4d deposition in LN. We retrospectively analyzed clinical and histopathological data of 20 SLE patients with renal biopsy-proven LN and 10 non-SLE renal biopsy samples as control. LN biopsies showed varying degrees of glomerular C4d staining associated with immune complex deposits, IgG (p = 0.015), C1q (p = 0.032) and C3 (p = 0.049). 7 LN biopsies had all of C4d, C1q and C3 deposits in their glomeruli, indicative of the activation of the classical pathway, whereas 2 LN biopsies had C4d and C3 deposits without accompanying C1q deposits, indicating the activation of the lectin pathway. Glomerular C4d deposition was correlated with the LN subtype (p < 0.001). In particular, a diffusely intense and coarsely granular pattern of C4d deposition in all glomeruli was detected in class V membranous LN. However, glomerular C4d deposition was correlated with neither disease activity of SLE nor histological activity and chronicity of LN. In conclusion, the activation of the lectin pathway as well as the classical pathway seems to play a crucial role in the pathogenesis of LN. Glomerular C4d staining could be helpful for diagnosing class V membranous LN, although glomerular C4d deposition does not reflect SLE disease activity and histological activity and chronicity.
PMCID: PMC3796238  PMID: 24133594
Lupus nephritis; C4d; classical pathway; lectin pathway; disease activity
21.  Analysis of Factors Contributing to Postoperative Spinal Instability after Lumbar Decompression for Spinal Stenosis 
Korean Journal of Spine  2013;10(3):149-154.
Decompressive laminectomy is one of the most commonly used surgical methods for the treatment of spinal stenosis. We retrospectively examined the risk factors that induce spinal instability, including slippage (spondylolisthesis) and/or segmental angulation after decompressive laminectomy on the lumbar spine.
From January 1, 2006 to June 30, 2010, 94 consecutive patients underwent first-time single level decompressive laminectomy without fusion and discectomy. Of these 94 patients, 42 with a follow-up period of at least 2 years were selected. We measured the segmental angulation and slippage in flexion and extension dynamic lumbar radiographs. We analyzed the following contributing factors to spinal instability: age/sex, smoking history, disc space narrowing, body mass index (kg/m2), facet joint tropism, effect of the lordotic angle on lumbar spine, asymmetrical paraspinal muscle volume, and surgical method and level.
Female patients, normal lordotic angle, and asymmetrical paraspinal muscle volume were factors more significantly associated with spondylolisthesis (p-value=0.026, 0.015, <0.01). Statistical results indicated that patients with facet tropism were more likely to have segmental angulation (p-value=0.046). Facet tropism and asymmetry of paraspinal muscle volume were predisposing factors to spinal instability (p-value=0.012, <0.01).
Facet joint tropism and asymmetry of paraspinal muscle volume are the most important factors associated with spinal instability; therefore, careful follow-up after decompressive laminectomy in affected patients is necessary.
PMCID: PMC3941765  PMID: 24757477
Spinal stenosis; Facet tropism; Paraspinal muscle; Instability
22.  The differential expression of TGF-β1, ILK and wnt signaling inducing epithelial to mesenchymal transition in human renal fibrogenesis: an immunohistochemical study 
Epithelial-to-mesenchymal transition (EMT) is a process for fully differentiated epithelial cells to undergo a phenotypic change to fibroblasts via diverse intracellular signaling pathways. While the pivotal role of fibroblasts in renal fibrosis is widely accepted, their origin remains undefined. In addition, although a large number of studies have provided evidence of EMT in human kidney diseases, specific signaling pathways leading to EMT have not yet been discovered in humans. To evaluate the origin of interstitial fibroblasts and signaling pathways involved in the EMT process, we analyzed the differential expression of EMT-related molecules in paraffin-fixed sections from 19 human fibrotic kidneys and 4 control kidneys. In human fibrotic kidneys, tubular epithelial cells (TECs) with intact tubular basement membrane (TBM) showed loss or down-regulation of an epithelial marker (E-cadherin), de novo expression of mesenchymal markers (vimentin and fibronectin), and significant up-regulation of inducers and mediators controlling the EMT process (transforming growth factor-β1 (TGF-β1), p-Smad2/3, β1-integrin, p38 mitogen-activated protein kinase (MAPK), WNT5B and β-catenin) in the areas of interstitial inflammation and fibrosis, compared with their expression in control kidneys. In conclusion, the type II EMT process in humans is thought to be an adaptive response of TECs to chronic injury and is regulated by interconnections of TGF-β/Smad, integrin/integrin-linked kinase (ILK) and wnt/β-catenin signaling pathways.
PMCID: PMC3759481  PMID: 24040439
EMT; TGF-beta/Smad signaling; integrin; wnt signaling; renal fibrosis; immunohistochemistry
23.  Melittin Suppresses HIF-1α/VEGF Expression through Inhibition of ERK and mTOR/p70S6K Pathway in Human Cervical Carcinoma Cells 
PLoS ONE  2013;8(7):e69380.
Melittin (MEL), a major component of bee venom, has been associated with various diseases including arthritis, rheumatism and various cancers. In this study, the anti-angiogenic effects of MEL in CaSki cells that were responsive to the epidermal growth factor (EGF) were examined.
Methodology/Principal Findings
MEL decreased the EGF-induced hypoxia-inducible factor-1α (HIF-1α) protein and significantly regulated angiogenesis and tumor progression. We found that inhibition of the HIF-1α protein level is due to the shortened half-life by MEL. Mechanistically, MEL specifically inhibited the EGF-induced HIF-1α expression by suppressing the phosphorylation of ERK, mTOR and p70S6K. It also blocked the EGF-induced DNA binding activity of HIF-1α and the secretion of the vascular endothelial growth factor (VEGF). Furthermore, the chromatin immunoprecipitation (ChIP) assay revealed that MEL reduced the binding of HIF-1α to the VEGF promoter HRE region. The anti-angiogenesis effects of MEL were confirmed through a matrigel plus assay.
MEL specifically suppressed EGF-induced VEGF secretion and new blood vessel formation by inhibiting HIF-1α. These results suggest that MEL may inhibit human cervical cancer progression and angiogenesis by inhibiting HIF-1α and VEGF expression.
PMCID: PMC3720276  PMID: 23936001
24.  Primary anaplastic large cell lymphoma in the dura of the brain: case report and prediction of a favorable prognosis 
Anaplastic large cell lymphoma (ALCL) is a rare T-cell lymphoma composed of CD30-positive lymphoid cells. ALCL arising in the dura matter of the brain is even more infrequent, in which only one case has been reported worldwide so far. We report a case of a 30-year-old immunocompetent male with a dura-based mass, radiographically consistent with meningioma. However, the excised mass via a left parieto-occipital craniotomy was composed of large, pleomorphic lymphoid cells to be immunopositive for CD3, CD30, anaplastic lymphoma kinase protein-1 (ALK-1) and epithelial membrane antigen (EMA), and immunonegative for CD20, CD15 and CD68. Multiple ALK gene fusion signals in the ALK locus were detected by fluorescence in situ hybridization (FISH) analysis. The patient was treated with CHOP chemotherapy and intrathecal methotrexate along with brain radiation therapy, which resulted in a complete remission. In an analysis of 25 previously reported primary CNS ALCLs, ALK-1 positivity was shown to be prevalent in younger age, as ALCL occurs outside the brain. Patient less than 23 years, ALK-1 positivity and unifocal tumor may be associated with a better prognosis. However, sex, dural or leptomeningeal involvement, immune status, and tumor necrosis do not appear to have any influence on survival.
PMCID: PMC3726981  PMID: 23923083
Anaplastic large cell lymphoma; ALK-positive; dura; prognosis; primary tumor
25.  Factors Affecting the Outcome of Extracorporeal Shock Wave Lithotripsy for Unilateral Urinary Stones in Children: A 17-Year Single-Institute Experience 
Korean Journal of Urology  2013;54(7):460-466.
Extracorporeal shock wave lithotripsy (ESWL) is a first-line treatment for pediatric urinary stone disease. We aimed to determine the factors affecting the outcome of ESWL for unilateral urinary stones in children.
Materials and Methods
A total of 81 pediatric patients aged 0 to 16 years with urinary stones treated by ESWL from January 1995 through May 2012 were retrospectively reviewed. All patients were required to have unilateral urinary stone disease. Children who underwent other surgical procedures before ESWL were excluded. Outcomes evaluated after ESWL were the stone-free rate at 3 months after ESWL, success within a single session, and success within three sessions. Factors affecting the success within three sessions were also analyzed.
The final analysis was for 42 boys and 22 girls (mean age, 9.2±5.2 years). Of these 64 patients, 58 (90.6%) were treated by ESWL without other surgical procedures and 54 (84.4%) were successfully treated within three ESWL sessions. In the multivariate analysis, multiplicity (odds ratio [OR], 0.080; 95% confidence interval [CI], 0.012 to 0.534; p=0.009) and large stone size (>10 mm; OR, 0.112; 95% CI, 0.018 to 0.707; p=0.020) were significant factors that decreased the success rate within three ESWL sessions.
Most of the pediatric urinary stone patients in our study (90.6%) were successfully treated by ESWL alone without additional procedures. If a child has a large urinary stone (>10 mm) or multiplicity, clinicians should consider that several ESWL sessions might be needed for successful stone fragmentation.
PMCID: PMC3715710  PMID: 23878689
Lithotripsy; Pediatrics; Treatment outcome; Urinary calculi

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