Replication of results of genome-wide association studies on esophageal squamous cell carcinoma susceptibility loci in a Korean population.

Two recent genome-wide association studies have identified that the rs2274223 single-nucleotide polymorphism inphospholipase C epsilon 1 and the single-nucleotide polymorphism rs13042395 in C20orf54 are involved in esophageal squamous cell carcinoma (ESCC) in Chinese populations. We hypothesized that genetic polymorphisms of phospholipase C epsilon 1 and C20orf54 are also associated with ESCC in a Korean population. The rs2274223 and rs13042395 genotyping was performed using high-resolution melting analysis. The rs2274223 GG genotype was significantly associated with an increased risk of ESCC (odds ratio [OR]=1.86, 95% confidence interval [CI]=1.08-3.25) compared with the rs2274223 AA genotype. The rs13042395 G allele showed a significantly decreased risk of ESCC in the younger age group (OR=0.71, 95% CI=0.52-0.97) and no significant association in the older group (OR=1.19, 95% CI=0.87-1.62). We observed that the rs2274223 polymorphism was associated with an increased risk of ESCC in this Korean case-control study and that age may modify the association between the rs13042395 polymorphism and the risk of ESCC.

Low serum vitamin D level is associated with high risk of metabolic syndrome in post-menopausal women.

BACKGROUND: Serum vitamin D status, as indicated by 25-(OH)D, is inversely associated with glucose homeostasis, lipid profiles, and blood pressure. Evidence on the association of serum vitamin D with metabolic syndrome (MS) however, is very limited in post-menopausal women. AIM: To investigate the association between serum vitamin D and MS. MATERIALS AND METHODS: This study was a crosssectional study including 778 Korean adults who visited a health promotion center in a university hospital from January 2010 to May 2011. MS was defined according to the American Heart Association/National Heart, Lung, and Blood Institute criteria and the Korean Society for the Study of Obesity. MS and its individual components were assessed, as well as serum 25-(OH)D levels with a multiple logistic regression analysis. RESULTS: The overall prevalence of the MS in participants of this study was 147 (18.9%). After multiple adjustments, compared with the highest quartile serum 25- (OH)D level group (19.9-55.9 ng/ml), the odds ratio for MS in the lowest level group (4.2-9.7 ng/ml) was 2.44 [95% confidence interval (CI)=1.32-4.48], in the lower level group (9.8- 14.1 ng/ml) was 2.20 (95% CI=1.24-3.90), and in the intermediate level group (14.3-19.8 ng/ml) was 1.81 (95% CI=1.02-3.20). Among the components of MS, the adjusted odds ratios for having an elevated blood pressure, and high triglyceride level in the lowest level group were 1.81 (95% CI, 1.15-2.85), 2.74 (95% CI, 1.64-4.57), respectively. CONCLUSIONS: We found that a low serum 25-(OH)D level is significantly associated with the presence of MS and some metabolic components, especially the high triglyceride level and blood pressure in post-menopausal women.

Novel and recurrent TRPV4 mutations and their association with distinct phenotypes within the TRPV4 dysplasia family.

BACKGROUND: Mutations in TRPV4, a gene that encodes a Ca(2+) permeable non-selective cation channel, have recently been found in a spectrum of skeletal dysplasias that includes brachyolmia, spondylometaphyseal dysplasia, Kozlowski type (SMDK) and metatropic dysplasia (MD). Only a total of seven missense mutations were detected, however. The full spectrum of TRPV4 mutations and their phenotypes remained unclear. OBJECTIVES AND METHODS: To examine TRPV4 mutation spectrum and phenotype-genotype association, we searched for TRPV4 mutations by PCR-direct sequencing from genomic DNA in 22 MD and 20 SMDK probands. RESULTS: TRPV4 mutations were found in all but one MD subject. In total, 19 different heterozygous mutations were identified in 41 subjects; two were recurrent and 17 were novel. In MD, a recurrent P799L mutation was identified in nine subjects, as well as 10 novel mutations including F471del, the first deletion mutation of TRPV4. In SMDK, a recurrent R594H mutation was identified in 12 subjects and seven novel mutations. An association between the position of mutations and the disease phenotype was also observed. Thus, P799 in exon 15 is a hot codon for MD mutations, as four different amino acid substitutions have been observed at this codon; while R594 in exon 11 is a hotspot for SMDK mutations. CONCLUSION: The TRPV4 mutation spectrum in MD and SMDK, which showed genotype-phenotype correlation and potential functional significance of mutations that are non-randomly distributed over the gene, was presented in this study. The results would help diagnostic laboratories establish efficient screening strategies for genetic diagnosis of the TRPV4 dysplasia family diseases.

p53 codon 72 polymorphism and the risk of esophageal cancer: a Korean case-control study.

The aim of this study was to assess whether p53 codon 72 polymorphism is associated with an increased risk of esophageal cancer (EC) in South Korea. We conducted a case-control study including 340 patients with EC, and 1700 controls. P53 codon 72 polymorphism was determined by real-time polymerase chain reaction. The frequencies of p53 codon 72 polymorphisms (Arg/Arg, Arg/Pro, and Pro/Pro) in EC were 39.4%, 45.6%, and 15.0%, respectively; frequencies in the controls were 43.2%, 45.6%, and 11.2%, respectively. Compared with the Arg/Arg genotype, the OR of the Arg/Pro genotype was 1.09 (95% CI = 0.85-1.41) and that of the Pro/Pro genotype was 1.47 (95% CI = 1.02-2.11) for EC overall. When adjusted by age, gender, and smoking status, the OR of the Arg/Pro genotype was 1.24 (95% CI = 0.92-1.67) and that of the Pro/Pro genotype was 1.77 (95% CI = 1.15-2.74) for EC overall. In never-smokers and ever-smokers, the OR of the Arg/Pro genotype was 0.59 (95% CI = 0.37-0.95) and 1.39 (95% CI = 1.00-1.91), respectively, and there was a significant difference in the homogeneity test (P= 0.011). We observed that the p53 codon 72 polymorphism was associated with an increased risk of EC in this Korean case-control study, and smoking status modified the association between the p53 codon 72 polymorphism and the risk of EC.

PAX5-induced upregulation of LINC01194 exerts oncogenic properties by regulating GOLPH3 expression via miR-486-5p in prostate cancer.

OBJECTIVE: Several studies have demonstrated that long non-coding RNA can act as crucial roles during the progression of various tumors, including prostate cancer (PCa). We aimed to determine lncRNA LINC01194(LINC01194) expression in prostate cancer (PCa) and examine its influence on tumor behaviors of PCa cells. PATIENTS AND METHODS: RT-PCR was performed to examine LINC01194 and PAX5's expression levels in PCa tissues and cell lines. Luciferase reporter and chromatin immunoprecipitation (ChIP) assays were performed to explore whether PAX5 could activate the transcription of LINC01194. Cell viability, migration and invasion were assessed by CCK-8, colony formation, transwell assay and Wound-healing assays. Bioinformatics and Dual-Luciferase assays were used to investigate the interaction between LINC01194 and miR-486-5p, as well as between miR-486-5p and GOLPH3. Western blot was applied for detecting the expressions of the related proteins. RESULTS: LINC01194 was highly expressed in PCa specimens and cell lines. PAX5 could bind directly to LINC01194 promoter region and activate its transcription. Functionally, the proliferation and metastasis of PCa cells were substantially impeded by LINC01194 silencing in vitro and in vivo. Mechanistically, LINC01194 promoted PCa progression by serving as a sponge of miR-486-5p to increase GOLPH3 expression. CONCLUSIONS: Our study identifies LINC01194 as a tumor promotor in PCa and implicates the LINC01194/miR-486-5p/GOLPH3 axis in the PCa progression.

Metabolic syndrome and quality of life (QOL) using generalised and obesity-specific QOL scales.

OBJECTIVES: We investigated the association between metabolic syndrome (MS) and health-related quality of life (HRQOL) assessed using generalised and obesity-specific QOL instruments. METHODS: We recruited 456 outpatients [age: 19-81 years, body mass index (BMI): 16.3-36.7 kg/m2] in the primary care division from 12 general hospitals in Korea. HRQOL was measured using EuroQol comprising the health states descriptive system (EQ-5D) and visual analogue scale (EQ-VAS) as a general instrument. The Korean Obesity-related QOL scale (KOQOL) composed of six domains was used as a disease-specific QOL instrument. MS was defined on the basis of International Diabetes Federation (IDF) criteria with Korean-specific waist circumference cutoffs (men: 90 cm, women: 85 cm). RESULTS: Subjects with MS displayed significantly higher impairment of EQ-5D and KOQOL. Binary logistic regression analysis of MS patients with controls for age, gender, smoking, alcohol, exercise, education, income, marital status and medication history disclosed odds ratio (OR) values of 2.13 (1.33-3.41) for impaired total KOQOL, 2.07 (1.31-3.27) for impaired physical health, 1.63 (1.03-2.60) for impaired work-related health, 2.42 (1.45-4.04) for impaired routine life, 2.08 (1.27-3.40) for impaired sexual life and 2.56 (1.59-4.11) for diet distress. Among the EQ-5D dimensions, only pain/discomfort displayed a significantly increased OR of 1.60 (1.01-2.56) in MS group. CONCLUSIONS: Subjects with MS displayed a significantly impaired HRQOL compared with those without MS. MS and HRQOL were more strongly associated in obesity-specific QOL than in generalised QOL.

Knockdown of long non-coding RNA LINC00324 inhibits proliferation, migration and invasion of colorectal cancer cell via targeting miR-214-3p.

OBJECTIVE: Increasing evidence demonstrated that long non-coding RNA (lncRNA) played a vital role in human tumorigenesis and progression, including colorectal cancer (CRC). However, the underlying mechanisms are still largely unknown. The aim of this study was to investigate the function of lncRNA LINC00324 on the development of CRC and explore the possible mechanisms. MATERIALS AND METHODS: The expression level of LINC00324 and miR-214-3p was measured by quantitative real time polymerase chain reaction (qRT-PCR) in CRC cells. The effects on cell proliferation, migration and invasion were assessed by MTT and transwell assays, respectively. In addition, the protein levels of cyclin D1, p21, p27 and three MMPs were detected by Western blot analysis. The target of LINC00324 was predicted by online software and confirmed by luciferase reporter assay. RESULTS: We first detected the expression of LIN00324 was increased while miR-214-3p was decreased in CRC cells. Knockdown of LIN00324 suppressed proliferation, migration and invasion in SW620 and HCT15 cells. Moreover, overexpression of miR-214-3p also inhibited CRC cell proliferation, migration and invasion. Then, we identified miR-214-3p as directly target of LINC00324 and the expression of miR-214-3p was downregulated by LINC00324. In addition, inhibiting miR-214-3p reversed the effects of LINC00324 on CRC cell proliferation, migration and invasion. CONCLUSIONS: Our results proved that LINC00324 regulated CRC cell proliferation, migration and invasion by sponging miR-214-3p, suggesting that it might be a potential therapeutic target for CRC therapy.

MRI study of the lumbar spine in achondroplasia. A morphometric analysis for the evaluation of stenosis of the canal.

We carried out an MRI study of the lumbar spine in 15 patients with achondroplasia to evaluate the degree of stenosis of the canal. They were divided into asymptomatic and symptomatic groups. We measured the sagittal canal diameter, the sagittal cord diameter, the interpedicular distance at the mid-pedicle level and the cross-sectional area of the canal and spinal cord at mid-body and mid-disc levels. The MRI findings showed that in achondroplasia there was a significant difference between the groups in the cross-sectional area of the body canal at the upper lumbar levels. Patients with a narrower canal are more likely to develop symptoms of spinal stenosis than others.

Supracondylar osteotomy with Ilizarov fixation for elbow deformities in adults.

Stable fixation after a corrective supracondylar osteotomy in adults is difficult because of the irregularity of the area of bony contact, displacement of the fragments, the predominance of cortical bone, and the need for early mobilisation. We have used the Ilizarov apparatus for fixation in 15 patients who were treated by complex osteotomies with displacement of fragments for cubitus varus or valgus. Most patients with cubitus varus required medial displacement with rotation of the distal fragment. Those with cubitus valgus required lateral shift of the distal fragment to reduce the medial prominence of the elbow that would otherwise result. All osteotomies united within the expected time without loss of correction, despite early mobilisation. Complications related to the fixation were few and had resolved at the long-term follow-up.

Preventing collapse in early osteonecrosis of the femoral head. A randomised clinical trial of core decompression.

We performed a randomised trial on 37 hips (33 patients) with early-stage osteonecrosis (ON). After the initial clinical evaluation, including plain radiography and MRI, 18 hips were randomly assigned to a core-decompression group and 19 to a conservatively-treated group. All the patients were regularly followed up by clinical evaluation, plain radiography and MRI at intervals of three months. Hip pain was relieved in nine out of ten initially symptomatic hips in the core-decompression group but persisted in three out of four initially painful hips in the conservatively-treated group at the second assessment (p < 0.05). At a minimum follow-up of 24 months, 14 of the 18 core-decompressed hips (78%) and 15 of the 19 non-operated hips (79%) developed collapse of the femoral head. By survival analysis, there was no significant difference in the time to collapse between the two groups (log-rank test p = 0.79). Core decompression may be effective tin symptomatic relief, but is of no greater value than conservative management in preventing collapse in early osteonecrosis of the femoral head.

Trochanteric rotational osteotomy for osteonecrosis of the femoral head.

The rate of success of transtrochanteric rotational osteotomy for osteonecrosis of the femoral head may be improved if patients are preselected using MRI. We have used three criteria for selection for osteotomy (i) minor collapse of the infarcted area, loss of congruity or the crescent sign, without narrowing of the joint space or acetabular involvement (ii) patients younger than 55 years and with a painful hip (iii) patients with an intact area constituting an arc of more than 120 degrees between the central vertical line of the femoral head and the posterior or anterior margin of the necrotic portion as seen on a midsagittal MRI. Seventeen patients were selected, with a follow-up of more than 42 months. A bone scan four weeks after operation showed adequate perfusion of the proximal segment in all hips. The hip score of Merle d'Aubigné et al improved from 13.5 points before operation to 17.2 points at the latest follow-up. Further collapse of the femoral head did not occur. The use of MRI instead of plain radiographs for the selection of patients has improved the success rate of transtrochanteric rotational osteotomy.

Risk period for developing osteonecrosis of the femoral head in patients on steroid treatment.

Patients who require long-term steroid use are at risk for the development of osteonecrosis. However, the risk period for developing osteonecrosis of the femoral head has not yet been defined. The authors attempted to determine the onset of osteonecrosis of the femoral head following steroid treatment. Medical record data of patients with steroid-related osteonecrosis of the femoral head from four university hospitals were reviewed. Information was collected regarding the duration and dose of steroid use for patients who were diagnosed at the early stage by magnetic resonance imaging (MRI) without positive findings on plain radiographs (Association Research Circulation Osseous stage I osteonecrosis). Twenty-two patients were diagnosed at Association Research Circulation Osseous stage I. There were eight male and 14 female patients ranging in age from 17 to 60 years (mean 33). The total dose of steroid, which was used until the time of detection of osteonecrosis by MRI, ranged from 1800 to 15 505 mg prednisolone or its equivalent (mean 5928 mg). The period from the start of steroid treatment to the diagnosis by MRI ranged from 1 month to 16 months (mean 5.3 months). Twenty-one of 22 patients were diagnosed within 12 months of the initiation of steroid treatment. The duration of steroid treatment within this period ranged from 1 month to 12 months (mean 4.5 months). There may be a risk period of 12 months for developing femoral head osteonecrosis in patients receiving long-term steroid treatment. Close observation and more aggressive screening are recommended within the first year of long-term steroid treatment to prevent advanced osteonecrosis of the femoral head.

Purification and characterization of iron superoxide dismutase and copper-zinc superoxide dismutase from Acanthamoeba castellanii.

Two superoxide dismutases (SOD I and SOD II) were purified from Acanthamoeba castellanii and characterized for several biochemical properties. Analysis of the primary structure and inhibition studies revealed that SOD I is iron SOD (Fe-SOD), with a molecular mass of 50 kDa, and SOD II is copper-zinc SOD (Cu,Zn-SOD), with a molecular mass of 38 kDa. Both enzymes have a homodimeric structure consisting of 2 identical subunits, each with a molecular mass of 26 and 19 kDa for SOD I and SOD II, respectively. The isoelectric points of SOD I and SOD II were 6.4 and 3.5, respectively, and there were no isoenzyme forms detected. Both enzymes show a broad optimal pH of 7.0-11.0. Because no differences were observed in the apparent molecular weight of SOD I after addition of the reducing agent 2-mercaptoethanol, the subunits do not appear to be linked covalently by disulfide bonds. However, the subunits of SOD II were covalently linked by intra- and interdisulfide bonds. Western blot analyses showed that the 2 enzymes have different antigenicity. Both enzymes occur as cytoplasmic and detergent-extractable fractions. These enzymes may be potential virulence factors of A. castellanii by acting both as antioxidants and antiinflammatory agents. These enzymes may be attractive targets for chemotherapy and immunodiagnosis of acanthamoebiasis.

Treatment of antecubital pterygium in the nail-patella syndrome.

Antecubital pterygium is rare in the nail-patella syndrome but common in the multiple pterygium syndrome and aplasia of the trochlea. It is known that there is the rebound phenomenon after treatment of congenital joint contracture. We describe the poor functional results due to rapid recurrence of the flexion contracture treated with the Ilizarov method for an antecubital pterygium in the nail-patella syndrome.

Clubfoot analysis with three-dimensional foot models.

The purpose of this study was to develop a method of defining, in mathematical terms, the interpositional relationships of the bones of the hindfoot complex in the idiopathic clubfoot and the neurogenic clubfoot. The neurogenic clubfoot and contralateral normal-appearing foot of a stillborn infant with myelomeningocele, and the normal foot of a 10-year-old were sectioned with a cryomicrotome. Magnetic resonance images (MRIs) of the clubfoot and the normal foot of a 3-month-old boy were obtained. Using a computer program, three-dimensional foot models were generated from the digitized cryomicrotome sections and from the MRIs. The central principal axes were determined for the talus and calcaneus. The long central principal axes of the talus and calcaneus were neutrally rotated with reference to the bimalleolar axis in the idiopathic clubfoot while in the neurogenic clubfoot the long central principal axis of the talus was medially rotated 52 degrees and that of the calcaneus 10 degrees. The talocalcaneal angles defined by the long central principal axes in the superior and medial views were 0 degree and 10 degrees, respectively, in the idiopathic clubfoot, and 42 degrees and 56 degrees, respectively, in the neurogenic clubfoot.

Antibiotic-impregnated cement beads in the treatment of chronic osteomyelitis.

Fifty-four patients with chronic osteomyelitis of the long bones were treated at Gyeong-Sang National University Hospital between 1985 and 1993 using the cement bead technique. We studied the results of thirty-one patients who were followed up for 3 years or more. The average duration of follow-up was 4 years and 2 months (range: 3 to 7 years). All of the patients were treated by a two-stage operation; primary saucerization with implantation of antibiotic-impregnated polymethylmethacrylate beads and secondary bone grafts. The most recent follow-up examinations and analyses revealed that 17 patients (55%) were completely free of infection. Ten patients (32%) required repeated procedures of curettage and/or bone grafting. Amputations were performed on 4 patients.

Modified Ilizarov technique for the treatment of forearm deformities in multiple cartilaginous exostoses: case series and literature review.

The aim of this study is to evaluate the results of gradual ulnar correction and lengthening using the modified Ilizarov technique for the treatment of forearm deformities in patients with multiple cartilaginous exostoses. We retrospectively reviewed 23 forearms in 16 patients. Three different types of operative procedures were performed: (1) corrective osteotomy and gradual lengthening of the ulna, (2) corrective osteotomy of the radius, and (3) excision of exostoses. We evaluated the radiographs; range of motion of the wrist, forearm, and elbow; and functional status using a questionnaire before and after operation. During the clinical interview, post-operative functional status was significantly improved than pre-operative functional status, 12 patients stated that they had no difficulty in performing daily activities, 11 patients stated that they had no pain, and 11 patients stated that the post-operative appearance of the operated forearm was satisfactory. At time of final follow-up, the mean range of motion of the wrist in ulnar/radial deviation, forearm pronation/supination was significantly improved. Also, the radiographic parameters including radial articular angle, carpal slip, radial bowing, and ulnar variance were significantly improved at time of final follow-up. In conclusion, we achieved successful clinical and radiological outcomes in our patients with forearm deformities after treatment with the modified Ilizarov method. However, there could be a recurrence of ulnar shortening and deformity during growth periods in skeletally immature patients.

Comparison between upper and lower limb lengthening in patients with achondroplasia: a retrospective study.

Lengthening of the humerus is now an established technique. We compared the complications of humeral lengthening with those of femoral lengthening and investigated whether or not the callus formation in the humerus proceeds at a higher rate than that in the femur. A total of 24 humeral and 24 femoral lengthenings were performed on 12 patients with achondroplasia. We measured the pixel value ratio (PVR) of the lengthened area on radiographs and each radiograph was analysed for the shape, type and density of the callus. The quality of life (QOL) of the patients after humeral lengthening was compared with that prior to surgery. The complication rate per segment of humerus and femur was 0.87% and 1.37%, respectively. In the humerus the PVR was significantly higher than that of the femur. Lower limbs were associated with an increased incidence of concave, lateral and central callus shapes. Humeral lengthening had a lower complication rate than lower-limb lengthening, and QOL increased significantly after humeral lengthening. Callus formation in the humerus during the distraction period proceeded at a significantly higher rate than that in the femur. These findings indicate that humeral lengthening has an important role in the management of patients with achondroplasia.

Growth disturbance after lengthening of the lower limb and quantitative assessment of physeal closure in skeletally immature patients with achondroplasia.

This study evaluated the effect of limb lengthening on longitudinal growth in patients with achondroplasia. Growth of the lower extremity was assessed retrospectively by serial radiographs in 35 skeletally immature patients with achondroplasia who underwent bilateral limb lengthening (Group 1), and in 12 skeletally immature patients with achondroplasia who did not (Group 2). In Group 1, 23 patients underwent only tibial lengthening (Group 1a) and 12 patients underwent tibial and femoral lengthening sequentially (Group 1b). The mean lengthening in the tibia was 9.2 cm (59.5%) in Group 1a, and 9.0 cm (58.2%) in the tibia and 10.2 cm (54.3%) in the femur in Group 1b. The mean follow-up was 9.3 years (8.6 to 10.3). The final mean total length of lower extremity in Group 1a was 526.6 mm (501.3 to 552.9) at the time of skeletal maturity and 610.1 mm (577.6 to 638.6) in Group 1b, compared with 457.0 mm (411.7 to 502.3) in Group 2. However, the mean actual length, representing the length solely grown from the physis without the length of distraction, showed that there was a significant disturbance of growth after limb lengthening. In Group 1a, a mean decrease of 22.4 mm (21.3 to 23.1) (4.9%) was observed in the actual limb length when compared with Group 2, and a greater mean decrease of 38.9 mm (37.2 to 40.8) (8.5%) was observed in Group 1b when compared with Group 2 at skeletal maturity. In Group 1, the mean actual limb length was 16.5 mm (15.8 to 17.2) (3.6%) shorter in Group 1b when compared with Group 1a at the time of skeletal maturity. Premature physeal closure was seen mostly in the proximal tibia and the distal femur with relative preservation of proximal femur and distal tibia. We suggest that significant disturbance of growth can occur after extensive limb lengthening in patients with achondroplasia, and therefore, this should be included in pre-operative counselling of these patients and their parents.

High tibial osteotomy using polycaprolactone-tricalcium phosphate polymer wedge in a micro pig model.

Medial open-wedge high tibial osteotomy has been gaining popularity in recent years, but adequate supporting material is required in the osteotomy gap for early weight-bearing and rapid union. The purpose of this study was to investigate whether the implantation of a polycaprolactone-tricalcium phosphate composite scaffold wedge would enhance healing of the osteotomy in a micro pig model. We carried out open-wedge high tibial osteotomies in 12 micro pigs aged from 12 to 16 months. A scaffold wedge was inserted into six of the osteotomies while the other six were left open. Bone healing was evaluated after three and six months using plain radiographs, CT scans, measurement of the bone mineral density and histological examination. Complete bone union was obtained at six months in both groups. There was no collapse at the osteotomy site, loss of correction or failure of fixation in either group. Staining with haematoxylin and eosin demonstrated that there was infiltration of new bone tissue into the macropores and along the periphery of the implanted scaffold in the scaffold group. The CT scans and measurement of the bone mineral density showed that at six months specimens in the scaffold group had a higher bone mineral density than in the control group, although the implantation of the polycaprolactone-tricalcium phosphate composite scaffold wedge did not enhance healing of the osteotomy.