PURPOSE: About 10% of all gastric cancers (GCs) are Epstein-Barr virus (EBV)-associated. However, the oncogene of EBV in gastric carcinogenesis has not yet been established. In the present study, we investigated the virus-derived transcripts in the EBV-infected GC cell line to explore the viral oncogene of EBV-positive GCs. MATERIALS AND METHODS: We used the SNU719 cell line, a naturally derived EBV-infected GC cell line. The individual expressed sequence tags from the cDNA libraries of SNU719 were searched against the mRNA subset extracted from the GenBank data base. Sequence reaction was carried out for the EBV-associated clones. Reverse transcription-polymerase chain reaction was performed after cells were partitioned into nuclear and cytoplasmic fractions. RESULTS: Using bioinformatic tools, we selected 13 EBV-associated clones from cDNA libraries of SNU719. By sequencing analysis, we revealed that they were all associated with RPMS1, one of the BamHI-A rightward transcripts (BART) of EBV. Some BART cDNAs such as RPMS1 and A73 are known to be translated into protein in vitro, and have been shown to have some biochemical functions relevant to tumorigenesis. But, presently, the BART transcripts were expressed only in the nucleus and not in the cytoplasm, arguing against their role as messenger RNAs. Some other BART transcripts expressed in GCs (BARF0, CST, vIL, BARF1, BLLF1, and BcLF1) were also extensively detected in the nucleus. CONCLUSION: BART transcripts are the predominant viral transcripts expressed in EBV-associated GCs, and they are located only in the nucleus. Therefore, it seems less likely that BART transcripts produce functional proteins to play a role in carcinogenesis of EBV-associated GCs.
Cell Line ; Cell Transformation, Neoplastic ; Clone Cells ; Cytoplasm ; Databases, Nucleic Acid ; DNA, Complementary ; Expressed Sequence Tags ; Gene Library ; Herpesvirus 4, Human ; Oncogenes ; Proteins ; RNA, Messenger ; Stomach Neoplasms

BACKGROUND: A receptor tyrosine kinase for ephrin ligands, EPHB2, is expressed in normal colorectal tissues and colorectal cancers (CRCs). The aim of this study was to investigate EPHB2 expression over CRC progression and determine its prognostic significance in CRC. METHODS: To measure EPHB2 mRNA and protein expression, real-time polymerase chain reaction and immunohistochemistry were performed in 32 fresh-frozen and 567 formalin-fixed paraffin-embedded CRC samples, respectively. We further investigated clinicopathological features and overall and recurrence-free survival according to EPHB2 protein expression. RESULTS: The EPHB2 level was upregulated in CRC samples compared to non-cancerous tissue in most samples and showed a strong positive correlation with AXIN2. Notably, CD44 had a positive association with both mRNA and protein levels of EPHB2. Immunohistochemical analysis revealed no difference in EPHB2 expression between adenoma and carcinoma areas. Although EPHB2 expression was slightly lower in invasive fronts compared to surface area (p < .05), there was no difference between superficial and metastatic areas. EPHB2 positivity was associated with lymphatic (p < .001) and venous (p = .001) invasion, TNM stage (p < .001), and microsatellite instability (p = .036). Kaplan–Meier analysis demonstrated that CRC patients with EPHB2 positivity showed better clinical outcomes in both overall (p = .049) and recurrence-free survival (p = .015). However, multivariate analysis failed to show that EPHB2 is an independent prognostic marker in CRCs (hazard ratio, 0.692; p = .692). CONCLUSIONS: Our results suggest that EPHB2 is overexpressed in a subset of CRCs and is a significant prognostic marker.
Adenoma ; Colorectal Neoplasms ; Humans ; Immunohistochemistry ; Ligands ; Microsatellite Instability ; Multivariate Analysis ; Prognosis ; Protein-Tyrosine Kinases ; Real-Time Polymerase Chain Reaction ; Receptor, EphB2 ; RNA, Messenger

OBJECTIVE: Water-tight closure of the dura in extracranial-intracranial (EC-IC) bypass is impossible because the superficial temporal artery (STA) must run through the dural defect. Consequently, subdural hygroma and subcutaneous cerebrospinal fluid (CSF) collection frequently occur postoperatively. To reduce these complications, we prospectively performed suturing of the arachnoid membrane after STA-middle cerebral artery (STA-MCA) and evaluated the clinical usefulness. MATERIALS AND METHODS: Between Mar. 2005 and Oct. 2010, extracranial-intracranial arterial bypass (EIAB) with/without encephalo-myo-synangiosis was performed in 88 cases (male : female = 53 : 35). As a control group, 51 patients (57 sides) underwent conventional bypass surgery without closure of the arachnoid membrane. Postoperative computed tomography (CT) scan was performed twice in three days and seven days later, respectively, for evaluation of the presence of subdural fluid collection and other mass lesions. RESULTS: The surgical result was excellent, with no newly developing ischemic event until recent follow-up. The additional time needed for arachnoid suture was five to ten minutes, when three to eight sutures were required. Post-operative subdural fluid collection was not seen on follow-up computed tomography scans in all patients. CONCLUSION: Arachnoid suturing is simple, safe, and effective for prevention of subdural fluid collection in EC-IC bypass surgery, especially the vulnerable ischemic hemisphere.
Arachnoid* ; Cerebral Arteries ; Cerebral Revascularization ; Cerebrospinal Fluid ; Female ; Follow-Up Studies ; Humans ; Membranes* ; Prospective Studies ; Subdural Effusion ; Sutures ; Temporal Arteries

BACKGROUND: During specimen processing in surgical pathology laboratories, specimen-related adverse events (SRAEs), such as mislabeling and specimen mixed-up might occur. In these situations, molecular techniques using short tandem repeat (STR) loci are required to identify the personal identity. Microsatellite instability (MSI) test is widely used for screening the hereditary non-polyposis colon cancer (Lynch syndrome) in surgical pathologies using polymorphic STR markers. We tried to evaluate the applicability of the MSI test for SRAEs. METHODS: We obtained 253 MSI test results to analyze the allele frequencies. After calibrating the estimated nucleotide lengths, we calculated the allele frequencies, a random match probability, and a likelihood ratio (LR) of three dinucleotide STR markers (D5S349, D17S250, and D2S123). RESULTS: The distribution of LR was 136.38 to 5,606,213.10. There was no case of LR<100. In addition, there were 153 cases (60.5%) of LR ranging from 100 to 10,000 and 100 cases (39.5%) of LR>10,000. Furthermore, the combined probability of identity was 9.23x10(-4) and the combined power of exclusion was 0.99908. CONCLUSIONS: Using the three STR markers that are recommended for MSI test, all the cases were positively identified in 1% range and about one-third cases showed high LR (>10,000). These results showed that MSI tests are useful to screen the personal identity in case of SRAE in pathology laboratories.
Biometric Identification ; Colonic Neoplasms ; Colorectal Neoplasms, Hereditary Nonpolyposis ; Gene Frequency ; Humans ; Mass Screening ; Microsatellite Instability ; Microsatellite Repeats ; Pathology, Surgical ; Succinimides

BACKGROUND: Cardiovascular disease is the leading cause of death in patients with type 2 diabetes. Clinically, evaluating cardiovascular autonomic neuropathy (CAN) is important to predict cardiovascular mortality because it is correlated with cardiovascular death. The pulse wave velocity (PWV) correlates well with arterial distensibility and stiffness. It is also a useful approach for evaluating the severity of systemic atherosclerosis in adults. So, we evaluated that the relationship between cardiac autonomic neuropathy and the brachial-ankle pulse wave velocity (baPWV) in patients with type 2 diabetes. METHODS: We retrospectively analyzed 465 patients (209 men and 256 women) with type 2 diabetes. We checked the clinical characteristics and the laboratory tests and we assessed the diabetic complications. Standard tests for CAN were performed by DiCAN (Medicore, Seoul, Korea): 1) heart rate variability during deep breathing (the E/I ratio), 2) a Valsalva maneuver, 3) 30:15 ratio of R-R interval the blood pressure response to standing, and 5) the blood pressure response to handgrip. The CAN score was determined according to the results of the test as following: 0 = normal, 0.5 = borderline, 1 = abnormal. We also measured the baPWV by using a VP 1000 (Colin, Japan) and all the analyses were performed with the SPSS version 14.0. P values < 0.05 were considered significant. RESULTS: The CAN score is associated with the maximal baPWV, age, systolic blood pressure, microalbuminuria, the duration of diabetes, angiotensin II receptor blocker treatment, calcium channel blocker treatment, beta-blocker treatment and nephropathy. After adjusting for age, the baPWV is a independent predictor of the risk for CAN (beta = 0.108, P = 0.021). CONCLUSION: The CAN is associated with the baPWV in patient with type 2 diabetes.
Adult ; Atherosclerosis ; Blood Pressure ; Calcium Channels ; Cardiovascular Diseases ; Cause of Death ; Diabetes Complications ; Heart Rate ; Humans ; Male ; Pulse Wave Analysis ; Receptors, Angiotensin ; Respiration ; Retrospective Studies ; Valsalva Maneuver

Background and Objectives: This work investigates the clinical characteristics of benign paroxysmal positional vertigo (BPPV) according to etiology by comparing idiopathic BPPV (iBPPV), BPPV occurring after head trauma (tBPPV) and BPPV associated with idiopathic sudden sensory neural hearing loss (sBPPV).Subjects and Method A total of 869 patients who were diagnosed and treated for BPPV were reviewed retrospectively. Patients were divided into three groups according to the probable etiology of BPPV: iBPPV vs. tBPPV vs. sBPPV. We investigated and compared demographics, the affected sides and canals, the number of canalith repositioning procedure (CRP) performed to achieve successful reposition, canal conversion and recurrence among the three groups. Among the three groups, BPPV patients who performed caloric test and/or video head impulse test (vHIT) were additionally evaluated and compared. Results: The iBPPV group (n=787) had greater female preponderance (72%, 567/787) than the tBPPV (n=51) and sBPPV groups (n=31, p<0.001). The mean number of CRPs needed for successful repositioning in the iBPPV group (1.40±0.03) was significantly (p<0.001) lower than that in the tBPPV and sBPPV groups (2.04±0.24 and 2.45±0.36). There was no difference between the tBPPV and sBPPV groups. Recurrence rate was not significantly different among three groups (14.6% vs. 17.7% vs. 16.2%) statistically. The presence of canal paresis and abnormal results of vHIT test were not related with a greater number of CRPs required and recurrence. Conclusion More CRPs were required for successful repositioning in the tBPPV and sBPPV patients than in the iBPPV patients and there was no difference between tBPPV and sBPPV patients. Recurrence rate was not different among the three groups. This information may be helpful for clinicians in counselling and managing BPPV patients.

BACKGROUND/AIMS: We evaluated the characteristics of the National Cancer Screening Program (NCSP) and opinions regarding the National Endoscopy Quality Improvement Program (NEQIP). METHODS: We surveyed physicians performing esophagogastroduodenoscopy and/or colonoscopy screenings as part of the NCSP via e-mail between July and August in 2015. The 32-item survey instrument included endoscopic capacity, sedation, and reprocessing of endoscopes as well as opinions regarding the NEQIP. RESULTS: A total of 507 respondents were analyzed after the exclusion of 40 incomplete answers. Under the current capacity of the NCSP, the typical waiting time for screening endoscopy was less than 4 weeks in more than 90% of endoscopy units. Performance of endoscopy reprocessing was suboptimal, with 28% of respondents using unapproved disinfectants or not knowing the main ingredient of their disinfectants and 15% to 17% of respondents not following reprocessing protocols. Agreement with the NEQIP was optimal, because only 5.7% of respondents did not agree with NEQIP; however, familiarity with the NEQIP was suboptimal, because only 37.3% of respondents were familiar with the NEQIP criteria. CONCLUSIONS: The NEQ-IP remains suboptimal in Korea. Given the suboptimal performance of endoscopy reprocessing and low familiarity with the NEQIP, improved quality in endoscopy reprocessing and better understanding of the NEQIP should be emphasized in Korea.
Colonoscopy ; Colorectal Neoplasms ; Disinfectants ; Early Detection of Cancer ; Electronic Mail ; Endoscopes ; Endoscopy* ; Endoscopy, Digestive System ; Korea* ; Mass Screening ; Quality Improvement* ; Recognition (Psychology) ; Stomach Neoplasms ; Surveys and Questionnaires

The purpose of this study was to investigate the long-term clinical course of non-specific interstitial pneumonia (NSIP) and to determine which factors are associated with a response to steroid therapy and relapse. Thirty-five patients with pathologically proven NSIP were included. Clinical, radiological, and laboratory data were reviewed retrospectively. The male-to-female ratio was 7:28 (median age, 52 yr). Thirty (86%) patients responded to steroid therapy, and the median follow-up was 55.2 months (range, 15.9-102.0 months). Five patients (14%) showed sustained disease progression and three died despite treatment. In the five with sustained disease progression, NSIP was associated with various systemic conditions, and the seropositivity of fluorescent antinuclear antibody was significantly associated with a poor response to steroids (P = 0.028). The rate of relapse was 25%, but all relapsed patients improved after re-treatment. The initial dose of steroids was significantly low in the relapse group (P = 0.020). In conclusion, progression is associated with various systemic conditions in patients who show progression. A low dose of initial steroids is significantly associated with relapse.
Adult ; Aged ; Antibodies, Antinuclear/blood ; Female ; Follow-Up Studies ; Humans ; Idiopathic Interstitial Pneumonias/drug therapy/pathology ; Lung Diseases, Interstitial/*drug therapy/mortality/pathology ; Male ; Middle Aged ; Prognosis ; Recurrence ; Retrospective Studies ; Steroids/*therapeutic use

BACKGROUND/AIMS: In Korea, the nationwide gastric cancer screening program recommends biennial screening for individuals aged 40 years or older by way of either an upper gastrointestinal series or endoscopy. The national endoscopic quality assessment (QA) program began recommending endoscopy in medical institutions in 2009. We aimed to assess the effect, burden, and cost of the QA program from the viewpoint of medical institutions. METHODS: We surveyed the staff of institutional endoscopic units via e-mail. RESULTS: Staff members from 67 institutions replied. Most doctors were endoscopic specialists. They responded as to whether the QA program raised awareness for endoscopic quality (93%) or improved endoscopic practice (40%). The percentages of responders who reported improvements in the diagnosis of gastric cancer, the qualifications of endoscopists, the quality of facilities and equipment, endoscopic procedure, and endoscopic reprocessing were 69%, 60%, 66%, 82%, and 75%, respectively. Regarding reprocessing, many staff members reported that they had bought new automated endoscopic preprocessors (3%), used more disinfectants (34%), washed endoscopes longer (28%), reduced the number of endoscopies performed to adhere to reprocessing guidelines (9%), and created their own quality education programs (59%). Many responders said they felt that QA was associated with some degree of burden (48%), especially financial burden caused by purchasing new equipment. Reasonable quality standards (45%) and incentives (38%) were considered important to the success of the QA program. CONCLUSIONS: Endoscopic quality has improved after 5 years of the mandatory endoscopic QA program.
Diagnosis ; Disinfectants ; Education ; Electronic Mail ; Endoscopes ; Endoscopy ; Korea* ; Mass Screening ; Motivation ; Specialization ; Stomach Neoplasms

BACKGROUND: While there is an evidence that the anti-inflammatory properties of spironolactone can attenuate proteinuria in type 2 diabetes, its effects on vascular endothelial growth factor (VEGF) expression in diabetic nephropathy have not been clearly defined. In this study, we examined the effects of spironolactone, losartan, and a combination of these two drugs on albuminuria, renal VEGF expression, and inflammatory and oxidative stress markers in a type 2 diabetic rat model. METHODS: Thirty-three Otsuka-Long-Evans-Tokushima-Fatty (OLETF) rats were divided into four groups and treated with different medication regimens from weeks 25 to 50; OLETF diabetic controls (n=5), spironolactone-treated (n=10), losartan-treated (n=9), and combination of spironolactone- and losartan-treated (n=9). RESULTS: At week 50, the albumin-to-creatinine ratio was significantly decreased in the losartan and combination groups compared to the control OLETF group. No decrease was detected in the spironolactone group. There was a significant reduction in renal VEGF, transforming growth factor (TGF)-beta, and type IV collagen mRNA levels in the spironolactone- and combination regimen-treated groups. Twenty-four hour urine monocyte chemotactic protein-1 levels were comparable in all four groups but did show a decreasing trend in the losartan and combination regimen groups. Twenty-four hour urine malondialdehyde levels were significantly decreased in the spironolactone- and combination regimen-treated groups. CONCLUSION: These results suggest that losartan alone and a combined regimen of spironolactone and losartan could ameliorate albuninuria by reducing renal VEGF expression. Also, simultaneous treatment with spironolactone and losartan may have protective effects against diabetic nephropathy by decreasing TGF-beta and type IV collagen expression and by reducing oxidative stress in a type 2 diabetic rat model.
Albuminuria ; Animals ; Chemokine CCL2 ; Collagen Type IV ; Diabetic Nephropathies ; Losartan ; Malondialdehyde ; Oxidative Stress ; Proteinuria ; Rats ; RNA, Messenger ; Spironolactone ; Transforming Growth Factor beta ; Transforming Growth Factors ; Vascular Endothelial Growth Factor A