Correlation of DEFA1 Gene Copy Number Variation with Intestinal Involvement in Behcet's Disease

Copy number variation has been associated with various autoimmune diseases. We investigated the copy number (CN) of the DEFA1 gene encoding α-defensin-1 in samples from Korean individuals with Behcet's disease (BD) compared to healthy controls (HC). We recruited 55 BD patients and 35 HC. A duplex Taqman® real-time PCR assay was used to assess CN. Most samples (31.1%) had a CN of 5 with a mean CN of 5.4 ± 0.2. There was no significant difference in the CN of the DEFA1 gene between BD patients and HC. A high DEFA1 gene CN was significantly associated with intestinal involvement in BD patients. Variable DEFA1 gene CNs were observed in both BD patients and HC and a high DEFA1 gene CN may be associated with susceptibility to intestinal involvement in BD

Is Ex Vivo Training before In Vivo Training Effective in Learning Gastric Endoscopic Submucosal Dissection?

Background/Aims The learning curve is essential in endoscopic submucosal dissection (ESD) training to improve outcomes and reduce the risk of procedure-related complications. We compared the outcomes of gastric ESD in live pigs performed by inexperienced endoscopists with or without ex vivo training. Materials and Methods At the Olympus Medical Training and Education Center, nine endoscopists inexperienced in ESD were randomly divided into two groups (group A: ex vivo training followed by in vivo training; group B: in vivo training only), and they performed gastric ESDs. Results A total of 18 ESDs were performed. The en bloc resection rate was 88.9% (16/18), and the complete resection rate was 94.4% (17/18). The median specimen size was 2.5 cm in group A and 2.1 cm in group B (P=0.227). There was no significant difference in the procedure time between the two groups, except for the marking time (0′58″ vs. 2′58″, P=0.027). However, group A took a shorter time in dissecting the same area than group B (109 vs. 246 sec/cm2, P=0.083). Complication rates were not significantly different between both groups. Conclusions The procedure time during in vivo ESD training in pigs may be shortened by prior ex vivo training. However, the ex vivo model presented poor air inflation, unstable fixation, and excessive mucosal hardness for cutting. An advanced simulator or sufficient ex vivo training may be effective in training for the ESD procedure

Extracellular High-Mobility Group Box 1 is Increased in Patients with Behçet's Disease with Intestinal Involvement

High-mobility group box 1 (HMGB1) protein has been demonstrated to play an important role in chronic inflammatory diseases including rheumatoid arthritis, and systemic lupus erythematosus. This study investigated the association between extracellular HMGB1 expression and disease activity, and clinical features of Behçet's disease (BD). Extracellular HMGB1 expression in the sera of 42 BD patients was measured and was compared to that of 22 age- and sex-matched healthy controls. HMGB1 expression was significantly increased in BD patients compared to healthy controls (78.70 ± 20.22 vs 10.79 ± 1.90 ng/mL, P = 0.002). In addition, HMGB1 expression was significantly elevated in BD patients with intestinal involvement compared to those without (179.61 ± 67.95 vs 61.89 ± 19.81 ng/mL, P = 0.04). No significant association was observed between HMGB1 concentration and other clinical manifestations, or disease activity. It is suggested that extracellular HMGB1 may play an important role in the pathogenesis of BD

Perinatal Outcome in Twin Pregnancies Complicated by Gestational Diabetes Mellitus: A Comparative Study

The purpose of this study is to compare perinatal outcomes of twin pregnancies complicated by gestational diabetes (GDM) with those unaffected by GDM. A total of 1,154 twin pregnancies who delivered at Cheil General Hospital, between January 1998 and December 2002 were recruited to participate in a retrospective analysis. Out of these twin pregnancies, 37 women were had GDM. Four pregnancies exposed to GDM were excluded due to the loss of medical records; therefore 33 twin pregnancies exposed to GDM were enrolled. We matched the GDM pregnancies with pregnancies unaffected by GDM in a 1:2 ratio; therefore there were 33 GDM/66 without GDM who delivered during the study period. Our findings show that there were no significant differences including birth weight, Apgar score, respiratory distress syndrome, meconium aspiration pneumonia, transient tachypnea of new born, hyperbilirubinemia, hypoglycemia, hypocalcemia and congenital anomalies. Therefore, well controlled GDM may not increase perinatal complications in twin pregnancies. Careful pregnancy management and fetal surveillance in twin pregnancies is important to decrease perinatal complications and maintain a sound pregnancy and healthy offspring

Molecular diagnosis of hereditary spherocytosis by multi-gene target sequencing in Korea: matching with osmotic fragility test and presence of spherocyte

Background Current diagnostic tests for hereditary spherocytosis (HS) focus on the detection of hemolysis or indirectly assessing defects of membrane protein, whereas direct methods to detect protein defects are complicated and difficult to implement. In the present study, we investigated the patterns of genetic variation associated with HS among patients clinically diagnosed with HS. Methods Multi-gene targeted sequencing of 43 genes (17 RBC membrane protein-encoding genes, 20 RBC enzyme-encoding genes, and six additional genes for the differential diagnosis) was performed using the Illumina HiSeq platform. Results Among 59 patients with HS, 50 (84.7%) had one or more significant variants in a RBC membrane protein-encoding genes. A total of 54 significant variants including 46 novel mutations were detected in six RBC membrane protein-encoding genes, with the highest number of variants found in SPTB (n = 28), and followed by ANK1 (n = 19), SLC4A1 (n = 3), SPTA1 (n = 2), EPB41 (n = 1), and EPB42 (n = 1). Concurrent mutations of genes encoding RBC enzymes (ALDOB, GAPDH, and GSR) were detected in three patients. UGT1A1 mutations were present in 24 patients (40.7%). Positive rate of osmotic fragility test was 86.8% among patients harboring HS-related gene mutations. Conclusions This constitutes the first large-scaled genetic study of Korean patients with HS. We demonstrated that multi-gene target sequencing is sensitive and feasible that can be used as a powerful tool for diagnosing HS. Considering the discrepancies of clinical and molecular diagnoses of HS, our findings suggest that molecular genetic analysis is required for accurate diagnosis of HS.Support was provided by: the National Research Foundation of Korea (NRF) grant funded by the Korea government(MSIT) (NRF-2017R1A2A1A17069780) http://www.nrf.re.kr/

Urinary Metabolomic Profiling to Identify Potential Biomarkers for the Diagnosis of Behcet’s Disease by Gas Chromatography/Time-of-Flight−Mass Spectrometry

Diagnosing Behcet’s disease (BD) is challenging because of the lack of a diagnostic biomarker. The purposes of this study were to investigate distinctive metabolic changes in urine samples of BD patients and to identify urinary metabolic biomarkers for diagnosis of BD using gas chromatography/time-of-flight–mass spectrometry (GC/TOF−MS). Metabolomic profiling of urine samples from 44 BD patients and 41 healthy controls (HC) were assessed using GC/TOF−MS, in conjunction with multivariate statistical analysis. A total of 110 urinary metabolites were identified. The urine metabolite profiles obtained from GC/TOF−MS analysis could distinguish BD patients from the HC group in the discovery set. The parameter values of the orthogonal partial least squared-discrimination analysis (OPLS-DA) model were R2X of 0.231, R2Y of 0.804, and Q2 of 0.598. A biomarker panel composed of guanine, pyrrole-2-carboxylate, 3-hydroxypyridine, mannose, l-citrulline, galactonate, isothreonate, sedoheptuloses, hypoxanthine, and gluconic acid lactone were selected and adequately validated as putative biomarkers of BD (sensitivity 96.7%, specificity 93.3%, area under the curve 0.974). OPLS-DA showed clear discrimination of BD and HC groups by a biomarker panel of ten metabolites in the independent set (accuracy 88%). We demonstrated characteristic urinary metabolic profiles and potential urinary metabolite biomarkers that have clinical value in the diagnosis of BD using GC/TOF−MS