Background: Charcot-Marie-Tooth disease type 1A (CMT1A) is caused by duplication of the 17p12 region including PMP22 gene. In CMT1A patients, anticipation showing increased severity by generations has been reported in the CMT1A patients. It has also been reported that severity increases in the non-de novo cases than in the de novo cases. This study was performed to examine epigenetic differences between CMT1A cases and controls as well as between de novo cases and non-de novo cases. Methods: This study examined 40 Korean CMT1A patients and 11 controls. Methylation level was determined using the SureSelect XT Methyl-Seq reagent kit and bisulfite sequence mapping program. Results: Many differentially methylated CpG sites (DMCs) were identified in the comparisonbetween cases and controls and between de novo cases and non-de novo cases. Most DMCs were located within or nearby genes related to the nervous system, mental stress, and motor ability. Conclusions This study is the first epigenetic study to uncover the mechanism of clinical heterogeneity among CMT1A patients. We suggest that weak severity in the de novo cases than the non-de novo cases may be related to the epigenomic differences in the nerve and stress-related genes.

Purpose: Junctional adhesion molecule (JAM)-A is an immunoglobulin-like molecule that colocalizes with tight junctions (TJs) in the endothelium and epithelium. It is also found in blood leukocytes and platelets. The biological significance of JAM-A in asthma, as well as its clinical potential as a therapeutic target, are not well understood. The aim of this study was to elucidate the role of JAM-A in a mouse model of asthma, and to determine blood levels of JAM-A in asthmatic patients. Materials and Methods: Mice sensitized and challenged with ovalbumin (OVA) or saline were used to investigate the role of JAM-A in the pathogenesis of bronchial asthma. In addition, JAM-A levels were measured in the plasma of asthmatic patients and healthy controls. The relationships between JAM-A and clinical variables in patients with asthma were also examined. Results: Plasma JAM-A levels were higher in asthma patients (n=19) than in healthy controls (n=12). In asthma patients, the JAM-A levels correlated with forced expiratory volume in 1 second (FEV1%), FEV1/forced vital capacity (FVC), and the blood lymphocyte proportion. JAM-A, phospho-JNK, and phospho-ERK protein expressions in lung tissue were significantly higher in OVA/OVA mice than in control mice. In human bronchial epithelial cells treated with house dust mite extracts for 4 h, 8 h, and 24 h, the JAMA, phospho-JNK, and phospho-ERK expressions were increased, as shown by Western blotting, while the transepithelial electrical resistance was reduced. Conclusion These results suggest that JAM-A is involved in the pathogenesis of asthma, and may be a marker for asthma.

BACKGROUND/AIMS: Helicobacter pylori (H. pylori) treatments fail at least in 10-20% of patients. However, retreatment strategies after failure of initial treatment have not been established. This study was conducted to evaluate the eradication rate of retreatment choices. METHODS: Twenty-seven peptic ulcer patients who were retreated with OAC (omeprazole + amoxicillin + clarithromycin) or BMT (bismuth + metronidazole + tetracycline) after failure of BMT or OAC were included. Quadruple therapy (omeprazole + BMT) was also tried after failure of two successive triple therapies. Furthermore, the effect of resistance of metronidazole or clarithromycin on the eradication of H. pylori was evaluated. RESULTS: Among 13 patients who were retreated with OAC after failure of BMT regimen, H. pylori was eradicated in 10 patients (76.9%). Among 14 patients retreated with BMT after failure of OAC regimen, H. pylori was eradicated in 11 patients (78.6%). Resistance of H. pylori to metronidazole or clarithromycin decreased the efficacy of BMT or OAC, respectively. CONCLUSIONS: Eradication regimen should be decided considering the resistance to H. pylori. However, in case of unknown state of resistance, OAC can be chosen if BMT fails. Similarly, BMT can be tried in cases that OAC therapy failed. After failures of both triple therapies, quadruple therapy can be tried as the next step.
Adult ; Anti-Bacterial Agents/*administration & dosage ; Anti-Ulcer Agents/*administration & dosage ; Drug Therapy, Combination ; Helicobacter Infections/*drug therapy ; *Helicobacter pylori ; Humans ; Male ; Middle Aged ; Peptic Ulcer/*drug therapy/microbiology ; Retreatment