Roles of 17-AAG-induced molecular chaperones and Rma1 E3 ubiquitin ligase in folding and degradation of Pendrin

AbstractPendrin is a transmembrane chloride/anion exchanger highly expressed in thyroid, kidney, and inner ear. Endoplasmic reticulum (ER)-retention of improperly folded Pendrin mutants is considered as the major cause for Pendred syndrome. However, the folding and degradation mechanisms of Pendrin are poorly understood. Here, we report that treatment of 17-AAG, an Hsp90 inhibitor, facilitates the folding of Pendrin through heat shock transcription factor 1 (Hsf1)-dependent induction of molecular chaperones. Furthermore, we demonstrate that Rma1, an E3 ubiquitin ligase localized in the ER membrane, is involved in Pendrin degradation

Evaluation of an immunochromatographic assay for the detection of anti-hepatitis A virus IgM

<p>Abstract</p> <p>Background</p> <p>Hepatitis A virus (HAV) is a causative agent of acute hepatitis, which is transmitted by person-to-person contact and via the faecal-oral route. Acute HAV infection is usually confirmed by anti-HAV IgM detection. In order to detect anti-HAV IgM in the serum of patients infected with HAV, we developed a rapid assay based on immunochromatography (ICA) and evaluated the sensitivity of this assay by comparing it with a commercial microparticle enzyme immunoassay (MEIA) that is widely used for serological diagnosis.</p> <p>Results</p> <p>The newly developed ICA showed 100% sensitivity and specificity when used to test 150 anti-HAV IgM-positive sera collected from infected patients and 75 negative sera from healthy subjects. Also, the sensitivity of ICA is about 10 times higher than MEIA used in this study by determining end point to detect independent on infected genotype of HAV. In addition, the ICA was able to detect 1 positive sample from among 50 sera from acute hepatitis patients that had tested negative for anti-HAV IgM using the MEIA.</p> <p>Conclusion</p> <p>Conclusively, ICA for the detection of anti-HAV IgM will be very effective for rapid assay to apply clinical diagnosis and epidemiological investigation on epidemics due to the simplicity, rapidity and specificity.</p

Markedly enhanced intratumoral spread and antitumor effect of oncolytic adenovirus expressing decorin

With the aim of improving viral distribution and tumor penetration, we have engineered decorin expressing replication-incompetent (dl-LacZ-DCNG) and -competent (Ad-[DELTA]E1B-DCNG) adenoviruses. In both tumor spheroids and established solid tumors in vivo, administration of dl-LacZ-DCNG resulted in greater transduction efficiency and viral spread throughout the tumor mass. Ad-[DELTA]E1B-DCNG also enhanced viral distribution and tumor spread, leading to an increased anti-tumor effect and survival advantage. Upon histological analysis, Ad-[DELTA]E1B-DCNG also elicited greater percentage of apoptotic cells and extensive necrosis compared to those from untreated or control virus-treated tumors. Furthermore, Ad-[DELTA]E1B-DCNG substantially decreased extracellular matrix components within the tumor tissue, while normal tissue adjacent to the tumor was not affected. Finally, intratumoral administration of Ad-[DELTA]E1B-DCNG did not enhance but inhibited the formation of pulmonary metastases of B16BL6 melanoma cells in mice. Taken together, these data demonstrate the utility of decorin as a dispersion agent and suggest its utility and potential in improving the efficacy of replicating adenovirus-mediated cancer gene therapy

A plan for strengthening pediatric emergency care: establishment of pediatric certified emergency center

Pediatric patients (younger than 19 years) account for approximately 25% of all emergency patients. Pediatric patients have large proportions of toddlers (aged 1-5 years), low severity, illness (rather than injury), and after-hours visits. Considering these features, the authors, affiliated with the policy research team in the Korean Society of Pediatric Emergency Medicine, suggest the establishment of the pediatric certified emergency center (PCEC) to stratify Korean pediatric emergency medical system according to the Korean Acuity and Triage Scale (KTAS). The PCEC is a facility dedicated to the emergency care for a large population of KTAS 3-4 patients (i.e., mildly ill). In addition, the PCEC may perform early stabilization and transfer to the pediatric emergency centers for pediatric patients having KTAS 1-2 illnesses and injuries. To facilitate the application of emergency centers for the PCEC, the designation criteria should be flexible in terms of manpower, facility, and equipment. Financial support from the government is essential for sustainable PCEC

Effect of software version and parameter settings on the marginal and internal adaptation of crowns fabricated with the CAD/CAM system

Objective This study investigated the marginal and internal adaptation of individual dental crowns fabricated using a CAD/CAM system (Sirona’s BlueCam), also evaluating the effect of the software version used, and the specific parameter settings in the adaptation of crowns.Material and Methods Forty digital impressions of a master model previously prepared were acquired using an intraoral scanner and divided into four groups based on the software version and on the spacer settings used. The versions 3.8 and 4.2 of the software were used, and the spacer parameter was set at either 40 μm or 80 μm. The marginal and internal fit of the crowns were measured using the replica technique, which uses a low viscosity silicone material that simulates the thickness of the cement layer. The data were analyzed using a Friedman two-way analysis of variance (ANOVA) and paired t-tests with significance level set at

Clinical characteristics of acute drug-induced dystonia in pediatric patients

Objecstonia is a movement disorder in which muscles contract uncontrollably. Acute drug-induced dystonia (DID) can be diagnosed through detailed history taking and physical examination. This study aimed to identify the clinical characteristics of DID in children, which could help emergency physicians diagnose these conditions more efficiently. Methods We reviewed medical rtive Dyecords of children aged below 18 years diagnosed with drug-related dystonia after discharge from the emergency department over 10 years. We collected the patients’ age, sex, suspected causative drugs, initial diagnosis of the prescribing physician, duration of drug-taking, diagnostic evaluations, treatment methods, and prognosis. Results Seventy-nine patients were enrolled. The mean age was 11.3±4.9 years (range, 4.0 months to 18.0 years), and 41 patients (51.9%) were boys. The most common cause of DID was gastrointestinal medications in 45 patients (57.0%), followed by antipsychotics in 23 patients (29.1%). Eleven (24.4%) out of 45 patients with DID due to gastrointestinal medications had the initial diagnosis of upper respiratory infection, and seven (30.4%) out of 23 patients with DID due to antipsychotics had the initial diagnosis of non-psychotic diseases. Younger children received more diagnostic procedures and were more frequently admitted. A benzodiazepine (67.1%) was the most common single drug for treatment. Conclusion Physicians should not only acknowledge DID in order to reduce unnecessary workup and admission, but also know that antiemetics and antipsychotics are common causes of DID. Therefore, physicians should try to avoid multidrug prescriptions in children

Removal of Blunt Esophageal Foreign Body Using Foley Catheter in Children

Purpose Foreign body ingestion is a common cause for children to visit the emergency department. Removal of esophageal foreign body was usually done by an endoscopy. After Bigler introduced the Foley catheter technique for esophageal foreign body in 1966, many studies were performed regarding such technique. However, only a few researchers in Korea have attempted to report this technique. This study reports a 10-year experience of the Foley catheter removal method for blunt esophageal foreign body at a single center in Korea. Methods Medical records of patients who were treated as esophageal foreign body with Foley catheters between March 2005 and February 2015 were retrospectively reviewed. Their clinical characteristics and outcomes were evaluated. Results A total of 73 patients were treated as esophageal foreign body impaction using the Foley catheter method. Foreign body removals were successful in 67 (91.8%) cases. Six failed cases were treated with esophagoscopy or endoscopy. The mean age was 3.7 years old. The most common foreign body was a coin (80.8%). Foreign bodies were lodged at the upper esophagus level most frequently (79.5%), followed by the middle esophagus (12.3%) and the lower esophagus (6.8%). During the removal procedure, 43.8% of patients were sedated, and 95.9% were treated with fluoroscopy. There were no positive correlations between the removal success and sedation (P=0.54) or using a fluoroscopy (P=0.23). In 69 cases (94.5%), there were no serious complications. However, in one patient, complications, such as vomiting, fever, and esophageal ulceration were observed. One patient complained fever and esophageal ulceration. In 3 (60%) of the total 5 patients with button battery ingestion, serious complications, such as fever or esophageal ulceration, occurred. Conclusion Removal of blunt esophageal foreign body using a Foley catheter in children is a useful and relatively safe method. However, patients with button battery ingestion need more attention when trying the Foley catheter removal technique

Regulation of acetate tolerance by small ORF-encoded polypeptides modulating efflux pump specificity in Methylomonas sp. DH-1

Abstract Background Methanotrophs have emerged as promising hosts for the biological conversion of methane into value-added chemicals, including various organic acids. Understanding the mechanisms of acid tolerance is essential for improving organic acid production. WatR, a LysR-type transcriptional regulator, was initially identified as involved in lactate tolerance in a methanotrophic bacterium Methylomonas sp. DH-1. In this study, we investigated the role of WatR as a regulator of cellular defense against weak organic acids and identified novel target genes of WatR. Results By conducting an investigation into the genome-wide binding targets of WatR and its role in transcriptional regulation, we identified genes encoding an RND-type efflux pump (WatABO pump) and previously unannotated small open reading frames (smORFs), watS1 to watS5, as WatR target genes activated in response to acetate. The watS1 to watS5 genes encode polypeptides of approximately 50 amino acids, and WatS1 to WatS4 are highly homologous with one predicted transmembrane domain. Deletion of the WatABO pump genes resulted in decreased tolerance against formate, acetate, lactate, and propionate, suggesting its role as an efflux pump for a wide range of weak organic acids. WatR repressed the basal expression of watS genes but activated watS and WatABO pump genes in response to acetate stress. Overexpression of watS1 increased tolerance to acetate but not to other acids, only in the presence of the WatABO pump. Therefore, WatS1 may increase WatABO pump specificity toward acetate, switching the general weak acid efflux pump to an acetate-specific efflux pump for efficient cellular defense against acetate stress. Conclusions Our study has elucidated the role of WatR as a key transcription factor in the cellular defense against weak organic acids, particularly acetate, in Methylomonas sp. DH-1. We identified the genes encoding WatABO efflux pump and small polypeptides (WatS1 to WatS5), as the target genes regulated by WatR for this specific function. These findings offer valuable insights into the mechanisms underlying weak acid tolerance in methanotrophic bacteria, thereby contributing to the development of bioprocesses aimed at converting methane into value-added chemicals.This work was supported by C1 gas refinery program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (MSIT) (2016M3D3A01913245)