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Background: The level of pollen in Korea has increased over recent decades. Research suggests that oral allergy syndrome (OAS) may be more frequent in childhood than previously recognized. We aimed to investigate the prevalence and characteristics of OAS in children aged 6–10 years from a general‐population‐based birth cohort. Methods: We analyzed 930 children from the cohort for childhood origin of asthma and allergic diseases (COCOA). Allergic diseases were diagnosed annually by pediatric allergists. The skin prick tests were performed with 14 common inhalant allergens and four food allergens for the general population of children aged 3 and 7 years. Results: Of the 930 eligible children, 44 (4.7%) aged 6–10 years were diagnosed with OAS. The mean age at onset was 6.74 years. OAS prevalence was 7.2% among children with allergic rhinitis (AR) and 19.1% among those with pollinosis, depending on comorbidity. OAS was more prevalent in schoolchildren with atopic dermatitis, food allergy, and sensitization to food allergens and grass pollen in early childhood. In schoolchildren with AR, only a history of food allergy until the age of 3 years increased the risk of OAS (aOR 2.971, 95% CI: 1.159–7.615). Conclusion: Food allergy and food sensitization in early childhood were associated with OAS in schoolchildren with AR. Further study is required to elucidate the mechanism by which food allergy in early childhood affects the development of OAS. [ABSTRACT FROM AUTHOR]

Idiopathic hypogonadotropic hypogonadism (IHH) comprises a group of rare genetic disorders characterized by pubertal failure caused by gonadotropin‐releasing hormone (GnRH) deficiency. Genetic factors involved in semaphorin/plexin signaling have been identified in patients with IHH. PlexinB1, a member of the plexin family receptors, serves as the receptor for semaphorin 4D (Sema4D). In mice, perturbations in Sema4D/PlexinB1 signaling leads to improper GnRH development, highlighting the importance of investigating PlexinB1 mutations in IHH families. In total, 336 IHH patients (normosmic IHH, n = 293 and Kallmann syndrome, n = 43) from 290 independent families were included in the present study. Six PLXNB1 rare sequence variants (p.N361S, p.V608A, p.R636C, p.V672A, p.R1031H, and p.C1318R) are described in eight normosmic IHH patients from seven independent families. These variants were examined using bioinformatic modeling and compared to mutants reported in PLXNA1. Based on these analyses, the variant p.R1031H was assayed for alterations in cell morphology, PlexinB1 expression, and migration using a GnRH cell line and Boyden chambers. Experiments showed reduced membrane expression and impaired migration in cells expressing this variant compared to the wild‐type. Our results provide clinical, genetic, molecular/cellular, and modeling evidence to implicate variants in PLXNB1 in the etiology of IHH. [ABSTRACT FROM AUTHOR]

Background: The effect of diet on allergic rhinitis (AR), its severity in children, and whether it modifies AR depending on genetic susceptibility are unknown. We investigated the association between dietary patterns and AR in school children and the influence of diet on AR according to a genetic risk score (GRS). Methods: Totally, 435 7‐year‐old school children were recruited from the Panel Study on Korean Children. We used dietary patterns (vegetable, sugar, and meat) and dietary inflammatory index (DII) as dietary parameters. AR and its severity were defined by questionnaires about treatment in the previous 12 months and the Allergic Rhinitis and its Impact on Asthma (ARIA) guideline, respectively. A GRS was calculated using 6 single nucleotide polymorphisms for allergic diseases. Results: A vegetable diet containing a lot of anti‐inflammatory nutrients and higher vitamin D level in blood were negatively correlated, while DII was positively correlated with triglyceride level and triglyceride/HDL cholesterol. Vegetable diet (aOR, 95% CI = 0.73, 0.58‐0.94) and DII (1.13, 1.01‐1.28) were associated with AR risk. In particular, a high‐vegetable diet resulted in a lower risk of mild and persistent AR (aOR, 95% CI = 0.24, 0.10‐0.56) while a high DII represented a higher risk (2.33, 1.06‐5.10). The protective effect of vegetable diet on AR appeared only among children with a lower GRS (adjusted P =.018). Conclusions: A vegetable dietary pattern characterized by high intake of anti‐inflammatory nutrients and higher vitamin D level in blood might be associated with a lower risk of mild and persistent AR. This beneficial effect is modified by a genetic factor. [ABSTRACT FROM AUTHOR]

Background: The most relevant time of PM10 exposure to affect airway hyperresponsiveness (AHR) and new development of asthma in school‐aged children is unclear. The aims of this study were to investigate the most critical time of PM10 exposure to affect AHR and new diagnosis of asthma from AHR in school‐aged children. Methods: Elementary schoolchildren (n = 3570) have been enrolled in a nationwide prospective 4‐year follow‐up survey in Korea from 2005 to 2006. Individual annual PM10 exposure was estimated by using an ordinary kriging method from the prenatal period to 7 years of age. AHR at 7 years was defined by a methacholine PC20 ≤8 mg/mL. Results: PM10 exposure during pregnancy and at 1 year of age showed significant effects on AHR (aOR: 1.694, 95% CI: 1.298‐2.209; and aOR: 1.750, 95% CI: 1.343‐2.282, respectively). PM10 exposure during pregnancy was associated with the risk of a new diagnosis of asthma (aOR: 2.056, 95% CI: 1.240‐3.409), with the highest risk in children with AHR at age 7 (aOR: 6.080, 95% CI: 2.150‐17.195). PM10 exposure in the second trimester was associated with the highest risk of a new diagnosis of asthma in children with AHR at age 7 (aOR: 4.136, 95% CI: 1.657‐10.326). Conclusions: Prenatal PM10 exposure in the second trimester is associated with an increased risk of a new diagnosis of asthma in school‐aged children with AHR at 7 years. This study suggests that PM10 exposure during a specific trimester in utero may affect the onset of childhood asthma via AHR. Higher PM10* exposure in the second trimester and AHR# at 7 years showed combined effect on the new diagnosis of asthma at school age (aOR 4.136).PM10* exposure in the second trimester may affect the development of childhood asthma via AHR#. *PM10: Particulate matter with an aerodynamic diameter of less than 10 μm. #AHR: Airway hyperresponsiveness. [ABSTRACT FROM AUTHOR]

Aim: We investigated airway function in preschoolers with postinfectious bronchiolitis obliterans (PIBO) using impulse oscillometry (IOS).Methods: This study enrolled 182 children aged three to five years: 12 with PIBO, 135 with asthma and 35 nonatopic controls. Respiratory resistance and reactance were assessed using IOS.Results: The percentage predicted (% predicted) of prebronchodilator respiratory resistance at 5 Hz was significantly higher in children with PIBO (177.9 ± 118.4%) than the asthma (126.1 ± 30.5%, p = 0.013) or control (121.1 ± 21.8%, p = 0.014) groups. After bronchodilator use, children with PIBO did not reach the values of Rrs5% predicted in the asthma and control groups. Respiratory reactance (Xrs5% predicted) in children with PIBO (337.1 ± 478.5%) was significantly higher than both asthma (130.0 ± 80.0%, p = 0.004) and control (105.1 ± 30.8%, p < 0.001) groups before bronchodilator use and significantly higher than the two groups after bronchodilator use (p = 0.010 and p = 0.004, respectively). The changes in Rrs5 and Xrs5 were not significantly different between the children with PIBO and asthma.Conclusion: Measuring Rrs5 and Xrs5 before and after bronchodilator use may help to discriminate PIBO from asthma in children aged three to five years with chronic or recurrent respiratory symptoms. [ABSTRACT FROM AUTHOR]

ABSTRACT Mutations in COCH ( coagulation factor C homology) cause autosomal-dominant nonsyndromic hearing loss with variable degrees of clinical onset and vestibular malfunction. We selected eight uncharacterized mutations and performed immunocytochemical and Western blot analyses to track cochlin through the secretory pathway. We then performed a comprehensive analysis of clinical information from DFNA9 patients with all 21 known COCH mutations in conjunction with cellular and molecular findings to identify genotype-phenotype correlations. Our studies revealed that five mutants were not secreted into the media: two von Willebrand factor A (v WFA) domain mutants, which were not transported from the endoplasmic reticulum to Golgi complex and formed high-molecular-weight aggregates in cell lysates, and three LCCL domain mutants, which were detected as intracellular dimeric cochlins. Mutant cochlins that were not secreted and accumulated in cells result in earlier age of onset of hearing defects. In addition, individuals with LCCL domain mutations show accompanying vestibular dysfunction, whereas those with v WFA domain mutations exhibit predominantly hearing loss. This is the first report showing failure of mutant cochlin transport through the secretory pathway, abolishment of cochlin secretion, and formation and retention of dimers and large multimeric intracellular aggregates, and high correlation with earlier onset and progression of hearing loss in individuals with these DFNA9-causing mutations. [ABSTRACT FROM AUTHOR]

ABSTRACT Saturated long chain-free fatty acids (FFAs), especially palmitate, have been implicated in apoptosis by inhibiting the activity of PKR (double-stranded RNA-dependent protein kinase). We recently found evidence that palmitate interacts directly with the kinase domain of PKR, subsequently inhibiting the autophosphorylation of PKR. To investigate the interactions of palmitate with PKR and its effects on PKR autophosphorylation, we performed extensive unbiased MD simulations combined with biochemical and biophysical experiments. The simulations predict multiple putative binding sites of palmitate on both the phosphorylated and unphosphorylated PKR with similar binding affinities. Ligand-protein interactions involving a large variety of different binding modes challenge the conventional view of highly specific, single binding sites. Key interactions of palmitate involve the αC-helix of PKR, especially near residue R307. Experimental mutation of R307 was found to affect palmitate binding and reduce its inhibitory effect. Based on this study a new allosteric mechanism is proposed where palmitate binding to the αC-helix prevents the inactive-to-active transition of PKR and subsequently reduces its ability to autophosphorylate. Proteins 2014; 82:2429-2442. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

ABSTRACT Background and objective: Expression of excision repair cross-complementation group 1 (ERCC1) is recognized as a favourable prognostic marker in patients who have undergone surgical resection of non-small cell lung cancer (NSCLC). However, in patients treated with adjuvant chemotherapy after surgical resection, ERCC1 correlated with poor prognosis. Class III beta tubulin (TUBB3) is also known to be a predictive marker of the efficacy of treatment with taxanes or vinorelbine. Methods: Tumour tissues ( n = 363) from patients with surgically resected NSCLC were analysed retrospectively. Tissue sections were labelled with ERCC1- and TUBB3-specific antibodies. Using genomic DNA from 262 patients, single nucleotide polymorphisms of the ERCC1 gene (T19007C and C8092A) were genotyped by PCR-restriction fragment length polymorphism analysis. Results: Only 5.9% of patients with stage I disease (14/238) and 61.6% of patients with stages II-III disease (77/125) received adjuvant chemotherapy. Relapses were noted in 30.6% (111) of patients, and among these, 31 ultimately succumbed. The relapse rate (RR) was 24.8% for stage I disease, and 41.6% for stages II-III disease. The RR was significantly lower in ERCC1-positive (24.3%) as compared with ERCC1-negative patients (36.3%, P = 0.014) and was lower in patients with the AA/CA genotype at the ERCC1 C8092A locus (29.5%) compared with those with the CC genotype (42.1%, P = 0.034). The median disease-free survival (DFS) time was 62.3 months. DFS was significantly greater in ERCC1-positive patients (62.3 months) than in ERCC1-negative patients (48.0 months, P = 0.042). In a multivariate analysis, ERCC1 expression and the C8092A polymorphism were independent prognostic factors in patients with stage I disease who were naïve to chemotherapy. Conclusions: ERCC1 expression and the AA/CA genotype at the C8092A locus were correlated with a good prognosis in patients who had undergone surgical resection of NSCLC. [ABSTRACT FROM AUTHOR]

α-Synuclein is the major filamentous constituent of Lewy bodies found in Parkinson’s disease (PD). The amyloid formation of α-synuclein was significantly facilitated by oxidized glutathione (GSSG) as the lag period of the aggregation kinetics was shortened by 2.5-fold from its absence. Reduced glutathione (GSH), on the other hand, did not influence the lag phase although it increased the final amyloid formation. The GSSG stimulation was specific for not only α-synuclein but also its intactness. The preferred GSSG interaction of α-synuclein to GSH was also demonstrated with dissociation constants of 0.53 and 43.5 mM, respectively. It is suggested that the oxidative stress favoring the GSSG generation from GSH could result in the augmented amyloid formation of α-synuclein, which ought to be related to the pathogenesis of PD. [Copyright &y& Elsevier]

In this study, the role of V12-Rac1 in the cisplatin-induced apoptosis was investigated. Cisplatin-induced apoptosis is associated with cytochrome c release, which can be inhibited by V12-Rac1 expression. The analysis of mitogen-activated protein kinase activity indicated that V12-Rac1 expression led to a decrease in p38 activity after exposure to cisplatin but not c-jun N-terminal kinase and extracellular signal-regulated kinase. Using pharmacological inhibitors, it was found that only p38 is a critical mediator in the cisplatin-induced apoptosis of NIH3T3 cells. This suggests that V12-Rac1 can stimulate the anti-apoptotic signaling pathway in response to cisplatin, and that decreased p38 activity caused by V12-Rac1 expression in cisplatin-treated NIH3T3 cells is crucial for V12-Rac1-dependent cell survival. [Copyright &y& Elsevier]