PURPOSE: Dysregulated cysteinyl leukotriene (CysLT) synthesis is prominent in exercise-induced bronchoconstriction (EIB). Secreted phospholipase A2 (sPLA2) plays a key regulatory role in the biosynthesis of CysLTs. We previously found that serum leptin levels correlate with (EIB) in children with asthma. The aim of this study was to address the relationship between plasma sPLA2/leptin levels and EIB. METHODS: Sixty-seven prepubertal children between the ages of 6 and 10 years were included in the study. They were asthmatics with EIB (n=25), asthmatics without EIB (n=21), and healthy subjects (n=21). We measured the plasma sPLA2 and leptin levels. We also performed pulmonary function tests at baseline, after bronchodilator inhalation, and after exercise. RESULTS: The sPLA2 and leptin levels were significantly higher in asthmatics with EIB than in those without and control subjects. In addition, sPLA2 levels were significantly correlated with body mass index (Speraman correlation coefficient r=0.343, P=0.023) and leptin levels (partial correlation coefficient r=318, P=0.033). The maximum decrease in % forced expiratory volume in 1 second after exercise was significantly correlated with both PLA2 levels (r=0.301, P=0.041) and leptin levels (r=0.346, P=0.018). CONCLUSION: The sPLA2 and leptin levels were significantly higher in asthmatics with EIB than in asthmatics without EIB and control subjects. In addition, sPLA2 levels were significantly correlated with leptin levels and EIB in asthmatic children.
Asthma ; Body Mass Index ; Bronchoconstriction* ; Child* ; Forced Expiratory Volume ; Humans ; Inhalation ; Leptin* ; Phospholipases A2* ; Plasma* ; Respiratory Function Tests

PURPOSE: Epidemiological data indicate that obesity is a risk factor in asthma, however effects related to obesity and adipokines on airway inflammation and bronchial hyper-responsiveness (BHR) have not yet been demonstrated in the human airway. The aim of this study was to investigate the relationship between serum adipokine levels and BHR to mannitol in asthmatic children. METHODS: Serum adipokine levels were measured and pulmonary function tests were perfomed: baseline, postbronchodilator inhalation, methacholine inhalation, and mannitol inhalation. The response to mannitol was expressed as the dose causing a 15% decrease in forced expiratory volume in one second (FEV1) (PD15), and as the response-dose ratio (RDR) (% fall in FEV1/cumulative dose). RESULTS: Sixty-nine prepubertal children between the ages of 6 and 10 years were participated in the study. They comprised asthmatic children (n=40) and healthy (n=29). Twenty-two subjects (55.5%) with asthma had a positive mannitol bronchial provocation test (BPT) result. The body mass index (BMI) was higher in those asthmatics with positive mannitol BPTs than in asthmatics with negative mannitol BPTs and in the control group (19.30 kg/m2 vs. 17.60 kg/m2 vs. 17.93 kg/m2, P=0.035, P=0.046). Serum leptin levels were also significantly higher in asthmatics with positive mannitol BPTs than in asthmatics with negative mannitol BPTs and in the control group (10.58 ng/mL vs. 5.49 ng/mL vs. 6.75 ng/mL, P=0.002, P=0.016). Leptin values were significantly associated with a PD15 (r=-0.498, P=0.022) and RDR to mannitol (r=0.346, P=0.033) in asthmatic children after adjustment for BMI. CONCLUSION: Serum leptin levels were significantly associated with BHR to mannitol in asthmatic children.
Adipokines ; Asthma ; Body Mass Index ; Bronchial Provocation Tests ; Child* ; Forced Expiratory Volume ; Humans ; Inflammation ; Inhalation ; Leptin* ; Mannitol* ; Methacholine Chloride ; Obesity ; Respiratory Function Tests ; Risk Factors

PURPOSE: Recently, component-resolved diagnosis (CRD) using microarray technology has been introduced to the field of clinical allergy. This study was aimed to investigate the clinical usefulness of microarray-based IgE detection for diagnosing clinical raw fruit allergy in birch pollen-sensitized children. METHODS: Thirty-one children with allergic disease who had been sensitized to pollen were studied. A pollen-sensitized patient was defined as having an allergen-specific history with concomitant positive skin-prick tests (SPTs) to natural allergen extracts or positive allergen-specific IgE. All subjects underwent SPTs for pollen and fruit. In all subjects, specific IgE to pollen and fruit were measured by ImmunoCAP. Specific IgE antibodies to allergen components were determined by a customized allergen microarray (ISAC). RESULTS: Thirteen of the 31 patients (41.9%) had a history of fruit hypersensitivity with positive SPTs. Measuring IgE to allergen components by ISAC, all the 13 patients with fruit hypersensitivity were positive to at least one of Mal d 1, Pru p 1, Pru p 3, Act d 8, and Act d 2 compared to 12 of the 13 patients (92.3%) who had at least 1 positive IgE to fruits (apple, peach, and kiwi) using ImmunoCAP. The sensitivity of ISAC microarray was 100.0% for the diagnosis of fruit hypersensitivity, but its specificity was 27.7% (5/18). The sensitivity of ImmunoCAP was 92.3%, and its specificity was 83.3%. CONCLUSION: The sensitivity of allergen components tested using microarray for the diagnosis of clinical fruit hypersensitivity in children with pollen allergy was high; however, its specificity was low.
Antibodies ; Betula* ; Child* ; Diagnosis* ; Fruit* ; Humans ; Hypersensitivity* ; Immunoglobulin E ; Pollen* ; Prunus persica ; Rhinitis, Allergic, Seasonal

Various cell types in higher multicellular organisms are genetically homogenous, but are functionally and morphologically heterogeneous due to the differential expression of genes during development, which appears to be controlled by epigenetic mechanisms. However, the exact molecular mechanisms that govern the tissue-specific gene expression are poorly understood. Here, we show that dynamic changes in histone modifications and DNA methylation in the upstream coding region of a gene containing the transcription initiation site determine the tissue-specific gene expression pattern. The tissue-specific expression of the transgene correlated with DNA demethylation at specific CpG sites as well as significant changes in histone modifications from a low ratio of methylated H3- lysine 4 or acetylated H3-lysine 9, 14 to acetylated H4 to higher ratios. Based on the programmed status of transgene silenced in cloned mammalian ear-derived fibroblasts, the transgene could be reprogrammed by change of histone modification and DNA methylation by inhibiting both histone deacetylase and DNA methylation, resulting in high expression of the transgene. These findings indicate that dynamic change of histone modification and DNA methylation is potentially important in the establishment and maintenance of tissue-specific gene expression.
Transgenes/*genetics ; Swine ; Organ Specificity/genetics ; Methylation ; Lysine/*metabolism ; Histones/*metabolism ; Histone Deacetylases/metabolism ; Gene Silencing ; *Gene Expression ; Fibroblasts ; Ear ; *DNA Methylation ; Cells, Cultured ; Animals, Genetically Modified ; Animals ; Acetylation

A substantial proportion of patients with autism spectrum disorder (ASD) display hyperactivity as a comorbid symptom. Exposure to valproic acid (VPA) during pregnancy produces ASD-like core behavioral phenotypes as well as hyperactivity in offspring both in human and experimental animals, which makes it a plausible model to study ASD-related neurobiological processes. In this study, we examined the effects of two of currently available attention defecit hyperactivity disorder (ADHD) medications, methylphenidate (MPH) and atomoxetine (ATX) targeting dopamine and norepinephrine transporters (DAT and NET), respectively, on hyperactive behavior of prenatally VPA-exposed rat offspring. In the prefrontal cortex of VPA exposed rat offspring, both mRNA and protein expression of DAT was increased as compared with control. VPA function as a histone deacetylase inhibitor (HDACi) and chromatin immunoprecipitation experiments demonstrated that the acetylation of histone bound to DAT gene promoter was increased in VPA-exposed rat offspring suggesting epigenetic mechanism of DAT regulation. Similarly, the expression of NET was increased, possibly via increased histone acetylation in prefrontal cortex of VPA-exposed rat offspring. When we treated the VPA-exposed rat offspring with ATX, a NET selective inhibitor, hyperactivity was reversed to control level. In contrast, MPH that inhibits both DAT and NET, did not produce inhibitory effects against hyperactivity. The results suggest that NET abnormalities may underlie the hyperactive phenotype in VPA animal model of ASD. Profiling the pharmacological responsiveness as well as investigating underlying mechanism in multiple models of ASD and ADHD may provide more insights into the neurobiological correlates regulating the behavioral abnormalities.
Acetylation ; Animals ; Autistic Disorder ; Child ; Autism Spectrum Disorder ; Chromatin Immunoprecipitation ; Dopamine ; Epigenomics ; Histone Deacetylase Inhibitors ; Histones ; Humans ; Methylphenidate ; Models, Animal ; Norepinephrine ; Norepinephrine Plasma Membrane Transport Proteins ; Phenotype ; Prefrontal Cortex ; Pregnancy ; Rats* ; RNA, Messenger ; Valproic Acid ; Atomoxetine Hydrochloride