145 research outputs found

    Factors associated with the severity of childhood rhinoconjunctivitis

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    AbstractBackgroundAllergic rhinitis is one of the most common chronic diseases in children. Although it has a large impact on the patient's quality of life, little is known about the factors associated with its severity. The aim of this study was to assess the factors associated with the severity of rhinoconjunctivitis among children in the general population.MethodsA survey was conducted using an online research panel in 2012. Parents were asked to answer an International Study of Asthma and Allergies in Childhood-based questionnaire to identify children with current rhinoconjunctivitis and evaluate factors associated with the severity of its symptoms. Severity was rated according to the degree of impairment caused by the symptoms in the patient's daily life.ResultsAmong 26,725 children aged 6–12 years old, rhinoconjunctivitis was defined in 5175 (19.4%), and of these, 688 children (13.3% of children with current rhinoconjunctivitis) presented severe symptoms. Living in areas with a high cedar and cypress pollen count and having concurrent eczema were associated with severe rhinoconjunctivitis [adjusted OR (95% CI): 1.21 (1.00–1.46) and 1.45 (1.20–1.75), respectively]. Further, a maternal history of asthma and allergic rhinitis was a significant risk factor for severe rhinoconjunctivitis [1.34 (1.04–1.74) and 1.30 (1.10–1.53), respectively]. However, living with fur-bearing animals (pets) before 1 year of age proved to be a protective factor against severe rhinoconjunctivitis [0.70 (0.52–0.94)].ConclusionsEnvironmental factors such as pets and pollen, together with comorbidities and a maternal history of allergic diseases, play an important role in determining the severity of rhinoconjunctivitis

    Influence of Microstructure on Chip Formation when Broaching Ferritic-Pearlitic Steels

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    Broaching is a specific process characterized by relatively low cutting speeds and uncut chip thicknesses. The latter is in the range of 0.1 to 0.25 mm in the roughing section of the tool but can decrease down to 0.0015 mm in the finishing one. This induces drastically different cutting behaviours compared to macroscale processes such as turning. The question of the scale effects in such conditions is thus clearly raising and especially the size and distribution of the microstructure. This paper proposes an investigation to assess the importance of the material heterogeneities on chip formation when broaching ferritic-pearlitic steels

    Mite-antigen Stimulates MAL Expression in Peripheral Blood T Cells of Mite-sensitive Subjects

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    ABSTRACTBackgroundDifferential gene expression in CD3+ T cells from allergic patients stimulated with allergen will provide important information on the responses of T cells.MethodsAfter stimulation of peripheral blood mononuclear cells (PBMCs) with mite extracts, levels of gene transcription were examined in CD3+ T cells from allergic patients.ResultsStimulation of PBMCs from mite specific IgE positive subjects resulted in specific upregulation of MAL transcription levels that was mediated by IL-4 secretion. The MAL protein in IL-4 stimulated primary T cells preferentially localized in glycolipid-enriched membrane (GEM) microdomains. When MAL was exogenously expressed in primary T cells, CD3ζ was concomitantly enriched, along with the expression of MAL, in GEM microdomains.ConclusionsGEMs are important for the formation and stabilization of TCR signaling complexes. Therefore, MAL may play a role in the formation of GEMs in activated T cells and the high expression of MAL may contribute to Th2 immune response

    Low-power display system enabled by combining oxide semiconductor and neural network technologies

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    An oxide semiconductor (OS)-based field effect transistor (OSFET) exhibits the advantage of having an extremely low off-state current; moreover, the OSFET displays an off-state current that is ten orders of magnitude lower than that of a CMOS-FET [1]. Recently, numerous applications that harness this feature have been reported [2]. For instance, charge leakage from a data retention node of a pixel significantly decreases when the display incorporates OSFETs in its pixel circuit (OS display) [3, 4]. This minimizes degradation in the image quality when the displayed image is static despite using lower refresh rates. Consequently, the consumed power of the display driver circuit can be reduced by a large margin. This driving method is termed idling stop (IDS) driving. The OSFET’s low-leakage can also effectively enable a type of ULSICs that we term OS-large-scale integrated circuits (OSLSI) [5, 6]. Please click Additional Files below to see the full abstract

    Haplotypes and a Novel Defective Allele of CES2 Found in a Japanese Population

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    ABSTRACT: Human carboxylesterase 2 (hCE-2) is a member of the serine esterase superfamily and is responsible for hydrolysis of a wide variety of xenobiotic and endogenous esters. hCE-2 also activates an anticancer drug, irinotecan (7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin, CPT-11), into its active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38). In this study, a comprehensive haplotype analysis of the CES2 gene, which encodes hCE-2, in a Japanese population was conducted. Human carboxylesterases are members of the serine esterase superfamily and are responsible for hydrolysis of a wide variety of xenobiotic and endogenous esters. They metabolize esters, thioesters, carbamates, and amides to yield soluble acids and alcohols or amines Although both hCE-1 and hCE-2 show broad substrate specificities, hCE-2 is relatively specific for heroin, cocaine (benzoyl ester), 6-acetylmorphine, procaine, and oxybutynin 1865 camptothecin (SN-38), a topoisomerase inhibitor, by carboxylesterases Previously, 12 exons and their flanking regions of CES2 were sequenced from 153 Japanese subjects, who received irinotecan or steroidal drugs, and 12 novel SNPs, including the nonsynonymous SNP, 100CϾT (Arg 34 Trp), and the SNP at the splice acceptor site of intron 8 (IVS8-2AϾG) were found Materials and Methods Chemicals. Irinotecan, SN-38, and SN-38G were kindly supplied by Yakult Honsha Co. Ltd. (Tokyo, Japan). Patients. A total of 262 Japanese subjects analyzed in this study consisted of 85 patients with allergies who received steroidal drugs and 177 patients with cancer who received irinotecan. The ethical review boards of the National Cancer Center, National Center for Child Health and Development, and National Institute of Health Sciences approved this study. Written informed consent was obtained from all participants. DNA Sequencing. Total genomic DNA was extracted from blood leukocytes or Epstein-Barr virus-transformed lymphocytes and used as a template in the polymerase chain reaction (PCR). Sequence data of the CES2 gene from 72 patients and 81 cancer patients were described previously Linkage Disequilibrium and Haplotype Analyses. LD analysis was performed by the SNPAlyze software (version 5.1; Dynacom Co., Yokohama, Japan), and a pairwise two-dimensional map between SNPs was obtained for the DЈ and rho square (r 2 ) values. All allele frequencies were in HardyWeinberg equilibrium. Some haplotypes were unambiguously assigned in the subjects with homozygous variations at all sites or a heterozygous variation at only one site. Separately, the diplotype configurations (combinations of haplotypes) were inferred by LDSUPPORT software, which determines the posterior probability distribution of the diplotype configuration for each subject on the basis of estimated haplotype frequencies Administration of Irinotecan and Pharmacokinetic Analysis. The demographic data and eligibility criteria for 177 cancer patients who received irinotecan in the National Cancer Center Hospitals (Tokyo and Chiba, Japan) were described elsewhere Each patient received a 90-min i.v. infusion at doses of 60 to 150 mg/m 2 , which varied depending on regimens/coadministered drugs: i.e., irinotecan dosages were 100 or 150 mg/m 2 for monotherapy and combination with 5-FU, 150 mg/m 2 for combination with mitomycin C (MMC), and 60 (or 70) mg/m 2 for combination with platinum anticancer drugs. Heparinized blood was collected before administration of irinotecan and at 0 min (end of infusion), 20 min, 1 h, 2 h, 4 h, 8 h, and 24 h after infusion. Plasma concentrations of irinotecan, SN-38, and SN-38G were determined as described previously Expression of Wild-Type and Variant CES2 Proteins in COS-1 Cells. Expression of wild-type and variant CES2 proteins in COS-1 cells was examined as described previously and ZERO-Dscan software (Raytest, Straubenhardt, Germany). The relative expression levels are shown as the means Ϯ S.D. of three separate transfection experiments. Determination of CES2 mRNA by Real-Time RT-PCR. Total RNA was isolated from transfected COS-1 cells using the RNeasy Mini Kit (QIAGEN, Tokyo, Japan). After RNase-free DNase treatment of samples to minimize plasmid DNA contamination, first-strand cDNA was prepared from 1 g of total RNA using the High-Capacity cDNA Archive Kit (Applied Biosystems, Foster City, CA) with random primers. Real-time PCR assays were performed with the ABI7500 Real Time PCR System (Applied Biosystems) using the TaqMan Gene Expression Assay for CES2 (Hs01077945_m1; Applied Biosystems) according to the manufacturer's instructions. The relative mRNA levels were determined using calibration curves obtained from serial dilutions of the pooled wild-type CES2 cDNA. Samples without reverse transcriptase were routinely included in the RT-PCR reactions to measure possible contributions of contaminating DNA, which was usually less than 1% of the mRNA-derived amplification. Transcripts of ␤-actin were quantified as internal controls using TaqMan ␤-Actin Control Reagent (Applied Biosystems), and normalization of CES2 mRNA levels were based on ␤-actin concentrations. Enzyme Assay. CPT-11 hydrolyzing activity of the postmitochondrial supernatants (microsomal fraction plus cytosol) was assayed over the substrate concentration range of 0.25 to 50 M as described previously Statistical Analysis. Statistical analysis of the differences in the AUC ratios among CES2 diplotypes, coadministered drugs. or irinotecan dosages was performed using the Kruskal-Wallis test, Mann-Whitney test, or Spearman rank correlation test (Prism 4.0, GraphPad Software, Inc., San Diego, CA). The t test (Prism 4.0) was applied to the comparison of the average values of protein expression and mRNA levels between wild-type and variant CES2. Results CES2 Variations Detected in a Japanese Population. Previously, the promoter region, all 12 exons, and their flanking introns of the CES2 gene were sequenced from 72 allergic patients and 81 cancer patients and resulted in the identification of 12 novel SNPs The nonsynonymous SNP 424GϾA (V142M) reported by our group LD and Haplotype Analysis. Using the detected SNPs, LD analysis was performed, and the pairwise values of r 2 and DЈ were obtained. A perfect linkage (r 2 ϭ 1.00) was observed between SNPs Ϫ363CϾG and IVS10-87GϾA. A close association (r 2 ϭ 0.85) was found between SNPs IVS10-108GϾA and 1749AϾG. Other associations were much lower (r 2 Ͻ 0.1). Therefore, the entire CES2 gene was analyzed as one LD block. The determined/inferred haplotypes are summarized i

    Coleosporium clematidis

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