In-Depth Serum Proteomics by DIA-MS with Spectral Libraries Reveals Dynamics during the Active Phase of Systemic Juvenile Idiopathic Arthritis.

In serum proteomics using mass spectrometry, the number of detectable proteins is reduced due to high-abundance proteins, such as albumin. However, recently developed data-independent acquisition mass spectrometry (DIA-MS) proteomics technology has made it possible to remarkably improve the number of proteins in a serum analysis by removing high-abundance proteins. Using this technology, we analyzed sera from patients with systemic juvenile idiopathic arthritis (sJIA), a rare pediatric disease.

The influence of tonsillectomy on allergic diseases in pediatric patients.

Background: The influence of tonsillectomy on allergic airway diseases is not well known.

Objectives: In the present study, the influence of tonsillectomy on perennial allergic rhinitis (PAR) and bronchial asthma (BA) among pediatric subjects was prospectively investigated.

Methods: The tonsillectomy (surgery group) and the age-matched non-surgical subjects (control group) were examined and followed prospectively.

Pranlukast reduces asthma exacerbations during autumn especially in 1- to 5-year-old boys.

Background: Leukotriene receptor antagonists have been used to prevent virus-induced asthma exacerbations in autumn. Its efficacy, however, might differ with age and sex.

Objective: This study aimed to investigate whether pranlukast added to usual asthma therapy in Japanese children during autumn, season associated with the peak of asthma, reduces asthma exacerbations.

Long-term safety, efficacy, pharmacokinetics and pharmacodynamics of omalizumab in children with severe uncontrolled asthma.

Background: Omalizumab is effective and well-tolerated in children with moderate to severe allergic asthma. However, the effects of long-term treatment with omalizumab in this population haven't been well investigated. The objective of this study is to evaluate the long-term safety, efficacy, pharmacokinetics and pharmacodynamics of omalizumab in children with uncontrolled severe asthma.

Induction of the Matrix Metalloproteinase 13 Gene in Bronchial Epithelial Cells by Interferon and Identification of its Novel Functional Polymorphism.

Matrix metalloproteinases (MMPs) are a class of extra-cellular and membrane-bound proteases involved in a wide array of physiological and pathological processes including tissue remodeling, inflammation, and cytokine secretion and activation. MMP-13 has been shown to be involved in lung diseases such as acute lung injury, viral infections, and chronic obstructive pulmonary disease; however, the molecular pathogenesis of MMP-13 in these conditions is not well understood. In this study, we investigated the mechanisms and roles of MMP-13 secretion in human small airway epithelial cells (SAECs) and functional polymorphisms of the MMP13 gene.

Omalizumab in Japanese children with severe allergic asthma uncontrolled with standard therapy.

Background: Omalizumab has demonstrated clinical benefits in children with moderate to severe allergic asthma. However, no studies have been performed in Japanese asthmatic children. The aim of this study was to evaluate the efficacy including free IgE suppression and safety of omalizumab in Japanese children with severe allergic asthma.

Optimised paediatric CT dose at a tertiary children's hospital in Japan: a 4-y single-centre analysis.

Since diagnostic reference levels (DRLs) for children are not currently established in Japan, the authors determined local DRLs for the full range of paediatric CT examinations in a single tertiary care children's hospital. A retrospective review of 4801 CT performance records for paediatric patients (<15 y old) who had undergone CT examinations from 2008 to 2011 was conducted. The most frequent examinations were of the head (52 %), followed by cardiac (15 %), temporal bone (9 %), abdomen (7 %), chest (6 %) and others (11 %).

Functional variants in the thromboxane A2 receptor gene are associated with lung function in childhood-onset asthma.

Background: The thromboxane A2 receptor (TBXA2R) gene is associated with asthma, but no functional genetic variations are known to associate with the disease or its related phenotypes.

Objective: To investigate the association of TBXA2R polymorphisms with asthma susceptibility and related phenotypes and to identify functionally relevant polymorphisms.

Methods: We performed comprehensive sequencing of the TBXA2R gene in 48 Japanese control subjects and found a set of variants (SNP1 G>T rs2238634, SNP2 T>G rs2238633, SNP3 C>T rs2238632 and SNP4 G>A rs2238631) in intron 1 in linkage disequilibrium with c.

Association study of matrix metalloproteinase-12 gene polymorphisms and asthma in a Japanese population.

Background: Matrix metalloproteinase 12 gene (MMP12) has been shown to be associated with asthma in a Caucasian population. In this study, we investigate whether single-nucleotide polymorphisms (SNPs) of MMP12 are associated with a risk for asthma in a Japanese population.

Methods: We tested for an association between SNPs in MMP12 and asthma, including its severity, in a Japanese population (630 pediatric and 417 adult patients with atopic asthma and 336 children and 632 adults as controls).

The use of complementary and alternative medicine by pediatric food-allergic patients in Japan.

Background: In developed countries, increasing food allergy prevalence and concern regarding food allergies have been reported. Although the use of complementary and alternative medicine (CAM) for the treatment of allergic diseases has increased in some Western countries, the actual proportion and patterns of CAM use for pediatric food allergies in Japan are still unknown.

Methods: Fourteen allergy centers in Japan participated in the study using a questionnaire survey regarding the use of CAM by pediatric patients.

Sublingual immunotherapy with house dust extract for house dust-mite allergic rhinitis in children.

Background: House dust extract is used in conventional immunotherapy for house dust-mite (HDM) allergic rhinitis in Japan. However, an alternative administration route is desired. The aims of the present double blind, placebo-controlled trial were to evaluate the therapeutic efficacy and safety of sublingual immunotherapy (SLIT) with house dust extract in pediatric patients with HDM allergic rhinitis.

CD14 -550 C/T, which is related to the serum level of soluble CD14, is associated with the development of respiratory syncytial virus bronchiolitis in the Japanese population.

Background: The contribution that genetic polymorphisms of Toll-like receptor (TLR) 4 and of CD14--both of which recognize respiratory syncytial virus (RSV) in the innate immune response--make to RSV bronchiolitis in the Japanese population has not yet been clarified.

Methods: This study genotyped 2 TLR4 mutations, Asp299Gly and Thr399Ile, and 2 single-nucleotide polymorphisms (SNPs) of CD14, -550 C/T and -159 C/T, in 54 children with RSV bronchiolitis and in 203 control subjects. CD14 SNPs and the serum level of soluble CD14 (sCD14) also were examined in 67 cord-blood specimens and in serum samples from 73 6-year-old children.

Negative C-reactive protein in children with bacterial infection.

Purpose: To evaluate the practical value of initial C-reactive protein (CRP) in the diagnosis of bacterial infection in children.

Methods: The subjects comprised 11 children, six boys and five girls, aged 3 months through to 3 years (median age 16 months), whose initial CRP levels were < 1.0 mg/dL despite bacterial infection.

The formation of thyrotropin receptor (TSHR) antibodies in a Graves' animal model requires the N-terminal segment of the TSHR extracellular domain.

Immunization of AKR/N mice with murine fibroblasts, transfected with the TSH receptor (TSHR) and a murine major histocompatibility complex class II molecule having the same H-2k haplotype (but not either alone), induces immune thyroid disease with the humoral and histological features of human Graves', including the presence of two different TSHR antibodies (TSHRAbs): stimulating TSHRAbs, which cause hyperthyroidism; and TSH-binding-inhibiting immunoglobulins. The primary functional epitope for both types of antibodies in Graves' patients is on the N-terminal portion of the extracellular domain of the TSHR, residues 25 to 165; most require residues 90-165 to express TSHRAb activity, as evidenced in studies using chimeras of the TSHR and lutropin-choriogonadotropin receptor (LH-CGR). To evaluate the role of this region of the TSHR in the formation of Graves' TSHRAbs, we immunized AKR/N mice with fibroblasts transfected with three human TSHR chimeras with residues 9-165 (Mc1+2), 90-165 (Mc2), or 261-370 (Mc4) substituted by equivalent residues of the rat LH-CGR.

New successful treatment with disinfectant for atopic dermatitis.

For the treatment of atopic dermatitis, a variety of therapies are used including folk medicine. At present, there is no single treatment which is effective to cure the symptoms of atopic dermatitis completely in all patients. We are drawing attention to the high isolation rate of Staphylococcus aureus when starting disinfectant treatment combined with topical steroid therapies for the purpose of killing S.

Diminished interferon-gamma (IFN-gamma) production by bacterial antigen-specific T cells in atopic patients.

In this study, we established and studied cytokine production of T cell lines (TCL) specific to either a purified protein derivative of Mycobacterium tuberculosis (PPD) or Dermatophagoides farinae (Df) from atopic patients and non-atopic healthy subjects. IFN-gamma was detected in the culture supernatants of all of 36 PPD-specific TCL established from healthy controls, whereas only 24 of 38 PPD-specific TCL from patients produced IFN-gamma. Furthermore, the amounts of IFN-gamma produced by PPD-specific TCL from patients were significantly lower than those from healthy controls.

Induction of Graves-like disease in mice by immunization with fibroblasts transfected with the thyrotropin receptor and a class II molecule.

Graves disease is an autoimmune thyroid disease characterized by the presence of antibodies against the thyrotropin receptor (TSHR), which stimulate the thyroid to cause hyperthyroidism and/or goiter. By immunizing mice with fibroblasts transfected with both the human TSHR and a major histocompatibility complex class II molecule, but not by either alone, we have induced immune hyperthyroidism that has the major humoral and histological features of Graves disease: stimulating TSHR antibodies, thyrotropin binding inhibiting immunoglobulins, which are different from the stimulating TSHR antibodies, increased thyroid hormone levels, thyroid enlargement, thyrocyte hypercellularity, and thyrocyte intrusion into the follicular lumen. The results suggest that the aberrant expression of major histocompatibility complex class II molecules on cells that express a native form of the TSHR can result in the induction of functional anti-TSHR antibodies that stimulate the thyroid.

[Nasal smear cytology in bronchial asthma: correlation of appearance and numbers of nasal smear mast cells, eosinophils or basophils and serum IgE antibodies to house dust mite in patients with bronchial asthma].

Nasal smear cytology was studied in pediatric patients with bronchial asthma with special reference with IgE RAST to house dust mite, Dermatophagoides pteronyssinus (Dp). Results obtained were as follows: (1) Numbers of eosinophils on the nasal smear correlated well with Dp RAST score, (2) mast cells were detected before Dp RAST becoming positive and appearance of eosinophils, (3) basophils appeared after detection of eosinophils and only in patients with nasal smear eosinophils. These results suggest that mast cells are the early marker for allergic inflammation and basophils and eosinophils appear in association with overt sensitization with house dust mite in house dust mite-sensitized asthmatic patients.

[The clinical manifestations of Sjögren's syndrome in children].

Sjögren's syndrome (SS) is thought to be uncommon in children. We studied the clinical manifestations and laboratory findings of 12 pediatric patients with SS, all of children did not have sicca symptoms but have lymphocytic infiltration of salivary glands, abnormal sialograms or abnormal results of scintigraphy compatible with typical SS. Seven cases had primary SS and five were secondary SS and had other autoimmune disorders (three cases with systemic lupus erythematosus, one case with dermatomyositis, and the other with mixed connective tissue disease).

[Identification and immunopathogenicity of a common T cell epitope between human thyroglobulin and human thyroid peroxidase].

Human thyroglobulin (hTg) and human thyroid peroxidase (hTPO) share common B cell epitopes recognized by autoantibodies in patients with chronic autoimmune thyroiditis. Furthermore, we have demonstrated a functional common T cell epitope between hTg and hTPO in mice. Four hTg peptides in which 5 amino acid residues were identical to those of hTPO, and one hTPO peptide were prepared.

[Chemical iodination of hormonogenic tyrosine residues of human thyroglobulin is critical for the production of anti-thyroglobulin autoantibody and for the induction of experimental autoimmune thyroiditis in mice].

There is evidence from animal models that the iodine content of thyroglobulin (Tg) may influence its antigenicity in thyroid autoimmunity. To elucidate the effect of iodination of hormonogenic sites of human Tg (hTg) on its autoantigenicity, a synthetic peptide (TB: hTg 2546-2571), containing two hormonogenic tyrosine residues of hTg, and a chemically-iodinated peptide (TB-I) were prepared. We immunized C3H/He (H-2k) mice, a high responder strain to Tg, and BALB/c (H-2d), a low responder strain, with TB or TB-I plus lipopolysaccharide.

Characterization of a thyroiditis-inducing thyroglobulin-specific T-cell clone restricted by the H-2 molecule of a low responder mouse strain.

We established a thyroglobulin (Tg)-specific, thyroiditis-inducing T-cell clone, B12G, from B6C3F1 mice by the immunization of mouse Tg with lipopolysaccharide (LPS) from Klebsiella strain LEN (O3:K1). B12G was Thy-1.2+, CD3+, CD4+, CD18+, and CD8-, and could transfer thyroiditis to recipient mice after in vitro stimulation with mouse or bovine Tg.