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Yasunari Miyazaki

Publications and source records attributed to Yasunari Miyazaki.

8 recordsLinked to original sources
PubMed2026

Idiopathic pulmonary fibrosis risk loci in East Asian populations mirror those of European populations.

RATIONALE: Common and rare variants that are associated with the risk of developing idiopathic pulmonary fibrosis (IPF) have been identified predominantly in European ancestry populations. OBJECTIVES: To better understand the genetic variants that contribute to IPF in individuals with Asian ancestry, we conducted a genome-wide association study of IPF in East Asian populations. METHODS: We included 1026 patients with IPF and compared them to 1723 unaffected controls of Japanese and Korean ancestry. Genome-wide association analysis was conducted in the Japanese and Korean ancestry cohorts separately and combined using meta-analysis. Restricted maximum likelihood was used to estimate the SNP-based heritability and local ancestry of chromosome 11 was inferred for each subject. MEASUREMENTS AND MAIN RESULTS: We identified loci on chromosomes 4 (FAM13A; rs7690839), 5 (TERT; rs7734992), 6 (DSP; rs2076295), and 11 (MUC5B; rs35705950) that were significantly associated with risk of IPF. Importantly, the sentinel variants in each of these loci are the same as, or in strong linkage disequilibrium with, the risk variants that have been observed in studies of European ancestry populations. In aggregate, common variants (not including the MUC5B promoter variant) account for approximately 25% of the risk of developing IPF in these East Asian ancestry cohorts. Moreover, local ancestry analysis indicates that the presence of MUC5B promoter variant in the East Asian population is not a result of admixture with European ancestry populations. CONCLUSIONS: We conclude that the IPF risk loci in East Asian populations are shared with those of European ancestry populations, although their risk allele frequencies and effect sizes differ. These findings indicate shared genetic risk factors of IPF across ancestries.

Aged↗
PubMed2003

Endotoxin contamination of ovalbumin suppresses murine immunologic responses and development of airway hyper-reactivity.

The reversible airway hyper-reactivity (AHR) of asthma is modeled by sensitizing and challenging mice with aerosolized ovalbumin. However, the C57BL/6 murine strain does not display the large increase in circulating IgG and IgE antibodies found in human atopy and asthma. We found that commercial ovalbumin was contaminated with lipopolysaccharide (LPS) in amounts sufficient to fully activate endothelial cells in an in vitro assay of the first step of inflammation. Desensitization of TLR4 by LPS pretreatment suppressed the inflammatory effect of ovalbumin. The presence of LPS was occult, because it does not require serum presentation and, like the LPS of Salmonella minnesota, was not suppressed by polymyxin B. Purified ovalbumin did not activate endothelial cells in vitro; however, endotoxin-free ovalbumin was far more effective than commercial material in stimulating IgE production and respiratory dysfunction in a C57BL/6 murine model of AHR. Moreover, endotoxin-free ovalbumin induced lung inflammation with alveolar enlargement and destruction in a histologic pattern that differed from the changes caused by commercial, endotoxin-contaminated ovalbumin. Reconstitution of purified ovalbumin with S. minnesota LPS decreased lung inflammation, decreased changes in lung function, and suppressed anti-ovalbumin antibody production. We conclude endotoxin contaminates ovalbumin preparations and that endotoxin co-administration with the ovalbumin antigen creates a state of tolerance in a murine model of AHR. Co-exposure to endotoxin and antigen occurs in humans through organic dusts, so murine models of AHR may reflect the clinical situation, but models based on commercial ovalbumin do not accurately reflect the effect of protein antigen alone on animal physiology.

Airway Obstruction↗
PubMed2003

Cyclosporin A followed by the treatment of acute exacerbation of idiopathic pulmonary fibrosis with corticosteroid.

OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a slowly progressive disease with a poor prognosis. Acute exacerbation is the worst stage in the clinical course of IPF, as the condition is unresponsive to most conventional therapies. Corticosteroids and other immunosuppressive drugs have been attempted for the treatment of acute exacerbation, but only with very limited effectiveness. This study was performed to examine the effect of cyclosporin A (CsA) on acute exacerbation of IPF. PATIENTS AND METHODS: Thirteen patients with acute exacerbation of IPF were retrospectively studied. All 13 patients received pulse-therapy with methylprednisolone (1,000 mg per day for 3 days), followed by oral prednisolone (40-60 mg per day). Seven patients were received CsA (1.0-2.0 mg/kg per day) after the treatment with corticosteroids. We attempted to keep the blood trough level of CsA between 100 and 150 ng/ml. RESULTS: Among the 7 patients treated with CsA, 4 patients have survived for 60, 120, 276 and 208 weeks, respectively; 2 did not respond to pulse-therapy with methylprednisolone and died within 8 weeks after the start of CsA treatment. The other patient experienced re-exacerbation and died 87 weeks after the discontinuation of CsA due to the development of viral encephalitis. In contrast, all 6 patients treated without CsA died within 66 weeks after the onset of acute exacerbation. Four of these patients responded to pulse-therapy with methylprednisolone, but their condition deteriorated again while the subsequent prednisolone was being tapered. CONCLUSION: CsA seems to prevent re-exacerbation of IPF and improve the patients' chances for long-term survival.

Acute Disease↗
PubMed2002

Usefulness of cyclosporine A on rapidly progressive interstitial pneumonia in dermatomyositis.

BACKGROUND: Interstitial pneumonia in polymyositis and dermatomyositis (PM/DM) is recognized to be a major complication of PM/DM. Rapidly progressive interstitial pneumonia (RPIP) in DM is frequently refractory to steroids and is the prognosis-determining factor in DM. Recently cyclosporine A (CyA) has emerged as an available treatment for interstitial pneumonia in PM/DM, but its efficacy on RPIP is unclear. AIM OF THE WORK: To evaluate the usefulness of CyA in the treatment of RPIP in DM. METHODS: We reviewed the medical charts of 10 cases with RPIP in DM to whom CyA was administered. RESULTS AND CONCLUSIONS: Combined administration of oral CyA and steroids with/without immuno-suppressants was likely to be beneficial in 4 of 10 cases that were refractory to the conventional preceding therapy. The values of PaO2/FIO2 when CyA were initiated were suggested to be a prognosis-determining factor for the outcome of the disease, showing that initiation of CyA should be considered in the early stage of RPIP in DM. The dosage of steroids was tapered in 3 out of 4 CyA-responsive cases without re-exacerbation. Therefore administration of CyA might be useful in lowering the dosage of steroids.

Adult↗
PubMedDate not supplied

Cytokine mRNA expression in isocyanate-induced hypersensitivity pneumonitis.

BACKGROUND: Diisocyanate is widely used as a polymerizing agent for manufacturing many products. However, repeated inhalation exposure to diisocyanates in the workplace can cause bronchial asthma, hypersensitivity pneumonitis (HP), and neoplasia. OBJECTIVES: In the current study, immunological tests were conducted to explore the mechanisms involved in the pathogenesis of diisocyanate-induced HP. METHODS: Evaluations included 4 patients with diisocyanate-induced HP, 4 volunteers with current occupational exposure to diisocyanates and 4 normal volunteers without a history of exposure to diisocyanates. IgG and IgA antibody levels to diisocyanates were determined by ELISA in sera and BAL fluids. Peripheral blood mononuclear cells (PBMCs) were cultured in the presence or in the absence of 10 microg/ml MDI-HSA (4, 4' diphenylmethane diisocyanate)-HSA (human serum albumin). (3)H-thymidine uptake, mRNA expression by RT-PCR (beta-actin, IL-1beta, IL-2R, IL-4, IL-5, IL-6, IL-10, IFN-gamma, TNF-alpha, TGF-beta) were estimated. RESULTS: Patients with diisocyanate-induced HP had detectable IgG and IgA antibodies to diisocyanates. In addition, PBMCs from HP patients proliferated in the presence of diisocyanates and showed enhanced expression of mRNA of proinflammatory cytokines. In contrast, normal volunteers with current occupational exposure showed elevated levels of mRNA expression of IL-10 and IL-2R, suggesting the presence of sensitized cells and protection from pathology as a result of enhanced IL-10 production. CONCLUSIONS: Patients with diisocyanate-induced HP are likely to override the protective effects of IL-10 as they express lower levels of this cytokine.

Alveolitis, Extrinsic Allergic↗