Showing papers by "Kenji Matsumoto published in 2014"
TL;DR: Daily application of moisturizer during the first 32 weeks of life reduces the risk of AD/eczema in infants and allergic sensitization during this time period is associated with the presence of eczematous skin but not with moisturizer use.
Abstract: Background Recent studies have suggested that epidermal barrier dysfunction contributes to the development of atopic dermatitis (AD) and other allergic diseases. Objective We performed a prospective, randomized controlled trial to investigate whether protecting the skin barrier with a moisturizer during the neonatal period prevents development of AD and allergic sensitization. Methods An emulsion-type moisturizer was applied daily during the first 32 weeks of life to 59 of 118 neonates at high risk for AD (based on having a parent or sibling with AD) who were enrolled in this study. The onset of AD (eczematous symptoms lasting >4 weeks) and eczema (lasting >2 weeks) was assessed by a dermatology specialist on the basis of the modified Hanifin and Rajka criteria. The primary outcome was the cumulative incidence of AD plus eczema (AD/eczema) at week 32 of life. A secondary outcome, allergic sensitization, was evaluated based on serum levels of allergen-specific IgE determined by using a high-sensitivity allergen microarray of diamond-like carbon–coated chips. Results Approximately 32% fewer neonates who received the moisturizer had AD/eczema by week 32 than control subjects ( P = .012, log-rank test). We did not show a statistically significant effect of emollient on allergic sensitization based on the level of IgE antibody against egg white at 0.34 kU A /L CAP-FEIA equivalents. However, the sensitization rate was significantly higher in infants who had AD/eczema than in those who did not (odds ratio, 2.86; 95% CI, 1.22-6.73). Conclusion Daily application of moisturizer during the first 32 weeks of life reduces the risk of AD/eczema in infants. Allergic sensitization during this time period is associated with the presence of eczematous skin but not with moisturizer use.
472 citations
TL;DR: It is shown that phospholipase C-β3-deficient mice spontaneously develop AD-like skin lesions and more severe allergen-induced dermatitis than wild-type mice, and STAT5 regulatory mechanisms in mast cells are important for AD pathogenesis.
75 citations
TL;DR: It is shown that B‐ALL with ATF7IP/PDGFRB translocation is included within the genomic lesions of a Philadelphia chromosome (Ph)‐like ALL subgroup and it is possible that measurement of the PDG FRB expression level can be utilized as a screening test for the detection of the cryptic PDGFRBs translocation.
Abstract: Summary
We identified ATF7IP as a novel PDGFRB fusion partner in B-progenitor acute lymphoblastic leukaemia (B-ALL) and showed that B-ALL with ATF7IP/PDGFRB translocation is included within the genomic lesions of a Philadelphia chromosome (Ph)-like ALL subgroup. Comprehensive analyses of previous repositories of gene expression data sets disclosed that B-ALL cases with high PDGFRB expression level in the context of the Ph-like ALL gene are likely to have a PDGFRB translocation. Thus, it is possible that measurement of the PDGFRB expression level can be utilized as a screening test for the detection of the cryptic PDGFRB translocation, especially within the Ph-like ALL subgroup.
30 citations
TL;DR: It is concluded that PU.1 and GATA1 are involved in FcεRIα transcription through recruitment to its promoter, whereas GATA2 positively regulates Fc²RIβ transcription, which leads to downregulation of Fc�RI expression and IgE-mediated degranulation activity.
Abstract: The high-affinity IgE receptor, FceRI, which is composed of α-, β-, and γ-chains, plays an important role in IgE-mediated allergic responses. In the current study, involvement of the transcription factors, PU.1, GATA1, and GATA2, in the expression of FceRI on human mast cells was investigated. Transfection of small interfering RNAs (siRNAs) against PU.1, GATA1, and GATA2 into the human mast cell line, LAD2, caused significant downregulation of cell surface expression of FceRI. Quantification of the mRNA levels revealed that PU.1, GATA1, and GATA2 siRNAs suppressed the α transcript, whereas the amount of β mRNA was reduced in only GATA2 siRNA transfectants. In contrast, γ mRNA levels were not affected by any of the knockdowns. Chromatin immunoprecipitation assay showed that significant amounts of PU.1, GATA1, and GATA2 bind to the promoter region of FCER1A (encoding FceRIα) and that GATA2 binds to the promoter of MS4A2 (encoding FceRIβ). Luciferase assay and EMSA showed that GATA2 transactivates the MS4A2 promoter via direct binding. These knockdowns of transcription factors also suppressed the IgE-mediated degranulation activity of LAD2. Similarly, all three knockdowns suppressed FceRI expression in primary mast cells, especially PU.1 siRNA and GATA2 siRNA, which target FceRIα and FceRIβ, respectively. From these results, we conclude that PU.1 and GATA1 are involved in FceRIα transcription through recruitment to its promoter, whereas GATA2 positively regulates FceRIβ transcription. Suppression of these transcription factors leads to downregulation of FceRI expression and IgE-mediated degranulation activity. Our findings will contribute to the development of new therapeutic approaches for FceRI-mediated allergic diseases.
30 citations
TL;DR: Dermal cells, but not epidermal keratinocytes, may be important cellular sources of TARC in AD skin and thus responsible for subclinical skin inflammation, and anti-inflammatory therapy may decrease TARC blood levels in AD patients indirectly, via its inhibitory effects on TNF-α- and/or IL-4-producing cells in the dermis.
29 citations
TL;DR: It is found that recombinant Gal-9 directly induced phosphorylation of Erk1/2 but not p38 MAPK in a human mast cell line, HMC-1, which does not express FcεRI, suggesting that Gal- 9 has dual properties as both a regulator and an activator of mast cells.
Abstract: Galectin-9 (Gal-9), a lectin having a β-galactoside-binding domain, can induce apoptosis of Th1 cells by binding to TIM-3. In addition, Gal-9 inhibits IgE/Ag-mediated degranulation of mast cell/basophilic cell lines by binding to IgE, thus blocking IgE/Ag complex formation. However, the role of Gal-9 in mast cell function in the absence of IgE is not fully understood. Here, we found that recombinant Gal-9 directly induced phosphorylation of Erk1/2 but not p38 MAPK in a human mast cell line, HMC-1, which does not express FceRI. Gal-9 induced apoptosis and inhibited PMA/ionomycin-mediated degranulation of HMC-1 cells. On the other hand, Gal-9 induced cytokine and/or chemokine production by HMC-1 cells, dependent on activation of ERK1/2 but not p38 MAPK. In addition, the lectin activity of Gal-9 was required for Gal-9-mediated cytokine secretion by HMC-1 cells. These observations suggest that Gal-9 has dual properties as both a regulator and an activator of mast cells.
27 citations
TL;DR: Treatment using tyrosine kinase inhibitors requires further investigation to optimize the genotype‐based treatment stratification for patients with SNX2‐ABL1 fusion.
Abstract: In addition to BCR, various rare fusion partners for the ABL1 gene have been reported in leukemia. We have identified the fusion gene SNX2-ABL1 in a pediatric case of acute lymphoblastic leukemia (ALL), which has only once previously been reported in an adult patient. Cytogenetic analysis detected this fusion gene arising from a t(5;9)(q22;q34) translocation. ALL cells carrying a SNX2-ABL1 fusion exhibited a BCR-ABL1+ ALL-like gene expression profile. The patient poorly responded to dasatinib but partially responded to imatinib. Treatment using tyrosine kinase inhibitors requires further investigation to optimize the genotype-based treatment stratification for patients with SNX2-ABL1 fusion.
24 citations
TL;DR: It is suggested that CRLF2 OE is not an independent prognostic factor in pediatric BCPALL, and a novel fusion transcript, CSF2RA‐CRLF 2, in a case with CRLf2 Oe is revealed, suggesting that this fusion is associated with C RLF2OE.
Abstract: For an overall characterization of pediatric B-cell precursor acute lymphoblastic leukemia (BCPALL) with CRLF2 overexpression (OE), we conducted genetic analysis of CRLF2 in 167 pediatric BCPALL patients. CRLF2 OE was detected in 30 (18%) of 167 patients, the P2RY8-CRLF2 fusion was identified in only 3 (1.8%) of 167 patients, all of which demonstrated CRLF2 OE. Moreover, CRLF2 gain was identified in 18 (11%) of 167 patients. Messenger RNA sequencing revealed a novel fusion transcript, CSF2RA-CRLF2, in a case with CRLF2 OE, suggesting that this fusion is associated with CRLF2 OE. In survival analysis, no significant differences in 5-year event-free survival (EFS) and overall survival were observed between patients with and without CRLF2 OE (70.7 vs. 75.4%, log rank P = 0.68 and 96.4 vs. 82.1%, log rank P = 0.11, respectively). However, a significant difference in 5-year EFS between CRLF2 OE patients with and without IKZF1 deletion was observed (44.4 vs. 83.1%, log rank P = 0.02). In multivariate analysis, only IKZF1 deletion was a significant predictor of inferior OS (hazard ratio: 2.427, P = 0.04).These findings suggest that CRLF2 OE is not an independent prognostic factor in pediatric BCPALL.
22 citations
TL;DR: Findings indicate that IL-17A, but notIL-17F or IL-25, is crucial for LPS-induced endotoxin shock, and that macrophages, DCs and eosinophils,but not Th17 cells or γδ T cells, may be sources of IL- 17A during LPS -induced endot toxin shock.
17 citations
TL;DR: A critical role of DA-Raf1 (DA-R Rafael)—a dominant-negative antagonist for the Ras-ERK signaling pathway—in alveolar formation is identified and a pivotal role is revealed in the dynamic regulation ofAlveolar development.
Abstract: Alveolar formation is coupled to the spatiotemporally regulated differentiation of alveolar myofibroblasts (AMYFs), which contribute to the morphological changes of interalveolar walls. Although the Ras-ERK signaling pathway is one of the key regulators for alveolar formation in developing lungs, the intrinsic molecular and cellular mechanisms underlying its role remain largely unknown. By analyzing the Ras-ERK signaling pathway during postnatal development of lungs, we have identified a critical role of DA-Raf1 (DA-Raf)—a dominant-negative antagonist for the Ras-ERK signaling pathway—in alveolar formation. DA-Raf–deficient mice displayed alveolar dysgenesis as a result of the blockade of AMYF differentiation. DA-Raf is predominantly expressed in type 2 alveolar epithelial cells (AEC2s) in developing lungs, and DA-Raf–dependent MEK1/2 inhibition in AEC2s suppresses expression of tissue inhibitor of matalloprotienase 4 (TIMP4), which prevents a subsequent proteolytic cascade matrix metalloproteinase (MMP)14–MMP2. Furthermore, MMP14–MMP2 proteolytic cascade regulates AMYF differentiation and alveolar formation. Therefore, DA-Raf–dependent inhibition of the Ras-ERK signaling pathway in AEC2s is required for alveolar formation via triggering MMP2 activation followed by AMYF differentiation. These findings reveal a pivotal role of the Ras-ERK signaling pathway in the dynamic regulation of alveolar development.
17 citations
TL;DR: It is shown that silica and double-stranded RNA (dsRNA) synergistically induces caspase-9-dependent apoptosis, but not inflammasome activation, of bronchial epithelial cells, suggesting that inhalation of silica-containing dust may cause inflamMASome-independent airway inflammation, possibly by damaging the epithelial barrier, especially at the time of viral infection.
Abstract: Silica crystals (silica), which are the main mineral component of volcanic ash and desert dust, can activate the caspase-1-activating inflammasome in phagocytic cells to secrete IL-1β. Although inhalation of silica-containing dust is known to exacerbate chronic respiratory diseases, probably through inflammasome activation, its direct effects on bronchial epithelial cells remain unclear. Here, we show that silica and double-stranded RNA (dsRNA) synergistically induces caspase-9-dependent apoptosis, but not inflammasome activation, of bronchial epithelial cells. Intranasal administration of silica and dsRNA to mice synergistically enhanced neutrophil infiltration in the airway without IL-1β release in the bronchoalveolar lavage fluid. Histopathological analysis revealed that silica or dsRNA alone induced slight airway inflammation, whereas combined administration significantly enhanced airway inflammation and epithelial damage. These novel findings suggest that inhalation of silica-containing dust may cause inflammasome-independent airway inflammation, possibly by damaging the epithelial barrier, especially at the time of viral infection. These responses may also be involved in acute lung injury caused by inhaled silica-containing dust.
TL;DR: It is shown that early introduction of egg and increased food diversity in the first year of life were associated with a subsequent decrease in allergic diseases, presumably through induction of ‘‘oral tolerance’’, and other epidemiologic studies have demonstrated that exposure to environmental peanut protein–containing household dust and use of hydrolyzed wheat protein-containing soap significantly increased the risk of allergic sensitization to peanut andwheat, respectively.
Abstract: One of the most significant recent advances in the field of food allergy is a paradigm shift in our understanding of allergen sensitization, namely the dual-allergen exposure hypothesis: oral intake of food proteins tends to induce tolerance, whereas epicutaneous exposure to food proteins tends to induce allergic sensitization. Several lines of epidemiologic study have demonstrated that avoidance of specific food proteins during pregnancy or lactation or early in life does not decrease the prevalence of allergic sensitization (as summarized by Fleischer et al). In contrast, early introduction of egg and increased food diversity in the first year of life were associated with a subsequent decrease in allergic diseases, presumably through induction of ‘‘oral tolerance.’’ On the other hand, other epidemiologic studies have demonstrated that exposure to environmental peanut protein–containing household dust and use of hydrolyzed wheat protein–containing soap significantly increased the risk of allergic sensitization to peanut andwheat, respectively. In addition, filaggrin loss-of-function mutations were a
Patent•
17 Nov 2014
TL;DR: In this article, the problem of identifying a mutation that can serve as an indicator for predicting the efficacy of treatment using a drug in a cancer such as leukemia, providing a means for detecting said mutation; providing a mean for identifying, on the basis of said mutation, cancer patients or subjects at risk of cancer in whom a drug that targets a gene having said mutation or a protein coded by same will produce therapeutic effects; etc.
Abstract: The present invention addresses the problem of: identifying a mutation that can serve as an indicator for predicting the efficacy of treatment using a drug in a cancer such as leukemia; providing a means for detecting said mutation; providing a means for identifying, on the basis of said mutation, cancer patients or subjects at risk of cancer in whom a drug that targets a gene having said mutation or a protein coded by same will produce therapeutic effects; etc. A method for detecting a gene fusion, which is the mutation responsible for a cancer (driver mutation), the method comprising a step for detecting ATF7IP-PDGFRB fused polynucleotide or a polypeptide coded by same in an isolated sample derived from a subject.
TL;DR: In Allergology International (AI) Vol.