Fumiya Yamaide

Maternal Prebiotic Ingestion Increased the Number of Fecal Bifidobacteria in Pregnant Women but Not in Their Neonates Aged One Month

Fructooligosaccharides (FOS) can selectively stimulate the growth of bifidobacteria. Here, we investigated the effect of maternal FOS ingestion on maternal and neonatal gut bifidobacteria. In a randomized, double-blind, placebo-controlled study, we administered 8 g/day of FOS or sucrose to 84 women from the 26th week of gestation to one month after delivery. The bifidobacteria count was detected using quantitative PCR in maternal (26 and 36 weeks of gestation) and neonatal (one month after delivery) stools. Maternal stool frequency was recorded from 24 to 36 weeks of gestation. The number of fecal Bifidobacterium spp. and Bifidobacterium longum in the FOS group was significantly higher than that in the placebo group at 36 weeks of gestation (2.7 × 1010/g vs. 1.1 × 1010/g and 2.3 × 1010/g vs. 9.7 × 109/g). In their neonates, these numbers did not differ between the groups. Also, stool frequency in the FOS group was slightly higher than that in the placebo group two weeks after the intervention (1.0 vs. 0.8 times/day), suggesting a potential constipation alleviation effect. In conclusion, the maternal FOS ingestion showed a bifidogenic effect in pregnant women but not in their neonates.

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 rs652438 A and G variants (N357S) were generated by site-directed mutagenesis and an assay with artificial peptide substrates was used to compare two types of MMP12 activity. The effect of MMP12 inhibition with MMP12-specific small interfering RNA (siRNA) on chemokine secretion from airway epithelial cells was also tested in vitro. Results: N357S showed a p value <0.05 for childhood and combined (adult plus childhood) asthma in the dominant model [odds ratio (OR) 1.60, 95% confidence interval (CI) 1.00–2.56, p = 0.047; OR 1.40, 95% CI 1.04–1.89, p = 0.028, respectively]. This risk variant is associated with asthma severity in adult patients. In the functional assay, the minor-allele enzyme showed significantly lower activity than the major-allele enzyme. MMP12-specific siRNA suppressed IP-10 secretion from airway epithelial cells upon stimulation with IFN-β. Conclusions: Our results suggest that MMP12 confers susceptibility to asthma and is associated with asthma severity in a Japanese population. MMP12 may be associated with asthma through inappropriate attraction of leukocytes to the inflamed tissue.

TGF-β Concentration in Breast Milk is Associated With the Development of Eczema in Infants

Background: Transforming growth factor (TGF)-β in breast milk is crucial for mucosal immune system in the neonatal period. We hypothesized that the level of exposure to TGF-β from breast milk in the first month of life is related to the development of eczema later in life. Thus, the present study investigated whether changes in TGF-β levels between colostrum and mature milk are associated with such occurrence in a birth cohort study. Methods: Colostrum and 1-month breast milk samples were collected from mothers who participated in our birth cohort study. TGF-β1 and TGF-β2 levels in breast milk were measured using a commercial ELISA kit. The development of eczema in the first 6 months after birth was assessed based on parents response to a questionnaire. Levels of TGF-β1 and TGF-β2 were compared in breast milk from mothers of infants with and without eczema. Results: In children with eczema, TGF-β1 levels were higher in colostrum, but lower in 1-month milk. A lower TGF-β1 ratio (1-month milk/colostrum) was related to the development of eczema during the first 6 months of life. There was no difference in TGF-β2 ratio (1-month milk/colostrum) between eczema group and control group. Conclusions: Concentration of TGF-β1 but not TGF-β2 in breast milk during the first month after birth may be associated with eczema later in life. Factors that increase TGF-β1 levels in breast milk may play a role in preventing allergic disease.

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. It was also evaluated the effect of age and sex on pranlukasts efficacy. Methods A total of 121 asthmatic children aged 1 to 14 years were randomly assigned to receive regular pranlukast or not according to sex, and were divided in 2 age groups, 1–5 years and 6–14 years. The primary outcome was total asthma score calculated during 8 weeks by using a sticker calendar related to the days in which a child experienced a worsening of asthma symptoms. This open study lasted 60 days from September 15 to November 14, 2007. Results Significant differences in pranlukast efficacy were observed between sex and age groups. Boys aged 1 to 5 years had the lower total asthma score at 8 weeks (p = 0.002), and experienced fewer cold episodes (p = 0.007). There were no significant differences between pranlukast and control group in total asthma score at 8 weeks (p = 0.35), and in the days in which a child experienced a worsening of asthma symptoms (p = 0.67). Conclusion There was a substantial benefit of adding pranlukast to usual therapy in asthmatic children, especially in boys aged 1 to 5 years, during autumn season.

Hsa-mir-144-3p is increased in umbilical cord serum of infants developing atopic dermatitis

Elevated hsa-miR-144-3p levels in umbilical cord serum may lower the threshold for allergen-induced skin inflammation. This gives insight in to possible mechanisms promoting early life atopic dermatitis and highlights the importance of skin barrier protection.

Search for a Novel Allergen in Hen’s Egg Allergy Using an IgE Immunoblotting Assay

Background: Food allergy is a serious health issue affecting roughly 4% of children, with a substantial effect on quality of life. Chicken egg allergy is frequently observed in infants. Therefore, some of them have to exclude hen’s eggs from their daily diet to avoid allergenic symptoms. Hen’s egg is composed of 2 soluble parts; one is egg white, which has been characterized as the major source of allergenicity, while the other is egg yolk, which is estimated as a miner source. Only 2 allergens from egg yolk, α-livetin (Gal d 5) and YGP42 (Gal d 6), have been described to date. Methods: Sera from 53 patients allergic to hen’s eggs and 2 patients allergic to sesame were obtained from the Department of Pediatrics, Chiba University Hospital. The study was performed using SDS-PAGE, IgE immunoblotting, and dot blotting. Results: Seven bands of egg yolk were detected by IgE immunoblotting. Out of these bands, a possible new allergen was further characterized by LC-MS/MS. The 33-kDa band was identified as yolk glycoprotein (YGP40) by LC-MS/MS. A total of 21 of the 53 patients (47%) had YGP40 detected by dot blotting. Conclusions: We identified YGP40 as a new hen’s egg yolk allergen and detected 4 sites of YGP40 as linear epitopes.