Decreased Basophil Activation against House Dust Mite after Japanese Cedar Pollen Subcutaneous Immunotherapy: A Retrospective Study.

BACKGROUND: Allergen-specific immunotherapy (AIT), an established treatment for allergic diseases, prevents the development of other allergic manifestations. Although the mechanisms remain unclear, AIT has been shown to reduce basophil activation (BA) against nontarget allergens. OBJECTIVES: The aim of this study was to assess immunological changes in Dermatophagoides farinae (Der f) after Japanese cedar pollen (JCP)-based subcutaneous immunotherapy (SCIT) monotherapy. METHOD: The data of 16 patients (age: 6-37 years) with JCP-induced allergic rhinitis who were sensitive to Der f (serum Der f-specific immunoglobulin E [IgE] level >0.34 kUA/L) and received JCP-based SCIT for 5 years were reviewed retrospectively. BA by Der f and JCP extracts and serum-specific IgE and immunoglobulin G4 (IgG4) levels against these allergens were evaluated before and after completing 5 years of JCP-based SCIT monotherapy. RESULTS: The areas under the dose-response curves of BA by Der f and JCP extracts were significantly reduced (p = 0.02 and p = 0.002, respectively). JCP-specific IgE levels decreased and JCP-specific IgG4 levels increased significantly (p < 0.001 for both), whereas Der f-specific IgE and IgG4 levels did not change significantly. CONCLUSIONS: JCP-based SCIT monotherapy reduced Der f-specific BA. These findings suggest that JCP-based SCIT has the potential to modulate immune response toward nontarget allergens.

Systemic herpes simplex virus infection in a child with eczema herpeticum.

Eczema herpeticum (EH) is a disseminated cutaneous infection with herpes simplex virus (HSV) that develops in patients with atopic dermatitis. The kinetics and clinical significance of HSV viremia in EH are poorly understood. Herein, we report HSV DNAemia in a child with EH 12 months after the completion of chemotherapy for Hodgkin lymphoma.

Phonon dispersion curves in the type-I crystalline and molten clathrate compound Eu8Ga16Ge30.

The dynamic structure factorS(Q,E), whereQandEare momentum and energy transfer, respectively, has been measured for liquid Eu8Ga16Ge30(EGG), using inelastic x-ray scattering. The excitation energy of the longitudinal acoustic mode in the liquid was scaled to that in liquid Ba8Ga16Sn30(BGS) with the effective mass. This result means that the local structure in both liquids are similar. The longitudinal acoustic excitation energy of type-I clathrate compound EGG disperses faster than that in the liquid, suggesting that the interatomic force is weakened on melting. The lower energy excitation was observed in both liquid EGG and liquid BGS. In comparison with the longitudinal phonon dispersion in crystalline clathrate compound EGG obtained by density functional theory-based calculations, the lower energy in the liquid was found to be near the optical mode energy. The result indicates that the lower energy mode arises from the relative motion between Eu and (Ga, Ge) atoms.

Serological examination for clinical cross-reactivity between salmon roe and pollock roe in patients with a salmon roe allergy.

Objectives: Fish roe is a common allergen in Japan. We have previously reported that although immunoglobulin (IgE) from patients with salmon roe (SR) or pollock roe (PR) allergies cross-react, 70% of patients with SR allergy can consume PR without developing any symptoms. However, a correlation between clinical cross-reactivity and serological cross-reactivity remains to be demonstrated. Methods: Serum samples were collected from 15 patients with SR allergy who had consumed cooked PR previously. Among these volunteers, four had experienced immediate symptoms after consuming cooked PR, while the others had exhibited no symptoms of PR allergy. A competitive enzyme-linked immunosorbent assay (ELISA) was performed to analyze the serological cross-reactivity with SR and PR. Immunoblotting inhibition assays were performed using serum samples that had been pre-incubated with SR or PR extracts. Results: In ELISAs, binding to SR was inhibited by >50% when the serum samples from patients with both SR and PR allergies were pre-incubated with PR extract (p=0.0256). In immunoblots, pre-incubation of serum samples with PR extract inhibited detection of the 16-kDa protein, which likely corresponds to the major SR allergen beta' component, significantly more for samples from patients with both SR and PR allergies (100%) than for samples from those with only an SR allergy (18.2%) (p=0.011). Conclusions: The superior competitive binding of the sera from patients with both SR and PR allergies to PR compared with that to SR may induce clinical cross-reactivity between SR and PR.

Identification of a Novel Mutation in Carboxyl Ester Lipase Gene in a Patient with MODY-like Diabetes.

Maturity-onset diabetes of the young (MODY) is a form of diabetes mellitus characterized by autosomal dominant inheritance, early onset, and the absence of pancreatic autoimmune markers. MODY-causing mutations have been identified in 14 genes, and carboxyl ester lipase (CEL) has been implicated in MODY8. We report a Japanese patient with MODY who harbored a heterogeneous mutation in CEL exon 2 (NM_001807.4:c.146_147delCT; NP_001798.2:p.Ser49CysfsTer52). A 13-year-old girl experienced her first episode of diabetic ketoacidosis, during which her endogenous insulin secretion was poor. However, her insulin secretion had apparently recovered 2 months after the commencement of insulin treatment, and no further treatment was required for the following 2 years. Diabetic ketoacidosis recurred when the patient was 15 years old, when her insulin secretion was again poor. Since that time, the patient, who is now 18 years old, has been undergoing continuous insulin treatment. The large fluctuations in her insulin secretory capacity led us to suspect MODY. MODY8 patients that carry a mutation in the variable number of tandem repeats in the last exon of the CEL gene typically show pancreatic exocrine dysfunction. However, in the present case, which features premature termination, there is no involvement of exocrine dysfunction, potentially demonstrating a genotype-phenotype correlation.

Pressure-Dependent Structure of Methanol-Water Mixtures up to 1.2 GPa: Neutron Diffraction Experiments and Molecular Dynamics Simulations.

Total scattering structure factors of per-deuterated methanol and heavy water, CD3OD and D2O, have been determined across the entire composition range as a function of pressure up to 1.2 GPa, by neutron diffraction. The largest variations due to increasing pressure were observed below a scattering variable value of 5 Å-1, mostly as shifts in terms of the positions of the first and second maxima. Molecular dynamics computer simulations, using combinations of all-atom potentials for methanol and various water force fields, were conducted at the experimental pressures with the aim of interpreting neutron diffraction results. The peak-position shifts mentioned above could be qualitatively reproduced by simulations, although in terms of peak intensities, the accord between neutron diffraction and molecular dynamics was much less satisfactory. However, bearing in mind that increasing pressure must have a profound effect on repulsive forces between neighboring molecules, the agreement between experiment and computer simulation can certainly be termed as satisfactory. In order to reveal the influence of changing pressure on local intermolecular structure in these "simplest of complex" hydrogen-bonded liquid mixtures, simulated structures were analyzed in terms of hydrogen bond-related partial radial distribution functions and size distributions of hydrogen-bonded cyclic entities. Distinct differences between pressure-dependent structures of water-rich and methanol-rich composition regions were revealed.

Equation of State of Liquid Iron under Extreme Conditions.

The density of liquid iron has been determined up to 116 GPa and 4350 K via static compression experiments following an innovative analysis of diffuse scattering from liquid. The longitudinal sound velocity was also obtained to 45 GPa and 2700 K based on inelastic x-ray scattering measurements. Combining these results with previous shock-wave data, we determine a thermal equation of state for liquid iron. It indicates that Earth's outer core exhibits 7.5%-7.6% density deficit, 3.7%-4.4% velocity excess, and an almost identical adiabatic bulk modulus, with respect to liquid iron.

Changes in the characteristics of patients with latex allergy from 1999 to 2014.

OBJECTIVES: We conducted a multicenter study using the same questionnaire in 1999 and 2014 to investigate changes in the characteristics of patients with latex allergy. METHODS: We mailed questionnaires on latex allergy to hospitals in Japan that were members of the Japanese Latex Allergy Society. RESULTS: We compared the 25 responses received in 2014 and the 81 responses received in 1999. With regard to the age distribution, the number of patients with latex allergy in their 20s declined significantly from 1999 to 2014 (P=0.004). The largest proportion of latex allergy cases was observed among those aged <10 years. The incidence of cases caused by medical rubber gloves decreased significantly (P=0.004). Moreover, latex-fruit syndrome increased from 15% to 40% (P=0.006). CONCLUSIONS: Our findings indicate that the frequency of occurrence of latex allergy in people in their 20s decreased from 1999 to 2014. The largest proportion of latex allergy cases was observed among those aged <10 years. Future measures to protect children are required.

Tolerability of partially and extensively hydrolysed milk formulas in children with cow's milk allergy.

BACKGROUND AND OBJECTIVES: The safety and tolerability of hydrolysed cow's milk protein-based formulas, particularly partially hydrolysed formulas (pHFs), in children with cow's milk allergy (CMA) remain poorly understood. We evaluated the tolerability of hydrolysed cow's milk-based formulas in children with CMA. METHODS AND STUDY DESIGN: A three-period double-blind crossover evaluation compared the allergic tolerance against three dietary cow's milk-based formulas: extensively hydrolysed cow's milk formula (eHF), pHF, and regular cow's milk formula (rCMF). The primary outcome was the rate of tolerance against a maximum of 20.0 mL of formula. RESULTS: Controlled food challenges were performed in 25 children (18 boys; 7 girls) with a median age of 4.25 years (range: 1-9 years) diagnosed with CMA. The median cow's milk-specific immunoglobulin E level was 31.9 UA/mL (range: 1.16-735 UA/mL). The tolerance rate ratios for rCMF were lower than those for pHF (2 vs 16; p<0.01) and eHF (2 vs 22; p<0.01). The allergic symptom scores induced by intake of pHF and eHF were significantly lower than those of rCMF (p=0.01 and p<0.01, respectively), and the pHF and eHF scores were not significantly different. CONCLUSIONS: Compared to rCMF, the partially and extensively hydrolysed whey and casein formulas evaluated in this study were better tolerated and therefore safer for children with CMA. Although further confirmation from additional centres is needed, our findings suggest the use of pHF in patients with mild CMA. Some children with CMA react to hydrolysed formulas; therefore, food challenge tests in these children should be undertaken with caution.

Oral Immunotherapy Using Partially Hydrolyzed Formula for Cow's Milk Protein Allergy: A Randomized, Controlled Trial.

BACKGROUND: Partially hydrolyzed cow's milk protein-based formula (pHF) possesses low allergenicity. Here, we investigate the safety and efficacy of oral immunotherapy using pHF for children with cow's milk protein allergy (CMPA). OBJECTIVES: A randomized, double-blind, controlled single-center trial was conducted to evaluate the efficacy and safety of pHF oral immunotherapy in children with CMPA. METHODS: Participants were randomized into double-blind pHF-pHF and extensively hydrolyzed cow's milk protein-based formula (eHF)-pHF groups. During this phase, the pHF-pHF group received pHF and the eHF-pHF group received eHF. During the open phase, all participants received pHF. The primary end point was a change in thresholds between baseline and the end of the first phase. Secondary end points were changes in thresholds between baseline and the end of the second phase, and casein-specific immunoglobulin (Ig)E, IgG4, and basophil activation. RESULTS: Twenty-five children, aged 1-9 years, were randomized into pHF-pHF and eHF-pHF groups. The threshold between baseline and the end of the first phase was significantly elevated in the pHF-pHF group (p = 0.048), but not in the eHF-pHF group. The threshold between other phases did not change significantly in either group. There were significant decreases in casein-specific IgE antibody levels between baseline and the second phase in the eHF-pHF group (p = 0.014). No participants suffered systemic allergic reactions requiring adrenaline or systemic corticosteroids after receiving the formulas. CONCLUSIONS: The results of this trial suggest that, in children with CMPA, tolerance to cow's milk might be safely enhanced by intake of pHF, relative to that of eHF.

Three infants with rotavirus gastroenteritis complicated by severe gastrointestinal bleeding.

Rotavirus gastroenteritis causes substantial morbidity and mortality worldwide in children. We report three infants with rotavirus gastroenteritis complicated by various severity of gastrointestinal bleeding. Two patients (cases 1 and 2) recovered completely without any specific treatments. One patient (case 3) died despite extensive treatments including a red blood cell transfusion and endoscopic hemostatic therapy. Rotavirus genotypes G1P[8] and G9P[8] were detected in cases 2 and 3, respectively. Rotavirus antigenemia levels were not high at the onset of melena, suggesting that systemic rotaviral infection does not play an important role in causing melena.

Carbon-depleted outer core revealed by sound velocity measurements of liquid iron-carbon alloy.

The relative abundance of light elements in the Earth's core has long been controversial. Recently, the presence of carbon in the core has been emphasized, because the density and sound velocities of the inner core may be consistent with solid Fe7C3. Here we report the longitudinal wave velocity of liquid Fe84C16 up to 70 GPa based on inelastic X-ray scattering measurements. We find the velocity to be substantially slower than that of solid iron and Fe3C and to be faster than that of liquid iron. The thermodynamic equation of state for liquid Fe84C16 is also obtained from the velocity data combined with previous density measurements at 1 bar. The longitudinal velocity of the outer core, about 4% faster than that of liquid iron, is consistent with the presence of 4-5 at.% carbon. However, that amount of carbon is too small to account for the outer core density deficit, suggesting that carbon cannot be a predominant light element in the core.

Nature of the Volume Isotope Effect in Ice.

The substitution of hydrogen (H) by deuterium (D) in ice Ih and in its H-ordered version, ice XI, produces an anomalous form of volume isotope effect (VIE), i.e., volume expansion. This VIE contrasts with the normal VIE (volume contraction) predicted in ice-VIII and in its H-disordered form, ice VII. Here we investigate the VIE in ice XI and in ice VIII using first principles quasiharmonic calculations. We conclude that normal and anomalous VIEs can be produced in ice VIII and ice XI in sequence by application of pressure (ice XI starting at negative pressures) followed by a third type-anomalous VIE with zero-point volume contraction. The latter should also contribute to the isotope effect in the ice VII → ice X transition. The predicted change between normal and anomalous VIE in ice VIII at 14.3 GPa and 300 K is well reproduced experimentally in ice VII using x-ray diffraction measurements. The present discussion of the VIE is general, and conclusions should be applicable to other solid phases of H(2)O, possibly to liquid water under pressure, and to other H-bonded materials.

Multicolor flow-cytometric analysis of milk allergen-specific T-helper type 2 cells revealed coexpression of interleukin-4 with Foxp3.

BACKGROUND: Allergen-specific T-helper type 2 (TH2) cells play an important role in the development of allergic inflammation; however, investigations of the properties of allergen-specific T cells have been challenging in humans. Despite clear evidence that forkhead box p3 (Foxp3) is expressed in conventional effector T cells, its function has remained unknown. OBJECTIVE: To characterize allergen-specific TH2 cells in milk allergy, with particular focus on the expression of Foxp3. METHODS: Twenty-one children with milk allergy and 11 children without milk allergy were studied. Peripheral blood mononuclear cells from subjects were stimulated with milk allergen for 6 hours and analyzed using multicolor flow cytometry to identify CD154(+) allergen-specific T-helper cells. Simultaneously, the expression of intracellular cytokines and Foxp3 was analyzed. RESULTS: The milk allergy group had significantly larger numbers of milk allergen-specific interleukin (IL)-4- and IL-5-producing CD4(+) T cells than the control group. Subjects in the milk allergy group had significantly more CD154(+)CD4(+) IL-10-producing cells and CD154(+)Foxp3(+)CD4(+) cells than those in the control group. In addition, the number of milk allergen-specific CD154(+)Foxp3(+)CD4(+) cells strongly correlated with that of CD154(+)IL4(+)CD4(+) cells. Bcl-2 expression in CD154(+)IL-4(+)Foxp3(+) T-helper cells was significantly lower compared with that in total CD4 cells. CONCLUSION: Increased numbers of IL-4-producing allergen-specific T-helper cells were found in patients with milk allergy. In addition, Foxp3 was coexpressed with IL-4 in allergen-specific TH2 cells from patients. This coexpression was associated with lower Bcl-2 levels and could contribute to the phenotype and function of TH2 cells.

Japanese cedar pollen-based subcutaneous immunotherapy decreases tomato fruit-specific basophil activation.

BACKGROUND: Some patients with Japanese cedar pollen (JCP)-induced allergic rhinitis develop pollen-food allergy syndrome (PFAS) as a reaction to tomato fruit. Pollen allergen-specific subcutaneous immunotherapy (SCIT) is reportedly beneficial for some associated food allergies; however, the reported changes in food allergen-specific immunoglobulin (Ig)E and IgG4 levels are inconsistent. Here, we investigated immunologic reactivity to tomato fruit after JCP-based SCIT. METHODS: Twenty-three children (aged 6-17 years) with JCP-induced allergic rhinitis and sensitized to tomato (serum tomato fruit-specific IgE level >0.34 UA/ml) received JCP-based SCIT. Basophil activation by tomato and JCP extracts and serum-specific IgE and IgG4 levels against these allergens were determined before and after 4 or 5 months of maintenance SCIT. Basophil activation was assessed by monitoring CD203c upregulation on flow cytometry. RESULTS: JCP-based SCIT significantly reduced the basophil activation caused by tomato fruit (p = 0.03) and JCP (p < 0.001) extracts. JCP-specific IgG4 levels markedly increased after SCIT (p < 0.001), whereas tomato fruit-specific IgG4 levels did not. After SCIT, no significant changes were observed in specific IgE levels for tomato fruit (p = 0.11) or JCP (p = 0.19). CONCLUSIONS: Tomato fruit-specific basophil activation decreases after JCP-based SCIT, suggesting that it is efficacious in relieving and preventing the symptoms of PFAS in patients with JCP-induced allergic rhinitis.

Allergen analysis of sea urchin roe using sera from five patients.

BACKGROUND: Sea urchin roe can cause anaphylactic reactions the first time they are consumed; therefore, careful clinical attention should be paid to their effects. However, no previous study has examined the allergens in sea urchin roe using sera from more than one patient. We attempted to identify sea urchin allergens using sera from 5 patients with sea urchin allergies. METHODS: We enrolled 5 patients with relevant medical histories, positive results on a skin prick test and/or a food challenge test, and high levels of sea urchin-specific IgE in an enzyme-linked immunosorbent assay. We performed SDS-PAGE, immunoblotting, immunoblot inhibition, and N-terminal amino acid sequence detection. RESULTS: Ten protein bands ranging from 18 to 170 kDa were detected in more than 2 patients' sera. In immunoblotting, the protein band for the 170-kDa major yolk protein was recognized by 4 of the 5 sera. Furthermore, the reaction between IgE and the protein band for egg cortical vesicle protein (18 kDa) was inhibited by the addition of salmon roe extract. CONCLUSION: Major yolk protein was confirmed to be one of the main allergens in sea urchin roe. In addition, egg cortical vesicle protein (18 kDa) was demonstrated to be an important protein for cross-reactivity with salmon roe.