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Allergenicity to heated egg yolks is known to be low in hen's egg allergy. However, there are few reports concerning the safety of an oral food challenge (OFC) with boiled egg yolks. This study aimed to determine the safety of a boiled egg yolk OFC and the clinical characteristics of patients who were OFC-positive.We retrospectively examined the data of patients who underwent an OFC with one boiled egg yolk at Miyagi Children's Hospital between January 2013 and December 2020. Patients were included if they had a history of immediate symptoms due to hen's egg or positive specific IgE levels to egg yolk or egg white.Among 600 patients, 15.0% were positive for OFC, only one patient required an intramuscular adrenaline injection, and 70% of OFC-positive patients had gastrointestinal symptoms.Boiled egg yolk OFC had a low symptom induction rate; however, when symptoms were induced, gastrointestinal symptoms were most commonly observed. Given the low risk of developing severe symptoms, we conclude that the likelihood of safely performing an OFC is high.

Background: Metal exposures could possibly affect allergic responses in pregnant women, although no studies have yet shown a clear relationship between the two, and such exposures might also affect the development of allergic diseases in children. Methods: We investigated the relationship between metal concentrations in whole blood and immunoglobulin E (IgE; total and specific) in 14,408 pregnant women who participated in the Japan Environment and Children’s Study. The subjects submitted self-administered questionnaires, and blood samples were collected from them twice, specifically, during the first trimester and again during the second=third trimester. Concentrations of the metals Cd, Pb, Hg, Se, and Mn, as well as serum total and allergen-specific IgEs for egg white, house dust-mites (HDM), Japanese cedar pollen (JCP), animal dander, and moth, were measured. Allergen-specific IgE(s) were divided based on concentrations, This work was supported by the Ministry of the Environment, Japan., Supplementary data related to this article can be found at https://doi.org/10.2188/jea.JE20180098.

Hen's egg is the most common allergen in IgE-mediated food allergy among children in Japan. Although the majority of patients with egg allergy can eat heated egg yolk safely because of its low allergenicity, severely allergic patients show an immediate-type reaction to heated egg yolk. We hypothesized that patients with hyperresponsiveness to boiled egg yolk may have difficulty in acquiring tolerance to egg. The purpose of this study was to examine the prognosis of patients with hyperresponsiveness to boiled egg yolk. Data from 121 patients with egg allergy who underwent oral food challenge (OFC) with boiled egg yolk between January 2012 and December 2013 were analyzed retrospectively. The proportion of patients who could consume heated whole egg 3 years after OFC was 15.4% in the OFC-positive group and 75.8% in the OFC-negative group. Hyperresponsiveness to boiled egg yolk in early life might lead to prolonged egg allergy in children. This finding might aid in the selection of an appropriate population requiring practical immunotherapy.

Pain management for needle-related procedures is poor in Japan. In many countries the use of lidocaine/prilocaine cream for the relief of pain associated with venipuncture has been approved. In children, a psychological approach has also been shown to be effective in reducing pain with venipuncture. We developed a multidisciplinary procedure that combines a cream (2.5% lidocaine and 2.5% prilocaine) and pharmacological approaches such as preparation, education, positioning and distraction. We evaluated the feasibility and acceptability of the procedure for young children. Among 132 pediatric participants, 58.3% did not cry during venipuncture. According to caregiver questionnaire, 71.9% felt that the multidisciplinary procedure eliminated the fear of needle-related procedures in the children; 90.9% were satisfied with it and 75.8% thought it should be applied to all children undergoing venipuncture. The present results suggest that the multidisciplinary procedure is feasible, acceptable and suitable for use in children undergoing venipuncture.

Mutations in genes critical for surfactant metabolism, including surfactant protein C (SP-C) and ABCA3, are well-recognized causes of interstitial lung disease. Recessive mutations in ABCA3 were first attributed to fatal respiratory failure in full-term neonates, but they are also increasingly being recognized as a cause of respiratory disorders with less severe phenotypes in older children and also adults. Here, we report a 20-month-old boy with interstitial lung disease caused by two distinct ABCA3 mutations. Initial treatment with methylprednisolone was unsuccessful, but the additional administration of hydroxychloroquine was effective. The family history revealed that the patient’s older brother had died of idiopathic interstitial lung disease at 6 months of age, suggesting a genetic etiology of the disease. Sequence analyses of SP-C and ABCA3 genes were performed using DNA samples from the patient himself, his parents, and his brother. These analyses revealed novel compound heterozygous mutations in the coding exons of ABCA3 in both the patient and his brother: c.2741A > G, of paternal origin, and c.3715_3716insGGGGGG, of maternal origin. Conclusion Since ABCA3 mutations seem to be a heterogeneous entity with various phenotypes, we recommend genetic testing for mutations in SP-C and ABCA3 genes to be considered in children with unexplained interstitial lung disease.

Signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) is an adaptor molecule containing a Src homology 2 (SH2) domain. SAP is expressed in T cells and natural killer (NK) cells and binds to the cytoplasmic domains of SLAM family receptors, resulting in the subsequent recruitment of Fyn. The SAP (SH2D1A) gene is located on the X chromosome and is responsible for X-linked lymphoproliferative disease, characterized by higher susceptibility to Epstein-Barr virus infection. The SAP-mediated signal is not only essential for the development of NKT cells, i.e. unconventional CD1d-restricted T cells with invariant Valpha14 T cell receptors, but also for the regulation of the function of NK cells and conventional T cells. The role of SAP-mediated signaling in the induction of autoimmune diseases has been analyzed using animal models such as lupus, hepatitis, and graft-versus-host disease and is considered important in their pathogenesis in humans. In this review we highlight the current findings on SAP-mediated signaling in hematopoietic cells and discuss its importance in autoimmune diseases and immunological disorders.

Problem statement: Mast cells develop from bone marrow-derived progenitor cells and are distributed in the skin or mucosa where they play proinflammatory roles in the first line of defense. Since some tumors in humans and experimental animals exhibited infiltration of increased mast cells, we investigated the contribution of mast cells to the override of tumor rejection. Approach: MRL/N-1 cells are malignant fibrous histiocytoma-like cells established from the spleen of a Fas ligand (FasL)-deficient MRL/Mp-FasLgld/gld (MRL/gld) mouse and are implantable in Fas-deficient MRL/Mp-Faslpr/lpr (MRL/lpr) mice. MRL/N-1 cells were implanted in MRL/gld, MRL/lpr and MRL/+mice after antibody treatments or with mast cells or macrophages and the tumor growth was observed. Results: MRL/N-1 cells were rejected by Fas-intact syngeneic MRL/+ mice in CD8+ T cell-mediated manner. This rejection was inhibited by the co-implanted mast cells. MRL/N-1 cells transfected with FasL were rejected by MRL/+ and MRL/gld mice. Conclusion: Mast cells abrogate the rejection of MRL/N-1 tumor cells and that this tumor rejection is mediated by CD8+ T cells and dependent on host Fas-FasL axis.

Coil resistance is broken down into DC resistance, resistance due to the skin effect and resistance due to the proximity effect. Most of the coil resistance is composed of resistance due to the proximity effect in the high-frequency range. Thus, the resistance due to the proximity effect, which is equal to the eddy current loss, must be reduced. The eddy current loss in a magnetoplated wire is smaller than that in a copper wire. The magnetoplated wire is a copper wire whose circumference is plated with a magnetic thin film. The eddy current losses in magnetoplated wire can be analyzed using the finite element method. However, the analysis time is long and there is a memory capacity restriction when using the finite element method. In this study, we derive the expressions of the skin effect and eddy current loss in a magnetoplated wire for ease of calculation. The result shows that eddy current loss in the magnetoplated wire is reduced to a factor of 0.25 or less in comparison with that in copper wire, and that the resistance of the magnetoplated wire can be reduced due to the proximity effect.

A 70-year old man was admitted to our hospital because of nonproductive cough, fever and increasing dyspnea associated with alveolar opacities on chest roentgenogram, which later migrated to previously unaffected areas. The diagnosis of Chlamydial pneumonitis was made on serological grounds. Organizing pneumonia was documented by transbronchial lung biopsies and the subsequent course was satisfactory under minocycline therapy. Chlamydial infection should be considered in the differential diagnosis of migratory pulmonary infiltrates.

Maternal depression has been widely studied but paternal depression is often overlooked. Depression in men is generally more difficult to detect as the symptoms are not apparent. Furthermore, Japanese couples tend to suppress their real emotions to avoid confrontation. We aimed to investigate the reliability and validity of the K6, K10 and PHQ-9 in assessing the mental health status of men when used by their pregnant partners, as well as the prevalence of paternal prenatal depression in a Japanese study sample. A total of 136 couples participated in this study. The prevalence of paternal prenatal depression reported by the men themselves was higher compared to that reported by their female partners (K6, 10.3 %; K10, 6.6 %; PHQ-9, 3.7 % vs. K6-FP, 2.2 %; K10-FP, 1.5 %; PHQ-9-FP, 0 %, respectively). Mental health issues in men may not be accurately rated by their female partners, suggesting the importance of self-rating and direct consultation.

Pain management for needle-related procedures is poor in Japan. In many countries the use of lidocaine/prilocaine cream for the relief of pain associated with venipuncture has been approved. In children, a psychological approach has also been shown to be effective in reducing pain with venipuncture. We developed a multidisciplinary procedure that combines a cream (2.5% lidocaine and 2.5% prilocaine) and pharmacological approaches such as preparation, education, positioning and distraction. We evaluated the feasibility and acceptability of the procedure for young children. Among 132 pediatric participants, 58.3% did not cry during venipuncture. According to caregiver questionnaire, 71.9% felt that the multidisciplinary procedure eliminated the fear of needle-related procedures in the children; 90.9% were satisfied with it and 75.8% thought it should be applied to all children undergoing venipuncture. The present results suggest that the multidisciplinary procedure is feasible, acceptable and suitable for use in children undergoing venipuncture.

We consolidated commercial MgB2 powders by two different shock consolidation methods: the single-stage propellant gun method and the underwater shock consolidation method. The samples prepared had anisotropic resistance–temperature features; the narrowest resistive transition width was observed along the directions of shock loading. In contrast, onset temperatures were independent of the directions and methods. No grain orientation previously observed would have resulted from the consolidation processes with a very short duration of . The samples showed higher diamagnetism than a cold isostatic pressed (CIPed) sample at a low field of 1 Oe. However, their diamagnetism relatively degraded with increasing fields and eventually became much less than even that of the CIPed sample. This is due possibly to thick, much distorted grain boundaries that would have behaved as weak links at high fields.

Some caregivers of children with food allergy may eliminate specific foods from the diet of these children without first consulting doctors. The aim of this study was to investigate the prevalence of such practice and the sensitization of the offending foods.All participants were patients aged one year or over who visited our outpatients unit with complaints of food allergy. Caregivers of the patients were asked to fill out a questionnaire to state the eliminated food items and the grounds for avoidance ("doctor's instructions", "family's judgment", and "not consumed in daily diet") of nine food items including chicken egg, cow's milk, wheat, soy bean, rice, buckwheat, peanut, sesame and shrimp. Data on food-specific IgE titers were extracted from the patients' electronic medical charts.A total of 463 subjects were included in the analyses. Prevalence of patients with specific food avoidance of each of the food item was higher in the lower age group than the higher age group. More than 83% of the patients who avoided chicken egg, cow's milk or wheat were advised by their doctors to do so, while less than 49% of patients who avoided buckwheat did so for the same reason. The percentage of the patients who showed positive sensitization to buckwheat, peanut or shrimp, and avoided it without doctor's instructions, was 46%, 48%, and 34%, respectively.While the majority of caregivers of the children who visited our outpatient unit eliminated specific foods according to doctor's instructions, a considerable proportion of them do so inappropriately without first consulting a doctor.

Background Although platelets play a key role in allergic inflammation in addition to their well-established role in hemostasis, the precise mechanisms of how platelets modulate allergic inflammation are not fully understood. IL-33 is an essential regulator of innate immune responses and allergic inflammation. Objective We sought to determine the expression of IL-33 protein by platelets and its functional significance in airway inflammation. Methods IL-33 protein in human platelets, the human megakaryocyte cell line MEG-01, and bone marrow–derived mouse megakaryocytes was detected by using Western blot analysis and fluorescent immunostaining. We examined the functional relevance of IL-33 protein in platelets by comparing platelet-intact and platelet-depleted groups in a murine model of IL-33–dependent airway eosinophilia elicited by intranasal administration of papain. We further compared the additive effect of administration of platelets derived from wild-type versus IL-33–deficient mice on the papain-induced eosinophilia. Results Platelets and their progenitor cells, megakaryocytes, constitutively expressed IL-33 protein (31 kDa). Papain-induced IL-33–dependent airway eosinophilia in mice was significantly attenuated by platelet depletion. Conversely, concomitant administration of platelets derived from wild-type mice but not IL-33–deficient mice enhanced the papain-induced airway eosinophilia. Conclusions Our novel findings suggest that platelets might be important cellular sources of IL-33 protein in vivo and that platelet-derived IL-33 might play a role in airway inflammation. Therefore platelets might become an attractive novel therapeutic target for asthma and probably allergic inflammation.

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.

In 1940, Kasabach and Merritt reported the case of an infant with a huge angioma causing thrombocytopeniarelated purple spots. This condition became known as the Kasabach–Merrit phenomenon (KMP), characterized by a huge hemangioma associated with thrombocytopenia and microangiopathic hemolytic anemia due to consumption coagulopathy [1]. The incidence of KMP in infants with a huge hemangioma is approximately 0.3%, but it is said that the mortality rate exceeds 30% among patients. A number of therapies have been reported for the treatment of KMP, but none have been uniformly effective. We report a case of life-threatening KMP, in which hemangioma of the right thigh (tufted angioma type) was successfully treated by low-dose radiotherapy after concurrent therapy with the agents prednisolone (PSL), interferon a-2a (IFN a-2a), and vincristine (VCR) failed to control it. 2 Case report

We studied the effect of AM-1155, a newly developed quinolone, against chronic airway infection with Pseudomonas aeruginosa using a previously described rat model. AM-1155 (25 mg/kg) or ciprofloxacin (25 mg/kg) or saline (controls) were injected s.c. for 14 days (from day 4 to day 17) after the inoculation of agar beads containing P. aeruginosa. The number of viable cells of intrapulmonary P. aeruginosa, histological findings of the lungs and immunoglobulin levels of serum and bronchoalveolar lavage fluid were examined in rats 11 and 18 days after the treatment. The findings indicated that the number of viable cells of P. aeruginosa in lungs was significantly decreased in the AM-1155- or ciprofloxacin-treated group compared with the non-treated control group. Histological examination in the non-treated control group showed hyperplasia of bronchus-associated lymphoid tissue as well as cellular infiltration in airways, but not prominently in the AM-1155- or ciprofloxacin-treated group. The IgG and IgA levels in serum and bronchoalveolar lavage fluid were significantly lower in the AM-1155- and ciprofloxacin-treated groups than in the control group. These in-vivo effects of AM-1155 were comparable to those of ciprofloxacin. These findings suggest that treatment with AM-1155 and ciprofloxacin suppressed excessive immune responses, preventing progression of airway damage in the chronic infectious state.

The immunologic pathogenesis of conditions characterized by chronic pulmonary infections, such as diffuse panbronchiolitis and those associated with cystic fibrosis, had not been fully clarified. Organized lymphoid tissue along the airway has been termed bronchus-associated lymphoid tissue (BALT), and hyperplasia of BALT is frequently observed in chronic pulmonary infections in humans. To investigate the role of BALT, we intratracheally inoculated rats with Pseudomonas aeruginosa (PA) enmeshed in agar beads according to the method of Cash et al., thereby establishing a chronic pulmonary infection model. Histopathological examination of tissue from this rat model revealed the accumulation of lymphocytes and foamy cells around bronchioles. This finding corresponds to chronic bronchiolitis in humans. Hyperplasia of BALT was also observed. Immunohistochemical examination demonstrated that Ia+ cells, helper T cells, surface IgM-positive (sIgM+) cells and sIgA+ cells had gradually increased in BALT and the walls of peripheral airways during the period from day 4 to 7. The anti-PA IgA antibody titer in bronchoalveolar lavage fluid (BALF) was also elevated during this period. After day 21, non-helper T cells became predominant in tissue sections, and the numbers of various immunoglobulin-positive cells as well as the anti-PA IgA antibody titer in BALF were reduced. Histological examination revealed that the inflammatory findings had also diminished. The time course of changes in the various immune cells in BALT and the walls of peripheral airways, paralleled the reductions in anti-PA IgA antibody titers in BALF. Our findings suggest that hyperplastic BALT may be one source of the Ig producing cells which play an important role in the local immune response characteristic of chronic pulmonary infections.

Background Epstein–Barr virus (EBV)-infected T or NK cells cause chronic active EBV infection (CAEBV). Allogeneic hematopoietic stem cell transplantation (HSCT) is curative treatment for CAEBV patients. However, chemotherapy prior to HSCT and optimal conditioning regimen for allogeneic HSCT are still controversial. Patients and Methods We retrospectively analyzed five patients with CAEBV treated with reduced-intensity conditioning (RIC) consisted of fludarabine, cyclophosphamide, and low-dose total-body irradiation followed by allogeneic bone marrow transplantation in a single institute. Only one of five patients received chemotherapy prior to transplantation. We analyzed EBV-infected cells in a patient whose EBV load increased after HSCT by T-cell repertoire assay, separation of T-cell subpopulations, in situ hybridization and microsatellite analysis. Results All five patients achieved engraftment, complete chimera, and eradication of EBV load. All patients have been alive without any serious regimen-related toxicity for more than 16 months following HSCT. However, one patient transplanted from HLA-matched sibling donor developed clonal proliferation of CD4+ Vβ3+ T cells caused by monoclonal EBV infection on day 99 after transplantation. Further analysis revealed that the CD4+ Vβ3+ T cells selectively harbored EBV genome, and these infected cells were derived from donor T cells. Conclusions Allogeneic HSCT with RIC is a safe and effective treatment for better overall survival and less regimen-related toxicity in patients with CAEBV. Our first pediatric case reported in the literature suggests that we should consider the possibility of persistent EBV infection in donor T cells as well as the relapse in recipient cells if EBV load increases after allogeneic HSCT.

Concanavalin A (Con A)-induced hepatitis is a T-cell-mediated murine experimental model of autoimmune hepatitis. Mice lacking Valpha14 NKT cells were found to be less sensitive to this hepatitis and the MRL/Mp-Fas(lpr/lpr) (MRL/lpr; i.e. Fas deficient) mice were also less sensitive. We report herein that MRL/Mp-Fas(lpr/lpr)-Sap(rpl/-) (MRL/lpr/rpl) mice lack Valpha14 NKT cells and are deficient in the Fas antigen but sensitive to Con A-induced hepatitis. The signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) is an adaptor molecule containing a Src homology 2 (SH2) domain. We previously reported new mutant mice found among MRL/lpr mice and revealed that SAP deficiency led to the regression of autoimmune phenotypes in mutant MRL/lpr/rpl mice. It was also revealed that CD4(+) and CD8(+) T cells were effector cells and that blockade of 2B4, one of the SLAM family receptors, inhibited the induction of hepatitis in MRL/lpr/rpl mice. These data suggest that signals mediated by molecules other than SAP from 2B4 in T cells played important roles in the induction of hepatitis in MRL/lpr/rpl mice.