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This study aimed to evaluate the associations between skin carotenoid measurements and fruit and vegetables intake among school children. We conducted a cross-sectional study for 10-y-old children in 2020 in Japan. We compared the optical skin carotenoid score, measured using Veggie Meter

X-linked agammaglobulinemia (XLA) is characterized by severe or recurrent infections, hypogammaglobulinemia, and circulating B cell deficiency. The frequent pathogens seen in patients with XLA include Streptococcus pneumoniae, Haemophilus influenzae, Pseudomonas aeruginosa, and enterovirus as well as Campylobacter and Helicobacter species. Here, we describe two patients with XLA who developed cellulitis and bacteremia caused by Helicobacter cinaedi even when administered an appropriate immunoglobulin replacement therapy. H. cinaedi may be difficult to isolate using a conventional blood culture system and could be identified by sequence analysis and mass spectrometry. H. cinaedi infection causes recurrent symptoms frequently, and patients require a long course of antibiotic treatment. Recently, the case of non-H. pylori Helicobacter (NHPH) infection such as H. cinaedi and H. bilis infection is increasing in number in patients with XLA. Systemic NHPH infection should be suspected, and extensive microbiological analysis should be performed to appropriately treat patients with XLA who present with fever and skin lesions.

Background: Although the incidence of cerebral infarction is higher in Duchenne muscular dystrophy (.75 per 100) than in the general population (7.5-11.4 per 100 000), only 18 cases have been reported, and prevention and management guidelines for infarction in this disorder remain lacking. Patients and Methods: We encountered 2 cases of Duchenne muscular dystrophy with cerebral infarction. To clarify risk factors for such infarction in Duchenne muscular dystrophy, we reviewed 20 cases, including our 2 patients. Results: Age at onset of infarction ranged from 4 to 31 years (n = 19). Most patients were 16-21 years old (14 of 19; 73.7%). Eighteen patients (90%) had dilated cardiomyopathy (DCM), showing a higher frequency than in the age-matched general Duchenne muscular dystrophy population. Left ventricular ejection fraction (LVEF) ranged from 10.2% to 42% (median, 20%; n = 9). Detectable cardiac thrombus and atrial fibrillation were rare (2 of 17; 11.8%, and 1 of 17; 5.9%, respectively). Conclusions: Presence of DCM with low LVEF seems to be the strongest risk factor for cerebral infarction in Duchenne muscular dystrophy.

Appropriate dietary assessment and health education are necessary for children to achieve a healthy physique. To explore the relationship between habitual reported dietary energy intake (EI) and physique in elementary schoolchildren by sex and age, we conducted a longitudinal study, in the fiscal year 2011, that included all elementary schools in Omihachiman City, Shiga Prefecture, Japan. The study lasted for four consecutive years, ending in fiscal year 2014, and included 545 7-y-old schoolchildren in the target city. The subjects completed a brief self-administered diet history questionnaire with their guardians. The results of the study demonstrated a negative relationship between energy intake and the estimated energy requirement ratio and body mass index percentile values for both 7-, 9-, and 10-y-old boys and 7- to 10-y-old girls. These results suggest that there is a need to keep in consideration the under-reporting of obese children and over-reporting of lean children for dietary energy evaluation.

Left ventricular noncompaction cardiomyopathy (LVNC) is characterized by prominent trabecular meshwork, and it is thought to result from arrest of the normal compaction process during embryogenesis. Patients with LVNC may be asymptomatic or have symptoms ranging from heart failure to stroke, life-threatening arrhythmias, or sudden death. The frequency of LVNC in children has increased with longer clinical courses. About 80% of patients with trisomy 13 have a congenital cardiac abnormality, but a clinical description of LVNC with trisomy 13 is lacking because of its poor prognosis and lack of awareness about LVNC. We described a patient with trisomy 13 who was diagnosed with LVNC-dilated phenotype and died suddenly, as well as two additional patients with LVNC. All three patients had chronic heart failure without congenital heart disease and were treated with diuretics. To manage trisomy 13 with or without congenital heart disease, cardiac disease such as LVNC may present at any ages, and therefore cardiac evaluation should be considered as a part of their appropriate management.

Cutis laxa (CL) syndromes are connective tissue disorders characterized by redundant, sagging, inelastic and wrinkled skin, with organ involvement. Here, we describe a patient with ALDH18A1-related CL who developed cyclic vomiting. The patient was a 12-year-old boy who presented with poor postnatal growth, hypotonia, short stature, joint hyperlaxity, microcephaly, strabismus, bilateral cataracts, facial dysmorphism and severe mental retardation. Bone radiographs showed osteopenia and osteoporosis, and magnetic resonance angiography showed marked kinking and tortuosity of the brain vessels. These findings were clinically compatible with ALDH18A1-related CL. Molecular analysis revealed a de novo heterozygous mutation (p.R138Q) in ALDH18A1. No mutations were found in PYCR1 gene. The patient developed cyclic vomiting with decreased blood levels of ornithine, citrulline, arginine and proline without hyperammonemia and other hypoaminoacidemias were also found. ALDH18A1 encodes Δ(1)-pyrroline-5-carboxylate synthase, which is related to the biosynthesis of ornithine, citrulline, arginine, and proline. Cyclic vomiting has never been reported in other ALDH18A1-related CL patients. This is the first case report of ALDH18A1-related CL with cyclic vomiting associated with amino acid abnormalities.

Meckel's diverticulum (MD) is the most prevalent congenital anomaly of the gastrointestinal tract and often presents a diagnostic challenge. Patients with trisomy 18 frequently have MD, but the poor prognosis and lack of consensus regarding management for neonates has meant that precise information on the clinical manifestations in infants and children with MD is lacking. We describe the cases of three children with trisomy 18 who developed symptomatic MD. Intussusception was diagnosed in Patient 1, intestinal volvulus in Patient 2, and gastrointestinal bleeding in Patient 3. All three patients underwent surgical treatment and only the Patient 1 died due to pulmonary hypertensive crisis. The other two patients experienced no further episodes of abdominal symptoms. In patients with trisomy 18, although consideration of postoperative complications and prognosis after surgical treatment is necessary, symptomatic MD should carry a high index of suspicion in patients presenting with acute abdomen.

Background Previous studies have shown that dietary pattern is associated with allergy prevention. Methods We conducted a prospective cohort study on all primary schools in Omihachiman City, Shiga Prefecture, Japan. Questionnaires regarding allergic symptoms and diet were distributed to the parents of all 759 7-year-old schoolchildren for 4 consecutive years, from 2011–2014. Specific immunoglobulin E to inhalant allergens were measured at 10 years of age. Participants were then categorized as low, medium, or high intake during the study period for four food groups (fruits, vegetables, fish and beans). Logistic regression analysis was performed to estimate odds ratios and 95% confidence intervals. Results A total of 520 children (68.5%) whose parents responded to the questionnaires all 4 years were included in the analysis. The prevalence of asthma, rhinitis, and any allergic symptoms at age 10 was significantly decreased with increases in fruit intake. In addition, the onset of any allergic symptoms during the study period was significantly decreased with increases in fruit intake (33.3%, 28.3%, and 14.3% in children with low, medium, and high fruit intake, respectively; P for trend = 0.01). The sensitization rate to ragweed at age 10 was significantly decreased with increases in fruit intake (P for trend = 0.046). No significant effect was observed for the other three food groups, except for the association between fish intake and new onset asthma symptoms. Conclusions These findings suggest that higher intake of fruit can help prevent respiratory allergic symptoms in schoolchildren. This article is protected by copyright. All rights reserved.

Crohn's disease (CD) is a chronic inflammatory disorder with an unknown etiology that commonly involves the gastrointestinal tract, and bronchopulmonary manifestations only occur in 0.4% of cases. There have not been any reports about pulmonary involvement in pediatric CD patients. We experienced a 14-year-old boy with Crohn's disease diagnosed with organizing pneumonia by chest CT-guided biopsy examination. His pneumonia was intractable despite the administration of multiple antibiotics, and steroid therapy was very effective. In pediatric patients with CD whose lung disease does not respond to antibiotics, OP should be considered as a possible diagnosis.

Febrile infection-related epilepsy syndrome (FIRES) is a severe epileptic syndrome that manifests with refractory seizures or status epilepticus in previously healthy children after banal febrile illness. The neuroimaging findings in the acute phase of FIRES are nonspecific or normal. We report the case of a 7-year-old boy with FIRES who presented with a reversible lesion in the splenium of the corpus callosum on brain magnetic resonance imaging (MRI). The patient developed clusters of clonic seizures with a deviation of the eyes after a 3-day history of fever. A reversible splenial lesion was observed on brain MRI and, therefore, the initial diagnosis was mild encephalitis/encephalopathy with a reversible splenial lesion (MERS). However, the intractable complex partial seizures necessitated a long-term midazolam infusion, indicating that FIRES was a more likely diagnosis than MERS. All other findings of this patient met the diagnostic criteria for FIRES. With this diagnosis, a high-dose phenobarbital was administrated, and the seizures were successfully controlled. This case indicated that FIRES should be considered even in patients with a reversible splenial lesion associated with encephalitis/encephalopathy.

Background Food allergy (FA) in childhood has been shown to be more prevalent in those born in autumn and winter. The mechanisms of this season-of-birth effect remain unclear, although shortage of vitamin D during infancy has been considered one possible mechanism. The purpose of this study was to investigate the effect of eczema on the season-of-birth effect on FA in infancy. Methods A questionnaire survey on the prevalence of allergic diseases was completed by the parents of 14 669 Japanese schoolchildren, aged 7–15 years, in Kyoto City, Japan. Logistic regression models were constructed to compare the prevalence of FA in infancy according to season of birth. Results Those born in autumn and winter had a significantly higher prevalence of FA in infancy compared to those born in spring and summer in a multivariate model (4.8% vs 3.6%, P = 0.001). The difference, however, was no longer significant when eczema before 6 months was included as either an additional or only confounding factor. The difference among those with and without eczema before 6 months was further analyzed, and it was found that, in both groups, there was no difference between those born in spring and summer and those born in autumn and winter. Conclusions The season-of-birth effect on FA in infancy was significantly affected by the existence of eczema before 6 months in Japanese children. Eczema before 6 months may be the factor directly related to the season-of-birth effect on FA in infancy.

This study was conducted to determine the frequency and characteristics of supplement use in pediatric patients with allergic disorders in Japan. A total of 229 patients with various allergic disorders aged between 0 and 15 years were enrolled. Supplements were defined as preparations that provided nutritional content in the form of a tablet, capsule, powder, liquid, or jelly. The parents of each subject were asked to complete a questionnaire on their child's use of supplements over the previous year. Demographic information, parents' perceived view of the child's health status over the previous month, and family history of both allergic disorders, and supplement use were collected. Four hundred eight age- and sex-matched healthy children served as the controls. Twenty-nine (12.7%) patients had used supplements. This frequency was not significantly different from that in the control group (15.0%). The types of supplements most commonly used were vitamins, followed by minerals, probiotics, and chlorella. Univariate analysis revealed that older age and a positive family history of supplement use were associated with patients' supplement use. The types of allergic disorders, health status from the point of view of the parents, and a family history of allergic disorders did not show any significant association. To our knowledge, this is the first cross-sectional study to demonstrate the frequency and the factors affecting supplement use in pediatric patients with allergic disorders.

To cite this article: Kusunoki T, Mukaida K, Morimoto T, Sakuma M, Yasumi T, Nishikomori R, Heike T. Birth order effect on childhood food allergy. Pediatric Allergy Immunology 2012: 23: 250–254. Abstract Higher birth order is associated with a smaller risk of allergy (birth order effect). The purpose of this study was to compare the significance of the birth order effect on the prevalence of specific allergic diseases [bronchial asthma (BA), atopic dermatitis (AD), allergic rhinitis (AR), allergic conjunctivitis (AC), and food allergy (FA)] among schoolchildren. A questionnaire survey dealing with the prevalence of allergic diseases was administered to the parents of 14,669 schoolchildren aged 7–15 yr. Based on the data, the prevalence of each allergic disease was compared according to birth order (1st, 2nd, and 3rd or later). Multiple regression analysis was performed to test the significance of the differences. There was no significant difference in the prevalence of BA or AD according to birth order. The prevalence of AR, AC, and FA decreased significantly as birth order increased. The prevalence of FA among those with 1st, 2nd, and 3rd or later birth order was 4.0%, 3.4%, and 2.6%, respectively (p = 0.01). With respect to symptoms in infancy, the prevalence of wheeze increased significantly and that of FA and eczema in infancy decreased significantly as birth order increased. The present data show a significant birth order effect on FA. The effect was also observed for the prevalence of FA and eczema in infancy. These data support the concept of early, non-allergen-specific programming of IgE-mediated immunity.

Background To evaluate the association between sports activities and allergic symptoms, especially rhinitis, among schoolchildren. Methods This longitudinal survey of schoolchildren collected data from questionnaires regarding allergic symptoms based on the International Study of Asthma and Allergies in Childhood (ISAAC) program and sports participation that were distributed to the parents of children at all 12 public primary schools in Ohmi-Hachiman City, Shiga Prefecture, Japan. Data were collected annually from 2011 until 2014, when the children reached 10 years of age. Blood samples were obtained in 2014, and the levels of immunoglobulin (Ig)E specific to four inhalant allergens were measured. Results Data from 558 children were analyzed. At 10 years of age, prevalence of asthma and eczema did not differ significantly, while rhinitis was significantly higher (p = 0.009) among children who participated in sports. Prevalence of rhinitis increased as the frequency or duration of sports participation increased (p < 0.01). The prevalence of new-onset rhinitis increased significantly among 10-year-olds with increasing duration of participation in sports (p = 0.03). Among those who participated in continuous sports activities, the prevalence of rhinitis was significantly higher with prolonged eczema (p = 0.006). Sports activities did not increase sensitization to inhalant allergens. Conclusion Sports activities enhance the prevalence of rhinitis in schoolchildren. Prolonged eczema, together with sports participation, further promotes the symptoms. The mechanisms of these novel findings warrant further investigation.

Although children allergic to eggs, milk or wheat in infancy tend to become tolerant by school age, the allergic status of these children at school age has not been well evaluated. To investigate the allergic status of schoolchildren who avoided eggs, milk or wheat because of an immediate-type allergic reaction at

In melanoma, several signaling pathways are constitutively activated. Among these, the protein kinase C (PKC) signaling pathways are activated through multiple signal transduction molecules and appear to play major roles in melanoma progression. Recently, it has been reported that tamoxifen, an anti-estrogen reagent, inhibits PKC signaling in estrogen-negative and estrogen-independent cancer cell lines. Thus, we investigated whether tamoxifen inhibited tumor cell invasion and metastasis in mouse melanoma cell line B16BL6. Tamoxifen significantly inhibited lung metastasis, cell migration, and invasion at concentrations that did not show anti-proliferative effects on B16BL6 cells. Tamoxifen also inhibited the mRNA expressions and protein activities of matrix metalloproteinases (MMPs). Furthermore, tamoxifen suppressed phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt through the inhibition of PKCalpha and PKCdelta phosphorylation. However, other signal transduction factor, such as p38 mitogen-activated protein kinase (p38MAPK) was unaffected. The results indicate that tamoxifen suppresses the PKC/mitogen-activated protein kinase kinase (MEK)/ERK and PKC/phosphatidylinositol-3 kinase (PI3K)/Akt pathways, thereby inhibiting B16BL6 cell migration, invasion, and metastasis. Moreover, tamoxifen markedly inhibited not only developing but also clinically evident metastasis. These findings suggest that tamoxifen has potential clinical applications for the treatment of tumor cell metastasis.

Osteolytic lesions are rapidly progressive during the terminal stages of myeloma, and the bone pain or bone fracture that occurs at these lesions decreases the patients' quality of life to a notable degree. In relation to the etiology of this bone destruction, it has been reported recently that MIP-1alpha, produced in large amounts in myeloma patients, acts indirectly on osteoclastic precursor cells, and activates osteoclasts by way of bone-marrow stromal cells or osteoblasts, although the details of this process remain obscure. In the present study, our group investigated the mechanism by which RANKL expression is induced by MIP-1alpha and the effects of MIP-1alpha on the activation of osteoclasts. RANKL mRNA and RANKL protein expressions increased in both ST2 cells and MC3T3-E1 cells in a MIP-1alpha concentration-dependent manner. RANKL mRNA expression began to increase at 1 h after the addition of MIP-1alpha; the increase became remarkable at 2 h, and continuous expression was observed subsequently. Both ST2 and MC3T3-E1 cells showed similar levels of increased RANKL protein expression at 1, 2, and 3 days after the addition of MIP-1alpha. After the addition of MIP-1alpha, the amount of phosphorylated ERK1/2 and Akt protein expressions showed an increase, as compared to the corresponding amount in the control group. On the other hand, the amount of phosphorylated p38MAPK protein expression showed a decrease from the amount in the control group after the addition of MIP-1alpha. U0126 (a MEK1/2 inhibitor) or LY294002 (a PI3K inhibitor) was added to ST2 and MC3T3-E1 cells, and was found to inhibit RANKL mRNA and RANKL protein expression in these cells. When SB203580, a p38MAPK inhibitor, was added, RANKL mRNA and RANKL protein expression were increased in these cells. MIP-1alpha was found to promote osteoclastic differentiation of C7 cells, an osteoclastic precursor cell line, in a MIP-1alpha concentration-dependent manner. MIP-1alpha promoted differentiation into osteoclasts more extensively in C7 cells incubated together with ST2 and MC3T3-E1 cells than in C7 cells incubated alone. These results suggested that MIP-1alpha directly acts on the osteoclastic precursor cells and induces osteoclastic differentiation. This substance also indirectly induces osteoclastic differentiation through the promotion of RANKL expression in bone-marrow stromal cells and osteoblasts. The findings of this investigation suggested that activation of the MEK/ERK and the PI3K/Akt pathways and inhibition of p38MAPK pathway were involved in RANKL expression induced by MIP-1alpha in bone-marrow stromal cells and osteoblasts. This finding may be useful in the development of an osteoclastic inhibitor that targets intracellular signaling factors.

The relationship between food avoidance during infancy and the growth of Japanese infants in a community health setting has not been well evaluated. In order to assess the growth of infants who avoided either of the three major allergen foods in Japan, eggs, milk or wheat, we employed the results of 4 physical checkups recorded in maternity passbooks and administrated a questionnaire on allergic diseases, height and weight at birth to the guardians of 1,132 infants at the age of 3.5 years. Data was obtained from 890 subjects (78.6%) and 662 subjects (58.5%) who met the inclusion criteria were analyzed. The height, weight and body mass index percentile scores of each subject were calculated. Subjects who avoided either of the three foods at 3.5 years had lower weight percentile scores at 1.5 years, lower height and weight percentile scores at 3.5 years, and lower weight growth rates, compared with the subjects who did not avoid any of the three foods at 3.5 years (P=0.02, 0.03, 0.03, 0.01). The results suggested that there was a negative relationship between physique and food avoidance in infants, and that physical and nutritional assessments are important for food avoiders.

The CpG motif in DNA plays a critical role in immunity via modulating the Th1/Th2 balance. In B cells, CpG-containing oligodeoxynucleotides (CpG ODNs) inhibit IL-4-mediated class switch recombination (CSR) to IgG1 and IgE through inhibition of the germline transcription (GLT) of these isotypes. However, the molecular mechanism of this inhibitory effect remains elusive. We showed here that Id2 and Bcl6, both of which inhibit IgE GLT and CSR, are not involved in this inhibitory pathway. We demonstrated that there is reduced activity of NF kappa B binding to the IgE promoter and a reduction of Irf4 protein in CpG ODN-treated B cells. These data indicate the critical role of NF kappa B and Irf4 in the regulation of IgE CSR through actions downstream of CpG signaling.

Th1 and Th2 cells mutually antagonize each other’s differentiation. Consequently, allergen-specific Th1 cells are believed to be able to suppress the development of Th2 cells and to prevent the development of atopic disorders. To determine whether a pre-existing Ag-specific Th1 response can affect the development of Th2 cells in vivo, we used an immunization model of Ag-pulsed murine dendritic cell (DC) transfer to induce distinct Th responses. When transferred into naive mice, Ag-pulsed CD8α+ DCs induced a Th1 response and the production of IgG2a, whereas CD8α− DCs primed a Th2 response and the production of IgE. In the presence of a pre-existing Ag-specific Th2 environment due to Ag-pulsed CD8α− DC transfer, CD8α+ DCs failed to prime Th1 cells. In contrast, CD8α− DCs could prime a Th2 response in the presence of a pre-existing Ag-specific Th1 environment. Moreover, exogenous IL-4 abolished the Th1-inducing potential of CD8α+ DCs in vitro, but the addition of IFN-γ did not effectively inhibit the potential of CD8α− DCs to prime IL-4-producing cells. Thus, Th1 and Th2 cells differ in their potential to inhibit the development of the other. This suggests that the early induction of allergen-specific Th1 cells before allergy sensitization will not prevent the development of atopic disorders.

Chronic infantile neurologic, cutaneous, articular syndrome (CINCA syndrome) is a severe inflammatory disease that was recently found to be associated with mutations in CIAS1. However, CIAS1 mutations have been detected in only half of CINCA syndrome patients, and it remains unclear which genes are responsible for the syndrome in the remaining patients. We describe here a patient with CINCA syndrome who exhibited CIAS1 somatic mosaicism. We genetically analyzed the CIAS1 gene in various blood cells and the buccal mucosa of the patient. The production of interleukin-1β (IL-1β) by peripheral blood mononuclear cells (PBMCs) was measured by enzyme-linked immunosorbent assay, and the ability of the mutant CIAS1 gene to enhance ASC-dependent NF-κB activation was assessed to confirm that the mutations of CIAS1 found were responsible for the patient's clinical manifestations of the CINCA syndrome. The patient had 1 heterologous single-nucleotide polymorphism, 587G>A (S196N), and 1 heterologous mutation, 1709A>G (Y570C), in exon 3 of CIAS1. The latter mutation was found to occur as somatic mosaicism. The patient's PBMCs produced a large amount of IL-1β in the absence of stimulation, unlike those from controls or from his mother, who also bore the S196N polymorphism. In addition, the Y570C mutation (with or without the S196N polymorphism) increased the ability of CIAS1 to induce ASC-dependent NF-κB activation, unlike the wild-type gene or the gene bearing the S196N polymorphism alone. The findings in this patient indicate that somatic mosaicism is one reason CIAS1 mutations have not been detected in some patients with CINCA syndrome.

最近, 様々な優れた特性を持つ鋼材が開発されている. しかし, それらの鋼材は, 必ずしも橋梁の性能と適合したものになっているわけではない. 橋梁の性能に適合した鋼材を選定することができれば, 橋梁の性能向上のほか, 橋梁の建設コストを縮減することも可能になる.本論文では, 日本における高強度鋼材の開発と使用の歴史をレヴューしたうえで, 橋梁用鋼材として求められる性能をまとめ, その性能を満足する鋼材を橋梁用高性能鋼材BHS500, BHS500WおよびBHS700として提案する. BHS500およびBHS500Wについては, 各種特性試験を行って要求性能を満足することを確認するとともに, これらの鋼材を用いるとどの程度のコスト縮減効果が得られるかを試設計により検討した.

Background: Although the T H 1/T H 2 balance is important in many clinical situations, the regulatory mechanisms in vivo have not been well elucidated. Objective: We sought to characterize the immunologic status of mice lacking Id2, an inhibitor of basic helix-loop-helix transcription factors. Methods: We analyzed serum immunoglobulin levels, gene-expression profiles in the spleen, T H 1/T H 2 balance, and dendritic cell (DC) populations of Id2 –/– mice. Results: Serum levels of T H 2-mediated IgG1 and IgE were increased more than 10-fold in Id2 –/– mice without antigenic stimulation. Gene-expression analysis in Id2 –/– splenocytes revealed enhanced expression of T H 2-related genes, such as IL-4, and reduced expression of T H 1-related genes, including IFN-γ and IL-12. Intracellular cytokine staining also confirmed that Id2 –/– splenic CD4 + T cells are substantially skewed to T H 2 cells. However, Id2 –/– naive CD4 + T cells differentiated into T H 1 cells comparably with wild-type T cells under the appropriate culture conditions. Id2 –/– mice displayed a selective and remarkable reduction of the CD8α + DC subset, which is known to induce preferential T H 1 differentiation. Conclusion: Id2 is an indispensable regulator of the T H 1/T H 2 balance, possibly through the proper development of CD8α + DCs, and could be a novel target to treat allergic diseases. J Allergy Clin Immunol 2003;111:136-42.

Serum concentrations of immunoglobulin E (IgE) in normal circumstances are kept much lower than those of other Ig isotypes to avoid allergic reactions. B cells lacking Id2 have increased E2A activity, which leads to specific enhancement of germline transcription of the immunoglobulin epsilon locus. As a consequence, Id2-deficient B cells undergo class switch recombination (CSR) to IgE at a much higher frequency than wild-type B cells. In contrast, Id2 is induced in wild-type B cells by transforming growth factor-beta1 (TGF-beta1) and suppresses IgE CSR. Our results provide evidence for the inhibitory and selective role of Id2 in IgE CSR in response to TGF-beta1. Id2 might act as molecular safeguard to suppress IgE CSR to prevent serious complications such as allergic hypersensitivity during the normal course of immune responses.

Analysis of general childhood population data showed that there was a significant positive association between total and low-density lipoprotein cholesterol levels and atopy, independent of obesity or sex, which suggest a relationship between hyperlipidemia and greater allergic sensitization among schoolchildren.

Background Valproate-induced Fanconi syndrome is a rare adverse effect of valproate. Severely disabled patients who require tube feeding are reported to be susceptible to valproate-induced Fanconi syndrome. Although most patients with valproate-induced Fanconi syndrome are asymptomatic and detected incidentally with findings such as hypophosphatemia, hypouricemia, increased urinary β2-microglobulin, and generalized hyperaminoaciduria, clinical symptoms such as bone fracture, fever, tachypnea, and edema have been reported. Patient description This 15-year-old, severely disabled, tube-fed, male patient with cytochrome oxidase deficiency had taken valproate for 3 years when he developed fever for 3 weeks. Hypophosphatemia, hypouricemia, hypokalemia, increased urinary β2-microglobulin, and generalized hyperaminoaciduria, as well as hypocarnitinemia, were found, indicating that he had Fanconi syndrome. Valproate was the most likely cause of Fanconi syndrome in this patient. After discontinuation of valproate, the fever resolved immediately, and the laboratory findings normalized. Conclusion Valproate-induced Fanconi syndrome should be considered when individuals taking valproate develop fever of unknown origin.

The high-affinity IgE receptor (FcepsilonRI) on mast cells and basophils consists of a ligand-binding alpha-chain and two kinds of signaling chains, a beta-chain and disulfide-linked homodimeric gamma-chains. Crosslinking by multivalent antigen results in the aggregation of the bound IgE/alpha-chain complexes at the cell surface, triggering cell activation, and subsequent internalization through coated pits. However, the precise topographical alterations of the signaling beta- and gamma-chains during stimulation remain unclarified despite their importance in ligand binding/signaling coupling. Here we describe the dynamics of FcepsilonRI subunit distribution in rat basophilic leukemia cells during stimulation as revealed by immunofluorescence and immunogold electron microscopy. Immunolocalization of beta- and gamma-chains was homogeneously distributed on the cell surfaces before stimulation, while crosslinking with multivalent antigen, which elicited optimal degranulation, caused a distinct aggregation of these signaling chains on the cell membrane. Moreover, only gamma- but not beta-chains were aggregated during the stimulation that evoked suboptimal secretion. These findings suggest that high-affinity IgE receptor beta- and gamma-chains do not co-aggregate but for the most part form homogenous aggregates of beta-chains or gamma-chains after crosslinking.