Search

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.

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

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.

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.

Month of birth has been shown to affect later development of allergic diseases.We sought to evaluate the relationship between month of birth and the prevalence of atopic dermatitis (AD) in a large-scale general population of schoolchildren and to elucidate the possible mechanism for this relationship.Questionnaire data on the prevalence of allergic diseases were obtained for 33,725 schoolchildren aged 7 to 15 years. In a separate study the water-holding capacity of "uninvolved" skin was compared for children with and without AD.We found striking differences in the prevalence of AD according to the month of birth (chi2 = 34.9, P.0001). Overall, those born in autumn showed the highest (7.5%), and those born in spring showed the lowest (5.5%), prevalence of AD. There was little or no such tendency for the prevalence of bronchial asthma (chi2 = 17.2, P =.103) and allergic rhinitis (chi2 = 24, P =.01). We found no statistical variation across birth month in the ratio of AD with no other allergic disease/total AD, indicating that this deviation was observed whatever the allergic predisposition of the subjects. In a separate study a significantly lower water-holding capacity of uninvolved skin was observed in children with AD even from early infancy.These findings lead us to speculate that the climate in early infancy affects the skin condition and that those born in autumn have dry skin in early infancy, which may ultimately result in a higher prevalence of AD among young schoolchildren. This might be at least one of the "nonallergic" etiologic factors of this complex disease.

Monocytes/macrophages have recently been shown to play a significant role in the pathogenesis of allergic diseases. As the level of soluble CD14 (sCD14) in serum is considered a marker of monocyte/macrophage activation, we measured the levels of sCD14 in allergic asthma and atopic dermatitis (AD), along with acute infectious and inflammatory diseases, to see its clinical relevance. Serum samples were taken from patients with acute infectious and inflammatory diseases, allergic asthma, and atopic dermatitis. sCD14 was measured with our own ELISA system and its level in each disease was compared with normal controls as well as its disease severity. sCD14 was elevated and correlated with C-reactive protein in infectious and inflammatory diseases (n = 26), confirming that it reflects inflammation. sCD14 was also significantly increased both in asthma (n = 94) and adult chronic AD (n = 22). In asthmatic patients, those with higher sCD14 tended to have more severe symptoms, but there was no statistical correlation between sCD14 and severity. In adult chronic AD patients, a correlation between sCD14 and disease severity was observed. However, sCD14 was not elevated in infant AD patients (n = 18) irrespective of severity, suggesting differences in the degree of monocyte/macrophage involvement in the pathogenesis between adult chronic and infant AD. The levels of sCD14 were shown to be upregulated in allergic diseases and might be useful as a marker of monocyte/macrophage involvement in allergic inflammation.

Grisel syndrome is a non-traumatic atlantoaxial subluxation and a rare complication of any inflammatory condition of the upper neck and otolaryngological procedures. Delayed diagnosis causes neurological impairment, ranging from radiculopathy to paralysis and death. Kawasaki disease is a very frequent and important acute febrile vasculitis of childhood that is seen worldwide, and upper neck involvement (cervical lymphadenopathy) is one of the common symptoms of Kawasaki disease. A case of Grisel syndrome that occurred as a complication of Kawasaki disease is reported. This is the first case report, in English, of Grisel syndrome as a complication of Kawasaki disease. Conclusion: Pediatricians should be aware of Grisel syndrome as a possible complication of Kawasaki disease.

Manganese-containing superoxide dismutase (Mn-SOD) content and its immunohistochemical localization in human thyroid tumours and some other thyroid diseases were examined and compared with adjacent normal thyroid tissue. Enzyme-linked immunosorbent assay (ELISA) was used in this study for the measurement of Mn-SOD. The content of Mn-SOD tended to increase in diffuse hyperplasia, adenomatous goitre, and follicular adenoma. In papillary carcinoma, it was significantly higher than in adjacent normal thyroid tissue. Follicular carcinoma also revealed a markedly high Mn-SOD content. In the immunohistochemical study, adjacent normal thyroid tissue showed granular positive staining of Mn-SOD in the cytoplasm. An increase of Mn-SOD was observed in the papillary proliferative lesion of diffuse hyperplasia and in the follicles adjacent to lymphoid tissue in chronic thyroiditis with hypothyroidism. Strong positive staining of Mn-SOD was observed in papillary and follicular carcinomas, whereas in anaplastic carcinoma staining was markedly less intense. These results indicate that the Mn-SOD content varies according to the degree of differentiation of thyroid carcinomas.

Kusunoki T, Morimoto T, Nishikomori R, Yasumi T, Heike T, Mukaida K, Fujii T, Nakahata T. Breastfeeding and the prevalence of allergic diseases in schoolchildren: Does reverse causation matter? Pediatr Allergy Immunol 2010: 21: 60–66. © 2010 John Wiley & Sons A/S Infants at higher risk of allergic diseases might be breastfed for longer periods compared with infants at lower risk in the hope that breastfeeding might reduce the risk of atopic disorders. Therefore, this intention could manifest as an apparent allergy-promoting effect of breastfeeding or reverse causation. To analyze the effect of breast feeding on the prevalence of allergic diseases at school age, a large questionnaire survey was administered to the parents of schoolchildren aged 7–15 yrs. 13,215 parents responded (response rate, 90.1%). Prevalence rates of allergic diseases were compared according to the type of feeding in infancy (either complete breastfeeding, mixed feeding or complete artificial feeding). In both univariate and multivariate analysis, compared with those with complete artificial feeding, those with mixed and complete breastfeeding showed a significantly lower prevalence of bronchial asthma (BA) (p = 0.01 and 0.003, respectively). On the other hand, in univariate analysis, the prevalence of atopic dermatitis (AD) and food allergy (FA) were significantly higher in those with complete breastfeeding (p = 0.04 and 0.01, respectively). There was a significantly higher proportion of complete breastfeeding among those with greater risk of allergic diseases (presence of family history, either eczema or wheeze within 6 months after birth, or FA in infancy). Therefore, our multivariate analysis included these risks as confounding factors, and we found that the promoting effects of breastfeeding on AD and FA disappeared. In conclusion, our data clearly showed the inhibitory effect of breastfeeding on the prevalence of BA at school age. The apparent promoting effect of breastfeeding on the prevalence of AD and FA is most likely because of reverse causation.

NF-kappaB acts as a signal transducer during tumor progression, cell invasion, and metastasis. Dimethylfumarate (DMF) is reported to inhibit tumor necrosis factor-alpha-induced nuclear entry of NF-kappaB/p65. However, only a few reports suggest that DMF inhibits tumor metastasis; also the molecular mechanisms underlying the inhibition of metastasis are poorly understood. We investigated the inhibition of tumor invasion and metastasis by DMF in a melanoma cell line, B16BL6. DMF inhibited B16BL6 cell invasion and metastasis by suppressing the expression and activities of MMPs. DMF also inhibited the nuclear entry of NF-kappaB/p65, thus inhibiting B16BL6 cell invasion and metastasis. These results suggest that DMF is potentially useful as an anti-metastatic agent for the treatment of malignant melanoma.

Although the association between obesity and bronchial asthma (BA) has been gaining more attention, few studies have been conducted concerning the relationship between obesity and other allergic diseases. The objective of this study was to determine whether and how childhood obesity is associated with allergic diseases other than BA, such as atopic dermatitis (AD), allergic rhinitis (AR), allergic conjunctivitis (AC), and either AR or AC (AR/AC). A questionnaire was administered to the parents of 50,086 Japanese schoolchildren. Associations between childhood obesity and the various allergic diseases were evaluated by univariate and multivariate logistic models. Significant associations were found between higher body mass index (BMI) and AD (p = 0.03), and lower BMI and AC (p < 0.0001), and AR/AC (p < 0.0001). There was a significantly higher prevalence of BA in girls with obesity (p = 0.009) than in those without obesity. Significantly lower prevalence of AC (p = 0.01) and AR/AC (p = 0.002) among children with obesity, and AR (p = 0.04) and AR/AC (p = 0.0004) among boys with obesity were observed than those without obesity. Those who were obese and had AD were significantly more likely to have severe symptoms (p = 0.01). Overall, childhood obesity has positive associations with BA prevalence and AD severity, whereas it has negative associations with AR and AC prevalence, especially among boys. Changes in the immunologic balance accompanied by obesity might have different effects on each type of allergic disease. Exploring the mechanisms by which childhood obesity affects allergic status should lead to new management options for childhood allergy.

Protein kinase C (PKC) has been shown to be a signal transducer during tumorigenesis, tumor cell invasion, and metastasis. Recent studies have reported that the PKC inhibitor, 7-hydroxystaurosporine, inhibits tumor cell invasion. However, the molecular mechanisms of this inhibition of invasion and metastasis are not well understood. In the present study, we attempt to clarify the mechanism by which H7, a PKC inhibitor, inhibits tumor cell invasion and metastasis in the melanoma cell line B16BL6. It was found that H7 inhibits B16BL6 cell invasion and metastasis. We also observed that H7 inhibits the mRNA expression and protein activities of matrix metalloproteinase (MMP)-1, -2, -9 and MT1-MMP. Furthermore, H7 suppresses phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2). However, other signal transduction factors, such as p38 mitogen-activated protein kinase (p38MAPK) and c-Jun N-terminal kinase 1/2 (JNK1/2), were unaffected. Moreover, U0126, a MEK1/2 inhibitor, also inhibited B16BL6 cell invasion and metastasis, as well as the mRNA expression and protein activities of MMP-1, -2, -9 and MT1-MMP. This indicates that H7 inhibits signal transduction through the PKC/MEK/ERK pathway, thereby inhibiting B16BL6 cell invasion and metastasis. These results suggest that PKC inhibitors have potential clinical applications in the treatment of tumor cell metastasis.

X-linked ectodermal dysplasia and immunodeficiency (XL-EDA-ID) is an X-linked recessive disease caused by a mutation in the nuclear factor-κB (NF-κB) essential modulator (NEMO). Here we report an XL-EDA-ID patient with atypical features of very few naive-phenotype T cells and defective mitogen-induced proliferation of peripheral blood mononuclear cells (PBMCs). The patient's NEMO defect was diagnosed by flow cytometric analysis of intracellular NEMO staining. Specific cell lineages (monocytes and neutrophils) expressed reduced levels of NEMO, but 2 populations of T, B, and NK cells were detected with normal and reduced expression of NEMO. Genomic analysis revealed that duplication of a 4.4-kb sequence ranging from intron 3 to exon 6 caused the reduced expression of NEMO. Polymorphism analysis showed that the patient's B- and T-cell lines with reduced and normal expression of NEMO had the same X chromosome, indicating that the somatic mosaicism was not due to fetomaternal transfusion but was most likely due to postzygotic reversion. This XLEDA-ID case adds to our understanding of NEMO biology, indicating that NEMO is critical for T-cell development and/or survival in humans as well as in mice. (Blood. 2004;103:4565-4572)

Background The prevalence of allergic diseases has been increasing dramatically and several studies have shown that atopy is related to asthmatic symptoms and bronchial hyperresponsiveness. Objective To observe the relationships between atopic status and asthmatic predisposition (obstructive change in lung function) in apparently healthy young adults in Japan. Methods A sample of 100 healthy Japanese medical students were subjected to a skin prick test for 11 common aeroallergens and food allergens, and their spirometric lung function was measured. Results Surprisingly, 90% of them showed a positive prick test result for at least one of the 11 allergens tested, and 59% of them showed allergic responses to more than three allergens. The positive rate for Dermatophagoides farinae (Der) was the highest (71.0%), followed by house dust (57.0%), Dactylois gloinerata (42.0%), Cryptomeria gromerata (Cry) (40.0%), and cat fur (39.0%). Furthermore, there was no statistical difference in the positive rates for Der and Cry between groups with and without either the present illness or past history of any of the three major allergic diseases: bronchial asthma (BA), atopic dermatitis (AD), or allergic rhinitis (AR). Compared with the positive rates for these aeroallergens, those for food allergens were much lower (4% to 9%). Several lung function parameters, including the levels of FEV 1 % and %V50 which reflect obstructive pulmonary changes, showed significant negative correlation to the number of skin prick test-positive allergens. The same correlation was observed for groups without either the present illness or past history of BA. Conclusion These data suggest that those who are multi-allergic tend to feature subclinical asthma-like changes in their lung functions. Further studies are needed to determine whether this multi-allergic status can lead to future onset of asthma or other allergic diseases.

Time intensity curves for gadolinium-diethylene triaminepentacetic acid (Gd-DTPA) enhanced magnetic resonance imaging (MRI), namely dynamic MRI, were determined for thyroid diseases and compared with findings of histopathologic examination. Time intensity curves for solid lesions were determined, excluding cases with secondary changes such as calcification, hemorrhage, necrosis and fibrosis. Three different patterns of time intensity curves were observed: rapid washout, delayed washout and no change. In our previous study, malignant grades of thyroid tumors were estimated immunohistochemically by epidermal growth factor receptor (EGFR) antibody. In most of malignant diseases and a few benign diseases that had marked cell proliferative activity with staining EGFR strongly, the time intensity curve displayed a delayed washout pattern, in which intensity was above 1/2-maximal value within 10 min after injection Gd-DTPA. Almost all benign diseases and a few well differentiated carcinomas displayed a rapid washout pastern, in which intensity was decreased to lower than 1/2 of peak grade within 10 min following injection and showed staining EGFR weakly. Benign diseases showing no change of time intensity curve, did not almost show aEGFR positive cell. These findings suggested that the time intensity curve obtained from dynamic MRI might indicate differentiated grades and cell proliferating activity of thyroid tumors.

M O N D A Y 719 DOHaD and Allergic Diseases in Schoolchildren: Does IUGR Affect Risk of Allergic Diseases? K. Mukaida, T. Kusunoki, T. Morimoto, M. Sakuma, N. Mito, T. Yasumi, T. Fujii, R. Nishikomori, T. Heike; Department of Pediatrics, Shiga Medical Center for Children, Shiga, JAPAN, Kumiko Allergy clinic, Kyoto, JAPAN, Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, JAPAN, Center for Medical Education, Graduate School of Medicine, Kyoto University, Kyoto, JAPAN. RATIONALE:Developmental Origins of Health andDisease (DOHaD) is the hypothesis that states that the change in fetal programming in response to preterm birth or intrauterine growth restriction (IUGR) is associated with metabolic diseases later in life. It is not clear whether it is also associated with allergic diseases. Our aim was to determine whether the prevalence of allergic diseases in schoolchildren was affected by DOHaD-related prenatal factors, such as being born late preterm (34-36 weeks) or light for dates (LFD). METHODS: A questionnaire-based survey on the prevalence of allergic diseases, such as bronchial asthma (BA), atopic dermatitis (AD), allergic rhinitis (AR), allergic conjunctivitis (AC), and food allergy (FA), as well as birth weight and gestational age, was administered to more than 13,000 schoolchildren. Multivariate analysis was performed to test the differences in the prevalence of allergic diseases between those with or without DOHaD-related factors. RESULTS: The prevalence of any allergic disease did not differ significantly between those born late preterm and term. On the other hand, the prevalence of those with any allergic diseases was significantly lower among LFD children than among non-LFD children (p50.03). Specifically, the prevalence of FAwas significantly lower in LFD children than in non-LFD children (1.9% vs. 3.9%, p50.004). Although not statistically significant, the prevalence of other allergic diseases was also lower in LFD children. CONCLUSIONS: The present data suggest that the change in fetal programming due to IUGR might suppress allergic diseases, especially food allergy, in schoolchildren. Possible mechanisms are discussed.

Background The influence of food avoidance due to allergic symptoms in infancy on the growth of children at school age has not been well evaluated. Methods To determine the growth of schoolchildren who avoided eggs, milk, or wheat due to immediate allergic symptoms in infancy (food avoiders in infancy) (FAI), a questionnaire on the presence of allergic diseases, as well as present height and weight, was administered to the parents of 14,669 schoolchildren. 11,473 subjects had available data. The height and weight standard deviation scores (HtSDS and WtSDS) and body mass index percentile (BMI percentile) of each subject were calculated. Results FAI had significantly lower WtSDS than non-FAI ( P = 0.01). Among those with avoidance at age 3 years, those who avoided two or more foods and those who avoided milk had significantly lower HtSDS than their counterparts ( P = 0.02 and 0.04, respectively). FAI had a significantly lower prevalence of obesity ( P = 0.01) and overweight ( P = 0.002), while there was no difference in the prevalence of underweight ( P = 0.58), resulting in a significantly higher prevalence of appropriate weight ( P = 0.01) compared to non-FAI. Significantly lower prevalence of obesity and overweight was observed even among those who terminated the avoidance by age 3 years. Conclusions FAI were less likely to be obese or overweight, resulting in a higher prevalence of appropriate weight at school age. Further investigation should contribute to better management of food allergy and obesity.

Background: Published data regarding changes in the prevalence of childhood allergic diseases in Japan have been limited. Methods: To observe changes in the recent trends of the childhood allergy epidemic in Japan, a population- based questionnaire survey of allergic diseases was conducted among 13,215 schoolchildren, aged 7 to 15 years, in Kyoto, Japan in 2006. The results were compared with those obtained in the 1996 survey using the same scale and methods in the same region. Results: The prevalences of bronchial asthma (BA), atopic dermatitis (AD), allergic rhinitis (AR), and allergic conjunctivitis (AC) in 1996 and 2006 were 5.1% and 5.0% (p = 0.58), 4.2% and 5.6% (p < 0.0001), 20.3% and 27.4% (p < 0.0001), and 13.3% and 25.2% (p < 0.0001), respectively. Although the distribution of BA severity improved, the severity distribution of AD, AR, and AC all deteriorated. The lifetime prevalence (present prevalence and past history combined) of BA increased from 6.5% to 7.6% (p < 0.0001). The sex ratio analysis showed that the female predominance in the prevalence of AD observed in 1996 disappeared in 2006, indicating a particular rise in AD prevalence among boys. Conclusions: Overall, the results indicate that the rising trend of allergic diseases, especially in AD, AR, and AC, continues among schoolchildren living in Kyoto, Japan. Special attention should be paid to skin and naso- ocular symptoms.