Rice protein-induced enterocolitis syndrome with transient specific IgE to boiled rice but not to retort-processed rice.

Described herein is the case of an 8-month-old girl with atypical food protein-induced enterocolitis syndrome due to rice. She presented with vomiting and poor general activity 2 h after ingestion of boiled rice. Oral food challenge test using high-pressure retort-processed rice was negative, but re-exposure to boiled rice elicited gastrointestinal symptoms. On western blot analysis the patient's serum was found to contain IgE bound to crude protein extracts from rice seed or boiled rice, but not from retort-processed rice. The major protein bands were not detected in the electrophoresed gel of retort-processed rice extracts, suggesting decomposition by high-temperature and high-pressure processing. Oral food challenge for diagnosing rice allergy should be performed with boiled rice to avoid a false negative. Additionally, some patients with rice allergy might be able to ingest retort-processed rice as a substitute for boiled rice.

Japanese pediatric guideline for the treatment and management of bronchial asthma 2012.

A new version of the Japanese pediatric guideline for the treatment and management of bronchial asthma was published in Japanese at the end of 2011. The guideline sets the pragmatic goal for clinicians treating childhood asthma as maintaining a "well-controlled level" for an extended period in which the child patient can lead a trouble-free daily life, not forgetting the ultimate goal of obtaining remission and/or cure. Important factors in the attainment of the pragmatic goal are: (i) appropriate use of anti-inflammatory drugs; (ii) elimination of environmental risk factors; and (iii) educational and enlightening activities for the patient and caregivers regarding adequate asthma management in daily life. The well-controlled level refers to a symptom-free state in which no transient coughs, wheezing, dyspnea or other symptoms associated with bronchial asthma are present, even for a short period of time. As was the case in the previous versions of the guideline, asthmatic children younger than 2 years of age are defined as infantile asthma patients. Special attention is paid to these patients in the new guideline: they often have rapid exacerbation and easily present chronic asthmatic conditions after the disease is established.

Japanese Guideline for Food Allergy 2014.

A food allergy is defined as "a phenomenon in which adverse reactions are caused through antigen-specific immunological mechanisms after exposure to given food." Various symptoms of food allergy occur in many organs. Food allergies are classified roughly into 4 clinical types: (1) neonatal and infantile gastrointestinal allergy, (2) infantile atopic dermatitis associated with food allergy, (3) immediate-type food allergy (urticaria, anaphylaxis, etc.), and (4) food dependent exercise-induced anaphylaxis and oral allergy syndrome (i.e., specific forms of immediate food allergy). The therapy for food allergies includes treatment of and prophylactic measures against hypersensitivity such as anaphylaxis. A fundamental prophylactic measure is the elimination diet. However, elimination diets should be used only if necessary because of the patient-related burden. For this purpose, it is very important that causative foods be accurately identified. There are a number of means available to identify causative foods, including the history taking, a skin prick test, detection of antigen-specific IgE antibodies in the blood, the basophil histamine release test, the elimination diet test, and the oral challenge test, etc. Of these, the oral challenge test is the most reliable. However, it should be conducted under the supervision of experienced physicians because it may cause adverse reactions, such as anaphylaxis.

Japanese Guideline for Food Allergy 2014.

A food allergy is defined as "a phenomenon in which adverse reactions are caused through antigen-specific immunological mechanisms after exposure to given food." Various symptoms of food allergy occur in many organs. Food allergies are classified roughly into 4 clinical types: (1) neonatal and infantile gastrointestinal allergy, (2) infantile atopic dermatitis associated with food allergy, (3) immediate-type food allergy (urticaria, anaphylaxis, etc.), and (4) food dependent exercise-induced anaphylaxis and oral allergy syndrome (i.e., specific forms of immediate food allergy). The therapy for food allergies includes treatment of and prophylactic measures against hypersensitivity such as anaphylaxis. A fundamental prophylactic measure is the elimination diet. However, elimination diets should be used only if necessary because of the patient-related burden. For this purpose, it is very important that causative foods be accurately identified. There are a number of means available to identify causative foods, including the history taking, a skin prick test, detection of antigen-specific IgE antibodies in the blood, the basophil histamine release test, the elimination diet test, and the oral challenge test, etc. Of these, the oral challenge test is the most reliable. However, it should be conducted under the supervision of experienced physicians because it may cause adverse reactions, such as anaphylaxis.

[Case of atopic dermatitis in infant treated with Chinese herbal medicines and nsaids ointment, which induced weight loss, electrolyte disturbance and hypoproteinemia].

We report here a 4-month-old girl with atopic dermatitis accompanied by weight loss, electrolyte disturbance, hypoproteinemia and hypogammaglobulinemia. She has suffered from eczema since one-month of age. Although she was treated with Chinese herbal medicines, including Syosaikotokakikyosekko, Tokishigyakukagoshuyushokyoto and Jumihaidokuto and ibuprofen ointment since three-month of age, she was referred to our hospital due to deteriorated eczema, severe diarrhea and failure to thrive. Laboratory examination revealed hyponatremia, hyperpotassemia, hypoproteinemia, hypogammaglobulinemia and elevated levels of serum IL-18, TARC and fecal EDN. Drug-induced lymphocyte stimulation tests were positive for the prescribed Chinese herbal medicines. Discontinuation of these medicines and application of steroid ointments improved loose bowels and skin lesions as well as laboratory data. It is suggested that the application of inadequate ointment and Chinese herbal medicines exaggerated inflammation in the skin and the intestinal mucosa leading to electrolyte disturbance, hypoproteinemia and hypogammaglobulinemia. Chinese herbal medicines are depicted as an additional therapy in Japanese guideline for atopic dermatitis, whereas their indication to infants with atopic dermatitis should be carefully assessed.

Immunotherapy with oligomannose-coated liposomes ameliorates allergic symptoms in a murine food allergy model.

BACKGROUND: Allergen-specific immunotherapy has been anticipated to be a disease-modifying therapy for food allergies. We previously reported that CD8(+) regulatory T cells may prevent antigen-sensitized mice from developing allergic diarrhea. Because oligomannose-coated liposomes (OML) have been shown to induce MHC class I-restricted CD8(+) T cell responses, we analyzed the adjuvant activities of OML for inducing regulatory CD8(+) T cells and mucosal tolerogenic responses in allergen-sensitized mice. METHODS: The BALB/c mice that were previously sensitized to ovalbumin (OVA) were intranasally immunized with OVA-encased in OML (OVA-OML) or OVA-encased in non-coated liposomes (OVA-NL). We assessed allergic diarrhea induced by oral OVA administration, OVA-specific immunoglobulin production, and cytokine production in the intestines and mesenteric lymph nodes (MLNs). RESULTS: Intranasal immunization with OVA-OML, but not OVA-NL, suppressed the development of allergic diarrhea. This was associated with in vitro Ag-induced IL-10 production and the in vivo expansion of CD8(+) CD28(-) and CD4(+) CD25(+) Foxp3(+) T cell populations among mesenteric lymph node mononuclear cells, and was significantly ablated by anti-SIGNR1 or anti-CR3 mAbs. Up-regulation of serum OVA-specific IgE was suppressed, whereas OVA-specific IgG1, IgG2a, and soluble IgA production were enhanced by intranasal administration of OVA-OML. Adoptive transfer of CD8(+) CD28(-) T cells but not CD28(+) CD8(+) T cells from the MLNs of OVA-OML-treated mice ameliorated the development of diarrhea. CONCLUSION: These results suggest that intranasal immunization with Ag-encased OML may be an effective immunotherapy for food allergies, as it induces a subset of regulatory CD8(+) T cells as well as CD4(+) CD25(+) Foxp3(+) T cell and modulates humoral immune responses in allergen-sensitized mice.

Japanese pediatric guidelines for the treatment and management of bronchial asthma 2008.

Abstract The fourth version of the Japanese Pediatric Guidelines for the Treatment and Management of Bronchial Asthma 2008 (JPGL 2008) was published by the Japanese Society of Pediatric Allergy and Clinical Immunology in December 2008. In JPGL 2008, the recommendations were revised on the basis of the JPGL 2005. The JPGL 2008 is different to the Global Initiative for Asthma guideline in that it contains the following items: a classification system of asthma severity; recommendations for long-term management organized by age; a special mention of infantile asthma; and an emphasis on prevention and early intervention. Here we show a summary of the JPGL 2008 revising our previous report concerning JPGL 2005.

Antigen-primed splenic CD8+ T cells impede the development of oral antigen-induced allergic diarrhea.

BACKGROUND: Although CD4+ T-cell populations are thought to be involved in the pathophysiology of food allergy and oral tolerance, the role of CD8+ T cells remains uncertain. OBJECTIVE: We analyzed regulatory effects of adoptively transferred CD8+ T cells on the development of allergic diarrhea in antigen-sensitized mice that had a significantly reduced number of conventional TCRalphabeta+ CD8+ T cells. METHODS: Ovalbumin-specific T-cell receptor transgenic mice were systemically sensitized to ovalbumin. Splenic CD8+ T cells purified from ovalbumin-sensitized or nonsensitized wild-type mice or IL-10 knockout mice were adoptively transferred to ovalbumin-sensitized ovalbumin-specific T-cell receptor transgenic mice. Allergic diarrhea induced by oral administration of ovalbumin, ovalbumin-specific immunoglobulin production, and cytokine production in intestines and mesenteric lymph nodes were assessed. RESULTS: Adoptive transfer of splenic CD8+ T cells from ovalbumin-primed mice, but not from nonprimed mice, suppressed the development of allergic diarrhea, which was associated with in vivo increased IL-10 mRNA expression and in vitro antigen-specific IL-10 production by mesenteric lymph node cells. Upregulation of serum ovalbumin-specific IgE was not suppressed by ovalbumin-primed CD8+ T-cell transfer. Although administration of IL-10 before ovalbumin challenge failed to alleviate allergic diarrhea, transfer of splenic CD8+ T cells from IL-10 knockout mice showed diminished preventive effects. CONCLUSION: Systemic immunization with allergen simultaneously induces regulatory CD8+ T cells that can inhibit the development of allergic diarrhea. IL-10 production by regulatory CD8+ T cells appears to be partially involved in these inhibitory mechanisms.

[Retrospective analysis of pervasive developmental disorder patients initially diagnosed with attention deficit/hyperactivity disorder].

We retrospectively analyzed 66 patients with pervasive developmental disorder (PDD) whose respective diagnoses had been changed from attention deficit/hyperactivity disorder (AD/HD) and compared their clinical characteristics with those in patients whose diagnoses was not altered (n = 135). Of 52 patients, 41 (79%) had language delay or hyperactivity at initial examination. Of the 47 patients treated with methylphenidate, 41 patients (87%) responded favorably. The patients with altered diagnoses were categorized into three groups with inappropriate diagnoses (n = 32), amended diagnoses (n = 6), and dual diagnoses (n = 28). Consequently, some patients increasingly showed PDD characteristics concomitantly with age; other patients had justified dual diagnoses with PDD and AD/HD. The total points for peculiar behavioral history were significantly higher in patients with altered diagnoses than in those with unaltered diagnoses (5.4 +/- 3.7 vs. 2.6 +/- 2.6, p < 0.001). In particular, the points for language delay, indifference, and persistence were significantly more positive in patients with altered diagnoses. Results suggest that close evaluation of an individual's behavioral history might suggest a differential diagnosis between PDD and AD/HD.

Determination of asymmetric dimethylarginine, an endogenous nitric oxide synthase inhibitor, in umbilical blood.

Endothelial cells produce nitric oxide (NO), a potent vasodilator. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthase. Little is known about the potential physiological roles of ADMA in a perinatal setting. This study measures concentrations of ADMA in umbilical blood using enzyme-linked immunosorbent assay and those of NO as nitrite/nitrate (NOx(-)) using the Griess assay. Their relationship to the degree of prematurity and maternal clinical condition is examined. Results show that ADMA concentrations in umbilical blood from control newborns were about twice as high as those of lactating women, healthy children, and healthy adults. Umbilical blood NOx(-) concentrations from control newborns were about half of those of lactating women, healthy children, and healthy adults. Consequently, the levels of ADMA relative to NOx(-) were about 4-fold higher in umbilical blood from control newborns than in blood from lactating women, healthy children, and healthy adults. Furthermore, the umbilical blood ADMA concentrations and the ratios of ADMA to NOx(-) in newborns were higher according to their birth prematurity and lower birth weight. The umbilical ADMA concentrations were independent of the delivery mode and maternal preeclampsia. We infer that the high ADMA levels play physiological roles in maintaining vascular tone and blood redistribution to vital organs during birth, thereby favoring the circulatory transition from fetal to neonatal life.

High levels of growth factors in human breast milk.

We found very high concentrations of vascular endothelial growth factor, hepatic growth factor, and epidermal growth factor in early breast milk samples obtained from healthy mothers of term infants. This is the first report of simultaneous measurements of three major gastrointestinal trophic substances in human milk.

Evaluation of a urinary multi-parameter biomarker set for oxidative stress in children, adolescents and young adults.

The involvement of reactive oxygen species (ROS) and oxidative stress in pediatric diseases is an important concern, but oxidative stress status in healthy young subjects and appropriate methods for its measurement remain unclear. This study evaluated a comprehensive set of urinary biomarkers for oxidative stress in healthy children, adolescents and young adults. Results show that urinary excretion of acrolein-lysine, 8-hydroxy-2'-deoxyguanosine (8-OHdG), nitrite/nitrate and pentosidine were highest in the youngest subjects and decreased to constant levels by early adolescence. Urinary acrolein-lysine, 8-OHdG, nitrite/nitrate and pentosidine showed significant inverse correlations with age, but pyrraline did not change significantly with age. No significant differences in biomarkers were apparent between males and females. Younger subjects grow rapidly and sustain immune activation, and are probably exposed to high concentrations of ROS and nitric oxide. Consequently, they are more vulnerable to oxidation of lipids, proteins, DNA and carbohydrates. Normal reported values in this study are a basis for future studies of disease mechanisms involving oxidative stress and for future trials using antioxidant therapies for oxidative stress-related diseases in the pediatric field.

Concentrations of thioredoxin, a redox-regulating protein, in umbilical cord blood and breast milk.

Growing evidence indicates that oxidative stress occurs during the fetal-to-neonatal transition. Such stress plays an important role in the pathogenesis of many neonatal diseases. Thioredoxin (TRX), a redox-regulating protein with antioxidant activity, is induced in various cells against oxidative stress and is secreted extracellularly. This study was undertaken to examine the clinical and biological importance of TRX in the perinatal setting. We measured concentrations of TRX in umbilical cord blood and breast milk using a sandwich ELISA. Our study demonstrated that concentrations of TRX in umbilical cord blood were six to seven times higher than those in blood of healthy adults. This study also showed that umbilical concentrations of TRX were correlated significantly with the extent of prematurity of the newborn, and that they were elevated significantly in newborns of mothers with preeclampsia compared to those of mothers without preeclampsia. In contrast, concentrations of coenzyme Q(10) and vitamin E in umbilical blood were lower than adult blood levels. Breast milk concentrations of TRX during the early postpartum period were seven to eight times higher than those in blood of lactating women. Those of the coenzyme Q(10) were lower than adult blood levels, while those of vitamin E were comparable to adult blood levels. Our findings suggest that the systemic release of TRX is enhanced at birth, and that early breast milk is a rich source of this protein. Consequent high levels of TRX in newborns may provide a unique protective mechanism that allows the maintenance of redox balance during the fetal-to-neonatal transition.

Effects of antioxidants and NO on TNF-alpha-induced adhesion molecule expression in human pulmonary microvascular endothelial cells.

Pro-inflammatory cytokines initiate the vascular inflammatory response via upregulation of adhesion molecules on the endothelium. Recent observations suggest that reactive oxygen intermediates may play a pivotal role in TNF-alpha signaling and upregulate gene expression. We therefore evaluated the effects of pyrrolidine dithiocarbamate (PDTC; 0.1 mM) and spermine NONOate (Sper-NO; 1 mM) on adhesion molecule expression and nuclear factor kappa B (NF-kappaB) activation induced by TNF-alpha (10 ng/ml) in cultured human pulmonary microvascular endothelial cells (PMVEC). Treatment of cells with TNF-alpha for 4 h significantly induced the surface expression of E-selectin and ICAM-1. Treatment with TNF-alpha for 8 h significantly induced the surface expression of E-selectin, ICAM-1 and VCAM-1. The upregulation of these adhesion molecules was suppressed significantly by pretreatment with PDTC or Sper-NO for 1 h. 8-Bromo-cyclic GMP (1 mM) had no such effect, suggesting that the NO donor's effect was non-cGMP-dependent. The mRNA expression of E-selectin, ICAM-1 and VCAM-1, and activation of NF-kappaB induced by TNF-alpha for 2 h were decreased significantly by the above two pretreatments. N-acetylcysteine (10 mM) and S-nitroso-N-acetylpenicillamine (1 mM) had little inhibitory effects on the cell surface and mRNA expression of these adhesion molecules stimulated by TNF-alpha. Treatment with TNF-alpha for 4 h enhanced HL-60 leukocyte adhesion to human PMVEC, the effect of which was inhibited significantly by pretreatment with PDTC or Sper-NO. These findings indicate that both cell surface and mRNA expression of adhesion molecules in human PMVEC induced by TNF-alpha are inhibited significantly by pretreatment with PDTC or Sper-NO, possibly in part through blocking the activation of NF-kappaB. Although our in vitro results cannot be directly extrapolated to the in vivo situation, they suggest a potential therapeutic approach for intervention in cytokine-mediated inflammatory processes in the human lung.

Quantification of L-type fatty acid binding protein in the urine of preterm neonates.

We measured urinary excretion of L-type fatty acid binding protein (L-FABP) in preterm neonates on days 1, 5-10, and 25-30 of life. Urinary L-FABP levels (expressed as the ratio to creatinine) in preterm neonates were considerably higher than those of healthy adults. They did not change significantly during the study period. Urinary L-FABP levels showed significant positive correlation with those of urinary N-acetyl-beta-D-glucosaminidase activity on day 1, and with those of 8-hydroxy-2'-deoxyguanosine on days 25-30. These results suggest that L-FABP is expressed in the neonatal kidney. Our results may also point to potential effects of proximal tubular damage and oxidative stress on urinary excretion of L-FABP.

Rat zinc-fingers and homeoboxes 1 (ZHX1), a nuclear factor-YA-interacting nuclear protein, forms a homodimer.

Zinc-fingers and homeoboxes 1 (ZHX1) is a protein which interacts with the activation domain of the A subunit of nuclear factor-Y. To analyze the physiological role(s) of ZHX1, we searched ZHX1-interacting protein(s) using a yeast two-hybrid system. The rat counterpart of ZHX1 cDNAs was cloned from an ovarian granulosa cell complementary DNA (cDNA) library, indicating that ZHX1 is able to form a homodimer. An analysis of the nucleotide sequence and its deduced amino acid sequence show that rat ZHX1 consists of 873 amino acid residues. Northern blot analysis shows that ZHX1 messenger RNA is expressed ubiquitously and that the level in the ovary are not regulated by gonadotropins. Furthermore, transfection experiments with green fluorescence protein (GFP) expression vectors into human embryonic kidney HEK293 cells reveal that full-length ZHX1 fused to the GFP is localized in the nuclei. Thus, we report on the molecular cloning, expression and characterization of full-length rat ZHX1 cDNA.

A randomized study of two long-course prednisolone regimens for nephrotic syndrome in children.

BACKGROUND: Long-course prednisolone regimens have been shown to be more effective than short-course regimens in sustaining remission of nephrotic syndrome in children. However, the most beneficial approach among the long-course regimens remains unknown. METHODS: Seventy-three children with new-onset nephrotic syndrome were allocated at random to the two long-course regimens and followed up for 2 years. Group A was administered prednisolone at a daily dose of 60 mg/m2 for 6 weeks, followed by an alternate-day dose of 40 mg/m2 for 6 weeks (the long daily regimen). Group B was administered the same daily dose for 4 weeks, followed by an alternate-day dose of 60 mg/m2 for 4 weeks, and doses were tapered by 10 mg/m2 every 4 weeks (the long alternate-day regimen). RESULTS: Group B had a lower incidence of corticosteroid toxicities than group A during the initial treatment. Kaplan-Meier analysis of the sustained remission rate of the two treatment groups showed a marginally significant difference (P = 0.069) and showed a significant difference when patients were stratified for age of disease onset (P = 0.048). In a subgroup of younger children (<4 years at onset), group B had a greater rate of sustained remission (P < 0.01) and fewer children with frequent relapses (P < 0.05) than group A, whereas in older children (> or =4 years at onset), both groups had similar good sustained remission rates. CONCLUSION: These findings collectively indicate that the long alternate-day regimen may be more beneficial, with less corticosteroid toxicities, than the long daily regimen, and children with younger age at disease onset may be susceptible to relapse and especially benefit from the long alternate-day regimen for sustaining remission of the disease.

High levels of urinary pentosidine, an advanced glycation end product, in children with acute exacerbation of atopic dermatitis: relationship with oxidative stress.

Pentosidine is an advanced glycation end product formed by sequential glycation and oxidation. The formation of pentosidine is increased in diseases associated with oxidative stress, such as inflammatory conditions. The aim of the present study was to determine the urinary concentration of pentosidine in atopic dermatitis (AD) and its relationship to the inflammatory status of AD. Urine samples of 32 children with AD and 30 age-matched healthy control subjects were assayed for pentosidine, pyrraline (another advanced glycation end product formed by nonoxidative glycation), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) (an established marker of oxidative stress). Of these 3 markers, urinary concentrations of pentosidine were significantly higher in patients with acute exacerbation of AD than in healthy controls and patients with stable AD. Urinary concentrations of 8-OHdG were significantly higher in AD patients with and without acute exacerbation than in healthy controls. Urinary pentosidine levels correlated significantly with those of 8-OHdG when all data of healthy controls and AD patients were plotted. In patients with acute exacerbation of AD, both urinary pentosidine and 8-OHdG significantly decreased after 7 to 9 days of treatment. Our findings in patients with acute exacerbation of AD suggest that pentosidine levels are partly determined by the prevailing oxidative stress in these patients.