Influence of SNPs in cytokine-related genes on the severity of food allergy and atopic eczema in children.

Although many single nucleotide polymorphism (SNP) studies have reported an association of atopy, allergic diseases and total serum immunoglobulin E (IgE) levels, almost all of these studies sought risk factors for the onset of these allergic diseases. Furthermore, many studies have analyzed a single gene and hardly any have analyzed environmental factors. In these analyses, the results could be masked and the effects of other genes and environmental factors may be decreased. Here, we described the correlation between four genes [interleukin (IL)-4 (C-590T), IL-4 receptor (A1652G), FCER1B (G6842A) and STAT6 (G2964A)] in connection with IgE production; the role of IL-10 (C-627A) as a regulatory cytokine of allergy; and the severity of food allergy (FA) and atopic eczema (AE) in 220 Japanese allergic children. In addition to these SNPs, environmental factors, i.e., patient's attitude, indoor environment, and so on, were also investigated in this study. Our study was retrospective, and the correlation was analyzed by our defined clinical scores divided into three terms: worst symptoms, recent symptoms and general amelioration at the most recent examination during the disease course. Our results indicated that IL-10 AA, the genotype with lower IL-10 production, is associated with higher IgE levels in the serum (p < 0.0001, estimate; 0.912). Marginal liver abnormalities were observed in the subject group with both FA and AE (p < 0.1191, estimate; 0.1490). Our defined clinical scores enabled evaluation of various aspects of disease severity. Based on the scores, while no single SNP selected in this study determined severity, the combination of the SNP with laboratory data and environmental factors appeared to determine severity.

Clinical applications of real-time PCR for diagnosis and treatment of human cytomegalovirus infection in children.

There are many methods of detecting human cytomegalovirus (HCMV) infection. So far, the quantitative polymerase chain reaction (PCR) has been very useful not only in aiding in the diagnosis of HCMV but also in determining the severity and predicting HCMV infection. However, it is time-consuming and labor intensive. Real-time PCR (RT-PCR) is an exception, for it allows rapid quantification of HCMV DNA load. Our group used this method for detecting and monitoring HCMV and compared it with the diagnostic criterion recommended by the Pediatric Branch of Chinese Medical Association, in 45 children suspected of having HCMV infection. The response to two types of antiviral treatment on HCMV DNA load was also monitored in HCMV hepatitis cases. RT-PCR was positive in 30 cases while the diagnostic criterion, which includes enzyme-linked immunosorbent assay (ELISA) and/or conventional PCR, was positive in 32 cases. The decrease in the HCMV DNA load was achieved earlier in the modified treatment group compared with the conventional treatment group. A 10(3) copies/ml of HCMV DNA load of is a useful cut-off value in predicting patients who will have symptoms of the disease. RT-PCR can be used not only in detecting HCMV but also in monitoring response to antiviral treatment and risk of having symptoms of the disease.

IgE binding to raw and boiled shrimp proteins in atopic and nonatopic patients with adverse reactions to shrimp.

BACKGROUND: Characterization of seafood allergens is important to understand the immune response to these allergens. Moreover, a detailed comparison between atopic and nonatopic patients with adverse reactions to shrimp has never been reported. METHODS: Raw and boiled shrimp extracts were analyzed by immunoblotting using sera from 9 atopic and 7 nonatopic patients with a history of adverse reactions to shrimp, and 13 control subjects. Total IgE, specific IgE and skin prick tests (SPT) to shrimp were also investigated. RESULTS: The level of specific IgE to shrimp was higher in atopic patients than nonatopic patients (p<0.05). Symptoms, SPT results and major allergens involved were similar in atopic and nonatopic patients. The 16.5-kD protein had the highest frequency of IgE binding followed by the 40-kD protein in these patients. Other minor IgE-binding proteins were observed at the 20-, 22-, 54-, 72-, 129- and 140-kD regions. Patients who had binding to the 16.5-kD protein had either positive (25% raw/31% cooked) or negative (13% raw/cooked) CAP-FEIA-RAST, while patients who recognized the 40-kD protein all had positive (31% raw/19% cooked) CAP-FEIA-RAST. All control subjects had negative immunoblots for these two proteins. CONCLUSION: The 16.5-kD protein was the most frequent protein identified regardless of CAP-FEIA-RAST results, while the 40-kD protein was only present in patients with positive CAP-FEIA-RAST. Therefore, 16.5-kD protein may be an important allergen that is clinically relevant in both atopic and nonatopic patients with adverse reactions to shrimp even if it is not detected by the CAP-FEIA-RAST system.

[The national survey of immediate type of food allergy].

BACKGROUND: The actual conditions regarding immediate type food allergy have not been fully understood. Appropriate countermeasures have not been taken so far. The objective of our research is to identify the actual conditions of immediate type food allergy in Japan for the purpose of contributing to future practices. SUBJECT: We conducted a survey on the patients in collaboration with 2689 domestic hospitals which have pediatrics and more than 100 beds. We focused on these cases who presented with symptoms of allergy within 60 minutes of the intake of any offending food. RESULT: 60.4% of collaborators returned the questionnaire. We investigated 1420 cases in 498 hospitals. Average age of cases was 6.7+/-13.1 (Mean+/-SD). Ages not more than 8 years-old comprised 80.1% of the whole population. The most common offending foods were eggs, milk products, wheat, buckwheat, fish and fruits. In addition, offending foods varied depending on age. The clinical symptoms appeared at 24.2 minutes+/-19.4 minutes (Mean+/-SD) after the intake of offending foods. The most common clinical symptom was observed on the skin and respiratory organs. CONCLUSION: Based on the results of this study, the Ministry of Health, Labor and Welfare amended the ministerial ordinance concerning the allergy food labeling system. Five major offending foods (eggs, milk, wheat, buckwheat, and peanuts) were designated as ingredients to be specified on the label.

[In vitro evaluation of allergenicity of dried food powders manufactured for food provocation test].

Food provocation test (FPT) is one of important diagnostic methods for food allergy, but no standard antigens for FPT have yet been developed. In this study, dried powders were manufactured from five kinds of foods (cow's milk, hen egg, chicken, soybean and wheat) by spray-drying or freeze-drying and examined in vitro for their usefulness as antigens for FPT. In SDS-PAGE, the migration pattern of the extract from each powder was the same as or closely similar to that of the extract from its material. When analyzed by ELISA, a good correlation (r=0.853-0.978) in the reactivity with sera from food-allergic patients was observed between the extracts from each powder and its material. Moreover, in cow's milk, hen egg and soybean, almost the same ELISA inhibition curves were drawn, regardless of whether the extracts from each powder and its material were used as immobilized antigens or inhibitors. These results demonstrated that each powder contains the same allergens as its material at almost the same levels, being useful as an antigen for FPT. Favorably, the powders were found to be stored without significant changes in IgE reactivity at -20 degrees C or 5 degrees C for more than 18 months, although their storage at room temperature was suggested to be avoided.

A comparison survey of seizures and other symptoms of Pokemon phenomenon.

On 16 December 1997, many Japanese children developed neurologic problems while watching the animated television series Pokemon. This study included children who visited the outpatient departments of 14 pediatric clinics for other reasons within 2 months after this incident. Volunteering children and parents or guardians were asked to complete questionnaires. We obtained 1,373 replies (including 800 males, 558 females, and 15 children without information on sex; mean age, 6.8 +/- 3.5 years). The majority of children included in this study (80%) watched this program, and 67 (6.1%; 40 males, 27 females) were affected by the program. There were 10 patients with seizures (0.9%; four males and six females). Fifty-seven patients developed other symptoms. Compared with nonaffected children, significantly more affected children reported that they concentrated on watching this program, watched it at a short distance from the screen, and did not watch this program in a brightly lit room. Seizures tended to occur in older children (average = 10.8 years) and in children with a high rate of familial histories of seizures. Symptoms other than seizures occurred more frequently, and autonomic and psychologic factors, such as motion sickness, could be considered possible mechanisms. Children who developed symptoms seemed to have problems in viewing conditions.

Pepsin-resistant 16-kD buckwheat protein is associated with immediate hypersensitivity reaction in patients with buckwheat allergy.

BACKGROUND: Buckwheat is becoming popular in many countries as a health food and the incidence of buckwheat allergy is increasing in Asia. The ingestion of small amounts sometimes provokes an anaphylactic reaction. However, it remains controversial which is the major allergen responsible for such reactions. METHODS: The patients whose sera are positive for buckwheat-specific IgE antibody measured by the CAP system fluorescein-enzyme immunoassay (CAP-FEIA) were classified into two subgroups depending on the history of immediate hypersensitivity reactions (IHR). Major buckwheat allergens were identified with immunoblotting, ELISA and N-terminal amino acid sequencing. Various treatments such as pepsin digestion were added to characterize the proteins. RESULTS: We found that the 24-kD protein that had previously been reported to be a major allergen reacted to IgE antibodies present in sera from almost all subjects (19/20) regardless of symptoms. On the other hand, 16- and 19-kD proteins were bound with IgE antibodies present in sera from 9 of the 10 patients with IHR including 8 patients with anaphylaxis but not in sera from buckwheat-specific IgE-positive subjects without IHR. After pepsin treatment, the 16-kD protein but not the 19- and 24-kD proteins remained undigested and preserved the capacity of IgE binding. This pepsin-resistant 16-kD protein had no homology with the 24-kD protein by the N-terminal amino acid sequencing. CONCLUSIONS: The 16-kD buckwheat protein was resistant to pepsin digestion and appeared to be responsible for IHR including anaphylaxis, while the pepsin-sensitive 24-kD protein was responsible for CAP-FEIA but not IHR.

Potter sequence complicated by congenital cystic lesion of the bladder.

We report a case complicated by oligohydramnios, pulmonary hypoplasia, bilateral renal dysplasia, and cystic lesion of the bladder. He was clinically compatible with Potter sequence. Congenital cystic bladder is the rarest form of the bladder. We can find no report of Potter sequence complicated by cystic lesion of the bladder. This lesion was similar to multilocular bladder. The diagnosis was confirmed it by autopsy, magnetic resonance imaging, and urography after his death.

Altered eosinophil levels as a result of viral infection in asthma exacerbation in childhood.

Respiratory viral infection is known to be a significant cause of asthma exacerbation. Eosinophils have been considered to play an important role in the pathogenesis of virus-induced asthma exacerbations. To determine how often asthma exacerbation is caused by virus infections and to examine the relationship between eosinophilia and asthma episode, we investigated 64 children who experienced asthma attacks between October 1999 and March 2000. We used rapid enzyme immunoassays to detect antigens of respiratory syncytial virus (RSV), influenza A virus, and adenovirus in nasopharyngeal secretions (NPS) of these children, and enumerated eosinophils in the blood and NPS. We detected RSV in 27% and influenza A virus in 17% of the patients. No adenovirus infection or RSV/influenza A co-infection was detected. RSV-infected children were younger (3.85 +/- 0.83 years old) than influenza A virus-infected patients (5.23 +/- 1.34 years old). Eighty-two per cent of patients in the RSV group and 36% of patients in the influenza A virus group had moderate-to-severe asthma episodes (p < 0.05). In RSV-infected children, the eosinophil counts in NPS were higher in the 'severe' group, and younger patients had a greater number of eosinophils in their NPS than older patients (p < 0.05). These trends were not found in influenza A virus patients. In conclusion, our results indicate that, compared with influenza A virus-induced asthma attacks, RSV infection had a higher probability of being associated with asthma exacerbation in infants and younger children and induced attacks of greater severity. The increase in the number of eosinophils in the NPS of RSV-infected children may be responsible, in part, for these differences.

Changes of the physiological parameters of very low-birthweight infants with chronic lung disease treated with dexamethasone.

BACKGROUND: Dexamethasone is widely used for the treatment of chronic lung disease (CLD), but its mechanism of action is still not clearly understood. METHODS: Respiratory status, bodyweight, blood pressure, urine volume, fluid intake and nutrient intake were investigated in 12 infants with CLD during treatment with dexamethasone. RESULTS: The mean gestational age of the patients was 26.3 +/- 2.5 weeks and their mean birthweight was 807 +/- 232 g. Treatment with dexamethasone was started at a mean age of 41 +/- 23 days. The ventilatory index (VI) improved after treatment was started. Blood pressure and urine volume increased significantly after treatment, but weight gain was poor during this time. Fluid and nutrient intake did not change before and after treatment. The degree of improvement in the VI after treatment was significantly correlated with an increase in urine volume. CONCLUSIONS: The results suggest that a rise in blood pressure as a result of dexamethasone treatment and the subsequent diuretic effect of this rise may play a role in improvement in respiratory status.

[Symptoms of sick house syndrome and contributory factors; study of general dwellings in Hokkaido].

OBJECTIVE: The aim of this study was to clarify the "Sick House Syndrome" which has recently received increasing attention, and to investigate relationships between symptoms and the state of general dwellings in Hokkaido. METHODS: Questionnaires were sent to residents in 1775 dwellings, mainly solitary houses built or remodeled within the past few years by 24 construction companies in Sapporo and its environs, and answers was received from 564. The questionnaires included queries about building structure and characteristics, the residents' habits in the home, and subjective symptoms. We requested one resident who had the most severe symptoms in the dwelling to answer a questionnaire about symptoms. We classified the symptoms into 11 categories, and selected those that developed or were aggravated after the building or remodeling. We defined dwellings in which inhabitants complained of one or more categories of symptoms as the group with sick-house-related disease (developed or aggravated group: DA group), and those in which the inhabitants complained of two or more symptoms as the group with sick house syndrome (more than one organic symptom group: MO group)". Associations between symptoms and dwellings were then studied. RESULTS: There were 201 dwellings for which residents complained of symptoms (37.2%). Of these, 94 were in the DA group (16.7%), and 57 (10.1%) in the MO group. The symptoms that developed or were aggravated after building or remodeling of the dwellings were throat, 7.1%, dermal, 6.9%, psychoneural, 5.3%, eye, 5.1%, and nasal problems, 4.1%. Unpleasant odors form furniture were significant in both groups (DA: crude odds ratio (OR) 2.66, MO: OR 3.24). Use of aromatics was significant in group DA (OR 1.78). Condensation on windows and mold growth in the dwellings were significant in both groups (condensation on windows; DA: OR 2.98, MO: OR 3.32, mold growth; DA: OR 3.11, MO: OR 3.24). In addition, the percentage of dwellings for which residents complained of symptoms increased with signs of dampness (condensation on windows and mold growth). On logistic regression analysis, condensation on windows and mold growth were significant in both groups, and unpleasant odors from furniture in the MO group. CONCLUSION: It is suggested that symptoms of sick house syndrome are associated with high humidity such as condensation on windows and mold growth, odors from furniture and use of aromatics.

Bronchial Response Study of Asthmatic Patients Using an Atmosphere-Changing Chamber.

We studied the bronchial response to low-pressure conditions by using an atmosphere-controlling chamber. When asthmatic patients were put in a chamber in which the pressure was reduced gradually, their small airways did not change until an estimated 1,000-meter level and from an estimated 1,500 m asthmatic patients' lung function crossed to that of normal subjects. For astmatics there was a remarkable change in saturation of oxygen under low-pressure conditions. Many patients complained of typanophonia under negative-pressure conditions. From these, data we must consider the barometric pressure influence on asthmatic patients.