bluuebunny/crossref_metadata_2025 huggingface dataset:
Is unrecognized anaphylaxis a cause of sudden unexpected death?
Authors: SCHWARTZ H. J. , YUNGINGER J. W. , SCHWARTZ L. B.
Published: April 2006

Background: Serum tryptase levels reflect mast cell activation and correlate with anaphylactic reactions. Elevated post‐mortem serum tryptase levels have been found in witnessed fatal anaphylaxis.

Objective: This study was designed to examine whether or not unwitnessed anaphylaxis may be a hitherto unrecognized cause of sudden unexplained death.

Methods: Mast cell tryptase was measured by immunoassay in 68 post‐mortem sera remaining from a previous study which reported elevated venom‐specific IgE antibodies in 22 (23%) of 94 victims of sudden unexpected death. Autopsies were performed in all cases. The cause of death was independently reported by pathologists unfamiliar with the nature of this study.

Results: Serum tryptase levels were elevated (> 10ng/mL) in nine of 68 cases. The levels could not be predicted from the clinical circumstances surrounding death. Sera from four individuals contained both elevated tryptase and previously reported elevated venom‐specific IgE.

Conlusions: We conclude that mast cell activation may accompany up to 13% of sudden unexpected deaths in adults. Measurement of both tryptase and specific IgE antibody levels in post‐mortem sera from persons experiencing sudden, unexpected death may identify a small subset of cases due to clinically unrecognized fatal anaphylaxis, including those due to insect stings.
Crossreactivity between Dermatophagoides siboney and other house dust mite allergens in sensitized asthmatic patients
Authors: FERRÁNDIZ R. , CASAS R. , DREBORG S. , EINARSSON R. , FERNÁNDEZ B
Published: April 2006

Background
The role of Pyroglyphid mites in IgE‐mediated serisitizalion has been well eslahlished. Although mites belonging to the genus Dermatophagoidess dominate in the acarofauna of domestic dust. non‐pyroglyphid mites might also be of clinical importance. In Cuba, Dermatophagoides siboney is found in dust coexisting with D. pteronyssiuus and Blomia tropicalis. Dermatophagoides forinae is not found. Storage mites, such as Acorus siro, Lepidoglyphus destructor and Tyrophagus putrescentiae might also be present.

Objective
The aim of this study was to investigate the allergenic relationships among the mites present in the environment of allergic patients in Cuba.

Methods
The crossreactivialty between an extract of D. siboney and the above mentioned six mites was studied by specific IgE inhibition, using sera of mite‐sensitive patients after incubation with serial dilutions of D. sibaney.

Results
The inhibitory effect of D. sidiney extract was more pronounced against D. farinae. 91%, than against D. pyteronyssinus, 62%. Specific IgE to B. tropicali, A. siro, L. destructor and T. putrescentiae were inhibited to a much lesser extent, i.e. between 47 and 58%. The correlation between IgE to D. siboney and IgE to D. pteronyssinus and D. farinae was of 0.92 and 0.90. respectively. A weaker correlation was found between D. siboney and L. destructor (0.7), A. siro (0.67), B. tropicalis (0.54) and T. putrescentiae (0.51).

Conclusion
Thus. D. siboney seems to be most closely related to D. farinae.
Perspectives of identity by descent (IBD) mapping in founder populations
Authors: TE MEERMAN G. J. , VAN DER MEULEN M. A. , SANDKUIJL L. A.
Published: April 2006

In a founder population patients with a genetic disease are likely to share predisposing genes from a common ancestor. We show that, depending on the distance of the relationship, patients are expected to share extended segments of DNA around the disease gene. Because of the size of the shared segment, a genomic search with DNA markers for such shared segments, identity by descent (IBD) mapping, can efficiently find the map position of genes, particularly due to genetic drift leading to reduction of heterogeneity and the large number of meioses that is implicitly observed. The statistical power of this method and the approximate cost are given as a function of the density of the map of tested markers and the number of generations since a common ancestor. Initial marker spacings between 5 and 15 centiMorgans are shown to be optimal. IBD mapping is applicable to many genetic diseases, because it does not presuppose a specific genetic model.
Pollen allergen homologues in barley and other crop species
Authors: ASTWOOD J. D. , MOHAPATRA S. S. , NI H. , HILL R. D.
Published: April 2006

Pollen from 10 agricultural plant species was surveyed for the presence of proteins crossreactive with group I, group IV and group IX allergens. Barley (Hordeum vulgare), maize (Zea mays), rye (Secale cerale), triticale (xTriticosecale cereale), oats (Avena saliva), Canola (Brassica napus) and sunflower (Helianthus annux) pollens contained numerous allergen cognate proteins. Northern blot analysis of barley pollen RNA revealed the presence of group I and group IX allergen transcripts. The barley pollen cDNA hvp9742, and three other cloned allergens: phlenum protense (Phip) V, Phl p Va and Lolium perenne (Lol p) 1b, were demonstrated to have extensive nucleotide and amino acid sequence similarity to the Poa p IX isoallergens. It was concluded that hvp9742 represents a Poa p IX isoallergen homologue expressed by barley pollen, and was therefore designated Hor v IX. It is further shown that the most highly conserved domains of all seven proteins, including Hor v IX, map to previously defined Poa p IX antibody binding epitopes.
Blood inflammatory response to inhaled endotoxin in normal subjects
Authors: MICHEL O. , DUCHATEAU J. , PLAT G. , CANTINIEAUX B. , HOTIMSKY A. , GERAIN J. , SERGYSELS R.
Published: April 2006

Previously we have reported that in asthmatics an inhalation of 20 μg lipopolysaccharide (LPS) produces a bronchial obstruction associated with an inflammatory blood response. The aim of the present study was to evaluate this response in normal subjects. Eight normal non‐atopic subjects were challenged by inhalation of a solution containing 20 μg LPS (from Escherichia coli 026:B6) a week after bronchial challenge with control solution. The lung function response was evaluated by the changes in forced expiratory volume in one second (FEV1), in specific conductance and in airway resistance while the blood inflammatory response was evaluated by serial measures of total white blood cells (WBC) and polymorphonuclear neutrophils (PMN) count, luminol enhanced‐chemiluminescence (luminol‐CL, as a marker of the PMN degree of activation), C‐reactive protein (CRP), haptoglobin, complement fraction C3, tumour necrosis factor‐α (TNF‐α) and adrenocorticotropic hormone (ACTH). No response in lung function was observed for 6 h after the LPS inhalation. The count in WBC and PMN increased 300 (P < 0.01) and 360 (P < 0.01) min after the LPS challenge associated with an increase in the level of luminol‐CL (P < 0.001). This rise in luminol‐CL level was significant at 120 min (P < 0.05) before any change in the PMN count. After 24 and 48 h the acute‐phase protein CRP raised significantly (P < 0.01), the other proteins C3 and haptoglobin being unchanged. A slight increase in ACTH was observed 240 and 360 min (P < 0.05) after the LPS challenge while the TNFα detectable level was not modified. In conclusion, in normal subjects, inhalation of a pro‐inflammatory agent is able to induce a systemic inflammatory response in the absence of any effect on lung mechanics, while in asthmatics the same bronchial challenge has been reported to induce a similar blood inflammation associated with a significant response in lung function.
A double‐blind, placebo‐controlled trial of local nasal immunotherapy in allergic rhinitis to Parietaria pollen
Authors: D'AMATO G. , LOBEFALO G. , LICCARDI G. , CAZZOLA M.
Published: April 2006

We assessed the efficacy and safety of local nasal immunotherapy (LNIT) using an extract in macronized powder form of Parietaria pollen, a very important allergenic plant in the Mediterranean and other parts of the world. Twenty‐six patients aged 13–37 years, with seasonal allergic rhinitis to this pollen, were enrolled in a double‐blind placebo‐controlled trial, carried out from autumn 1991 to the end of June 1992. They were selected on the basis of a positive skin‐prick test, radioallergosorbent test (RAST) and intranasal challenge to Parietaria antigen. Patients were randomly divided into two groups of 13; the first group was given Parietaria antigen, and the second placebo. We recorded mean weekly symptom scores and drug consumption for 17 weeks during the pollen season in the year 1992, and specific serum‐IgE and IgG levels. Three patients in the active group withdrew from the study because of bronchial symptoms. A significant difference was observed in mean weekly nasal symptom scores, in drug consumption and in specific nasal threshold to Parietaria allergenic extract in the treated and control groups. No difference was observed in serum IgE and IgG levels. Serum IgE levels rose significantly only in the control group after the pollen season. This study indicates that LNIT may be a useful alternative to traditional subcutaneous immunotherapy in patients with allergic rhinitis.
Epithelial pathways for luminal entry of bulk plasma
Authors: ERJEFÄLT J. S. , ERJEFÄLT I. , SUNDLER F. , PERSSON C. G. A.
Published: April 2006

Inflammatory challenges of the airway mucosa cause luminal entry of bulk plasma. Extravasation of plasma is well described but the routes for epithelial passage of plasma are largely unknown. Using colloidal gold (5 nm) as tracer we have now examined the fate of extravasated plasma in the airways. The tracer was given intravenously to anaesthetized, ovalbumin‐sensitized guinea‐pigs 2min prior to airway mucosal challenge with 12pmol ovalbumin (the dose was selected from a separate dose‐response study). Tissue specimens were collected 30s, 3 and 6 min after end of challenge (separate time course experiments suggested that the peak rate of entry of plasma occurred at about 5 min). The colloidal gold particles were visualized by autometallographic silver intensification. The gold produced no circulatory disturbance and had a uniform vascular distribution with negligible adherence to vascular endothelium. After challenge gold was first widely distributed in the lamina propria. At 3 and 6 min the tracer was also in the epithelium and airway lumen. It appeared that plasma was moved distinctly between and all around each epithelial cell. Bright field‐, scanning‐, and transmission electron‐microscopy indicated that the luminal entry of plasma did not affect the integrity of the epithelial lining. This study demonstrates that the plasma exudate moves across an intact epithelial layer through ubiquitous paracellular pathways. Even at a pronounced acute plasma exudation response exceedingly small amounts of plasma may pass around a single cell explaining the non‐injurious nature of mucosal exudation of bulk plasma in health and disease.
House dust mite allergen levels in two cities in Canada: effects of season, humidity, city and home characteristics
Authors: CHAN‐YEUNG M. , BECKER A. , LAM J. , DIMICH‐WARD H. , FERGUSON A. , WARREN P. , SIMONS E. , BRODER I. , MANFREDA J.
Published: April 2006

The homes of 120 patients with asthma, 57 in Vancouver and 63 in Winnipeg, were studied. The characteristics of the homes were assessed by a questionnaire. Dust samples were collected and the indoor relative humidity was measured four times during the year covering all four seasons in both cities. Mite allergen levels were determined using monoclonal antibodies against Der p I and Der f I by the ELISA method. The mean levels of both mite allergens in mattress and floor samples in the homes in Vancouver and in Winnipeg were relatively low for all seasons. Mite allergen levels were found to be associated with city, season and individual home differences. They were significantly higher in Vancouver than in Winnipeg. Der p I and Der f I in mattress samples in both cities and Der f I in floor samples in Vancouver, varied by season. The indoor relative humidity level in the homes in Vancouver were also significantly higher than those in Winnipeg. There was, however, no significant association between the levels of indoor relative humidity and the levels of mite allergens after adjusting for variations in city, season and individual home. Although individual home differences were highly associated with mite allergen levels, only a few home characteristics were found to be related to mite allergen levels such as the type and the age of the home, the type of heating, the use of feather pillows and the number of occupants in the homes. Whether low levels of mite allergens are partially responsible for the relatively low prevalence of childhood asthma in Canada remains to be investigated.
A standardized densitometric immunoblotting analysis of Candida albicans protein allergens
Authors: SAVOLAINEN J.
Published: April 2006

Sera from 196 patients with a strong skin reactivity to Candida albicans and a history of atopic disease were used for C. albicans IgE‐immunoblotting. The IgE‐immunoblots were analysed by densitometry and integration of the densitogram peaks. A standardized reference disc system allowed parallel analysis of several different immunoblotting experiments. Altogether 105 patients had C. albcans specific IgE antibodies in immunoblotting. The IgE‐response against C. albicans was extremely polyspecific and was directed against 42 different bands. The most important IgE binding bands were 46 kDa and 27 kDa bands against which 44 (42%) and 29 (28%) patients, respectively, had IgE responses. A combination of IgE‐immunoblotting and densitometry was found practical in analysis of large number of patient sera allowing a profound and accurate analysis and characterization of C. albicans allergen extract. This data evolved from a sufficiently large patient population can be utilized in further standardization of C. albicans extracts.
Antiallergic activity of loratadine: inhibition of leukotriene C4 release from human leucocytes
Authors: MIADONNA A. , MILAZZO N. , LORINI M. , MARCHESI E. , TEDESCHI A.
Published: April 2006

The H1 antagonist loratadine has the capacity to inhibit histamine release from human basophils. The aim of this study was to investigate whether loratadine can also inhibit leukotriene C4 (LTC4) release from human leucocytes. Basophil‐enriched mononuclear cell suspensions were prepared by centrifugation of peripheral venous blood (n= 10) on discontinuous Percoll gradients. Leucocytes were stimulated with anti‐IgE, N‐formylmethionyl‐leucyl‐phenylalanine (FMLP) and Ca2+ ionophore A23187; immunoreactive (i) LTC4 release in the cell supernatant was measured by a competitive radioimmunoassay and histamine release was evaluated by an automated fluorometric technique. Loratadine, in the concentration range of 1–50μM, exerted a dose‐dependent inhibitory effect on IgE‐mediated and IgE‐independent histamine and iLTC4 release. The concentrations inhibiting 50% of histamine release were 30 μM (anti‐IgE), 27μM (FMLP) and 19μM (Ca2+ ionophore A23187). The concentrations inhibiting 50% of iLTC4 release were 2–3 μM (anti‐IgE). 11 μM (FMLP) and 1.7μM (Ca2+ ionophore A23187). The inhibitory activity on iLTC4 release was optimal after preincubation for 2h at 37°C, and was no longer evident when leucocytes were stimulated 2h after cell washing. Increased extracellular Ca2+ concentrations reduced the inhibitory activity of loratadine. These results indicate that loratadine has the capacity to inhibit the release of preformed and newly generated mediators from human basophil‐enriched mononuclear cell suspensions.
Ability of inhaled procaterol, a β32 adrenoceptor agonist, to attenuate eicosanoid‐induced airflow obstruction and airway microvascular leakage
Authors: TOKUYAMA K. , ARAKAWA H. , MOCHIZUKI H. , MORIKAWA A.
Published: April 2006

Beta‐2 adrenoceptor agonists are widely used as bronchodilators in the treatment of asthma mainly via inhalation. In the present study, we evaluated the ability of inhaled procaterol, a β2 adrenoceptor agonist, to reduce eicosanoid‐induced airway micro‐vascular leakage, and compared the ability with its inhibitory effect against bron‐choconstriction. Tracheostomized guinea‐pigs were given aerosolized procaterol (10 or 100 μg/ml) for 10min under spontaneous breathing. Immediately after the end of inhalation, the animals were mechanically ventilated. Fourteen minutes after the end of inhalation, Evans blue dye (20mg/kg) was given i.v. One minute later, 2nmol/kg leukotriene D4 (LTD4), 50 nmol/kg U‐46619, a thromboxane A2 mimetic, or vehicle was administered i.v. LTD4‐ or U‐46619‐induced increase in lung resistance was measured for 6 min. After removing the lungs, the amount of extravasated Evans Blue due in the lower airways was examined as an index of microvascular leakage. Inhaled procaterol significantly attenuated increases in both lung resistance and Evans Blue dye extravasation caused by these eicosanoids. The degree of inhibition was almost complete for lung resistance (approximately 90%), but it was only partial (range 18.5–61.2%) for the dye extravasation. No significant changes in mean systemic blood pressure and in heart rate was observed after an inhalation of 10μg/ml procaterol. These results suggest that inhaled β2 adrenoceptor agonists may reduce airway microvascular leakage caused by inflammatory mediators such as eicosanoids without affecting systemic circulation. However, these agonists may attenuate airway microvascular leakage only partially even in doses which can inhibit bronchoconstric‐tion almost completely.
Asthmatic symptoms and indoor levels of micro‐organisms and house dust mites
Authors: BJÖRNSSON E. , NORBÄCK D. , JANSON C. , WIDSTRÖM J. , PALMGREN U. , STRÖM G. , BOMAN G.
Published: April 2006

As a part of a worldwide investigation on the prevalence of respiratory symptoms, we have performed a study on the relationship between the indoor environment and asthma‐like symptoms in the population of a central Swedish municipality. The study comprised 88 individuals, aged 20–45 years who underwent a structured interview, spirometry, a methacholine provocation test, skin‐prick tests and blood samples for measurements of serum concentrations of eosinophil cationic protein (S‐ECP), blood eosinophil count and total immunoglobulin E (S‐IgE). In the homes, the room temperature, air humidity, respirable dust, house dust mites (HDM) and airborne micro‐organisms were measured. The relative humidity in all the homes was found to be above 33%. HDM were found in 13% of homes. In the homes of the 47 subjects with asthma related symptoms, significantly higher total levels of bacteria and mould (P<0.05) and a higher proportion of detected HDM (OR = 5.3) was found than in subjects with no asthma related symptoms, after adjustment for age, sex, smoking, indoor temperature and air humidity. HDM were found to be an independent risk factor for asthma related symptoms (OR = 7.9) and nocturnal breathlessness (OR = 6.2) (P<0.05), while the total level of bacteria was a risk factor for asthma related symptoms and wheezing (P<0.05). We conclude that although HDM is relatively infrequently found in the homes of central‐Sweden, the presence of HDM is related to asthmatic symptoms. A relation between levels of airborne bacteria and asthma related symptoms was also found.
Validation and application of a new simple strategy for measurements of urinary leukotriene E4 in humans
Authors: KUMLIN M. , STENSVAD F. , LARSSON L. , DAHLÉN B. , DAHLEN S.‐E.
Published: April 2006

To monitor endogenous production of cysteinyl‐containing leukotrienes, the end‐metabolite leukotriene E4 (LTE4) was analysed in urine. Results obtained with a sensitive enzyme immunoassay (EIA), performed on crude urine samples correlated well with data obtained from a previously reported radioimmunoassay. Enzyme immunoassay analysis of unextracted urine was justified by an excellent agreement between analyses in crude samples and measurements achieved after purification on solid phase extraction followed by separation on reversed‐phase high performance liquid chromatography. Moreover, LTE4 was stable in urine samples stored at ‐20°C, for months without the addition of preservatives. The stability of LTE4 in urine was not improved by addition of the antioxidant 4‐hydroxy‐TEMPO and pH adjustment to 9. As assessed by EIA analysis in crude urine samples, baseline values for urinary leukotriene E4 were not significantly different between atopic asthmatic subjects and non‐asthmatic individuals, and there was no diurnal variation in urinary excretion of LTE4 in healthy subjects. However, we confirmed earlier data on significantly higher basal levels of urinary LTE4 in aspirin‐intolerant asthmatics. In addition, a post‐challenge increase in urinary LTE4 levels was detected in association with allergeninduced airway obstruction in atopic asthmatics. The per cent increase in urinary LTE4 was similar, irrespective of whether the samples were purified or not prior to EIA. Thus, combined with random validation by high performance liquid chromatography, the strategy of direct EIA of serially diluted urine samples was found to be a good index of in vivo production of leukotrienes. This was further reinforced by the demonstration that pretreatment with the leukotriene biosynthesis inhibitor Bay × 1005 inhibited the post allergen‐challenge increase in urinary LTE4, as shown both with unpurilied and purified samples.
Psychiatry in the allergy clinic: the nature and management of patients with non‐allergic symptoms
Authors: HOWARD L. M. , WESSELY S.
Published: April 2006

Patients with multiple unexplained somatic symptoms attributed to allergy frequently present to physicians and often the physician fails to find evidence for allergic or immunological mechanisms underlying the presenting symptoms. This article discusses the social and cultural background to this disorder. We then consider current explanatory models for symptoms and finally, we consider appropriate management, starting with the initial consultation, the identification of psychiatric disorders when present, and concluding with suggestions for subsequent treatment and guidance on appropriate referral.
Characterization of IgE‐binding epitopes on Candida albicans enolase
Authors: ITO K. , ISHIGURO A. , KANBE T. , TANAKA K. , TORH S.
Published: April 2006

Candida albicans enolase is one of the important allergens in Candida allergy. We isolated and purified 46 kDa C. albicans enolase (CAE) from C. albicans and characterized epitopes for IgE antibody by lectin‐blotting and enzymatic digestion followed by sodium dodecyl sulfale polyacrylamide gel electrophoresis (SDS‐PAGE) and immunobiotting. Lectin blotting and deglycozilation indicated that this protein did not contain polysaccharide side chains. The purified CAE and recombinant fusion protein produced from CAE gene possessed common epitopes for IgE antibody. We estimated IgE binding epitopes on the basis of reported amino acid sequences from the analysis of cDNA encoding CAE. V8 protease digestion of CAE gave six polypeptide fragments (A‐F). The N‐termini of each fragment were confirmed by amino acid sequence and the C‐termini were estimated by molecular weights of each fragment and the specific cutting site of V8 protease. Fragment C (25.0 kDa; F‐171‐I‐399) reacted to 90% IgE antibodies examined, whereas fragments D (21.0 kDa; F‐171‐1‐360), E (16.2kDa: F‐171‐D‐317) and F (13.0kDa; A‐47‐E‐170) showed no IgE binding. Our results suggest that epitopes for IgE antibodies exist near the C‐terminal of the protein.
Differential dependence of TH‐0, TH‐1 and TH‐2 CD4 4+ T cells on co‐stimulatory activity provided by the accessory molecule LFA‐1
Authors: FAITH A. , HIGGINS J. A. , O'HEHIR R. E. , LAMB J. R.
Published: April 2006

Background The adhesion molecule LFA‐1 contributes to the activation response of peripheral blood human CD4+ T cells. Less is known of its contribution to stimulation of long‐term CD4+ T cell lines and clones or of its potential to co‐stimulate CD4+ T cells of different functional phenotype.

Objective This study was therefore performed to investigate co‐stimulatory properties of the LFA‐1 (CD11a/CD 18) complex in the activation of human CD4+ T cell lines and clones of TH‐0. TH‐1 and TH‐2 subsets.

Methods Co‐stimulatory activity was measured by cross‐linking antibodies to CD 11a or CD18 with anti‐CD3 antibodies to plastic and then measuring the proliferative response of CD4+ T cells to these antibodies.

Results A house duct mite allergen‐specific CD4+ T cell line (TH‐2) demonstrated much greater dependence on both C'DI la and CD IK than a mycobacterial antigen‐specific CD4+ T cell line (TH‐1). Co‐stimulatory activity through LFA‐1 was also provided to a house dust mite‐specific CD4+ T cell clone (DE‐9; TH‐2) but not to an influenza haemagglutinin‐specific CD4+ T cell clone (HA 1.7: TH‐0). In contrast, soluble antibodies to CD 18 inhibited proliferativc responses of both DE‐9 and HA1.7 to an immunogenic challenge of antigen and to stimulation by unti‐CD3 antibodies. However, the allergen‐specific T cells were more susceptible to inhibition. Signal transduction was also observed from the T‐cell receptor to LFA‐1. Ligation of the T‐cell receptor modulated the phenotypic expression of LFA‐1 and ICAM‐1 on both HA1‐7 and DE‐9). Phenotypic modulation was observed as a result of both activation and the induction of non‐responsiveness.

Conclusion These experiments indicate that CD4+ T cells of TH‐2 functional phenotype may have a greater requirement for the co‐stimulatory activity of LFA‐1 than CD4+ T cells of TH‐0 or TH‐1 phenotypes.
Regulation of cytokine and chemokine transcription in a human TH2 type T‐cell clone during the induction phase of anergy
Authors: O'HEHIR R. E. , LAKE R. A. , SCHALL T. J. , YSSEL H. , PANAGIOTOPOULOU E. , LAMB J. R.
Published: April 2006

Background
Selected cytokines produced by allergen specific CD4+ T cells from atopic individuals contribute to both the specific and non‐specific effector mechanisms of the allergic itnmune response. The chemokine family of cytokines and tumour necrosis factor (TNF)‐α are leucocyte regulatory and proinflanimatory molecules. The chemokines include interleukin (IL)‐8 and the RANTES/SIS cytokines.

Objective
There has been no systematic survey of chemokine production in T‐cell subtypes. Because of their wide range of biological properties, it might be expected that they would be closely regulated by T cells. This paper illustrates one way (through the characterization of T‐cell clones) these questions might be addressed.

Methods
Northern blot analysis was used to quantitate steady state transcription of selected cytokine genes and enzyme linked imtiiunosorbent assay (ELISA) was used to quantitate soluble product.

Results
mRNA expression of the chemokines (IL‐8, HuMIP‐1α and HuMIP‐1β) and TNFα is upregulated in TH2‐like cloned house dust mite reactive human CD4+ T cells under conditions of activation and during the induction phase of anergy. Although the development of anergy superinduces mRNA for both IL‐8 and TNFα. protein production is low compared with that released during activation. In contrast. RANTES, a chemoattractant for CD4+/CD45RO+ memory T cells, eosinophils and basophils, is constitutively expressed at the RNA level by the T cells and not modulated by signals of activation and anergy induction. The production of IL‐2, IL‐4 and IL‐5 mRNA and proteins during the induction of anergy peaks at 2h after stimulation, whereas the kinetics following activation of the T cells is delayed in comparison.

Conclusion
These data show that the induction of the anergic state coincides with post‐transcriptional regulation of selected cytokine genes. Further study of these phenomena will impact on our understanding of the mechanisms of induction of anergy and the regulation of allergic immune responses in desensitization.
Absence of continuous epitopes in the house dust mite major allergens Der p I from Dermatophagoides pteronyssinus and Der f I from Dermatophagoides farinae
Authors: COLLINS S. P. , BALL G. , VONARX E. , HOSKING C. , SHELTON M. , HILL D. , HOWDEN M.E.H.
Published: April 2006

Background
The house dust mite has been shown to be an important source of domestic allergens associated with immediate hypersensitivities. The Group I mite allergens Der p I from Dermatophagoides pteronyssinus and Der f I from D. farinae display extensive amino acid sequence homology and have similarities with cysteine protease enzymes.

Objective
The availability of the complete amino acid sequences for these allergens allowed us to search for the allergic detertninants within these molecules. The aim of the present investigation was to identify any continuous IgE‐binding epitopes within these amino acid sequences. We also sought to test the validity of previously reported Der p I peptide epitope sequences.

Methods
In order to identity any continuous IgE epitopes, the amino acid sequences of Der p I and Der f I were synthesized as decapeptides overlapping in sequence and coupled to plastic pins. The specific IgE‐binding capacity of these peptides was assayed using an enzyme‐linked biotin‐streptavidin procedure and sera from patients known to be sensitive to these allergens. Previously reported Der p I peptide epitopes were synthesized as free peptides and tested for their ability to inhibit specific IgE binding to allergen extract discs.

Results
None of the pin‐coupled Der p I or Der f I peptides was found by the continuous epitope mapping procedure to bind significantly to specific IgE in the sera of hypersensitive patients. The previously reported Der p I peptide epitopes did not inhibit specific IgE binding to mite extract discs.

Conclusion
The specific IgE binding epitopes of the house dust mite allergens Der p I and Der f I are discontinuous in nature.
Fel d I levels in cat anal glands
Authors: DE ANDRADE A. DORNELAS , BIRNBAUM J. , MAGALON C. , MAGNOL J. P. , LANTEAUME A. , CHARPIN D. , VERVLOET D.
Published: April 2006

Background
Major cat allergen Fel d I is produced consistently by skin and by sebaceous glands before being spread on the fur.

Objective
Since cats have tubular anal glands secreting sebum, proteins and lipids, we looked at the possible presence of Eel d I in these secretions and compared the levels found to those already reported in other cat tissues or secretions.

Methods
Thirty‐seven cats were studied. Eel d I dosage in the anal sacs’ secretions was performed using an enzyme linked immunosorbent assay (ELISA) method and total protein evaluation by the Bradford's method.

Results
The geometric mean Eel d I concentration was 41 U/g secretion which represents 3.4% of the total protein levels. This amount is the highest ever reported in cat tissues or secretions.

Conclusion
The close association of Eel d I protein with skin sebaceous glands and anal sacs both with holocrine function and lipids’ secretions in one hand, and the homology of chain I of Eel d I with some steroid‐binding proteins in other hand, suggest a possible physiological role for Eel d I in the regulation of lipids on skin and cat fur.
Intestinal inflammation in children with atopic eczema: faecal eosinophil cationic protein and tumour necrosis factor‐α as non‐invasive indicators of food allergy
Authors: MAJAMAA H. , MIETTINEN A. , LAINE S. , ISOLAURI E.
Published: April 2006

Background
Food allergy is contemplated in atopic eczema. Early recognition of food allergies is difficult and the diagnosis is often missed because of the non‐specificity of symptoms. New non‐invasive tests are clearly needed.

Objeetive and methods
We measured the concentrations of tumour necrosis factor‐α, eosinophil cationic protein and α‐1 antitrypsin in faeces as indicators of intestinal inflammation induced by double‐blind placebo‐controlled oral cow's milk challenge in infants and young children with atopic eczema.

Results
An increased α‐l antitrypsin concentration (>2mg/g) after cow's milk challenge was detected in 43% of the infants positive as compared with 11% of the infants negative to challenge P= 0.02. The concentration of eosinophil cationic protein in faeces increased after cow's milk challenge in patients positive to challenge (P=0.02) but not in those negative to challenge (P=0.79). The concentration of eosinophil cationic protein was enhanced particularly in patients manifesting immediate‐type reactions to the cow's milk challenge. The concentration of tumour necrosis factor‐α increased after cow's milk challenge in patients positive to challenge (P=0.005) but not in those negative to challenge (P =0.25). The concentration of tumour necrosis factor‐α in faeces was enhanced particularly in patients manifesting delayed‐type reactions to the cow's milk challenge.

Conclusion
We conclude that in children with atopic eczema food allergy is associated with intestinal inflammation indicating that more general immunologic disturbances than previously thought take place in these patients. We further suggest that faecal eosinophil cationic protein, tumour necrosis factor‐α and α‐1 antitrypsin distinctly indicate various reaction types of food allergy. Parallel testing with eosinophil cationic protein and tumour necrosis factor‐α may signiticantly enhance the accuracy in diagnosis of food allergy in patients with atopic eczema.
The effects of a kinin antagonist on changes in lung function and plasma extravasation into the airways following challenge of sensitized guinea‐pigs
Authors: FEATHERSTONE R. L. , PARRY J. E. , CHURCH M. K.
Published: April 2006

Background
It has been suggested that kinins may play a role in allergic pathophysiology of the airways, contributing to bronchoeonstrietion and oedema formation. Raised levels of kinin generating enzymes and kinins are found in the airways during allergic responses.

Objective
Using an in vivo animal model of allergen induced increase in airways resistance we investigated the effects of the brady kinin antagonist Hoe 140, in order to assess the possible contribution of kinins to this response.

Methods
Guinea‐pigs were sensitized and challenged with ovalbumin (OA) or saline via the endotracheal route and the resulting increase in airways resistance was measured by whole body plethysmography. At 240min after challenge, bronchoalveolar lavage fluid (BALF) was taken and albumin content and kallikrein‐like activity defennined by rocket immunoelectrophoresis and use of artificial substrates respec tively. Pretreatment of animals with the bradykinin antagonist Hoe 140 at 6.7, 20 or 66.7nmol/kg or aprotinin (46 000 kallikrein inhibitor units/kg) was by i.p. injection 10 min before challenge.

Results
Pre‐treatment with Hoe 140 dose dependently attenuated the increase in airways resistance following allergen challenge. Kallikrein‐like activity and albumin in BALF were unaltered. Aprotinin reduced the kallikrein‐like activity in BALE but did not alter airways resistance.

Conclusion
Kinins may contribute to a significant part of allergen‐induced airways resistance increase in this model but not via an effect on plasma extravasation.
Does an allergy skin test on school‐children predict respiratory symptoms in adulthood?
Authors: KAGAMIMORI S. , NARUSE Y. , KAKIUCHI H. , YAMAGAMI T. , SOKEJIMA S. , MATSUBARA I. , BI‐LI‐FU  , KATOH T.
Published: April 2006

Background
It is interesting from the correct point of preventive health care whether allergy skin tests at entry have the positive relationship with common respiratory symptoms such as persistent cough, persistent phlegm and wheeze with colds at end point in longitudinal studies.

Objective
The purpose of this study is to investigate this relationship in subjects followed from when they were school‐children until they were young adults. Methods Young adults aged 18–31 years who had participated in an allergy skin test and a health survey for common respiratory symptoms during primary and junior high school were asked about their respiratory symptoms at the end‐point in the follow‐up study. Three cohort groups were employed in the follow‐up study.

Results
According to a multiple logistic analysis with adjustments made for sex. symptoms at entry in childhood, and age and smoking habits at the end‐point. young adults with a positive skin test to an extract of house dust as school‐children showed a higher prevalence of wheeze with colds compared with those with a negative skin test. However. this relationship was not found for persistent cough or persistent phlegm. indeed. the latter symptom was significantly associated with negative skin tests in one cohort group.

Conclusion
The respective symptoms at entry in childhood were also predictors of their occurrence in young adults. The results show that the common respiratory symptoms such as persistent phlegm and wheeze with colds in childhood are related to those in young adults rather than is an allergy skin test to an extract of house dust in childhood.
CD28 expression is increased in venom allergic patients but is not modified by specific immunotherapy
Authors: TSICOPOULOS A. , LABALETTE M. , AKOUM H. , DUEZ C. , WALLAERT B. , DESSAINT J. P. , TONNEL A. B.
Published: April 2006

Background
Recognition of antigen bound to the major histocompatibility complex by the T cell receptor is insufficient to lead to T cell proliferation and effector function, which require co‐stimulatory signals, such as those resulting from the interaction of CD28 expressed on T lymphocytes and CD80/CD86 expressed on APCs. Lack of interaction between these accessory molecules during antigen stimulation leads to a state of antigen‐specific lymphocyte unresponsiveness. Previous studies have shown that rush venom immunotherapy decreases venom‐specific T cell proliferation very early after the initiation of the rush.

Objective
In order to see whether this hyporeactivity was associated with a down regulation of accessory molecules, we studied CD28 surface expression on T lymphocytes from 10 non‐atopic controls and from 10 non‐atopic patients undergoing rush venom immunotherapy.

Methods
Peripheral blood samples were collected before the rush (day 0), at the end of the rush (day 1), at day 15 and at day 45. CD28 expression was analysed using flow cytometry with double labelling of the CD4+ and CD8+ lymphocyte subpopulations.

Results
At baseline CD28 was expressed at a higher level on T lymphocytes from allergic patients than from control subjects (P < 0.04), and in particular on the CD8 subset (P < 0.01), reflecting a decrease in the suppressive CD8+CD28– subpopulation. No changes were found in the percentages of total CD28+ T cells, CD4+ CD28+ or CD8+CD28+ cells at the different time points after the initiation of immunotherapy.

Conclusion
These results suggest that the CD28 pathway is probably involved in the development of allergic reactions, but at least at the phenotypic level, CD28 expression remained unchanged after rush venom immunotherapy.
Lack of evidence of a significant association between HLA‐DR, DQ and DP genotypes and atopy in families with HDM allergy
Authors: HOLLOWAY J. W. , DOULL I. , BEGISHVILI B. , BEASLEY R. , HOLGATE S. T. , HOWELL W. M.
Published: April 2006

Background
HLA class II genetic polymorphism has been variably implicated in susceptibility to specific immune responsiveness to house dust mite (HDM) allergens, and may also influence the development of atopy.

Objective
In order to assess accurately the influence of HLA alleles in the atopic immune response, we typed 22 families selected from 131 previously obtained randomly selected families (i.e. without regard to atopy or asthma), chosen on the basis of two or more members having skin prick reactivity to HDM.

Methods
Each individual was fully typed for HLA‐DRB1, DQA1, DQB1 and DPB1 class II alleles using a combination of sequence‐specific oligonucleotide probes (SSOP) and sequence‐specific primer (SSP) polymerase chain reaction (PCR) typing and direct sequencing.

Results
Using appropriate statistical tests, no significant allelic associations were found between any DRBl, DQB1 or DPBl alleles and atopy or skin prick reactivity to Dermataphagoides pteronyssinus (Der p) or D. farinae (Der f). However, positive associations were found between DQA 1*0301 and skin prick reactivity to Der f (P= 0.009) and atopy (P= 0.027). Sib‐pair analysis revealed no significant sharing of alleles between affected sib pairs for any of the phenotypes studied.

Conclusion
These results fail to confirm a previously reported association between the DRB1*04 and 07 haplotypes and atopy, and suggest that HLA class II restriction does not play a major role in the development of the IgE response to domestic house dust mite allergens in the British population.
A comparison of serum haptoglobin levels between acute exacerbation and clinical remission in asthma
Authors: KOH Y. Y. , KIM Y. W. , PARK J. D. , OH J. W.
Published: April 2006

Background
Bronchial asthma is characterized by airway inflammation, which underlies the phenomenon of bronchial hyperresponsiveness. The concentration of serum haploglobin (Hp), one of the acute phase reactant proteins, has been reported to correlate with bronchial hyperresponsiveness. The extent to which bronchoconstriction or airway inflammation contributes to airflow obstruction of exacerbation is presumed to determine the responsiveness to the initial bronchodilator therapy.

Objective
To see whether the Hp levels vary with the disease status of asthma, and also to test whether the Hp level at an acute exacerbation(AE) is correlated with the degree of response to initial bronchodilator therapy.

Methods
We measured serum Hp levels in 50 children with asthma at the times of an AE and a clinical remission(CR), and analysed the data according to the response to the initial bronchodilator therapy at AE.

Results
The serum concentration of Hp at AE (228.5 ± 80.8mg/dl, mean ± SD) was significantly (P < 0.01) higher than that at CR (152.3 ± 49.8mg/dl) in the total study population. The difference of Hp levels between AE and CR was more marked (101.7 ± 82.2 mg/dl) in the subjects (n= 19) who responded poorly (post‐bronchodi‐lator FEV1 < 75% predicted) to the initial bronehodilator therapy at AE than that (61.0 ± 56.5mg/dl) of those (n= 31) who responded well (post‐bronchodilator FEV1± 75% predicted). The Hp level at AE eorrelated with the degree of response to initial bronchodilator therapy (r=−0.36, P < 0.05), whereas it had no relationship with the severity of exacerbation (r= 0.04. P= 0.79).

Conclusion
Our results showed that Hp levels may be increased al ihe time of exacerbation in a given asthma patient. The finding that the elevation of Hp level at AE is more marked in the cases with poor response to initial bronchodilaior therapy at AE suggests that the increased Hp level at AE in asthma might relied the degree of airway inflammation.
New mattresses: how fast do they become a significant source of exposure to house dust mite allergens?
Authors: CUSTOVIC A. , GREEN R. , SMITH A. , CHAPMAN M. D. , WOODCOCK A.
Published: April 2006

Background
Sensitization and exposure to mile allergens is a major risk factor for asthma. Little is known about the rate of build‐up of allergens in the mite microhabitats.

Objectives
To investigate the rate of increase in mite allergen levels in new mattresses.

Methods
Der p 1 was measured in the dust samples collected from six identical new single mattresses over a period of 2 years.

Results
Der p 1 increased significantly at 4 months as compared with baseline level (P < 0.01), but no difference was found between the concentrations at 4. 8, 12 and 24 months. There was a significant correlation between Der p 1 concentration in mattresses at 4.8, 12 and 24 months and Der p 1 levels in the bedroom carpet at the beginning of the study.

Conclusions
New mattresses can become a significant source of exposure to mite allergens after a short period of time (< 4 months). There is little justification for advising mite sensitive patients to replace their mattresses as a part of avoidance regime.
Drug‐associated anaphylaxis: 20 years of reporting in the Netherlands (1974–1994) and review of the literature
Authors: VAN DER KLAUW M. M. , WILSON J. H. P. , STRICKER B. H. CH.
Published: April 2006

Background
Since 1963, the Drug Safety Unit of the Dutch Inspectorate for Health Care (DSU) holds a voluntary reporting system.

Objective
To analyse all reports received in the years 1974 to 1994, registered as anaphylaxis or as a diagnosis that could contain cases of anaphylaxis.

Methods
All reports were classified as probable or possible anaphylaxis according to previously described criteria and the causal relationship between exposure and anaphylaxis was assessed.

Results
Nine hundred and ninety‐two reports possibly concerning anaphylaxis were received between 1974 and 1994. Fifty‐six were unclassifiable. The remaining 936 reports concerned 326 men and 610 women. Three hundred and forty‐five reports were classified as anaphylaxis probable, 485 as anaphylaxis possible, and 106 as anaphylaxis unlikely by previously specified criteria. Drugs frequently associated with anaphylaxis (causal relationship certain or probable) were: glafenine (326 reports classified as anaphylaxis probable or possible), combination preparations with (propy)phenazone or propyphenazone/phenacetine (39), diclofenac (30), dextran (20), ibuprofen (14), floctafenine (12), allergen extracts (12), sulfamethoxazole with trimethoprim (12), and trimethoprim (11). There is probably substantial under‐reporting as well as reporting bias in these data. Furthermore, many reports were classified as possible and not as probable anaphylaxis because the temporal relationship was unknown or not reported.

Conclusion
Drugs that caused anaphylaxis most frequently were glafenine, NSAID and certain antibiotics. Data from a voluntary reporting system such as the DSU are valuable as an early warning system for drugs that may induce anaphylactic reactions.
Intradermal challenge with interleukin‐8 causes tissue oedema and neutrophil accumulation in atopic and non‐atopic human subjects
Authors: DOUGLASS J. , DHAMI D. , BULPITT M. , LINDLEY I. J. , SHUTE J. , CHURCH M. K. , HOLGATE S. T.
Published: April 2006

Background
Interleukin‐8 (IL‐8) is a cytokine with potent neutrophil chemotactic and activating properties and is active in inflammatory conditions in man. It has been identified in human inflammatory skin conditions where it is likely to be responsible for both neutrophil recruitment from the circulation and possibly T‐lymphocyte chemoattraction. Studies in animals also suggest that IL‐8 may augment skin oedema.

Objective
To study the effects of intradermally administered IL‐8 in humans on tissue oedema and cellular recruitment in atopic and non‐atopic volunteers.

Method
Interleukin‐8 (1.2 ± 10−7M) in the presence and absence of histamine was administered by intradermal injection. Wheal and erythema area were measured at regular intervals and 3 h following challenge punch biopsies were taken for immunocytochemistry. Cellular infiltrate was measured by immunocytochemical identification of neutrophils, eosinophils and T‐lymphocytes in glycol‐methacrylateembedded sections.

Results
In the presence of histamine, IL‐8 provoked a significantly greater wheal area when compared to that produced by histamine alone (P < 0.001). In the presence of histamine, IL‐8 produced a significantly greater neutrophil infiltrate (P < 0.05); however, neither lymphocyte or eosinophil infiltration was found to be increased with IL‐8 challenge. There was no difference observed between atopic and non‐atopic subjects, nor were any effects of IL‐8 demonstrated in the absence of histamine.

Conclusion
This study demonstrates that in human skin, IL‐8 induces increased microvascular permeability and neutrophil infiltration, but not eosinophil or T‐lymphocyte chemoattraction.