bluuebunny/crossref_metadata_2025 huggingface dataset:
Bee venom immunotherapy induces a shift in cytokine responses from a TH‐2 to a TH‐1 dominant pattern: comparison of rush and conventional immunotherapy
Authors: McHUGH S. M. , DEIGHTON J. , STEWART A. G. , LACHMANN P. J. , EWAN P. W.
Published: April 2006

Background: The mechanism of immunotherapy is unclear. Allergic disease is known to involve enhanced TH‐2 cytokine responses to allergen.

Objective: In order to investigate the mechanisms of immunotherapy, we have examined changes in cytokine secretion before (13 patients) and during (nine patients) both rush and conventional venom immunotherapy (VIT) in nee venom allergic patient.

Method Peripheral blood mononuclear cells were stimulated in vitro with see venom, non‐specific antigen or mitogen and secretion of IL‐4 (TH‐2) and IFNγ (TH‐1) over the culture period measured.

Results: Untreated patients had TH‐2 responses to venom and TH‐1 responses to antigen and strong proliferative responses to venom. Controls showed no response (proliferation or cytokines) to venom and the normal TH‐1 response to antigen. VIT resulted in marked changes in cytokine secretion to venom, with reduction of the abnormal TH‐2 response and induction of a TH‐1 response. The pattern differed in rush and conventional VIT. One day after rush VIT there was a significant fall in IL‐4 secretion (P < 0.01), which rose by 3 weeks then declined. In conventional ViT there was a gradual reduction of IL‐4 production significant after 2 months and undetectable by 6 months. IFNγ secretion was induced by VIT. Proliferative responses mirrored the IL‐4 changes. One day after rush VIT there was a loss of T cells, monocytes and NK cells from peripheral blood.

Conclusion: This study shows that immmotherapy shifted cytokine responses to allergen from a TH‐2 to a TH‐1 dominant pattern, suggesting direct effects on T cells. How these cytokine changes relate to clinical desensitization is not clear. In the longer term they would result in an isotype switch from IgE to IgG. Early changes in cytokine or chemokine production might down regulate mast cell or basophil reactivity and explain the rapid desensilization in rush VIT.
Challenge of mast cells with increasing amounts of antigen induces desensitization
Authors: SHALIT M. , LEVI‐SCHAFFER F.
Published: April 2006

Background
In vivo rush desensitization is a procedure widely employed to quickly desensitizo allergic patients by administering increasing doses of the offending antigen at short intervals. The mechanism(s) underlying this process and the possible role of mast cells in it have not been well delineated.

Objective
To define an ex vivo model for rush desensitization utilizing the mast cell‐fibroblast coculture system.

Methods
Rat peritoneal mast cells were cultured on 3T3 fibroblasls and were pre‐incubated with saturating or suboptimal concentrations of IgE anti‐DNP antibodies. Mast cells were then repeatedly challenged at 30 min intervals, with increasing amounts (0.001 100ng/mL) of the antigen DNP‐HSA, in the presence of calcium ions. Parallel control cultures were stimulated only once by each antigen concentration. In another set of experiments, mast cells were repeatedly activated with increasing concentrations (0.1‐1000 ng/mL) of compound 48/80. Supernatants and cell sonicates were assessed for histamine content and the percentage of histamine released was calculated.

Results
When saturating concentrations of IgE anti‐DNP antibodies were used, mast cells challenged repeatedly with DNP‐HSA did not release significant amounts of histamine up to an antigen concentration of I ng/mL. At this stage they were partially desensitized, releasing only 108.3 . 17.1 ng histamine/plate (7.9±0.8%). A marked desensitization was observed at optimal antigen concentration (100 ng/mL). where experimental mast cells released only 45.6±10.9ng/plate, compared with 661.9±48.2ng/plate in firstly challenged cultures. Desensitization was probably not due to mast cells histamine depletion, since the cells still contained large amounts of histamine (579.5±108.6ng/plate) at the end of the procedure. A similar pattern of desensitization was observed when mast cell were preincubated with a subotimal concentration of IgE antibodies. Activation of mast cells with increasing amounts of the IgE‐independent secretagogue, compound 48/80. did not cause desensitization since at each concentration both repetitively challenged and control cultures released similar amounts of histamine. Furthermore, challenge of antigen‐desensitized mast cells with compound 48/80 caused the release of 75.9±4.9% histamine comparable to the percentage of histamine released from controls (79.5±6.7).

Conclusion
Repeated exposure of mast cells to gradually increasing amounts of antigen induces their refractoriness. This observation would suggest a role for mast cells in rush desensitization procedure in vivo. Our coculture system may serve as a useful model for studying this process.
Epidemiology of the effects of air pollutants on allergic disease in children
Authors: Carswell F.
Published: April 2006

9.21. Extensive studies now indicate that many atmospheric pollutants can provoke respiratory symptoms. Usually a complex mixture affects children but it seems that ozone, particulates and nitrogen dioxide are virtually certainly implicated and the organic substances released with dense traffic are likely to be involved. There is commonly difficulty specifically identifying the pollutant because of the complex mixture and their interactive effects. Other environmental conditions such as weather can interact both by increasing the concentration of the pollutant and by increasing the effectiveness of the same concentration of the pollutant and by increasing the effectiveness of the same concentration of pollutants such as particulates. It is only with regard to NO2 where a convenient and easy system of monitoring is available that detailed personal monitoring results are obtainable, so that despite the rather modest effect of NO2 it is well documented, whereas those pollutants which still have to be centrally monitored may have a greater biological effect. All the studies indicate the importance of considering the interactive effects of environmental cigarette smoke as another possible confounder, as is exercise. Although many of the studies imply that atmospheric pollution can produce an increase in clinically apparent infection, it is not established that the symptoms which are analogous to those produce by virus infection are actually produced by a virus infection are actually produced by a virus. Given these difficulties, it is surprising that some evidence with regard to the timing of the effect has been produced; thus suphur dioxide commonly produces a same‐day effect whereas particulates tend to produce a more delayed effect.
Human auto‐anti‐idiotypic antibodies to mite‐specific IgE can degranulate human basophils in vitro
Authors: WEYER A. , LE MAO J. , ETIEVANT M. , DAVID B. , GUINNEPAIN M. T. , SAINT‐REMY J. M. R.
Published: April 2006

Background
Anti‐idiotypic antibodies (anti‐Ids) to specific IgE antibodies are formed spontaneously during an anti‐allergen immune response and can be induced by immunotherapy. Although anti‐Ids can down‐regulate the production of IgF. antibodies, at least in experimental models, their possible role in the modulation of target cell reactivity remains ill‐defined.

Objective
The capacity of human anti‐Ids to modulate the release of histamine was examined in an in vitro system of human basophil degranillation. Anti‐Ids were prepared from the serum of six Dermatophagoides pteranyssinus (DP)‐hypersensitive patients suffering from atopic dermatitis and who had never been desensitized. Basophils were obtained from the blood of atopic donors. The extent of histaminc release was determined using a fluorometric assay.

Results
We show that: anti‐Ids trigger the release of histamine in an allergen‐specific, dose‐ and IgE‐dependent manner; the release is not due to the presence of allergen and/ or anti‐IgE antibodies: and that the degranulating activity can be removed by absorption with affinity‐purified anti‐Dp antibodies of the corresponding patient.

Conclusion
These results indicate that spontaneously produced human anti‐Ids can modulate the reactivity of human basophils.
The lack of effect of benzalkonium chloride on the cilia of the nasal mucosa in patients with perennial allergic rhinitis: a combined functional, light, scanning and transmission electron microscopy study
Authors: BRAAT J. P. M. , AINGE G. , BOWLES J. A. K. , RICHARDS D. H , VAN RIESSEN D. , VISSER W. J. , RIJNTJES E.
Published: April 2006

Background
Controversy still exists about the effect of 0.02% benzalkonium chloride (BKC). a preservative in many nasal sprays, on human nasal epithelium in vivo. Objective To determine the safety of BKC by assessing its effect on the function and morphology of cilia of human nasal epithelium.

Methods
A single‐centre, double‐blind nasal biopsy study in 22 patients with perennial allergic rhinitis, receiving fluticasone propionate aqueous nasal spray (FPANS) containing BKC. BKC plus placebo or placebo alone for 6 weeks. Before, at two weekly intervals during treatment and 2 weeks after treatment ceased an indigocarmine saccharine transport time (ICST) was performed. Results ICST results did not significantly vary between the groups. There was no statistical relationship between the number of ciliated cells present and the treatment the patients received. Scanning and transmission electron microscopy examination showed no effects of BKC.

Conclusion
Despite reports of its ciliostatic effects in vitro. BKC did not have such an effect when it was applied for 6 weeks (with/without fluticasone propionale) to the nasal mucosa of perennial allergic rhinitis patients in vivo.
Antihistamine activity, central nervous system and cardiovascular profiles of histamine H1 antagonists: comparative studies with loratadine, terfenadine and sedating antihistamines in guinea‐pigs
Authors: HEY J. A. , DEL PRADO M. , CUSS F. M. , EGAN R. W. , SHERWOOD J. , LIN C.‐C. , KREUTNER W.
Published: April 2006

Background
Sedation limits the clinical utility of classical H, antihistamines. while newer antihistamincs such as loratadine and terfenadine arc non‐sedating. However, clinical use of terfenadine has been associated with rare but severe cardiac arrhythmias, in particular lorsades de pointes.

Objective
To establish a quantitative experimental model for assessing the sedating and cardiotoxicity potential of non‐sedating and sedating antihistamines.

Methods
Drugs were administered intravenously and the integrated amplitude of the conical electroencephalogram (EEC) signal was recorded. The threshold dose that depressed EEG activity was compared with the dose required lo inhibit by 50% the peripheral bronchospasm elicited by 10 μg/ kg i.v., of histamine. In separate studies, the electrocardiogram (ECG) and cardiovascular effects of loratadine (30 and 100mg/kg, i.v.). terfeuadine (10mg/kg. i.v.). promethazine (5mg/kg. i.v.) and diphenhydramine (20 mg kg, i.v.) were evaluated.

Results
The sedating antihistamines. diphenhydramine and promethazine. depressed the integrated EEG at doses between 0.6 and 2.0 limes their peripheral antihisiamine doses. Loratadine had no EEG depressant activity at 100 mg kg. i.v., a dose more than I 70 times its LD50 (0.58 mg kg, i.v.) against histamine bronchospasm. We were unable lo evaluate the EEG effects of terfenadine. because it produced cardiovascular collapse at 10 mg/kg. i.v. Loratadine and promethazinc did not produce adverse cardiovascular effects. nor did they alter normal ECG activity. Diphenhydramine produced brady‐cardia followed by a transient hypertensive phase without affecting the QTc interval. In contrast, terfenadine elicited hypotension, bradycardia and significant arrhythmogenic activiy, causing a prolongation of the QTc interval and a torsades de pointes like ventricular arrhythmia. Pharmacokinetic studies after i.v. administration of loraladine (30 and 100 mg/kg) demonstrated plasma levels of loratadine and its major metabolite descarboethoxyloratadine to be several orders of magnitude greater than levels found in humans at the clinical dose of 10mg.

Conclusion
The CNS depressant effects of H1 antihislamines arc promcthazine≅ diphenhdramine ≫ loratadine = placebo. Of the non‐sedating antihistamines. loratadine was devoid of adverse cardiovascular effects whereas terfenadine caused a pronounced disruption of the normal ECG. characterized by a torsades de pointes‐like effect.
Raising the pH of the pepsin‐catalysed hydrolysis of bovine whey proteins increases the antigenicity of the hydrolysates
Authors: SCHMIDT D. G. , MEIJER R. J. G. M. , SLANGEN C. J. , VAN BERESTEIJN E. C. H.
Published: April 2006

Background
Hypersensitivity to cow milk protein is frequently observed in infancy. Since the pH in the infant's stomach is relatively high (pH 3–4) compared with adults (pH 2). an incomplete digestion of the milk proteins is expected to occur.

Objective
The determination of the degree of hydrolysis by pepsin of the four main proteins of bovine whey. i.e. α‐lactalbumin (αLa). β‐lactoglobulin (βLg). bovine serum albumin (BSA) and bovine immunoglobulin G (B‐IgG). in the pH range 2.0‐ 4.0 and of the antigenic properties of the resulting hydrolysates.

Methods
Whey proteins were successively hydrolysed with pepsin at pH values ranging from 2.0 to 4.0 and with pancreatic enzymes at pH 7.5 using a pH‐stat. The resulting hydrolysates were characterized by their degree of hydrolysis, and analysed by sodium dodecyl sulfale polyacrylamide gel electrophoresis, gel permeation chromatography and immunologically by competitive enzyme‐linked immunosorhent assay.

Result
In general, the degree of hydrolysis, the gel electrophoretic patterns, the contents of peptides of molecular mass > 5kDa and the residual hurnan‐immunoglohulin E and G antigenicities of the hydrolysates did not differ much whether the pepsin incubation was done at pH 2.0 or 3.0. Pepsin incubation at pH 4.0. however, resulted in a decreased hydrolysis and enhanced residual antigenicity of αLa, BSA and B‐IgG. but not of βLg.

Conclusion
The poor and slow degradation of the antigenic epitopes of whey proteins when pepsin digestion occurs under conditions that prevail in the stomach of infants could be of much importance for the development of cow milk hypersensitivity. The immature gastrointestinal mucosal barrier of infants allows large antigenic fragments of these proteins to pass into the systemic circulation.
Genetic control of indirect airway responsiveness in the rat
Authors: PAUWELS R. A. , GERMONPRÉ P. R. , KIPS J. C. , JOOS G. F.
Published: April 2006

Many of the airway responses to endogenous and exogenous stimuli are caused by indirect mechanisms such as the activation of neurons and/or inflammatory cells. In the present study we compare the bronchoamstrictor and the plasma protein extravasation response to adenosine and tachykinins in two highly inbred rat strains. F344 and BDE. BDE‐rats have a bronchoconstrictor response to adenosine at lower doses. Challenge with the A3‐adenosine receptor agonist APNEA demonstrates that the difference in airway responsiveness to adenosine between BDE‐ and F344‐rats is probably related to a higher number of A3‐receptors on the airway mast cells of BDE‐rats. In contrast. F344‐rats have a higher airway responsiveness to lachykinins than BDE‐rats. Taehykinins cause bronchoconstriction in F344‐rats mainly by an indirect mechanism, involving stimulation of NK1‐receptors and mast cell activation. In BDE‐rats they cause bronchoconstriction by a direct effeet on airway smooth muscle via activation of NK2‐receptors. Finally we also observed a difference between F344‐and BDE‐rats with regard to the mechanisms involved in the plasma protein extravasation in the airways caused by substance P or capsuicin. In K344‐rats but not in BDE‐rats mast cell activation and the release of 5‐hydroxytryptamine is partly responsible for this plasma protein extravasation.
The incidence and nature of adverse reactions to injection immunotherapy in bee and wasp venom allergy
Authors: YOULTEN L. J. F. , ATKINSON B. A. , LEE T. H.
Published: April 2006

The incidence, time course and nature of systemic reactions to injections of bee and wasp venom during immunotherapy have been estimated in an open, prospective, single centre study. One hundred and nine survivors of moderate to severe systemic reactions to stings from hymenoptera, received courses of bee or wasp venom by monthly subcutaneous injection for up to 3 years. Systemic reactions were recorded after 7.5% of 946 weekly venom injections during the initial phase of treatment, and after 2.1% of 1789 monthly maintenance injections. In both phases of treatment, reactions were more frequent after bee (17% of initial phase, 7.8% of maintenance treatment) than after wasp (3% of initial phase, 0.3% of maintenance treatment) venom injections. The percentage of patients experiencing at least one reaction was also higher for bee (46%) than for wasp (14%) sensitive patients. Over 80% of reactions began within 30 min of injection, over 90% within 1 h and only two (2%), between 1 and 2 h, the remaining six (5.5%) starting more than 2 h after injection. Only 0.47% of venom injections produced a systemic reaction which was severe enough to require adrenaline treatment. The female patients experienced more reactions (21% of the wasp, 60% of the bee, sensitive) than the males (5.5% wasp, 20% bee). Age and atopy did not appear to be significant risk factors for systemic reactions. We conclude that wasp and bee venom immunotherapy in a conventional dosage regimen was generally well tolerated. No safety advantage was apparent in keeping the patients under observation for more than 1 h after injections. Reactions are more likely to occur during the initial phase of treatment, in women and after bee, rather than wasp, venom injections.
Nasal cytokines in common cold and allergic rhinitis
Authors: LINDEN M. , GREIFF L. , ANDERSSON M. , SVENSSON C. , ÅKERLUND A. , BENDE M. , ANDERSSON E. , PERSSON C. G. A.
Published: April 2006

Coronavirus‐induced common cold and allergen‐induced rhinitis are characterized by nasal mucosal exudation of bulk blood plasma. The mucosal exudation process involves ‘flooding’ of the lamina propria with plasma‐derived binding proteins and it is possible that subepithelial inflammatory cytokines and mediators may be moved by the exudate to the mucosal surface. In this study, we have analysed cytokine levels in nasal lavage (NAL) fluids from non‐allergic subjects inoculated with coronavirus (n= 20) and from subjects with allergic (birch pollen) rhinitis subjected to additional allergen challenge (samples were obtained 35min post challenge) in the laboratory (n= 10). Ten of the 20 inoculated subjects developed common cold and 10 remained healthy. Interferon‐γ (IFN‐γ), interleukin‐1β (IL‐1β), granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), IL‐4, and IL‐6 were analysed in unprocessed NAL fluids using immunoassays. The subjects who developed common cold had increased NAL fluid levels of IFNγ (P < 0.05) that correlated well with the symptoms (P < 0.001). IFNγ did not increase in subjects with allergic rhinitis. IL‐1β levels were similar in NAL fluids obtained from all inoculated subjects. In the subjects with allergic rhinitis NAL fluid levels of both IL‐1β and GM‐CSF were increased (P < 0.05). GM‐CSF was not detected in common cold. IL‐4 and IL‐6 were not detectable in any of the NAL fluids. The present cytokines may not only emanate from superficial mucosal cells. By aiding plasma exudation subepithelial cytokines may potentially also be retrieved on the mucosal surface. Our study provides original in vivo data supporting the notion that a TH‐1 profile of cytokines, notably IFNγ, is present in viral infection and further supporting the view that GM‐CSF is an important cytokine in allergic airways disease.
Regulation of IgE production from human mononuclear cells by β2‐adrenoceptor agonists
Authors: COQUERET O. , DUGAS B. , MENCIA‐HUERTA J. M. , BRAQUET P.
Published: April 2006

The present study examined the effect of β2‐adrenoceptor agonists on the interleukin‐4 (IL‐4)‐driven IgE production and on the possible mechanisms of action of these compounds. We present evidence that salbutamol and fenoterol potentiated the IL‐4‐induced IgE production by human peripheral blood mononuclear cells (PBMC). No significant effect of incubation in the presence of β2‐adrenoceptor agonists on IgG, IgA and IgM production was observed. Salbutamol and fenoterol inhibited interferon‐(IFN)‐γ production by PHA‐activated human PBMC suggesting that the blockade of the production of this cytokine could possibly explain the enhancement of IgE production. Salbutamol and fenoterol potentiated the IL‐4‐induced production of sCD23 whereas no effect on CD23 expression was observed. The potentiating effect of salbutamol on IgE production was blocked by two antagonists of β2‐adrenoceptor, namely butoxamine and D,L‐propranolol, suggesting a β‐adrenoceptor‐mediated event. These results demonstrate that β2‐adrenoceptor stimulation results in an increase in IgE production by human B lymphocytes.
Lack of association between HLA‐DQ and ‐DR genotypes and asthma in southern Chinese patients
Authors: LI P. K. T. , LAI C. K. W. , POON A. S. Y. , HO A. S. S. , CHAN C. H. S. , LAI K. N.
Published: April 2006

Asthma is an inflammatory disease with a strong genetic predisposition. We have studied a group of unrelated asthmatic patients of southern Chinese origin on their HLA‐DR and ‐DQ regions using molecular techniques and compared them with 104 healthy controls of the same ethnic origin. Restriction fragment length polymorphism (RFLP) was used to genotype the MHC class II DR β, DQ α and DQ β loci of the subjects. Polymerase chain reaction (PCR) using sequence specific primer (SSP) for DQ β genes was also performed. No significant difference was found in the HLA‐DQ and ‐DR loci between the patients and the controls. All patients had their serum IgE antibody levels measured, bronchial reactivity assessed by histamine broncho‐provocation and cutaneous reactivity to common allergens determined by skin‐prick tests to Dermatophagoides pteronyssinus, Dermatophagoides farinae, mixed grass pollens, Aspergillus fumigatus, cat fur and dog dander and they were classified respectively. The HLA‐DR and ‐DQ genotypes of these subgroups of patients were compared. There was no significant difference among these subgroups of patients according to their serum IgE levels, the degree of bronchial reactivity and whether they were positive for the skin tests for the various allergens respectively. The results suggest that HLA‐DQ and ‐DR genotypes are not associated with asthma in southern Chinese people.
Cyclic nucleotide phosphodiesterases from purified human CD4+ and CD8+ T lymphocytes
Authors: TENOR H. , STANICIU L. , SCHUDT C. , HATZELMANN A. , WENDEL A. , DJUKANOVIC R. , CHURCH M. K. , SHUTE J. K.
Published: April 2006

Background
CD4+ and CD8+ T‐lymphocytes are suggested to differentially affect airway inflammation in asthma. Agents which increase intracellular cAMP levels, such as PDE inhibitors, have been shown to diminish lymphocyte growth and differentiation, and to affect cytokine expression. Differences in the PDE isoenzyme profile between CD4+ and CD8+ cells might form a basis to differentially modify their functions by PDE inhibitors.

Objective
The study investigates and compares the PDE isoenzyme activity profiles of human peripheral blood CD4+ and CD8+ T‐lymphocytes.

Methods
CD4+ and CD8+ T‐lymphocytes were purified (>98%) from peripheral blood mononuclear cells by negative selection. PDE isoenzyme activity profiles were investigated using PDE isoenzyme selective inhibitors and activators.

Results
In CD4+ and CD8+ T‐lymphocyte homogenates, PDE IV and PDE III activities were the predominant PDE isoenzyme activities at 0.5μM cyclic nucleotide substrate concentrations. PDE IV was localized in the soluble fraction whereas PDE III was membrane bound. Low PDE I, II and V activities were detected. About 20% of total eAMP hydrolysing capacity at 0.5 μM cAMP was insensitive to PDE isoenzyme selective inhibitors and activators and therefore could not be assigned to PDE I‐IV. The PDE isoenzyme pattern was not different between CD4+ and CDS+ T‐lymphocytes. Moreover, representative inhibitors of PDE HI and IV activity inhibited cAMP hydrolysis in soluble fractions of both T‐lymphocyte subsets with similar potency. Enzyme kinetic analysis similarly did not reveal differences between CD4h and CD8+ T‐lymphocytes.

Conclusion
Normal CD4+ and CD8+ T‐lymphocytes are likely to be equally sensitive targets for the effects of PDE inhibitors.
Prohevein from the rubber tree (Hevea brasiliensis) is a major latex allergen
Authors: ALENIUS H. , KALKKINEN N. , LUKKA M. , REUNALA T. , TURJANMAA K. , MÄKINEN‐KILJUNEN S. , YIP E. , PALOSUO T.
Published: April 2006

Background
There is general agreement that proteins eluting from different natural rubber latex products can cause immediate type hypersensitivity reactions in latexallergic patients. However, there is as yet no consensus as to what are the most important allergens in natural rubber latex.

Objective
We wanted to purify and characterize at the primary structure level three natural latex proteins, suggested to represent significant allergens.

Methods
Proteins were purified from ultracentrifuged bottom fraction of natural rubber latex using high performance liquid chromatography gel filtration and reversed phase chromatography. Purified proteins were subjected to tryptic cleavage, peptide separation and amino acid sequencing. Immunoblotting was used to demonstrate IgE antibodies to the purified proteins in sera from latex‐allergic patients.

Results
A 20 kDa protein was identified by amino acid sequencing as prohevein, a major protein in the rubber tree Hevea brasiliensis, and a 30 kDa natural rubber latex protein as hevamine. another essential rubber tree protein. A third, previously undescribed natural rubber latex protein, showed high homology to several plant endo‐1,3‐β‐glucosidases. In immunoblolting, the purified prohevein bound IgE antibodies from 24/29 (83%) sera of latex‐allergic patients including positive results in 4/6 latex‐allergic children with spina bifida or other congenital anomalies. The purified prohevein elicited positive skin‐prick test reactions in all six latex‐allergic patients showing IgE to prohevein. The purified 36 kDa protein bound IgE from 6/29 (21%) latex‐allergic sera, and the purified hevamine from only 1/29 patient sera.

Conclusion
The observed high frequency of IgE antibodies to prohevein suggests that this protein is a major natural rubber latex allergen
Upregulation of IgE synthesis by staphylococcal toxic shock syndrome toxin‐1 in peripheral blood mononuclear cells from patients with atopic dermatitis
Authors: HOFER M. F. , LESTER M. R. , SCHLIEVERT P. M. , LEUNG D. Y. M.
Published: April 2006

Background Atopic dermatitis (AD) is a chronic skin disease associated with increased IgE synthesis and colonization with Staphyiococcus aureus secreting exotoxins, such as Toxic Shock Syndrome Toxin‐1 (TSST‐1).

Objectives In this study, we were interested in determining the in vitro effects of TSST‐1 on IgE synthesis in peripheral blood mononuclear cells from patients with AD.

Methods We stimulated peripheral blood mononuclear cells (PBMC) from AD patients with a wide range of TSST‐1 concentrations and measured IgE synthesis by enzyme‐linked immunosorbent assay (ELISA) after 14 days.

Results We show herein that TSST‐1 produced antagonistic effects on IgE synthesis by PBMC from AD patients, depending on the concentration used: IgE synthesis was inhibited at 1000 pg/mL (P<0.05) and enhanced at 0.01 pg/mL (P<0.01) of toxin. TSST‐1 was found to induce the production of much higher amounts of interferon‐gamma (IFNγ) at 1000 pg/mL than at 0.01pg/mL of toxin (P= 0.0001). More importantly, immunoglobulin E (IgE) synthesis was enhanced by TSST‐1 at 1 pg/mL in the presence of antibodies blocking IFN‐γ activity. The other immunoglobulin (Ig) isotypes were also increased after TSST‐1 stimulation suggesting that the enhanced IgE synthesis was secondary to a polyclonal B cell activation rather than an isotype switch. TSST‐1‐stimulated IgE synthesis was T cell‐dependent because purified tonsil B cells were only able to synthesize increased amounts of IgE when small numbers of T cells were added to the cultures. Anti‐HLA‐DR and anti‐LFA‐1 monoclonal antibodies (MoAb) inhibited TSST‐1‐enhanced IgE synthesis, suggesting that the bridging of the T cell receptor (TCR) and major histocompalibilily complex (MHC) class II on B cells was necessary for activation of B cell differentiation.

Conclusion These data indicate that staphylococcal superantigens are able, at concentrations inducing low amounts of IFNγ, to stimulate IgE synthesis by PBMC from AD patients, and suggest that staphylococcal toxins may contribute to elevated IgE synthesis in AD.
Serological and skin‐test diagnosis of birch pollen allergy with recombinant Bet v I, the major birch pollen allergen
Authors: MENZ G. , DOLECEK C. , SCHÖNHEIT‐KENN U. , FERREIRA F. , MOSER M. , SCHNEIDER T. , SUTER M. , BOLTZ‐NITULESCU G. , EBNER C. , KRAFT D. , VALENTA R.
Published: April 2006

Background
Type I allergy represents a severe health problem in industrialized countries where up to 20% of the population suffer froin allergic rhinitis, conjunctivitis and allergic asthma bronchiale and in severe cases from anaphylaxis. leading to death.

Objective
The aim of this study was to evaluate recombinant Bet v I, the major birch pollen allergen for in vivo and in vitro diagnosis of birch pollen allergy.

Methods
A group of 51 birch pollen allergic patients and eight non‐allergic control individuals were tested for birch pollen allergy by skin‐prick and intradennal testing, comparing commercial birch pollen extracts with recombinant Bet v I. Quantitative and qualitative serological testing was done with natural and recombinant allergens by radioallergosorbent test (RAST), enzyme‐linked immunosorbent assay (ELISA) and immunoblotting.

Results
Recombinant Bet v I allowed accurate in vivo and in vitro diagnosis of tree pollen allergy in 49/51 patients tested. No false positive results were obtained in any in vitro assay system (ELISA. Westernblot) or by skin testing (skin‐prick, intradermal test) with recombinant Bet v I.

Conclusion
Our results document that recombinant Bet v I produced in bacterial expression systems allows accurate in vitro and in vivo diagnosis of birch pollen allergy in > 95% of birch pollen allergic patients.
A comparison of the development of antibody responses to the polysaccharide antigen (Candida albicans mannan) in atopic and healthy infants and children
Authors: NERMES M. , FÅLTH‐MAGNUSSON K. , SAVOLAINEN J. , VIANDER M. , BJÖRKSTEN B.
Published: April 2006

Background
Defeetive antibody response againsl bacterial polysaccharide antigens is known to be associated with recurrent pyogenic infectiotis. The role of childhood allergy as a risk factor for repeated infections with capsulated micro‐organisms has been controversial.

Objective
To compare the devetopment of polysaccharide specific antibody responses in atopic and healthy infants and children.

Methods
The antibody responses against a common polysaccharide antigen, Candida albicans mannan, were studied longitudinally in 18 atopic and 19 non‐atopic children over the first 5 years of life. Determinations of IgA, IgG and IgM antibodies were carried out by enzyme‐linked immunosorbent assay and IgE antibodies by nitrocellulose‐based radioallergosorbent test.

Results
The polysaccharide specific antibody responses were similar in both groups, except that anti‐mannan IgM levels were higher at 5 years in the atopic children (P<0.05. student's t‐test).

Conclusion
Atopic children are not more susceptible to bacterial infections on the basis of poorer ability to produce antibodies against polysaccharide antigens.
Immune reactivity of cow‐asthmatic dairy farmers to the major allergen of cow (BDA20) and to other cow‐derived proteins. The use of purified BDA20 increases the performance of diagnostic tests in respiratory cow allergy
Authors: VIRTANEN T. , ZEILER T. , RAUTIAINEN J. , TAIVAINEN A. , PENTIKÅINEN J. , RYTKÖNEN M. , PARKKINEN S. , PELKONEN J. , MÄNTYJÄRVI R.
Published: April 2006

Background
Cow dust is one of the most important inducers of occupational allergic diseases in Finland. For example, in 1991 it accounted for almost 40% of the new occupational asthma cases.

Objective
This study compares the performance of the purified major cow allergen (BDA20) and crude bovine epithelial extract (BEA) in diagnostic tests and examines the role of milk allergy‐associated bovine proteins (bovine serum albumin, α‐lactalbumin, β‐lactoglobulin, casein) in respiratory cow allergy.

Methods
The humoral responses of cow‐asthmatic and healthy farmers to the various components of BEA were analysed with sodium dodecyl sulfate‐polyacrylamide gel electrophoresis (SDS‐PAGE) and immunoblotting. The levels of specific Ige and IgG antibodies were quantifieated with enzyme‐linked inimunosorbent assays (FLISAs). The cellular responses were analysed with antigen‐specific lymphoeyte proliferation tests.

Results
The specific anti‐BDA20 IgE measurement was found to be best in distinguishing between the asthmatic farmers and their healthy colleagues. It proved possible to determine a cut‐off value that gave the analysis a specificity and sensitivity of 100%; the distinction between the two groups was highly significant (P 0.0001). In the lymphocyte proliferation analysis, cow asthma was more closely associated with reactivity to BDA20 than to BEA. In the measurement of anti‐BDA20 and anti‐BEA IgG antibody levels, considerable overlap between the groups was observed, suggesting that these antibodies are not directly involved in cow allergy. When proteins associated with milk allergy were used as test reagents, no statistically significant differences could be observed between the groups, except for anti‐casein IgE antibodies the level of which, however, overlapped considerably between the farmer groups.

Conclusion
These findings suggest that purified BDA20 is better than BEA for diagnosing cow asthma and that proteins associated with milk allergy are of only marginal significance in this disease.
Exposure to gaseous formaldehyde induces IgE‐mediated sensitization to formaldehyde in school‐children
Authors: WANTKE F. , DEMMER C. M. , TAPPLER P. , GÖTZ M. , JARISCH R.
Published: April 2006

Background
Children attending a primary school showed symptoms such as headache, cough, rhinitis and epistaxis. Assessment of specific IgE to formaldehyde gave positive results in some children.

Objective
Was IgE‐mediated sensitization as well as symptoms in children associated with formaldehyde exposure at school?

Methods
Sixty‐two 8‐year‐old children attending three forms at a primary school were investigated. Indoor formaldehyde concentrations were measured in classrooms of both schools (one frame construction with particleboard used extensively as panelling vs a brick building) which were consecutively attended. Assessment of specific IgE to formaldehyde was done in all children. Children were transferred to a brick building and 3 months later specific IgE to formaldehyde in pupils showing initially elevated radioallergosorbent test (RAST) values reassessed. In all children symptoms were evaluated by questionnaire before and 3 months after changing school.

Results
In the school panelled with particleboard the World Health Organization (WHO) threshold for formaldehyde of 0.050 ppm was crossed in two classrooms (0.075 ppm and 0.069 ppm) whereas in one classroom 0.043 ppm was found. RAST classes of >2 were found in three children, two of them attending the classroom with 0.075 ppm formaldehyde. Elevated RAST classes of ≥1.3 were found in another 21 pupils. Thirty‐eight pupils as well as 19 control children showed RAST classes in the normal range of ≤1.2. Headache, nose bleeding, rhinitis, fatigue, cough, dry nasal mucosa and burning eyes were found in the affected children. There was a good correlation between symptoms and the formaldehyde concentrations in the classrooms. However, elevated IgE levels to formaldehyde did not correlate with symptoms. Formaldehyde concentrations in the classrooms of the brick built school were 0.029 ppm, 0.023 ppm and 0.026 ppm. After transferral specific IgE to formaldehyde decreased significantly from 1.7 ± 0.5 to 1.2 ± 0.2 (P> 0.002) as did the incidence of symptoms.

Conclusion
Gaseous formaldehyde, besides its irritant action, leads to IgE‐mediated sensitization. As children are more sensitive to toxic substances than adults, threshold levels for indoor formaldehyde should be reduced for children.
Recovery of human basophils after FMLP‐stimulated secretion
Authors: DVORAK A. M. , WARNER J. A. , FOX P. , LICHTENSTEIN L. M. , MACGLASHAN D. W.
Published: April 2006

Backgrottnd
Basophils arc circulaling, secretory grunulocytes that are generally considered to be end‐stage cells. In one species of guinea‐pigs, basophilic leucocytes have been shown to recover from stimulated secretion in short‐term cultures. Similar studies have not been done using human basophils.

Objective
The purpose of this study was to examine human hasophils in short‐term recovery intervals following stimulation of secretion to determine whether visual evidence of recovery occurred.

Methods
We examined the ultrastrucural morphology of early recovery (l0 min‐6h) of human basophils following secretion stimulated by formyl‐mcthionyl‐lcucyl‐phenyl‐alanine (FMLP). A combined technique for electron microscopy consisted of postfixation exposure to cationizcd ferritin and reduced osmium, providing maximum quality images and allowing identification of intracellular spaces/organelles that opened to the cell surface, often out of the plane of section.

Results
The ultrastructural evaluation revealed that control basophils (0 time–6h) did not undergo regulated secretion or develop the morphologies associated with recovery following secretion. FMLP‐stimulated basophils underwent an overlapping continuum of piecemeal degranulation ‐ anaphylactic degranutation (0 time‐ I min), producing vesicle‐ and granule‐free, completely degranulated, viable, mature basophils with polylobed nuclei. The early recovery period (10 min‐h) following FMLP stimulation was characterized by reconstitution of granules. Morphological mechanisms for granule reconstitution included a mixture of conservation, condensation, and synthetic events.

Coticlttsion
Human basophils, like guinea pig basophils, have the polential to recover from regulated secretion.
The importance of the pecan tree pollen in allergic manifestations
Authors: RACHMIHL M. , VERLEGER H. , WAISEL Y. , KEYNAN N. , KIVITY S. , KATZ Y.
Published: April 2006

Background
Pecan tree pollen is considered to be highly allergenic. However, no specific scienlific data about its role in causing allergic diseases are avaliable.

Ohjective
To study the role of pecan tree pollen in the development of allergy.

Methods
The presence of pecan tree pollen was determined by weekly and monthly counting of airborne grains. The incidence of pecan tree pollen atopy and clinical manifeslations were studied in 395 participants, aged 4–70 years, who comprised 78.2% of the whole eligible population of a rural community. The participants were skin tested for different extracts of allergens, completed detailed questionnaires, and their medical files were evaluated.

Results
During May. pecan tree pollen grains comprised 70% of the total airborne gruins. A positive skin‐prick test (SPT) to pecan was shown by 46(11.6%) participants, constituting 25.4% of the atopic population. Of those who were found atopic to one or more allergens 50.3% had symptoms, whereas the parallel figure for those atopic to pecan pollen was 76.1% (P< 0.0()5); 58.7% of the pecan atopic participants had hay fever, 43.5% had asthma, and 31.5% had both hay fever and asthma. Among peean atopic participants the incidence of hay fever increased with age (P‐ 0.05) while the incidence of bronchial asthma, as a sole manifestation of allergy, decreased in the > 17‐year‐old age group (P<0.0I). Of the pecan atopies 65.2% had clinical symptoms coinciding only wilh the pecan pollen season and an additional 10.9% had perennial symptoms.

Conclusion
Pecan tree releases highly allergenie pollen grains, which are correlated to the incidence of hay fever in the exposed population. The contribution of pecan tree pollen to the symptoms was highly significant after discounting olive and cypress trees thai also pollinate in the spring. In children, the pecan tree constitutes a possible etiologic agent for the development of asthma.
Sensory neuropeptides are not directly involved in bronchial hyperresponsiveness induced by interleukin‐8 in guinea‐pigs in vivo
Authors: FUJIMURA M. , TSUJIURA M. , NOMURA M. , MIZUGUCHI M. , MATSUDA T. , MATSUSHIMA K.
Published: April 2006

Background
Interleukin‐8 (IL‐8) hus been shown to be a chemotactic factor for netitrophils, T‐lymphocytes and eosinophils. Repeated intranasal administration of IL‐8 enhances bronchial responsiveness to inhaled histamine in guinea‐pigs. Neuropeptides which arc released trotn C‐fibre nerve‐endings have been postulated to induce bronchial hyperresponsiveness through neurogenic inflammation.

Objective
This study was conducted to examine whether sensory neuropeptides are involved in the IL‐8‐induced bronchial hyperresponsiveness.

Methods
IL‐8 at a dose of 5μg/kg was administered intranasally to guinea‐pigs twice a week for 3 weeks. One day after the last administration, animals were anesthetized and artificially ventilaled through tracheal cannula, and lateral pressure at the tracheal cannula (Pao) was measured as an overall index of airway responses lo increasing concentrations of inhaled histamine (25, 50, 100, and 200 μg/mL). A NKI and NK2 dual antagonist FK224(10mg/kg), a selective NK1 antgonist FK888 (10mg/kg) or vehicle was intravenously administered 10min before measurement of bronchial responsiveness.

Result
The IL‐8 treatment significantly enhanced bronchial responsiveness to histamine (ANOVA P < 0.01). FK224 or FK888 did not alter the IL‐8‐induced bronchial hyperresponsiveness.

Conclusion
We conclude that repeated intranasal administratioti of IL‐8 causes bronchial hyperresponsiveness (BHR) and that neuropeptides such as neurokinin A and substance P do not directly contribute to the development of BHR induced by IL‐8.
Cloning and sequencing of the group 6 allergen of Dermatophagoides pteronyssinus
Authors: BENNETT B. J. , THOMAS W. R.
Published: April 2006

Background
The allergen Der p 6 from Dermatophagoides pteronyssinus has been described by substrate affinity as mite chymotrypsin.

Objective
The aim of this paper was to describe a cDNA clone encoding the allergen.

Methods
cDNA was cloned from a λ library using oligonucleotides published for Der p 6.

Results
The clone P6.1.1 had the N‐terminal amino acid residues as reported for Der p 6, and at position 189 the Ser was conserved in chymotrypsin for substrate specificity as well as the catalytic triad of His57, Asp102 and Ser195 for serine proteases. The estimated Mr was 24.9K and it was 37% identical to the trypsin allergen Der p 3.

Conclusion
cDNA encoding Der p 6 has been described.
Fine structural specificity differences of trimethoprim allergenic determinants
Authors: PHAM N. H. , BALDO B. A. , MANFREDI M. , ZERBONI R.
Published: April 2006

Background
Adverse reactions, including immediate hypersensitivity, to the widely used antibacterial agent trimethoprim occur quite frequently. In recent years some progress has been made in developing an immunoassay to aid diagnosis of type 1 allergic reactions to trimethoprim and to define the basis of IgE antibody recognition of the drug.

Objectives
The molecular basis of IgE binding to trimethoprim was examined more closely with a view to defining the fine structural recognition differences between patients' sera. Utilization of such information may lead to immunoassays that are more specific and sensitive and of greater diagnostic value.

Methods
Immunoassays for specific IgE antibodies and quantitative hapten inhibition studies with trimethroprim and selected structural analogues were employed, together with sera from eight subjects clearly defined clinically as allergic to trimethoprim.

Results
Three different allergenic determinant structures have been identified on the trimethoprim molecule. Identification of the 3,4‐dimethoxybenzyl group as a determinant was achieved on the basis of inhibitory activities of diaveridine, 3,4‐dimethoxy‐phenylethylamine, 3,4‐dimethoxybenzoic acid and 3,4,5‐trimethoxycinnamic acid. Evidence that the opposite end of the trimethoprim molecule was not being recognized was obtained from results with some pyrimidine derivatives, each of which showed no activity. Identification of the second determinant, the 2,4‐diamino‐5‐(3′,4′‐dimethoxybenzyl) pyrimidine group, rested mainly on the superior inhibitory potency of diaveridine, which differs from trimethoprim by just one methoxy group. With sera from some trimethoprim‐allergic subjects, only trimethoprim was active, suggesting that the entire molecule was a third IgE‐binding determinant structure.

Conclusion
As with other drug allergenic determinants defined so far, heterogeneity of trimethoprim IgE‐binding determinants exists, and fine structural differences between determinants may be as small as a single methoxy group. Identification of the 2,4‐diamino‐5‐(3′,4′‐dimethoxybenzyl) pyrimidine group as an allergenic determinant increases the number of known trimethoprim determinants to three, and suggests that the number and heterogeneity of determinants will be a reflection of the number of allergic subjects studied.
IgE cross‐reactivity between birch pollen, mugwort pollen and celery is due to at least three distinct cross‐reacting allergens: immunoblot investigation of the birch‐mugwort‐celery syndrome
Authors: BAUER L. , EBNER C. , HIRSCHWEHR R. , WÜTHRICH B. , PICHLER C. , ERITSCH R. , SCHEINER O. , KRAFT D.
Published: April 2006

Background
Allergy to celery is often associated with sensitization to birch and/or mugwort pollen.

Objective and methods
In a multi‐centre study, sera from 23 patients suffering from type I allergy to celery and 15 patients with positive celery RAST but wo clinical sensitization were compared. To examine whether cross‐reactivity between celery and mugwort pollen iticludes cross‐sensitization to birch pollen allergens, we determined cross‐reacting structures in birch pollen, mugwort pollen and celery by means of immunoblotting. Inhibition studies were performed by preincubation of sera with extracts of birch pollen, mugwort pollen, and celery.

Results
We identified three groups of proteins—homologues of Bet v I and birch profilin (Bet v 2) as well asa group of proteins with a molecular range of 46 to 60 kD—displaying IgE‐cross‐reactivity, which were shared by birch pollen and celery. Two of these groups of allergens (profilin and the 46 to 60 kD proteins) were also present in mugwort pollen. In this paper we demonstrate that most cross‐reacting allergens present in mugwort pollen and celery can also be detected in birch pollen extract.

Conclusion
Therefore we propose, from a serological point of view, to extend the mugwort‐celery syndrome to the birch‐mugwort‐celery syndrome.