bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pruritus‐associated response mediated by cutaneous histamine H3 receptors
Authors: Sugimoto Y. , Iba Y. , Nakamura Y. , Kayasuga R. , Kamei C. 
Published: March 2004

SummaryBackground  Histamine is one of the most common chemical mediators causing pruritus, and H1 receptor antagonists have been used as a first choice in its treatment. On the other hand, although the presence of H3 receptors has been identified in the skin, few studies have investigated the involvement of H3 receptors on pruritus.Objective  The purpose of this study was to examine whether H3 receptor agonist or antagonist influences the incidence of scratching behaviour in ICR or mast cell‐deficient WBB6F1‐W/WV mice.Methods  The mice were given an intradermal injection of H3 receptor agonist or antagonist into the rostral part of the back, and the occurrence of scratching behaviour at the injected site by the hind paws was counted over 60 min.Results  H3 receptor antagonists, thioperamide and AQ0145 significantly increased the incidence of scratching behaviour in ICR mice. H3 receptor agonist, (R)‐alpha‐methylhistamine, had no effect. On the other hand, (R)‐alpha‐methylhistamine significantly inhibited thioperamide or AQ0145‐induced scratching behaviour. In addition, both thioperamide and AQ0145 elicited scratching behaviour in mast cell‐deficient WBB6F1‐W/WV mice.Conclusion  From these results, it may be concluded that H3 receptors are involved in the modulation of pruritus in the skin, and mast cells are not essential in this response. In addition, H3 receptor agonists can be useful as a novel therapeutic approach against pruritus.
Protein sequence analysis of a novel 103‐kDa Dermatophagoides pteronyssinus mite allergen and prevalence of serum immunoglobulin E reactivity to rDer p 11 in allergic adult patients
Authors: Lee C.‐S. , Tsai L.‐C. , Chao P.‐L. , Lin C.‐Y. , Hung M.‐W. , Chien A.‐I. , Chiang Y.‐T. , Han S.‐H. 
Published: March 2004

SummaryBackground
House dust mites are regarded as important indoor allergens. While the most studies mite allergens are low molecular weight (mw), a high mw Dermatophagoides farinae mite paramyosin (Der f 11) has recently been cloned. We have also cloned a novel high mw Dermatophagoides pteronyssinus (Dp) mite allergen, Der p 11.Objective
The aim of this study was to isolate and express a cDNA gene coding for a Der p 11 allergen, to compare the sequence of Der p 11 with other antigens and to evaluate the presence of IgE reactivity to the recombinant protein (rDer p 11) in the sera of allergic adult patients.Methods
The full‐length Der p 11 gene was isolated by cDNA library screening, 5′‐3′ rapid amplification of cDNA ends and PCR. The cDNA gene was expressed as a glutathione‐S‐transferase fusion protein in Escherichia coli. The allergenicity of rDer p 11 was tested by human IgE immunodot or immunoblot assay in a large panel of 100 allergic patients with bronchial asthma, allergic rhinitis or eczema.Results
Der p 11 is a 2965 bp cDNA gene with a 2625 bp open reading frame coding for a 875 amino acid protein. The deduced amino acid sequence of the Der p 11 showed significant homology with various invertebrate paramyosins. The prevalence of serum IgE reactivity to rDer p 11 on immunodot assay ranged from 41.7% to 66.7% in different allergic patient groups, whereas it was rare in non‐atopic patients with urticaria (18.8%) and in normal individuals (8%). A high frequency (five out of eight) of MAST(Dp)− allergic serum samples had specific IgE‐binding activity to rDer p 11 or its fragments on immunoblot assay, even though their IgE‐binding activity to Dp extract was either weak or negative.Conclusion
The 103‐kDa Der p 11 appears to be major Dp mite allergen with a high frequency of IgE reactivity in sera of patients allergic to mites.
Bronchoalveolar lavage fluid concentrations of transforming growth factor (TGF)‐β1, TGF‐β2, interleukin (IL)‐4 and IL‐13 after segmental allergen challenge and their effects on α‐smooth muscle actin and collagen III synthesis by primary human lung fibroblasts
Authors: Batra V. , Musani A. I. , Hastie A. T. , Khurana S. , Carpenter K. A. , Zangrilli J. G. , Peters S. P. 
Published: March 2004

SummaryRationale
Asthmatic airway remodelling is characterized by myofibroblast hyperplasia and subbasement membrane collagen deposition. We hypothesized that cytokines and growth factors implicated in asthmatic airway remodelling are increased in bronchoalveolar lavage (BAL) fluid of asthmatics after segmental allergen challenge (SAC), and that these growth factors and cytokines increase α‐smooth muscle actin (α‐SMA) and collagen III synthesis by human lung fibroblasts (HLFs).Methods
Transforming growth factor (TGF)‐β1, TGF‐β2, IL‐4 and IL‐13 levels were measured in BAL fluid from 10 asthmatics and 9 non‐asthmatic controls at baseline and then 1 day, 1 week and 2 weeks after SAC. Confluent cultures of HLFs were stimulated by exogenous addition of TGF‐β1, TGF‐β2, IL‐4 or IL‐13 (concentration range 0.01–10 ng/mL) over 48 h. Collagen III was measured in culture supernates and α‐SMA in cell lysates by Western blot.Results
At baseline, there was no difference in BAL fluid concentrations of TGF‐β1, IL‐4 and IL‐13 between asthmatics and controls; however, non‐asthmatics had higher concentrations of total TGF‐β2. In asthmatics, BAL fluid concentrations of all four factors increased significantly 1 day after SAC. TGF‐β1, TGF‐β2 and IL‐13 concentrations returned to baseline by 1 week after SAC, but BAL fluid IL‐4 concentration remained elevated for at least 2 weeks. TGF‐β1, TGF‐β2 and IL‐4 significantly increased α‐SMA in fibroblasts, but only IL‐4 caused corresponding increases in collagen III synthesis. IL‐13 had no direct effects on collagen III synthesis and α‐SMA expression.Conclusions
Because IL‐4 caused a dose‐dependent increase in α‐SMA and collagen III synthesis, it may be an important cytokine mediating asthmatic airway remodelling. TGF‐β1 and TGF‐β2 may also play a role in airway remodelling by stimulating phenotypic change of fibroblasts to myofibroblasts. Additionally, collagen III synthesis appears to be independent of myofibroblast phenotype and is apparently regulated by different growth factors and cytokines.
Increased airway responsiveness, allergy‐type‐I skin responses and systemic anaphylaxis in a humanized‐severe combined immuno‐deficiency mouse model
Authors: Herz U. , Botchkarev V. A. , Paus R. , Renz H. 
Published: March 2004

SummaryBackground
In patients with allergic bronchial asthma, a strong relationship between elevated serum IgE antibody titres and the development of increased airway responsiveness (AR) has been demonstrated. To further elucidate the relationship between human (hu) IgE and development of increased AR, we developed an in vivo model utilizing immuno‐compromised severe combined immuno‐deficiency (SCID) mice.Methods
SCID mice were either reconstituted with peripheral blood mononuclear cells (PBMC) from non‐atopic, healthy or atopic individuals sensitized against house dust mite allergen (Der p), or passively sensitized with plasma from non‐atopic, healthy or atopic individuals.Results
In both systems, atopic hu‐SCID mice developed increased AR. The following results suggest that these responses were mediated via IgE antibodies: increased AR did not occur after transfer of either PBMC or IgE‐negative plasma from non‐atopic individuals; increased AR occurred simultaneous with increased serotonin release detected 15 min after allergen–aerosol challenge in bronchoalveolar lavage fluid; and increased AR required at least two allergen–aerosol challenges. SCID mice reconstituted with serum containing anti‐Der p IgE antibodies developed positive immediate‐type skin test responses to intradermal injection of Der p as well as anti‐hu‐IgE antibody. In addition, IgE binding to skin mast cells was demonstrated by immunohistochemistry. Furthermore, intravenous challenge of hu anti‐Der p positive SCID mice with Der p resulted in systemic anaphylaxis.Conclusion
These data provide evidence that passive immunization of SCID mice with hu IgE alters AR and that T cells and eosinophils were not a requirement for the development of increased AR in this model.
Association of polymorphisms in Th1, Th2 cytokine genes with hayfever and atopy in a subsample of EPIC‐Heidelberg
Authors: Nieters A. , Linseisen J. , Becker N. 
Published: March 2004

SummaryBackground
Hayfever is determined by an interaction of environmental and genetic factors and biologically characterized by an imbalanced T helper cell 1 (Th1) and Th2 immune response and elevated IgE levels against inhalant allergens. Indications exist that polymorphisms in cytokine genes involved in the regulation of the Th1/Th2 balance may contribute to the allergic phenotype.Objective
We investigate whether polymorphisms in genes directly or indirectly involved in Th1, Th2 immune response are associated with hayfever and elevated IgE levels against inhalant allergens.Methods
From a subsample of the European Prospective Investigation into Cancer and Nutrition‐Heidelberg, 322 subjects with hayfever and 322 age‐ and sex‐matched non‐allergic controls were selected and genotypes determined for 15 polymorphisms in 13 genes. Plasma IgE against inhalant allergens was measured via CAPSX1 (Phadiatop) test. We computed odds ratios (ORs) by logistic regression, tests on group differences of IgE‐levels in dependence upon genotype and tests for trend by means of non‐parametric methods.Results
We found decreased OR for hayfever (OR=0.60, 95%CI=0.4–0.9) and sensitization to inhalant antigens (OR=0.5, 95%CI=0.4–0.8) in heterozygotes of the IL‐6 −174 G/C polymorphism. Homozygotes of the G‐allele in IL‐2 −330 T/G were at increased risk of hayfever (OR=2.6, 95%CI=1.3–5.2). Moreover, we found indications for differences in IgE levels against inhalant allergens in dependence upon genotypes of polymorphisms in IL‐4R, IL‐6, IL‐13, and IL‐18.Conclusion
Our data suggest an association of genetic variants in IL‐6 and IL‐2 with hayfever, confirm a role of polymorphisms in IL‐4R, IL‐13, and IL‐18 for the elevated IgE phenotype, and add IL‐6 to the list of candidate genes.
The relation of markers of fetal growth with asthma, allergies and serum immunoglobulin E levels in children at age 5–7 years
Authors: Bolte G. , Schmidt M. , Maziak W. , Keil U. , Nasca P. , Von Mutius E. , Weiland S. K. 
Published: March 2004

SummaryBackground
It has been suggested that fetal growth and maturation have an impact on the development of allergic diseases later in life.Objective
To examine the association between measures of fetal growth and allergic disease in children at age 5–7 years.Methods
As part of the German International Study of Asthma and Allergies in Childhood phase II surveys, a random sample of school beginners (n=1138) was examined in 1995. Data on anthropometric measures at birth and gestational age were obtained from maternal copies of birth records. Data on symptoms and doctor‐diagnosed asthma, atopic dermatitis and hayfever were gathered by parental questionnaires. Atopic sensitization was assessed by serum IgE and skin prick tests to common aeroallergens. Children (741) had complete data for the explanatory variables of interest and were thus eligible for this analysis. Confounder‐adjusted prevalence odds ratios (PORs) and means ratios with 95% confidence intervals (CI) were calculated using multiple logistic and linear regression.Results
Birth weight and gestational age were positively associated with atopic sensitization (Ptrend=0.025 and 0.035, respectively). Children with a low birth weight relative to head circumference had a decreased risk of sensitization (POR 0.44, 95% CI 0.21–0.91; Ptrend=0.020). Moreover, total serum IgE increased with increasing birth weight (Ptrend=0.042). No consistent relationship was observed between markers of fetal growth and wheezing, doctor‐diagnosed asthma, atopic dermatitis and hayfever.Conclusion
These data suggest that fetal growth and maturity are associated with atopic sensitization and total serum IgE levels in childhood.
In vitro allergy diagnosis: should we follow the flow?
Authors: Ebo D. G. , Hagendorens M. M. , Bridts C. H. , Schuerwegh A. J. , De clerck L. S. , Stevens W. J. 
Published: March 2004

SummaryDuring the last 5 years, an increasing number of studies have demonstrated that flow cytometric quantification of in vitro basophil activation can be a quite performant and reliable tool to measure IgE‐dependent allergen‐specific responses in allergic patients. So far, most assays have used CD63 as a basophil activation marker and native allergen extracts for stimulation. However, other basophil markers and recombinant allergens have recently been introduced. The technique has been applied for the diagnosis of allergy to pollen, house dust mite, food, natural rubber latex, hymenoptera venom and drugs. In addition, the technique has proven to be useful in non‐IgE‐mediated reactions such as hypersensitivity to drugs as well as detection of auto‐antibodies in chronic urticaria. This review will focus on some specific issues: (1) principles of flow cytometric analysis of in vitro‐activated basophils, (2) general technical aspects of the technique (including passive sensitization), (3) clinical applications and (4) recommendations for further development and evaluation of the technique.
The recombinant major allergen of Parietaria judaica and its hypoallergenic variant: in vivo evaluation in a murine model of allergic sensitization
Authors: Orlandi A. , Grasso F. , Corinti S. , Marinaro M. , Bonura A. , Boirivant M. , Colombo P. , Di Felice G. 
Published: March 2004

SummaryBackground  Par j 1 represents the major allergenic component of Parietaria judaica pollen. Its three‐dimensional structure is stabilized by four disulphide bridges. A family of three‐dimensional mutants of the recombinant Par j 1 (rPar j 1) allergen, showing reduced allergenicity and retained T cell recognition has been recently developed by site‐directed mutagenesis.Objective  To develop and characterize a murine model of IgE sensitization to rPar j 1. To evaluate similarities between the murine model and the human IgE response. To investigate in this model the recognition of a hypoallergenic mutant of Par j 1, and to study the immune responses elicited in mice by the mutant itself.Methods  BALB/c mice were sensitized by two intraperitoneal immunizations with rPar j 1 in alum on days 0 and 21. Allergen‐specific serum IgE and IgG responses were studied by direct ELISA and immunoblotting, ELISA inhibition and competitive ELISA. Cell proliferation was evaluated in splenocyte cultures.Results  Sensitization with rPar j 1 induced high levels of IgE and IgG1 vs. low levels of IgG2a. Mouse antibodies specific to rPar j 1 were able to compete with human IgE for recognition of rPar j 1. IgE from mice immunized with rPar j 1 showed a significantly reduced binding activity towards the hypoallergenic variant rPjC, which lacks three disulphide bridges. On the contrary, rPjC was recognized by IgG1 and IgG2a antibodies as well as rPar j 1. The proliferative response to rPjC by splenocytes from mice immunized with rPar j 1 was comparable to that stimulated by rPar j 1. Immunization with rPjC induced low levels of IgE antibodies to the rPjC itself, while IgG and proliferative responses were similar to those induced by rPar j 1.Conclusion  Conformational variants of allergens, displaying reduced allergenicity accompanied by retained IgG and T cell recognition, offer a safe, specific and flexible approach to immunotherapy of type I allergy. Our mouse model of IgE sensitization to a recombinant allergen, mimicking the human response to its native counterpart, could provide valuable information for pre‐clinical testing of such hypoallergenic molecules.
Prolonged allergen challenge in mice leads to persistent airway remodelling
Authors: Mcmillan S. J. , Lloyd C. M. 
Published: March 2004

SummaryBackground
Inflammatory infiltrates, airway hyper‐responsiveness, goblet cell hyperplasia and subepithelial thickening are characteristic of chronic asthma. Current animal models of allergen‐induced airway inflammation generally concentrate on the acute inflammation following allergen exposure and fail to mimic all of these features.Objective
The aim of this study was to use a murine model of prolonged allergen‐induced airway inflammation in order to characterize the cells and molecules involved in the ensuing airway remodelling. Moreover, we investigated whether remodelling persists in the absence of continued allergen challenge.Methods
Acute pulmonary eosinophilia and airways hyper‐reactivity were induced after six serial allergen challenges in sensitized mice (acute phase). Mice were subsequently challenged three times a week with ovalbumin (OVA) (chronic phase) up to day 55. To investigate the persistence of pathology, one group of mice were left for another 4 weeks without further allergen challenge (day 80).Results
The extended OVA challenge protocol caused significant airway remodelling, which was absent in the acute phase. Specifically, remodelling was characterized by deposition of collagen as well as airway smooth muscle and goblet cell hyperplasia. Importantly, these airway changes, together with tissue eosinophilia were sustained in the absence of further allergen challenge. Examination of cytokines revealed a dramatic up‐regulation of IL‐4 and tumour growth factor‐β1 during the chronic phase. Interestingly, while IL‐4 levels were significantly increased during the chronic phase, levels of IL‐13 fell. Levels of the Th1‐associated cytokine IFN‐γ also increased during the chronic phase.Conclusion
In conclusion, we have demonstrated that prolonged allergen challenge results in persistent airway wall remodelling.
Low numbers of interleukin‐12‐producing cord blood mononuclear cells and immunoglobulin E sensitization in early childhood
Authors: Nilsson C. , Larsson A.‐K. , Höglind A. , Gabrielsson S. , Blomberg M. Troye , Lilja G. 
Published: March 2004

SummaryBackground
Successful pregnancies are associated with skewing towards a Th2 cytokine profile. Cytokine responses to allergens can be detected in cord blood mononuclear cells (CBMC), suggesting allergen priming already in utero.Objective
To investigate the cytokine profile in CBMC after in vitro stimulation with allergens and to relate the responses to the outcome in terms of allergic disease at 2 years of age.Methods
CBMC were isolated from 82 children. The responses to ovalbumin (OVA), birch, cat and phytohaemagglutinin (PHA) were investigated by the ELISpot technique. The numbers of IFN‐γ‐, IL‐4‐ and IL‐12‐producing CBMC were counted for each stimulation. The children were followed prospectively; skin prick test (SPT) and RAST towards food and inhalant allergens were assessed at 24 months of age.Results
Sixteen (19.5%) children were classified as IgE sensitized (positive SPT; 3 mm and/or RAST; 0.35 kUA/L). The numbers of IL‐12‐producing CBMC after stimulation with birch, OVA and cat were lower among IgE‐sensitized children, statistically significant for cat. IFN‐γ‐producing cells, did not differ in numbers between the sensitized and non‐sensitized children. Children who had atopic eczema/dermatitis syndrome (AEDS) during the observation (n=53) had significantly lower numbers of IFN‐γ‐producing CBMC after stimulation with OVA and cat than their non‐AEDS counterparts.Conclusions
Although the numbers of infants in our study are limited our data suggest that a low number of IL‐12‐producing CBMC is associated with IgE sensitization during early childhood and that a reduced number of IFN‐γ‐producing CBMC promotes the development of AEDS during the first 2 years of life.
Identification by immunoblot of venom glycoproteins displaying immunoglobulin E‐binding N‐glycans as cross‐reactive allergens in honeybee and yellow jacket venom
Authors: Hemmer W. , Focke M. , Kolarich D. , Dalik I. , Götz M. , Jarisch R. 
Published: March 2004

SummaryBackground
IgE antibodies against carbohydrate epitopes have been identified recently as a major cause of in vitro double positivity to honeybee (HB) and vespid venom in patients with stinging‐insect allergy. As these antibodies possibly have low clinical relevance they may be misleading in the diagnosis of venom allergy.Objective
To confirm the role of carbohydrate epitopes in double positivity and to locate the responsible glycoallergens in HB and yellow jacket (YJ) venom by western blot.Methods
Immunoblot inhibition using HB venom, YJ venom and two glycoprotein sources displaying 1‐3‐fucosylated N‐glycans (i.e. oilseed rape (OSR) pollen, and the synthetic neo‐glycoprotein fucosylated/xylosylated N‐glycans from bromelain coupled to bovine serum albumin (MUXF‐BSA)) as inhibitors were performed with sera from 15 double‐positive patients with stinging‐insect allergy. Additionally, reactivity with blotted hymenoptera venoms of a carbohydrate‐specific rabbit antiserum against OSR pollen was investigated.Results
Major venom glycoallergens binding with carbohydrate‐specific human IgE and rabbit IgG were detected in HB venom at 42 (hyaluronidase (HYA)), 46, 65 and 95 kDa, and in YJ venom at 38 and 43 kDa (HYA). Antibody binding to these allergens was completely lost after periodate treatment. Glycans of HB phospholipase were bound by patients' IgE only after protein denaturation. In 10 of the 15 patients the reactivity was with the second venom because of carbohydrates alone. The high‐molecular‐weight glycoallergens identified in HB venom probably correspond to similar proteins described earlier, including allergens B and C. The 38‐kDa YJ allergen might represent a homologue of V mac 3.Conclusions
The data confirm the proposed role of carbohydrate‐specific IgE in double positivity to HB and YJ venom and shed new light on some previously described minor hymenoptera allergens of uncertain clinical significance. The consideration of carbohydrate‐specific IgE may allow to discriminate between patients with potentially relevant and patients with non‐relevant double sensitization.
Investigation into the mechanisms by which nedocromil sodium, frusemide and bumetanide inhibit the histamine‐induced itch and flare response in human skin in vivo
Authors: Willis E. F. , Clough G. F. , Church M. K. 
Published: March 2004

SummaryBackground
In a previous study, iontophoresis of nedocromil sodium into human skin in vivo was shown to reduce histamine‐induced itch and flare. In asthma, the Na+/K+/2Cl− cotransporter inhibitors, frusemide and bumetanide, have been reported to have many similar actions to nedocromil sodium.Objective
To compare the effects of these drugs in the histamine‐induced itch, flare and weal response in human skin in vivo and elucidate their site of action.Methods
Nedocromil sodium, frusemide bumetanide and reversed osmosis water (control), were introduced by iontophoresis into the forearm skin of 10 volunteers in each of two single‐blind studies. In study 1, histamine (20 μL of 100 μm) or vehicle was injected into the area of iontophoresis 10 min later. In study 2, histamine or vehicle was injected 5 mm outside the area of iontophoresis so the flare developed over the area of iontophoresis. Itch was scored on a visual analogue scale every 20 s for 5 min, flare areas were assessed using scanning laser Doppler imaging up to 10 min and weal was assessed by planimetry at 10 min.Results
In study 1, nedocromil sodium, frusemide and bumetanide reduced itch scores by 36%, 48% and 34%, respectively, and flare areas by 17%, 26% and 15% respectively (all P<0.05). Weal areas and blood flux in the flare were unaffected. In study 2, itch scores, flare areas and weal areas were not inhibited. Also, blood flux values in areas of drug and water iontophoresis were not different.Conclusion
This study has provided evidence to support the hypothesis that nedocromil sodium, frusemide and bumetanide inhibit sensory nerve activation to reduce the itch and flare responses induced by histamine in human skin in vivo. It is likely that inhibition of a Na+/K+/2Cl− cotransporter in the sensory nerve membrane is a possible mechanism of action.