bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparing tacrolimus ointment and oral cyclosporine in adult patients affected by atopic dermatitis: a randomized study
Authors: Pacor M. L. , Di Lorenzo G. , Martinelli N. , Mansueto P. , Rini G.B. , Corrocher R. 
Published: April 2004

SummaryBackground
Atopic dermatitis (AD) is a chronic allergic inflammatory disease, which manifests itself with eczematous skin lesions.Objective
We compared the clinical efficacy of tacrolimus ointment (0.1%) given twice a day and oral cyclosporine (3 mg/kg) given once daily. Rescue medication for itching included cetirizine 10–20 mg (equal to one or two tables).Methods
Thirty patients, aged 13–45 years (mean±SD 27.1±10.9), with a history of moderate‐to‐severe AD were randomized to treatments, 15 patients for each treatments. Assessment of efficacy was based on SCORAD, on scores of daily itching, erythema, interference with sleep, due to the skin condition and days without use of cetirizine tablets. SCORAD, measured on a scale (0–103), was evaluated before treatment (0) and at 7, 14, 21, 28, 35 and 42 days after treatment. Similarly, the means of daily symptoms, on a scale (0–3), were evaluated before the treatment (0) and at 7, 14, 21, 28, 35 and 42 days after treatment; finally, on day without use of cetirizine tablets. The safety of the study treatments was assessed through haematologic, biochemical and urinary testing and on systolic and diastolic blood pressures and heart rate measurements.Results
SCORAD decreased in the two treatment groups 14 days after the beginning of the period study. However, the patients in tacrolimus ointment group reported significantly lower SCORAD than those treated with oral cyclosporine. Overall SCORAD, as assessed by the area under the curve (AUC) day0–42 (score/day), was significantly lower in the tacrolimus ointment group when compared with oral cyclosporine (P<0.001). Similarly, AUC day0–42 (score/day) for itching, erythema and number of nights without interference with the sleep due to skin condition were significantly lower in the group of patients treated with tacrolimus compared with those treated with cyclosporine (P=0.003, 0.005 and 0.01, respectively). As regards the use of rescue medication, expressed by median of number of days without use of anti‐H1, it was significantly lower in the group treated with tacrolimus (82.5) than in the cyclosporine group (76.5) (P=0.03). There were no appreciable changes in haematological and biochemical indices, in both treatments groups.Conclusion
The results of this comparative study demonstrate that tacrolimus ointment twice daily and cyclosporine administered orally once daily are effective on SCORAD, daily symptoms and anti‐H1 rescue. When we compared tacrolimus and cyclosporine there was a faster onset of action in the group treated with tacrolimus. The two drugs presented the same safety. However, these data support the preferential use of topical tacrolimus 0.1% in AD, because cyclosporine has potential side‐effects.
Differential activation of signal transducer and activator of transcription 6 in B cells from allergic children and their non‐allergic siblings
Authors: Deveikaite V. , Fila C. , Laurencikiene J. , Klein E. , Kihlström A. , Lilja G. , Sverremark ekström E. , Severinson E. 
Published: April 2004

SummaryBackground
The germline (GL) ɛ promoter is regulated by IL‐4 and is essential for class switching to IgE. IL‐4‐induced gene expression is largely mediated through activation of latent transcription factor STAT6 (signal transducer and activator of transcription 6).Objective
We investigated whether increased levels of IgE in allergic individuals may be associated with alteration in the level or activation of STAT6 and subsequent increase in GL ɛ promoter activity.Methods
Electrophoretic mobility shift assay and Western blotting assays were used to investigate the level of expression and activation of STAT6 in Epstein–Barr virus (EBV)‐transformed B cell lines from children with birch pollen allergy and their non‐allergic siblings. The activity of the GL ɛ promoter was tested in a transient transfection assay.Results
STAT6 was expressed at the same level in all B cell lines tested. In two out of five sibling pairs STAT6 was activated by IL‐4 more efficiently in the allergic individuals but in the three other pairs the opposite was found. In transient transfections, no difference in IL‐4‐induced GL ɛ promoter function was detected, although basal promoter activity varied between allergic and healthy siblings in two out of five pairs.Conclusions
We demonstrate for the first time that upon IL‐4 signalling STAT6 transcription factor activation differs in B cells from different individuals. Although we did not find any association between STAT6 activation and allergy, we do not exclude a possibility that stronger activation of this transcription factor is associated with an expression of allergic phenotype.
Efficacy and safety of a recombinant anti‐immunoglobulin E antibody (omalizumab) in severe allergic asthma
Authors: Holgate S. T. , Chuchalin A. G. , Hébert J. , Lötvall J. , Persson G. B. , Chung K. F. , Bousquet J. , Kerstjens H. A. , Fox H. , Thirlwell J. , Cioppa G. Della ,   on behalf of the Omalizumab 011 International Study Group
Published: April 2004

SummaryBackground
Patients with severe asthma are often inadequately controlled on existing anti‐asthma therapy, constituting an unmet clinical need.Objective
This randomized, double‐blind, placebo‐controlled trial evaluated the ability of omalizumab, a humanized monoclonal anti‐IgE antibody, to improve disease control sufficiently to enable inhaled corticosteroid reduction in patients with severe allergic asthma.Methods
After a run‐in period when an optimized fluticasone dose (1000 μg/day) was received for 4 weeks, patients were randomized to receive subcutaneous omalizumab [minimum 0.016 mg/kg/IgE (IU/mL) per 4 weeks; n=126] or matching placebo (n=120) at intervals of 2 or 4 weeks. The study comprised a 16‐week add‐on phase of treatment followed by a 16‐week fluticasone‐reduction phase. Short‐/long‐acting β2‐agonists were allowed as needed.Results
Median reductions in fluticasone dose were significantly greater with omalizumab than placebo: 60% vs. 50% (P=0.003). Some 73.8% and 50.8% of patients, respectively, achieved a 50% dose reduction (P=0.001). Fluticasone dose reduction to 500 μg/day occurred in 60.3% of omalizumab recipients vs. 45.8% of placebo‐treated patients (P=0.026). Through both phases, omalizumab reduced rescue medication requirements, improved asthma symptoms and asthma‐related quality of life compared to placebo.Conclusion
Omalizumab treatment improves asthma control in severely allergic asthmatics, reducing inhaled corticosteroid requirements without worsening of symptom control or increase in rescue medication use.
Eosinophil activation and cysteinyl leukotriene production in infants with respiratory syncytial virus bronchiolitis
Authors: Dimova‐Yaneva D. , Russell D. , Main M. , Brooker R. J. , Helms P. J. 
Published: April 2004

SummaryBackground
It has been suggested that acute infantile bronchiolitis associated with respiratory syncytial virus (RSV) may share some pathogenic features with atopic asthma in that virus‐specific IgE is produced and cysteinyl leukotrienes (cLTs) and eosinophil cationic protein (ECP) have been detected in airway secretions. ECP is a specific marker of eosinophil activation although leukotrienes can be released from a variety of cells including mast cells, eosinophils and monocytes.Objective
To test the association between eosinophil activation and cysteinyl leukotriene production in the upper airway secretions of infants with RSV positive (RSV+ve) bronchiolitis.Methods
Nasal lavage samples were performed in 78 infants (0.0–11.5 months) admitted to hospital with RSV+ve bronchiolitis soon after admission (0–48 h). Leukotriene C4 (LTC4) was assayed by enzyme immunoassay (EIA) and eosinophil cationic protein (ECP) by fluoroimmunoassay (FIA).Results
LTC4 was detectable in 51 and ECP in 57 of 78 samples with a significant positive relationship between LTC4 and ECP (r=0.557, P<0.001).Conclusion
In the majority of our subjects with RSV+ve bronchiolitis ECP and LTC4 were detectable in upper airway secretions and were significantly associated with each other. In this clinical setting much of the detected LTC4 within upper airway secretions is likely to originate from the eosinophil, an observation that may have implications for clinical management and for delineation of the underlying mechanisms associated with this illness.
The hevein domain of the major latex‐glove allergen Hev b 6.01 contains dominant T cell reactive sites
Authors: De Silva H. D. , Gardner L. M. , Drew A. C. , Beezhold D. H. , Rolland J. M. , O'Hehir R. E. 
Published: April 2004

SummaryBackground
Sensitization to natural rubber latex (Hevea brasiliensis) is a major cause of occupational asthma and rhinitis affecting frequent latex‐glove users. Hev b 6.01, a known major latex allergen, is cleaved naturally into hevein (4.7 kDa) and a C‐terminal fragment (14 kDa). Hevein is an abundant protein in latex‐glove extracts. As the immune response to allergens is initiated by activation of allergen‐specific CD4+ T cells, identification of dominant T cell epitopes is crucial for the development of specific immunotherapy.Objective
To identify dominant T cell epitopes of Hev b 6.01 in latex‐allergic glove users.Methods
Ten latex‐allergic frequent glove users and six non‐latex‐allergic atopic control subjects were selected, based on clinical symptoms and positive latex‐specific serum IgE. Serum IgE reactivity to glove extract and recombinant Hev b 6.01 (rHev b 6.01) were analysed by ELISA. Latex‐specific short‐term oligoclonal T cell lines were generated from peripheral blood of latex‐allergic subjects. These lines were tested for proliferative responses to overlapping 20‐mer peptides of the Hev b 6.01 molecule. CD4+ T cell intracellular cytokines, IL‐4 and IFN‐γ were assessed following stimulation with immobilized anti‐CD3 in the presence of IL‐2.Results
All ten of the latex‐allergic patients showed serum IgE binding to glove extract while eight of these also showed IgE binding to rHev b 6.01 by ELISA. Western blotting confirmed reactivity with rHev b 6.01 at around 20 kDa. T cell proliferation assays showed that latex‐specific T cell lines from all subjects responded to one or more peptides, with greatest frequency of reactivity to peptides Hev b 6.01 p(10–29) and Hev b 6.01 p(19–38) in the hevein domain. An allergic‐type cytokine profile with considerable IL‐4 in addition to IFN‐γ was evident from intracellular cytokine staining.Conclusion
Hevein is an important T cell as well as B cell immunogen and contains dominant T cell reactive sites.
Random outcomes of allergen‐specific responses in atopic families
Authors: Jackola D. R. , Liebeler C. L. , Blumenthal M. N. , Rosenberg A. 
Published: April 2004

SummaryBackground
Allergens are common non‐infectious antigens to which people will mount T cell dependent humoral responses. Among genetically susceptible individuals, an antigen‐specific response results involving the production of allergen‐specific IgE (atopy).Objective
Determine if this susceptibility is manifested as an inherited, allergen‐specific trait or a random response to allergens among susceptible people.Methods
We evaluated allergen‐specific outcomes in 1099 members of families with positive atopic history (26 multi‐generation and 112 nuclear families). Each was tested for sensitivity to 14 common allergens by standardized skin prick test (SPT), a marker of specific IgE production. Over 15 000 individual SPT's were evaluated. Among five randomly selected multi‐generation families (N=163), semi‐quantitative determinations of Amb a 1‐specific IgA1,2 and IgG1–4 were determined in three groups: (A) Amb a SPT+/Amb a 1‐IgE+, (B) Amb a SPT−/Amb a 1‐IgE+, (C) Amb a SPT−/Amb a 1‐IgE−.Results
By rank correlation statistics, there were no discernible ‘patterns’ of specific SPT outcomes among any of the multi‐generation families, suggesting that environmental exposure rather than allergen‐specific inheritance determined the responses. This was confirmed among the nuclear families since the conditional SPT outcomes among children were independent of the SPT responses of their parents. Among five randomly selected multi‐generation families, the relative proportionate concentrations of the Amb a 1‐specific IgA and IgG subclasses were comparable, regardless of atopic sensitization to the ragweed allergen Amb a.Conclusion
While the general propensity for atopy may be inherited, an individual's specific atopic outcome is a random variable independent of familial sensitization patterns.
Reduced levels of soluble CD14 in atopic children
Authors: Zdolsek H. A. , Jenmalm M. C. 
Published: April 2004

SummaryBackground
A reduced microbial stimulation has been reported as a reason for the increasing prevalence of atopic diseases in industrialized countries. Antigen‐presenting cells (APC), responding to microbial signals by pattern recognition receptors such as CD14, have an important role in the development of the Th1/Th2 balance.Objective
We hypothesized that atopic children have a lower expression of CD14 on monocytes and lower soluble CD14 levels (sCD14).Methods
Seventy‐six children were followed prospectively from birth and signs of atopic disease were evaluated. The expression of CD14 on monocytes was analysed with flow cytometry at 0, 3, 6, 12 and 18 months. Circulating levels of sCD14 were analysed by ELISA and total IgE was analysed by fluoroenzymo immunoassay at these ages, and in a subgroup, followed up at 7 years.Results
Levels of sCD14 were reduced at 7 years both in children with a current or a cumulative history of atopy compared to non‐atopic children with P=0.002 and 0.001, respectively. Sensitized children with atopic symptoms had lower sCD14 at 3 and 18 months and at 7 years of age than non‐atopic non‐sensitized children with P=0.023, 0.039 and 0.008, respectively.Conclusion
The lower levels of sCD14 observed in atopic children may be a consequence of an atopic family heredity and/or atopic disease, but it may also reflect a reduced capacity to respond to microbial signals.
Relevance of Ara h1, Ara h2 and Ara h3 in peanut‐allergic patients, as determined by immunoglobulin E Western blotting, basophil–histamine release and intracutaneous testing: Ara h2 is the most important peanut allergen
Authors: Koppelman S.J. , Wensing M. , Ertmann M. , Knulst A.C. , Knol E.F. 
Published: April 2004

SummaryBackground
A number of allergenic proteins in peanut has been described and the relative importance of these allergens is yet to be determined.Objectives
We have investigated the relevance of previously identified peanut allergens in well‐characterized peanut‐allergic patients by in vitro, ex vivo and in vivo assays.Methods
Thirty‐two adult peanut‐allergic patients were included based on careful and standardized patient history and the presence of peanut‐specific IgE. The diagnosis peanut allergy was confirmed using double‐blind placebo‐controlled food challenges in 23 patients. Major peanut allergens Ara h1, Ara h2 and Ara h3 were purified from peanuts using ion‐exchange chromatography. IgE immunoblotting was performed and IgE‐cross‐linking capacity was examined by measuring histamine release (HR) after incubating patient basophils as well as passively sensitized basophils with several dilutions of the allergens. Intracutaneous tests (ICTs) using 10‐fold dilution steps of the purified allergens and crude peanut extract were performed.Results
Ara h2 was recognized most frequently (26 out of 32) in all tests and induced both positive skin tests and basophil degranulation at low concentrations, whereas Ara h1 and Ara h3 were recognized less frequently and reacted only at 100‐fold higher concentrations as analysed with HR and intracutaneous testing (ICT). Next to the three tested allergens, proteins with molecular weights of somewhat smaller than 15 kDa were identified as a IgE‐binding proteins on immunoblot in the majority of the patients (20 out of 32).Conclusion
We conclude that Ara h2 is, for our patient group, the most important peanut allergen, and that previously unidentified peanut proteins with molecular weights of somewhat smaller than 15 kDa may be important allergens as well. ICT in combination with basophil–HR and IgE immunoblotting provides insight in the patient specificity towards the individual peanut allergens.
Effect of ingestion of cow's milk hydrolysed formulas on whey protein‐specific Th2 immune responses in naïve and sensitized mice
Authors: Peng H.‐J. , Su S.‐N. , Tsai J.‐J. , Tsai L.‐C. , Kuo H.‐L. , Kuo S.‐W. 
Published: April 2004

SummaryBackground
For genetically predisposed atopic infants, cow's milk protein hydrolysed formulas have been widely used.Objective
Whether hydrolysed formulas can induce oral tolerance to whey proteins will be extensively studied in naïve and sensitized mice.Methods
Antigenicity of hydrolysed formulas was first studied using immunoblotting. Naïve mice fed hydrolysed formulas for 1–4 weeks were sensitized with whey allergens. In contrast, mice sensitized with whey allergens were fed hydrolysed formulas continually for 12 weeks.Results
Whey allergens were found in Nan and Neoangelac FL. Large whey peptides with antigenicity were found in Nan‐HA. Profound suppression of IgE, IgG1 and IgG responses to whey allergens were induced in those fed Nan for 1 week, or Nan‐HA for 4 weeks. IgE responses to whey allergens were suppressed in those fed Neoangelac FL for 4 weeks, or Nan‐HA for 1–2 weeks. In contrast, those fed extensively hydrolysed formulas for 1–4 weeks failed to show decreased responses. On the other hand, IgE responses to β‐lactoglobulin, but not to bovine serum albumin or α‐lactalbumin, were decreased in sensitized mice fed Nan for 12 weeks. There was no suppression in sensitized mice fed hydrolysed formulas.Conclusion
Suppression of IgE responses to whey proteins was readily induced in naïve mice fed Nan or Nan‐HA for 1 week. In contrast, it was hardly induced in sensitized mice even after prolonged feeding of Nan for 12 weeks, let alone hydrolysed formulas.
Are maternal psychosocial factors associated with cord immunoglobulin E in addition to family atopic history and mother immunoglobulin E?
Authors: Lin Y.‐C. , Wen H.‐J. , Lee Y.‐L. , Guo Y. L. 
Published: April 2004

SummaryBackground
Atopy in maternal and family histories is known to be a risk factor for elevated umbilical cord immunoglobulin E (cIgE). However, the association between cIgE and psychosocial factors remains under investigation.Objective
To explore whether psychosocial factors in addition to atopy contribute to elevated cIgE.Methods
Four private maternity hospitals fitting the quantile levels of SO2 in 2000 cooperated with us by recruiting participants for this study: pairs of mothers and neonates living within 3‐km catchment areas of air‐monitoring stations. We used a questionnaire to collect exposure data, and the Pharmacia UniCap IgE assay test system to determine the levels of IgE in gravidas and cord blood.Results
Between July 2001 and March 2003, 334 mother and neonate pairs participated in this study. The frequencies of sensitization, serum IgE (sIgE)>100 IU/mL, or cIgE0.35 IU/mL were not different between the four different hospitals. By multi‐variate logistic regression analysis adjusted for environmental factors, genetic factors, and psychosocial factors, the risk factors for elevated cIgE were being a male neonate (odds ratio (OR)=3.5, 95% confidence interval (CI)=[1.5, 8.5]), carpets at home (OR=3.0, 95% CI=[1.02, 8.4]), maternal allergy to dog dander (OR=9.7, 95% CI=[1.2, 98.8], maternal total serum IgE>100 IU/mL (OR=5.1, 95% CI=[2.2, 12.8]), maternal regularly/mostly/often self‐reported nervousness (OR=4.0, 95% CI=[1.3, 12.8]), family income $11 574–17 361/year (OR=3.7, 95% CI=[1.3, 11.5]), incense burning (OR=4.0, 95% CI=[1.4, 13.3]), and atopy in maternal grandparents (OR=4.8, 95% CI=[1.7, 14.0]). By principle component analysis and logistic regression, psychosocial stress (β±standard error=0.26±0.13, P=0.04) was associated with increased cIgE.Conclusion
Psychosocial factors are potentially important risk factors for elevated cIgE.
Component‐resolved diagnosis of house‐dust mite allergy with purified natural and recombinant mite allergens
Authors: Pittner G. , Vrtala S. , Thomas W. R. , Weghofer M. , Kundi M. , Horak F. , Kraft D. , Valenta R. 
Published: April 2004

SummaryBackground
Mites belong to the most frequent and potent allergen sources. Immunotherapy with mite allergen extracts is frequently performed if allergen avoidance is not possible or successful. However, highly controversial results have been reported for mite‐specific immunotherapy.Objective
The aim of this study was to develop diagnostic concepts that may contribute to an improved selection of patients for immunotherapy with Der p allergen extracts and that may be used for immunological monitoring of patients undergoing this treatment.Methods
The IgE reactivity profiles to Der p extract were determined in a Middle European mite‐allergic population by IgE immunoblotting and by using a panel of seven purified natural or recombinant Der p allergens (nDer p 1, nDer p 4, rDer p 2, rDer p 5, rDer p 7, rDer p 8, rDer p 10). Furthermore, we investigated the sensitization and cross‐reactivity to house‐dust‐ and storage‐mite allergen extracts by CAP FEIA measurements and by IgE competition studies.Results
More than 95% of the patients could be diagnosed with a combination of nDer p 1 and rDer p 2. With the methods used, we could discriminate mite‐allergic patients who were mainly sensitized to the major Der p allergens (Der p 1, Der p 2) from patients with a broad sensitization profile, including highly cross‐reactive allergens (e.g. Der p 10: tropomyosin) as well as reactivity to storage mites.Conclusions
Diagnostic tests containing the major mite allergens (i.e. Der p 1, Der p 2) and highly cross‐reactive mite allergens (e.g. Der p 10) may improve the diagnostic selection of patients for immunotherapy with Der p extracts. These tests may also be used for the immunological monitoring of patients undergoing immunotherapy.