bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retrospective assessment of seasonal allergic symptoms: over‐rating but useful
Authors: Bodtger U. , Poulsen L. K. , Malling H.‐J. 
Published: December 2004

SummaryBackground The history of the severity of seasonal allergic symptoms is often obtained post‐seasonally as a retrospective assessment. Correct rating is essential when determining the efficacy of pharmaceutical treatment, indications for allergen‐specific immunotherapy (SIT), or inclusion into controlled clinical studies.Objectives To investigate the agreement between in‐ and post‐seasonal ratings of seasonal symptoms, and to investigate whether the effect of SIT could be detected retrospectively.Material and methods Thirty‐five birch pollen‐allergic patients were allocated to SIT or placebo in a double‐blind study. Assessment of severity of symptoms from the nose, eyes and lungs were performed daily during the season 2000, and post‐seasonally 6 months after the season in 1999 and 2000. A four‐point verbal descriptor scale (VDS‐4) was used at all occasions. A mean in‐seasonal symptom rating was calculated for four periods: the day, the week and the 2 weeks with the highest symptoms score, and the arithmetic season (the period covering the mid‐90% of the accumulated pollen count). In‐ and post‐seasonal ratings were compared with Cohen's weighted kappa (κw).Results Agreement between in‐seasonal and retrospective ratings was fair to moderate (κw: 0.30–0.60). Post‐seasonal ratings were most related to symptoms experienced in the week with the highest symptom scores, and least related to the arithmetic season. The post‐seasonal ratings were significantly skewed towards higher symptom scores than the mean of in‐seasonal ratings in periods ≥ 2 weeks. Despite being comparable before intervention, only in the SIT‐treated group was a significant decrease in post‐season ratings of severity of rhinoconjunctivitis apparent (P < 0.05). Asthma scores were not reduced but fewer patients in the SIT group reported lung symptoms (P < 0.001).Conclusion Post‐seasonal assessment of seasonal allergic symptoms generally describes a shorter period than the arithmetic season. Post‐season assessment tends to over‐rate average symptom severity, but appears sufficiently sensitive to detect treatment efficacy.
House‐dust mite sublingual‐swallow immunotherapy in perennial conjunctivitis: a double‐blind, placebo‐controlled study
Authors: Mortemousque B. , Bertel F. , De Casamayor J. , Verin P. , Colin J. 
Published: December 2004

SummaryBackground The safety and the efficacy of sublingual‐swallow immunotherapy (SLIT) in perennial conjunctivitis caused by house dust mite were evaluated in a double‐blind, placebo‐controlled study including 60 patients for 24 months.Methods Patients received either placebo or SLIT with standardized Dermatophagoides pteronyssinus (D.pt.) and D. farinae (D.f.) 50/50 extract. The evaluation of the efficacy of the SLIT was obtained by using standardized D. pteronyssinus (D.pt.) extracts on the antigen‐specific conjunctival provocation test (CPT). Specific CPT, skin sensitivity and serum‐specific IgE were performed before starting treatment and 6, 12, 18 and 24 months.Results Of the 60 patients included, only 45 completed the study (26 in the active group and 19 in the placebo group, P < 0.05). Two out of 30 (6.6%) patients dropped out because of insufficient efficacy in the active group compared to eight out of 30 (26.6%) in the placebo group (P < 0.05). There was a significant increase in the antigen threshold required to obtain a positive CPT from 8.2 IR [95% confidence interval (CI) 5.9–11.4] at baseline to 21.7 IR (95% CI 15.4–30.4) at 2 years (M24) in the active group, compared to 8.1 IR (95% CI 5.4–12.1) at baseline to 8.1 IR (95% CI 5.1–12.4) at M24 in the placebo group (P < 0.04 for overall treatment difference, P < 10−7 for the time–treatment interaction; repeated measures ANOVA). Differences between groups at individual time points were significant from 18 months on. Despite increased antigen concentrations, CPT scores were lower overall in the active than in the placebo group (P < 0.001). No serious adverse effects were reported.Conclusion SLIT effectively increased the antigenic threshold required to obtain a positive CPT to house‐dust mite antigen. Tolerance to and innocuity of SLIT were comparable to previous studies. This could justify recommending SLIT for the preventive treatment of perennial conjunctivitis caused by house dust mites.
Specific patterns of responsiveness to microbial antigens staphylococcal enterotoxin B and purified protein derivative by cord blood mononuclear cells are predictive of risk for development of atopic dermatitis
Authors: Sharp M. J. , Rowe J. , Kusel M. , Sly P. D. , Holt P. G. 
Published: December 2004

SummaryBackground Mononuclear cells from children with active atopic dermatitis (AD) have been reported to be hyper‐responsive to certain microbial stimuli, in particular staphylococcal enterotoxin B (SEB). However, it is not known whether this responsiveness is acquired during disease development, or is inherent. We investigated this question in a cohort of children at high risk of atopy followed prospectively from birth to age 3 years. We asked whether their cord blood mononuclear cell (CBMC) cytokine responses to SEB, to an unrelated microbial stimulus purified protein derivative (PPD), or to common allergens, were predictive of risk for subsequent AD development during infancy.Methods Children at high risk of developing atopy were randomly selected from an ongoing prospective cohort. Cord blood was collected at birth. The children were seen at 6 months, 1, 2 and 3 years and examined for the development of AD. IFN‐γ, IL‐5, IL‐10 and IL‐13 production by CBMC cultured in the presence of SEB, PPD, PHA, house dust mite (HDM) allergen, ovalbumin (OVA) and cat allergen was determined.Results SEB‐induced IL‐5 production by CBMC was elevated in children who developed AD at 6 months (P = 0.01) and 2 years (P = 0.009). PPD‐induced IL‐5 responses were also elevated in CBMC from children who developed AD at 6 months, 2 years and 3 years (P = 0.05, P = 0.06 and P = 0.06, respectively), as were PPD‐induced IL‐10 responses (P = 0.05 at 1 years, P = 0.007 at 2 years, P = 0.003 at 3 years) and corresponding IFN‐γ responses (P = 0.05 at 6 months, P = 0.003 at 2 years, P = 0.0004 at 3 years). Increased IL‐10 responses to HDM allergen were also observed throughout the observation period in CBMC from children who developed AD.Conclusion Children who develop infantile AD appear to have a predisposition to respond to SEB in a Th2‐dominant manner involving selective stimulation of IL‐5 production. The increased IL‐10 and IFN‐γ induced in response to PPD by children with AD may point to additional intrinsic differences in responses to microbial stimuli between those at high vs. those at low risk for AD, which merit more detailed investigations.
Onset of allergy and asthma symptoms in extra‐European immigrants to Milan, Italy: possible role of environmental factors
Authors: Tedeschi A. , Barcella M. , Bo G. A. Dal , Miadonna A. 
Published: December 2004

SummaryBackground Allergy and asthma are typical disorders of the affluent societies. Migrants from developing to industrialized countries seem to be at increased risk of allergy and asthma development.Objective To evaluate time of onset, spectrum of sensitization and clinical features in a population of extra‐European immigrants to Milan, Italy, complaining of allergy and asthma symptoms.Methods Data regarding 243 extra‐European immigrants checked at an allergy clinic from 1994 to 2000 were collected retrospectively. The demographic data were compared with those of the extra‐European immigrants living in Milan at the end of 1999.Results The patients were complaining of asthma (63.7%), rhinoconjunctivitis (56.7%), rhinitis alone (21%) or urticaria (3%). One hundred and eighty‐seven out of 222 patients (84.3%) declared they were healthy before migrating and allergy/asthma symptoms started to appear after their arrival in Italy, namely after an average period of 4 years and 7 months. The proportion of male patients was lower than the proportion of men in the extra‐European immigrant population (48% vs. 55%), suggesting that in adult immigrants allergy and asthma are more common in women than in men. Furthermore, there was an over‐representation of Central‐South Americans attending the clinic, which seemed to be due to a genetic predisposition to allergy/asthma development. When data were analysed for single countries, a trend towards an increased risk of allergy and asthma was found in immigrants from all Central‐South American countries. A skin test positivity for at least one inhalant allergen was found in 196 out of 232 patients (81%), and the spectrum of allergic sensitization was similar to that of the Italian population living in the North of Italy.Conclusion Most extra‐European immigrants declared that they were healthy at home and that allergy and asthma symptoms had appeared after immigration to Milan; lifestyle and environmental factors in a western industrialized city seem indeed to facilitate allergy/asthma onset in immigrants from developing countries. Allergy/asthma risk seems to be different in different ethnic groups.
CD14 and development of atopic disease at 2 years of age in children with atopic or non‐atopic mothers
Authors: Holmlund U. , Höglind A. , Larsson A.‐K. , Nilsson C. , Sverremark Ekström E. 
Published: December 2004

SummaryBackground CD14, a myeloid cell marker and LPS receptor has been acclaimed to play a role in development and manifestation of atopic allergy, as the gene encoding CD14 is located in a chromosomal region linked to total IgE levels and atopic disease.Objective To investigate the levels of soluble (s) and membrane bound (m) CD14 in cord blood and at 2 years of age from children with atopic or non‐atopic mothers and relate these parameters to atopy development at 2 years of age.Methods Blood samples were collected at delivery (cord blood) and at 2 years of age among infants with atopic (n = 41) and non‐atopic (n = 32) mothers. Blood samples were also obtained from mothers at the same occasions. Levels of sCD14 and total IgE were measured in plasma, and percentages of CD14+ cells were measured in cord and peripheral blood mononuclear cells.Results We observed significant differences in sCD14 levels in cord blood, where children with atopic mothers had the highest levels. The same pattern could be observed in the mothers at delivery. At 2 years of age no significant differences in sCD14 levels were observed between children with atopic mothers and children with non‐atopic mothers and no association between sCD14 and atopic disease was found. Further, we observed large differences in sCD14 and mCD14 with respect to age, where newborns displayed a higher frequency of CD14+ cells compared with the 2‐year‐olds and the mothers. The reverse was observed for sCD14, with significantly lower values in cord blood than those seen in the 2‐year‐olds and mothers.Conclusion Based on our findings, we suggest that CD14 could be involved in the regulation of IgE production, but that it might also be important for the maturation and development of the neonatal immune system.
A single nasal allergen challenge increases induced sputum inflammatory markers in non‐asthmatic subjects with seasonal allergic rhinitis: correlation with plasma interleukin‐5
Authors: Beeh K. M. , Beier J. , Kornmann O. , Meier C. , Taeumer T. , Buhl R. 
Published: December 2004

SummaryBackground Seasonal allergic rhinitis (SAR) is a risk factor for asthma in affected individuals. Nasal allergic inflammation enhances bone‐marrow eosinophil production, mainly via IL‐5, and rhinitis patients have increased airway inflammation during the pollen season.Objective To assess the impact of nasal allergy on sputum inflammatory markers.Methods In an open‐labelled, randomized, placebo‐controlled cross‐over study with 16 non‐asthmatic SAR patients (median age 25 years, 56% males), the effect of a single nasal allergen challenge performed out of season on induced sputum inflammatory parameters was evaluated. SAR patients were identified by history, skin‐prick test and specific IgE. All patients had normal lung function/bronchial hyper‐responsiveness out of season and a negative asthma/wheezing history. Sputum cells and supernatant levels of ECP, sICAM, IL‐5 and IL‐10, and plasma levels of IL‐5 and ECP, were measured before and 24 h after nasal allergen challenge. After a washout period of at least 4 weeks, the procedure was repeated with placebo challenge (diluent).Results Nasal allergen challenge led to an increase in sputum ECP (pre = 60 ± 12, post = 212 ± 63 µg/L, P = 0.02 vs. placebo), and sICAM (4.8 ± 2.7 to 6.5 ± 2.9 ng/mL, P = 0.02 vs. placebo), whereas IL‐10 decreased after provocation (44 ± 11 to 29 ± 6 pg/mL, P = 0.06 vs. placebo). Sputum IL‐5 was undetectable in all patients. The absolute number of blood and sputum eosinophils did not change significantly after allergen or placebo challenge (P > 0.07, both comparisons). Plasma levels of IL‐5 increased after allergen challenge (8.7 ± 2.9 to 14.5 ± 3.9 pg/mL, P = 0.001), and the increase in plasma IL‐5 was positively correlated with the rise in sputum ECP in a subgroup of ‘responders’ (n = 12, r = 0.71, P = 0.01).Conclusions A single nasal allergen challenge in SAR patients increased markers of allergic inflammation in the lower respiratory tract, possibly via pronounced activation of inflammatory cells through circulating immediate‐type reaction cytokines like IL‐5. These findings may provide additional explanatory data for the high susceptibility of SAR patients to incident asthma.
Dendritic cells exposedin vitroto TGF-β1 ameliorate experimental autoimmune myasthenia gravis
Authors: YARILIN D , DUAN R , HUANG Y-M , XIAO B-G 
Published: December 2004

SummaryExperimental autoimmune myasthenia gravis (EAMG) is an animal model for human myasthenia gravis (MG), characterized by an autoaggressive T-cell-dependent antibody-mediated immune response directed against the acetylcholine receptor (AChR) of the neuromuscular junction. Dendritic cells (DC) are unique antigen-presenting cells which control T- and B-cell functions and induce immunity or tolerance. Here, we demonstrate that DC exposed to TGF-β1 in vitro mediate protection against EAMG. Freshly prepared DC from spleen of healthy rats were exposed to TGF-β1 in vitro for 48 h, and administered subcutaneously to Lewis rats (2 × 106DC/rat) on day 5 post immunization with AChR in Freund’s complete adjuvant. Control EAMG rats were injected in parallel with untreated DC (naive DC) or PBS. Lewis rats receiving TGF-β1-exposed DC developed very mild symptoms of EAMG without loss of body weight compared with control EAMG rats receiving naive DC or PBS. This effect of TGF-β1-exposed DC was associated with augmented spontaneous and AChR-induced proliferation, IFN-γ and NO production, and decreased levels of anti-AChR antibody-secreting cells. Autologous DC exposed in vitro to TGF-β1 could represent a new opportunity for DC-based immunotherapy of antibody-mediated autoimmune diseases.
Immunoglobulins in children with epilepsy: the Dutch Study of Epilepsy in Childhood
Authors: CALLENBACH P M C , JOL-VAN DER ZIJDE C M , GEERTS A T , ARTS W F M , VAN DONSELAAR C A , PETERS A C B , STROINK H , BROUWER O F , VAN TOL M J D 
Published: December 2004

SUMMARYIn an unselected cohort of 282 children, serum immunoglobulin (Ig) concentrations were determined shortly after the first presentation with one or more unprovoked epileptic seizures and before the start of treatment with anti-epileptic drugs (AEDs), and after 9–18 months of AEDs use. At intake, IgA, IgG1, IgG2 and IgG4 concentrations were significantly higher than published reference values in healthy age-matched controls. In a subset of 127 children, Ig levels at intake were compared with those after AEDs use for 9–18 months. IgA and IgG4 levels had decreased significantly to normal concentrations, but IgG1 and IgG3 levels increased significantly. To determine the influence of AEDs, Ig levels in children who used carbamazepine or valproic acid monotherapy were analysed separately. The use of carbamazepine was associated with a significant decrease of IgA and IgG4 levels, and the use of valproic acid with a significant decrease of IgA and increase of IgG1 levels. In conclusion, humoral immunity is already altered in children shortly after the first presentation with epileptic seizures. Whether this is the consequence of an exogenous event, and to what extent this is related to an interaction of the central nervous system and the immune system, remains to be evaluated. Treatment with AEDs, such as carbamazepine and valproic acid, is associated with significant changes of Ig (sub)class concentrations.
Differences in MHC-class I presented minor histocompatibility antigens extracted from normal and graft-versus-host disease (GVHD) mice
Authors: ROSSET M BRULEY , TIENG V , CHARRON D , TOUBERT A 
Published: December 2004

SUMMARYGraft-versus-host disease (GVHD) may develop after allogeneic bone marrow transplantation (BMT) between donors and recipients incompatible for minor histocompatibility antigens (mHAg). Here, we examined the possible relationship between tissue-specific distribution of dominant mHAg peptides and specific organ destruction caused by GVHD. In the B6 anti-Balb/b (H-2b) strain combination, a GVHD developed against Balb/b mHAgs. Despite the high number of incompatible mHAgs between these two strains, both cytotoxic T lymphocyte (CTL) response and GVHD could be attributed to a limited number of dominant mHAgs. We studied CTL-defined expression of dominant mHAgs in normal tissues and their GVHD-related modifications. mHAg peptides were prepared by acid elution and reversed-phase high pressure liquid chromatography fractionation from the spleen, liver, gut and skin as GVHD target tissues and from the heart and kidney as control tissues. Peptidic fractions extracted from normal and GVHD tissues were incubated with RMA-S targets and analysed using bulk B6 anti-Balb/b CTL. In each tissue several fractions were recognized with a given pattern of mHAg expression. GVHD induced qualitative and quantitative changes in antigenic peptide expression. Modifications in mHAg presentation during GVHD concerned preferentially GVHD target organs as opposed to non-GVHD target organs. In addition, when immunizing tissues were derived from GVHD mice instead of normal mice, the profile of CTL recognition was different. In conclusion, these data indicate that broad differences could exist in peptide presentation between various normal and GVHD-target organs.
Elevated angiogenin levels in synovial fluid from patients with inflammatory arthritis and secretion of angiogenin by cultured synovial fibroblasts
Authors: LIOTÉ F , CHAMPY R , MOENNER M , BOVAL-BOIZARD B , BADET J 
Published: December 2004

SUMMARYAngiogenesis is a key process in the pathogenesis of inflammatory arthritis. Angiogenin is one of the most potent inducers of neovascularization in experimental models in vivo. To look for evidence that angiogenin is involved in inflammatory joint disease, we examined plasma and synovial fluid (SF) samples from rheumatology patients and synovial fibroblast cell culture supernatants. Angiogenin levels were determined by radioimmunoassay and ELISA. Plasma angiogenin concentrations ranged from 96 to 478 ng/ml, with no significant difference between patients and normal controls. In SF, angiogenin concentrations were significantly higher in patients with acute or chronic synovitis (rheumatoid arthritis (RA): median, 104 ng/ml; range 13–748, n= 14; crystal-induced arthritis (CIA): median, 149 ng/ml; range, 37–616, n= 14, and other chronic inflammatory arthritis: median, 42 ng/ml; range, 15–205; n= 9) than in the 18 patients with osteoarthritis (OA) (median, 20 ng/ml; range 8–116) (P &lt; 0·0001, anova). Angiogenin levels in SF from RA patients in remission with secondary OA were similar to those achieved in primary OA, and decreased in parallel with the resolution of acute gout. Angiogenin protein was released by cultured synovial fibroblasts from OA and RA patients, and reached 1·18 ng/106 cells/day. These data suggest that angiogenin may mediate local inflammation in arthritis via effects on angiogenesis and leucocyte regulation.
Evaluation of CD4+ T cells proliferating to grass pollen in seasonal allergic subjects by flow cytometry
Authors: RIMANIOL A C , GARCIA G , TILL S J , CAPEL F , GRAS G , BALABANIAN K , EMILIE D , HUMBERT M 
Published: December 2004

SUMMARYOur objective was to characterize T-cell responses to Phleum pratense in grass pollen allergic individuals and healthy controls using the fluorescent dye PKH26. Peripheral blood mononuclear cells were stimulated with P. pratense, or with recall antigens, and CD3+/CD4+ and CD3+/CD8+ T-cells that had proliferated were analysed by flow cytometry. In the presence of P. pratense CD4+/CD3+ T-cells proliferated more in grass pollen sensitive atopic patients than in nonallergic controls or in nongrass pollen sensitive atopic subjects. PPD and TT recall antigens elicited uniformly high proliferation in all T-cell subsets. Only half of pollen sensitive patients also had an increased proliferation of CD3+/CD8+ T-cells in response to P. pratense. We determined precursor frequency of CD4+ T cells in the original population that responded to P. pratense and found values ranging from 1 × 10−3 to 0·6 × 10−1, in the same range as those measured for PPD and TT. In conclusion, grass pollen sensitive atopic patients show enhanced CD4+ T-cell reactivity to P. pratense, and this could be related to the presence of elevated numbers of circulating allergen-specific CD4+ T cells. This flow cytometric method should allow the identification of other phenotypic markers such as intracellular cytokines in allergen specific responding CD4+ T cells.
Clearance of red cells by monoclonal IgG3 anti-Din vivois affected by the VF polymorphism of FcγRIIIa (CD16)
Authors: KUMPEL B M , DE HAAS M , KOENE H R , VAN DE WINKEL J G J , GOODRICK M J 
Published: December 2004

SUMMARYHuman red cells (RBC) coated with IgG anti-D are cleared from the circulation to the spleen by macrophages which express IgG receptors (Fcγ R). Polymorphisms of Fcγ RIIa and Fcγ RIIIa affect IgG binding in vitro, and may alter the efficiency of clearance of immune complexes in vivo. In a RBC clearance study, 22 Rh D-negative subjects were given 100–400 µg human monoclonal or polyclonal IgG anti-D i.m. followed 48 h later by 51Cr-labelled D+ RBC. The half lives of the infused D+ RBC were determined, together with the coating levels of anti-D on the D+ RBC. Fcγ RIIA and FcγRIIIA genotyping was performed. Large ranges of phagocytosis and extracellular lysis of RBC in vitro, and of half lives of RBC in vivo, were observed. Clearance of RBC coated with monoclonal IgG3 anti-D (BRAD-3) was more rapid in five subjects homozygous for Fcγ RIIIa-F/F158 than in three subjects expressing the Fcγ RIIIa-V158 allele (P = 0·024). This effect was not observed, however, for those individuals given polyclonal anti-D. There was also no significant difference in the efficiency of RBC destruction in vitro or of RBC clearance in vivo between the subjects analysed for individual genotypes or alleles or combinations of alleles. In conclusion, the presence of the Fcγ RIIIa-V158 allele compromised the efficiency of removal of RBC coated with IgG3 anti-D.