bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of the platelet activating factor antagonists BN 52021 and BN 50730 on antigen‐induced bronchial hyperresponsiveness and eosinophil infiltration in lung from sensitized guinea‐pigs
Authors: LAGENTE V. , BOICHOT E. , CARRE C. , GUINOT PH. , MENCIA‐HUERTA J. M. , BRAQUET P. 
Published: April 2006

SummaryThe involvement of platelet activating factor (PAF) in antigen‐induced bronchial hyperresponsiveness was investigated by the use of the PAF antagonists BN 52021 and BN 50730, in a guinea‐pig model where sensilization and challenge were performed by aerosol. Male Hartley guinea‐pigs were sensitized by two aerosol exposures at 48 hr intervals to a 0.9% NaCl solution (saline) containing 2 mg/ml ovalbumin lor 30 min. Fifteen to 20 days later, guinea‐pigs were challenged by exposure to five successive aerosols ofincreasing concentrations of ovalbumin (OA) or respectively, 10 μg ml. KM) μ/ml, 1 mg/ml. 5 mg/ml and 10 mg/ml for 15 min each, orsaline alone. Three to four hr and 18‐24 hr after the aerosol challenge the guinea‐pigs were prepared for recording of bronchopulmonary response and aerosol administrations were then generated with an ultrasonic nebulizer. The bronchopulmonary responses induced by successive I‐min aerosol bursts of acetylcholine(ACh) was assessed. As compared with saline‐challenged guinea‐pigs, an enhanced bronchopulmonary response to aerosol administration of cumulative doses of ACh was observed, 3 4 hr and 18 24 hr post‐ovalbumin challenge. When the sensitized guinea‐pigs were pretreated I hr before ovalbumin exposure with BN 52021 or BN 50730 (25 mg/kg, per ox), a significant inhibition of the increase in the bronchopulmonary response to ACh was observed, both at 3–4 hr and 18–24 hr. Furthermore, when guinea‐pigs were treated 3–4 hr after the ovalbumin exposure with BN 52021 or BN 50730, a significant inhibition of the hyperresponsiveness to ACh was recorded at 18 24 hr. A marked accumulation of eosinophils in the peribronchial regions was observed on histological preparations of lung specimens collected 4 hr or 24 hrafler ovalbumin exposure. Pretreatment of the guinea‐pigs by BN 50730 or BN 52021 did not modify the eosinophil accumulation in the peribronchial area. No significant difference in the number of eosinophils collected in the bronchoalveolar lavage fluid is observed, 24 hr posl‐ovalbumin challenge, under the pretreatment with BN 52021 or BN 50730. Pretrealment of guinea‐pigs by BN 50730 or BN 52021 significantly reduced the PAF‐induced (100μg/ml) increase in eosinophil number in the peribronchial area. By contrast, they did not inhibit the eosinophilia induced by aerosol administration of LTB4 (5 μg/ml). These results suggest that the bronchial hyperresponsiveness observed in this study is associated with eosinophil accumulation in the lung. The potent inhibition of the bronchial hyperresponsiveness by the two unrelated antagonists of PAF suggests that the lipid mediator is involved in its triggering and duration, but not in the eosinophil infiltration.
Neutrophil–induced human bronchial hyper responsiveness in vitro—pharmacological modulation
Authors: HUGHES J. M. , McKAY K. O. , JOHNSON P. R. , TRAGOULIAS S. , BLACK J. L. , ARMOUR C. L. 
Published: April 2006

SummaryAlthough it has been postulated that inflammatory cells cause the bronchial hyper‐responsiveness which is diagnostic of asthma [1], until recently there has been little direct evidence of such a link. We have recently shown that calcium ionophore‐activated human neutrophils and eosinophils can induce a state of human airway hyperresponsiveness in vitro [2]. In this study we have shown that the anti‐inflammatory agent nedocromil sodium, 10‐7m, inhibited the hyperresponsiveness induced by products released from ionophore activated neutrophils but did not inhibit the release of leukotriene B4 from the same cells. Neutrophil‐induced bronchial hyperresponsiveness was also inhibited by pre‐treatment of the bronchial tissues with a thromboxane A2 and prostaglandin receptor antagonist, GR32191,10‐7m. These findings indicate that cyclooxygenase products are involved in bronchial hyperresponsiveness induced by inflammatory cell products in vitro and that their release can be inhibited by nedocromil sodium.
Lack of increased numbers of low‐density eosinophils in the circulation of asthmatic individuals
Authors: BRUIJNZEEL P. L. B. , JNR. J‐CHR VIRCHOW , RIHS S. , WALKER C. , VERHAGEN J. 
Published: April 2006

SummaryThe density distribution pattern of eosinophils over discontinuous isotonic Percoll gradients from the blood of normal, asymptomatic allergic and non‐allergic asthmatic individuals was investigated. There was a completely identical distribution pattern between the investigated groups. Analysis of the expression of surface markers for complement receptors CR1 and CR3 and immunoglobulin G receptor on eosinophils derived from the density bands 1.080. 1.085 and 1.090 g/ml supported this finding since they did not reveal differences in expression between the bands within one group but also not between the three groups. Eosinophils of the various density bands were further purified and stimulated in vitro to produce leukotriene C4 (LTC4) by the calcium ionophore A23187 or serum treated zymosan. Equal amounts of LTC4 were synthesized by the eosinophils of the various density bands within one group. However, it appeared that the eosinophils of all density bands of allergic and non‐allergic asthmatics synthesized significantly more LTC4 than the eosinophils from normal individuals (five‐to tenfold). Probably this indicates in vivo priming of the eosinophils in asthmatic individuals which is not reflected by a change in density. Control experiments, dealing with possible artifacts due to the isolation procedure or the patient selection, to find differences in distribution patterns over discontinuous Percoll density gradients of the eosinophils of asthmatic compared to normal individuals failed to show such a difference. Therefore, the density distribution pattern of eosinophils over these gradients does not reflect cell activation, whereas LTC4 formation clearly does. This could mean that LTC4 formation is a more sensitive parameter for cell activation than density distribution or cell surface marker expression.
Increase in non‐specific bronchial responsiveness after repeated inhalation of low doses of allergen
Authors: IHRE E. , ZETTERSTROM O. 
Published: April 2006

SummaryThe development of bronchial hyperresponsiveness (BHR) in asthma is considered to be caused by inflammation of the airway. In IgE‐mediated allergy BHR is related to the occurrence of late phase reactions. We have previously shown that exposure to low doses of allergen can cause isolated late reactions. These findings are potentially of clinical importance, since exposure to low, subclinical allergen doses may lead to bronchial inflammation and increasing bronchial responsiveness without necessarily causing immediate bronchoconstriction. This study was performed to investigate whether repeated exposure to low doses of allergen could induce a change in BHR. The trial comprised two groups of five and eight patients with a history of allergic asthma. They were submitted to a series of allergen inhalations for 5–7 days. They were given the same low allergen dose (1–10 biological units) each day. Before and after the allergen exposure period histamine challenges were performed. After the week of allergen inhalation the bronchial responsiveness was increased in 11 of 13 patients.
The main allergen of Olea europaea (Ole e I) is also present in other species of the oleaceae family
Authors: OBISPO T. M. , MELERO J. A. , CARPIZO J. A. , ARREIRA J. C. , LOMBARDERO M. 
Published: April 2006

SummaryThree major pollen allergens from Fraxinus excelsior, Ligustrurn vulgare and Syringa vulgaris belonging to the Oleaceae family were purified. Monoclonal antibodies previously raised against the main allergen of Olea europaea (Ole e I) were used for their purification by affinity chromatography. The three new purified allergens were able to bind human IgE from serum of olive‐allergic patients in a way analogous to Ole e I. Crossed radioimmunoelectrophoresis of the four allergens, using anti‐olive extract rabbit serum, showed a unique immunoprecipitation arc with the same characteristics. The four purified proteins had similar molecular weights on SIX‐PAGE and the N‐terminal sequences for the first 20 amino acids were identical. Furthermore, the concentration of the allergens could be determined using a two‐site solid phase assay previously developed for the allergen Ole e I. Our results indicate that the four purified proteins share, to a great extent, antigenic and allergenic epitopes leading to cross‐reactivities which could cause common clinical manifestations. We propose for the newly purified allergens the nomenclature of Fra e I, Lig v I and Syr v I.
Steroid sparing effect of nedocromil sodium in asthmatic patients on high doses of inhaled steroids
Authors: WONG C. S. , COOPER S. , BRITTON J. R. , TATTERSFIELD A. E. 
Published: April 2006

SummaryNedocromil sodium is a non‐steroidal prophylactic agent developed for the management of asthma. We have assessed the steroid sparing potential of inhaled nedocromil sodium 4 mg four limes daily in a randomized, double blind, placebo controlled study in 69 asthmatic subjects controlled on inhaled beclomethasone dipropionate in the dose range 1000 2000 μg daily. Following a 4 week run‐in period subjects added nedocromil sodium or placebo by metered dose inhaler to their usual medication for a further 4 weeks. The dose of inhaled steroid was then reduced at fortnightly intervals according to a predetermined schedule, with monitoring of asthma severity, symptom scores, bronchodilator use and peak flow recordings. Sixty subjects entered the steroid reduction phase and achieved median (range) % decreases in steroid dose of 80 (17‐100)% with nedocromil sodium compared to 65 (0‐100)% with placebo (P = 0.34) with 14 patients in the nedocromil sodium group and 10 in the placebo group being withdrawn completely from inhaled steroids. Subjective global assessment scores were significantly better with nedocromil sodium (mean 2.14) than with placebo (2.93; P<0.02) though there was no difference between individual daily symptom scores. In this study therefore in asthmatic patients controlled on high doses of inhaled steroids, nedocromil sodium was well tolerated but the smalt differences in steroid sparing effect between nedocromil and placebo were not statistically significant.
Monoclonal antibodies specific for guinea pig eosinophil major basic protein: their use in an ELISA, immunocytochemistry and flow cytometry
Authors: HUNT T. C. , SUMMERS J. A. , CAMPOS M. G. , RIMMER S. J. , STURTON G. , PALFAI S. , CHURCH M. K. 
Published: April 2006

SummaryEosinophil, major basic protein (M BP), purified from guinea pig eosinophil granules was used to raise five monoclonal antibodies (MoAbs). Their reactivity with MBP was confirmed by immunoblotting and indirect ELISA. Two of the MoAbs were used to develop a sensitive and specific antigen capture (sandwich) ELISA for guinea pig eosinophil M BP which gives an accurate and reproducible standard curve over the range of 10‐10000 ng/ml. The specificity of the ELISA for MBP was confirmed and its suitability for testing biological samples ascertained by measurement of MBP in bronchoalveolar lavage fluid (BALF) and plasma from guinea pigs sensitized and challenged with ovalbumin. The ELISA was also capable of detecting MBP in culture supernatants from purified eosinophil preparations challenged with calcium ionophore in vitro. One of the monoclonal could be used to strongly and specifically stain guinea pig eosinophils in immunocytochemistry, whilst all five could be used to visualize eosinophils in suspension in BALF or peritoneal lavage fluid by flow cytometry. There was no staining of other guinea pig leucocyte types, nor crossreactivity with human eosinophils by immunocytochemistry or Row cytometry.
Exposure to house dust mite allergen of children admitted to hospital with asthma
Authors: SPORIK R. , PLATTS‐MILLS T. A. E. , COGSWELL J. J. 
Published: April 2006

SummaryEighty‐two children admitted to hospital with exacerbations of asthma were studied to determine how many were exposed to house dust mites at the time of admission and displayed immediate hypersensitivity to house dust mites. The concentration of house dust mite allergen (Der p I) was measured in dust obtained from the child's mattress, bedroom floor and living room floor. Sixty‐two (75%) children admitted had been exposed to > 10 μg Der p I/g. Sixty‐seven (82%) children were sensitive to house dust mite(RAST 1 +, or weal 3 mm): 49 (60%) children were both exposed and sensitive. In contrast in a control group of 44 children, 31 (70%)(n.s.) were exposed to > 10μg Der p I/g, 10 (23%) (P < 0.001) were sensitive to house dust mite, and 7 (16%) (P < 0.001) were both exposed and sensitive. Seventy‐three homes were revisited 6 months after the child's initial admission. During the preceding month 14 children had been readmitted, 12 were fully investigated; of these 10 were both sensitive to house dust mite and still exposed to > 10 μg Der p I/g. In contrast, of the remaining 62 children who were not readmitted, only 19 were both sensitive and still exposed to > 10μg Der p I/g (P < 0.001). In conclusion, the majority of children admitted to hospital with exacerbations of asthma were exposed to house dust mite allergen and were house dust mite sensitive. Further the results suggest that continued exposure to higher concentrations of mite allergen may be associated with the risk of readmission.
The renin angiotensin system and hymenoptera venom anaphylaxis
Authors: HERMANN K. , RING J. 
Published: April 2006

SummaryComponents of the renin angiotensin system, namely renin, angiotensinogen, angiotensin I and II and aldosterone were measured in plasma of patients with hymenoptera venom anaphylaxis (n= 50) and healthy non‐allergic controls (n= 25). Patients with a history of anaphylactic reactions to hymenoptera venom who did not undergo immunotherapy showed significantly reduced renin, angiotensinogen, angiotensin I and angiotensin II in plasma as compared with controls (P<0.05). There was no difference in the aldosterone concentration between patients and controls. Angiotensin I, angiotensin II, renin and angiotensinogen levels were the same in male and female patients. There was also no difference in the angiotensin I, II, renin or angiotensinogen levels between young and older patients. A significant inverse correlation between the severity of clinical symptoms and the plasma levels of renin (r=‐0.382, P<0.001), angiotensinogen (r=‐0.567, P<0.0001), angiotensin I (r= ‐0.656, P<0.0001) and angiotensin II (r = 0.0762, P < 0.0001) was found: the lower the levels the more severe the clinical symptoms. No correlation was found for aldosterone. Hymenoptera venom allergic patients with repeated anaphylactic reactions during hyposensitization did not tolerate the sting of a living insect (n= 6). In these patients, renin, angiotensinogen, angiotensin I and II remained significantly lower than in healthy non‐allergic controls. Patients with successful immunotherapy (n= 27) who tolerated the sting of a living insect had renin, angiotensin I and II significantly higher than patients without immunotherapy. These findings suggest a possible role of the renin angiotensin system in hymenoptera venom anaphylaxis.
Treatment of steroid‐dependent asthma with recombinant interferon‐gamma
Authors: BOGUNIEWICZ M. , SCHNEIDER L. C. , MLLGROM H. , NEWELL D. , KELLY N. , TAM P. , IZU A. E. , JAFFE H. S. , BUCALO L. R. , LEUNG D. Y. M. 
Published: April 2006

SummaryWe have recently reported that treatment of patients with severe atopic dermatitis with recombinanl interferon‐gamma (rIFN‐y) resulted in clinical improvement as well as a reduction of circulating eosinophils. Since IgE‐dependent late phase allergic reactions and eosinophilic infiltration are thought to play an important role in the pathogenesis of asthma, we conducted a two centre randomized double‐blind placebo‐controlled trial of rIFN‐y in the treatment of steroid‐dependent asthma. Patients were treated with daily subcutaneous injections of either 0.05 mg/m2 rIFN‐y (n= 9) or placebo (n=11) for 90 days. All patients completed the study without significant drug toxicity noted. Oral prednisone dose, forced expiratory volume in 1 second (FEV), peak expiratory flow rates (PEFR) and circulating eosinophil counts were monitored throughout the trial. There was no significant difference between the two treatment groups in per cent reduction from baseline of daily prednisone (P=0.51). There was also no significant difference between the two treatment groups in per cent change from baseline in FEV1 (P= 0.54)or in PEFR (P=0.75). Total circulating eosinophil counts decreased by 31% in the rIFN‐y group and increased by 8.5% in the placebo group (P= 0.09). We conclude that this treatment regimen was not effective in patients with steroid‐dependent asthma.
Occupational allergy to bumble bee venom
Authors: KOCHUYT A. M. , VAN HOEYVELD E. , STEVENS E. A. M. 
Published: April 2006

SummaryThe clinical profile of anaphylactic reactions to bumble bees is described and successful immunotherapy with honey bee venom in seven bumble bee allergic patients is reported. The cause of the high frequency of sensitization to pollen in these patients is discussed.
In vitro allergenicity of cows' milk substitutes
Authors: DEAN T. P. , ADLER B. R. , RUGE F. , WARNER J. O. 
Published: April 2006

SummaryThere are numerous alternatives to cows' milk formula for allergic children. We have investigated the allergenicity of several of these using RAST and RAST inhibition on serum from 16 patients with a known history of cows' milk protein intolerance (CMPI) and 16 atopic controls. A RAST grade of ≥3 for cows' milk was present in all those with CMPI, whilst all the controls gave RAST of ≤1 ‐ Modified cows' milk formula, goats' infant formula, sheep and goats' milk produced similar results to cows' milk. Only two patients had RAST ≥3 for soya milk and the soy/beef hydrolysate gave positive results in only three patients. One had positive RAST to Nutramigen and two to Pregestimil. Of the whey hydrolysates investigated, Pepti‐junior gave seven positive RASTs whilst we were unable to hind Alfare to the sepharose in sufficient quantities to interpret the results which were negative in all cases. RAST inhibition data on pooled sera from the same patients agreed with the RAST results. The inhibition curves showed high inhibition with goats', sheep, modified cows' milk formula and the casein formula. AL110 (50%). Soy and soy/beef hydrolysate showed a much lower inhibition pattern. Casein hydrolysates showed low inhibition while the whey hydrolysate produced higher inhibition. We have shown that despite claims of low allergenicity. some of these alternative formulae are antigenically recognized in vitro by some cows' milk intolerant patients.
Total blood eosinophils, serum eosinophil cationic protein and eosinophil protein X in childhood asthma: relation to disease status and therapy
Authors: ZIMMERMAN B. , LANNER A. , ENANDER I. , ZIMMERMAN R. S. , PETERSON C. G. B. , AHLSTEDT S. 
Published: April 2006

SummaryBlood eosinophils, and serum levels of the eosinophil proteins, eosinophil cationic protein (ECP) and eosinophil protein X (EPX) were measured in childhood asthma. Seventeen patients mean age 11–9 years who were symptomatic with asthma, were enrolled in a study examining the eosinophil counts and eosinophil proteins at the onset of study and after treatment in relation to changes in their baseline forced expiratory volume at 1 second (FEV1) and % predicted FEV1. The patients with symptomatic asthma were compared with 17 patients mean age 12.0 years with asymptomatic asthma maintained on daily inhaled steroid and 13 patients, mean age 12.0 years, without asthma but with urticaria who served as non‐asthma controls. Patients with symptomatic asthma did not have significantly higher initial eosinophil counts compared with those with asymptomatic asthma (0.43 × 109/1 vs 0.26 × 109/1, P= 0.09) but had higher serum ECP levels (28.9 μ/1 vs 18.5 μg/1). Both asthma patient groups had significantly higher serum ECP levels (P<0.01) than the controls (9.8 μg/1). After therapy consisting of increased dose of inhaled steroids and/or oral steroids, patients in the symptomatic asthma group demonstrated a significant rise in FEV1 (1.67 1/sec at Visit 1 vs 2.08 1/ sec at Visit 2, 1<0.01). A similar rise was seen for % predicted FEV1. Patients in the asymptomatic asthma group showed no significant change in FEV1 between visits (2.23 1/sec vs 2.37 1/sec), which was verified with the % predicted FEV1, Patients in the symptomatic asthma group showed a significant decrease in ECP level following treatment (28.9 μ/1 to 9.6 μ/1. P<0.001) while the values in the asymptomatic group did not change (18.6 μ/1 to 15.2 μ/1 not significant). There was a significant correlation between the initial ECP level in the symptomatic asthma group and the change in the FEV| with treatment. Serum EPX levels showed similar trends but there was no significant correlation between the initial EPX levels and the changes in FEV1. Neither did blood eosinophil counts show such a correlation. This data suggests that the changes in serum ECP levels correlate with the changes in lung function subsequently to anti‐inflammation therapy.
Sensitization to four common inhalant allergens within 302 nuclear families
Authors: KUEHR J. , KARMAUS W. , FORSTER J. , FRISCHER T. , HENDEL‐KRAMER A. , MOSELER M. , STEPHAN V. , URBANEK R. , WEISS K. 
Published: April 2006

SummaryThe coincidence of allergic sensitization was investigated in 302 school‐aged children and their parents. Specific sensitization to four common inhalant allergens (grass and birch pollens, cat dander, Dermatophagoides pteronyssinus) was ascertained by means of skin‐prick tests (SPT) carried out on the complete family unit at the beginning of a 22‐month follow‐up period. The same test procedure was then repeated on the children twice at 11‐month intervals to provide cumulative prevalences of sensitization. A clinical history of atopy in the children (hay fever or asthma; n= 47), which was derived from an interview, is associated with sensitization (positive SPT in 89%). For three allergens (grass and birch pollens, cat dander) sensitization occurs significantly more frequently in the children of mothers who are sensitized to the same allergen (odds‐ratios (ORs), 2.5–4.1). Additionally, in three of the four explanatory models related to a single antigen, maternal sensitization to one of the complementary allergens is of importance (ORs, 2.7–3.7). In contrast to this finding, none of the paternal sensitizations has statistical significance. Based on a reaction to at least one of the four allergens, the child's relative risk to be sensitized is increased in case of maternal (OR, 2.88; P= 0.001) but not of paternal (OR, 1.06; P= 0.83) sensitization. In conclusion, our data indicate that the maternal status is more predictive than that of the father with regard to the child's risk of sensitization.