bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of aerosolized administration of KF19514, a phosphodiesterase 4 inhibitor, on bronchial hyperresponsiveness and airway inflammation induced by antigen inhalation in guinea‐pigs
Authors: Myou  , Fujimura  , Kurashima  , Tachibana  , Hirose  , Nakao
Published: March 2003

Background

Although phosphodiesterase (PDE) 3 and 4 inhibitors have received much attention for the treatment of bronchial asthma, systemic adverse effects have also been reported.

Objective

The purpose of this study was to investigate the effect of inhaled olprinone, a newly developed PDE3 inhibitor, and KF19514, a PDE1 and 4 inhibitor, on antigen‐induced airway reactions in guinea‐pigs.

Methods

Fifteen minutes after inhalation of olprinone (0.1 or 1.0 mg/mL) and KF19514 (0.1 or 0.01 mg/mL), animals were given an antigen challenge. Bronchial hyper‐responsiveness and bronchoalveolar lavage fluid cell analysis were performed 24 h after the antigen challenge.

Results

Inhalation of olprinone and KF19514 caused a dose‐related inhibition of antigen‐induced bronchoconstriction. Antigen inhalation significantly increased bronchoconstrictor responses to methacholine, and airway accumulation of neutrophils and eosinophils, 24 h after the antigen challenge. These responses were dose‐dependently prevented by KF19514, but not by olprinone.

Conclusion

The results indicate that inhaled PDE inhibitors might be useful for treatment of bronchial asthma.
Why do some dietary migraine patients claim they get headaches from placebos?
Authors: Strong
Published: March 2003

Background

In six double‐blind studies involving 182 tests of dietary migraine patients sensitive to tyramine and β‐phenylethylamine, 18% reported headaches from placebos which were all concealed in gelatin capsules.

Objective

The purpose of this research was to test a hypothesis: gelatin is partially hydrolysed animal protein; (partially) hydrolysed vegetable protein (PHVP) is known to cause migraine; perhaps the gelatin caused some of the headaches.

Method

The author tested this hypothesis on himself because he suffers from dietary migraine. He proved this in a double‐blind test with tyramine hydrochloride (TYH). The amount required for the test was so small (1 mg) that it was tasteless and capsules were unnecessary. The author then undertook tests with a capsule, PHVP, monosodium glutamate (MSG) aspartame (a dipeptide) and TYH, adjusting quantities to give a moderate headache. Samples were mixed with foods to simulate normal eating: the capsule with potato chips, aspartame with orange juice and the rest with cottage cheese or ricotta cheese. Times were measured from ingestion (1) to start of the headache and (2) to maximum headache intensity. Each experiment was repeated three times. The headaches were relieved with caffeine.

Results

Of eight double‐blind test samples, the author identified correctly the two placebos and five of the six samples containing tyramine. Quantities giving moderate headaches were: 1 gelatin capsule, 400 mg MSG, 118 mg PHVP, 4.0 mg aspartame and 1.0 mg TYH. Typical times for the three repetitions of the two time periods were 8, 9 and 11 and 17, 19 and 22 min.

Conclusions

Capsules may give headaches to dietary migraine patients that are similar to those from foods. This would explain some of the headaches of patients from placebos. The double‐blind test and the repeatability of the time measurements demonstrated the validity of the experiments.
Preventive treatment of intranasal fluticasone propionate reduces cytokine mRNA expressing cells before and during a single nasal allergen provocation
Authors: Kleinjan A. , Holm A. F. , Dijkstra M. D. , Boks S. S. , Severijnen L.‐A. F. , Mulder P. G. , Fokkens W. J.
Published: March 2003

Background

The local production and release of a number of cytokines regulate allergic upper airway inflammation. Medication is usually used at the presentation of the first symptoms. There are, however, clues that it is advisable to start taking the corticosteroid before the grass pollen season begins.

Methods

This single allergen provocation study was conducted in autumn, out of the hay fever season. Nasal mucosa biopsies were taken twice before provocation (before and after 4 weeks of preventive treatment) and three times after allergen provocation (1 h, 24 h and 1 week). The preventive treatment used was fluticasone propionate aqueous nasal spray (FPANS) (n = 10) or a placebo (n = 9). Eosinophils and mRNA positive cells (in situ hybridization for IL‐2, IL‐3, IL‐4, IL‐5, IL‐6, IL‐8, IL‐10, IL‐13, IFNγ, RANTES and TNFα) were counted in the biopsies.

Results

Preventive treatment with FPANS out of season resulted in a decrease in eosinophils and mRNA positive cells for IL‐5 and IL‐6. After allergen provocation, levels of most of the measured cytokines (IL‐3, IL‐5, IL‐6, IL‐13, IFNγ, RANTES and TNFα) and eosinophils were reduced using corticosteroids. The numbers of cells (eosinophils, IL‐3, IL‐6 and IL‐8) correlated with nasal symptoms. Significant correlations in the early and late allergic phase were found between eosinophils and cytokines (IL‐3, IL‐10 and IL‐13).

Conclusion

These results indicate that preventive treatment with FPANS prior to contact with grass pollen is effective in reducing the increase of cytokine mRNA positive cells in reaction to grass pollen contact.
The relationship of eosinophil granule proteins to ions in the sputum of patients with cystic fibrosis
Authors: Halmerbauer G. , Arri S. , Schierl M. , Strauch E. , Koller D. Y.
Published: March 2003

Increased sputum levels of eosinophil granule proteins have been reported despite normal eosinophil numbers in peripheral blood and in the lung in cystic fibrosis (CF). Mechanisms of eosinophil priming and activation are still unclear in CF.

In the present study we investigated whether ion concentrations in the sputa of CF patients are related to eosinophil activity.

We assessed concentrations of eosinophil cationic protein (ECP), eosinophil protein X (EPX), major basic protein (MBP) and ions (Na+, Cl−, Ca2+, Mg2+) in sputum samples of 29 children with CF as well as in 10 controls with bronchial asthma.

Patients with CF demonstrated significantly higher levels of ECP, Na+, Cl− and Ca2+ levels than asthmatics (P < 0.04, P < 0.0001, P < 0.0001, P < 0.02). No differences were seen between concentrations of EPX and Mg2+ in the two groups. In CF, eosinophil granule proteins correlated significantly with Ca2+ and Mg2+ concentrations (ECP, P < 0.0001, r = 0.65, P < 0.0001, r = 0.66; MBP, P < 0.03, r = 0.41, P < 0.03, r = 0.42), furthermore inversely with Cl− concentrations (ECP, P < 0.0003, r = − 0.63; EPX, P < 0.02, r = − 0.45; MBP, P < 0.03, r = − 0.41) but not with Na+ levels. ECP, Na+ and Cl− were also correlated with lung function variables (FVC, P < 0.04, r = − 0.38, P < 0.02, r = 0.44, P < 0.03, r = 0.41; FEV1, P < 0.007, r = − 0.49, P < 0.006, r = 0.5, P < 0.008, r = 0.48; MEF50, P < 0.003, r = − 0.54, NS, P < 0.03, r = 0.42; MEF25, P < 0.039, r = − 0.4, P < 0.005, r = 0.51, P < 0.05, r = 0.37).

Our results demonstrated a significant relationship of eosinophil degranulation and ions in CF, indicating that ion composition in CF sputa may be at least partly be responsible for high levels of eosinophil products despite low eosinophil numbers.
Nasal endoscopy in asthmatic children: assessment of rhinosinusitis and adenoiditis incidence, correlations with cytology and microbiology
Authors: Tosca M. A. , Riccio A. M. , Marseglia G. L. , Caligo G. , Pallestrini E. , Ameli F. , Mira E. , Castelnuovo P. , Pagella F. , Ricci A. , Ciprandi G. , Canonica G. W.
Published: March 2003

Background Upper respiratory airway diseases may induce a worsening of asthma. Sinusitis represents one of the most common chronic diseases. The association of asthma and sinusitis varies greatly in different studies, depending on diagnostic procedures.

Objective The aims were: (i) to demonstrate that nasal endoscopy may be easily feasible in asthma at paediatric age; (ii) to evaluate the incidence of rhinosinusitis and adenoiditis in children with asthma by nasal endoscopy; (iii) to correlate inflammatory parameters such as cytology and microbiological cultures with nasal endoscopy findings.

Subjects and methods One hundred and forty‐five asthmatic children were evaluated, 48 males and 97 females, with an average age of 7.27 years. Evaluated parameters were the incidence of rhinosinusal infections in asthmatic children, and the role of: (i) nasal endoscopy, (ii) nasal cytology, and (iii) nasal microbiology in their diagnoses.

Results Nasal endoscopy was successfully performed on 128 patients. Twenty‐six children had endoscopic rhinosinusitis alone, 10 had adenoiditis alone, and 35 showed endoscopic rhinosinusitis associated with adenoiditis. There were significant correlations between endoscopic rhinosinusitis and adenoiditis (P < 0.001), between clinical and endoscopic rhinosinusitis (P < 0.001), between endoscopic rhinosinusitis and adenoiditis and microbiology (P < 0.05 and P < 0.0001, respectively), and between microbiology and cytology (P < 0.05).

Conclusion This study shows that rhinosinusal infections are common in asthmatic children. Moreover, nasal endoscopy might represent a fruitful tool in the management of asthmatic children.
Image analysis and quantification in lung tissue
Authors: De Boer W.I. , Hiemstra P.S. , Sont J.K. , De Heer E. , Rabe K.F. , Van Krieken J.H.J.M. , Sterk P.J.
Published: March 2003

On 9–10 September 1999, an international workshop on image analysis and quantification in lung tissue was held at the Leiden University Medical Center, Leiden, The Netherlands. Participants with expertise in pulmonary and/or pathology research discussed the validity and applicability of techniques used for quantitative examination of inflammatory cell patterns and gene expression in bronchial or parenchymal tissue in studies focusing on asthma and chronic obstructive pulmonary disease (COPD). Differences in techniques for tissue sampling and processing, immunohistochemistry, cell counting and densitometry are hampering the comparison of data between various laboratories. The main goals of the workshop were to make an inventory of the techniques that are currently available for each of these aspects, and in particular to address the validity and unresolved problems of using digital image analysis (DIA) as opposed to manual scoring methods for cell counting and assessment of gene and protein expression. Obviously, tissue sampling and handling, fixation and (immunohistochemical) staining, and microscope settings, are having a large impact on any quantitative analysis. In addition, careful choices will have to be made of the commercially available optical and recording systems as well as the application software in order to optimize quantitative DIA. Finally, it appears to be of equal importance to reach consensus on which histological areas are to be analysed. The current proceedings highlight recent advances and state of the art knowledge on digital image analysis for lung tissue, and summarize the established issues and remaining questions raised during the course of the workshop.
Long‐term asthma control with oral montelukast and inhaled beclomethasone for adults and children 6 years and older
Authors: Williams B. , Noonan G. , Reiss T. F. , Knorr B. , Guerra J. , White R. , Matz J.
Published: March 2003

Background Leukotriene receptor antagonists have demonstrated clinical benefits in chronic asthma studies of up to 3 months in duration. The effects of these agents over extended periods of time have not been reported.

Objective To describe the long‐term effect of oral montelukast, a potent and specific cysteinyl leukotriene receptor antagonist, compared with inhaled corticosteroids in both adult and paediatric patients with chronic asthma.

Methods Male and female patients with chronic, stable asthma (adults aged 15–85 years, children aged 6–14 years), who had completed double‐blind, placebo‐controlled clinical studies, participated in three extension studies with oral montelukast taken once daily (10 mg tablet for adults, 5 mg chewable tablet for paediatric patients) or inhaled corticosteroids (beclomethasone 200 μg twice daily for adults, beclomethasone 100 μg or equivalent three times daily for children). A double‐blind adult extension study was 37 weeks in duration; open‐label adult extension studies were 156 (adults) and 112 (paediatric) weeks in duration. A total of 436, 374, and 245 patients entered these extension studies, respectively.

Results Treatment with both montelukast and inhaled corticosteroids resulted in improvement in multiple parameters of asthma control. Improvements in daytime symptom scores were generally comparable among treatment groups. No tachyphylaxis to the effects of montelukast was evident. In the adult open‐label study, however, the effect of beclomethasone on mean forced expiratory volume in 1 second (FEV1) gradually decreased from start of the study to the end of the follow‐up treatment period.

Conclusion Both montelukast and inhaled corticosteroids were effective in controlling mild to moderate chronic asthma; the relative effectiveness of montelukast and beclomethasone were similar in open‐label conditions. The hypothesis, that clinical practice conditions (e.g., adherence) may have a significant impact on the effectiveness of these therapies, should be tested in future clinical trials.
Rhinovirus infection up‐regulates eotaxin and eotaxin‐2 expression in bronchial epithelial cells
Authors: Papadopoulos N. G. , Papi A. , Meyer J. , Stanciu L. A. , Salvi S. , Holgate S. T. , Johnston S. L.
Published: March 2003

Background Human rhinoviruses (RVs) are the most common precipitants of asthma exacerbations. RV infection of bronchial epithelium results in local airway inflammation inducing eosinophil recruitment and activation. Induction of eosinophil chemoattractants could represent a central mechanism, as well as a prime target for intervention.

Objective To assess the effect of RV infection on mRNA expression and production of eosinophil chemoattractants by bronchial epithelial cells in‐vitro.

Methods BEAS‐2B cells were infected with major and minor RVs and the mRNA expression of IL‐8, RANTES, MIP‐1α, eotaxin, eotaxin‐2, MCP‐2, MCP‐3 and MCP‐4 was assessed by reverse transcription PCR. In cases where mRNA induction was observed, a fluoroimmunoassay was used to confirm protein production. To assess the virus‐specificity of the observed reactions, cells were also exposed to inactivated RVs.

Results RV infection was able to up‐regulate mRNA expression of IL‐8, RANTES, MIP‐1α, eotaxin and eotaxin‐2, did not affect MCP‐4, while MCP‐2 and MCP‐3 were not expressed either at baseline or after virus infection. Protein production was confirmed for IL‐8, RANTES and eotaxin, but not for MIP‐1α. When RVs were inactivated cytokine up‐regulation was almost completely lost.

Conclusion Infection of bronchial epithelial cells with RVs results in the production of a wide array of mediators that are able to chemoattract eosinophils. These include the eosinophil‐specific molecules eotaxin and eotaxin‐2, in addition to IL‐8 and RANTES, which are the most abundant. Eosinophil recruitment after RV infection of bronchial epithelium could represent a central event in the pathogenesis of virus‐induced asthma exacerbations.
Chronic urticaria: novel clinical and serological aspects
Authors: Asero R. , Tedeschi A. , Lorini M. , Salimbeni R. , Zanoletti T. , Miadonna A.
Published: March 2003

Background Recently, distinct studies have shown that: (a) chronic idiopathic urticaria (CIU) is autoimmune in 30–50% of cases; (b) in patients with CIU the autologous serum skin test is inhibited by heparin; and (c) basophil histamine release induced in vitro by CIU sera maybe complement‐dependent.

Objective To carry out a comprehensive clinical and serological study on CIU based upon these observations.

Methods Three hundred and six adults with CIU underwent intradermal (ID) test with autologous serum; 57 of them with autologous heparinized plasma as well. Sera from 121 patients (plasmas from 17) were employed to induce in vitro histamine release from basophils of normal donors. The effects of heating (56 °C, 60 min), filtration through membrane, and preincubation with heparin were evaluated as well.

Results Autologous serum and plasma induced a weal and flare reaction in 205 out of 306 (205/306; 67%) and in 8/57 (14%) patients, respectively. Positive plasma skin tests were observed only in patients showing strongly positive serum skin tests. Plasma did not elicit any skin reaction in 3/3 patients with dermatographism who showed a positive intradermal test with saline. Sera from 20/121 (16.5%) patients induced significant histamine release from basophils of normal donors. 19/20 sera were from patients with a positive intradermal test; thus, basophil histamine release assay was positive in 19/87 (21.8%) patients with a positive serum skin test. Heating at 56 °C × 1 h markedly reduced the histamine‐releasing activity of both serum and plasma from in vitro reactors. Ultrafiltered fractions > 100 kDa of both sera tested retained the histamine‐releasing activity, whereas fractions < 100 kDa were not able to induce any histamine release. Heparin dose‐dependently inhibited histamine release induced by sera and plasma, and by basophil agonists such as anti‐IgE, formyl‐methionyl‐leucyl‐phenilalanine, and interleukin (IL)‐3.

Conclusions 67% of our patients with CIU showed a positive autologous serum skin test. Sera from about 20% of those positive on autologous serum skin test induced histamine release from normal basophils in vitro probably as a consequence of the presence of functional autoantibodies. The marked difference between in vivo and in vitro findings could reflect the existence of a mast cell‐specific histamine‐releasing factor which does not release histamine from basophils of healthy blood donors. However, it might be also the result of in vivo priming of patients' cutaneous mast cells or of heterogeneity of basophil donors. At least in some cases complement seems essential for histamine‐releasing activity of serum from patients with CIU. Heparin inhibits histamine release from both basophils (in vitro) and mast cells (in vivo), probably acting directly at a cellular level.
Eosinophils are activated in middle ear mucosa and middle ear effusion of patients with intractable otitis media associated with bronchial asthma
Authors: Iino Y. , Nagamine H. , Yabe T. , Matsutani S.
Published: March 2003

Background Although patients with intractable otitis media associated with bronchial asthma have extensive accumulation of eosinophils in the middle ear mucosa and middle ear effusion, systematic histological and immunohistochemical studies have not been performed.

Objectives To clarify the pathogenesis of middle ear diseases, we carried out immunohistochemical studies on middle ear specimens, particularly focusing on the characteristics of accumulated eosinophils.

Methods Middle ear specimens obtained from eight adult patients and from 17 controls were immunohistochemically stained using monoclonal antibodies against EG1, EG2, mast cell tryptase, IgA and IgE. The concentration of eosinophil cationic protein (ECP) in middle ear effusion samples was also measured.

Results In the asthmatic patients, severe round‐cell infiltration was observed in the submucosa and most of the EG1‐positive cells were also EG2‐positive. In the control patients, the mucosa showed a fibrotic change with a few inflammatory cells, and EG1‐ or EG2‐positive cells were quite few. The expression of IgE was found not only on the surface of mast cells but also within the plasma cells in the asthmatic patients, and the number of IgE‐positive cells was about twice as high as that of mast cells. A significantly higher concentration of ECP was noted in middle ear effusion obtained from the asthmatic patients than that from the control patients.

Conclusion Most of the eosinophils in the middle ear mucosa and middle ear effusion were activated, resulting in degranulation and release of ECP, and local IgE production occurs in the middle ear mucosa, indicating that the intractable inflammation is closely associated with IgE‐mediated late phase response with eosinophil accumulation.
Maternal atopy and parity
Authors: Sunyer J. , Antó J. M. , Harris J. , Torrent M. , Vall O. , Cullinan P. , Newman‐Taylor A.
Published: March 2003

Background Family size and high birth order were related to the prevalence of hayfever and positive skin prick test. However, this association may be explained by maternal atopy. We examined the relationship between maternal atopy and the number of offspring in three European cohorts of pregnant women.

Methods The mothers and their children (n = 1487) were recruited for the Asthma Multi‐centre Infants Cohort Study (AMICS). The three concurrent cohorts (Ashford, Kent (UK); Menorca island (Spain) and Barcelona city (Spain) followed the same research protocol. Maternal and paternal atopy was identified by skin prick tests at different times at the three centres.

Results Maternal atopy was inversely related to the number of offspring, an association which occurred in each of the three cohorts and remained when atopy was defined separately for individual allergens (a positive response to testing with either Der p 1 or grass pollen) and which was not confounded by maternal age, smoking nor social class (the adjusted odds ratios were 0.71, 0.79 and 0.26 for increasing number of offspring, P = 0.002). Neither maternal asthma (P = 0.43) nor paternal atopy (P = 0.58) were associated with the number of offspring. Maternal atopy was not related to reproductive outcomes.

Conclusions The association between maternal atopy and parity challenges the role of family size on child atopy, which should be studied in other populations.
The allergenic yeast Malassezia furfur induces maturation of human dendritic cells
Authors: Buentke E. , Heffler L. C. , Wallin R. P. A. , Löfman C. , Ljunggren H. G. , Scheynius A.
Published: March 2003

Background The yeast Malassezia furfur (M. furfur), present in the normal microflora of human skin, can act as an allergen that incites specific IgE reactivity and T cell proliferation in atopic dermatitis (AD) patients. The role of antigen presenting dendritic cells (DCs) in the onset and maintenance of AD is not well established.

Objective The objective of the present study was to assess whether the interaction of M. furfur with human DCs will result in DC maturation, cytokine production and lymphocyte proliferation.

Methods Monocyte‐derived dendritic cells (MDDCs) were generated from human peripheral blood. Immature MDDCs were cultured with or without M. furfur or plastic beads, and with or without CD40L stimulation. Interaction of yeast cells by MDDCs was studied by time‐lapse photography and cytokines were detected in culture supernatants with ELISA. The ability of MDDCs pre‐incubated with M. furfur to induce proliferation in autologous lymphocytes was measured by [3H]‐thymidine incorporation.

Results Time‐lapse photography showed that the majority of immature MDDCs internalized whole M. furfur yeast cells within 1 h. The presence of M. furfur induced maturation (CD83 expression) of MDDCs, and up‐regulation of the costimulatory molecules CD80 and CD86. Production of TNF‐α, IL‐1β and IL‐18 by MDDCs increased significantly (P < 0.05 for TNF‐α and IL‐1β, and P < 0.01 for IL‐18) after the addition of M. furfur, while IL‐10 and IL‐12p70 levels remained unaltered. The CD40L‐stimulated IL12p70 production by MDDCs was decreased in the presence of M. furfur (P < 0.05). Finally, immature MDDCs pre‐incubated with M. furfur induced a proliferative response in autologous CD14‐depleted peripheral blood mononuclear cells, in a dose‐dependent manner.

Conclusion The data indicate that immature MDDCs can internalize the opportunistic yeast M. furfur. This process was associated with MDDC maturation, production of pro‐inflammatory and immunoregulatory cytokines, which might favour induction of a Th2‐type immune response, and a capacity to stimulate lymphocyte proliferation. This chain of events most likely contributes to the inflammatory reaction in AD.
Airway epithelial cells promote transmigration of eosinophils in a new three‐dimensional chemotaxis model
Authors: Kato Y. , Fujisawa T. , Shibano M. , Saito T. , Gatto W. , Kamiya H. , Hirai K. , Sumida M. , Yoshie O.
Published: March 2003

Background Prominent infiltration of eosinophils in airway mucosa is the pathognomonic sign of asthma. The role of airway epithelial cells in eosinophil infiltration, however, has not been fully elucidated.

Objective The aim of this study is to develop a new in vitro transmigration system composed of airway epithelial cells and extracellular matrix, and to investigate the role of airway epithelial cells in eosinophil infiltration.

Methods A layer of type I collagen gel was formed in Netwell™, and BEAS‐2B bronchial epithelial cells were cultured on the gel. Then the wells covered with epithelial monolayer were filled with medium, inverted, and new upper chambers were constructed on the gel side by applying a ring cap. After further incubation with or without exogenous cytokines for 48 h, eosinophils or neutrophils were loaded in upper chambers (the gel side) and cells transmigrated to lower chambers (the epithelial cell side) were counted. Immunohistochemical analyses were also performed.

Results While a simple collagen gel hardly promoted eosinophil migration even in the presence of eotaxin or RANTES, significant numbers of eosinophils migrated to lower chambers in the presence of the epithelial cells. Replacement of medium in the lower chamber (the epithelial cell side) with fresh medium, addition of exogenous eotaxin or RANTES in the upper chamber (the gel side), or pre‐treatment of eosinophils with anti‐CCR3 all inhibited transmigration. We found that the epithelial cells produced and deposited extracellular matrix proteins such as type IV collagen onto the type I collagen gel. Separately, we found that type IV collagen itself was capable of enhancing eotaxin‐induced eosinophil migration in a standard chemotaxis assay. Neutrophils also efficiently migrated in the present transmigration system. Pre‐treatment of epithelial cells with TNF‐α and IL‐4 enhanced eosinophil transmigration, while that of neutrophils was enhanced by TNF‐α but suppressed by IL‐4.

Conclusion By utilizing a new in vitro transmigration system mimicking the airway mucosa, we have demonstrated that airway epithelial cells play an essential role in transmigration of eosinophils and that multiple factors such as chemokines, extracellular matrix proteins and exogenous inflammatory cytokines are involved in efficient transmigration.
Paradoxical low nasal nitric oxide in nasal polyposis
Authors: Colantonio D. , Brouillette L. , Parikh A. , Scadding G. K.
Published: March 2003

Background Nitric oxide (NO) is synthesized in the respiratory tract. Three isoforms of NO synthase have been described in man, with the inducible form related to inflammatory disease. In the paranasal sinuses constitutive production of nitric oxide has been demonstrated, with levels of 20–25 p.p.m. being found in sinus puncture. Nasal polyposis is a chronic inflammatory condition in which inducible nitric oxide synthase (iNOS) expression is elevated in nasal polyp epithelium.

Objectives 1. Measurement of upper airway nitric oxide in nasal polyposis patients compared with those with allergic rhinitis, and with normal controls. 2. To assess the effect of polyp treatment on nasal NO levels.

Methods NO levels (parts per billion) were measured in nasal and pulmonary exhaled air using a LR 2000 Logan Sinclair nitric oxide gas analyser. This utilizes the chemiluminescence principle. Eighty‐two patients were studied: 44 with rhinitis, but without polyps, and 38 with nasal polyps. NO levels were compared with those of 20 normal controls. In 23 further polyp patients, levels were measured pre‐ and post‐treatment and the changes were compared with alterations in polyp size, as assessed by rigid nasendoscopy.

Results Nasal NO levels were significantly lower (Kruskal–Wallis, P = 0.000, χ2 = 27.5, d.f. = 3) in patients with polyps than those found in uncomplicated allergic rhinitis. NO levels were correlated directly with extent of polyposis as graded by the Lund‐McKay index. Successful treatment, with reduction in polyp volume, was associated with a rise in NO levels (P = 0.042).

Conclusion NO levels are low in nasal polyposis, despite high levels of iNOS, possibly related to blockage of the ostiomeatal complex and failure of NO generated constitutively in the sinuses to reach the nasal airway. A rise in the NO levels is seen with successful polyp treatment, and is proportional to the reduction in endoscopically assessed polyp size, suggesting that with both medical and surgical therapy, the ostiomeatal complex obstruction is decreasing. We propose the following scenario. Nasal NO levels are the result of two processes: inducible NO production by inflamed nasal mucosa plus constitutive sinus mucosal production, detectable in normals. In uncomplicated allergic rhinitis with patent sinus ostia NO levels tend to be elevated, but when inflammation is sufficient to obstruct sinus ostia (as in nasal polyps), NO levels fall because sinus NO makes the major contribution.
The descriptive epidemiology of house dust mite‐specific and total immunoglobin E in England using a nationally representative sample
Authors: Court C. S. , Cook D. G. , Strachan D. P.
Published: March 2003

Background Previous studies have shown that IgE levels vary according to factors such as age, gender and smoking but most studies have been small and none have been based on a nationally representative sample.

Objectives To investigate the influence of epidemiological factors on serum total IgE and house dust mite‐specific IgE levels.

Methods An interviewer‐led questionnaire was carried out and blood samples taken from 24 952 people aged 11 and over as part of the 1995 and 1996 Health Surveys for England. Serum total IgE and house dust mite‐specific IgE were measured.

Results Both total and house dust mite‐specific IgE were more frequently raised in men and in younger age groups. After adjusting for age and sex, raised total IgE was more common in current smokers and non‐white ethnic groups and was not related to social class. The higher levels in non‐white ethnic groups was not explained by smoking, urban living or being born outside the UK. Whilst total IgE levels declined in older age groups in non‐smokers, among smokers they increased across successive age groups from 50 years onwards. In contrast, following adjustment for age and sex, raised house dust mite IgE was more common in non‐manual workers and in some non‐white ethnic groups but was not related to smoking.

Conclusions This large nationwide study provides further confirmation of differing epidemiological patterns for total serum IgE and allergen‐specific sensitization. Indicative ranges for ‘usual’ values for a wide range of ages among men and women in England are given.
Relationship between sensitization to citrus red mite (Panonychus citri) and the prevalence of atopic diseases in adolescents living near citrus orchards
Authors: Kim S. ‐H. , Kim Y. ‐K. , Lee M. ‐H. , Hong S. ‐C. , Bae J. ‐M. , Min K. ‐U. , Kim Y. ‐Y. , Cho S. ‐H.
Published: March 2003

BackgroundRecent investigations have demonstrated that the citrus red mite (Panonychus citri, CRM) is the most important allergen in citrus fruit farmers with asthma and rhinitis and a common sensitizing allergen in children living near citrus orchards.

ObjectiveTo evaluate the sensitization rate to CRM and the association between sensitization to CRM and atopic diseases, such as athma, allergic rhinitis and atopic dermatitis, in adolescents living in rural areas with citrus orchards.

MethodsA total of 2005 adolescents (aged from 16 to 18 years) living in rural areas with citrus orchards were enrolled. Subjects were evaluated by a questionnaire and a skin prick test with 11 common aeroallergens including CRM.

ResultsThe prevalences of current wheeze, rhinoconjuntivitis, and eczema on the questionnaire were 13.0%, 13.6%, and 8.8%, respectively. On skin prick tests, the most common sensitizing allergen was CRM [20.6%], followed byDermatophagoides pteronyssinus(18.5%),D. farinae(14.6%) and cockroach (9.8%). The prevalence of current eczema was significantly associated with the sensitization to CRM (OR = 1.9, 95% CI 1.3–2.9), although the prevalence of current wheeze and rhinoconjunctivitis was not associated with it. Among adolescents living near citrus orchards, however, the prevalences of current wheeze and rhinoconjuncitivitis were significantly higher in those with sensitization to only CRM than in those without sensitization to any allergens (20.3% vs. 14.1% and 20.3% vs. 15.0%,P < 0.05, respectively).

ConclusionCRM is the most common sensitizing allergen in adolescents living in rural areas with citrus orchards, and sensitization to CRM was significantly associated with the prevalence of atopic dermatitis.
Comparison between the native glycosylated and the recombinant Cup a1 allergen: role of carbohydrates in the histamine release from basophils
Authors: Iacovacci P. , Afferni C. , Butteroni C. , Pironi L. , Puggioni E. M. R. , Orlandi A. , Barletta B. , Tinghino R. , Ariano R. , Panzani R. C. , Di Felice G. , Pini C.
Published: March 2003

Background Cypress pollinosis is an important cause of respiratory allergies. Recently, the Cupressus arizonica major allergen, Cup a1, has been cloned and expressed. The native counterpart of this allergen has been purified and characterized by our group. It has been suggested that sugar moieties play a role in the in vitro IgE binding on Cupressus arizonica pollen extract.

Objective To characterize the immunoreactivity of the recombinant major allergen in comparison with its native counterpart. To evaluate the role of carbohydrate moieties in the IgE‐mediated in vitro histamine release from basophils by using the native glycosylated Cup a1 as compared with the recombinant one.

Methods Recombinant Cup a1 was expressed in E. coli. IgE reactivity of Cupressaceae‐allergic patients on the native as well as the recombinant molecule was investigated by immunoblotting, ELISA experiments and histamine release test from passively sensitized basophils.

Results Fourteen out of 17 Cup a1‐positive sera had IgE antibodies reactive with the native molecule only and lost their reactivity after periodate deglycosylation of the allergen. Moreover, only native molecule was capable of inducing histamine release by this group of sera. Both the recombinant and the native molecules were recognized by three out of the 17 sera and were equally capable of triggering degranulation.

Conclusion A large number of sera reactive with the major allergen recognize carbohydrate epitopes only. IgE from these sera are able to induce histamine release from basophils and they might play a functional role in the clinical symptoms of allergy.
Age‐related T cell responses to allergens in childhood
Authors: Smart J. M. , Suphioglu C. , Kemp A. S.
Published: March 2003

Background T cell priming, as determined by allergen‐induced proliferative responses, is believed to occur principally in early childhood in both atopic and non‐atopic infants under the influence of multiple factors including environmental allergen exposure. It is considered that T cell priming with expansion of Th2 cells is a crucial factor in the development of atopic disease.

Objective To examine T cell priming to commonly encountered allergens in childhood in relation to age.

Methods In a cross‐sectional study T cell proliferation in relation to age was examined for three common allergens, ovalbumin (OVA), house dust mite (HDM) and rye grass pollen (RYE), in atopic and non‐atopic children. The effect of age on Th1 (IFN‐γ) and Th2 (IL‐5 and IL‐13) cytokine production in response to these allergens was investigated to examine the possibility of immune deviation with time.

Results A significant increase in T cell proliferation with age was observed with RYE among atopic children only. However, the same was not observed with the two other allergens studied (i.e. OVA and HDM). In addition, RYE‐induced (but not HDM or OVA) cytokine production showed an increased Th2 deviation with age as reflected in the increasing IL‐5/IFN‐γ and IL‐13/IFN‐γ ratios only among the atopic subjects with rye grass pollen sensitivity.

Conclusion These findings suggest that grass pollen sensitivity in childhood is accompanied by a progressive accumulation of allergen‐primed T cells and progressive deviation of the allergen‐induced cytokine response towards a Th2 response in atopic subjects throughout childhood.
Absence of immunoglobulin E synthesis and airway eosinophilia by vaccination with plasmid DNA encoding ProDer p 1
Authors: Jacquet A. , Magi M. , Haumont M. , Jurado M. , Garcia L. , Bollen A.
Published: March 2003

Background Various studies have shown that immunization with naked DNA encoding allergens induces T helper 1(Th1)‐biased non‐allergic responses.

Objective To evaluate the polarization of the immune responses induced by vaccinations with plasmid DNA encoding the major mite allergen precursor ProDer p 1.

Methods A DNA vaccine was constructed on the basis of a synthetic cDNA encoding ProDer p 1 with optimized codon usage. The immunogenicity of ProDer p 1 DNA in CBA/J mice was compared with that of purified natural Der p 1 or recombinant ProDer p 1 adjuvanted with alum. Vaccinated mice were subsequently exposed to aerosolized house dust mite extracts to provoke airway inflammation. The presence of inflammatory cells was examined in bronchoalveolar lavage (BAL) fluids and allergen‐specific T cell reactivity was measured.

Results Naive mice immunized with ProDer p 1 DNA developed Th1 immune responses characterized by high titres of specific IgG2a antibodies, low titres of specific IgG1 and, remarkably, the absence of anti‐ProDer p 1 IgE. No specific responses were observed in animals vaccinated with the blank DNA vector. By contrast, natural Der p 1 or recombinant ProDer p 1 adsorbed to alum induced pronounced Th2 allergic responses with strong specific IgG1 and IgE titres. Spleen cells from DNA ProDer p 1‐vaccinated mice secreted high levels of IFN‐γ and low production of IL‐5. Conversely, both adjuvanted allergens stimulated typical Th2‐type cytokine profile characterized by high and low levels of IL‐5 and IFN‐γ, respectively. Whereas BAL eosinophilia was clearly observed in Der p 1‐immunized animals, ProDer p 1 DNA as well as ProDer p 1 vaccinations prevented airway eosinophil infiltrations.

Conclusions These results suggest that vaccination with DNA encoding ProDer p 1 effectively fails to induce the allergen‐induced IgE synthesis and airway cell infiltration. Plasmid DNA encoding ProDer p 1 may provide a novel approach for the treatment of house dust mite allergy.
Human platelet inhibition ofToxoplasma gondiigrowth
Authors: Chumpitazi B F F , Simon J , Polack B , Peyron F , Picot S , Ricard J , Ambroise-Thomas P
Published: March 2003

The human platelet contribution against the intracellular growth of the parasite in vitro in human pulmonary fibroblasts was explored. It was observed that tachyzoites of Toxoplasma gondii induced activation of human platelets and additionally that platelets mediated inhibition of intracellular growth in a virulent T. gondii strain. A prominent role for platelet-derived growth factor (PDGF) was demonstrated in this phenomenon, by testing human recombinant PDGF-AA, -AB and -BB and antibodies to human PDGF-AB that partially reversed its effects. Moreover, the effect of PDGF was significantly higher if the host cells were treated 2 h before parasite infection. PDGF was not directly ‘toxic’ to free tachyzoites, but only affected parasites within host cells. PDGF-mediated inhibition may involve the cyclooxygenase cycle of the fibroblasts being partially reversed by the cyclooxygenase inhibitors, acetylsalicylic acid and indomethacin. However, a thromboxane synthetase pathway was not implicated. PDGF action against intracellular tachyzoites may also include increased IL-6 production in fibroblasts. Finally, transforming growth factor-beta 1 (TGF-β1), another component of α-granules released at the same time as PDGF, may not be antagonistic to the PDGF parasite inhibitory effect in confluent host cells.
A blockade of complement activation prevents rapid intestinal ischaemia-reperfusion injury by modulating mucosal mast cell degranulation in rats
Authors: Kimura T , Andoh A , Fujiyama Y , Saotome T , Bamba T
Published: March 2003

We attempted to define the putative role of complement activation in association with mucosal mast cell (MMC) degranulation in the pathogenesis of rapid intestinal ischaemia-reperfusion (I/R) injury. We prepared complement activity-depleted rats by the administration of the anti-complement agent K-76COOH and the serine-protease inhibitor FUT-175. Autoperfused segments of the jejunum were exposed to 60 min of ischaemia, followed by reperfusion for various time periods, and the epithelial permeability was assessed by the 51Cr-EDTA clearance rate. The number of MMC was immunohistochemically assessed. In control rats, the maximal increase in mucosal permeability was achieved by 30–45 min of reperfusion. This increase was significantly attenuated by the administration of either K-76COONa alone or in combination with FUT-175. In contrast, the administration of carboxypeptidase inhibitor (CPI), which prevents the inactivation of complement-derived anaphylatoxins such as C5a, significantly enhanced the increase in I/R-induced mucosal permeability. These findings were confirmed morphologically by light microscopy and scanning electron microscopy. In addition, the I/R-induced mucosal injury was accompanied by a marked decrease in the number of MMC, and administration of K-76COOH significantly inhibited this change. These results indicate that complement activation and the generation of complement-derived anaphylatoxins are key events in I/R-induced mucosal injury. It is likely that intestinal I/R-induced mucosal injury may be partially mediated by MMC activation associated with the complement activation.
Up-regulation of Fas ligand (FasL) mRNA expression in peripheral blood mononuclear cells (PBMC) after major surgery
Authors: Sugimoto M , Shimaoka M , Hosotsubo K , Tanigami H , Taenaka N , Kiyono H , Yoshiya I
Published: March 2003

FasL, which is expressed mainly on activated lymphocytes, can induce apoptosis (programmed cell death) of cells which express Fas. Fas/FasL interaction is primarily beneficial in maintaining immunological and physiological homeostasis by eliminating unnecessary cells. Dysregulation of the interaction, however, leads to tissue damage. We investigated how Fas/FasL levels changed after major surgery. The major aim of this study was to elucidate the involvement of the Fas/FasL system in postoperative inflammation. The investigation involved 10 patients admitted to the intensive care unit after surgery. Although the percentage of Fas+ cells and the amount of Fas expression tended to increase, there was no significant difference between pre- and post-operative samples. In contrast, the levels of FasL mRNA were dramatically up-regulated after operation. Post-operative C-reactive protein (CRP) levels increased and correlated well with FasL levels (r = 0.91, P < 0.01). Lymphocyte counts decreased after operation and were inversely proportional to FasL levels (r = 0.58, P < 0.05). These results suggest that the enhanced FasL expression is likely to be related to systemic inflammatory responses induced during the perioperative period. FasL up-regulation may be involved in the aggravation of tissue damage, including lymphocytopenia, in the early post-operative period.
Characterization of the CDR3 region of rearranged α heavy chain genes in human fetal liver
Authors: Baskin B , Islam K B , Smith C I E
Published: March 2003

The human fetal liver is an early site for B cell development. Pre B cells are first detectable in human fetal life at 8 weeks of gestation, when the rearrangement of the μ heavy chain genes starts. In this study we characterize the CDR3 region of rearranged α heavy chain transcripts from four human fetal livers ranging from 8 to 11 weeks of gestation. Each fetal liver showed a limited number of variations in CDR3 sequences compared with adult peripheral blood mononuclear cells (PBMC). Sequence analysis of 91 clones demonstrated that there was no preference for the usage of a certain JH gene segment, whereas a preference for usage of DH family genes, DXP and DLR, was seen in most cases during early fetal life. This is the first study where rearranged α heavy chain genes in fetal liver have been characterized. Our data suggest that the usage of JH genes is random, while there is a preference for DH family genes in human fetal liver.
Progressive decrease of CD8high+ CD28+ CD57− cells with ageing
Authors: Merino J , Martínez-González M A , Rubio M , Inogés S , Sánchez-Ibarrola A , Subirá M L
Published: March 2003

An age-dependent decrease in T cell responsiveness to CD28 costimulation has been described. In order to test the hypothesis that an age-related decrease in CD28 expression by CD8+ T lymphocytes might be involved, we analysed 67 healthy donors ranging in age from 15 to 69 years for their CD8+ T cell expression of CD28 and CD57. We found a statistically significant decrease of CD28 expression through ageing and a significant increase of CD57 expression, both markers being mutually exclusive. Given that cytomegalovirus (CMV) is reported to induce CD57 expression, and since the carrier status for this ubiquitous virus increases with age in the general population, it seemed essential to evaluate whether the phenotypic age-related changes described in CD8high+ cells were not influenced by the CMV carrier status of the individuals. Accordingly, we performed a multivariate analysis to assess the independent association of age and CMV carrier status with CD28 and CD57 expression in CD8high+ cells. Results showed that the progressive decrease in CD8high+ CD28+ CD57− cells was associated only with age, while the expansion of the CD8high+ CD28− CD57+ subset depended both on age and CMV, although mainly on age. We conclude that ageing is accompanied by a progressive loss of CD28 expression in CD8+ T cells and a reciprocal enhancement of CD57 expression, both facts being probably related to the repeated antigenic stimulation occurring throughout life.