bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histological aspects and role of mast cells in Helicobacter pylori‐infected gastritis
Authors: Nakajima S. , Bamba N. , Hattori T. 
Published: August 2004

SummaryBackground : Mast cells are one of the main pro‐inflammatory cells, while their knowledge in Helicobacter pylori infection has not been summarized.Methods : We reviewed studies on mast cells in H. pylori infection, and summarized the histological aspects and roles.Results : The density of mast cells is greater in H. pylori‐infected than in non‐infected subjects. Increased mast cell density in infected gastritis significantly decreases after eradication. On electron microscopy, mast cells in infected gastric mucosa show degranulation. Some experimental studies demonstrate that mast cells are degranulated with H. pylori‐derived products.Conclusions : Mast cells are actively involved in the pathogenesis of H. pylori‐infected gastritis. The possible roles are to initiate and promote the formation of oedema through degranulated and secreted mediators, and to release multiple chemotactic factors, which induce inflammatory cells to infiltrate to the site of oedema, showing acute inflammatory changes. Mast cells also stimulate the degradation of pericellular matrices and the growth of cells in their vicinity, and thereby promote tissue turnover. In chronic H. pylori infection, these reactions continue until the bacteria are eradicated. Mast cells may act both to maintain gastritis and to repair tissue damage in H. pylori‐infected chronic gastritis.
Oesophageal hypersensitivity in Japanese patients with non‐erosive gastro‐oesophageal reflux diseases
Authors: Miwa H. , Minoo T. , Hojo M. , Yaginuma R. , Nagahara A. , Kawabe M. , Ohkawa A. , Asaoka D. , Kurosawa A. , Ohkusa T. , Sato N. 
Published: August 2004

SummaryBackground : Visceral hypersensitivity plays a major role in the pathogenesis of non‐erosive oesophageal reflux disease (NERD). Prevalence of NERD differs according to the population and geographical region. Oesophageal hypersensitivity in NERD has not been well studied, especially in Japanese patients.Aim : To investigate oesophageal hypersensitivity in Japanese NERD patients.Patients and methods:  We performed upper GI endoscopy and the modified acid perfusion test on 14 control subjects and 68 GERD patients, including 26 with NERD, 34 with erosive GERD, and six with Barrett's oesophagus. The stimulus‐response function to acid was quantified by three parameters (lag time, intensity rating and the acid perfusion sensory score) and compared among four groups.Results : The mean value of the lag time, intensity rating, and acid perfusion scores in NERD patients (4.6 ± 3.4, 4.4 ± 3.4, 27.8 ± 26.7, respectively) were higher than in erosive GERD (3.2 ± 3.3, 3.0 ± 3.2, 18.2 ± 24.8) and Barrett patients (2.5 ± 4.0, 1.8 ± 3.3, 15.0 ± 28.8), and significantly higher than in the control group (1.7 ± 2.7, 1.1 ± 2.0, 5.4 ± 11.8). The ratio of patients with higher sensory scores was also greater in the NERD group (57.7%) than in erosive GERD (32.3%) and Barrett group (16.7%), and significantly greater than in control group (6.7%).Conclusion : Our findings suggest that oesophageal sensitivity is likely to be enhanced especially in NERD patients also in Japanese population in comparison with erosive GERD, Barrett's oesophagus and controls.
Farming exposure in childhood, exposure to markers of infections and the development of atopy in rural subjects
Authors: Radon K. , Windstetter D. , Eckart J. , Dressel H. , Leitritz L. , Reichert J. , Schmid M. , Praml G. , Schosser M. , Von Mutius E. , Nowak D. 
Published: August 2004

AbstractBackground
Within the context of the hygiene hypothesis, we aimed to study the potential association between farming‐related risk factors and Toxoplasma gondii (T. gondii) as well as Helicobacter pylori (H. pylori) seropositivity.Methods
The study included questionnaire data and serum samples of 321 young adults living in a rural environment. Serum samples were analysed for specific IgE to a common panel of aeroallergens (SX1) as well as IgG against T. gondii and H. pylori.Results
Regular contact with animal stables before the age of 3 years (odds ratio (OR) (95% confidence interval): 2.0 [1.0; 4.0]) and unpasteurized milk consumption at age 6 years (1.8 [1.0; 3.3]) were the strongest risk factors for T. gondii infection. None of the farming‐related factors were significantly associated with H. pylori infection. Current consumption of raw farm milk was not significantly associated with H. pylori infection (2.1 [0.8; 5.3]). Regular contact with animal houses before the age of 7 years was the strongest predictor for atopy (0.49 [0.26–0.96]). The reduction in risk could not be further decreased by any other factor under consideration. After adjustment for animal house contact, the OR for atopy was decreased by raw milk consumption and H. pylori infection in an additive manner.Conclusion
Exposure to farming environments in childhood might predict T. gondii seropositivity in rural subjects. Nevertheless, the strongest predictor for atopy in rural subjects seems to be regular contact with farm animals. Whether T. gondii infection is an intermediate factor in the association between farm contact and atopy needs to be confirmed in larger studies.
Induction of T ‘regulatory’ cells by standardized house dust mite immunotherapy: an increase in CD4+CD25+ interleukin‐10+ T cells expressing peripheral tissue trafficking markers
Authors: Gardner L. M. , Thien F. C. , Douglass J. A. , Rolland J. M. , O'Hehir R. E. 
Published: August 2004

SummaryBackground
Clinically effective subcutaneous allergen‐specific immunotherapy (SIT) is associated with altered circulating T cell cytokine production and altered local cytokine responses with increased IL‐10 following allergen challenge in target organs.Objective
This study aimed to elucidate mechanisms for these T cell changes, by examining surface expression of markers for peripheral tissue trafficking on circulating cytokine‐positive T cells following standardized house dust mite‐ (HDM‐) SIT.Methods
A randomized conventional HDM immunotherapy study was performed on a panel of 12 HDM‐allergic subjects. Nine subjects received treatment with conventional HDM immunotherapy using a standardized extract and three subjects were treated by standard pharmacotherapy alone. Symptom and medication scores and allergen‐induced cutaneous late‐phase responses were assessed before and 9 months after institution of therapy. Before and at 3 and 9 months of SIT, peripheral blood mononuclear cells were cultured for 14 days with HDM extract and CD4+ and CD8+ T cell expression of CD62L, CD49d and CCR5 and production of IL‐10, IFN‐γ and IL‐4 were analysed by flow cytometry. Allergen‐specific T cell proliferation was assessed by 3H‐thymidine incorporation.Results
At 9 months, all SIT‐treated patients showed reduced symptom scores and late‐phase cutaneous responses to HDM compared with baseline levels. The proportions of CD4+ T cells which were IL‐10+ were increased (P<0.01), and the proportions of CD4+ and CD8+ T cells which were IL‐4+ decreased (P<0.05) compared with baseline. CD4+ and CD8+ T cell IFN‐γ production, expression of surface markers for peripheral tissue trafficking and allergen‐specific proliferation remained unchanged during SIT treatment. However, increased proportions of CD4+CD62L−, CD4+CD49dhi, CD4+CCR5+ T cells expressing IL‐10 were detected at 9 months of SIT compared with baseline (P<0.05). IL‐10 staining co‐localized with CD4+CD25+ T cells.Conclusion
Clinically effective subcutaneous immunotherapy with a standardized HDM Dermatophagoides pteronyssinus preparation results in decreased numbers of IL‐4+ T cells and expansion of CD4+IL‐10+ T cells expressing a peripheral tissue trafficking phenotype. The co‐localization of IL‐10+ staining to CD4+CD25+ T cells is consistent with the induction of a T regulatory cell population by SIT.
Interactions between eotaxin, histamine and mast cells in early microvascular events associated with eosinophil recruitment to the site of allergic skin reactions in humans
Authors: Menzies‐Gow A. , Ying S. , Phipps S. , Kay A. B. 
Published: August 2004

SummaryBackground
The mechanism whereby allergen induces eotaxin expression at the site of allergic inflammation is incompletely understood. Structural cells, including endothelial cells, are a major source of eotaxin.Objective
We have investigated, in vivo and in vitro, the relationship between mast cell activation and the expression of eotaxin (eotaxin 1) by endothelial cells.Methods
The effects of intradermal allergen challenge and histamine injection on eotaxin mRNA and protein generation were studied in atopic subjects using immunofluorescence, immunohistochemistry and in situ hybridization. Histamine‐induced expression of eotaxin mRNA and protein by endothelial cells was also measured, as was histamine‐induced eosinophil adhesion to cultured endothelial cells.Results
A rapid increase in degranulating cutaneous mast cells, together with a concomitant increase in eosinophils, was observed 60 min after allergen challenge. This was accompanied by the appearance of immunoreactive eotaxin that peaked at 1 h around blood vessels and at 3 h within the tissue. Intradermal histamine injection produced an increase in the number of eotaxin+ cells in the tissues, which was maximal at the 3‐h time‐point. In vitro, endothelial cells produced eotaxin mRNA and protein product in a dose‐ and time‐dependent fashion following incubation with histamine, an effect that was blocked by levocetirizine. Pre‐incubation of endothelial cells with histamine also induced a significant increase in eosinophil adherence, an effect that was inhibited with an anti‐eotaxin blocking monoclonal antibody.Conclusion
The antigen‐induced expression of eotaxin by endothelial cells and the adherence and subsequent migration of eosinophils from the microvasculature to the tissues are rapid events partially under the control of histamine released from degranulating mast cells.
Gene–gene interaction between interleukin‐4 and interleukin‐4 receptor α in Korean children with asthma
Authors: Lee S.‐G. , Kim B.‐S. , Kim J.‐H. , Lee S.‐Y. , Choi S.‐O. , Shim J.‐Y. , Hong T.‐J. , Hong S.‐J. 
Published: August 2004

AbstractBackground
Interleukin‐4 receptor α (IL‐4Rα), which binds IL‐4 and IL‐13, is involved in signal transduction of those cytokines that lead to IgE production, and is also a key functional component of the Th2 lymphocyte phenotype.Objective
To determine whether IL‐4 and IL‐4Rα polymorphisms are associated with susceptibility to asthma and whether there are gene–gene interactions between IL‐4 and IL‐4Rα polymorphisms.Methods
We genotyped three groups of Korean children, consisting of 196 atopic asthmatics, 60 non‐atopic asthmatics, and 100 healthy children, for an IL‐4 promoter polymorphism (C‐590T) and three IL‐4Rα polymorphisms (Ile50Val, Pro478Ser, and Arg551Gln) using PCR‐RFLP (restriction fragment length polymorphism) assays.Results
The allele frequencies of the IL‐4 (C/T) polymorphism and the Ile50Val and Pro478Ser polymorphisms of IL‐4Rα did not differ statistically among the three groups of children. For the Arg551Gln polymorphism, the combined genotype frequency of the Arg/Gln heterozygote and the Arg/Arg homozygote was significantly higher in atopic asthmatics (27.6%) than in healthy children (16.0%) (odds ratio (OR)=1.97, 95% CI (confidence interval)=1.07–3.71). The eosinophil fraction (%) and bronchial responsiveness were higher in children with the Arg/Gln and Arg/Arg genotype than in those with the Gln/Gln genotype (P=0.036 and 0.024, respectively). In asthmatic children, combinations of the IL‐4 CT/TT genotype and the IL‐4Rα Arg/Gln and Arg/Arg genotypes were associated with significantly increased risk for development of asthma (OR=3.70, 95% CI=1.07–12.78, P=0.038).Conclusions
In Korean children, the IL‐4Rα Arg551 allele may play a role in susceptibility to atopic asthma and correlate with markers of asthma pathogenesis, including increased eosinophil fraction and enhanced bronchial hyper‐responsiveness. In addition, a significant gene–gene interaction between the IL‐4‐590C and the IL‐4Rα Arg551 allele significantly increases an individual's susceptibility to asthma.
Bronchial hyper‐responsiveness to hypertonic saline and blood eosinophilic markers in 8–13‐year‐old schoolchildren
Authors: De Meer G. , Postma D. S. , Janssen N. A. H. , De Jongste J. C. , Brunekreef B. 
Published: August 2004

SummaryBackground
In adult asthma, bronchial hyper‐responsiveness (BHR) to indirect stimuli reflects eosinophilic activation more closely than BHR to stimuli that directly cause smooth muscle contraction.Aim
To assess the relationship between BHR to the indirect stimulus hypertonic saline (HS), blood eosinophil numbers, and serum eosinophilic cationic protein (ECP) in children with and without current wheeze.Methods
A cross‐sectional survey among 8–13‐year‐old schoolchildren, using the International Study of Asthma and Allergic disease in Childhood questionnaire, bronchial challenge with HS, skin prick tests, serum IgE, blood eosinophil counts and ECP (in a subset). Based upon the presence of current wheeze (WHE) and BHR, we defined three case groups (WHE+BHR+, WHE−BHR+, WHE+BHR−) and the reference group (WHE−BHR−). By regression analyses, each case group was compared with the reference group for differences in atopic sensitization, blood eosinophil counts and serum ECP.Results
Complete data were obtained for 470 children. BHR was present in 103 children (22%), 66 being asymptomatic and 37 symptomatic. Children of all three case groups were more often atopic. Sensitization to indoor allergens particularly occurred in children with BHR, irrespective of symptoms (P<0.05).Children with WHE+BHR+ had highest values for blood eosinophils and serum ECP (P<0.05). Children with WHE−BHR+ had less severe responsiveness. In atopic children with WHE−BHR+, serum ECP was higher than in children with WHE‐BHR‐(P<0.05).Conclusions
BHR to HS is associated with blood markers of eosinophilic activation, particularly in atopic children.
Differential modulation of human basophil functions through prostaglandin D2 receptors DP and chemoattractant receptor‐homologous molecule expressed on Th2 cells/DP2
Authors: Yoshimura‐Uchiyama C. , Iikura M. , Yamaguchi M. , Nagase H. , Ishii A. , Matsushima K. , Yamamoto K. , Shichijo M. , Bacon K. B. , Hirai K. 
Published: August 2004

SummaryBackground
Both prostaglandin (PG) D receptor (DP) and CRTH2 (chemoattractant receptor‐homologous molecule expressed on Th2 cells)/DP2 are high‐affinity receptors for PGD2. Previous studies have demonstrated that PGD2 enhances releasability and induces CRTH2/DP2‐mediated migration in human basophils, but the precise effects of PGD2 on basophils as well as receptor usage have not been fully clarified.Objective
We comprehensively explored the roles of DP and CRTH2/DP2 in basophil functions by using selective agonists and antagonists for each receptor.Methods
DP and CRTH2/DP2 transcripts were quantified by real‐time PCR. We studied the effects of selective agonists (DP: BW245C; CRTH2/DP2: 13,14‐dihydro‐15‐keto (DK)‐PGD2) and/or antagonists (DP: BWA868C; CRTH2/DP2: ramatroban) on Ca2+ mobilization, migration, degranulation, CD11b expression and survival of human basophils.Results
Basophils expressed transcripts of both DP and CRTH2/DP2, but the levels of CRTH2/DP2 transcripts were ca. 100‐fold higher compared with DP transcripts. Ca2+ influx was induced in basophils by either PGD2 or DK‐PGD2/CRTH2 agonist but not by BW245C/DP agonist. Basophils treated with PGD2 were completely desensitized to subsequent stimulation with DK‐PGD2, but not vice versa. DK‐PGD2 as well as PGD2 up‐regulated CD11b expression, induced migration and enhanced degranulation, and those effects were completely antagonized by ramatroban/CRTH2 antagonist. In contrast, BW245C/DP agonist exhibited an inhibitory effect on basophil migration and IgE‐mediated degranulation, and the migration inhibitory effect was effectively antagonized by BWA868C/DP antagonist. On the other hand, while PGD2 significantly shortened the basophil life‐span, neither DK‐PGD2/CRTH2 agonist nor BW245C/DP agonist did.Conclusion
CRTH2/DP2 is primarily responsible for the pro‐inflammatory effects of PGD2 on human basophils, while DP introduces negative signals capable of antagonizing the effects of CRTH2/DP2 in these cells. The effects of PGD2 on longevity imply a mechanism(s) other than via DP or CRTH2/DP2. CRTH2/DP2 on basophils may afford opportunities for therapeutic targeting in allergic inflammation.
The effect of supplementation with fish oil during pregnancy on breast milk immunoglobulin A, soluble CD14, cytokine levels and fatty acid composition
Authors: Dunstan J. A. , Roper J. , Mitoulas L. , Hartmann P. E. , Simmer K. , Prescott S. L. 
Published: August 2004

SummaryBackground
Breast milk contains many immunomodulatory factors (soluble CD14 (sCD14), IgA and cytokines) with the potential to influence infant immune development.Objective
To determine if changes in breast milk ω‐3 polyunsaturated fatty acid (n‐3 PUFA) composition as a result of maternal dietary fish oil supplementation during pregnancy can modify levels of these immunological parameters in breast milk.Method
In a randomized controlled trial, 83 atopic women received either 4 g fish oil capsules (containing 3.7 g n‐3 PUFA) (n=40) or 4 g olive oil capsules (n=43) from 20 weeks gestation until delivery. Breast milk was collected 3 days post‐partum and fatty acids were analysed by gas liquid chromatography and IgA, sCD14 and cytokines (IL‐5, IL‐6, IL‐10, TNF‐α and IFN‐γ) were quantitated by ELISA or time resolved fluorescence (TRF).Results
ω‐3 docosahexaenoic acid (DHA; 22:6n‐3) and eicosapentaenoic acid (EPA; 20:5n‐3) levels were significantly higher (P<0.001) in breast milk from women supplemented with fish oil (n=33, DHA mean 1.15%, SD 0.47% and EPA mean 0.16%, SD 0.07%) than in samples from the control group (n=40, DHA mean 0.50%, SD 0.17% and EPA mean 0.05%, SD 0.02%). Breast milk arachidonic acid (AA; 20:4n‐6) levels were significantly lower (P=0.045) in the fish oil group (mean 0.55%, SD 0.12%) compared with the control group (mean 0.61%, SD 0.14%). Breast milk IgA was positively correlated with DHA (P=0.046) and 22:5n‐3 (P=0.003), but inversely correlated with linoleic acid (LA; 18:2n‐6) (P=0.034). Levels of sCD14 were also positively correlated with 22:5n‐3 (P=0.009). Cytokines involved in IgA synthesis (IL‐10 and IL‐6) were also significantly correlated with both IgA and n‐3 PUFA levels, although there were no differences in the levels of breast milk IgA, sCD14 or cytokines between study groups.Conclusion
Supplementation with fish oil during pregnancy significantly alters early post‐partum breast milk fatty acid composition. ω‐3 PUFA levels were positively associated with IgA and sCD14 levels, suggesting a relationship between fatty acid status and mucosal immune function.
Urinary leukotriene E4 in Henoch–Schonlein purpura
Authors: Tsuji Y. , Abe Y. , Hisano M. , Sakai T. 
Published: August 2004

SummaryBackground
Children with Henoch–Schonlein purpura (HSP) occasionally have allergic disease. We have previously shown that pranlukast hydrate was effective for purpura in HSP. Pranlukast hydrate is a leukotriene (LT) receptor antagonist; therefore, it is likely that LTs take part in the cause of HSP. Urinary leukotriene E4 (LTE4u) levels are a useful index of whole‐body cysteinyl LT production in vivo. In this study, LTE4u was examined in children with HSP.Objective
The purpose of this study was to examine the relation between the level of LTE4u and the cause of HSP.Methods
Eighteen HSP children (six boys and 12 girls) and six healthy children were enrolled.Results
LTE4u levels in patients with HSP were significantly higher (P<0.05) at the onset than those in healthy children. Four weeks therapy with pranlukast hydrate lowers LTE4u levels in patients with HSP (P<0.05). There were no differences in LTE4u between the group of HSP patients with purpura nephritis and the group of HSP patients without purpura nephritis.Conclusion
These results indicate that csyteinyl LTs may play a role in the pathophysiology of purpura in HSP.
Interleukin‐4 increases murine airway response to kinins, via up‐regulation of bradykinin B1‐receptors and altered signalling along mitogen‐activated protein kinase pathways
Authors: Bryborn M. , Adner M. , Cardell L.‐O. 
Published: August 2004

SummaryBackground
IL‐4 is believed to play a role in asthma and chronic obstructive pulmonary disease through promotion of eosinophilic inflammation and mucus hypersecretion. Whether IL‐4 can induce a direct effect on airway smooth muscle remains unknown.Objective
To investigate the effect of IL‐4 on airway smooth muscle, focusing on the contractile response to des‐Arg9‐bradykinin and bradykinin.Methods
Tracheal segments from murine airways were cultured for 1–8 days in the absence and presence of IL‐4. The smooth muscle response induced by des‐Arg9‐bradykinin and bradykinin was investigated in myographs. Expression levels for the IL‐4‐, bradykinin B1‐ and B2‐receptors were characterized using RT‐PCR. Specific inhibitors were used to study signal changes along the IL‐4 receptor‐ (IL‐4R‐) coupled mitogen‐activated protein (MAP) kinase (MAPK) pathways.Results
IL‐4 treatment increased the contractile response to des‐Arg9‐bradykinin and bradykinin in a concentration‐ and time‐dependent manner. Dexamethasone and the transcriptional inhibitor actinomycin D blocked this effect. c‐Jun N‐terminal kinase inhibitor SP600125 also blocked the effect of both des‐Arg9‐bradykinin and bradykinin, whereas p38 inhibitor SB203580 blocked only the former and the MAPKK inhibitor PD098059, only the latter agonist responses. IL‐4 treatment increased the mRNA levels representing bradykinin B1‐ but not B2‐receptors. Levels of IL‐4R were not altered during culture.Conclusion
Long‐term exposure to IL‐4 increases the contractile response induced by des‐Arg9‐bradykinin and bradykinin in cultured murine airways. This effect appears to be mediated via an up‐regulation of B1‐receptors and altered signalling along the MAPK pathways.