Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eosinophil degranulation is a characteristic feature of asthma and allergic rhinitis. However, degranulated eosinophils have not been convincingly demonstrated in the common mouse models of these airway diseases. This study uses eosinophil peroxidase (EPO) histochemistry and transmission electron microscopy (TEM) analysis to assess eosinophil degranulation in the airways of ovalbumin (OVA)-sensitized and challenged BALB/c and C57BL/6 mice. Using TEM we also examined mouse and human blood eosinophils after in vitro incubation with formyl-Met-Leu-Phe (fMLP) or phorbol myristate acetate (PMA). Although OVA exposure induced significant nasal and lung eosinophilia, we did not observe any of the known cellular processes by which eosinophils release their granule products, i.e., eosinophil cytolysis, piecemeal degranulation, and exocytosis. The occurrence of other allergen-induced degranulation events was ruled out because no difference in granule morphology was observed between lung-tissue eosinophils and blood or bone-marrow eosinophils from control animals. Accordingly, there was no detectable extracellular EPO in lung tissues of allergic mice. Similarly, mouse blood eosinophils remained nondegranulated in vitro in the presence of fMLP and PMA, whereas the same treatment of human eosinophils resulted in extensive degranulation. This investigation indicates that OVA-induced airway inflammation in the present mouse strains does not involve significant eosinophil degranulation. It is speculated that this dissimilarity from the human disease may be due to a fundamental difference in the regulation of mouse and human eosinophils.
Am J Respir Cell Mol Biol 2001 Mar
PMID:Degranulation status of airway tissue eosinophils in mouse models of allergic airway inflammation. 1124 36

Interleukin (IL)-13 has been associated with asthma, allergic rhinitis, and chronic sinusitis, all conditions where an imbalance in epithelial fluid secretion and absorption could impact upon the disease. We have investigated the effects of IL-13 on the ion transport characteristics of human bronchial epithelial cells cultured at an apical-air interface. Ussing chamber studies indicated that 48 h pretreatment with IL-13 or IL-4 significantly reduced the basal short-circuit current (I(sc)) and inhibited the amiloride-sensitive current by >98%. Furthermore, the I(sc) responses were increased by more than six- and twofold over control values when stimulated with UTP or forskolin, respectively, after cytokine treatment. The IL-13-enhanced response to UTP/ionomycin was sensitive to bumetanide and DIDS and was reduced in a low-chloride, bicarbonate-free solution. Membrane permeablization studies indicated that IL-13 induced the functional expression of an apical Ca(2+)-activated anion conductance and that changes in apical or basolateral K(+) conductances could not account for the increased I(sc) responses to UTP or ionomycin. The results indicate that IL-13 converts the human bronchial epithelium from an absorptive to a secretory phenotype that is the result of loss of amiloride-sensitive current and an increase in a DIDS-sensitive apical anion conductance.
Am J Physiol Lung Cell Mol Physiol 2002 Feb
PMID:Interleukin-13 induces a hypersecretory ion transport phenotype in human bronchial epithelial cells. 1179 27

Atopic diseases such as asthma, rhinitis, eczema and food allergies have increased in most industrialised countries of the world during the last 20 years. The reasons for this increase are not known and different hypotheses have been assessed including increased exposure to sensitising allergens or decreased stimulation of the immune system during critical periods of development. In allergic diseases there is a polarisation of the Th2 response and an increase in the production of type 2 cytokines which are involved in the production of immunoglobulin E and the development of mast cells, basophils and eosinophils leading to inflammation and disease. The effector phase of atopy is initiated by interaction with Fc epsilon RI expressed on effector cells such as mast cells and basophils but also found on an ever increasing list of cells. Binding of a polyvalent allergen to the variable part of IgE leads to a cross-link of the receptor that triggers the cell to release histamine and pharmacological mediators of the symptomatic allergic response. Cross-linking of Fc epsilon RI by autoantibodies against the alpha-chain of the Fc epsilon RI, causing subsequent histamine release is thought to be involved in the pathogenesis of other diseases such as chronic idiopathic urticaria (CIU). To date, most therapeutic strategies are aimed at inhibiting and controlling components of the inflammatory response. Recently, new treatment strategies have emerged that focus on the development of preventive and even curative treatments. The most promising therapeutic approaches are aimed at inhibiting the IgE-Fc epsilon RI interaction with the use of non-anaphylactogenic anti-IgE or anti-Fc epsilon RIalpha autoantibodies. Clinical trials in humans using an humanised anti-IgE antibody showed that this antibody was well tolerated and reduced both symptoms and use of medication in asthma and allergic rhinitis. Thus interruption of the atopic cascade at the level of the IgE-Fc epsilon RI interaction with the use of non-anaphylactogenic antibodies is effective and represents an attractive therapy for the treatment of atopic disease.
Mol Aspects Med 2002 Dec
PMID:Molecular aspects of allergy. 1238 47

Atopic dermatitis (AD) is a genetically determinated, chronic inflammatory skin disorder associated with cutaneous erythema and severe pruritus, affecting 10-15% of children with increasing incidence and socio-economical relevance. Frequently, AD is associated with development of allergic rhinitis and/or asthma later in childhood. In most of patients AD is associated with a sensitization to food and/or environmental allergens and increased serum-IgE, while only a fewer percentage missed links to the classical atopic diathesis. Currently investigated pathogenetic aspects of AD include imbalanced Th1/Th2 responses, altered prostaglandin metabolism, intrinsic defects in the keratinocyte function, delayed eosinophil apoptosis, and IgE-mediated facilitated antigen presentation by epidermal dendritic cells. An inflammatory response of the two-phase-type and the effects of staphylococcal superantigens (SAgs) are also reported. At present a standardized cure of AD and a consensus on therapeutical approach of the severe form of the disease have not been established. Current management of AD is directed to the reduction of cutaneous inflammation and infection, mainly by S. aureus, and to the elimination of exacerbating factors (irritants, allergens, emotional stresses). Since patient with AD show abnormalities in immunoregulation, therapy directed to adjustment of their immune function could represent an alternative approach, particularly in the severe form of the disease. In this review, we analyse the clinical and genetic aspects of AD, the related molecular mechanisms, and the immunobiology of the disease, focusing our attention on current treatments and future perspectives on this topic.
Curr Mol Med 2003 Mar
PMID:Atopic dermatitis: molecular mechanisms, clinical aspects and new therapeutical approaches. 1263 May 59

Genentech, Novartis and Tanox have co-developed Genentech's anti-IgE humanized monoclonal antibody omalizumab for the treatment of allergic rhinitis and asthma. The antibody is currently undergoing phase II clinical trials for allergic rhinitis in Canada and phase III clinical trials for both indications in Japan. Omalizumab is at the pre-registration stage for both indications in the US, New Zealand, Switzerland and Western Europe, and is currently registered for both indications in Australia.
Curr Opin Mol Ther 2003 Feb
PMID:Technology evaluation: omalizumab, Genentech/Novartis/Tanox. 1266 76

We identified a novel heterozygous single-nucleotide substitution 1400 T right curved arrow C (Leu 467 Pro) in the seventh exon of the interferon-gamma receptor 1 (IFNGR1) gene. This substitution was detected in 6 of the 89 allergic patients but not in the 72 non-allergic subjects. There was a difference in the L467P frequency between the allergic patients and the non-allergic subjects (Fisher's exact test: p=0.033). The 6 patients with L467P have allergic diseases such as bronchial asthma and/or allergic rhinitis. Furthermore, a familial analysis for L467P revealed a linkage between allergic diseases and L467P. Serum IgE levels of the patients with L467P were higher than those of the non-allergic subjects (p=0.001). Our previous studies have been shown that interferon-gamma (IFN-gamma) production by PBMCs in the allergic patients was lower than that in the non-allergic subjects. In this study, although IFN-gamma production in the allergic patients with L467P was equivalent to that in the non-allergic subjects, their serum IgE levels were high and they had allergic diseases. Our results suggest that some allergic patients have IFNGR dysfunction, and that L467P in the IFNGR1 gene is one of candidate susceptibility genes for allergic diseases.
Int J Mol Med 2003 Aug
PMID:A novel single-nucleotide substitution, Leu 467 Pro, in the interferon-gamma receptor 1 gene associated with allergic diseases. 1285 15

BACKGROUND: We previously demonstrated in a group of patients with perennial allergic rhinitis alone impairment of spirometric parameters and high percentage of subjects with bronchial hyperreactivity (BHR). The present study aimed at evaluating a group of polysensitized subjects suffering from allergic rhinitis alone to investigate the presence of spirometric impairment and BHR during the pollen season. METHODS: One hundred rhinitics sensitized both to pollen and perennial allergens were evaluated during the pollen season. Spirometry and methacholine bronchial challenge were performed. RESULTS: Six rhinitics showed impaired values of FEV1 without referred symptoms of asthma. FEF 25-75 values were impaired in 28 rhinitics. Sixty-six patients showed positive methacholine bronchial challenge. FEF 25-75 values were impaired only in BHR positive patients (p < 0.001). A significant difference was observed both for FEV1 (p < 0.05) and FEF 25-75 (p < 0.001) considering BHR severity. CONCLUSIONS: This study evidences that an impairment of spirometric parameters may be observed in polysensitized patients with allergic rhinitis alone during the pollen season. A high percentage of these patients had BHR. A close relationship between upper and lower airways is confirmed.
Clin Mol Allergy 2004 Mar 14
PMID:Bronchial hyperreactivity and spirometric impairment in polysensitized patients with allergic rhinitis. 1501 19

Assessment of the value of exhaled NO (eNO) is an attractive tool for studying pulmonary disease, considering its wide advantages (i.e., fast analysis, noninvasive sampling, ability to measure large numbers of subjects [including children], and inexpensive in use). Increased concentrations of eNO have been observed in asthmatic patients' airway infections, allergic rhinitis, and bronchiectasis. During inflammation, specific and nonspecific stimuli elicit expression and de novo synthesis of inducible nitric oxide (iNOS). Once generated in the bronchiolar cells, NO is released from the tissue and diffuses to the lumen of the bronchiolis. Of the two sampling ways (on-line and off-line), the off-line method is suitable for monitoring environmental health effects of air pollution and for obtaining an impression of the prevalence of atopy in epidemiological surveys. For this off-line measurement, a balloon method is developed (sampling exhaled air at location) that includes a sample device assuring inflation of balloons at a controlled flow rate and back-pressure. Cigarette smoking and alcohol consumption significantly reduces NO levels in exhaled air because of downregulation of iNOS. Although eNO can be reliably measured and analyzed, the prospective value to detect asthma or allergy is rather low (low sensitivity and low specificity), which makes the diagnostic value of eNO for predicting either allergy or asthma doubtful. Promising results have, however, been observed in corticoid-sparing therapies under guidance of eNO. In addition, measurement of eNO helps to understand the mechanisms of pulmonary disease and may be useful in detecting adverse effects of air pollution.
Methods Mol Biol 2004
PMID:Measurement of exhaled nitric oxide. 1519 36

The family of T-cell immunoglobulin domain and mucin domain (TIM) proteins is identified to be expressed on T cells. A member of Tim family, Tim-3 (T cell immunoglobulin mucin 3) is selectively expressed on the surface of differentiated Th1 cells. Tim-3 might have an important role in the induction of autoimmune diseases by regulating macrophage activation and interacts with Tim-3 ligand to regulate Th1 responses. To determine the variation sites in the coding and promoter region of human Tim-3 gene, we performed variation scanning by direct sequencing using the genomic DNA isolated from the patients with asthma or allergic rhinitis and healthy controls without asthma and allergic rhinitis. We identified four single nucleotide polymorphisms (SNPs) including one novel SNPs (-1541C>T) and two variation sites (-1292_-1289delTAAA and -1282_-1278dupTAAAA) in the coding and promoter region of human Tim-3 gene in both the patients and healthy groups.
Exp Mol Med 2004 Jun 30
PMID:Molecular variations in Th1-specific cell surface gene Tim-3. 1527 40

Soy sauce (Shoyu) is a traditional fermented seasoning of East Asian countries and available throughout the world. We obtained polysaccharides from raw soy sauce, and showed the anti-allergic activities of these Shoyu polysaccharides (SPS) in vitro and in vivo. The present study determined whether oral supplementation of SPS is an effective intervention for patients with perennial allergic rhinitis. In a 4-week randomized, double-blind, placebo-controlled parallel group study, patients with mild perennial allergic rhinitis were treated with 600 mg of SPS (n=11) or placebo (n=10) each day. After 4 weeks of treatment with SPS, a reduction in symptom scores for runny nose, sore throat, and itchy eyes were significantly changed from the baseline within the group (p<0.05), but no change in these scores was observed over 4 weeks of treatment in the placebo group. However, differences in the symptom scores during the study period were not significantly different between the groups. The total symptom score, calculated from the sum of individual scores, showed a significant difference between the 2 groups after 4 weeks of treatment (p<0.05). The efficacy of global symptoms score, which was defined as the adjusted mean change from baseline during 4 weeks of treatment, also showed a significant improvement in the SPS group (p<0.05). An overall evaluation of the medication's effectiveness after 4 weeks treatment showed significant differences between the SPS- and placebo-treated groups (p<0.05). In conclusion, SPS of soy sauce improved the quality of life for patients with perennial allergic rhinitis, and soy sauce would be useful in an anti-allergic therapy utilizing everyday foods.
Int J Mol Med 2004 Nov
PMID:Quality of life improvement with soy sauce ingredients, Shoyu polysaccharides, in perennial allergic rhinitis: a double-blind placebo-controlled clinical study. 1549 61


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