Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In recent years, studies of the regulation of the airways have focused to an increasing degree on the roles of neuropeptides. Several peptides have been shown to be present in airways and mediate such diverse responses as ion transport, mucus secretion, bronchospasm or relaxation, edema, cough, changes in vascular permeability, and neutrophil chemotaxis. More recently, studies have described the roles of peptidases, most notably neutral endopeptidase (NEP, also known as enkephalinase, or E.C. 3.4.24.11) and kininase II (also known as angiotensin-converting enzyme, or E.C. 3.4.15.1) in modulating peptide-induced responses. The enzymes cleave a wide variety of peptides, generating metabolites that are inactive in the systems studied to date. Thus inhibitors of NEP potentiate responses to peptides that are cleaved by it. Therefore, NEP plays roles in modulating peptide-induced effects analogous to the role of acetylcholinesterase in modulating cholinergic neurotransmission. In several experimental respiratory diseases, the activity of neutral endopeptidase is decreased, resulting in increased responses to peptides. The therapeutic application of recombinant NEP protects the airways from the adverse actions of stimuli that release inflammatory peptides, and induction of the NEP gene expression by glucocorticoids suggest a possible mechanism for the action of these steroids in treating airway diseases such as asthma, chronic bronchitis, or cystic fibrosis.
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PMID:Roles of neutral endopeptidase in airways. 201 45

Neutral endopeptidase exists on the membranes of many cells in the airways. By cleaving and thus inactivating tachykinins released from sensory nerves, NEP limits the actions of these peptides. The selectivity of the enzyme is due, at least in part, to its close association with tachykinin receptors. By cleaving and inactivating the tachykinins, it limits the concentration of tachykinin that reaches the receptor. Decreased NEP activity produced by selective enzyme inhibitors, air pollutants, infections, and oxidants leads to exaggerated neurogenic inflammation. We speculate that the multiple stimuli that enter the airways of healthy individuals normally produce small, nonsymptomatic neurogenic inflammatory responses. However, when NEP activity is decreased, the responses become exaggerated and may contribute to the pathogenesis of diseases such as asthma and bronchitis.
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PMID:Decreased neutral endopeptidases: possible role in inflammatory diseases of airways. 216 84

We investigated 10 healthy control subjects, 15 asthmatics without occupational exposure to isocyanate, and 45 "isocyanate workers" with workplace-related respiratory symptoms. In none of the cases did the skin test or the IgE-RAST reveal a type I sensitisation to isocyanate. The investigation programme included a lung function test, provocation with metacholine or acetylcholine, and an isocyanate challenge test under controlled clinical conditions. A total of 17 "isocyanate workers", and 1 asthma patient with no occupational exposure to isocyanate revealed a positive bronchial obstructive reaction to the isocyanate challenge test. In 10 of the patients, the MCH (ACH) test was positive; 2 were chronically obstructive, but 6 patients showed no signs of bronchial hyperreactivity. No significant differences in the severity of the bronchial obstructive reaction induced by isocyanate exposure were observed between patients with and those without bronchial hyperreactivity. In the group of "isocyanate workers", the isocyanate challenge test was observed to be superior to the MCH (ACH) provocation test in terms of sensitivity (0.68 versus 0.62) and specificity (1.0 versus 0.61), this difference being more obvious in the overall group (sensitivity 0.71 versus 0.62; specificity 0.98 versus 0.49).
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PMID:[Diagnosis of irritative-toxic isocyanate asthma with the isocyanate exposure test]. 236 73

Neuropeptides such as substance P are implicated in inflammation mediated by sensory nerves (neurogenic inflammation), but the roles in disease of these peptides and the peptidases that degrade them are not understood. It is well established that inflammation is a prominent feature of several airway diseases, including viral infections, asthma, bronchitis, and cystic fibrosis. These diseases are characterized by cough, airway edema, and abnormal secretory and bronchoconstrictor responses, all of which can be elicited by substance P. The effects of substance P and other peptides that may be involved in inflammation are decreased by endogenous neutral endopeptidase (NEP; also called enkephalinase, EC 3.4.24.11), which is a peptidase that degrades substance P and other peptides. In the present study, we report that rats with histories of infections caused by common respiratory tract pathogens (parainfluenza virus type 1, rat corona-virus, and Mycoplasma pulmonis) not only have greater susceptibility to neurogenic inflammatory responses than do pathogen-free rats but also have a lower activity of NEP in the trachea. This reduction in NEP activity may cause the increased susceptibility to neurogenic inflammation by allowing higher concentrations of substance P to reach tachykinin receptors in the trachea. Thus decreased NEP activity may exacerbate some of the pathological responses in animals with respiratory tract infections.
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PMID:Neutral endopeptidase and neurogenic inflammation in rats with respiratory infections. 254 62

A significant correlation between the degree of bronchial reactivity to ACH, Hi and A.E. was found in a series of 23 dogs. An increase in receptors sensitivity responsible for the organic manifestation of allergy must be assumed. This increased receptors sensitivity is an important phenomenon in asthma clinically relevant.
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PMID:The correlation between allergen, acetylcholine and histamine-induced bronchoconstriction. 653 73

In a double blind 3-year prospective study 40 grass pollen allergic patients were allocated to specific immunotherapy (hyposensitization) with two timothy major allergens, 19, 25, or partially purified timothy extract. The extracts were biologically standardized and coupled to aluminium hydroxide for treatment. Efficacy of hyposensitization was evaluated by titrated nasal provocations and skin prick tests with the two treatment extracts and a five-gram mixture. The threshold dose for skin prick test (skin thresholds) produced reactions identical to histamine chloride 5.43 mmol/l and the threshold dose for nasal provocations (nasal thresholds) produced two of the three reactions: at least 0.5 ml of nasal secretion, at least five sneezes, and/or at least a 20% fall in nasal peak flow. Nasal thresholds showed highest efficacy from partially purified timothy extract but equal protection against timothy and the five-grass mixture. Nasal thresholds of 14 untreated patients corresponded to treatment with the two major allergens. Changes in skin and nasal thresholds after 12 and after 54 weeks of treatment predicted the severity of hay fever. Increase in nasal thresholds coincided with a marked effect on asthma. Nasal thresholds below 1 HEP before treatment predicted major systemic side effects.
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PMID:Nasal and skin sensitivity during immunotherapy with two major allergens 19, 25 and partially purified extract of timothy grass pollen. 681 82

Basic benefit and attendance benefit to children in Norway have increased substantially in recent years. In 1992 more than 2% of children 0-15 years of age received benefits totalling NOK 350 million. The main reason for the increase seems to be that more and more children are suffering from allergic diseases, like asthma and eczema. Cohort analyses give reason to believe that allergic diseases among children will continue to increase in the years to come. Ways of dealing with the problem have recently been proposed in a publication from the health authorities. In order to evaluate the effectiveness of programmes that are implemented, a monitoring system has been suggested based on a current analysis of the prevalence of children who receive basic and attendance benefits because of allergic diseases.
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PMID:[Basic and attendance benefits to children--extent and medical causes]. 807 22

Extracts modified with glutaraldehyde (allergoid) have been offered to allergologists for immunotherapy in the last few years as supposedly clinically effective agents that diminish undesirable side-effects (allergenicity vs. immunogenicity). In order to acquire experience in the use of this therapeutic resource, we monitored a group of patients with pollinosis sensitive to Olea, grass pollens or both, who suffered from seasonal rhinoconjunctivitis (SRC) or rhinoconjunctivitis and seasonal asthma (RCSA) and were administered allergoid treatments standardized in biological units (HEP). The patients were monitored by determination of specific IgE and IgG4, endpoint prick tests and conjunctival provocation tests (CPT) with two types of antigen: Lolium perenne and Olea europaea. Measurements were made at baseline (T1), when the maximal tolerated dose had been given (T2) and 1 year after the treatment was started (T3). According to our results, this type of extract is tolerated quite well and causes no alterations in specific IgG4 or IgE levels. On the other hand, it features significantly decreased allergen-specific skin reactivity and increased response thresholds to the CPT (p < 0.01). A high correlation between skin and conjunctival provocation tests was observed at some stages (r = 0.79, p < 0.01).
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PMID:Linear monitoring of patients sensitive to Olea and grass pollens treated with immunotherapy based on glutaraldehyde-modified (allergoid) extracts. 828 51

We comparatively studied clinical efficacy, tolerance and modifications of different in vivo and in vitro parameters induced by two biologically standardized Dermatophagoides pteronyssinus extracts (HEP units), one glutaraldehyde-modified, in patients with allergic rhinitis and/or bronchial asthma after a year of treatment. A decrease in drug consumption was observed in both treatment groups (p < 0.0001). Of all the in vivo parameters studied (cutaneous, conjunctival and bronchial reactivity to the allergen), a decrease in specific bronchial reactivity was only observed in the group treated with the modified extract (p < 0.05). The modifications in total IgE, specific IgE and specific total IgG levels are superimposable on those described in previous papers on immunotherapy. However, IgG4 levels remained stable with respect to time. Tolerance was good and very similar for both treatments; both types of extracts are equally efficacious and safe.
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PMID:Immunotherapy with a standardized Dermatophagoides pteronyssinus glutaraldehyde-modified extract against an unmodified extract: a comparative study of efficacy, tolerance and in vivo and in vitro modification of parameters. 865 20

We tested peptide immunotherapy in cat-allergic humans, using a formation of two synthetic peptides, IPC-1 and IPC-2, each of which is 27 amino acids long and contains T cell-reactive regions of Fel d 1, the major cat allergen. In this exploratory, randomized, double-blind, parallel-group study, 42 subjects received s.c. injections of treatment peptides 250 micrograms or placebo weekly for four consecutive weeks. Changes in immediate- and late-phase skin test reactivity, and in antigen-driven cytokine synthesis were assessed. Epicutaneous (end-point titration) and intradermal tests were performed with cat extract (ALK SQ Cat Hair) containing Fel d 1, before the first injection, then 2, 6 and 24 weeks after the fourth and last injection of peptides or placebo. IL-4, IL-10 and IFN-gamma expression by circulating peripheral blood mononuclear cells (PBMC) in response to cat extract was measured using short-term bulk culture of PBMC and short-term limiting dilution analysis. Subjects who received peptide immunotherapy did not tolerate significantly more cat extract containing Fel d 1 in the skin tests 2, 6 or 24 weeks after the last injection than they did at baseline, and their late-phase responses did not decrease significantly compared to baseline. Substantial IL-4, IL-10 and IFN-gamma responses were observed following primary culture of cat antigen-stimulated PBMC; however, the intensity of cytokine synthesis and the IFN-gamma: IL-4 ratio were unchanged in peptide- and placebo-treated groups 6 and 24 weeks after the last injection. A few hours after the injections, subjects receiving peptides reported more allergic rhinitis and asthma symptoms and more pruritus than those receiving placebo. We conclude that under the conditions tested, peptide immunotherapy did not reduce immediate- or late-phase skin reactivity to cat extract containing Fel d 1 or modify cat antigen-specific cytokine production significantly.
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PMID:Fel d 1 peptides: effect on skin tests and cytokine synthesis in cat-allergic human subjects. 898 78


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