Biomedical subjects
Publications and source records attributed to A Tedeschi.
Having briefly recalled the close functional interaction of diseases which often involve both syplay between skin and kidney, the authors suggest a new model for the nosographic classificastems and are at present observed with increasing frequency.
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Clonidine, a common antihypertensive agent, was recently shown to inhibit antigen-induced wheal and flare reactions, as well as allergen-evoked bronchoconstriction in allergic patients. In this study we investigated the in vitro anti-allergic properties of clonidine. This alpha 2 adrenoceptor agonist inhibited, in a dose-dependent fashion, basophil histamine secretion elicited by anti-IgE and f-met peptide; it also blocked, though to a lesser extent, the calcium ionophore A23187-induced histamine release. H2 receptor stimulation seems to be responsible for the reduction in histamine release observed, since it can be antagonized by cimetidine, but not by alpha 1, alpha 2 and H1 blockers.
The steps of the morphological relapse occurring during gluten-challenge in coeliac children were for the first time investigated by scanning electron microscopy and compared with the morphological changes observed in untreated and treated coeliac patients, in pathological and normal controls. Some peculiar morphological changes, not reported up to now, were observed in treated and relapsed coeliac patients. No relationship was found among the degrees of mucosal atrophy observed by SEM and the duration of the challenge performed by an uncontrolled ingestion of gluten.
Transmembrane calcium flux is a critical step in basophil and mast cell activation and subsequent histamine release. This calcium flux is likely to take place through specialized membrane ion channels. Two types of calcium channels have been described so far: the first type is voltage operated and the second type is receptor operated. Depolarization of cell membrane by K+-rich solutions is followed by voltage-operated channel opening in excitable cells, such as smooth muscle cells. We evaluated whether high K+ extracellular concentrations can trigger basophil activation and histamine release. We found that human basophil leucocytes, showing a normal response to activating signals, such as anti-IgE antiserum and formylmethionine peptide, release no histamine when exposed to K+-rich media, alone or in combination with the K+ carrier valinomycin. These results are consistent with there being receptor-operated, but not voltage-operated, calcium channels in the basophil leucocyte plasma membrane.
Lyso-PAF-acether and PAF-acether (formerly platelet-activating factor) were detected in nasal secretions from patients with hay fever who underwent local antigen challenge. Lyso-PAF release was observed in 12 of 13 patients, with a maximum (p less than 0.001) 5 min after stimulation and a progressive decrease during the first hour. PAF was detected in the 5-min postchallenge nasal washings from two of 13 subjects. After HPLC, this mediator was found in four of seven postchallenge nasal washings submitted to this procedure, with a peak 5 min and 10 min after provocation. Histamine analysis revealed a significant (p less than 0.001) but time-limited (5 min) release in nasal secretion. The pattern of immunoreactive leukotriene C4 showed a maximal peak (p less than 0.01) 5 min after allergen provocation, with raised levels for 20 min. Nasal stimulation with nebulized saline solution or grass pollens in healthy subjects and in patients suffering from allergic rhinitis caused by Dermatophagoides pteronyssinus was followed by no local mediator release. These data indicate that, in addition to histamine and peptide-leukotrienes, lyso-PAF and PAF are released in nasal secretions after local antigen stimulation in patients with hay fever, with a preponderance of lyso-PAF response. On the basis of these results, it is conceivable that these ether-phospholipids may be involved in allergic inflammation of human nasal airways.
Immunological challenge of human lung parenchyma causes formation of arachidonate metabolites: prostaglandin D2 (PGD2) (70% of the formed mediators), leukotrienes E4 (LTE4) (15%) and D4 (LTD4) (10%). Leukotriene B4 (LTB4) was barely detectable (2%). Inhibition of PGD2 formation by indomethacin (15 microM) was approximately 90%, but was not accompanied by redistribution of arachidonate metabolism towards sulphidopeptide leukotrienes, as postulated for aspirin-sensitive asthma. Specific binding sites for leukotrienes C4 (LTC4) have been identified in membrane preparations of human bronchi. Binding of 3H-LTC4 is rapid (1 min) and quickly reversible following addition of excess. The sites are specific for LTC4 and competition curves fitted a two-site model. Moreover, clinical studies on specific endobronchial challenge of patients allergic to Dermatophagoides pteronyssinus, revealed narrowing of bronchial diameter and oedema of the bronchial mucosa; these symptoms were accompanied by an increase of immunoreactive-LTC4 and PGD2 present in the bronchial lavage fluids.
When human polymorphonuclear basophils, a type of white blood cell with antibodies of the immunoglobulin E (IgE) type on its surface, are exposed to anti-IgE antibodies, they release histamine from their intracellular granules and change their staining properties. The latter can be demonstrated at dilutions of anti-IgE that range from 1 x 10(2) to 1 x 10(120); over that range, there are successive peaks of degranulation from 40 to 60% of the basophils, despite the calculated absence of any anti-IgE molecules at the highest dilutions. Since dilutions need to be accompanied by vigorous shaking for the effects to be observed, transmission of the biological information could be related to the molecular organization of water.
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The distribution pattern of some labelled lectins (WGA, SBA, PNA, DBA, ConA, LCA) has been investigated in small intestinal mucosa of coeliac children (119 cases) and normal (short stature) and pathological (postenteritis syndrome) controls. The oligosaccharide side chains of glycoproteins present in the cytoplasm and in the brush border of enterocytes, goblet cells and luminal crypt surface have been revealed. The most important differences in lectin binding reactivity between coeliac and controls mucosae are discussed.
In the present study we investigated the effect of substance P, bombesin, beta lipotropin, alpha and gamma endorphins, and metionin and leucin enkephalins on in vitro histamine release from partially purified human lung mast cells and peripheral blood basophils. In the concentration range of 10-100 microM, these neuropeptides and endogenous opioid peptides neither elicited a significant histamine secretions from human lung mast cells and blood basophils, nor influenced the anti-IgE-induced histamine release. These data indicate that human lung mast cells and blood basophils are resistant to the activity of substance P, bombesin, beta lipotropin, alpha and gamma endorphins, and metionin and leucin enkephalins, and confirm the functional heterogeneity of mast cells, depending on the species and the tissue origin.
Local antigen challenge in patients with respiratory allergy is associated with histamine and arachidonic acid metabolites release, both in upper and in lower respiratory airways. Raised histamine levels can be detected in nasal secretions 5 min after allergen stimulation. Increased leukotriene C4 and prostaglandin D2 concentrations persist for a longer period (respectively 20 and 30 min). Endobronchial antigen stimulation is also followed by release of histamine, leukotriene C4 and prostaglandin D2, which can be detected in bronchial lavage fluid. Elevated concentrations of these mediators can be found 5 and 15 min after challenge. Moreover, endobronchial antigen stimulation is associated with an increase in the number of bronchial epithelial cells recovered in bronchial lavage fluids.
This study was performed to evaluate mediator (histamine and leukotriene C4) release from cord blood and adult blood basophils, challenged with IgE-independent (calcium ionophore A23187) and IgE-mediated (anti-IgE) stimuli. IgE-independent mediator release was similar in adult blood and umbilical blood basophils. Conversely, the anti-IgE-induced histamine and immunoreactive leukotriene C4 (iLTC4) release was significantly reduced in cord blood basophils. Passive sensitization with an IgE-rich serum was followed by a significant increase in the number of eluted IgE molecules from cord blood basophils and by an increase in IgE-mediated histamine release. iLTC4 production was not affected by passive sensitization of umbilical blood basophils. The IgE-dependent mediator release from cord blood basophils was not correlated with the number of cell-bound IgE. In addition, histamine secretion and leukotriene C4 production from cord blood basophils seem to be independent events.
Liberation of histamine and LTC4 by cord-blood basophils was measured in the newborn from healthy and atopic parents. The cord-blood basophils of the second classification produced more histamine than those from the first, after challenge with anti-IgE. Thus, a newborn from atopic parent(s) probably carries more fixed IgE on the basophils than a newborn from healthy parents and so the capacity of cord-blood basophils to liberate mediators may be a good marker of allergy.
Nasal challenge and intradermal injection with substance P (SP) were performed in five normal subjects and in five patients suffering from allergic rhinitis. No clinical symptoms, local histamine release, or modifications of nasal airway resistance were observed when SP was insufflated in the nose. Conversely, intradermal injection with SP caused a wheal and flare reaction in all the studied subjects. The different response to SP is likely to be due to the heterogeneity of human skin and nasal mucosa mast cells as far as sensitivity to histamine-releasing agents is concerned. Our findings indicate that SP has no relevant effect on human nasal mucosa, even if a synergetic action of SP with other allergic mediators cannot be excluded. The role of SP in the pathogenesis of allergic diseases in humans remains to be defined and deserves further study.
By means 55 cases of HCC in Varese district, according to international Studies, the Authors try to value the absolute risk of falling sick of HCC.
The role of mediators in allergic inflammation of respiratory airways has recently been elucidated through the development of experimental systems for in vivo evaluation of hypersensitivity reactions in humans. Antigen challenge in hay-fever patients has been shown to be associated with the release of histamine, kinins, peptidoleukotrienes, leukotriene B4 and prostaglandin D2 in nasal secretions. Endobronchial antigen stimulation in asthmatic patients has been shown to induce local release of histamine, prostaglandin D2 and leukotriene C4. The effects of inflammatory mediators seem to be different: nasal challenge with histamine causes rhinorrhea, itching, sneezing and nasal obstruction, whereas local stimulation with leukotriene C4 and prostaglandin D2 induces only a marked obstruction. Bronchial provocation with histamine is associated with smooth muscle contraction, hypersecretion, vasodilation and increase in vascular permeability. Leukotriene C4 or prostaglandin D2 inhalation induces a marked bronchoconstriction. On molar basis, the potencies of these arachidonic acid derivatives are respectively about 1000 fold and 30 fold higher than that of histamine. Mast cells seem to play a pivotal role in the pathogenesis of immediate allergic responses, whereas eosinophils, neutrophils and basophils seem to be mainly involved in late phase reactions. Since paf-acether is a potent chemotactic factor for eosinophils and neutrophils, it is reasonable to suppose that this lipid mediator is generated during the immediate allergic reaction and is involved in the appearance of late phase responses.