Evidence for an impairment of the immune-adrenal circuit in patients with acquired immunodeficiency syndrome.
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Biomedical subjects
Publications and source records attributed to C Zanussi.
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Congenital heterozygous dysfibrinogenemia was diagnosed in a young woman with bleeding tendency. 3 other asymptomatic members of her family (mother and the 2 sisters) had abnormal fibrinogen. The proposita's plasma exhibited prolonged thrombin and reptilase times. Plasma fibrinogen concentration determined by functional assay was 0.3 g/l, whereas immunologic assay revealed normal fibrinogen levels. Turbidity curves, representing the rate of thrombin-induced fibrin formation, were markedly delayed both in the presence and absence of Ca2+. Isoelectric focusing and SDS electrophoresis of reduced fibrinogen showed normal charge and size of the subunit chains. Release of fibrinopeptide B by thrombin was normal, whereas HPLC elution diagrams of fibrinopeptide A showed an abnormal peak A* with a slightly shorter retention time than the normal fibrinopeptide A. The amino acid analysis showed that the arginine in peak A* is replaced by histidine (A alpha 16 Arg----His).
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The relationships between autoantibodies to soluble cellular antigens and clinical features in systemic lupus erythematosus (SLE) were investigated in a large clinical-serological study. The absence of these precipitins in serum was associated with a low prevalence of vasculitis and membranous nephropathy (MGN). Other significant findings were the associations between nRNP antibody and Raynaud's phenomenon and MGN, SSB antibody and sicca complex, PCNA antibody and a young age at onset, and Bu antibody and an old age at onset. However, the most impressive findings were in DA1-positive patients which showed a unique prevalence of photosensitive skin lesions, lymphoadenopathy and hepatosplenomegaly. The present study confirms the usefulness of antibodies to soluble cellular antigens in the classification of patients with SLE.
The behaviour of some serological aspects of autoimmunity was studied in patients with inflammatory bowel disease (IBD) by determining the incidence and levels of serum IgM, IgG and IgA rheumatoid factors (RF) and of circulating immune-complexes (IC) in 67 patients suffering from ulcerative colitis (UC) and 53 from Crohn's disease (CD). Sera from 40 young healthy subjects were included as controls. RF were detected by an enzyme linked immuno-assay (ELISA) and IC by the CIC-conglutinin and the CIC-C1q assays. ELISA detected a higher incidence of IgM RF in both UC and CD groups than the routine agglutination tests, although the mean levels were non significantly higher than in controls. Mean IgG RF levels were significantly above normal in UC and CD patients, the latter showing a greater incidence of elevated values and higher mean levels. IgA RF were significantly elevated only in CD patients; mean values for the UC group were within the normal range. The CIC-conglutinin test did not detect a significant incidence or high mean levels of IC and the CIC-C1q assay turned up a sizeable number of positive samples only in the CD group. Although still only preliminary, these overall findings suggest that RF activity is somehow present in patients with IBD. The greater prevalence of IC in CD patients, together with the patterns of IgG and IgA RF support the concept that this disease possibly involves autoimmune phenomena more than ulcerative colitis.
Foremost among the various mechanisms which have developed during the evolution of living creatures are those taking place during the inflammatory process, triggering defense mechanisms vs. chemical, physical and biological toxic agents. The present review aims at explaining some of the physiopathological mechanisms which play a role during inflammation.
Sera from patients affected either by the classic/Mediterranean form (5 patients) and human immune deficiency virus (HIV)-associated (12 patients) form of Kaposi's sarcoma (KS) were compared in supporting endothelial cell in-vitro proliferation. Healthy blood donors (15) and a group of 7 HIV-positive drug addicts with no dermatological involvement were used as control groups. Endothelial cell growth was assessed by means of a [3H]thymidine incorporation and by an optical density direct cell-counting assay. Our results indicate that, at the highest concentrations, sera obtained from patients affected by KS with no sign of HIV infection induced significantly higher levels of endothelial cell proliferation when compared with HIV-associated KS and with normal controls. This growth-promoting activity was apparently cell selective, being present in endothelial cell but not in fibroblast cultures.
A new simplified radioassay for measuring polymorphonuclear leukocyte (PMN) chemotaxis is proposed using 51Cr-labeled cells and a single-filter system. The technique offers all the advantages described for the double-filter radioassay and permits a reproducible measurement of random locomotion, chemokinesis and chemotaxis. Moreover the single-filter radioassay utilizes commercially available and disposable chambers gathered in a multichamber apparatus; this makes the method very easy to learn and rapid to perform.
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The aim of the study was to check whether, after a period of complete exclusion of the offending foods in adult subjects suffering from food allergy, these foods could subsequently be safely reintroduced into the diet. Patients with chronic urticaria and/or perennial rhinitis negative for secondary pathology or other allergies were subjected to a strict diagnostic protocol for food allergy. Briefly, out of a case list of 207 patients, we found 23 patients whose symptoms were clearly related, on open reintroduction, to at least one food. The really offending foods in these patients were subsequently identified by double-blind, placebo-controlled food challenges. Only 10 of the 23 patients had positive challenges for 13 foods. Double-blind challenges were repeated after 1 year or more of avoidance of the offending foods to evaluate the persistence or disappearance of sensitivity. We found that five (38%) of the 13 previously offending foods were well tolerated. Thus, in adults, as previously proved in children, dietary avoidance of the offending foods appears to be an effective measure for dealing with food allergy. The kind of foods involved and the completeness of their avoidance appeared to be important factors favoring the reestablishment of tolerance in adults.
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 efficacy of hyposensitization with a standardised extract of Dermatophagoides pteronyssinus (D. pteronyssinus) conjugated to alginate and containing known amounts of antigen P1 (Conjuvac) was tested in a double blind, placebo controlled, multi-centre study in 66 adult patients with perennial rhinitis. Patients received 11 weekly injections of increasing concentrations of Conjuvac containing from 56 x 10(1) to 448 10(3) IU D. pteronyssinus or placebo injections of the alginate diluent to some of which 5 micrograms of histamine has been randomly added. This was followed by 15 monthly injections of Conjuvac or placebo. The severity of nasal blockage, sneezing and rhinorrhoea was recorded twice daily in a diary and visual analogue assessments (VAS) made at each clinic visit. Nasal provocation testing (NPT) was performed with increasing concentrations of the same extract of D. pteronyssinus as used in the hyposensitization injections, and changes in nasal airways resistance measured by passive anterior rhinomanometry. VAS was recorded and NPT was performed on entry to the study and after the fifth, ninth and final monthly injection. Conjuvac injections were well tolerated. Large local reactions (greater than 5 cm) occurred within 30 min in only 1% of patients but later in 23%. No systemic reactions or anaphylaxis occurred within 30 min of injections, but urticaria or worsening of asthma and rhinitis was reported later in 3% of patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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.
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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.
Literature data show that TRH may have either stimulatory or inhibitory actions on GH release according to pathophysiological conditions of the subject. In view of this dual effect of TRH, we studied the possible interaction of TRH and GRF on GH secretion. Six healthy male volunteers received iv in different occasions and in random order: 1) GRF 0.05 micrograms/Kg; 2) GRF 0.1 micrograms/Kg; 3) GRF 1 microgram/Kg; 4) GRF 0.05 micrograms/Kg + TRH 400 micrograms, simultaneously; 5) GRF 0.05 micrograms/Kg + TRH 20 micrograms, simultaneously; 6) GRF 1 microgram/Kg + TRH 400 micrograms, simultaneously, 7) the vehicle as control treatment. Blood samples were obtained at several time intervals and plasma GH, PRL and TSH were measured by RIA methods. Plasma GH significantly increased in all subjects after all the tested doses of GRF and after the combination of the highest and of the lowest doses of GRF + TRH (treatments 6 and 5). GH responses increased progressively with the dose of GRF administered, even if a clear dose-response relationship could not be demonstrated, owing to the considerable interindividual variability in the responsiveness. The administration of GRF 0.05 micrograms/Kg increased significantly plasma GH levels vs control treatment. The simultaneous administration of a low effective dose of GRF (0.05 micrograms/kg) plus a high dose of TRH (400 micrograms) was able to significantly inhibit the GH secretion elicited by GRF 0.05 micrograms/Kg alone. The other GRF + TRH combinations tested (treatments 5 and 6) did not modify the GH response to the same doses of GRF given alone. Plasma PRL and TSH did not change either after GRF at any dose or after the vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)