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Biomedical subjects

C Zanussi

Publications and source records attributed to C Zanussi.

At least 73 records · Page 4Linked to original sources

Prevalence of late-onset adrenal hyperplasia in postmenarchal hirsutism.

The response of plasma 17-hydroxyprogesterone (17-OHP) to exogenous ACTH was investigated in 85 consecutive women referred for postmenarchal hirsutism, in order to assess the prevalence of late-onset adrenal hyperplasia due to 21-hydroxylase deficiency and its relevance to the clinical practice. An exaggerated response of plasma 17-OHP to ACTH, indicating 21-hydroxylase deficiency, was found in only one patient with a prevalence of 1.1%. The patient with late-onset adrenal hyperplasia presented signs of virilism and had high basal levels of 17-OHP. On the basis of our results, late-onset adrenal hyperplasia accounts for a very small proportion of cases of hirsutism; moreover, from this and previous studies it is apparent that the determination of basal plasma 17-OHP may be sufficient to discover late-onset 21-hydroxylase deficiency. Therefore, we do not consider ACTH testing an advisable step in the routine screening for hirsutism.

Adolescent↗

Heterogeneity of immune responsiveness in healthy elderly subjects.

We studied a group of healthy elderly subjects (satisfying the SENIEUR Protocol admission criteria), chosen as a model of age-associated immune deficiency on the basis of their reduced skin reactivity to recall antigens. Results show that aged subjects, taken as a whole, display impaired T-cell functions: reduced blastogenetic responses to mitogens, IL-2 production, responsiveness to exogenous IL-2, and percentage of Tac positive blasts. However, the age-associated immune defect shows a wide range of impairment, even in a relatively homogeneous group of anergic/hypoergic subjects. In fact, a considerable proportion of our elderly subjects displays responses comparable with those of adult controls. These observations suggest that (a) immune deficiency is not a characteristic of aging per se; (b) cutaneous delayed hypersensitivity is not a criterion sensitive enough to identify people with age-associated immune deficit; and (c) more than one test is required to evaluate T-cell impairment in aging.

Aging↗

In vivo immunopotentiating activity of thymopentin in aging humans: modulation of IL-2 receptor expression.

The effect of thymopentin treatment was investigated in immunocompromised elderly subjects. Thymopentin was able to increase IL-2 production and IL-2 receptor expression, as assessed on PHA-activated blasts by percentage of Tac-positive cells and response to exogenous IL-2. After treatment, an increased precursor frequency, estimated by limiting dilution analysis, of PHA-responding lymphocytes was observed in two out of six subjects tested. In vitro experiments with thymopentin show that the drug was able to enhance blastogenesis by PHA of elderly lymphocytes but not of adult cells. These results indicate that (a) the increased IL-2 synthesis/IL-2 receptor expression may be the crucial mechanism of the immunopotentiating activity of the drug in elderly subjects and (b) an increased intrinsic T-cell responsiveness seems to be responsible for this immunopotentiating activity, although an increase in the size of the responsive T-cell pool could not be excluded.

Adjuvants, Immunologic↗

Effects of cyclosporin A on in vitro lymphocyte response to autologous or allogeneic stimulation: influence of HLA phenotypes.

In this study we investigated whether the interindividual variability of lymphocyte sensitivity to cyclosporin A (CsA) could be controlled by the HLA region. The models used were the in vitro primary and secondary autologous (AMLR) and allogeneic mixed lymphocyte (MLR) cultures of cells from 32 healthy subjects from our HLA reference panel. Our results show that CsA inhibited primary allogeneic MLR to a much greater extent than primary AMLR (-81 +/- 2% vs -38 +/- 8%, P less than 0.001). The same pattern was observed when cells harvested from CsA-treated primary cultures were rechallenged in secondary cultures with the original sensitizing stimulator cells (-40 +/- 6% vs -17 +/- 9%, P less than 0.05). No differences were observed in primary autologous and allogeneic cultures among responders of different HLA phenotypes. In contrast, the secondary responses did vary according to the HLA types: in secondary AMLR, CsA-priming did not lower, or even enhance, the proliferative responses of DR5+ and/or DR2+ lymphocytes (+7 +/- 13%), whereas it significantly lowered the responses of DR2-5- cells (-46 +/- 8%). In secondary MLR, lymphocytes proliferation was lowered by CsA-priming in all but DRW11(5)+ subjects (-45 +/- 7% vs +2 +/- 23%, P less than 0.05). It is concluded that the individual HLA phenotype influences the pattern of lymphocyte sensitivity to CsA.

Adult↗

In vitro and ex vivo effect of RU41740 on human polymorphonuclear leukocyte function.

We investigated the effect of RU41740, a glycoprotein extracted from Klebsiella pneumoniae and possessing immunomodulating properties, on human neutrophil functions in vitro and ex vivo. Our in vitro results showed that RU41740 increased complement- and Fc receptor-dependent phagocytosis. Moreover, the drug enhanced the oxidative metabolism (assessed by chemiluminescence) both in resting and stimulated cells; in the latter case the RU41740-induced enhancement was observed when neutrophils were stimulated with opsonized particles of N-formyl-methionyl-leucyl-phenylalanine (FMLP) but not when phorbol myristate acetate was used. Using otherwise effective experimental conditions, RU41740 did not affect spontaneous or FMLP-induced neutrophil migration. For the ex vivo experience we tested neutrophils of ten elderly subjects with a previously demonstrated phagocytic defect. These subjects were treated orally with RU41740 at a daily dose of 2 mg for 1 week during the first month, and of 1 mg for 1 week in the second month. In this population, RU41740 was able to restore the impaired phagocytic activity and to induce a significant increase of spontaneous chemiluminescence (CL); stimulated CL was also positively influenced. These effects on neutrophils provide new explanatory bases for the immunostimulatory activity of RU41740.

Adjuvants, Immunologic↗

HLA-associated susceptibility to AIDS: HLA B35 is a major risk factor for Italian HIV-infected intravenous drug addicts.

Thirty-one AIDS patients were typed for HLA A, B, C, and DR antigens. We confirmed that frequency of B35 is significantly higher in patients than in controls. No significant frequency differences in other HLA antigens were found. The analysis of HLA distribution in AIDS patients by risk categories suggests that B35 is a major risk factor, primarily mainly for patients belonging to the category of intravenous (IV) drug addicts.

Acquired Immunodeficiency Syndrome↗

Mediators and allergic inflammation of human airways.

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.

Adult↗

Cord blood basophil releasability: evaluation of histamine release and leukotriene C4 generation.

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.

Antibodies, Anti-Idiotypic↗

Food allergies.

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Food Hypersensitivity↗

Cord blood basophil releasability: a predictive marker for allergy?

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.

Adult↗

Activity of substance P on human skin and nasal airways.

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.

Adult↗

Clinical reliability of diagnostic tests in allergic rhinoconjunctivitis.

To determine the diagnostic value and precision of the quantitative skin test (QST), RAST, specific nasal (NPT) and conjunctival (CPT) provocation tests, we studied 91 patients, suffering from allergic rhinoconjunctivitis with positive skin prick tests (SPT) to common allergens, among whom sixty-nine of them had symptoms related to the positive SPT, and 22 had no clinical correspondence. In these two groups, by comparing the threshold of positivity, we investigated whether there was any parallelism between responses to the tests considered. We also compared the level of specific IgE (RAST) to the wheal-areas evoked by preliminary SPT for the corresponding allergen in order to detect any quantitative relationship between these investigations. Increasing concentrations of standardized allergen extracts (from 10 to 100,000 BU/ml) were used in all in vivo tests. NPT was evaluated on the basis of multiple recordings of nasal resistances by anterior passive rhinomanometry. QST proved to correlate well with RAST and its easier method ensures it a major role in assessing the levels of allergic sensitization. SPT wheal-areas and RAST vales correlated well only for grass and birch, presumably because of better standardization of these allergen extracts. When provocation tests, especially NPT, were positive, patients were almost always symptomatic for the allergen tested (high positive predictive value). Likewise, 21 out of the 22 asymptomatic subjects had negative NPT (high specificity). These results suggested the utility of standardized provocation tests in order to restrict diagnosis to the truly causative allergens in patients with multiple positive SPT results.

Adolescent↗

Relationship between anti-cardiolipin and anti-endothelial cell antibodies in systemic lupus erythematosus.

Anti-endothelial cell antibodies (AECA) have been detected in 51 lupus sera by cell surface radioimmunoassay with a prevalence of 39.2% for IgG and 45.1% for IgM-AECA. No correlations were found between AECA and different clinical or laboratory parameters, including the presence of anti-cardiolipin antibodies and signs associated with the presence of anti-phospholipid antibodies. However, absorption with cardiolipin liposomes partially inhibited endothelial cell binding, and affinity purified anti-cardiolipin antibodies were able to react with intact human endothelial cells. The binding did not occur via Fc receptors since blocking of Fc receptors with rabbit IgG did not affect the endothelial cell reactivity. Taken together our findings support the hypothesis that antibodies directed against negatively charged phospholipids can be part of the anti-endothelial cell antibodies in certain lupus sera. The possible role of these cross-reacting antibodies in the pathogenesis of vascular thrombosis in lupus patients is discussed.

Antibodies↗

Silybin inhibition of human T-lymphocyte activation.

Silybin, a 3-oxyflavone occurring in the thistle Silybum marianum, displays a dose-dependent inhibition of in-vitro lymphocyte blastogenesis induced by lectins (phytohaemagglutinin, Concanavalin A and pokeweed) and by anti-CD3 monoclonal antibody. The drug has no effect on cell viability and spontaneous 3H-thymidine incorporation, suggesting that the inhibitory activity is not due to aspecific toxicity. Since all the T-cell responses investigated require cell-membrane-associated events, the effect of silybin is probably at the level of the cell membrane, as for other flavonoids. Addition of CuSO4 prevents the inhibitory activity of silybin on PHA-induced proliferative response, indicating that the drug could exert its activity also by virtue of a chelation mechanism.

Antibodies, Monoclonal↗

Inhibition of neutrophil oxidative metabolism by nimesulide.

Oxygen derived free radical release from activated neutrophils may be in part responsible of tissue damage in the acute phase of inflammation. We have shown that the methane sulfonanilide antiinflammatory agent nimesulide inhibits the respiratory burst of phagocytosing neutrophils without affecting their phagocytic or chemotactic responsiveness. In fact, chemiluminescence and superoxide anion generation by polymorphonuclear leukocytes (PMN) stimulated with zymosan particles or with the synthetic peptide FMLP are inhibited by nimesulide and its 4-OH metabolite in a dose dependent fashion without affecting cell viability. The control of the extracellular flux of radical species by pharmacological compounds may affect the course of inflammation reducing tissue damage. Our data suggest that the inhibition of superoxide anion production by neutrophils is an additional mechanism of action of the antiinflammatory agent nimesulide.

Anti-Inflammatory Agents, Non-Steroidal↗