Biomedical subjects
Publications and source records attributed to G Ciprandi.
A case of transverse colon volvulus is described. The authors illustrate the procedures adopted for diagnosing the condition, which are mainly radiological consisting in plain film of the abdomen and barium enema, where necessary. The treatment is invariably surgical: detorsion of the volvulus and colopexy, and resection of the transverse colon in the presence of ischaemic lesions or right hemicolectomy.
Patients with active Graves' disease almost constantly show phenotypic alterations of T lymphocytes, such as an increase of "activated" cells recognized by various surface markers (e.g. la antigens). Such alterations are present in a certain number of apparently cured patients. The data herein reported refer to 25 patients with Graves' disease in clinical remission, in whom we have attempted to correlate T cell subset imbalances, the presence of thyroid-stimulating antibodies (TSAb) and the outcome of the subsequent relapse. The results obtained show a significant association between TSAb and the increase of la-positive T cells: no relationship was found between TSAb and other T lymphocyte subsets. One-year clinical follow-up of the patients enabled us to see relapses of hyperthyroidism in only two patients, who had shown in the first control both TSAb positivity and increased la-positive T cells. These results, in our opinion, suggest a role of la antigens expression on T lymphocytes in the clinical course of Graves' disease.
The results obtained in vivo in a group of 24 patients treated with oral cromolyn and compared to a group of 10 patients treated with placebo are reported. All patients were affected by adverse clinical reactions (urticaria and/or angioedema) related to food ingestion. A significant reduction of signs and symptoms were observed after oral cromolyn therapy only in the patients affected by true food allergy (FA), i.e., IgE mediated reactions. No adverse reactions appeared in the treated patients. Because we found an enhancing effect exerted in vitro by cromolyn (SCG) on T-cell responsiveness in previous studies, in the present investigation we analyzed in more detail in vitro effects of SCG on T lymphocytes [i.e., phytohemagglutinin-induced interleukin-2 (IL-2) production] and IL-2 receptor expression on T cells. No significant effect was induced by SCG on IL-2 production, whereas IL-2 receptor expression on surface of T cells appeared significantly increased (P less than 0.001) by adding SCG in cultures. These clinical and immunological results are analyzed and discussed in relation to a possible in vivo effect(s) of cromolyn in allergic diseases.
Fifteen patients with cutaneous signs and symptoms caused by adverse reactions to foods were treated in an open trial with ketotifen for 4 to 6 weeks. Seven subjects were allergic and 8 had food intolerance. Each patient was treated with a single dose of ketotifen daily: 2 mg half an hour before going to sleep. Clinical improvement was achieved in 6 out of 7 allergic patients and in 6 out of 8 patients with food intolerance. Since several drugs have been demonstrated to have an influence on immune response, the in vitro effects of ketotifen on some immunological parameters were also studied. Ketotifen showed a significant inhibitory effect on autologous mixed lymphocyte reaction responsiveness.
The authors evaluated the in vitro effects of Bacillus subtilis on the following parameters of the immune response: mitogenic T cell proliferation (by PHA and OKT3) and mitogenic-induced lymphokine production (IL-2 and IFN-gamma). The spores of Bacillus subtilis did not influence the immune response, while its vegetative forms enhanced mitogenic-induced T cell proliferation. Both spores and vegetative forms did not modify lymphokine production.
The authors evaluated the clinical efficacy of an adjunctive treatment with spores of Bacillus subtilis in 20 adult patients with urticaria-angioedema syndrome from food allergy. The patients treated with B. subtilis showed a significant reduction in frequency and severity of clinical features in respect to the patients who received no treatment. Bacillus subtilis spores may increase S-IgA synthesis or protect gastroenteric mucosa.
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The proliferative responsiveness of T cells of aged individuals is known to be depressed in both autologous mixed lymphocyte reaction (AMLR) and in PHA-stimulated cultures. In the present study we confirm previous results and also report decreased IL-2 and normal IFN-gamma production (PHA-induced) in aged subjects as compared to young normals. In addition, similar percentages of T lymphocytes expressing surface IL-2 receptors both in the peripheral blood and after different stimulations, i.e. AMLR and PHA, were detected in young and aged individuals. The addition of exogenous IL-2 induces a sharp increase of spontaneous and AMLR proliferation in young individuals, whereas the increase is only slight in aged subjects. The experiments reported herein suggest that in general the T cell proliferation in AMLR is not completely dependent on the presence of IL-2 in the cultures and that aged subjects are probably defective in the production of other factor(s) presumably involved in AMLR proliferation, since the addition of exogenous IL-2 does not produce T-cell proliferation comparable to normal young subjects. The possible meanings of these experimental evidences in AMLR and in the defective immune responses of aged subjects are discussed.
The autologous mixed lymphocyte reaction (AMLR), i.e. the ability of T lymphocytes to proliferate when cultured with autologous non-T cell fractions, is an 'in vitro' phenomenon showing immunological memory and specificity, probably related to the cooperation ability of immunocompetent cells. We have evaluated AMLR in 27 patients with Graves' disease of varying clinical status (untreated and treated with antithyroid drugs, surgery or 131I). The results obtained show: Impaired AMLR in untreated patients (as in other autoimmune diseases). Significantly higher AMLR in cured patients, and that AMLR in cured patients varies with the treatment (higher after surgery or radioiodine than after medical treatment). These results are consistent with the hypothesis of a functional defect of T cells in Graves' disease, which improves when clinical remission is achieved.
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In previous reports we demonstrated imbalances of T cell subsets in patients with autoimmune thyroid disease. In the present investigation, we studied several T cell markers with different functional meaning (Fc gamma-receptors, HLA-Ia antigens, MLR4 and 5/9 antigens) in first degree relatives of Graves' disease patients. Our data suggest that imbalances of circulating T cell subpopulations are apparent only when abnormal hormone levels and/or thyroid autoantibodies are present.
Two cases of pretibial and atypical dermopathy in Graves' disease, showing many similarities in clinical pictures and natural histories, are reported. In both patients we observed abnormalities of some immunological parameters, namely reduction of Fc-positive T lymphocytes and positive TBI indexes. These abnormalities were concomitant to the appearance of dermopathy and apparently unrelated to other clinical manifestations of Graves' disease.
In allergic patients the authors previously observed high proportions of circulating T lymphocytes bearing Ia antigens, assumed to be "activated" T cells. In the present investigation they employed other T cell activation markers (4F2, insulin receptor, MLR4) which differ in the kinetics of appearance upon the surface of stimulated T cells. They report high proportions of Ia and 4F2-positive T cells, normal levels of MLR4-positive T lymphocytes and no insulin binding on T cells. However, T cells of allergic subjects are able to express insulin receptors in PHA-induced culture, such as normal subjects do. The authors conclude that these data, supported by similar observations in autoimmune diseases, indicates differences between in vivo and in vitro features of expression of T cell activation markers. In addition the autologous mixed lymphocyte reaction (AMLR) in atopic patients was studied. The results indicate that AMLR responsiveness is defective in allergic patients.
T cell subpopulations recognized by surfaces markers of different functional meaning have been evaluated in 12 female patients with euthyroid Graves' disease and in 2 patients with ophthalmopathy and Hashimoto's thyroiditis. We have used the following markers: i) receptors for Fc fragments of IgG; ii) antigens recognized by the monoclonal antibodies MLR4, 5/9, BT 2/9 (anti-DR). In the 12 patients with euthyroid Graves' disease a marked decrease of TG cells (which proved to exert suppressor function in several in vitro systems) was observed, as previously reported in hyperthyroid Graves' disease. The 2 Hashimoto's patients with eye changes had normal or high TG. 5/9+ T cells (which contain cells with helper activity in vitro), as well as MLR4+ and BT 2/9+ cells (activated T cells) were normal in the majority of patients, but elevated in the 2 Hashimoto's thyroiditis. The observed abnormality of TG cells in euthyroid Graves' disease might be consistent with the hypothesized autoimmune pathogenesis of endocrine ophthalmopathy.
Blood samples of patients with severe respiratory allergic diseases contain increased numbers of T cells bearing surface HLA-DR antigens, indicating the presence of activated T cells. In the same group of patients, MLR3 and MLR4, two monoclonal antibodies (Mab) directed to subsets of activated peripheral T cells, recognize T cell percentages within the normal range. Thus, it seems possible that specialized subsets of activated T cells (HLA-DR+/MLR3-MLR-) are represented in the peripheral blood of atopic patients. Such cells are lacking in patients after specific immunotherapy. Similar results--an increased percentage of 5/9+ T cells in untreated patients and normal counts of 5/9+ T cells in treated ones--were obtained in the two groups of patients by using another Mab, 5/9, which serves as a reliable marker of helper T cells in resting peripheral T lymphocytes. These data further support the concept of a T cell imbalance in allergic patients and suggest a possible role of specific immunotherapy in correcting the modification of peripheral T cell abnormalities.
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A rapid and simple enzyme-linked immunosorbent assay (ELISA) for anti-thyroglobulin IgG antibodies is described. The method is based on a 'sandwich' using purified human thyroglobulin adsorbed to polystyrene microplates, human serum and anti-human IgG antiserum conjugated to alkaline phosphatase. The sensitivity of the method is about 8 ng/ml, as evaluated with a purified anti-thyroglobulin antibody preparation. High concentrations of antibodies were observed, as expected, in autoimmune thyroid disease; however, the majority of normal subjects have detectable, although very low, antibody levels. We conclude the method is suitable for current clinical use.
Allergen-specific challenge was first shown to induce ICAM-1 expression on epithelial cells (ECs) of conjunctiva in allergic patients. The data have also been confirmed in the nose. We then checked for the presence of ICAM-1 consequent to natural exposure to allergens. For both conjunctivitis and rhinitis due to pollen we confirmed, during the pollen season, the presence of ICAM-1 on ECs. We demonstrated the endogenous source of ICAM-1 by in situ hybridization both in vitro and in vivo. ICAM-1 could be an activation marker on ECs, or could, enhanced EC susceptibility to bind offending cells such as eosinophils (LFA-1+). ICAM-1 is also a receptor for the vast majority of rhinoviruses, which are known to provoke, mainly in children, asthma attacks. Since we found that mite allergens can induce ICAM-1 on ECs, even during clinical latency, allergy may be considered as a primary event leading to asthma (through rhinovirus infection) and non-specific hyperreactivity.