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Biomedical subjects

M Bagnasco

Publications and source records attributed to M Bagnasco.

At least 127 records · Page 7Linked to original sources
PubMed1987

Pharmacologic treatment of adverse reactions to foods: comparison of different protocols.

The authors evaluated four different therapeutic protocols employing 80 adult patients with clinical symptoms (urticaria and/or angioedema) due to food ingestion. Thirty-seven patients were allergic. In these cases the diagnosis was made on the basis of simultaneous positivity of the following criteria: history, exclusion diet and challenge tests, positive prick tests, and a positive PRIST and RAST. The other 43 subjects were considered to have pseudo-allergic reactions (PSAR). The pharmacologic treatment was performed for 4 to 6 weeks and each patient had a free diet during the study. At the end of the treatment, both the patient and the allergist filled a score questionnaire concerning the clinical status in order to evaluate the clinical improvement. Our data indicate that anti-H1 antihistamines do not significantly differ from placebos, that oral cromolyn is more successful in food allergy than in PSAR patients (P less than .05), that ketotifen is helpful, and that the association of H1 and H2 anti-histamine drugs is even more effective. Finally, by considering the effect on the immune system exerted by these drugs, as recently demonstrated in our laboratory, a detailed balance of each therapeutic protocol is then analyzed.

Adolescent↗
PubMed1986

T cell nature of some lymphokine-activated killer (LAK) cells. Frequency analysis of LAK precursors within human T cell populations and clonal analysis of LAK effector cells.

The cell lineage of the lymphokine-activated killer (LAK) cells has been reinvestigated. Both T and non-T cells, isolated on the basis of rosette formation with sheep erythrocytes (E), generated LAK activity after 3-4 days of culture in recombinant interleukin 2 (rIL 2) in 8 different individuals tested. By applying a microculture technique which allows clonal expansion of virtually all E rosetting T cells, we further analyzed the frequency of clonogenic LAK precursors within T cell populations. Approximately 1 of 25 T cells was found to be a LAK precursor. Moreover, microcultures with LAK activity lysed both the natural killer-sensitive K562 cell line and the P815 target cells in the presence of phytohemagglutinin (PHA). Since cytolytic T lymphocytes capable of lysing P815 cells in the PHA-dependent assay were approximately 1/3, it is evident that only a minor subset of cytolytic T lymphocyte precursors can acquire LAK activity even in the presence of large amounts of IL 2. Several LAK clones obtained by limiting dilution were further expanded and analyzed for their phenotypic and functional properties. Twelve out of 14 clones analyzed expressed the T3+ T11+ phenotype whereas 2 were T3- T11+. All had maintained their original cytolytic pattern; moreover, the large majority of the T3+ clones produced IL 2 and interferon-gamma following PHA stimulation.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1986

T cell subsets and thyroid-stimulating antibodies in patients with Graves' disease in clinical remission.

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.

Antigens, Surface↗
PubMed1986

Oral cromolyn in food allergy: in vivo and in vitro effects.

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.

Administration, Oral↗
PubMed1985

Proliferation of T8-positive cytolytic T lymphocytes in response to thyroglobulin in human autoimmune thyroiditis: analysis of cell interactions and culture requirements.

These experiments were designed to analyze the involvement of T-lymphocyte subpopulations in autoimmune thyroid disorders such as Graves' Disease (GD) and Hashimoto's Disease (HD). In a first set of experiments, lymphocytes isolated from thyroid infiltrates or from peripheral blood of GD and HD patients were analyzed for the expression of various surface antigens. While HLA-DR + T cells were numerous among thyroid infiltrating T lymphocytes in both groups of patients, the proportions of T8 + cells (as defined by their reactivity with the B 9.4 monoclonal antibody specific for T8 surface molecule) were strikingly different in HD and GD. In the latter group of patients only 19% of infiltrating T cells were T8 +, whereas these cells represented approximately 50% in four HD patients. Given the previous demonstration that all T cells expressing T8 antigen are cytolytic T lymphocytes (CTL) or their precursors (CTL-P) in conjunction with the fact that lymphocytes from HD or GD patients are known to proliferate in vitro in response to human tg (Htg), we further analyzed the T-cell subset(s) responsible for in vitro proliferation to Htg. In these experiments, peripheral blood T lymphocytes purified from patients with GD or HD were cultured with 1 microgram/ml Htg and irradiated autologous T-depleted mononuclear cells as the source of antigen presenting cells (APC). The proportions of T8 + cells declined considerably during culture in GD patients, but at Days 6 to 9, T8 + cells represented as much as 51% of cultured T lymphocytes from patients with HD. Moreover, the majority of T8 + cells were medium-large size lymphoblasts. Removal of Htg at Day 6 resulted in both abrogation of proliferative responsiveness and in decreases of T8 + percentages. Further analysis of the cell interactions leading to T8 + cell proliferation in response to Htg showed that helper/inducer T cells, as defined by 5/9 antigen expression, were strictly required. Collectively, these features are reminiscent of the T-cell involvement in experimental autoimmune thyroiditis of mice and stress for the first time the potential role of CTL in tissue damage occurring in Hashimoto's thyroiditis.

Adult↗
PubMed1985

Autologous mixed lymphocyte reaction in Graves' disease: relationship to clinical status.

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.

Adult↗
PubMed1984

Incidence of T cell subset imbalance in relatives of Graves' disease patients.

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.

Adolescent↗
PubMed1984

Variations of thyroid hormones during total fasting in obese and in obese diabetic subjects.

Fasting and hypocaloric diets are known to induce a reduction of triiodothyronine (T3) and to increase reverse triiodothyronine (rT3) in normal and obese subjects. The effect of 8-day fasting was evaluated on T3, thyroxine (T4), free T4, rT3, TSH, immunoreactive insulin (IRI), thyroxine binding globulin (TBG) and glycemia in 21 obese subjects (5 males, 16 females) grouped according to the average starting blood glucose concentration in: group I, diabetic obese subjects (9 patients); group II, non diabetic obese subjects (12 patients). All patients had no history of recent weight loss due to dietetic therapy or drugs. Blood samples were drawn in the morning at 0, 2, 4, 6, 8 days after total caloric deprivation and 2 days after refeeding. A superimposable variation of weight and glucose concentration were seen in both groups. In addition, no difference was observed in ketone body excretion, SH, TBG, T4, free T4. In group II a significant decrease of IRI was observed during diet (p less than 0.05); T3 decreased (p less than 0.01) and rT3 increased (p less than 0.01) significantly. No variations in T3 and rT3 values were observed in group I. These results are consistent with a possible role of glucose metabolism in the genesis of the low T3 syndrome.

Adult↗
PubMed1984

Autoimmune thyroid disease: purification and phenotypic analysis of intrathyroid T cells.

A phenotypic analysis of T cells infiltrating the thyroid of patients with autoimmune thyroid disease (both Graves' disease and Hashimoto's thyroiditis) was performed. T lymphocytes were purified from mononuclear cells extracted from surgically removed tissue. The following markers were evaluated: la antigens, MLR4 antigen (expressed on activated T cells) 5/9 antigen (expressed on a subset of lymphocytes containing the whole "helper-inducer" activity in vitro), Fc gamma-receptors, B9 antigen (expressed by cytotoxic, or precursor of cytotoxic, T cells). We observed increased percentages of 5/9-, MLR4- and la-positive T cells with respect to peripheral blood in both HT and GD: on the contrary, in specimens from nonautoimmune thyroid diseases mononuclear infiltrate was minimal, and even T cell evaluation was not possible. In addition, B9- and Fc gamma-positive T cells were increased in Hashimoto's, but not in Graves' thyroid tissue, thus suggesting a different role of cytotoxic effector mechanisms in the two diseases.

Adult↗
PubMed1984

Thyroglobulin-induced T-cell in vitro proliferation in Hashimoto's thyroiditis: identification of the responsive subset and effect of monoclonal antibodies directed to Ia antigens.

Recently it was reported that the peripheral blood and thyroid gland of patients with Hashimoto's thyroiditis contain activated (Ia+ and/or MLR4+) T cells and high levels of 5/9+ ("helper") T lymphocytes. In normal individuals the 5/9 monoclonal antibody recognizes a T-cell fraction that includes all T lymphocytes with inducer activities. Here, circulating 5/9+ and 5/9- T lymphocytes were isolated from patients with Hashimoto's disease, and the proliferative response induced by human thyroglobulin was investigated. The results show that the total thyroglobulin-induced lymphocyte DNA synthesis is confined to the 5/9+ T-cell fraction. Further subfractionation of 5/9+ into MLR4+ and MLR4- cells clearly indicates that no substantial differences exist in their proliferative capacities. Whether 5/9, MLR4, and Ia antigens, all expressed on the thyroglobulin-responsive T-cell subset, are involved in thyroglobulin-induced cell proliferation, was also analyzed. Although both 5/9 and MLR4 monoclonal antibodies had no effect, complete inhibition of antigen-induced blastogenesis was observed upon addition of monoclonal antibodies (D1/12 and BT2/9) directed to common determinants of Ia antigens. This inhibitory effect was also observed when T or non-T fractions were separately incubated with the monoclonal antibodies before culture. These results indicate that in humans, as in animals, the major histocompatibility complex may play a role in autoimmune thyroiditis. The data show that (a) the thyroglobulin-induced proliferative response is confined to a subset (5/9+) of T lymphocytes and (b) Ia antigens are involved in thyroglobulin-induced lymphocyte DNA synthesis in Hashimoto's disease.

Adult↗
PubMed1984

Insulin binding on MOLT 4 cells: effect of a sulfonylurea.

Cultured neoplastic cell lines are widely considered an adequate model for insulin receptor studies. In this work the insulin receptor of a well-known continuous T-cell line (MOLT 4) was characterized. These cells showed specific insulin receptor with binding properties quite similar to those of other lymphoblastoid cells. Therefore, we used MOLT 4 receptor to evaluate the effect of the sulfonylurea glipizide on insulin binding. After a 24-hour preliminary incubation of cells with glipizide, we found a 44% increase of insulin receptor binding apparently due to an increase of insulin binding sites.

Cell Line↗
PubMed1984

Deficiency of the autologous mixed lymphocyte reaction in patients with autoimmune thyroid disease.

The proliferative response of T lymphocytes when cocultured with autologous non-T cells in the absence of any other stimulating substance has been termed the autologous mixed lymphocyte reaction (AMLR). The AMLR has been shown to be impaired in several autoimmune disorders, such as systemic lupus erythematosus, Sjögren's syndrome, and primary biliary cirrhosis. In this study we report marked deficiency in the AMLR in two autoimmune disorders: Hashimoto's and Graves' diseases. This impaired AMLR, probably related to previously described T cell subset imbalances, provides further evidence of altered interactions between the immunocompetent cellular subsets in patients with these pathological conditions. Additional preliminary observations suggest defective allogeneic mixed lymphocyte reactions as well.

Adult↗
PubMed1984

Activation of T lymphocytes and autologous mixed lymphocyte reaction in allergic patients.

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.

Adult↗
PubMed1983

Circulating T cell subsets in euthyroid Graves' disease.

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.

Adult↗
PubMed1983

Circulating T-cell subsets in Graves' disease: differences between patients with active disease and in remission after 131I-therapy.

In the present investigation some surface markers in peripheral blood T lymphocytes of patients with active Graves' disease and subjects in remission after 131I-therapy have been studied. We confirmed low TG levels in untreated patients and normal values in treated subjects. Increased percentages of DR+, MLR4+ (activated T cells), and 5/9+ (inducer-helper) T cells were detected in patients with active disease, thus indicating the presence of activated T cells and suggesting increased levels of helper T cells. High percentages of MLR4+ and 5/9+, but normal levels of DR+ were found in 131I-treated subjects. The different distribution of DR and MLR4 positivities on 5/9+ and 5+9-T cells confirm the different meaning of these two markers of the activation state. The imbalance of T-cell subsets found in 131I-treated subjects and the normal values observed in patients with hyperthyroidism due to toxic adenoma indicate that hyperthyroidism per se is not sufficient to explain the T-cell alterations. The possible meaning of these findings is discussed with respect to previous hypotheses on the pathogenesis of Graves' disease.

Adult↗