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M Bagnasco

Publications and source records attributed to M Bagnasco.

At least 109 records · Page 6Linked to original sources
PubMed1990

The effect of methimazole on the immune system is unlikely to operate directly on T lymphocytes.

It has been shown that the antithyroid drug methimazole (MMI) may affect B cells and possibly accessory cell function. In the present study we investigated in detail the effects of MMI on T cell in vitro proliferation. The following variables were evaluated: T cell proliferation following stimulation with phytohemagglutinin (PHA), and anti-CD3 or anti-CD2 monoclonal antibodies; interleukin-2 (IL-2) and gamma-interferon (gamma-IFN) production by PHA-stimulated T cells in bulk culture and by T cell clones; PHA-induced IL-2 receptor expression; LPS-induced interleukin-1 production by accessory cells. The results obtained failed to demonstrate any effect of MMI on T cells in vitro proliferation, whatever the activation pathway considered. In addition, IL-2 and gamma-IFN productions were substantially unaffected by the drug, as well as IL-1 production by accessory cells. However, a slight reduction of PHA-induced IL-2 receptor expression was observed. Although the hypothesis of an effect of MMI on some specialized T cell functions cannot be ruled out, it is likely that the supposed "immunosuppressive" effect of the drug does not concern primarily the T lymphocyte.

Cell Division↗
PubMed1990

Functional involvement of the LFA-1/ICAM-1 adhesion system in the autologous mixed lymphocyte reaction.

The integrin surface molecule termed lymphocyte functional antigen-1 (LFA-1), and its physiological ligand intercellular adhesion molecule-1 (ICAM-1), have been proven to play a relevant role in several immune reactions where cell-to-cell contact is required: these reactions include allogeneic mixed lymphocyte reaction (MLR) and direct cytotoxicity. In the present study, we show that monoclonal antibodies (mAbs) directed to LFA-1 as well as to ICAM-1 molecules are able to inhibit T cell proliferation in autologous MLR (AMLR). Such an in vitro reaction is generally considered a functional model of Ia-mediated immunocompetent cell cooperation, and is impaired in several pathological conditions. It is noteworthy that the LFA-1 molecule is largely represented on the T cell surface, whereas ICAM-1 is poorly expressed on resting T cells: autologous stimulation slightly increases ICAM-1 expression. Pretreatment studies indicate that the inhibitory effect of anti-ICAM-1 mAb on T cell proliferation in AMLR is exerted on responder T cells.

Antibodies, Monoclonal↗
PubMed1990

Genotoxicity of chromium compounds. A review.

This article reviews approximately 700 results reported in the literature with 32 chromium compounds assayed in 130 short-term tests, using different targets and/or genetic end-points. The large majority of the results obtained with Cr(VI) compounds were positive, as a function of Cr(VI) solubility and bioavailability to target cells. On the other hand, Cr(III) compounds, although even more reactive than Cr(VI) with purified nucleic acids, did not induce genotoxic effects in the majority of studies using intact cells. Coupled with the findings of metabolic studies, the large data-base generated in short-term test systems provides useful information for predicting and interpreting the peculiar patterns of Cr(VI) carcinogenicity.

Animals↗
PubMed1989

T cell activation via the CD2 molecule is associated with protein kinase C translocation from the cytosol to the plasma membrane.

T cell activation via the CD2 molecule involves phospholipase C and phosphoinositide hydrolysis. Here we demonstrate that the triggering of subclones of the human T leukemia Jurkat cell line by anti-CD2 as well as anti-CD3 monoclonal antibodies is able to induce activation (i.e. translocation from cytosol to cell membrane) of protein kinase C (PKC), which is dependent on the formation of 1,2-diacylglycerol from inositol 4-5-bisphosphate. The kinetics of PKC translocation parallels the rise in intracellular calcium following both CD2 and CD3 stimulations. These results further demonstrate that CD2 and CD3 activation pathways use similar signal transduction mechanisms.

Antibodies, Monoclonal↗
PubMed1989

Cholera toxin inhibits the increase in cytoplasmic free calcium induced via the CD2 pathway of human T-lymphocyte activation.

We investigated the action of cholera toxin on the intracellular ionized calcium [Ca2+]i increase induced by anti-CD2 and anti-CD3 monoclonal antibodies in the leukemic human T-cell line Jurkat. Cholera toxin inhibits in a dose-dependent manner these two pathways of human T-lymphocyte activation but with different half maximal inhibition doses (75 ng/ml for CD3, 30 ng/ml for CD2). This effect cannot be accounted for only by the increase in cAMP induced by cholera toxin because forskolin, which raises cellular cyclic adenosine monophosphate (cAMP) to the same levels, induced only a small inhibition of the [Ca2+]i increase in similar conditions. Cholera toxin induced a decrease in the surface expression of the CD3 molecule, suggesting a down-regulation of the CD3 molecules. On the other hand, the expression of CD2 remained unchanged. Cell surface disappearance of the CD3 molecule cannot account for all the inhibitory effects of cholera toxin because CD2 molecule expression was not affected (no modifications in the half maximal binding of anti-CD2 monoclonal antibodies). All together, these results suggest that cholera toxin acts on substrates, possibly G proteins, that could regulate the [Ca2+]i increase induced by anti-CD2 and anti-CD3 mAbs in Jurkat cells. In addition, the present study demonstrated that the rise in cellular cAMP partially inhibits the [Ca2+]i increase induced by anti-CD2 and anti-CD3 mAbs.

Antibodies, Monoclonal↗
PubMed1989

Mutagenicity of polycyclic aromatic hydrocarbon fractions extracted from urban air particulates.

Polycyclic aromatic hydrocarbon (PAH) fractions, purified from extracts of airborne particles collected in the area of Genoa municipality, were assayed for mutagenicity in the Salmonella/microsome test. PAH fractions accounted for only a portion of the total mutagenic activity and also displayed a different specificity of genetic activity, as compared to unfractionated material. The analysis of 224 samples collected from January 1986 to November 1987 in 10 different localities led to a large number of positive results in strain TA100 with S9 mix and, less frequently, also in TA98 without metabolic activation. Mutagenicity was related to the intensity of anthropogenic atmospheric pollution, and showed some seasonal variations, although it was not possible to discriminate particular sources of pollution on the basis of mutagenicity patterns. The mutagenic potency in TA100 (S9+) of airborne PAH fractions was significantly correlated with the concentration of individual PAHs in most of the monitored localities. The spectrum of mutagenicity of monthly samples pooled from several localities in S. typhimurium strains, with and without S9 mix, provided evidence for some contribution of nitro derivatives of PAHs or possibly also of other compounds present in the same fractions. The results obtained are discussed in view of their predictive value as indicators of potential health hazards, and of the reliability of this biological tool as a complement to chemical analyses in the evaluation of ambient air pollution.

Air Pollutants↗
PubMed1989

Effects of tetroxoprim and sulfadiazine on T lymphocyte proliferation and gamma-interferon production.

The in vitro effects exerted by tetroxoprim and sulfadiazine on T lymphocyte proliferation were evaluated at drug concentrations equal to and twice the plasmatic peak level of each drug. The two drugs did not exert any significant effect on spontaneous and mitogen (PHA) or monoclonal antibody (MAb anti-CD3) induced T lymphocyte proliferation at the studied concentrations, both when tested separately and combined. In addition the two compounds did not significantly interfere in gamma-interferon (IFN-gamma) production.

Adult↗
PubMed1989

Enhanced metabolic activation of chemical hepatocarcinogens in woodchucks infected with hepatitis B virus.

The metabolism of chemical carcinogens was investigated in liver preparations from 28 captive woodchucks (Marmota monax). Of these, 23 were naturally infected with the woodchuck hepatitis virus (WHV), and eight also had primary hepatocellular carcinoma (PHC). Twenty-nine parameters were investigated in liver subcellular fractions, including cross-reactivity with HBsAg, and biochemical parameters, such as gamma-glutamyl transpeptidase, cytochrome P-450 and microsomal monooxygenases (aryl hydrocarbon hydroxylase, ethoxycoumarin and ethoxyresorufin deethylases, aminopyrine and dimethylnitrosamine demethylases, and testosterone 7 alpha-, 16 alpha- and 6 beta-hydroxylases), uridine 5'-diphosphoglucuronosyl transferase, GSH and related enzymes (peroxidase, reductase and S-transferase), as well as other cytosolic enzyme activities (glucose 6-phosphate and 6-phosphogluconate dehydrogenases, NADPH- and NADH-dependent diaphorases, and DT diaphorase). In addition, liver preparations were used in order to quantify the metabolic activation into bacterial mutagens of five procarcinogens (aflatoxin B1, the pyrolysis products Trp-P-2 and MeIQ, 2-aminofluorene and dimethylnitrosamine) and the decrease of potency of three direct-acting mutagens (sodium dichromate, ICR 191 and 4-nitroquinoline 1-oxide). WHV infection produced a significant stimulation of carcinogen metabolism, as shown by the simultaneous change in detoxification parameters (GSH depletion) and activation indices (enhancement of microsomal monooxygenases and of procarcinogen activation into mutagenic metabolites). There were no significant differences between WHV-positive samples from animals without PHC and the noncancerous tissue of PHC-bearing animals, whereas a decrease of both activation and detoxification indices was recorded in the tumorous tissue. There was a considerable interindividual variability among WHV carriers, which was tentatively ascribed to genetic factors. Pregnancy was the only known factor influencing the results in WHV carriers. However, even by excluding pregnant animals, the effects on carcinogen metabolism produced by WHV infection were still statistically significant. These results, together with previous data obtained in humans, revealed that metabolic factors may play a role in the synergism between viral hepatitis and chemical hepatocarcinogens in the etiopathogenesis of PHC.

Animals↗
PubMed1989

Carcinogen metabolism studies in human bronchial and lung parenchymal tissues.

The pulmonary metabolism of xenobiotics was investigated by measuring the glutathione content and the activity of the aryl hydrocarbon hydroxylase, epoxide hydrolase, glutathione S-transferase, and uridine 5' -diphosphoglucuronosyl transferase enzymes in S-12 fractions of bronchial tree and peripheral lung parenchyma obtained at surgery from 21 patients. In parallel, the same preparations were used to assess either the activation of promutagens, i.e., benzo(a)pyrene, 2-aminofluorene, cyclophosphamide, and a cigarette smoke condensate, to metabolites reverting his- Salmonella typhymurium strains, or the decrease of direct-acting mutagens, i.e., sodium dichromate, 4-nitroquinoline N-oxide, epichlorohydrin, and ICR 191. As compared to bronchus preparations, parenchymal preparations contained considerably higher concentrations of reduced glutathione, had a significantly higher epoxide hydrolase activity, and, as assessed by means of a quantitative index, were more efficient in activating 2-aminofluorene and in reducing the mutagenicity of dichromate and 4-nitroquinoline N-oxide. These data may suggest that parenchymal lung tissue is more capable than bronchial tissue to detoxify reactive intermediates of xenobiotics, possibly explaining the greater susceptibility of bronchi to cigarette smoke-induced cancers.

4-Nitroquinoline-1-oxide↗
PubMed1989

Phenotypic and functional analysis at the clonal level of infiltrating T lymphocytes in papillary carcinoma of the thyroid: prevalence of cytolytic T cells with natural killer-like or lymphokine-activated killer activity.

We investigated the phenotype and function of thyroid tumor-, metastatic lymph node-, and peripheral blood-derived T lymphocytes of four patients with papillary thyroid cancer. Both phenotypic analysis of freshly isolated cells and clonal analysis, using a high efficiency cloning technique, were performed. For comparison, intrathyroid and peripheral blood T lymphocytes derived from patients with autoimmune thyroid diseases (Graves' disease and Hashimoto's thyroiditis) have been studied. In papillary cancer, the phenotype of thyroid and lymph node-derived T lymphocytes did not differ from that of peripheral blood lymphocytes of the same patients or lymphocytes from normal peripheral blood. At variance with respect to autoimmune thyroid disease, activation markers were poorly represented. The functional analysis of T cell clones showed similar proportions of interleukin-2-producing (helper-inducer) clones in thyroid, lymph node, and peripheral blood, slightly lower than in Hashimoto's thyroiditis and slightly higher than in Graves' disease. With regard to effector function, we found lower proportion of clones with cytolytic activity in a lectin-dependent assay compared to that in Hashimoto's thyroiditis. Interestingly, however, the proportions of cytolytic clones displaying cytolytic activity against the neoplastic cell line K562 (natural killer-like activity) or fresh unrelated tumor cells (lymphokine-activated killer activity) were relatively high in thyroid cancer infiltrates.

Adult↗
PubMed1988

T cell activation through different membrane structures (T3/Ti, T11, T44) and frequency analysis of proliferating and interleukin-2 producer T lymphocyte precursors in aged individuals.

It is well known that the proliferative responsiveness of T cells of aged subjects is depressed in both autologous mixed lymphocyte reaction (AMLR) and in PHA-induced cultures. In the present study we analyzed T cell activation through different stimulatory pathways (such as T3/Ti antigen receptor, T11 complex and T44 molecule). Moreover, we studied Interleukin-2 (IL-2) release performing a limiting dilution analysis of the proliferative capability of peripheral blood T cells, employing a high efficiency cloning technique. Our results demonstrate normal proliferation of T3-induced T cells in aged subjects, whereas T11- and T44-induced T cell proliferations are depressed in aged subjects. In addition, studies at clonal level reveal a normal percentage of IL-2 producer T cell in aged individuals. In conclusion, our data suggest that the T cell in aged subjects are normal in number, but they have a decreased capacity of lymphokine production.

Adult↗
PubMed1988

Graves' disease: phenotypic and functional analysis at the clonal level of the T-cell repertoire in peripheral blood and in thyroid.

We have investigated at the clonal level the repertoire of intrathyroid and peripheral T lymphocytes in three patients with Graves' disease using a high efficiency cloning technique. Clonal efficiencies ranged from 10 to 31% for intrathyroid, and from 19 to 100% for peripheral T cells. In Graves' disease the phenotypic analysis showed similar percentages of CD3+ CD4+ CD8- and CD3+ CD4- CD8+ clones in thyroid infiltrates and peripheral blood. The functional evaluation showed similar or lower proportions of cytolytic clones in thyroid infiltrates with respect to peripheral blood. Furthermore, the proportions of intrathyroid and peripheral T-cell clones capable of releasing interleukin-2 and/or gamma-interferon in response to mitogen stimulation were similar. Finally, 44% of intrathyroid clones were neither cytolytic nor able to release IL-2 and gamma-interferon. These results are strikingly different from those obtained in Hashimoto's thyroiditis, where the large majority of intrathyroid T-cell clones are cytolytic and the proportions of clones able to release gamma-IFN are remarkably increased in thyroid infiltrates when compared to those obtained from peripheral blood. Taken together, these data suggest a different role for T lymphocytes in the pathogenesis of the two major human autoimmune thyroid diseases.

Adult↗
PubMed1987

Glycoproteic nature of surface molecules of effector cells with lymphokine-activated killer (LAK) activity. Evidence that T11, T8 or T3 molecules are not involved in tumor-cell lysis by LAK effector T cells.

Human peripheral blood mononuclear cells cultured in the presence of interleukin-2 (IL-2) acquire the capability of lysing NK-resistant fresh tumor target cells. In an attempt to delineate the surface structure(s) present on the effector cells, the latter were first treated with different amounts of pronase and neuraminidase. The effect of the enzymes on cytolytic activity against fresh melanoma cells was evaluated and compared with the NK-like activity against K562 target cells of the same effector population. At a pronase concentration of 0.01 mg/ml, no inhibition of NK-like activity was detected, whereas LAK activity was inhibited by more than 75%. In addition, neuraminidase had no effect on NK-like activity, even at 1 U/ml, whereas as little as 0.03 U/ml inhibited LAK activity by more than 75%. Metabolic inhibition of N-linked glycosylation with Tunicamycin prevented the generation of LAK activity, even when added late (18 hr before termination of the culture). Tunicamycin, on the other hand, had no effect on the boost of NK activity induced by IL-2. Provided that LAK activity can also be generated in T-cell (E-rosetting) populations, in the presence of adherent cells, we analyzed the inhibitory activity of monoclonal antibodies (MAbs) to T11, T3 and T8 molecules. While all these MAbs strongly inhibited the specific target cell lysis by alloreactive CTLs, they had no effect on the LAK activity.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

Occurrence of lymphocyte proliferative response to thyroglobulin and antithyroglobulin antibodies in normal individuals: lack of correlation with HLA.

Peripheral mononuclear cells (MNC) of patients with autoimmune thyroid disease have been shown to proliferate when cultured with human thyroglobulin (hTg). In addition, such a phenomenon is apparent in a certain number of healthy individuals. In this study we have attempted to correlate hTg-induced MNC proliferation, occurrence of anti-hTg autoantibodies and HLA phenotype (including Class II DR and DQ loci) in a population of HLA-typed normal blood donors. Fourteen out of 56 subjects showed a significant MNC proliferation to hTg. Three of them had anti-hTg autoantibodies in the serum, while none of the hTg-unresponsive subjects showed such antibodies. No correlation with HLA phenotype (including Class II DR5 specificity, referred as associated with Hashimoto's thyroiditis, and DQ alleles) was observed.

Adult↗
PubMed1987

Clonal analysis of T lymphocytes infiltrating the thyroid gland in Hashimoto's thyroiditis.

T cells isolated from thyroid tissue and peripheral blood of 2 patients with Hashimoto's thyroiditis were studied by a high cloning efficiency microculture technique. Clonal efficiencies of 37 and 24% were obtained from thyroid-derived T cell cultures, while 40 and 90% efficiencies resulted from peripheral-blood-derived cultures. A prevalence of T4-/T8+ T cell clones were found in thyroid infiltrates. The functional analysis of the clones demonstrated significantly higher proportions of clones with cytolytic activity in a lectin-dependent assay in thyroid-derived microcultures, as compared to peripheral blood-derived ones. The proportion of clones displaying natural-killer-like activity was increased in 1 patient only. Cytolytic activity was displayed not only by all T4-/T8+, but also by several T4+/T8- intrathyroid clones. Remarkable proportions of cytolytic clones were also able to release interleukin-2 upon phytohemagglutinin stimulation. Finally, the proportion of T cell clones able to release gamma-interferon following mitogen stimulation was significantly higher in thyroid- vs. peripheral-blood-derived microcultures. These results provide further data about the possible pathogenetical role of both regulatory and effector T lymphocytes in human autoimmune thyroiditis.

Adult↗
PubMed1987

T cell activation surface markers and autologous mixed lymphocyte reaction do not differ in true and pseudo food allergy.

Eighteen patients affected by itching, urticaria, eczema, angioedema, and asthma related to food-stuff intake were studied and classified in two groups (true food allergy and pseudoallergy) on the basis of clinical data, skin prick tests, total and specific IgE levels (PRIST and RAST) and double-blind challenge test. Autologous mixed lymphocyte reaction (AMLR) and T cell activation markers were thought to be tests possibly useful to discriminate between 'true' food allergy and 'pseudoallergy'. The present study failed to show either a significant increase in T cell activation markers (MLR4, Ia) or a significant decrease in AMLR proliferation in such subjects as compared to normal controls. In addition, we found no differences between 'true' allergic and 'pseudoallergic' patients on the basis of the parameters evaluated. Although the AMLR defect was reported both in asthma and in dermatitis, and therefore was thought to be related to atopy, the present data do not confirm this hypothesis in 'true' food allergy.

Adult↗