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Biomedical subjects

M Bagnasco

Publications and source records attributed to M Bagnasco.

At least 19 recordsLinked to original sources
PubMed1992

Expression of very late activation antigen-1 on intrathyroid lymphocytes in autoimmune thyroid disease.

Very late activation antigen-1 (VLA-1) is a beta 1-integrin implied in interaction with extracellular matrix components. It is expressed by T lymphocytes upon prolonged activation in vitro. In this work we have evaluated VLA-1 expression in thyroid infiltrates and peripheral blood of patients with autoimmune thyroid disease (AITD), by immunofluorescence on dispersed cells and by in situ analysis on frozen tissue sections. The results obtained showed increased proportions of VLA-1 positive lymphocytes in thyroid infiltrates, similarly to that observed with "early" activation antigens. No positivity of thyroid follicular cells was observed. Given the role of the VLA-1 molecule in lymphocyte adhesion, the increased VLA-1 positivity of infiltrating lymphocytes is consistent with intrathyroidal homing of long-term activated cells, possibly relevant to AITD pathogenesis.

Adult↗
PubMed1992

Metabolic alterations produced by cigarette smoke in rat lung and liver, and their modulation by oral N-acetylcysteine.

Male Sprague-Dawley rats were exposed whole-body to the mainstream smoke produced by a commercial filter cigarette for 8 consecutive days, accounting for a cumulative exposure to the smoke of 75 cigarettes. Liver and lung S12 fractions were used in the Salmonella mutagenicity test in order to assess either the decrease of potency of a direct-acting mutagen (sodium dichromate) or the metabolic activation of promutagens, including cigarette smoke itself and its condensate, benzo[a]pyrene and its 7,8-diol, the aromatic amine 2-aminofluorene, and the heterocyclic amine 3-amino-1-methyl-5H-pyrido(4,3)indole. Moreover, individual biochemical parameters were measured in the liver and lung of the same rats and, in the case of cytochrome P-450-dependent monooxygenases, also in the heart of untreated or Aroclor-treated rats. The monitored biochemical parameters included aryl hydrocarbon (benzo[a]pyrene) hydroxylase and ethoxyresorufin deethylase in microsomal fractions, epoxide (benzo[a]pyrene-4,5-oxide) hydrolase in both microsomal and cytosolic fractions, glutathione (GSH) and GSH S-transferase in the cytosol. Exposure to cigarette smoke resulted in a number of significant metabolic changes, as compared to sham-exposed rats. The most pronounced alterations consisted in a 2.6-fold induction of aryl hydrocarbon hydroxylase in the lung and 8-fold induction of ethoxyresorufin deethylase in the liver, and in a marked stimulation of the liver metabolic activation of all promutagens. The last effect was inhibited by the oral administration of the chemopreventive agent N-acetylcysteine. On the whole, there was a poor correlation between the monitored biochemical and mutagenicity endpoints.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcysteine↗
PubMed1992

Expression of CD56 (NKH-1) differentiation antigen in human thyroid epithelium.

Leu-19 (CD56) MoAb is well known to recognize gp220 expressed on natural killer (NK) cells and is widely used as a NK cell marker. The expression of CD56 antigen was tested by means of sensitive alkaline phosphatase-anti-alkaline phosphatase (APAAP) immunohistochemical technique and the above mentioned MoAb as a primary antibody, on frozen sections of various fresh human tissues. Out of 11 organs examined only thyroid gland provided a distinct reaction confined to cell membranes of epithelial follicular cells. The reaction had a diffuse pattern in cases of Graves' disease and colloidal goitre while in Hashimoto's thyroiditis presented as a focal pattern. Other anti-NK cell MoAbs such as VD4 (CD16) and Leu-7 (CD57) reacted only with single cells of thyroid stroma. The results of APAAP staining were confirmed by the cytofluorimetric assessment of isolated thyroid cells. It is speculated that CD56 expression on thyroid cells may have a functional significance, perhaps related to neural-endocrine interactions.

Antibodies, Monoclonal↗
PubMed1992

Carcinogen-DNA adducts in human alveolar macrophages.

The occurrence of 7 beta,8 alpha-dihydroxy-(9 alpha,10 alpha)-epoxy-7,8,9,10- tetrahydrobenzo(a)pyrene (BPDE-)-DNA adducts was investigated by synchronous fluorescence spectrophotometry in human pulmonary alveolar macrophages (PAM) collected by bronchoalveolar lavage. In preliminary assays BPDE-DNA adducts were consistently detected in PAM of smokers, whereas samples from nonsmokers did not exhibit specific peaks.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1992

Thyroid hormones and atrial natriuretic hormone secretion: study in hyper- and hypothyroid patients.

Plasma atrial natriuretic hormone (ANH) values were evaluated in 28 hyperthyroid patients and in 11 hypothyroid patients and compared with 20 healthy subjects. In hyperthyroid patients plasma ANH basal levels were significantly (p less than 0.01) higher (14.2 +/- 1.6 pmol/l) than in controls (7.8 +/- 0.4 pmol/l) and in hypothyroid patients (6.4 +/- 0.3 pmol/l). No significant differences were found between controls and hypothyroid patients. The propranolol-induced decrease in heart rate in hyperthyroid patients did not significantly affect the plasma ANH values. Conversely, after the methimazole-induced euthyroidism a return within the normal range of ANH values was observed. The thyroxine replacement in hypothyroid patients determined a small but significant (p less than 0.05) increase in plasma ANH values. Observed data suggest that in humans thyroid hormones may influence plasma ANH concentrations independently of their effect on heart rate.

Adolescent↗
PubMed1991

Genotoxic, carcinogenic, and teratogenic hazards in the marine environment, with special reference to the Mediterranean Sea.

Genotoxic, carcinogenic, and teratogenic hazards arising out of pollution in the marine environment are discussed in this article, with special reference to the situation in the Mediterranean area. A number of chemical compounds or complex mixtures relevant to marine pollution, either natural or of anthropogenic origin, are tentatively listed, along with protective factors which may play a counteracting role in the same environment. Harmful substances tend to undergo interactions and transformations in seawater, sediments, and marine biota, due to physical, chemical, microbial, or light-mediated mechanisms. Bioaccumulation phenomena in marine organisms may result from food-chain biomagnification processes or from concentration of pollutants by filter feeders. A variety of sources can account for marine pollution by genotoxic, carcinogenic, and teratogenic compounds, but there is a relative paucity of analytical data concerning the Mediterranean. Metabolic transformations of xenobiotics occur in all marine organisms, the biochemical mechanisms in fish being comparable to those which have been extensively investigated in mammals. Induction of metabolic pathways, and especially of the mixed-function oxygenase system, represents the earliest warning signal of exposure to pollutants. Occurrence of neoplastic diseases is documented by experimental and field studies in marine vertebrates as well as in invertebrates. The association with local pollution phenomena has been recognized in several studies, but other etiopathogenetic factors may be also involved, and in some cases tumors have been reported to be unrelated to chemical pollution. Genotoxic agents have been detected by means of suitable techniques in seawater, sediments, and marine organisms. Several studies have investigated the presence of carcinogen-DNA adducts, DNA damage and repair processes, and cytogenetic alterations, such as chromosomal aberrations, sister-chromatid exchanges, and micronuclei, in tissues of marine organisms. However, monitoring of these end-points under field conditions encounters some limitations and problems. Even more fragmentary is the information on teratogenic effects in marine organisms, although interesting test systems have been set up. On the whole, a quite extensive database on all these toxicological issues is already available in the literature, but further studies are warranted for an adequate assessment of genotoxic, carcinogenic, and teratogenic hazards, and possibly counteracting factors in the marine environment, and specifically in the Mediterranean Sea.

Animals↗
PubMed1991

Enhanced liver metabolism of mutagens and carcinogens in fish living in polluted seawater.

Specimens of the seawater fish annular seabream (Diplodus annularis) were caught from a polluted harbor area and from a clean reference area. Seawater concentrates and fish-muscle extracts were not mutagenic in the Salmonella reversion test. Liver preparations of fish from the 2 sources were comparatively assayed for microsomal mixed-function oxidases and cytosolic biochemical parameters, as well as for the ability of S12 fractions to activate promutagens or to detoxify direct-acting mutagens. A shift of the cytochrome P-450 peak from 450.3 to 448.5 was accompanied by a 4.5-fold increase in arylhydrocarbon hydroxylase activity in fish living in the polluted environment. At the same time, glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were doubled in the cytosol of the same animals, while reduced glutathione (GSH) peroxidase and GSH S-transferase were slightly yet significantly depressed. No significant difference was recorded for other biochemical parameters, including GSH, oxidized glutathione (GSSG) reductase, NADH- and NADPH-dependent diaphorases, and DT diaphorase. In parallel, fish exposed to polluted seawater exhibited a significant and marked enhancement of the metabolic activation of the pyrolysis product Trp-P-2 and of benzo[a]pyrene-trans-7,8-diol, and at the same time were less efficient in detoxifying the antitumor compound ICR 191. Liver S12 fractions from both sources efficiently decreased the direct mutagenicity of sodium dichromate, and failed to activate benzo[a]pyrene and aflatoxin B1 to mutagenic metabolites. These results provide evidence that both biochemical parameters and the overall capacity of fish liver to activate or detoxify certain mutagens can be assumed to be sensitive indicators of exposure to mixed organic pollutants in the marine environment.

Animals↗
PubMed1991

Xenobiotic metabolizing enzymes in rainbow trout exposed to river water.

1. Juvenile rainbow trout were exposed to river water in a flow-through system. After 15 days of exposure, hepatic biotransformation activities and related parameters were measured and compared to those of the control group organisms that were maintained in tap water under identical experimental conditions. 2. Liver somatic index (LSI), microsomal protein and cytochrome P-450 contents, benzo[a]pyrene hydroxylase (AHH), ethoxyresorufin-O-deethylase (EROD) and UDP glucuronyl transferase activities were not significantly affected. 3. Aminopyrine-N-demethylase (APD) activity showed a slight yet significant increase in exposed trout.

Animals↗
PubMed1991

Benzo[a]pyrene diolepoxide-DNA adducts in alveolar macrophages of smokers.

The presence of benzo[a]pyrene diolepoxide (BPDE)-DNA adducts was investigated by synchronous fluorescence spectrophotometry in cells recovered by bronchoalveolar lavage from 39 individuals. Pulmonary alveolar macrophages constituted, on average, 90% of these cells. No adduct was detected in samples from non-smokers or ex-smokers, whereas 84.6% of samples from current smokers exhibited typical fluorescence peaks. The samples from four subjects who had stopped smoking during the last 6 months were also positive. A considerable variability was observed in the intensity of signals, which in positive samples was significantly correlated with the number of cigarettes currently smoked but not with the cumulative total of cigarettes smoked during a lifetime. In any case, part of the recorded quantitative variations could not be ascribed to the daily number of cigarettes but probably depended on interindividual variability in smoking habits or in toxicokinetics and metabolism. On the whole, detection of BPDE-DNA adducts in alveolar macrophages, compared to other surrogate cell populations, appears to represent a sensitive and specific biomonitoring tool, assessing the internal dose of inhaled benzo[a]pyrene in the proximity of target cells of the respiratory tract. Exploitation of this end-point in molecular epidemiology and cancer prevention studies warrants further investigation.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1991

Expression of intercellular adhesion molecule-1 (ICAM-1) on thyroid epithelial cells in Hashimoto's thyroiditis but not in Graves' disease or papillary thyroid cancer.

In order to study the possible role of antigen-independent adhesion systems in thyroid autoimmunity, we evaluated by indirect immunofluorescence the expression of lymphocyte functional antigen-1 (LFA-1) and its ligand ICAM-1 on mononuclear cell infiltrates (when present) and thyroid follicular cells of four patients with Hashimoto's thyroiditis, 30 with Graves' disease, five with papillary cancer, two with follicular adenoma, and two normal thyroid specimens. The expression of MHC class I and class II antigens was also evaluated. Most mononuclear infiltrates were LFA-1 positive, as expected. A positivity for ICAM-1 on follicular cells was observed in three out of four Hashimoto's thyroiditis specimens; such a phenomenon was totally absent in Graves' disease or any other pathological condition, or in normal tissue. MHC class II expression on thyrocytes was observed in all the patients with Hashimoto's thyroiditis, in 27 out of 30 with Graves' disease and in three out of five papillary cancer specimens.

Adult↗
PubMed1991

Comparative study between two immunoassays for detection of allergen-specific IgG4.

In the present work two commercially available immunoassays for allergen-specific IgG4 detection were compared, IgG4 FAST Test and ALLERBLOCK-MS IgG4 EIA Kit. For this purpose 30 serum samples were tested for IgG4 antibodies (Abs) specific to Dermatophagoides pteronyssinus (Dp) by the two immunoassays. Eleven serum samples were collected from normal subjects, 6 from Dp-atopic patients never treated by specific immunotherapy (ITS) and 13 from Dp-atopic patients previously treated by ITS. Pearson's linear correlation analysis showed a significant correlation of results from the two immunoassays. However, a better discrimination of Dp-specific IgG4 values between ITS-treated and untreated patients or normal subjects was obtained by FAST than ALLERBLOCK-MS method; moreover, the former showed a better intra-assay coefficient of variation than the latter.

Animals↗
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↗