Ocular challenge and hyperresponsiveness to histamine in patients with allergic conjunctivitis.
Explore the source record for details and available documents.
Adolescent↗
Biomedical subjects
M Bagnasco
Publications and source records attributed to M Bagnasco.
Multiple genotoxicity biomarkers in fish exposed in situ to polluted river water.
Specimens of rainbow trout (Oncorhynchus mykiss) were either kept in an aquarium under laboratory conditions or caged in the River Po (Northern Italy), upstream or downstream the confluence with the River Lambro, a small yet heavily polluted tributary. Genotoxicity biomarkers, evaluating the internal dose or early biological effects, were monitored after 7, 15 and 30 days of in situ exposure. With the exception of a slight increase of aminopyrine-N-demethylase and uridine-5'-diphospho-glucuronosyl-transferase, no significant effect was produced in fish kept upstream the River Lambro, as compared to control fish kept in the aquarium. In contrast, the responsibility of this tributary in carrying sublethal doses of both genotoxic agents and enzyme inducers into the main river was proved by the significant occurrence of early biological alterations in fish caged downstream. In fact, (a) bile extracts contained frameshift mutagens requiring metabolic activation, with a prevalence of liposoluble components after a short exposure, followed by a time-related increase of conjugated components, in minor part with glucuronic acid; (b) the monooxygenases aminopyrine-N-demethylase, uridine-5'-diphospho-glucuronosyl-transferase and, with sharp differences, arylhydrocarbon hydroxylase and 7-ethoxyresorufin-O-deethylase were enhanced in liver microsomal fractions; (c) the liver cytosolic fractions had an enhanced ability to convert 3-amino-1-methyl-5H-pyrido(4,3)indole into mutagenic metabolites in S. typhimurium; (d) cytogenetic damage was demonstrated by an increased frequency of micronuclei in peripheral blood erythrocytes.
Animals↗
Anti-T11.1 and -T11.2 monoclonal antibodies play a different role in CD2-mediated signal transduction.
We comparatively evaluated (Ca2+)i mobilization after triggering with a stimulatory pair of CD2 (CD2.9, anti-T11.1 + CD2.1, anti-T11.2) or CD3 mAbs in the differentiated T-cell line Jurkat, using INDO-1 labeling and cytofluorimetry. The results obtained showed different (Ca2+)i mobilization kinetics following CD2 or CD3 stimulation (the former being slower than the latter), not due to different association kinetics of mAbs. In a nonreciprocal manner, however, preliminary interaction with CD2.1 (anti-T11.2) followed by CD2.9 (anti-T11.1) induces a rapid (Ca2+)i rise, similar to CD3 stimulation, as shown by preincubation experiments. There is no interference between CD2.9 and CD2.1 mAb binding. CD2.1 mAb by itself is unable to induce (Ca2+)i mobilization; in addition, preincubation with CD2.1 mAb did not modify the CD2, CD3, CD45, or CD28 immunoprecipitation patterns. Triggering of the epitope recognized by CD2.1 mAb may favor, possibly via conformational changes of CD2 molecule or (Ca2+)i-unrelated metabolic effect(s), optimal signal transduction.
Antibodies, Monoclonal↗
Post-mortem stability of benzo[a]pyrene diolepoxide--DNA adducts in rat organs.
In order to evaluate the stability of benzo[a]pyrene diolepoxide--DNA adducts two separate studies were carried out in rats, either treated i.p. with benzo[a]pyrene (100 mg/kg body wt) or sham-exposed. The measurement of DNA adducts in 155 samples of liver, lung or heart, each of them tested in duplicate, was performed by synchronous fluorescence spectrophotometry. In the first study fragments of rat liver or lung were stored for varying times at varying temperatures. No decrease of adduct levels occurred at 4 degrees C for at least 72 h, whereas a significant decrease was recorded in both liver and lung after 48 h at 20 degrees C or 24 h at 37 degrees C. In the second study liver, lungs and heart were collected from rats either immediately after killing or after storage of cadavers for 16 h at 20 degrees C or 16 h at 20 degrees C plus 24 h at 4 degrees C, thereby mimicking typical storage conditions of human cadavers before autopsy. Under these conditions no significant variation of fluorescent adducts was observed in any organ. In conclusion, at least for this kind of adduct, the use of autopsy samples following proper storage of cadavers seems to be acceptable.
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
CD28 mAbs with distinct binding properties differ in their ability to induce T cell activation: analysis of early and late activation events.
A panel of eight different CD28 mAbs was used to analyse the structure-function relationships of the CD28 molecule. The results of binding inhibition experiments show a complex and heterogeneous pattern of inhibition; however a subgroup of mAbs was identified, namely CD28.1, CD28.3, and CD28.5, which exhibited almost identical inhibition profiles. To test the hypothesis that the different binding specificities are related to functionally distinct subregions of the CD28 molecule, the ability of each mAb to (i) induce IL-2 release and (ii) increase intracellular calcium [(Ca2+)i] in Jurkat T cells was analysed. The results show that the mAbs CD28.1, CD28.3, and CD28.5 are almost totally unable to induce IL-2 release, and their ability to increase (Ca2+)i is relatively low. All other mAbs are able to induce a marked (Ca2+)i rise, however they strongly differ in their ability to induce IL-2 release. Such differences cannot be explained by differences in the isotypes or binding kinetics of the mAbs. These results imply the existence of functionally distinct subregions on the CD28 molecule. In addition, the (Ca2+)i rise may be associated with either high or low IL-2 secretion following CD28 triggering.
Animals↗
Deflazacort protects against late-phase but not early-phase reactions induced by the allergen-specific conjunctival provocation test.
The protective effects of deflazacort against the inflammation that follows the conjunctival provocation test (CPT) by specific allergen were assessed in 24 patients with rhinoconjunctivitis caused by Parietaria judaica in a double-blind study. After a screening CPT, patients were randomized into four treatment groups, each being given deflazacort (oral tablets) at 6, 30, and 60 mg once daily, or matching placebo, for 3 d, outside the pollen season. Clinical evaluation (itching, hyperemia, lacrimation, and swelling of eyelids) and cytologic assessment (number of inflammatory cells in conjunctival scraping and evaluation of ICAM (intercellular adhesion molecule)-1/CD54 expression on epithelial cells) were performed at base line, 30 min (early-phase reaction (EPR), 6 h and 24 h (late-phase reaction (LPR)) after specific CPT, and before and after treatment. Neither the EPR clinical reactions nor the EPR total number of inflammatory cells was modified by deflazacort. However, the LPR clinical effects were significantly reduced by deflazacort at 30 or 60 mg/d (P < 0.01), as compared with placebo. The total number of inflammatory cells during LPR was significantly reduced by deflazacort at 30 or 60 mg/d (P < 0.01), as compared with placebo. Furthermore, CD54 expression was significantly reduced by deflazacort at 30 or 60 mg/d both in the EPR (P < 0.01) and LPR (P < 0.01), as compared with placebo. None of the studied indicators were modified at the 6 mg/d dose. This study shows that deflazacort has a highly protective action against clinical and cellular LPR effects induced by the specific CPT. In addition, deflazacort markedly reduces CD54 expression on the conjunctival epithelium during both EPR and LPR.
Adolescent↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
Metabolic and genetic effects of marine pollution on aquatic organisms.
Explore the source record for details and available documents.
Animals↗