N Fiorino

Università degli Studi di Genova, Genova, Liguria, Italy

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Publications (13)52.41 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Cultured thyroid epithelial cells can be induced to express intercellular adhesion molecule-1 (ICAM-1, or CD54). However, constitutive follicular expression of ICAM-1 has been reported only in thyroid autoimmunity. We evaluated the expression of ICAM-1 mRNA and protein on thyroid tissue from different autoimmune thyroid diseases, and its relationship with other immunologically relevant surface markers, namely costimulatory molecules of B7 family. Thyroid tissue sections were obtained by surgically removed thyroid glands from 6 patients with Hashimoto's thyroiditis (HT), 6 with Graves' disease (GD) and 3 with multinodular nontoxic goiter. We used in situ hybridization to localize ICAM-1 mRNA, and immunohistochemical analysis by alkaline phosphatase anti-alkaline phosphatase (APAAP) method. We showed a clear hybridization pattern, localized in follicular cells, in sections of glands with HT. The hybridization pattern was far less pronounced in GD: no staining was apparent on follicular cells. These results were strictly consistent with those obtained by means of immunohistochemistry. Moreover, double-staining experiments demonstrated colocalization of ICAM-1 and B7.1 molecules in HT, whereas no B7.1 expression was observed in Graves' or in non-autoimmune thyroid diseases. These data agree with the hypothesis of distinct immunoregulatory phenomena and effector mechanisms in the 2 main autoimmune thyroid diseases.
    Journal of endocrinological investigation 04/2002; 25(3):289-95. · 1.65 Impact Factor
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    ABSTRACT: We have previously shown aberrant expression of the 'leukocyte' integrin LFA-1 on epithelial cells in chronic autoimmune thyroiditis. In the present study we investigated whether conjunctival epithelial cells, which bear the adhesion molecule ICAM-1 on their surface during allergic inflammation, may also aberrantly express its natural ligand, the 'leukocyte' integrin LFA-1. We studied 13 patients with rhinoconjunctivitis allergic to mites, chronically exposed to the allergen, 11 patients allergic to pollen tested out of the pollen season and 8 normal volunteers. Single and double immunocytochemical staining of conjunctival smears was employed. LFA-1 staining on epithelial cells was demonstrated in 12/13 patients allergic to mites and not in normal controls or in patients allergic to pollen tested out of the pollen season. The epithelial localization of LFA-1 was confirmed by double staining with anti-LFA-1 and anti-cytokeratin antibodies (both immunocytochemical and immunofluorescence). Coexpression of LFA-1 and ICAM-1 during persistent allergen stimulation may be relevant for interaction between epithelial cells and activated effector cells, such as eosinophils, which bear on their surface both ICAM-1 and its beta2 integrin ligands.
    International Archives of Allergy and Immunology 07/2001; 125(2):160-3. · 2.25 Impact Factor
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    ABSTRACT: The molecules of the B7 family play a major role in T-lymphocyte costimulation through interaction with their counterreceptors CD28 and CTLA4. In the present study, we analyzed the possible expression of B7 molecules on surgically removed thyroid tissue of patients with autoimmune [Hashimoto's thyroiditis (HT) or Graves' disease (GD)] or nonautoimmune [nontoxic goiter (NTG) or papillary cancer (PC)] thyroid diseases. We found clear positivity of thyroid follicular cells for B7.1 in HT but not in GD, nor in nonautoimmune specimens (NTG, PC) using in situ analysis by alkaline phosphatase anti-alkaline phosphatase (APAAP) technique. Double immunostaining experiments in combination with an anti-human thyroglobulin antibody confirmed follicular B7.1 localization. On the contrary, no follicular B7.2 expression was observed in any specimen analyzed. These findings were confirmed by immunofluorescence flow cytometry on isolated follicular cells. The cytokines IL1beta and LPS were able to induce de novo B7.1 expression on cultured thyroid follicular cells. Intrathyroid T cells proved responsive to stimulation via the B7 ligand CD28, even in the absence of IL2. Moreover preliminary evidence was obtained for an inhibitory effect of anti-B7.1 mAb on T-cell proliferation in coculture with isolated thyroid follicular cells. It is conceivable that in HT, expression of B7.1 on follicular cells, together with MHC class II antigens and ICAM1, could provide a local costimulatory signal for T-lymphocyte differentiation toward the type 1 cytokine secretion pattern and maintenance of the autoimmune process.
    Journal of Clinical Endocrinology &amp Metabolism 12/1998; 83(11):4130-9. · 6.43 Impact Factor
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    Allergy 06/1998; 53(5):545-6. · 5.88 Impact Factor
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    ABSTRACT: The intercellular adhesion molecule ICAM-1 has been detected by immunohistochemical methods on epithelial cells of the conjunctiva and nose during allergic inflammation. The aim of the present study was to evaluate whether ICAM-1 expression on conjunctival epithelium derives from endogenous synthesis or is merely due to passive uptake of soluble ICAM-1 released from inflammatory cells. In situ hybridization was performed using a 3' end dygoxygenin-labelled specific DNA oligonucleotide probe on fixed conjunctival smears from allergic subjects challenged with, or naturally exposed to the allergen, and from healthy subjects. Immunocytochemistry for ICAM-1 was performed by alkaline phosphatase antialkaline phosphatase. In allergic patients, both naturally exposed to the allergen and after specific challenge, a clear hybridization pattern on epithelial cells was apparent. Out of allergen exposure, some symptomfree pollinosic subjects, as well as a few healthy volunteers showed mild ICAM-1 mRNA cytoplasmic staining in the absence of immunohistochemically detectable ICAM-1. This finding may explain the very early appearance of ICAM-1 on conjunctival epithelium following specific challenge in allergic individuals. These results indicate that the presence of ICAM-1 on conjunctival epithelium during allergic inflammation derives from endogenous synthesis and not from uptake of soluble ICAM-1.
    Clinical & Experimental Allergy 08/1997; 27(7):737-43. · 4.79 Impact Factor
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    ABSTRACT: Azelastine is a topical antihistamine, clinically demonstrated to be effective in allergic rhinitis. We evaluated the clinical efficacy and the antiallergic activity of azelastine nasal spray, administered 0.56 mg per day, 0.28 mg per day, or on demand over a 3-month period during natural allergen exposure, in a double-blind, placebo-controlled fashion. Thirty patients, sensitized to grass or Parietaria pollen, were allocated to three treatment groups: those receiving the standard dosage (0.14 mg/nostril two times a day), half the dosage (0.07 mg/nostril two times a day), or placebo daily for 3 months. All patients were allowed to take additional doses of azelastine when needed. Evaluation parameters were as follows: clinical symptoms recorded on a diary card, number of additional, on-demand azelastine puffs, nasal inflammatory cell count, intercellular adhesion molecule-1 expression on nasal epithelial cells, and pollen count. This study showed the following: (1) the half dose (0.28 mg/day) and the standard dose (0.56 mg/day) were equally effective in reducing clinical symptoms (p = NS), although the standard dosage required fewer additional puffs during times of peak pollen counts (p < 0.05); (2) both dosages were able to reduce the allergic inflammation (p < 0.05 vs placebo); and (3) on-demand use achieved acceptable clinical control but did not significantly reduce allergic inflammation. Continuous treatment was more effective than on-demand use as assessed by both clinical evaluation and antiinflammatory action.
    Journal of Allergy and Clinical Immunology 04/1997; 99(3):301-7. · 12.05 Impact Factor
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    ABSTRACT: Azelastine is a selective H1-receptor antagonist, which has previously been demonstrated to be effective in the treatment of allergic rhinitis. We have recently demonstrated that nasal azelastine inhibits the clinical and inflammatory events following nasal allergen challenge. Particularly, we focused our attention on ICAM-1 expression on epithelial cells, since it is the natural ligand of LFA-1, an adhesion molecule expressed by leucocytes, including eosinophils. Since azelastine ocular drops are now available, the aim of the present study was the evaluation of the anti-allergic activity in the model of allergen specific conjunctival challenge (ASCC). Twenty outpatients with allergic rhinoconjunctivitis due to Parietaria Judaica (Wall Parietary) were included outside the pollen season. The study was designed as randomized, placebo-controlled, double-blind and parallel group, developed in two parts. The former investigated the onset of effect of a single dose of azelastine eye drops administered 20 min after clinical response due to ASCC. The latter evaluated the clinical and inflammatory parameters following ASCC after 7-days treatment with azelastine. Clinical parameters (hyperaemia, itching, lacrimation and eyelid swelling) were evaluated at baseline, 5, 10, 20 and 30 min (i.e. early phase reaction-EPR) and 6 h (i.e. late phase reaction-LPR) after ASCC. Cytological assessment (number of neutrophils, eosinophils. monocytes and lymphocytes) and ICAM-1 expression on conjunctival epithelial cells were evaluated at baseline, 30 min (i.e. early phase reaction-EPR) and 6 h (i.e. late phase reaction-LPR) after ASCC. When administered 30 min after ASCC, azelastine produced a clinical effect ranging between 10 and 20 min after eye drops administration (P < 0.01). After 7 days of treatment, 30 min after ASCC, azelastine induced a reduction of symptom scores during EPR and LPR (P < 0.01), a reduction of inflammatory cell infiltration during both EPR (P < 0.01) and LPR (P < 0.01), and a reduction of ICAM-1 expression during EPR and LPR (both P < 0.01). Placebo did not modify any of the studied parameters. Azelastine eye drops exert anti-allergic activity, inducing a rapid improvement of clinical events when administered after ASCC, and reducing both symptoms and cellular infiltration when administered before ASCC. Finally, azelastine down-regulates ICAM-1 expression on epithelial conjunctival cells, confirming the results obtained at nasal level.
    Clinical & Experimental Allergy 03/1997; 27(2):182-91. · 4.79 Impact Factor
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    ABSTRACT: Lodoxamide is an antiallergic drug acting as a mast-cell stabilizer, which is effective in the treatment of allergic conjunctivitis. The study aimed to evaluate the effect of lodoxamide eye-drops on the inflammatory early-phase reaction (EPR) changes induced by allergen-specific conjunctival challenge (ASCC). This was a cross-over, double-blind, placebo-controlled, randomized study, including 10 outpatients suffering from allergic rhinoconjunctivitis due to Parietaria judaica. Patients received one drop of lodoxamide tromethamine 0.1% or placebo 30 min before each ASCC. Clinical evaluation and cytologic assessment were done at baseline and 30 min after each ASCC. Lodoxamide induced a reduction in total symptom score and hyperemia during the EPR (P < 0.05). Lacrimation, itching/burning, and eyelid swelling were only slightly (nonsignificantly) reduced. Lodoxamide induced a reduction in the total number of inflammatory cells and neutrophils during the EPR (P < 0.02). Eosinophil and lymphocyte number and ICAM-1 expression showed only a slight, not statistically significant decrease. Placebo did not affect the studied parameters. Lodoxamide reduced early clinical events and cellular changes after ASCC consistently with its activity as mast-cell stabilizer. Moreover, lodoxamide was able to downregulate in vitro ICAM-1 expression on the continuously cultured, differentiated conjunctival cell line WK. This was shown both in basal conditions (P < 0.05) and upon interferon-gamma stimulation (P < 0.03), although at high concentration.
    Allergy 01/1997; 51(12):946-51. · 5.88 Impact Factor
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    ABSTRACT: Levocabastine is a selective topical H1 antagonist, effective in the treatment of seasonal allergic rhinitis and conjunctivitis. We evaluated the possible effects of levocabastine eye drops on early (EPR) and late phase (LPR) inflammatory changes induced by allergen-specific conjunctival challenge (ASCC). We focused our attention on the possible effect of levocabastine on expression of the intracellular adhesion molecule-1 (ICAM-1) on epithelial cells. Such a phenomenon is likely to play an important role in allergic inflammation. The study was a double-blind, placebo-controlled, randomized trial, performed in cross-over, outside the pollen season. Ten out-patients suffering from allergic rhinoconjunctivitis due to parietaria judaica (wall parietary) were enrolled. Patients randomly received levocabastine eye drops (0.5 mg/mL) or placebo eyedrops, one drop in the left eye (right eye as control), 30 min before ASCC. Clinical evaluation (hyperaemia, burning-itching, lacrimation and eyelid swelling) and cytological assessment (number of neutrophils, eosinophils and lymphocytes, and ICAM-1 expression on conjunctival epithelium) were evaluated at baseline, 30 min and 6 h after ASCC. In parallel, we evaluated the in vitro effect of levocabastine at concentrations ranging from 2 x 10(-9) M to 2 x 10(-5) M on ICAM-1 expression and shedding by a continuously cultured differentiated epithelial cell line (WK). Levocabastine reduced symptom scores during EPR (15 min and 30 min, P < 0.002), inflammatory cell infiltration during EPR (P < 0.002 for neutrophils, eosinophils and lymphocytes) and ICAM-1 expression on epithelium both during EPR (P < 0.002) and LPR (P < 0.02). LPR symptom scores and inflammatory cell infiltration were only slightly modified by levocabastine treatment. In vitro levocabastine at 2 x 10(-5) M concentration was able to down-regulate basal ICAM-1 expression, although it exerted no effect on ICAM-1 release by epithelium. Levocabastine exerts anti-allergic activity, in that it reduces in vivo inflammatory cell infiltration due to ASCC, and also adhesion molecule expression on conjunctival epithelium. The latter phenomenon may be due, at least in part, to a direct effect of levocabastine on epithelial cells.
    Clinical & Experimental Allergy 10/1996; 26(10):1188-96. · 4.79 Impact Factor
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    ABSTRACT: We have evaluated the expression of different molecular forms of T cell antigen receptor (TcR) in duodenal biopsies of pediatric patients with different forms of villous atrophy: celiac disease, autoimmune enteropathy, intractable diarrhea of unknown origin, and severe cow milk intolerance. A panel of monoclonal antibodies recognizing alpha/beta and gamma/delta TcR (and gamma/delta TcR subsets) was used for immunostaining. The results showed an increase of T cells with gamma/delta-type TcR in celiac patients and also in patients with other forms of villous atrophy with respect to normal controls. Amongst the gamma/delta TcR-positive cells, the subset expressing the molecular product of V delta 1 region was the most represented. The gamma/delta TcR-positive T cells were mainly located within the epithelium: few of them were observed in the lamina propria. On the basis of these results, we hypothesize that the increased homing of gamma/delta TcR-positive T lymphocytes in gut epithelium observed in celiac disease is, at least in part, related to villous atrophy per se.
    International Archives of Allergy and Immunology 08/1996; 110(3):233-7. · 2.25 Impact Factor
  • Journal of Allergy and Clinical Immunology - J ALLERG CLIN IMMUNOL. 01/1996; 97(1):290-290.
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    ABSTRACT: We have evaluated the expression of different molecular forms of T cell antigen receptor (TcR) in duodenal biopsies of pediatric patients with different forms of villous atrophy: celiac disease, autoimmune enteropathy, intractable diarrhea of unknown origin, and severe cow milk intolerance. A panel of monoclonal antibodies recognizing α/β and γ/δ TcR (and γ/δ TcR subsets) was used for immunostaining. The results showed an increase of T cells with γ/δ-type TcR in celiac patients and also in patients with other forms of villous atrophy with respect to normal controls. Amongst the γ/δ TcR-positive cells, the subset expressing the molecular product of Vδ1 region was the most represented. The γ/δ TcR-positive T cells were mainly located within the epithelium: few of them were observed in the lamina propria. On the basis of these results, we hypothesize that the increased homing of γ/δ TcR-positive T lymphocytes in gut epithelium observed in celiac disease is, at least in part, related to villous atrophy per se.
    International Archives of Allergy and Immunology. 01/1996; 110(3):233-237.
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    ABSTRACT: In the present study we have evaluated the expression of different molecular forms of the antigen receptor (TcR) on lymphocytes derived from thyroid tissue of patients with Graves' disease, Hashimoto thyroiditis and papillary cancer both in situ by APAAP technique and on isolated lymphocytes by indirect immunofluorescence. A panel of monoclonal antibodies (mAbs) recognizing alpha/beta and gamma/delta TcR-positive subsets was used. The results showed that the large majority of T-cells in thyroid infiltrates were alpha/beta TcR+, gamma/delta TcR+ ones being very rare or nearly absent, whatever the disease (autoimmune or neoplastic). No difference between gamma/delta TcR+ T-cell subsets (V delta 1+ or V delta 2+) was observed. Thus, neither in autoimmune thyroid diseases nor in papillary cancer gamma/delta TcR+ cells are likely to be a major effector-T cell population.
    Journal of endocrinological investigation 05/1995; 18(4):295-8. · 1.65 Impact Factor