TY - JOUR T1 - Immunohistologic analysis of the duodenal bulb: a new method for celiac disease diagnosis in children. JF - Gastrointest Endosc Y1 - 2018 A1 - De Leo, Luigina A1 - Villanacci, Vincenzo A1 - Ziberna, Fabiana A1 - Vatta, Serena A1 - Martelossi, Stefano A1 - Di Leo, Grazia A1 - Zanchi, Chiara A1 - Bramuzzo, Matteo A1 - Giudici, Fabiola A1 - Ventura, Alessandro A1 - Not, Tarcisio KW - Adolescent KW - Autoantibodies KW - Celiac Disease KW - Child KW - Child, Preschool KW - Duodenum KW - Female KW - Humans KW - Immunoglobulin A KW - Immunohistochemistry KW - Infant KW - Male KW - Prospective Studies KW - Transglutaminases AB -

BACKGROUND AND AIMS: Anti-tissue transglutaminase antibodies (anti-tTG) have simplified celiac disease (CD) diagnosis. However, in atypical forms of CD, intestinal biopsy sampling is still required. This prospective study investigates whether histologic analysis of the duodenal bulb combined with intestinal IgA anti-tTG deposit immunoassay makes CD diagnosis possible in at-risk children with low concentrations of serum anti-tTG.

METHODS: Histologic and intestinal IgA anti-tTG deposit immunoassays were used.

RESULTS: Two hundred forty-five symptomatic children positive for serum anti-tTG (>7 U/mL) were enrolled and divided into 3 groups: extensive duodenal atrophy (n = 209), with IgA anti-tTG deposits throughout the duodenum and high serum anti-tTG concentrations (157 ± 178 U/mL); bulb duodenal atrophy (n = 22), with widespread IgA anti-tTG deposits in 9 and in the bulb alone in 13 and low serum anti-tTG concentrations (13.9 ± 8.7 U/mL); and normal duodenum (n = 14), with widespread IgA anti-tTG deposits in 8 and in the bulb alone in 6 and low serum anti-tTG concentrations (10.6 ± 6.2 U/mL). All patients in the first 2 groups were diagnosed with CD and 8 from the third group. All improved after 1 year of gluten-free diet. Bulb duodenal analysis led to a 12% (30/245) increase in CD diagnosis. No CD-related lesions were observed in the 30 control subjects.

CONCLUSIONS: In children at risk for CD, bulb duodenum biopsy sampling is essential to identify villous atrophy and detect IgA anti-tTG deposits even in absence of intestinal lesions. These mucosal autoantibodies could well represent a new standard for diagnosing CD.

VL - 88 IS - 3 U1 - http://www.ncbi.nlm.nih.gov/pubmed/29807020?dopt=Abstract ER - TY - JOUR T1 - Association between thyroid hormones and TRAIL. JF - Clin Biochem Y1 - 2017 A1 - Bernardi, Stella A1 - Bossi, Fleur A1 - Toffoli, Barbara A1 - Giudici, Fabiola A1 - Bramante, Alessandra A1 - Furlanis, Giulia A1 - Stenner, Elisabetta A1 - Secchiero, Paola A1 - Zauli, Giorgio A1 - Carretta, Renzo A1 - Fabris, Bruno KW - Aged KW - Female KW - Gene Expression Regulation KW - Humans KW - Hyperthyroidism KW - Hypothyroidism KW - Leukocytes, Mononuclear KW - Male KW - Middle Aged KW - Thyroxine KW - TNF-Related Apoptosis-Inducing Ligand KW - Triiodothyronine AB -

INTRODUCTION: Recent studies suggest that a circulating protein called TRAIL (TNF-related apoptosis-inducing ligand) might have a role in the regulation of body weight and metabolism. Interestingly, thyroid hormones seem to increase TRAIL tissue expression. This study aimed at evaluating whether overt thyroid disorders affected circulating TRAIL levels.

METHODS: TRAIL circulating levels were measured in euthyroid, hyperthyroid, and hypothyroid patients before and after thyroid function normalization. Univariate and multivariate analyses were performed to evaluate the correlation between thyroid hormones and TRAIL. Then, the stimulatory effect of both triiodothyronine (T3) and thyroxine (T4) on TRAIL was evaluated in vitro on peripheral blood mononuclear cells.

RESULTS: Circulating levels of TRAIL significantly increased in hyperthyroid and decreased in hypothyroid patients as compared to controls. Once thyroid function was restored, TRAIL levels normalized. There was an independent association between TRAIL and both fT3 and fT4. Consistent with these findings, T3 and T4 stimulated TRAIL release in vitro.

CONCLUSION: Here we show that thyroid hormones are associated with TRAIL expression in vivo and stimulate TRAIL expression in vitro. Given the overlap between the metabolic effects of thyroid hormones and TRAIL, this work sheds light on the possibility that TRAIL might be one of the molecules mediating thyroid hormones peripheral effects.

VL - 50 IS - 16-17 U1 - http://www.ncbi.nlm.nih.gov/pubmed/28551332?dopt=Abstract ER - TY - JOUR T1 - Puzzling Results from Germline Mutations Analysis in a Group of Asbestos-Exposed Patients in a High-risk Area of Northeast Italy. JF - Anticancer Res Y1 - 2017 A1 - Rizzardi, Clara A1 - Athanasakis, Emmanouil A1 - Cammisuli, Francesca A1 - Monego, Simeone Dal A1 - DE Spelorzi, Yeraldin Chiquinquira Castillo A1 - Costantinides, Fulvio A1 - Giudici, Fabiola A1 - Pinamonti, Maurizio A1 - Canzonieri, Vincenzo A1 - Melato, Mauro A1 - Pascolo, Lorella KW - Aged KW - Aged, 80 and over KW - Asbestos KW - Environmental Exposure KW - Female KW - Germ-Line Mutation KW - Humans KW - Italy KW - Lung Neoplasms KW - Male KW - Mesothelioma KW - Middle Aged KW - Risk KW - Tumor Suppressor Proteins KW - Ubiquitin Thiolesterase AB -

BACKGROUND: Germline mutations of the oncosuppressor gene breast cancer 1-associated protein 1 (BAP1) were recently related to an autosomal-dominant tumor predisposition syndrome (BAP1-TPDS), characterized by uveal melanoma, malignant mesothelioma (MM), cutaneous melanoma, and other malignancies. The demonstration that BAP1 mutations are strongly associated with MM has provided a real breakthrough in the study of genetic predisposition in MM, that may explain why only a fraction of asbestos-exposed individuals go on to develop MM.

MATERIALS AND METHODS: To evaluate the possible role of BAP1 mutations in the epidemiology of sporadic MM, and their relationship with asbestos exposure, we determined the prevalence of germline BAP1 mutations by the Sanger method in a group of 29 asbestos-exposed patients, 21 of which were diagnosed with MM. They were residents of Trieste, a ship-building town in Northeast Italy with a very high incidence of mesothelioma.

RESULTS: We identified non-obviously pathogenetic germline sequence variants of BAP1 in 3/29 patients and in 2/21 MM cases (10%).

CONCLUSION: Non obviously pathogenic germline sequence variants of BAP1 were found. Nevertheless, limitations of predictive web tools allowed us to comment on some interesting peculiarities of our findings.

VL - 37 IS - 6 U1 - http://www.ncbi.nlm.nih.gov/pubmed/28551647?dopt=Abstract ER -