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Genetic analysis of Italian patients with congenital tufting enteropathy

世界儿科杂志:英文版 2016年第2期12卷 219-224页

作者： Maria d'Apolito Daniela Pisanelli Flavio Faletra Ida Giardino Maddalena Gigante Massimo Pettoello-mantovani Olivier Goulet Paolo Gasparini Angelo Campanozzi Unit of Pediatrics Department of Medical and Surgical SciencesUniversity of FoggiaItaly Institute for Maternal and Child Health-IRCCS"BurloGarofolo" TriesteItaly Laboratory Medicine Department of Clinical and Experimental MedicineUniversity of FoggiaFoggiaItaly Department of Medical and Surgical Sciences University of FoggiaFoggiaItaly Department of Pediatric Gastroenterology-Hepatology and Nutrition and Reference Center for Rare Digestive Disease Hopital Necker-EnfantsMaladesParisFrance

Background:Congenital tufting enteropathy(CTE),an inherited autosomal recessive rare disease,is a severe diarrhea of infancy which is clinically characterized by absence of infl ammation and presence of intestinal villous *** in the EpCAM gene were identified to cause *** cases of syndromic tufting enteropathy harboring the SPINT2(19q13.2)mutation were ***:Four CTE Italian patients were clinically and immunohistochemically *** DNA sequencing of EpCAM and SPINT2 genes was ***:All patients were of Italian *** different mutations were detected(***219Metfs*15,Tyr186Phefs*6 and ***146Asn)in the EpCAM gene;one of them is novel(***146Asn).Two patients(P1 and P2)showed compound heterozygosity revealing two mutations in separate alleles.A third patient(P3)was heterozygous for only one novel EpCAM missense mutation(***146Asn).In a syndromic patient(P4),no deleterious EpCAM mutation was *** SPINT2 mutational analysis was performed.P4 showed a homozygous SPINT2 mutation(p.Y163C).No SPINT2 mutation was found in ***7 was also evaluated as a candidate gene by mutational screening in P3 but no mutation was identifi ***:This study presented a molecular characterization of CTE Italian patients,and identified three mutations in the EpCAM gene and one in the SPINT2 *** of EpCAM mutations was novel,therefore increasing the mutational spectrum of allelic variants of the EpCAM *** analysis of the SPINT2 gene also allowed us to identify a SPINT2 substitution mutation(c.488A>G)recently found to be associated with syndromic CTE subjects.

关键词： diarrhea gastroenterology gene mutation

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Generation and Disruption of Subducted Lithosphere in the Central-Western Mediterranean Region and Time-Space Distribution of Magmatic Activity Since the Late Miocene

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International Journal of Geosciences 2022年第9期13卷 830-854页

作者： Enzo mantovani Marcello Viti Caterina Tamburelli Daniele Babbucci Dipartimento di Scienze Fisiche Della Terra e dell’Ambiente Università di Siena Siena Italy

The long migration of the Balearic Arc (Alpine-Apennine and Alpine-Maghrebian belts) in the Early-Middle Miocene caused the formation of a subducted lithospheric edifice in the western and central Mediterranean regions. Then, since the Late Miocene, this slab was almost completely disrupted, only maintaining a narrow and deformed remnant beneath the southernmost Tyrrhenian basin. This work describes a tentative reconstruction of the tectonic processes that caused the formation of major tears and breakoffs in the original slabs and the consequent disruption of the subducted lithosphere. In particular, it is suggested that this relatively fast process was produced by the collision between the Anatolian-Aegean system and the continental Adriatic domain, which triggered a number of extrusion processes. Possible connections between the proposed tectonic evolution and the spatio-temporal distribution and geochemical signatures of magmatic activity are then discussed. It is supposed that such activity has been mainly conditioned by the occurrence of transtensional tectonics in the wake of escaping orogenic wedges.

关键词： Deep Tectonics Slab Tears and Slab Breakoffs Magmatism Central-Western Mediterranean

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Unique immunological profile in patients with COVID-19

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Cellular & Molecular Immunology 2021年第3期18卷 604-612页

作者： Stefania Varchetta Dalila Mele Barbara Olivier Stefania mantovani Serena Ludovisi Antonella Cerino Raffaele Bruno Alberto Castelli Mario Mosconi Marco Vecchia Silvia Roda Michele Sachs Catherine Klersy Mario U.Mondelli Division of Infectious Diseases Ⅱ and Immunology Fondazione IRCCS Polidinico San MatteoPaviaItaly Department of Internal Medicine and Therapeutics University of PaviaPaviaItaly Division of Infectious Diseases I Fondazione IRCCS Polidinico San MatteoPaviaItaly Department of Clinical SurgicalDiagnosticand Pediatric SciencesUniversity of PaviaPaviaItaly Division of Orthopaedics and Traumatology Fondazione IRCCS Polidinico San MatteoPaviaItaly Department of Clinical-Surgical Diagnostic and Pediatric SciencesUniversity of PaviaPaviaItaly Clinical Epidemiology&Biometry Unit IRCCS Fondazione Polidinico San MatteoPaviaItaly

The relationship between severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)and host immunity is poorly *** performed an extensive analysis of immune responses in 32 patients with severe COVID-19,some of whom succumbed A control population of healthy subjects was *** with COVID-19 had an altered distribution of peripheral blood lymphocytes,with an increased proportion of mature natural killer(NK)cells and low T-cell *** cells and CD8^(+)T cells overexpressed T-cellimmunoglobulin and mucin domain-3(TIM-3)and *** cell exhaustion was attested by increased frequencies of programmed cell death protein 1(PD-1)positive cells and reduced frequencies of natural killer group 2 member D(NKG2D)-,DNAX accessory molecule-1(DNAM-1)-and sialic acid-binding Ig-like lectin 7(Siglec-7)-expressing NK cells,associated with a reduced ability to secrete interferon(IFN)γ.Patients with poor outcome showed a contraction of immature CD56^(bright) and an expansion of mature CD57^(+)F_(CEI)Rlγ^(eng) adaptive NK cells compared to *** serum levels of IL-6 were also more frequently identified in deceased patients compared to *** note,monocytes secreted abundant quantities of IL-6,IL-8,and IL-1β which persisted at lower levels several weeks after recovery with concomitant normalization of CD69,PD-1 and TIM-3 expression and restoration of CD8^(+)T cell numbers.A hyperactivated/exhausted immune response dominate in severe SARS-CoV-2 infection,probably driven by an uncontrolled secretion of inflammatory cytokines by *** findings unveil a unique immunological profile in COVID-19 patients that will help to design effective stage-specific treatments for this potentially deadly disease.

关键词： C0VID-19 NK cells TIM-3 IL6 Monocytes

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Effects of chronic therapy with non-steroideal antinflammatory drugs on gastric permeability of sucrose: A study on 71 patients with rheumatoid arthritis

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World Journal of Gastroenterology 2006年第31期12卷 5017-5020页

作者： Marta Maino Nicola mantovani Roberta Merli Giulia Martina Cavestro Gioacchino Leandro Lucas Giovanni Cavallaro Vincenzo Corrente Veronica Iori Alberto Pilotto Angelo Franzè Francesco Di Mario Chair of GastroenterologyDepartment of Clinical Science University of ParmaItaly Gastroenterological UnitAzienda Ospedaliera "C.Poma" MantovaItaly IRCCS Castellana Grotte (BA)Italy Gastroenterological UnitAzienda Ospedaliera ParmaItaly IRCCS San Giovanni Rotondo (FG)Italy

AIM： To evaluate the gastric permeability after both acute and chronic use of non-steroidal anti-inflammatory drugs （NSAIDs） and to assess the clinical usefulness of sucrose test in detecting and following NSAIDs-induced gastric damage mainly in asymptomatic patients and the efficacy of a single pantoprazole dose in chronic users. METHODS： Seventy-one consecutive patients on chronic therapy with NSAIDs were enrolled in the study and divided into groups A and 13 （group A receiving 40 mg pantoprazole daily, group B only receiving NSAIDs）. Sucrose test was performed at baseline and after 2, 4 and 12 wk, respectively. The symptoms in the upper gastrointestinal tract were recorded. RESULTS： The patients treated with pantoprazole had sucrose excretion under the limit during the entire follow-up period. The patients without gastroprotection had sucrose excretion above the limit after 2 wk, with an increasing trend in the following weeks （P = 0.000）. A number of patients in this group revealed a significantly altered gastric permeability although they were asymptomatic during the follow-up period. CONCLUSION： Sucrose test can be proposed as a valid tool for the clinical evaluation of NSAIDs-induced gastric damage in both acute and chronic therapy. This tecnique helps to identify patients with clinically silent gastric damages. Pantoprazole （40 mg daily） is effective and well tolerated in chronic NSAID users .

关键词： Non-steroidal anti inflammatory drugs Gastric mucosal permeability Gastrointestinal toxicity Sucrose test Pantoprazole

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Pramipexole, a dopamine D3/D2 receptor-preferring agonist, attenuates reserpine-induced fibromyalgia-like model in mice

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Neural Regeneration Research 2022年第2期17卷 450-458页

作者： Carlos Pereira Martins Rodrigo Sebben Paes Gabriela mantovani Baldasso Eduarda Gomes Ferrarini Rahisa Scussel Rubya Pereira Zaccaron Ricardo Andrez Machado-de-Avila Paulo Cesar Lock Silveira Rafael Cypriano Dutra Laboratory of Autoimmunity and Immunopharmacology Department of Health SciencesCampus AraranguaUniversidade Federal de Santa CatarinaAraranguáSCBrazil Post-Graduate Program of Neuroscience Center of Biological SciencesUniversidade Federal de Santa CatarinaFlorianópolisSCBrazil Laboratory of Experimental Physiopathology Program of Postgraduate in Science of HealthUniversidade do Extremo Sul CatarinenseCriciumaSCBrazil

Fibromyalgia(FM) is a complex pathology described as persistent hyperalgesia including somatic and mood dysfunctions, depression and anxiety. Although the etiology of FM is still unknown, a significant decrease in biogenic amines is a common characteristic in its pathogenesis. Here, our main objective was to investigate the role of dopamine D3/D2 receptor during the reserpine-induced pain in mice. Our results showed that pramipexole(PPX) – a dopaminergic D3/D2 receptor agonist – inhibited mechanical allodynia and thermal sensitivity induced by reserpine. Relevantly, PPX treatment decreased immobility time and increased the number of grooming in the forced swimming test and splash test, respectively. Animals that received PPX remained longer in the open arms than the reserpine group using elevated plusmaze apparatus. The repeated PPX administration, given daily for 4 days, significantly blocked the mechanical and thermal allodynia during FM model, similarly to pregabalin, although it failed to affect the reserpine-induced thermal nociception. Reserpine administration induced significant downregulation of dopamine concentration in the central nervous system, and repeated treatment with PPX restored dopamine levels in the frontal cortex and spinal cord tissues. Moreover, PPX treatment inhibited oxidants production such as DCFH(2′,7′-dichlorodihydrofluorescein) and nitrite, also decreased oxidative damage(carbonyl), and upregulated the activity of superoxide dismutase in the spinal cord. Together, our findings demonstrated the ability of dopamine D3/D2 receptor-preferring agonist in reducing pain and mood dysfunction allied to FM in mice. All experimental protocols were approved by the Universidade Federal de Santa Catarina(UFSC) Ethics Committee(approval No. 2572210218) on May 10, 2018.

关键词： dopamine dopaminergic system fibromyalgia hyperalgesia pain pramipexole reserpine

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白细胞与内皮细胞的交流信号—细胞因子

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国外医学（免疫学分册） 1990年第4期13卷 206-209页

作者： mantovani A Dejana E 陈华粹

血管内皮已经不再视为一种被动性血管上的复盖物,它与有免疫作用的细胞的相互作用参与内平衡、炎症反应和免疫。由内皮细胞产生的或作用于内皮细胞的细胞因子就是介导白细胞与血管成份间复杂的双向作用的介质。细胞因子对内皮细胞(EC)... 详细信息

血管内皮已经不再视为一种被动性血管上的复盖物,它与有免疫作用的细胞的相互作用参与内平衡、炎症反应和免疫。由内皮细胞产生的或作用于内皮细胞的细胞因子就是介导白细胞与血管成份间复杂的双向作用的介质。细胞因子对内皮细胞(EC)功能的调节白介素1(IL-1)是一种由多种细胞,

关键词：细胞因子白细胞介素内皮细胞

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Genetic distinctions between autoimmune hepatitis in Italy and North America

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World Journal of Gastroenterology 2005年第12期11卷 1862-1866页

作者： Paolo Muratori Albert J.Czaja Luigi Muratori Georgios Pappas Silvana Maccariello Fabio Cassani Alessandro Granito Rodolfo Ferrari Vilma mantovani Marco Lenzi Francesco B.Bianchi Department of Internal Medicine Division of Gastroenterology and Hepatology Laboratorio Centralizzato Settore Genetica

AIM: Our goals were to analyze the known genetic predispositions for autoimmune hepatitis (AIH) in AIH Italian population and to compare them with North American counterparts. METHODS: Human leukocyte antigens (HLA) B8, C7, DR3, DR4, DR7, DR11, DR13, DQ2 and the B8-DR3-DQ2 phenotype were determined by microlymphocytotoxicity and polymerase chain reaction in 74 Italian patients (57 with type 1 and 17 with type 2 AIH) and 149 North American patients with type 1 AIH, and in adequate controls. RESULTS: B8-DR3-DQ2 occurred more frequently in Italian patients with type 1 AIH than in Italian controls (30% vs 7%, P<0.0001), but less frequently than in North American counterparts (30% vs 48%, P= 0.02). DR4 occurred less frequently in Italian patients with type 1 AIH (23% vs 43%, P= 0.01) and in controls (16% vs 34%, P= 0.0003) than in North American counterparts. No differences were found in alleles' frequency between type 1 and type 2 Italian AIH patients. DR11 had a frequency lower in type 1 Italian AIH patients than controls (17% vs 35%, P= 0.01). CONCLUSION: HLA DR4 is not associated with AIH in Italy. The known HLA risk factors for AIH occur similarly in Italian patients with type 1 and type 2 AIH, and they are less frequent than in North American patients. B8-DR3-DQ2 is the predominant phenotype of type 1 AIH also in Italy, and HLA DR11 may be a regionally distinctive protective factor against type 1 AIH.

关键词： Type 1 autoimmune hepatitis Type 2 autoimmune hepatitis Human leukocyte antigen

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印尼全球海洋支点战略研究

印尼全球海洋支点战略研究

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作者： ANISA PRATITA KIRANA mantovani 厦门大学

学位级别：硕士

本文研究印度尼西亚总统佐科(Joko Widodo)的“全球海洋支点战略”(Poros Maritim Dunia,PMD)。通过对印尼政府涉海机构、海洋地理、海洋经济和资源以及印度尼西亚海军(Tentara Nasional Indonesia Angkatan Laut,TNI AL)等方面的研究"...

本文研究印度尼西亚总统佐科(Joko Widodo)的“全球海洋支点战略”(Poros Maritim Dunia,PMD)。通过对印尼政府涉海机构、海洋地理、海洋经济和资源以及印度尼西亚海军(Tentara Nasional Indonesia Angkatan Laut,TNI AL)等方面的研究"评估了印尼实现其愿景的能力。本文认为印尼政府需要改进军事预算、海事法以及推动海军的现代化"才能实现其“全球海洋支点战略”的愿景。

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Possible Multiple Sources of the Strong 1117 Po Plain Earthquake, Inferred from the Plio-Quaternary Evolution of the Northern Adriatic Area

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International Journal of Geosciences 2021年第4期12卷 381-403页

作者： Enzo mantovani Giuliano Brancolini Daniele Babbucci Caterina Tamburelli Marcello Viti Dipartimento di Scienze Fisiche della Terra e dell’Ambiente Università di Siena Siena Italy Istituto Nazionale di Oceanografia e Geofisica Sperimentale—OGS Trieste Italy

The strongest documented seismic disaster ever occurred in the Po Plain area (January 3, 1117, M = 6.5) involved significant damage over a large zone. The genetic mechanism of such an event, most probably caused by more than one earthquake, is still an object of debate. Above all, the sources so far proposed cannot account for significant features of the observed macroseismic field. In this work, we suggest that the damage in the Verona zone was caused by the activation of a fault in the Lessini tectonic district, while damage in the central Po Plain may be related to a thrust fault located beneath the Giudicarie belt. The effects felt in northern Tuscany might derive from the seismic activation of the presumed SW-ward buried prolongation of the Giudicarie fault. The presence of such transpressional lithospheric discontinuity in the Adriatic domain since the upper Miocene and its reactivation (Pliocene-Pleistocene) as a thrust zone is mainly suggested by an accurate analysis of the observed deformation pattern in the central Mediterranean region. The proposed Giudicarie source may also help to explain the damage observed in the central Po Plain on December 25, 1222, which is not compatible with the seismic sources so far proposed.

关键词： Northern Adriatic Tectonics Po Plain Giudicarie Thrust Zone January 3 1117 Earthquake Sources

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Seismotectonics of the Padanian Region and Surrounding Belts: Which Driving Mechanism?

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International Journal of Geosciences 2016年第12期7卷 1412-1451页

作者： Marcello Viti Enzo mantovani Daniele Babbucci Caterina Tamburelli Nicola Cenni Dipartimento di Scienze Fisiche Della Terra e dell’Ambiente Università degli Studi di Siena Siena Italy Dipartimento di Fisica ed Astronomia Università degli Studi di Bologna Bologna Italy

It is argued that the complex tectonic pattern observed in the study area can plausibly be explained as an effect of the kinematics of the Iberia and Adria blocks, induced by the NNE ward motion of Africa and the roughly westward motion of the Anatolian-Aegean system with respect to Eurasia. These boundary conditions cause the constrictional regime which is responsible for the observed shortening processes in the Padanian region and Western Alps. The proposed dynamic context can plausibly account for the peculiar distribution of major seismic sources, located in the northern Apennines, the Giudicarie fault system, the offshore of the western Ligurian coast and the Swiss Alps. The observed tectonic pattern in Western Europe and the study area can hardly be reconciled with the implications of the roughly NWward convergence between Africa and Eurasia proposed by global kinematic models, whereas it is compatible with the alternative Africa-Eurasia kinematics and plate mosaic proposed by [1].

关键词： Seismotectonics Geodynamics GPS Mediterranean Padanian

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