1,721,117 research outputs found
AUTOIMMUNITY, ENVIRONMENT AND GENETICS IN INFLAMMATORY DISORDERS OF CENTRAL AND PERIPHERAL NERVOUS SYSTEM
Get PDFInflammatory demyelinating diseases are a broad group of disorders characterized by immune-mediated myelin damage of suspected autoimmune aetiology. Clinical and experimental evidences support the general concept that environmental microbial and non-microbial triggers may lead in genetic susceptible individuals to disruption of self-tolerance, including activation of self-reactive lymphocytes and generation of autoantibodies. However, the environmental triggers remain in most cases elusive, there is no easy way to assess the polygenic susceptibility trait in affected individuals, and we often fail to demonstrate the presence of circulating antibodies or other markers of an auto-immune signature. These limits ultimately result in diagnostic uncertainty and possible misdiagnosis. Finally, many of these disorders show a chronic progressive phase, which is clinically paralleled by increasing disability and resistance to treatment, and for which the ultimate cause is still unknown. This work tried to address some of these issues in the field of immune-mediated inflammatory disorders of the central and peripheral nervous system. In the first part of this work, we investigated the role of air pollution as novel environmental factor impacting on Multiple Sclerosis disease course. We found an association between respiratory exposure to particulate matter and occurrence of contrast-enhancing lesions on brain Magnetic Resonance Imaging in MS patients and we identified a candidate mechanism underlying this association involving up-regulation on peripheral blood lymphocytes of adhesion molecules and chemokine receptors and amplification of Th17 cells response. Secondly, we investigated the clinical and serological features of patients with contemporary demyelination of the central and peripheral nervous system (CCPD). The data suggested that CCPD manifests with heterogeneous features, frequent post-infectious onset, primary PNS or CNS involvement, monophasic or chronic disease course, unsatisfactory response to treatments, and generally poor outcome. As opposed to a previous report in a Japanese cohort, antibodies to Neurofascin-155, a transmembrane protein expressed on both CNS and PNS does not seem to represent a marker of the disease in Caucasian patients. The hypothesis of a distinctive genetic susceptibility profile in patients with CCPD, as well as in patients with other acute demyelinating syndromes of CNS, is currently under investigation. Contrarily, antibodies to NF155, as well as to other proteins involved in axo-glial coupling at the paranodal regions flanking the node of Ranvier, were found in 5.5% of a large multi-centre cohort of patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and are associated with particular clinical features, a more aggressive disease course and a poor response to immunoglobulins. Moreover we identified that up to 40% of CIDP patients show reactivity to axonal of myelin nerve components, and sera are currently being investigated for identification of novel targets. Despite their low prevalence, the identification of these novel antibodies as reliable hallmark of the immune-mediated process of CIDP is highly valuable in terms of both advancement in the understanding of the disease-causing mechanisms as well as a tool to assist clinician in its diagnosis. In fact, the diagnosis of this CIDP is challenging and even in highly specialized centres half of the patients are misdiagnosed. Finally, we addressed the topic of the relationship between inflammatory and degenerative pathologic processes in sporadic inclusion body myositis (IBM), the most common muscle disease in adults aged older than 50 years, and found that TDP43-dependent splicing is altered in IBM suggesting that more widespread changes of RNA metabolism due TDP43 loss-of-function may bear pathogenic relevance to immunotherapy-resistant muscle and nerve degeneration.Inflammatory demyelinating diseases are a broad group of disorders characterized by immune-mediated myelin damage of suspected autoimmune aetiology. Clinical and experimental evidences support the general concept that environmental microbial and non-microbial triggers may lead in genetic susceptible individuals to disruption of self-tolerance, including activation of self-reactive lymphocytes and generation of autoantibodies. However, the environmental triggers remain in most cases elusive, there is no easy way to assess the polygenic susceptibility trait in affected individuals, and we often fail to demonstrate the presence of circulating antibodies or other markers of an auto-immune signature. These limits ultimately result in diagnostic uncertainty and possible misdiagnosis. Finally, many of these disorders show a chronic progressive phase, which is clinically paralleled by increasing disability and resistance to treatment, and for which the ultimate cause is still unknown. This work tried to address some of these issues in the field of immune-mediated inflammatory disorders of the central and peripheral nervous system. In the first part of this work, we investigated the role of air pollution as novel environmental factor impacting on Multiple Sclerosis disease course. We found an association between respiratory exposure to particulate matter and occurrence of contrast-enhancing lesions on brain Magnetic Resonance Imaging in MS patients and we identified a candidate mechanism underlying this association involving up-regulation on peripheral blood lymphocytes of adhesion molecules and chemokine receptors and amplification of Th17 cells response. Secondly, we investigated the clinical and serological features of patients with contemporary demyelination of the central and peripheral nervous system (CCPD). The data suggested that CCPD manifests with heterogeneous features, frequent post-infectious onset, primary PNS or CNS involvement, monophasic or chronic disease course, unsatisfactory response to treatments, and generally poor outcome. As opposed to a previous report in a Japanese cohort, antibodies to Neurofascin-155, a transmembrane protein expressed on both CNS and PNS does not seem to represent a marker of the disease in Caucasian patients. The hypothesis of a distinctive genetic susceptibility profile in patients with CCPD, as well as in patients with other acute demyelinating syndromes of CNS, is currently under investigation. Contrarily, antibodies to NF155, as well as to other proteins involved in axo-glial coupling at the paranodal regions flanking the node of Ranvier, were found in 5.5% of a large multi-centre cohort of patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and are associated with particular clinical features, a more aggressive disease course and a poor response to immunoglobulins. Moreover we identified that up to 40% of CIDP patients show reactivity to axonal of myelin nerve components, and sera are currently being investigated for identification of novel targets. Despite their low prevalence, the identification of these novel antibodies as reliable hallmark of the immune-mediated process of CIDP is highly valuable in terms of both advancement in the understanding of the disease-causing mechanisms as well as a tool to assist clinician in its diagnosis. In fact, the diagnosis of this CIDP is challenging and even in highly specialized centres half of the patients are misdiagnosed. Finally, we addressed the topic of the relationship between inflammatory and degenerative pathologic processes in sporadic inclusion body myositis (IBM), the most common muscle disease in adults aged older than 50 years, and found that TDP43-dependent splicing is altered in IBM suggesting that more widespread changes of RNA metabolism due TDP43 loss-of-function may bear pathogenic relevance to immunotherapy-resistant muscle and nerve degeneration
Contraction or sequence variant of an intergenic repeat-Alu element leads to inherited thyroid disease
No full textGenomic and epigenomic techniques identify a new variation type causing Mendelian disease by altering the non-coding regulatory network in thyroid cells — solving a hidden cause linked for 20 year
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
[The role of magnetic resonance imaging with a low-intensity field (0.2 T) in assessing expansive lesions of the hand and wrist].
No full textThe diagnostic capabilities of a small-size low-field (0.2-T) MR unit with a dedicated coil were investigated in the study of expansive lesions of the hand and wrist. Twenty-five patients suffering from the following diseases were examined: synovial cyst (6 patients), ganglion cyst (4), acute suppurative tenosynovitis (3), stenosing tenosynovitis (2), arteriovenous fistula (1), lipoma (1), fibrolipoma (2), chondroma (1), glomus tumor (1), fibromatosis palmaris (3), villonodular synovitis (1). Spin Echo (SE) and Gradient Echo (GE) scans were performed on all patients. The MR findings were compared with US, surgical and pathologic results. In synovial and ganglion cysts, acute suppurative and stenosing tenosynovitis, fibromatosis palmaris, fibrolipoma and lipoma, MRI showed typical patterns. In arteriovenous fistula, chondroma, glomus tumor and villonodular tenosynovitis, an accurate diagnosis could not be made: in these cases US failed to yield unquestionable results and the lesions could be diagnosed only at pathology. MRI yielded very accurate information as to lesion site and relationship with the surrounding structures; this kind of information, which is extremely important for the surgical approach, is not always provided by US. Low-field MRI can be considered a valuable diagnostic tool in the study of some expansive lesions of the hand and wrist. In other lesions this method can play a major role for both their characterization and the surgical approach
Chronic Cough as a Genetic Neurological Disorder? Insights from Cerebellar Ataxia with Neuropathy and Vestibular Areflexia Syndrome (CANVAS)
No full textChronic cough is common, and in many cases unexplained or refractory to otherwise effective treatment of associated medical conditions. Cough hypersensitivity has developed as a paradigm that helps to explain clinical and research observations that frequently point towards chronic cough as a neuropathic disorder. Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a recently described neurological condition whose clinical features include gait ataxia, unsteadiness, peripheral neuropathy, and autonomic dysfunction. Chronic cough is also a common feature of the syndrome, with features of hypersensitivity, often preceding core neurological symptoms by up to 30 years or more. The genetic basis in a majority of cases of CANVAS appears to be biallelic variable repeat intron expansion sequences within RFC1, a gene normally involved in the regulation of DNA replication and repair. The same polymorphism has now been identified at an increased frequency in patients with unexplained or refractory chronic cough in the absence of defining clinical features of CANVAS. This review expands on these points, aiming to increase the awareness of CANVAS amongst clinicians and researchers working with chronic cough. We discuss the implications of a link between RFC1 disease and cough. Improved understanding of CANVAS may lead to an enhanced grasp of the pathophysiology of chronic cough, and new approaches to antitussive treatments
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
I soggetti privati e la valorizzazione del patrimonio culturale
No full textIl saggio analizza il tema del “patrimonio culturale” sotto il profilo statico della tutela (prevenzione) ma anche sotto quello dinamico delle opportunità di sviluppo (valorizzazione). Il Codice dei beni culturali e alcuni recenti interventi legislativi tendono a riconoscere ai privati un ruolo sempre più importante. Le forme di collaborazione pubblico-privato, oltre ad aver il pregio di coniugare un interesse pubblico (utilità sociale) con un interesse privato (il profitto), sono in grado di assicurare vantaggi ulteriori, sotto il profilo dell’efficienza e dell’efficacia
Il giudice amministrativo ed il biodiritto: “soggettività” della giurisdizione e “sovranità” del corpo
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