1,721,177 research outputs found

    Gut microbiome investigation in celiac disease: from methods to its pathogenetic role

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    Our body is inhabited by a variety of microbes (microbiota), mainly bacteria, that outnumber our own cells. Until recently, most of what we knew about the human microbiota was based on culture methods, whereas a large part of the microbiota is uncultivable, and consequently previous information was limited. The advent of culture-independent methods and, particularly, of next-generation sequencing (NGS) methodology, marked a turning point in studies of the microbiota in terms of its composition and of the genes encoded by these microbes (microbiome). The microbiome is influenced predominantly by environmental factors that cause a large inter-individual variability (~20%) being its heritability only 1.9%. The gut microbiome plays a relevant role in human physiology, and its alteration ("dysbiosis") has been linked to a variety of inflammatory gut diseases, including celiac disease (CD). CD is a chronic, immune-mediated disorder that is triggered by both genetic (mainly HLA-DQ2/DQ8 haplotypes) and environmental factors (gluten), but, in recent years, a large body of experimental evidence suggested that the gut microbiome is an additional contributing factor to the pathogenesis of CD. In this review, we summarize the literature that has investigated the gut microbiome associated with CD, the methods and biological samples usually employed in CD microbiome investigations and the putative pathogenetic role of specific microbial alterations in CD. In conclusion, both gluten-microbe and host-microbe interactions drive the gluten-mediated immune response. However, it remains to be established whether the CD-associated dysbiosis is the consequence of the disease, a simple concomitant association or a concurring causative factor

    Electrophoretic behaviour and partial characterization of disease-associated serum forms of gamma-glutamyltransferase.

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    We have recently devised an improved procedure for the rapid electrophoretic separation of multiple forms of serum gamma‐glutamyltransferase (GGT). This procedure is based on the separation on cellulose acetate strips, usually employed for lipoprotein electrophoresis, followed by visualization with a fluorescent reagent. The method is highly sensitive and the fractions are more clearly resolved than with other, procedures. Reference intervals have been evaluated in the sera from 142 healthy subjects and the patterns (two GGT forms comigrating with alpha1 and alpha2‐globulin) are reproducible. In 150 sera from patients with various hepatobiliary diseases (including neoplasias), acute pancreatitis and non liver‐involving neoplasias, we observed some disease‐specific GGT forms: an albumin comigrating enzyme (Alb‐GGT) specific of liver neoplasia; a gamma‐globulin comigrating GGT (gamma‐GGT) and a nonmigrating isoform (dep‐GGT) both specifically associated to extrahepatic jaundice. Multiple lipoprotein fraction precipitation showed that beta‐gamma‐ and dep‐GGT are complexes between GGT and low density lipoprotein and very low density lipoproteins (LDL + VLDL), and that some of the alpha1‐GGT from cirrhotic patients is a complex between GGT and high density lipoprotein (HDL). GGT fractions from normal subjects and Alb‐GGT from patients with liver neoplasia do not appear to be complexed with lipoproteins. The amount of GGT complexed with LDL + VLDL differs in various hepatobiliary diseases, and using a cutoff of 20 U/L it is possible to use this test to distinguish non‐cholestatic diseases from liver malignancies (i. e. in monitoring cirrhotics and other high risk groups of patients as to the possible evolution to liver cancer, in patients with gastrointestinal tumor which frequently metastasizes to the liver). Furthermore, treatment of GGT with neuraminidase confirms the association of sialic acid with all the GGT fractions, although Alb‐GGT is more sensitive to this treatment than is beta‐GGT. Our study, indicating the existence of clinical biochemistry correlations between isoenzyme patterns of serum GGT and diseases of hepatobiliary nature including neoplasias, opens up the possibility of enlarging the vocabulary of biochemical signals in these disorders. Furthermore, the lipoprotein‐precipitated fractions of serum GGT are an additional test for discriminating hepatocarcinoma from noncholestatic chronic hepatitis and cirrhosis

    Serum type 2 macro creatine-Kinase isoenzyme is not a useful marker of severe liver diseases or neoplasia.

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    We studied the creatine kinase (CK) isoenzyme pattern in sera from 332 patients affected by hepatic cirrhosis and several neoplastic diseases (102 cirrhosis, 36 hepatocarcinoma, 16 metastatic liver tumor, 40 breast cancer, 18 other neoplastic diseases and 120 cases of leukemia or lymphoma) to evaluate both its diagnostic utility for cancer diagnosis and its power as a prognostic index. Type-2 macro CK (mitochondrial creatine kinase) was detected, with no statistical difference in cirrhosis (14%), hepatocarcinoma (16%), metastatic liver tumor (31%), breast cancer (5%) and other tumors (6%). It was not detected in any patient with leukemia or lymphoma. The presence of type-2 macro CK was unrelated to the stage of either cirrhosis or hepatocarcinoma, according to Child and Okuda, respectively, nor was it correlated to serum cytolytic enzyme levels or to gamma-globulin levels. In cirrhotics, type-2 macro CK was not linked to serum levels of the following tumor markers: alpha-fetoprotein, pseudouridine and gamma-glutamyltransferase isoenzymes complexed to low-density lipoprotein. In addition, the atypical band persisted in several patients with cirrhosis monitored for six months who did not show any evidence of evolution toward hepatocarcinoma. Thus, type-2 macro CK has poor diagnostic sensitivity for neoplastic diseases, and lacks prognostic value both in cirrhosis and neoplastic diseases. © 1990 The Canadian Society of Clinical Chemists

    Il contraddittorio endoprocedimentale: esigenze di tutela del contribuente tra princìpi costituzionali e dell’Ue

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    Il contraddittorio endoprocedimentale: esigenze di tutela del contribuente tra princìpi costituzionali e dell’U

    Multivariate discriminant analysis of biochemical parameters for the differential diagnosis of clinically confounding liver diseases.

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    We describe a series of studies on the contribution of laboratory medicine to the differential diagnosis of clinically confounding diseases in the field of chronic hepatobiliary diseases. Ascitic cholesterol and lactate dehydrogenase (LD), selected by multivariate discriminant analysis (MDA) from a multitude of serum and ascitic analytes, correctly classified 100% of patients with malignant ascites or non-malignant ascites. In addition, ascitic pseudouridine differentiated hepatocarcinoma (HC) from cirrhotic ascites with a diagnostic effectiveness (overall discrimination power) of 90%. A panel of analytes constituted by serum gamma-glutamyltransferase (GGT), the GGT isoenzyme complexed with low- and very low-density lipoprotein, aspartate aminotransferase, copper, hepatic alkaline phosphatase (AP), the LD-5 isoenzyme and alpha-fetoprotein (AFP), selected by the MDA, correctly classified 93% of about 200 cases of cirrhosis or HC. Finally, MDA also identified an equation, based on serum values of the LD-4/LD-5 and carcinoembryonic antigen/AFP ratios, AP and iron that correctly classified 96% of HC or secondary liver neoplasia cases in 100 patients. This approach based on panels of analytes selected by a sophisticated statistical analysis is a rapid and non-invasive contribution to the differential diagnosis of chronic liver disease including neoplasia

    The gamma-glutamyltransferase isoenzyme pattern in serum as a signal discriminating between hepatobiliary diseases, including neoplasias.

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    We have used the gamma-glutamyltransferase (GGT) isoenzyme pattern in serum as a means for discriminating between hepatobiliary diseases, including neoplasias. The reference pattern, determined in 142 normal subjects with a simplified conventional cellulose acetate electrophoretic procedure, contained two GGT bands, alpha1-GGT and alpha2-GGT, in proportions of 60-80% and 20-40%, respectively. Sera from 95 hepatobiliary patients showed typical isoenzyme features: (a) a beta-migrating GGT form that was < 10% of the total GGT in chronic hepatitis and cirrhosis, and ≤ 30% of the total GGT in cirrhosis with intrahepatic cholestasis and in cases of extra- and intrahepatic obstructive jaundice, including liver neoplasias; (b) a gamma-migrating GGT band and (or) a 'dep-GGT' (nonmigrating) band in cases of extrahepatic jaundice; and (c) an albumin-migrating GGT band that had a diagnostic sensitivity of 75% for hepatic tumors. The diagnostic specificity of this last band is 92% toward other hepatic disorders and 91% toward nonhepatic neoplasias; we consider it a potential specific marker for primary or metastatic liver neoplasias

    The gamma-glutamyltransferase isoenzyme pattern in serum as a signal discriminating between hepatobiliary diseases, including neoplasias.

    No full text
    We have used the gamma-glutamyltransferase (GGT) isoenzyme pattern in serum as a means for discriminating between hepatobiliary diseases, including neoplasias. The reference pattern, determined in 142 normal subjects with a simplified conventional cellulose acetate electrophoretic procedure, contained two GGT bands, alpha1-GGT and alpha2-GGT, in proportions of 60-80% and 20-40%, respectively. Sera from 95 hepatobiliary patients showed typical isoenzyme features: (a) a beta-migrating GGT form that was < 10% of the total GGT in chronic hepatitis and cirrhosis, and ≤ 30% of the total GGT in cirrhosis with intrahepatic cholestasis and in cases of extra- and intrahepatic obstructive jaundice, including liver neoplasias; (b) a gamma-migrating GGT band and (or) a 'dep-GGT' (nonmigrating) band in cases of extrahepatic jaundice; and (c) an albumin-migrating GGT band that had a diagnostic sensitivity of 75% for hepatic tumors. The diagnostic specificity of this last band is 92% toward other hepatic disorders and 91% toward nonhepatic neoplasias; we consider it a potential specific marker for primary or metastatic liver neoplasias

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

    Variations on the Author

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    “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
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