9,109,104 research outputs found
Adenomyosis: histological remarks about 1500 hysterectomies
No full text1500 surgical bits had been histologically examined. There were 556 total hysterectomies and 994 total hysterectomies with bilateral salpingo-oophorectomy. In all we have found 310 cases of adenomyosis (20,6%); 60,3% of them had a submucosal location. A clear correlation between adenomyosis and pregnancy resulted, expecially, between submucosal adenomyosis and number of pregnancies
High throughput sequencing analysis for the molecular diagnosis of Inherited Thrombocytopenias
No full textInherited thrombocytopenias are a heterogenous group of rare genetic disorders characterized by reduced platelet count sometimes combined with bleeding tendency and/or other clinical defects. The molecular diagnosis of ITs is essential to make clinical decision and infer personalized prognosis and risks.
More than 30 genes have been identified that harbor mutations responsible for ITs (Balduini et al., 2017). In addition, ITs often show phenotypic overlaps that hamper the correct diagnosis with the traditional diagnostic algorithm based on step-wise specialized investigations.
However, the advent of next generation sequencing has changed the diagnostic approach of diseases characterized by high genetic heterogeneity like ITs.
In order to improve the diagnosis of IT, we designed a targeted next generation sequencing panel (IT-NGS) to screen the 28 genes more commonly mutated in ITs. Ninety-seven consecutive probands with a suspicious of ITs had been sequenced.
The analysis led us to reach a definite diagnosis for 37 probands. In these probands we identified known or novel likely pathogenic mutations causing specific diseases, including monoallelic Bernard Soulier syndrome (N=14), biallelic Bernard Soulier syndrome (N=4), ACTN1-related thrombocytopenia (N=4), MYH9-related disease (N=7), ANKRD26-related thrombocytopenia (N=4), congenital amegakaryocytic thrombocytopenia (N=1), grey platelet syndrome (N=1), Wiskott-Aldrich syndrome (N=1) and Acute Myelogenous Leukemia (N=1). In another 34 cases we identified variants of uncertain significance (VUS) whose pathogenic role has to be supported by segregation analysis and in-depth functional studies. Since 17 probands had no potential candidate variant impacting IT-NGS genes, they are eligible for whole exome sequencing (WES) to clone novel genes involved in ITs.
In conclusion, since some IT forms predispose to additional acquired disease during life, an accurate diagnosis is essential to infer personalized prognosis and define proper treatments and follow-up.
Because of clinical and genetic heterogeneity, the molecular diagnosis of ITs represents a lengthy and expensive challenge using conventional technologies.
The use of IT-NGS in clinical practice aided by specific investigations clarifying the role of variant of uncertain significance, overcomes these issues facilitating a definite diagnosis in patients with a suspicious of known ITs forms
Distribuzione geografica relativa a reperti operatori Gozzo con eutiroidismo.dell'Ospedale dell'Aquila (dal 1954 al 1979) e di Popoli ( dal 1960 al 1979).
No full textSite-Directed Mutagenesis and Chemical Modification of the Six Native Cysteine Residues of the Rat Mitochondrial Carnitine Carrier: Implications for the Role of Cysteine-136
No full textBy use of site-directed mutagenesis in combination with chemical modification of mutated proteins, the role of the six Cys residues in the transport function of the rat mitochondrial carnitine carrier (CAC) was studied. Several CAC mutants, in which one or more Cys residues had been replaced with Ser, were overexpressed in Escherichia coli, purified, and reconstituted in liposomes. The efficiency of incorporation into liposomes of the reconstituted proteins was lower for all constructs lacking Cys-23. Single, double, and quadruple replacement mutants showed V(max) comparable to that of the wild type. On the basis of the values of internal and external transport affinities (K(m)) for carnitine and of their comparison with those measured in mitochondria, the recombinant CAC is oriented unidirectionally in the liposomes, right side out compared to mitochondria. Substitution of Cys-136 with Ser caused a nearly complete loss of sensitivity of the CAC to N-ethylmaleimide, (2-aminoethyl)methanethiosulfonate hydrobromide (MTSES), and other hydrophilic SH reagents but not to the very hydrophobic N-phenylmaleimide. The wild-type CAC and the mutants containing Cys-136 showed substrate protection against NEM and MTSES inhibition and against NEM labeling. The data show that none of the native cysteines is essential for the transport mechanism and that Cys-136 is the major target of SH reagents and raise the hypothesis that Cys-136 is accessible from the external medium and is located at, or near, the substrate binding site. A model of the CAC is proposed in which the matrix hydrophilic loop containing Cys-136 protrudes into the membrane between the transmembrane domains of the protei
What’s behind increasing wage inequality? Explaining the Italian case using RIF-OLS
No full textThis paper aims to identify how and to what extent the Italian labour market structure, in terms of job composition and institutional changes, shaped the dynamics of wages and wage inequality in the decade between 2007 and 2017. We investigate the main determinants behind the rise in wage inequality in Italy by using Recentered Influence Function (RIF) regressions. This econometric approach allows - on the one hand - to directly assess the effects on the unconditional distribution and on "beyond the mean" statistics, like the Gini coefficient. On the other, it decomposes inequality into endowment and wage effects, following the standard Oaxaca-Blinder technique. We observe that working structures and institutional changes - contractual arrangements (permanent vs temporary contracts) and working hours (full-time vs part-time) - are the main factors in explaining the deterioration in wages at the bottom of the income distribution scale, and the consequent increase in wage inequality
The role of tasks, contractual arrangements and job composition in explaining the dynamics of wage inequality: Evidence from France
No full textStudio del trasporto e diffusione di inquinanti radioattivi nel suolo e sottosuolo
No full textNel presente lavoro è stato affrontato lo studio del trasporto e della destinazione degli inquinanti radioattivi nel suolo e sottosuolo tramite l’utilizzo della piattaforma software FRAMES ed in particolare del modulo MEPAS.
La prima parte dell’opera è stata dedicata alla trattazione della radioattività, analizzandone gli aspetti generali e soffermandosi sul concetto di rifiuto radioattivo e sulla gestione e sullo smaltimento dello stesso.
Si sono poi analizzati i principali modelli di trasporto per la valutazione del destino dei contaminanti nell’ambiente, fase complessa nella valutazione del rischio o in qualsiasi altra valutazione di impatto ambientale. Lo studio complessivo del problema ha richiesto la suddivisioni in tre momenti distinti, che si riferiscono al modello concettuale di analisi di rischio:
le sorgenti di contaminazione;
le vie di migrazione;
i bersagli di contaminazione
The mitochondrial carnitine/acylcarnitine carrier protein: cDNA, primary structure and comparison with other mitochondrial carriers
No full textGENBANK/o acid sequence of the rat carnitine carrier protein, a component of the inner membranes of mitochondria, has been deduced from the sequences of overlapping cDNA clones. These clones were generated in polymerase chain reactions with primers and probes based on amino acid sequence information, obtained from the direct sequencing of internal peptides of the purified carnitine carrier protein from rat. The protein sequence of the carrier, including the initiator methionine, has a length of 301 amino acids. The mature protein has a modified alpha-amino group, although the nature of this modification and the precise position of the N-terminal residue have not been ascertained. Analysis of the carnitine carrier sequence shows that the protein contains a 3-fold repeated sequence about 100 amino acids in length. Dot plot comparisons and sequence alignment demonstrate that these repeated domains are related to each other and also to the repeats of similar length that are present in the other mitochondrial carrier proteins sequenced so far. The hydropathy analysis of the carnitine carrier supports the view that the domains are folded into similar structural motifs, consisting of two transmembrane alpha-helices joined by an extensive extramembranous hydrophilic region. Southern blotting experiments suggest that both the human and the rat genomes contain single genes for the carnitine carrier. These studies provide the primary structure of the mitochondrial carnitine carrier protein and allow us to identify this metabolically important transporter as a member of the mitochondrial carrier family, and the sixth of the members whose biochemical function has already been identifie
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