1,721,056 research outputs found
Identification of Novel FBN1 Mutations in Patients with Marfan Syndrome using DHPLC Analysis.
No full textIdentification of Novel FBN1 Mutations in Patients with Marfan Syndrome using DHPLC Analysis.
M. Grasso 1, S. Ansaldi 1, A. Mori 1, A. Pisani 1, L. Lanzarini 2, A. Pilotto 1,
C. Lucchelli 1, L. Tavazzi 2, E. Arbustini 1;
1 Cardiovascular Pathology and Molecular Diagnostic Lab, Transplant
Research Area, IRCCS Policlinico San Matteont, Pavia, Italy, 2
Cardiology Division, IRCCS Policlinico San Matteo, Pavia, Italy.
Marfan Syndrome (MFS, MIM#154700) is an autosomal dominant
inherited connective tissue disorder (prevalence:1/5000) caused
by mutations in the fibrillin-1 gene (FBN1, 15q21). The disorder is
characterised by highly variable phenotypic manifestations, mainly in
cardiovascular, ocular and skeletal systems. The FBN1 (230 Kb, 65
exons, 2871 amino acids) has revealed more than 500 mutations.
We describe 11 novel mutations that were identified in 12 probands
(one with sporadic and ten with familial disease). The MFS diagnosis
was evaluated following the revised diagnostic criteria of the Ghent
nosology. The FBN1 gene was analysed using DHPLC technology
(Transgenomic) and automated sequencing (ABI 3100).All family members were tested for the mutations found. These mutations were absent in 50 controls. Our results suggest that DHPLC is a reliable and cost-effective
technique for the screening of such a large gene and that FBN1 screening could be a helpful tool to confirm and possibly anticipate the clinical diagnosis in familial cases
Functional, structural, and genetic mitochondrial abnormalities in myocardial diseases
No full textMyocardial tissue is highly dependent on energy supplied by normal mitochondrial function. Therefore defects of energy production or utilization affect the heart in both syndromic and isolated disorders. Knowledge of the peculiar structural, functional, and genetic characteristics of mitochondria provides the basis for identification and classification of mitochondrial defects as well as for establishment of a diagnostic workup useful for related cardiac disorders. This review is therefore dedicated to the characteristics of normal mitochondria and the pathologic alterations of these organelles in various cardiovascular diseases
Molecular imaging of misfolded protein pathology for early clues to involvement of the heart
No full textUltrastructural definition of apoptosis in heart failure
No full textCardiac myocytes die through apoptosis, oncosis, and autophagy. Apoptosis affects single cells and is morphologically characterized by nuclear fragmentation with generation of apoptotic bodies that can be seen either within dying cells or free in the interstitial spaces. Dead myocytes are removed by macrophages through phagocytosis without triggering inflammation. The circulating markers of myocyte necrosis are not increased by apoptosis. The morphologic changes of the induction and early execution phases are seen at electron microscopy while late fragmentation is visible on both light and electron microscopy. Immunoelectron microscopy provides combined functional and structural information showing cytochrome c immuno-labelling release from mitochondria, TUNEL labelling of apoptotic nuclei, annexin V translocation in the outer plasma cell layer. Oncosis is characterized by specific morphologic features that may coexist with apoptosis, especially in ischemic myocardium. Autophagy is a defense process that is associated with significant myocardial damage and necrosis when removal of the lysosomal content is impaired. Morphological features of apoptosis, oncosis, and autophagocytosis may coexist at the same time. Although dead myocytes showing characteristics of autophagy and apoptosis are rarely observed in human decompensated hearts, autophagic vacuoles, and early apoptotic changes may be seen more often in morphologically viable myocytes. Such features may occur in failing hearts of both ischemic and non-ischemic etiology. The shared mode of cardiac myocyte death in failing human hearts of different etiologies suggests that preservation of myocyte integrity may be possible by similar therapeutic strategies
High sensivity and specificity of denaturing high performance liquid chromatography (DHPLC) for mutation analysis of the FBN1 gene in patients with Marfan syndrome.
No full textHigh sensivity and specificity of denaturing high performance liquid chromatography (DHPLC) for mutation analysis of the FBN1 gene in patients with Marfan syndrome.
A. Mori 1 , S. Ansaldi 1 , M. Grasso 1 , A. Pilotto 1 , C. Lucchelli 1 , L.
Lanzarini 2 , M. Diegoli 3 , L. Tavazzi 2 , E. Arbustini 1 ;
1 Cardiovascular Pathol. and Molec. Diagn. - Res.Transplantation
Lab. , IRCCS Policlinico S.Matteo, Pavia, Italy, 2 Cardiology Division,
IRCCS Policlinico S.Matteo, Pavia, Italy, 3 Department of Pathology
- University of Pavia, Pavia, Italy.
Marfan syndrome is an autosomal dominant inherited disorder of the
connective tissue that principally involves the cardiovascular,ocular
and skeletal systems. The incidence is estimated to be 1:5000, with
25% sporadic cases. The leading cause of death is related to the
cardiovascular involvement, in particular aortic root dilatation and
rupture.
The disease is caused by alteration in FBN1 gene (65 exons, located
at 15q15-q21.1). Causal mutations are scattered throughout the gene
and are largely unique to individual families.
The FBN1 gene was analyzed in 29 unrelated patients suspected
to be affected by Marfan syndrome. To develop an efficient and
faster method capable of identify all possible mutations in this gene,
we introduced DHPLC technology in the analysis of 25 exons in
which mutations recur. We first analysed the FBN1 exons and exon-
flanking non coding regions gene coding regions with automated
sequencing of all 65 exons (ABI PE- 373 DNA Sequencer) to
identify mutations and polymorphisms. Then, DHPLC analysis
was carried out on the WaveTM DNA Fragment Analysis System
(Transgenomic, Cheshire, UK). DNA fragment elution profiles were
displayed using the Transgenomic WAVEMAKER-TM software.
Chromatograms were analysed and amplified fragments showing
alterations were re-confirmed by automated sequencing. Overall, by
direct sequencing we indentify 19 variants (14 in coding regions and
5 in intronic sequences). A corresponding number of heteroduplex
297 profiles was detected with DHPLC with 100% correspondence to the
variant-containing regions previously identified by direct sequencing.
Our results confirms that DHPLC is a highly sensitive and specific
technology for DNA sequence variant detection
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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