1,720,968 research outputs found
Animal and cell models for Lesch-Nyhan syndrome
No full textLesch–Nyhan Disease (LND) is a rare X-linked recessive metabolic and neurological syndrome due to the deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT). Peculiar neurological symptoms occur in LND: dystonia, choreoathetosis, compulsive self-injurious behaviour, with no obvious correlation to the deficiency of this purine salvage anzyme. A dopaminergic deficit was found to underlie the neurologic symptoms, but the aetiology for such alteration seemed inexplicable. Several lines of research were carried out to find the molecular basis for the neurological phenotype, and HPRT deficient animal and cellular models were developed. None of them, animal or cellular model, can be considered the completely proper one. Available animal models are rodents, which share several biochemical and molecular abnormalities with HPRT deficient patients, but do not display similar neurologic symptoms. Cellular models obtained from different cell lines present notable biochemical and molecular aberrations though many discrepancies suggest significant differences depending upon cell types and tissue source. Nevertheless, experimental studies on both models provided remarkable information on the biochemical and molecular pathways potentially responsible for the neurological damage in this disease, demonstrating transcriptional aberrations affecting different genes in various metabolic pathways and gene dysregulations in neuronal development and differentiation, producing neurotransmission defects. These findings led to attribute an unexpected paramount role in neurodevelopment to HPRT, beside the well-known metabolic functions.
© 2019 Elsevier Lt
Thiopurine methyltransferase activity in the erythrocytes of adults and children: and HPLC-linked assay
No full textA non-radioactive method that uses reverse-phase high performance liquid chromatography is described for the determination of thiopurine methyltransferase (E.C. 2.1.1.67) activity in human erythrocytes. The method is based on the direct quantitation of 6-methyl-mercaptopurine produced from 6-mercaptopurine by crude erythrocyte lysates. The method is accurate and reliable and suitable for diagnostic use. Activity values in control adults ranged from 5 to 32 pmol/h/mg haemoglobin. The activity in the erythrocytes of adult males was significantly higher compared to females (21±5 and 15±8 pmol/h/mg haemoglobin, respectively). The activity measured in the erythrocytes of children (22±5 pmol/h/mg haemoglobin) did not show any significant difference compared to adults. Thiopurine methyltransferase activity was measured in a female patient with systemic sclerosis who developed severe bone marrow depression after treatment with azathioprine and allopurinol. Activity (6.3 ± 0.5 pmol/h/mg haemoglobin) was found in the lowest range of controls thus supporting the hypothesis that it could be responsible for increased azathioprine cytotoxicity
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
Identification of the 5’-nucleotidase activity altered in neurological syndromes
No full text5'-Nucleotidases comprise a family of enzymes involved in the regulation of intracellular and extracellular nucleotide concentration. There is increasing knowledge about an involvement of these activities in the aetiology of neurological disorders. In this paper we present a protocol for the identification of the altered enzyme in fibroblasts primary culture from patients and controls
Identification of the nucleotidase responsible for the AMP hydrolysing hyperactivity associated with neurological and developmental disorders
No full textNucleoside monophosphate phosphohydrolases comprise a family of enzymes dephosphorylating nucleotides both in intracellular and extracellular compartments. Members of this family exhibit different sequence, location, substrate specificity and regulation. Besides the ectosolic 5'-nucleotidase, several cytosolic and one mitochondrial enzymes have been described. Nevertheless, researchers refer any AMP-dephosphorylating activity to as 5'-nucleotidase, lacking a more accurate identification. Increase of AMP hydrolysing activity has been associated with neurological and developmental disorders. The identification of the specific enzyme involved in these pathologies would be fundamental for the comprehension of the linkage between the enzyme activity alteration and brain functions. We demonstrate that the described neurological symptoms are associated with increased ectosolic 5'-nucleotidase activity on the basis of radiochemical assays and immunoblotting analysis. Furthermore, present data evidence that the assay conditions normally applied for the determination of cytosolic 5'-nucleotidases activity in crude extracts are affected by the presence of solubilised ectosolic nucleotidase
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
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