1,720,962 research outputs found
Methylmalonic acid as a marker for cobalamin deficiency: fact or fantasy? Elucidations from the cobalamin-deficient rat
No full textFurther evidence for the involvement of epidermal growth factor in the signaling pathway of vitamin B12 (cobalamin) in the rat central nervous system
No full textIn order to get further evidence for a mandatory involvement of epidermal growth factor (EGF) in the neutrophic action of vitamin B12 (cobalamin (Cbl)) in the central nervous system (CNS) of the rat, we observed the effects of repeated intracerebroventricular (ICV) microinjections of EGF in rats made Cbl-deficient through total gastrectomy. Morphometric analysis demonstrated a significant reduction in both intramyelinic and interstitial edema in the white matter of the spinal cord (SC) of totally gastrectomized (TGX) rats after treatment. Intramyelinic and interstitial edema are characteristic of Cbl-deficient central neuropathy in the rat. Similar lesions were also present in SC white matter of rats treated with repeated ICV microinjections of specific anti-EGF antibodies without any modification in their Cbl status. These results, together with those of a previous study showing the cessation of EGF synthesis in the CNS of TGX rats, demonstrate that: a) EGF is necessarily involved in the signaling pathway of Cbl in the rat CNS; and b) the lack of a neurotrophic growth factor EGF, and not the mere withdrawal of Cbl, causes or at least contributes to neurodegenerative Cbl-deficient central neuropathy
Subacute combined degeneration in totally gastrectomized rats: an ultrastructural study
No full textSevere permanent cobalamin (Cbl) deficiency was induced in rats either by total gastrectomy (TG) or through prolonged dietary Cbl deprivation. This paper deals with an ultrastructural investigation of different parts of the central nervous system (CNS) of rats made Cbl-deficient through one of these of two procedures. In both totally gastrectomized (TGX) rats and in rats chronically fed a Cbl-deficient diet, we observed intramyelin edema, with splitting of the lamellae, and interstitial edema affecting the white matter, mainly in the spinal cord (SC). These lesions were also present in the subcortical white matter, although to a lesser degree. In both TGX-rats and in rats chronically fed a Cbl-deficient diet the pyramidal tract and the optic nerve were completely spared. Vascular lesions were never observed. Intramyelin edema and interstitial edema of the white matter account for the patchy myelopathic spongy vacuolation, which is the histological hallmark of human subacute combined degeneration and has been previously seen in SC white matter of TGX-rats. Macro- and micro-glial cells in the white matter were activated, at least as seen ultrastructurally. Interestingly enough, there were activated glial cells even in the gray matter, in which neurons showed absolutely no alterations. Chronic subcutaneous Cbl administration of TGX-rats partially repaired the CNS damage. However, the amelioration produced by this treatment was greater when Cbl was given shortly after TG than when given three and four months after TG, i.e. when the lesions have already been formed
Subacute combined degeneration in the spinal cords of totally gastrectomized rats. Ornithine decarboxylase induction, cobalamin status, and astroglial reaction
No full textThe totally gastrectomized (TGX) rat is a new experimental model with which to produce widespread spongy vacuolation in spinal cord (SC) white matter, strongly reminiscent of that observed in subacute combined degeneration (SCD) of human SC
Epidermal growth factor as a local mediator of the neurotrophic action of vitamin B(12) (cobalamin) in the rat central nervous system
No full textWe have recently demonstrated that the myelinolytic lesions in the spinal cord (SC) of rats made deficient in vitamin B(12) (cobalamin) (Cbl) through total gastrectomy (TG) are tumor necrosis factor-alpha (TNF-alpha)-mediated. We investigate whether or not permanent Cbl deficiency, induced in the rat either through TG or by chronic feeding of a Cbl-deficient diet, might modify the levels of three physiological neurotrophic factors-epidermal growth factor (EGF), vasoactive intestinal peptide (VIP), and somatostatin (SS)-in the cerebrospinal fluid (CSF) of these rats. We also investigated the ability of the central nervous system (CNS) in these Cbl-deficient rats to synthesize EGF mRNA and of the SC to take up labeled Cbl in vivo. Cbl-deficient rats, however the vitamin deficiency is induced, show a selective decrease in EGF CSF levels and an absence of EGF mRNA in neurons and glia in various CNS areas. In contrast, radiolabeled Cbl is almost exclusively taken up by the SC white matter, but to a much higher degree in totally gastrectomized (TGX) rats. Chronic administration of Cbl to TGX rats restores to normal both the EGF CSF level and EGF mRNA expression in the various CNS areas examined. This in vivo study presents the first evidence that the neurotrophic action of Cbl in the CNS of TGX rats is mediated by stimulation of the EGF synthesis in the CNS itself. It thus appears that Cbl inversely regulates the expression of EGF and TNF-alpha genes in the CNS of TGX rats
Myelinolytic lesions in spinal cord of cobalamin-deficient rats are TNF-alpha-mediated
No full textRepeated intracerebroventricular (i.c.v.)microinjection of tumor necrosis factor-alpha (TNF-alpha) into normal rats causes intramyelin and interstitial edema in the white matter of the spinal cord (SC). This response is identical to that observed in the SC white matter of rats made cobalamin (Cbl) deficient by total gastrectomy (TG). Immunoblot analysis showed that: 1) the level of the biologically active form of the TNF-alpha protein (17 kDa) is higher in the SC of totally gastrectomized (TGX) rats 2 months after TG, i.e., at the postoperative time when edema is observed; 2) SC levels of TNF-alpha protein (17 kDa) in 2-mo-TGX-, Cbl-treated rats are reduced to control. Repeated i.c.v. microinjections of anti-TNF-alpha antibodies, transforming growth factor-beta1 (TGF-beta1) or interleukin-6 (IL-6) into TGX rats, begun shortly after TG, substantially reduced both intramyelin and interstitial edema in the SC white matter. This study provides the first evidence that the hallmark myelin damage of Cbl-deficient central neuropathy, which is a pure myelinolytic disease, is not caused directly by the withdrawal of the vitamin itself, but reflects enhanced production of the biologically active form of TNF-alpha by SC cells. This study thus supports the view that TGF-beta1 and IL-6 may act as neuroprotective agents in Cbl deficiency central neuropathy
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
Regulation of the ferritin H subunit by vitamin B12 (cobalamin) in rat spinal cord
No full textCobalamin-deficient (Cbl-D) central neuropathy is a pure myelinolytic disease, in which gliosis is also observed. Iron is abundant in the mammalian central nervous system, where it is required for various essential functions including myelinogenesis. It is predominantly located in the white matter and oligodendrocytes, which also actively synthesize the major iron proteins (e.g., ferritin, transferrin). We investigated the expression of the main proteins of iron metabolism in the spinal cord (SC) of totally gastrectomized Cbl-D rats 2 months after surgery (i.e., when the Cbl-D status has become severe). There were no significant changes in iron content, the activity of iron regulatory proteins, or the expression of transferrin or its receptor in the SC. We observed a significant decrease in the levels of both H and L ferritin subunits, with a more marked reduction in the latter. Post-operative cobalamin replacement therapy normalized only the H-ferritin subunits, and only in the SC. Our results therefore suggest that permanent cobalamin deficiency affects iron metabolism in the rat SC preferentially from a functional point of view, because H-ferritin is known to be involved in the uptake and release of iron
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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