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Browsing by Author "GUIMARAES, A."

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  • Activation of ERK1/2 MAP kinases in familial amyloidotic polyneuropathy
    Publication . MONTEIRO, F.A.; SOUSA, M.M.; CARDOSO, I.; Barbas-Amaral, J.; GUIMARAES, A.; SARAIVA, M.J.
    J Neurochem. 2006 Apr;97(1):151-61. Epub 2006 Mar 3. Activation of ERK1/2 MAP kinases in familial amyloidotic polyneuropathy. Monteiro FA, Sousa MM, Cardoso I, do Amaral JB, Guimarães A, Saraiva MJ. Molecular Neurobiology, Instituto de Biologia Celular e Molecular, ICBAS, University of Porto, and Estomatology, Maxillofacial Surgery, Hospital Geral de Santo António, Portugal. Abstract Familial amyloidotic polyneuropathy (FAP) is a neurodegenerative disorder characterized by the extracellular deposition of transthyretin (TTR), especially in the PNS. Given the invasiveness of nerve biopsy, salivary glands (SG) from FAP patients were used previously in microarray analysis; mitogen-activated protein (MAP) kinase phosphatase 1 (MKP-1) was down-regulated in FAP. Results were validated by RT-PCR and immunohistochemistry both in SG and in nerve biopsies of different stages of disease progression. MKP-3 was also down-regulated in FAP SG biopsies. Given the relationship between MKPs and MAPKs, the latter were investigated. Only extracellular signal-regulated kinases 1/2 (ERK1/2) displayed increased activation in FAP SG and nerves. ERK1/2 kinase (MEK1/2) activation was also up-regulated in FAP nerves. In addition, an FAP transgenic mouse model revealed increased ERK1/2 activation in peripheral nerve affected with TTR deposition when compared to control animals. Cultured rat Schwannoma cell line treatment with TTR aggregates stimulated ERK1/2 activation, which was partially mediated by the receptor for advanced glycation end-products (RAGE). Moreover, caspase-3 activation triggered by TTR aggregates was abrogated by U0126, a MEK1/2 inhibitor, indicating that ERK1/2 activation is essential for TTR aggregates-induced cytotoxicity. Taken together, these data suggest that abnormally sustained activation of ERK in FAP may represent an early signaling cascade leading to neurodegeneration. PMID: 16515552 [PubMed - indexed for MEDLINE]
    2006-04Journal article Open access Show more
  • Cervical spondylodiscitis in an infant
    Publication . OLIVEIRA, T.; BARBOSA, C.; NEVES, E.; GUIMARAES, A.; SEXTO, C.; CRUZ, R.
    An Esp Pediatr. 2000 Apr;52(4):398-400. [Cervical spondylodiscitis in an infant] [Article in Spanish] Oliveira T, Barbosa C, Neves E, Guimarães A, Sexto C, Cruz R. Servicio de Pediatría, Hospital Maria Pia, Porto, Portugal. Abstract Spondylitis in childhood is rare, presenting a great variety of symptoms that are related to the child s age and to the site of the inflammatory process. We present the case of a nine-month-old infant, who presented to the emergency department with a torticollis of six weeks evolution. The diagnosis of spondylitis (C6-C7) was confirmed by MRI. Intravenous antibiotic therapy was administered. The patient showed complete regression of symptoms and imaging tests were normal. The rarity of this disease in patients in this age group, as well as the site and form of presentation are emphasised as is the importance of diagnosing this disease to prevent permanent neurological injuries or bone deformities. PMID: 11003937 [PubMed - indexed for MEDLINE]
    2000-04Other Open access Show more