Biomedical subjects

José Vale

Publications and source records attributed to José Vale.

5 recordsLinked to original sources

PubMed2006

Exclusion of mutations in the PRNP, JPH3, TBP, ATN1, CREBBP, POU3F2 and FTL genes as a cause of disease in Portuguese patients with a Huntington-like phenotype.

Huntington disease (HD) is an autosomal dominant neurodegenerative disorder characterised by chorea, cognitive impairment, dementia and personality changes, caused by the expansion of a CAG repeat in the HD gene. Often, patients with a similar clinical presentation do not carry expansions of the CAG repeat in this gene [Huntington disease-like (HDL) patients]. We report the genetic analysis of 107 Portuguese patients with an HDL phenotype. The HDL genes PRNP and JPH3, encoding the prion protein and junctophilin-3, respectively, were screened for repeat expansions in these patients. Given the partial clinical overlap of SCA17, DRPLA and neuroferritinopathy with HD, their causative genes (TBP, ATN1, and FTL, respectively) were also analysed. Finally, repeat expansions in two candidate genes, CREBBP and POU3F2, which encode the nuclear transcriptional coactivator CREB-binding protein and the CNS-specific transcription factor N-Oct-3, respectively, were also studied. Expansions of the repetitive tracts of the PRNP, JPH3, TBP, ATN1, CREBBP and POU3F2 genes were excluded in all patients, as were sequence alterations in the FTL gene. Since none of the genes already included in the differential diagnosis of HD was responsible for the disease in our sample, the genetic heterogeneity of the HDL phenotype is still open for investigation.

Adolescent↗

PubMed2005

[Thyrotoxic periodic paralysis: a case report].

Thyrotoxic periodic paralysis (TPP) is characterized by recurrent episodes of muscle weakness and hypokalemia associated with thyroid hyperactivity. Reported predominantly among individuals of Asian descent, TPP is a rare manifestation of hyperthyroidism in western populations. We describe a typical case of TPP in a 33-year-old portuguese male, who presented with acute tetraparesis associated with hypokalemia (K+ 2.6 mEq/L). The patient had a 8-week history of several episodes of paraparesis of variable intensity; these attacks were usually nocturnal, preceded by strenuous exercise and resolved spontaneously after a few hours. The presence of tachycardia, weight loss, and goiter led to the diagnosis of Graves's disease. The correction of the hyperthyroid function with metimazol and propranolol prevented further episodes of muscle weakness. Thyrotoxic periodic paralysis should be considered in the differential diagnosis of acute episodes of motor paralysis in young patients. The maintenance of a euthyroid status is an essential part of management as this prevents the paralytic episodes.

Adult↗

PubMed2003

A study of the leachate toxicity of metal-containing solid wastes using Daphnia magna.

This paper examines the ecotoxicity of different actual inorganic wastes containing some potentially toxic metals commonly found in many industrial residues and the reduction in ecotoxicity obtained when the wastes are submitted to a solidification/stabilization process. The ecotoxicity was assessed as defined in the Spanish regulations on hazardous wastes, by means of the Daphnia magna Straus acute toxicity test applied to the toxicity characteristic leaching procedure (TCLP) waste leachate. On the basis of the EC50 values of the individual metals and the effect of the pH of the aqueous medium on D. magna, we have explored a method for estimating the toxicity of the TCLP waste leachate by calculating its EC50 value in the D. magna test. Although the method is only valid in cases in which a clear cause for the toxicity exists, the procedure described allows us to more completely explain the observed effects on the daphnids. The ecotoxicity of the residues after stabilization is less than that of the untreated waste, generally as a consequence of the reduction in metal leachability achieved by the immobilization treatment. The stabilization process was analyzed in terms of both the chemical and the ecotoxicological parameters, and the influence of leachate pH on the objectives of waste treatment is discussed.

Animals↗

PubMed2003

Portuguese families with dentatorubropallidoluysian atrophy (DRPLA) share a common haplotype of Asian origin.

Dentatorubropallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder characterized by a variable combination of progressive ataxia, epilepsy, myoclonus, choreoathetosis and dementia. This disease is caused by a (CAG)(n) expansion in the DRPLA gene, on chromosome 12p13. DRPLA is prevalent in Japan, but several families of non-Japanese ancestry have already been published. To identify the origin of expanded alleles in Portuguese families with DRPLA, we studied two previously reported intragenic SNPs in introns 1 and 3, in addition to the CAG repeat of the DRPLA gene. The results showed that all four Portuguese DRPLA families shared the same haplotype, which is also common to that reported for Japanese DRPLA chromosomes. This haplotype is also the most frequent in Japanese normal alleles, whereas it was rare in Portuguese control chromosomes. Thus, our findings support that a founder DRPLA haplotype of Asian origin was introduced in Portugal, being responsible for the frequency of the disease in this country.

Alleles↗

PubMed2003

Molecular diagnosis of Huntington disease in Portugal: implications for genetic counselling and clinical practice.

Huntington disease (HD) is a neurodegenerative, autosomal dominant disorder of late-onset, caused by the expansion of a CAG repeat in the coding region of the gene. Ours is the reference laboratory for genetic testing in HD, in Portugal, since 1998; 90.1% of all 158 families known were identified for the first time, including patients with unusual presentation or without family history. A total of 338 genetic tests were performed: 234 for diagnosis, 96 for presymptomatic and four for prenatal testing (four were done for family studies). Most referring physicians were neurologists (90.6%); 82.8% of all clinical diagnosis were confirmed, while 83.1% of those sent for exclusion were in fact excluded. In presymptomatic testing, an excess of female subjects (59.4%) was again verified; 37.5% of the consultands were found to be carriers. None of the foetuses, in four prenatal tests, were mutation carriers. One juvenile case was inherited from her mother. Our patient population is very similar to others described so far, namely in terms of mean age at onset and (CAG)(n) distribution, except perhaps for a higher frequency of large normal (class 2) alleles (3.7%). We also identify cases posing particular problems for genetic counselling, such as, 'homozygosity' that can pose a serious ethical dilemma, carriers of large normal alleles, and 'homoallelism' for a normal gene, which will demand further procedures and may delay results in presymptomatic and prenatal testing.

Adolescent↗