RESUMO
BACKGROUND: Prevalence and time of occurrence of prodromal symptoms of Parkinson's disease (PD) in relation to the onset of classical motor manifestation varies between patients. Possible modifying factors might be different genetic architectures predisposing to varying burden of manifestations. OBJECTIVES: To characterize the prodromal phase in PD patients with heterozygous mutations in the GBA gene compared to PD patients without GBA mutation. METHODS: In a retrospective design, 151 participants [47 PD patients carrying a GBA mutation (PDGBA ), 52 idiopathic PD patients (PDidiopathic ), 52 healthy elderly (CON)] underwent a validated structured interview designed to assess prevalence and time of occurrence of prodromal symptoms. RESULTS: PDGBA showed a higher prevalence of prodromal symptoms and almost simultaneous occurrence of non-motor and early motor symptoms shortly before PD diagnosis whereas PDidiopathic reported a longer prodromal phase starting with non-motor symptoms. CONCLUSION: The short and severe prodromal phase in PDGBA might call for shorter assessment intervals in yet premanifest GBA mutation carriers.
Assuntos
Glucosilceramidase/genética , Mutação , Doença de Parkinson/genética , Sintomas Prodrômicos , Idoso , Feminino , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de TempoRESUMO
Pichia stipitis CBS 6054 will grow on D-xylose, D-arabinose, and L-arabinose. D-Xylose and L-arabinose are abundant in seed hulls of maize, and their utilization is important in processing grain residues. To elucidate the degradation pathway for L-arabinose, we obtained a mutant, FPL-MY30, that was unable to grow on D-xylose and L-arabinose but that could grow on D-arabinitol. Activity assays of oxidoreductase and pentulokinase enzymes involved in D-xylose, D-arabinose, and L-arabinose pathways indicated that FPL-MY30 is deficient in D-xylitol dehydrogenase (D-XDH), D- and L-arabinitol dehydrogenases, and D-ribitol dehydrogenase. Transforming FPL-MY30 with a gene for xylitol dehydrogenase (PsXYL2), which was cloned from CBS 6054 (GenBank AF127801), restored the D-XDH activity and the capacity for FPL-MY30 to grow on L-arabinose. This suggested that FPL-MY30 is critically deficient in XYL2 and that the D-xylose and L-arabinose metabolic pathways have xylitol as a common intermediate. The capacity for FPL-MY30 to grow on D-arabinitol could proceed through D-ribulose.
Assuntos
Arabinose/metabolismo , Pichia/crescimento & desenvolvimento , Pichia/genética , Xilose/metabolismo , D-Xilulose Redutase , Teste de Complementação Genética , Mutagênese , Pichia/metabolismo , Sementes , Estereoisomerismo , Especificidade por Substrato , Desidrogenase do Álcool de Açúcar/genética , Desidrogenase do Álcool de Açúcar/metabolismo , Zea maysRESUMO
A 52-year-old female complained about non-distinct symptoms such as fatigue, night sweats and bone pain. Because of a febrile bronchitis, chest X-ray was performed, which disclosed enlarged hilar nodes and intestinal and acinar pulmonary infiltrates. Endobronchial biopsy and cultures from bronchial aspirate permitted to diagnose infection by legionella concomitant with sarcoidosis. After antibiotic treatment for legionellosis over four weeks, immunosuppressive therapy for sarcoidosis was initiated with glucocorticoids.
