RESUMEN
The association between thrombosis and cancer has been recognized since Trousseau's report in 1865. We present a case of bladder squamous cell carcinoma associated with multiple cerebral infarctions. This patient was diagnosed as having Trousseau's syndrome and received radiotherapy for bladder cancer treatment, along with anticoagulation therapy.
RESUMEN
Mutations in the presenilin 1 (PS1) gene are associated with early onset familial Alzheimer's disease (FAD). In this study, we found that the expression of mutant-PS1 in stable transfectants of SH-SY5Y neuroblastoma cells results in a reduction of the biosynthesis and steady-state levels of glucosylceramide. As an in vivo corroboration of these data, there was a significant reduction of brain glucosylceramide and gangliosides in an animal model of FAD. In mutant-PS1-transfectants (I143T, G384A), immunocytochemistry disclosed a remarkable reduction of glucosylceramide synthase (GlcT-1)-like immunoreactivity in the cells when compared with those of mock- and wild-PS1 transfectants. Immunoprecipitation of GlcT-1 protein from mutant-PS1 transfectants demonstrated a marked reduction in GlcT-1 protein, but there was no reduction in the levels of GlcT-1 mRNA. Both coprecipitation and γ-secretase inhibition experiments suggest that mutant-PS1 seems to form a complex with GlcT-1 protein and to be involved in GlcT-1 degradation, which was never found in other cell types. Thus, mutations in the PS1 gene result in profound glycosphingolipids abnormalities by abnormal molecular interaction with GlcT-1.
Asunto(s)
Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Glicoesfingolípidos/biosíntesis , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Presenilina-1/genética , Presenilina-1/metabolismo , Sustitución de Aminoácidos , Secretasas de la Proteína Precursora del Amiloide/antagonistas & inhibidores , Animales , Secuencia de Bases , Encéfalo/metabolismo , Carbamatos/farmacología , Línea Celular , Cartilla de ADN/genética , Dipéptidos/farmacología , Inhibidores Enzimáticos/farmacología , Glucosiltransferasas/genética , Glucosiltransferasas/metabolismo , Humanos , Ratones , Ratones Transgénicos , Mutación , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , TransfecciónRESUMEN
Previous studies have shown that patients with the axonal form of Guillain-Barré syndrome (GBS) develop autoantibodies against GM1 ganglioside (GM1). Nerve growth factor (NGF) is essential for neuronal survival in vivo and its functional receptor is Trk-tyrosine kinase. Here, we examined the biological effects of sera from patients with the axonal form of GBS on the morphology and the phosphorylation state of Trk-tyrosine kinase in PC12 cells. Furthermore, we examined the effect of the sera on the integrity of membrane lipid rafts biochemically. The data show that anti-GM1 antibodies found in patients' sera but not control sera inhibit NGF-induced Trk autophosphorylation. Most intriguingly, the autoantibodies alter the distribution of Trk in lipid rafts without shifting the distribution of a rafts marker protein. These data strongly suggest that anti-GM1 antibodies directly influence the integrity of the signaling platform, lipid rafts, implicating the importance of lipid rafts in the development of this disorder.
Asunto(s)
Autoanticuerpos/metabolismo , Gangliósido G(M1)/inmunología , Síndrome de Guillain-Barré/metabolismo , Microdominios de Membrana/metabolismo , Adulto , Anciano , Animales , Autoanticuerpos/inmunología , Western Blotting , Línea Celular , Femenino , Síndrome de Guillain-Barré/inmunología , Humanos , Inmunoprecipitación , Masculino , Persona de Mediana Edad , Factor de Crecimiento Nervioso/metabolismo , Células PC12 , Fosforilación , Ratas , Receptor trkA/metabolismo , Adulto JovenRESUMEN
Acute autonomic, sensory and motor neuropathy (AASMN) is a rare peripheral nerve disorder characterized by prominent dysautonomia with somatic sensory and motor impairment. Dysautonomia in AASMN is intractable even with corticosteroid therapy or plasmapheresis. Here we report a case of AASMN with severe orthostatic hypotension. Although the effectiveness of corticosteroid was insufficient, high dose intravenous immunoglobulin therapy (IVIg) was effective for not only sensorimotor symptoms but also autonomic symptoms. This is the first case of AASMN showing favorable responses to IVIg treatment, suggesting that IVIg should be considered when corticosteroid therapy or plasmapheresis is ineffective or insufficient.
