RESUMEN
OBJECTIVE: The characteristic pathological muscular findings of polymyositis (PM) and dermatomyositis (DM) have been shown to reflect their different pathogeneses. Here, we characterized the muscle biopsy findings of PM and DM patients with or without malignancy. METHODS: We evaluated the muscle biopsy findings of 215 consecutive PM and DM patients admitted to our hospital between 1970 and 2009. Pathology of the lesion biopsy sections was classified into 3 types: endomysial infiltration-type, perivascular infiltration-type, and rare-infiltrative-type. RESULTS: There was no difference between the muscle pathology of PM patients with and without malignancy. However, the incidence of rare-infiltrative type muscle pathology in DM patients with malignancy was significantly higher than in those without such tumors (p=0.0345). CONCLUSION: The incidence of rare-infiltrative type muscle pathology may be a predictive marker of DM with malignancy.
Asunto(s)
Biopsia/métodos , Dermatomiositis/diagnóstico , Dermatomiositis/patología , Músculo Esquelético/patología , Síndromes Paraneoplásicos/diagnóstico , Síndromes Paraneoplásicos/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Dermatomiositis/epidemiología , Femenino , Genes MHC Clase I/genética , Humanos , Inmunohistoquímica , Antígeno de Macrófago-1/genética , Masculino , Persona de Mediana Edad , Debilidad Muscular/etiología , Debilidad Muscular/patología , Neoplasias/epidemiología , Neoplasias/etiología , Síndromes Paraneoplásicos/epidemiología , Valor Predictivo de las Pruebas , Adulto JovenRESUMEN
BACKGROUND: We previously reported no difference in the efficacies of high-dose alternate-day (ADT) and daily-dose (DDT) prednisolone therapies in myositis patients, but that the incidence of side effects was lower in the former. The aim of the present study was to compare the long-term outcomes of both treatments in polymyositis patients. METHODS: We compared clinical courses, efficacies, adverse reactions, and outcomes of 115 consecutive, biopsy-proven polymyositis patients treated between 1970 and 2008 with ADT (32 patients) or DDT (83 patients). RESULTS: Mean onset ages, disease severity, incidences of malignancy, and response rates did not differ between the ADT and DDT groups. Adverse reactions (incidence of diabetes) were significantly higher in the DDT group. In this group, the incidences of hyperlipidemia, infection, hypertension, and psychiatric symptoms were also slightly higher, but not significantly so. The 20-year survival rate of the ADT group (68%) was significantly higher (p = 0.0112) than that of the DDT group (37%). CONCLUSION: ADT might be useful as an initial treatment option for polymyositis.
Asunto(s)
Antiinflamatorios/uso terapéutico , Polimiositis/tratamiento farmacológico , Prednisolona/uso terapéutico , Adulto , Anciano , Diabetes Mellitus/inducido químicamente , Esquema de Medicación , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Unfolded protein responses, including induction of stress sensor kinases, chaperones, and apoptotic mediators, are involved in the familial amyotrophic lateral sclerosis (ALS) model related to mutant Cu/Zn superoxide dismutase (SOD1) and sporadic ALS. We hypothesized that the endoplasmic reticulum-resident factor Derlin-1 plays a pivotal role in the regulation of misfolded proteins evoked by mutant SOD1. We show that Derlin-1 overexpression reduced mutant SOD1-induced cell toxicity and increased cell viability by suppressing the activation of the ER stress pathway factors: immunoglobulin-binding protein, activating transcription factor 6 p50, and C/EBP homologous protein. Interestingly, exogenous Derlin-1 resulted in a decrease in the amount of mutant SOD1, and a lesser decrease in that of wild-type SOD1, in transfected cells. Reduced SOD1 protein expression was observed in the microsomal fraction of wild-type and mutant SOD1 cells. Our results indicate that Derlin-1 regulates the turn over of SOD1 by promoting the proteasomal and autophagosomal degradation of SOD1 protein, but not by decreasing mutant SOD1 mRNA levels. Insights into the effects of Derlin-1 on mutant SOD1 may facilitate advancements in the treatment of motor neuron degeneration associated with ALS.
Asunto(s)
Esclerosis Amiotrófica Lateral/metabolismo , Retículo Endoplásmico/metabolismo , Proteínas de la Membrana/biosíntesis , Neuronas/metabolismo , Estrés Fisiológico/genética , Superóxido Dismutasa/genética , Esclerosis Amiotrófica Lateral/enzimología , Esclerosis Amiotrófica Lateral/genética , Animales , Autofagia/genética , Línea Celular Tumoral , Regulación hacia Abajo/genética , Retículo Endoplásmico/enzimología , Humanos , Proteínas de la Membrana/genética , Ratones , Mutación/fisiología , Neuronas/enzimología , Complejo de la Endopetidasa Proteasomal/metabolismo , ARN Mensajero/biosíntesis , Superóxido Dismutasa/antagonistas & inhibidores , Superóxido Dismutasa/metabolismo , Superóxido Dismutasa-1RESUMEN
In order to investigate the mechanism of dystrophin localization in the central nervous system (CNS), we generated adenovirus vectors that contained minidystrophin or truncated minidystrophin cDNA. We infected a primary neuronal culture derived from mdx mouse hippocampus with these viruses. Minidystrophin was observed along the plasma membrane as punctate dots or very short segments. In double immunofluorescence staining with anti-dystrophin and anti-postsynaptic density-95 antibodies, we observed that these proteins entirely colocalized. On the other hand, the truncated minidystrophin, which has deleted WW, cysteine-rich and C-terminal domains, was homogenously expressed in cytoplasm, neurites and axons. These findings suggest that a binding site to postsynaptic densities exists in the region extending from the WW domain to the C-terminal domain of dystrophin and that this site is necessary for binding to membrane.
Asunto(s)
Encéfalo/metabolismo , Distrofina/metabolismo , Proteínas de la Membrana/metabolismo , Sinapsis/metabolismo , Adenoviridae/genética , Secuencia de Aminoácidos , Animales , Sitios de Unión , Western Blotting , Células COS , Técnicas de Cultivo de Célula , Línea Celular , Chlorocebus aethiops , Distrofina/química , Distrofina/genética , Técnica del Anticuerpo Fluorescente , Vectores Genéticos/genética , Humanos , Inmunohistoquímica , Proteínas de la Membrana/genética , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos mdx , Datos de Secuencia Molecular , Unión Proteica , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Eliminación de Secuencia , TransfecciónRESUMEN
Coexistence of migraine with tension-type headache, that is, so-called combined headache is a disabling chronic headache disorder and is often seen in daily practice. Combined headache is a common disease, but it is not so easy to do an accurate diagnosis and adequate treatment because clinical spectrum is wide. For clinician, it is especially important to understand characteristics of patient's headache enough to diagnose correctly by using such as a headache diary and, to educate patients to differentiate between migraine and tension-type headache in order to select the right treatment and to prevent medication-overuse headache.