RESUMEN
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RESUMEN
Centronuclear myopathy (CNM) is a slowly progressive congenital myopathy with characteristic histopathological findings of chains of centrally located myonuclei in a large number of muscle fibers. Recently, different missense mutations in the dynamin 2 gene (DNM2, 19p13.2) have been shown to cause autosomal dominant CNM. We re-evaluated patients with a histopathological diagnosis of CNM and report on the clinical phenotype, the biopsy findings and the genetic results of these patients and review the current literature. Two of the three patients showed an unusually late disease onset (> 40 years). Interestingly, intramuscular nerve fascicles found in the muscle biopsy of a patient harboring the E368K DNM2 mutation contained nerve fibers with disproportionately thin myelin sheaths. Schwann cells of unmyelinated nerve fibers showed abnormal plasma membrane and basal lamina protrusions, indicating peripheral nerve involvement.
Asunto(s)
Dinamina II/genética , Mutación/genética , Miopatías Estructurales Congénitas/genética , Miopatías Estructurales Congénitas/patología , Adulto , Exones/genética , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Starting after the age of 35 years this German man had a slowly progressive distal myopathy greater in the legs than in the arms. First he realized gait difficulties with reduced ankle dorsiflexion. Serum creatine kinase activity was normal. Muscle biopsy studies showed myopathic changes, rimmed vacuoles and the presence of rods in 66% of the type 1 muscle fibers. Ultrastructural examination revealed cytoplasmatic aggregates of tubulofilaments measuring 15-18 nm in diameter, myeloid bodies and rod formation. The nosological situation of this distal myopathy with tubulofilamentous inclusions is discussed.
Asunto(s)
Cuerpos de Inclusión/patología , Miopatías Nemalínicas/patología , Periodicidad , Vacuolas/patología , Adulto , Edad de Inicio , Progresión de la Enfermedad , Humanos , MasculinoRESUMEN
We report two patients with polyglycosan body disease manifesting in adulthood. Clinical, electrophysiological, and histopathological characteristics of their disorders are summarized, and diagnostic classification is discussed.
Asunto(s)
Enzima Ramificadora de 1,4-alfa-Glucano/deficiencia , Sistema de la Enzima Desramificadora del Glucógeno/deficiencia , Enfermedad del Almacenamiento de Glucógeno Tipo III/genética , Enfermedad del Almacenamiento de Glucógeno Tipo IV/genética , Miositis por Cuerpos de Inclusión/genética , Enzima Ramificadora de 1,4-alfa-Glucano/genética , Anciano , Biopsia , Diagnóstico Diferencial , Femenino , Sistema de la Enzima Desramificadora del Glucógeno/genética , Enfermedad del Almacenamiento de Glucógeno Tipo III/diagnóstico , Enfermedad del Almacenamiento de Glucógeno Tipo III/patología , Enfermedad del Almacenamiento de Glucógeno Tipo IV/diagnóstico , Enfermedad del Almacenamiento de Glucógeno Tipo IV/patología , Humanos , Masculino , Músculo Esquelético/patología , Miositis por Cuerpos de Inclusión/diagnóstico , Miositis por Cuerpos de Inclusión/patología , Vacuolas/patologíaRESUMEN
In order to investigate renin- and angiotensin-independent mechanisms of the angiotensin converting enzyme (ACE) inhibitor ramipril we examined the effects of ramiprilat on calcium mobilization in cultured vascular smooth muscle cells. Ramiprilat (10(-7) M) induced a slow increase of basal [Ca2+]i from 52 +/- 7 nM to 162 +/- 12 nM (p less than .001). This increase of basal [Ca2+]i was associated with contraction of vascular smooth muscle cells as assessed by microscopy in vitro. While ramiprilat itself induced an increase of basal [Ca2+]i, the Ca(2+)-mobilizing effect of angiotensin II (AII) was blunted in the presence of the ACE inhibitor (659 +/- 38 nM vs 360 +/- 45 nM, p less than .001). The calcium channel blocker verapamil did not affect the stimulatory effect of ramiprilat on basal [Ca2+]i. The intracellular Ca2+ antagonist TMB 8 attenuated the ramiprilat-induced increase of basal [Ca2+]i (162 +/- 12 nM vs 101 +/- 14 nM, p less than .05). In the present study, the effect of ramiprilat on [Ca2+]i was not blocked by inhibition of prostaglandin synthesis by meclofenamate (10(-5) M); however, this finding does not rule out in vivo effects of ramiprilat-stimulated prostaglandins. These results suggest that ramipril affects Ca2+ kinetics in vascular smooth muscle cells. Ramiprilat-induced contraction of cultured smooth muscle cells may not be relevant in vivo, but the increase of basal [Ca2+]i by ramiprilat may reflect a "reset" of the cellular Ca(2+)-mobilizing mechanism or a depletion of cellular Ca2+ stores and may thus explain the attenuation of the Ca(2+)-mobilizing effect of AII. This mechanism may result in a decrease of vasopressor-dependent vascular tone in vivo and may contribute to the vasodilatory effect of ramipril.