RESUMEN
Neurturin (NTN) a structural and functional relative of glial cell line-derived neurotrophic factor, was originally identified based on its ability to support the survival of sympathetic neurons in culture. Similar to glial cell line-derived neurotrophic factor (GDNF), Neurturin has been shown to bind to a high affinity glycosylphosphatidylinositol (GPI)-linked receptor (GFRalpha2) and induce phosphorylation of the tyrosine kinase receptor Ret, resulting in the activation of the mitogen activated protein kinase (MAPK) signalling pathway. A panel of six novel murine monoclonal antibodies (MAbs) specific to human Neurturin has been developed and characterized. Four of the MAbs tested inhibit, to varying degrees, binding of NTN to the GPI-linked GFRalpha2 receptor. Three MAbs cross-react with the murine homolog. These antibodies have been shown to be useful reagents for Western blotting, immunohistochemistry, and also for the development of a sensitive, quantitative enzyme-linked immunosorbent assay (ELISA) for human NTN. Novel, specific MAbs with varying epitope specificities and blocking activity will be valuable tools for both the in vitro and in vivo characterization of NTN and its relationship to the GFRalpha2 and Ret receptors.
Asunto(s)
Anticuerpos Monoclonales/inmunología , Especificidad de Anticuerpos/inmunología , Factores de Crecimiento Nervioso/inmunología , Animales , Anticuerpos Monoclonales/aislamiento & purificación , Afinidad de Anticuerpos/inmunología , Unión Competitiva/inmunología , Western Blotting , Supervivencia Celular/fisiología , Cricetinae , Reacciones Cruzadas/inmunología , Inhibidores Enzimáticos/inmunología , Ensayo de Inmunoadsorción Enzimática , Epítopos/inmunología , Receptores del Factor Neurotrófico Derivado de la Línea Celular Glial , Humanos , Inmunización , Inmunohistoquímica , Ratones , Ratones Endogámicos BALB C , Proteínas del Tejido Nervioso/inmunología , Neuritas/fisiología , Neuroblastoma/inmunología , Neuroblastoma/patología , Neuroblastoma/ultraestructura , Neurturina , Ratas , Sustancia Negra/citología , Sustancia Negra/inmunología , Ganglio Cervical Superior/inmunologíaRESUMEN
Dexamethasone has been used to manage brain edema in patients with intracranial abscess. However, its administration has often been delayed or avoided for fear of adverse effects upon normal host responses to infection. An experimental model of brain abscess in the rat was developed to determine if dexamethasone produced adverse effects on immune competence and collagen deposition in the region of the abscess. Sprague-Dawley rats were inoculated with Staphylococcus aureus and treated intraperitoneally each day with either dexamethasone (0.25 mg/kg) or saline solution. Surviving animals were sacrificed at 4, 8, 12, or 18 days after treatment. The brains were examined grossly for abscess formation and microscopically for intensity of the inflammatory response, abscess diameter, and wall thickness. There were no differences in mortality rates, abscess production rates, or abscess diameters when groups were compared. The intensity of inflammatory response was similar in both groups. In the group sacrificed 8 days after inoculation, a delay in collagen deposition was apparent, manifested as a thinner abscess wall in the experimental group (mean: 17.8 mu in dexamethasone-treated animals and 85 mu in saline-treated control animals: p = 1.0041). At 12 and 18 days after inoculation, there was no difference in abscess wall thickness between the control and experimental groups. Therapeutic doses of dexamethasone had little effect on mortality rates, incidence of abscess production, or intensity of inflammatory response in the experimental animals. Thus, dexamethasone did cause a delay in collagen deposition in the walls of experimental brain abscesses, but wall thickness 18 days after inoculation was not affected.
Asunto(s)
Absceso Encefálico/tratamiento farmacológico , Dexametasona/farmacología , Animales , Absceso Encefálico/etiología , Absceso Encefálico/patología , Colágeno/metabolismo , Inflamación/etiología , Inflamación/patología , Recuento de Leucocitos , Ratas , Ratas Endogámicas , Infecciones Estafilocócicas/tratamiento farmacológico , Factores de TiempoRESUMEN
A 12-year-old boy presented with enuresis, leg weakness, and lower extremity spasticity. An initial lumbar water-soluble contrast myelogram disclosed an arachnoid diverticulum. After the insertion of a cystopleural shunt, the patient improved and was dry. However, 2 months later the patient became enuretic and developed weakness. Repeat myelography showed a second arachnoid diverticulum located in the midthoracic region. This second diverticulum was treated by marsupialization of the cyst wall to the subfascial space. The authors stress the need for complete myelography in patients with intradural spinal arachnoid diverticuli and present a brief review of the literature.
Asunto(s)
Aracnoides/diagnóstico por imagen , Divertículo/diagnóstico por imagen , Mielografía/métodos , Aracnoides/cirugía , Niño , Quistes/diagnóstico por imagen , Quistes/cirugía , Divertículo/cirugía , Enuresis/etiología , Humanos , Masculino , Complicaciones Posoperatorias/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
The enzyme which converts to norepinephrine to epinephrine, phenylethanolamine N-methyltransferase (PNMT), is found in brain as well as in the adrenal medulla. PNMT activity is subject to regulation by glucocorticoids, hormones which have a diurnal rhythm. We asked (1) whether a diurnal fluctuation exists in adrenal and brain PNMT activity and (2) what relationship this fluctuation might have to the diurnal rhythm in circulating glucocorticoids. Rats were sacrificed at 4-hour intervals over a 24-hour period. The PNMT activity in the adrenals and brainstems of these animals was determined by radioenzymatic assay, and the plasma levels of corticosterone were measured by competitive protein binding. No significant temporal variation was found in adrenal PNMT activity. Brainstem PNMT activity, however, showed a distinct diurnal fluctuation in activity, with a nadir at 7 a.m. and a peak at 3 p.m. The rise in brainstems PNMT clearly preceded by several hours the circadian rise in plasma corticosterone. We conclude that the circadian rhythm in circulating corticosterone does not drive the diurnal variation in brain PNMT activity. In unstressed animals, injection of exogenous corticosterone failed to elevate brainstem PNMT activity, whereas injection of specific inhibitors of PNMT activity significantly elevated plasma corticosterone levels. These data raise the possibility that the converse is true: changes in epinephrine synthesis may modulate the diurnal rhythm in pituitary-adrenal activity.