RESUMEN
Although jejunal atresia occasionally may occur with a familial pattern, an association with renal disease has not been described. The authors report on three family members treated over two generations, all of whom had both proximal jejunal atresia and renal dysplasia. This association was most likely inherited as an autosomal dominant trait.
Asunto(s)
Enfermedades en Gemelos/genética , Atresia Intestinal/genética , Yeyuno/anomalías , Riñón/anomalías , Adulto , Femenino , Genes Dominantes , Humanos , Recién Nacido , Masculino , Gemelos DicigóticosRESUMEN
Microtubules are a primary cytoskeletal constituent of axons and growth cones. In addition to serving as a scaffolding for axon assembly, they also provide a means of transport of organelles that are essential for outgrowth and maintenance of synaptic function. Pharmacological manipulations that disrupt net assembly of microtubules also interfere with growth cone advance and axon extension. Less is known after the effects of disrupting microtubule dynamics without affecting net assembly. To investigate this, we studied the effects of low doses of nocodazole on axon extension and microtubule organization in rat superior cervical ganglion neurons. We report that 165-330 nM nocodazole significantly reduces axon extension rate and increases axon diameter without affecting the rate of production of axoplasm or microtubule polymer, and without decreasing the average length or number of microtubules. Two observations suggested that microtubule dynamics were depressed by this dose of nocodazole. First, this treatment eliminated the highly divergent lengths and positions of microtubules characteristic of normal growth cones, inducing an array in which each microtubule terminated at roughly the same position in the proximal regions of the growth cone. Second, there was a decrease in the proportion of microtubule length containing mostly tyrosinated (newly assembled) alpha-tubulin and an increase in the proportion of microtubule length containing mostly acetylated (older, more stable) alpha-tubulin. Together, these data suggest that a decrease in dynamic instability of microtubules is sufficient to disrupt axon extension but does not interfere with axoplasm production.
Asunto(s)
Axones/fisiología , Microtúbulos/fisiología , Neuritas/fisiología , Animales , Células Cultivadas , Microscopía Electrónica , Neuritas/efectos de los fármacos , Nocodazol/farmacología , Ratas , Factores de TiempoRESUMEN
It was the aim of this study to test the hypothesis that abnormal thickening of capillary basal laminae in the diabetic organism may be due to postulated cycles of capillary cell turnover of increasing frequency. The accelerated cell turnover, it was theorized, may lead to laminar thickening through adhesion of basal laminae synthesized by regenerating cells with residual laminae of previously degenerated capillaries. Nine streptozotocin-diabetic rats and six nondiabetic controls were injected ip with tritiated thymidine, 1.0 microCi/g body weight. Three additional controls, for the purpose of identifying a potentially toxic action of streptozotocin which may affect the incorporation of thymidine into DNA, were treated in an identical manner. One hour postinjection, the animals were sacrificed, the heart was excised and sliced transversely. The tissue slices were fixed in 10% neutral buffered Formalin, dehydrated, and embedded in paraffin. Sections 6 microns thick were dipped in Kodak emulsion and were developed following an exposure of 4 weeks. Examination of the autoradiographs revealed distinctly labeled capillary endothelial cells in the myocardium of nondiabetic controls; labeling of these cells was strikingly reduced in the diabetic rats. These results indicate that proliferative activity of capillary endothelial cells is markedly retarded in the diabetic myocardium and that the reduced labeling can be ascribed genuinely to the diabetic environment. This finding does not provide support for the hypothesis that an accelerated cell turnover may be responsible for basal laminar thickening in the diabetic.