RESUMO
Active zone material is an organelle that is common to active zones along the presynaptic membrane of chemical synapses. Electron tomography on active zones at frog neuromuscular junctions has provided evidence that active zone material directs the docking of synaptic vesicles (SVs) on the presynaptic membrane at this synapse. Certain active zone material macromolecules connect to stereotypically arranged macromolecules in the membrane of undocked SVs, stably orienting a predetermined fusion domain of the vesicle membrane toward the presynaptic membrane while bringing and holding the two membranes together. Docking of the vesicles is required for the impulse-triggered vesicle membrane-presynaptic membrane fusion that releases the vesicles' neurotransmitter into the synaptic cleft. As at other synapses, axon terminals at frog neuromuscular junctions contain, in addition to SVs, vesicles that are larger, are much less frequent and, when viewed by electron microscopy, have a distinctive electron dense core. Dense core vesicles at neuromuscular junctions are likely to contain peptides that are released into the synaptic cleft to regulate formation, maintenance and behavior of cellular apparatus essential for synaptic impulse transmission. We show by electron tomography on axon terminals of frog neuromuscular junctions fixed at rest and during repetitive impulse transmission that dense core vesicles selectively dock on and fuse with the presynaptic membrane alongside SVs at active zones, and that active zone material connects to the dense core vesicles undergoing these processes in the same way it connects to SVs. We conclude that undocked dense core vesicles have a predetermined fusion domain, as do undocked SVs, and that active zone material directs oriented docking and fusion of these different vesicle types at active zones of the presynaptic membrane by similar macromolecular interactions.
RESUMO
PURPOSE: The overall incidence of pulmonary metastasis of T1 renal cell carcinoma is low. We evaluated the usefulness of chest x-rays based on the current AUA (American Urological Association) guidelines and NCCN Guidelines® for T1a renal cell carcinoma surveillance. MATERIALS AND METHODS: Between 2006 and 2012, 258 patients with T1a renal cell carcinoma were treated with partial nephrectomy, radical nephrectomy or radio frequency ablation with surveillance followup at our institution. A retrospective chart review was performed to identify demographics, pathological findings and surveillance records. The primary outcome was the incidence of asymptomatic pulmonary recurrences diagnosed by chest x-ray in cases of T1a disease. Our secondary outcome was a comparison of diagnoses by treatment modality (partial nephrectomy, radical nephrectomy or radio frequency ablation). RESULTS: Pulmonary metastases developed in 3 of 258 patients (1.2%) but only 1 (0.4%) was diagnosed by standard chest x-ray surveillance. Median followup in the entire cohort was 36 months (range 6 to 152) and 193 of 258 patients (75%) had greater than 24 months of followup. A mean of 3.3 surveillance chest x-rays were completed per patient. When assessed by treatment type, there was no significant difference in the recurrence rate for partial nephrectomy (0 of 191 cases), radical nephrectomy (0 of 22) or radio frequency ablation (1 of 45 or 2.2%) (p = 0.09). CONCLUSIONS: Chest x-rays are a low yield diagnostic tool for detecting pulmonary metastasis in patients treated for T1a renal cel carcinoma. Treatment mode does not appear to influence the need for chest x-ray surveillance.
