Heterogeneous conductance levels of native AMPA receptors.

The single-channel properties of AMPA receptors can affect information processing in neurons by influencing the amplitude and kinetics of synaptic currents, yet little is known about the unitary properties of native AMPA receptors in situ. Using whole-cell and outside-out patch-clamp recordings from granule cells in acute cerebellar slices, we found that migrating granule cells begin to express AMPA receptors before they arrive in the internal granule cell layer and receive synaptic input. At saturating agonist concentrations, the open probability of channels in outside-out patches from migrating cells was very high, allowing us to identify patches that contained only one or two active channels. Analysis of the single-channel activity in these patches showed that individual AMPA receptors exhibit as many as four distinguishable conductance levels. The conductance levels observed varied substantially for different channels, although on average the values fell within the range of unitary conductances estimated previously for synaptic AMPA receptors. In contrast to patches from migrating granule cells, we rarely observed directly resolvable single-channel currents in patches excised from the somata of granule cells in the internal granular layer, even though these cells gave large AMPA receptor whole-cell currents. We did, however, detect AMPA receptors with apparent unitary conductances of <1 pS in patches from both migrating and mature granule cells. Our results suggest that granule cells express a heterogeneous population of AMPA receptors, a subset of which are segregated to postsynaptic sites after synaptogenesis.

The American College of Surgeons Commission on Cancer and the American Cancer Society. Adenocarcinoma of the small bowel: review of the National Cancer Data Base, 1985-1995.

BACKGROUND: Small bowel adenocarcinoma (SBA) accounts for 2% of gastrointestinal (GI) tumors and 1% of GI cancer deaths. The objective of this study was to review the National Cancer Data Base (NCDB) to identify case-mix characteristics, patterns of treatment, and factors influencing survival of patients with SBA. METHODS: NCDB data from patients diagnosed with primary SBA between 1985-1995 were analyzed. Chi-square statistics were used to compare differences between groups. Disease specific survival (DSS) was calculated using the life table method for patients diagnosed between 1985-1990; univariate differences in survival were compared using the Wilcoxon statistic, and multivariate analyses were performed using a Cox regression model. RESULTS: There were 4995 SBA cases reported to the NCDB between 1985-1995, 55% of which occurred in the duodenum, 18% in the jejunum, 13% in the ileum, and 14% in nonspecified sites. The overall 5-year DSS was 30.5%, with a median survival of 19.7 months. By multivariate analysis, factors significantly correlated with DSS included patient age, tumor site, disease stage, and whether cancer-directed surgery was performed. CONCLUSIONS: SBA is found most commonly in the duodenum, and patient DSS is reduced at this site compared with those patients with jejunal or ileal tumors. This reduction in survival was associated with a lower percentage of cancer-directed surgery. Patients age > 75 years had a reduced DSS and more duodenal tumors, and were less frequently treated by cancer-directed surgery than their younger counterparts. This study reflects the experience with SBA from a large cross-section of U.S. hospitals, allowing for the identification of prognostic factors and providing a reference with which results from single institutions may be compared.