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William C Hall

Publications and source records attributed to William C Hall.

6 recordsLinked to original sources

An in vitro study of horizontal connections in the intermediate layer of the superior colliculus.

Some models propose that the spatial and temporal distributions of premotor activity in the intermediate layer of the superior colliculus are shaped by neuronal ensembles that give rise to local excitatory and distant inhibitory connections. One function proposed for these connections is to mediate a "winner-take-all" network; the short-range excitatory connections build up the activity of neighboring cells that command orienting movements in one direction, whereas the wide-ranging inhibitory projections attenuate the activity of remote cells that command incompatible movements. We used in vitro photostimulation and whole-cell patch-clamp recording to test these models by measuring the spatial extent of synaptic interactions within the rat intermediate layer. Uncaging glutamate over whole-cell patch-clamped cells in the intermediate layer elicited long-lasting inward currents, resulting from direct activation of glutamate receptors expressed by the cells, and brief synaptic currents evoked by activation of presynaptic neurons. The synaptic responses comprised clusters of excitatory and inhibitory currents. The size of these responses depended on the location of the stimulus with respect to the clamped cell. Large responses were commonly evoked by stimuli within 200 microm of the soma in the intermediate layer; smaller responses could occasionally be evoked from sites as distant as 500 microm. Responses evoked by stimulation beyond this distance were rare. Although the results demonstrated powerful local excitatory and inhibitory connections, they did not support the pattern of short-range excitation and widespread inhibition predicted by the winner-take-all hypothesis.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Organization of the intermediate gray layer of the superior colliculus. I. Intrinsic vertical connections.

A pathway from the superficial visual layers to the intermediate premotor layers of the superior colliculus has been proposed to mediate visually guided orienting movements. In these experiments, we combined photostimulation using "caged" glutamate with in vitro whole cell patch-clamp recording to demonstrate this pathway in the rat. Photostimulation in the superficial gray and optic layers (SGS and SO, respectively) evoked synaptic responses in intermediate gray layer (SGI) cells. The responses comprised individual excitatory postsynaptic currents (EPSCs) or EPSC clusters. Blockade of these EPSCs by TTX confirmed that they were synaptically mediated. Stimulation within a column (approximately 500 microm diam) extending superficially from the recorded cell evoked the largest and most reliable responses, but off-axis stimuli were effective as well. The EPSCs could be evoked by stimuli 1,000 microm off-axis from the postsynaptic neuron. The dimensions of this wider region (approximately 2 mm diam) corresponded to those of the dendrites of superficial layer wide-field neurons. SGI neurons differed in their input from SGS and SO; neurons in the middle of the intermediate layer (SGIb) were less likely to respond to visual layer photostimulation than were those in sublayers just above and below them. However, focal stimulation within SGIa did evoke responses within SGIb, indicating that SGIb neurons may receive input from the visual layers indirectly. These results demonstrate a columnar pathway that may mediate visually guided orienting movements, but the results also reveal spatial attributes of the pathway which imply that it also plays a more complex role in visuomotor integration.

Anesthetics, Local↗

Transcription profiling of estrogen target genes in young and old mouse uterus.

The goal of this study was to identify age-related changes in the expression of estrogen target genes in mouse uterus. We developed a novel 'estrogen response element (ERE) Chip' microarray bearing 297 genes including both known estrogen target genes and genes identified by searching the mouse genome database to have EREs, AP-1 sites, and Sp1 sites, all targets of estrogen receptor (ER) regulation. 400-500 bp PCR products of these 297 genes were printed onto nylon membranes creating the 'ERE Chip' microarray. This microarray is unique because it is the first estrogen-responsive gene-specific microarray to identify changes in uterine gene expression in young versus old mice. Using this ERE microarray we identified 10 uterine genes whose expression was up-regulated in old mice, e.g. beta-actin, calcium binding protein 45a, Sp1, and COUP-TFII. In contrast, the expression of only 4 uterine genes, i.e., complement C3, lactoferrin, Muc-1, and 17-beta-hydroxysteroid dehydrogenase 8 (H2-Ke6) was down-regulated in old mice. These changes may reflect an increase in stromal and a decrease in glandular epithelial gene expression, and may be associated with age-related changes in these tissue compartments within the uterus, possibly leading to the decline in reproductive function in C57Bl/6 mice.

Aging↗

Review of efforts to decrease costly leg wound complications in the medicare population following coronary revascularization.

BACKGROUND: Current trends show that patients referred for coronary artery bypass grafting (CABG) are significantly older, sicker, and at higher risk for complications than ever before. Eliminating leg wound complications would significantly benefit these patients and reduce the consumption of health care time and dollars. Endoscopic vein harvesting (EVH) decreases the risk of wound complications in patients following CABG and may decrease costly long-term wound-related problems. METHODS: In this retrospective study, the cases of 1909 Medicare patients who had undergone EVH or open vein harvesting (OVH) for CABG were reviewed. The risk factors of these patients were examined and compared with those of 1485 non- Medicare patients. Readmissions, home health care costs, and office lengths of service were reviewed and analyzed. RESULTS: The results of univariate analyses of the Medicare versus non-Medicare populations indicated significant differences for peripheral vascular disease (25.4% versus 17.2%; P <.0001), renal failure (6.0% versus 2.8%; P <.0001), hypertension (75.4% versus 71.5%; P =.011), female sex (31.1% versus 22.4%; P <.0001), mean age (69.8 years versus 57.1 years; P <.0001), and mortality risk (4.6% versus 2.2%; P <.0001). The wound rates in the Medicare group were 1.1% for EVH (n = 741) versus 2.8% for OVH (n = 1168), and this difference was significant (P =.0163) despite a higher frequency of morbid obesity in the EVH population (P <.0001). No significant differences were found in readmission frequency, home health care costs, or office length of service. CONCLUSION: EVH benefits Medicare patients. Although this study is the largest to date to use disposable instruments, there is a lack of statistical power in the analysis of cost comparisons due to the small sample size of wound complications. However, there appears to be a general trend toward a lower treatment cost per patient and less resource use with EVH.

Aged↗

In vivo pharmacodynamic effects of Hu1D10 (remitogen), a humanized antibody reactive against a polymorphic determinant of HLA-DR expressed on B cells.

The humanized monoclonal antibody Hu1D10 (Remitogen, Protein Design Labs, Fremont, CA) recognizes a polymorphic determinant of human leukocyte antigen-DR expressed on the majority of B-cell lymphomas and on normal B cells of most individuals. Hu1D10 mediates complement-mediated cytotoxicity, antibody-dependent cell-mediated cytotoxicity, and apoptosis of 1D10 antigen (Ag)-positive B cells in vitro. The 1D10 Ag is expressed on a variety of tissues but is restricted primarily to lymphocytes, macrophages, and mesenchymal dendritic cells. The safety and pharmacology of Hu1D10 were investigated in rhesus macaques. Animals were prescreened for 1D10 Ag expression on circulating B cells. Sixteen animals received either placebo (4 Ag+ animals), 1 mg/kg Hu1D10 (4 Ag+ animals), or 10 mg/kg Hu1D10 (4 Ag+ animals and 4 Ag- animals) daily via intravenous (i.v.) bolus-injection for 5 consecutive days, and 4 Ag+ animals received 10 mg/kg Hu1D10 via 90 min i.v. infusion x 5 days. Bolus-injection of Hu1D10 resulted in type 1 hypersensitivity reactions in the majority of Ag+ animals and one death due to anaphylaxis. Slow infusion of Hu1D10 was associated with only mild hypersensitivity reactions after the first dose but not subsequent doses. In animals treated with 10 mg/kg Hu1D10 via bolus-injection, the median terminal elimination half-life of Hu1D10 was 2.6 and 8.4 days in Ag+ and Ag- animals, respectively. Administration of Hu1D10 to Ag+ animals resulted in rapid and profound depletion of circulating B cells for 7-10 days following the last dose. No B-cell depletion was observed in Ag- animals, despite slower elimination of Hu1D10. These studies demonstrate that Hu1D10 reacts with antigen-presenting cells in rhesus macaques. It can be safely administered as a slow i.v. infusion but causes severe toxicity when given as a bolus. This study provides the foundation for testing Hu1D10 for the treatment of B-cell malignancies in humans.

Anaphylaxis↗