Evidence for glaucoma-induced horizontal cell alterations in the human retina

In this study we investigated changes to horizontal cells in human retinae affected by glaucoma. Glaucoma is characterized by raised intraocular pressure and is responsible for retinal ganglion cell and, possibly, photoreceptor degeneration. It was therefore assumed that horizontal cells might also be affected. The carbocyanine dye DiI was placed at discrete points on fixed, whole-mounted retinae obtained from normal and glaucomatous patients. After allowing 6-24 weeks for intramembranous diffusion within the lipid layers of the nerve cells and, therefore, fluorescent labeling, we measured horizontal cell soma and dendritic field sizes. Selected cells were then embedded in Araldite and cut at 4 microns. Horizontal cells in glaucomatous eyes appeared larger and had a granulated outline as compared with cells from normal retinae. Analysis of the mean cell soma size indicated that cells were 26% larger in the glaucomatous retinae and that this increase was significantly different from that seen in normal retinae (P < 0.05). The dendritic field size was unaffected (P > 0.05). As seen in cross section there was a clear loss of photoreceptor outer segments, and shrunken silhouettes of photoreceptor inner segments with pyknotic nuclei were observed. It is proposed that the increase in some size is indicative of horizontal cell responses that are likely to culminate in degeneration as a result of heightened intraocular pressure. In addition, this paper provides further evidence that photoreceptors are affected by advanced glaucoma.     

A microdialysis study of the effects of the nicotinic agonist RJR-2403 on cortical release of acetylcholine and biogenic amines

Transcortical dialysis was employed to investigate the effects of subcutaneous (s.c.) injections of RJR-2403 (1.2-7.2 mumol/kg) on extracellular levels of acetylcholine (ACh), norepinephrine (NE), dopamine (DA), and serotonin (5-HT) in rat. Systemic administration of RJR-2403 produced a 90% increase of cortical extracellular ACh levels that persisted for up to 90 minutes after injection. Norepinephrine and DA release were increased 124% and 131% above basal values, respectively. Serotonin (5-HT) levels in the dialysate were also significantly elevated by RJR-2403 (3.6 mumol/kg, s.c.) 70% above baseline at 90 minutes post-injection. Comparison of these responses to those of (-)nicotine from a previous study reveals little difference between the two compounds in their ability to influence cortical neurotransmitter release following systemic administration.     

Transmembrane organization of mouse P-glycoprotein determined by epitope insertion and immunofluorescence

P-glycoprotein (P-gp) is an integral membrane protein that causes multidrug resistance when overexpressed in tumor cells. Efforts to identify the position and polarity of its 12 putative transmembrane (TM) domains have so far failed to yield a consistent topological model. Recently, we have described a method for topology mapping based on the insertion of a small antigenic peptide epitope (YPYDVPDYA) in predicted intra- or extracellular loops of the protein. The tagged proteins are then functionally expressed in Chinese hamster ovary cells, and the polarity of the inserted tag with respect to plasma membrane is deduced by immunofluorescence in intact or permeabilized cells. We previously localized segments between TM1 and TM2, and TM5 and TM6 as extracellular and segments between TM2 and TM3 and downstream of TM6 as intracellular (Kast, C., Canfield, V., Levenson, R., and Gros, P. (1995) Biochemistry 34, 4402-4411). We have now inserted single epitope tags at positions 207, 235, 276, 741, 782, 797, 815, 849, 887, 961, and 1024; double epitope tags at positions 736, 849, and 961; and a triple epitope tag at position 849. Insertions of epitopes at positions 235, 736, 741, 849, 887, 961, and 1024 resulted in functional proteins, whereas insertions at positions 207, 276, 782, 797, and 815 abrogated the capacity of P-gp to confer multidrug resistance. The epitope tags inserted at positions 736, 849, and 961 were localized extracellularly, whereas tags at positions 235, 887, and 1024 mapped intracellularly. These results indicate that the intervening segments separated by TM4-TM5, TM10-TM11, and downstream of TM12 are cytoplasmic; segments delineated by TM7-TM8, TM9-TM10, and TM11-TM12 are extracellular. Our combined analysis of the amino- and carboxyl-terminal halves of P-gp supports a 12-TM domain topology with intracellular amino and carboxyl termini and ATP binding sites and an extracellular glycosylated loop (TM1-TM2) in agreement with hydropathy prediction. These results are clearly distinct from those obtained by the analysis of truncated P-gps in vitro and in heterologous expression systems.     

Concurrent engineering infrastructure. Tools, technologies andmethods in British industry

Concurrent engineering (CE) is a vital concept in the world of new product development, and up-to-date information about the extent of its adoption and the use of the enabling tools in the engineering industry is of great value. This article presents the data from an industry-wide survey of technical managers and analyses the significance of the information obtained. This reveals that CE is beginning to be widely applied, but there are significant differences between large and smaller companies, and between different industrial sectors     

Modelling diffusion-controlled kinetics in equilibrium and driven alloys

Summary We introduce a very simple model for thermally activated atomic migration on a lattice, and several techniques to handle it. For thermodynamical systems, the model can be used for simulating decomposition paths taking into account relevant metallurgical features. Close to equilibrium, the simplest mean-field approximation of the model can be linearized with respect to the departure from equilibrium; one then gets a microscopic interpretation of classical phenomenological coefficients, such as mobility, interfacial transfer coefficient, rate constants for the coupled relaxation of concentration and order fields. Further away from the equilibrium, the nonlinearities can be taken into account in a consistent way. For driven alloys, i.e. alloys submitted to external forcing, forced atomic migration is added to the model and new features emerge: the model is supported by several experimental results some of which confirmed its predictions a posteriori.     

Design of a submersible, low-cost, flat-response net radiometer

A fundamental analysis and design of a flat-response, temperature-compensated net radiometer is presented. The developed detector was tested in the laboratory, and its suitability was assessed for a fixed level and scanning measurements. Practical recommendations for field use as a fixed level or scanning radiation transmission detector are discussed.     

Improved node for frequency-domain TLM: the `distributed node'

A new node is presented for frequency-domain TLM (TLM-FD). It is shown by propagation analysis that the new node has the advantage of being much less dispersive than previous TLM-FD nodes     

Behavioral and computational models of spatial attention.

Pigeons pecked for food in a spatially cued choice reaction time (RT) task. A brief (50-msec) white light appeared on a left or right key and probabilistically predicted the location (on either the left or right key) of a subsequent target stimulus. The time between cue and target onset (stimulus onset asynchrony), the base rate of left cues, and the probability that the cue correctly predicted the target (cue validity) were experimentally varied. The mean RT to respond to the target key was faster on correctly cued trials (defining a validity effect), decreased for both valid and invalid trials as stimulus onset asynchrony increased (defining an alerting effect), showed a variety of base-rate effects, and did not depend on cue validity. It is shown with a computational-processing model that dynamic interactions of short-term and associative memory processes are sufficient to produce these attention-like empirical phenomena. (PsycINFO Database Record (c) 2010 APA, all rights reserved)