The decrease in the threshold on the dark side of the luminance edge in the after-flash effect

Foveal thresholds were measured for a small, briefly presented test slit as a function of the distance from the edge of a luminance-step pattern. A luminance-step pattern was briefly presented after the test slit. By this experiment, the edge threshold effect (i.e. the rise in threshold at the luminance edge) and the fall in threshold on the dark side of the edge were found. On the other hand, the fall in threshold was never obtained at a steadily presented luminance edge. This fall in threshold found here was briefly discussed.     

Role of joint afferents in relation to the initiation of forelimb stepping in thalamic cats

To analyze the roles of joint afferents in relation to initiation of forelimb stepping in thalamic cats, we recorded the unit spikes of the cervical dorsal roots, stimulated the joint afferents, and applied local anesthesia to the joint capsule. Almost all of the joint afferents of the shoulder, elbow, wrist and finger adapted slowly and exhibited alternating firing during forelimb stepping. About 45% of the afferents of each joint showed firings as the limb moved from forward to backward. About 44% of the afferents exhibited discharges as the limb moved from backward to forward. The remaining afferents showed firings as the limb moved in both directions. The application of local anesthesia to joints of the shoulder, elbow or wrist resulted in a marked reduction of forelimb stepping. Forelimb stepping was evoked by electric stimulation of the joint capsule, when excitabilities of flexor motoneurons were increased due to muscle stretching. Impulses originating in the joint afferents of the forelimb entered the spinal cord and ascended to the dorsolateral funiculus of the cervical cord, since forelimb stepping was abolished after bilateral transection of this part. Our results indicate that joint afferents may play an important role in the initiation of forelimb stepping in thalamic cats walking on a motor-driven treadmill.     

Effects of Electrical Stimulation of the Substantia Nigra on Responses of the Lateral Geniculate Body Neurons to Light

Effects of electrical stimulation of the sub-stantia nigra on responses of the lateral geniculate neurons to light were studied. Responses of the neurons to flash were enhanced or inhibited by conditioning stimulation of the substantia nigra. Enhancement of firing by nigral stimulation more often occurred in neurons excited primarily by flash, but inhibition was more commonly observed in those which showed a primary neuronal silence after light.     

Wavelength-specific brightness contrast as a function of surround luminance

We studied the effect of a monochromatic surround of varying wavelength on the brightness of five monochromatic test fields using a binocular matching technique. The results showed that brightness reduction of the test field was greatest when the wavelength of the surround was similar to that of the test field, particularly within the three wavelength regions of red, green and blue. In addition, the slope of brightness reduction with increase in surround luminance was found to vary as a function of surround wavelength: also, the wavelength-selective brightness reduction was much more prominent for the higher luminance surrounds. A two-factor model with channel-specific and channel-nonspecific lateral inhibition is proposed.     

Effects of electrical stimulation of the substantia nigra on responses of lateral geniculate body neurons to light.

Effects of electrical stimulation of substantia nigra on responses of the lateral geniculate neurons to light were studied. Responses of the neurons to flash were enhanced or inhibited by conditioning stimulation of the substantia nigra. Enhancement of firing by nigral stimulation more often occurred in neurons excited primarily by flash, but inhibition was more commonly observed in those which showed a primary neuronal silence after light.     

Determination of binding site residues responsible for the subunit selectivity of novel marine-derived compounds on kainate receptors

Dysiherbaine (DH) and related molecules are high-affinity, subunit-selective kainate receptor (KAR) ligands originally isolated from a marine sponge. To elucidate why DH, an agonist, and MSVIII-19, a competitive antagonist, bind selectively to glutamate receptor (GluR) 5 but not to the KA2 KAR subunit, we used molecular dynamics simulations to generate binding models that were tested experimentally in radioligand binding and electrophysiological assays. Three candidate sites, Val685, Leu735, and Ser741 in GluR5, corresponding to Ile669, Phe719, and Met725 in KA2, were predicted to underlie the distinct binding profiles of the marine toxins. Single or multiple reciprocal mutations introduced into the receptor subunits produced a variety of effects on binding affinity. Most notably, mutation of Met725 to serine in KA2 increased the affinity of DH by 350-fold; in contrast, mutation of one or more of the residues in GluR5 did not markedly alter DH binding. MSVIII-19 affinity for the KA2 subunit was significantly increased in multiple site mutants, and reciprocal mutations in the GluR5 subunit produced substantial (700-fold) reductions in MSVIII-19 affinity. Physiological characterization of the double- and triple-mutant subunits demonstrated altered functional behavior consistent with the changes in binding affinity. The results provide experimental support for the importance of these three ligand binding domain (LBD) residues and suggest steric hindrance in the KA2 subunit LBD is largely responsible for the very low affinity for the two compounds. In this study, we identified the molecular basis for subunit selectivity of these marine-derived molecules on KARs, which could facilitate the rational design of selective ligands with distinct pharmacological profiles.     

An evaluation of mass screening for breast cancer

In Tokushima Prefecture, Japan, 41,922 women (26,669 in actual number) were subjected to mass screening with physical examination from 1970–1977. In 42 including 10 of so-called “interval cancer”, breast cancer was detected. Those with breast cancer detected by mass screening were in the earlier stage of the discase as compared to those diagnosed through regular medical care at our out-patient clinic during the same period. Procedures such as inspection and palpation are readily carried out and early occurrences of breast cancer can be detected.     

Synergistic effect of fosfomycin and fluoroquinolones against Pseudomonas aeruginosa growing in a biofilm

Ulifloxacin is the active form of the prodrug prulifloxacin and shows a highly potent antipseudomonal activity. In this study, we examined the combined effect of fosfomycin and ulifloxacin against Pseudomonas aeruginosa (P. aeruginosa) growing in a biofilm using a modified Robbins device with artificial urine, and compared it to that of the combination of fosfomycin and ciprofloxacin or levofloxacin. An ATP bioluminescence assay was used to evaluate the antibacterial activity of the agents against sessile cells in a mature biofilm developed on a silicon disk. The total bioactivity of P. aeruginosa growing in a biofilm that had not been fully eradicated by fosfomycin or any of the fluoroquinolones alone at 10 times the MIC decreased after combination treatment with fosfomycin and fluoroquinolones. Morphological changes occurred in a time-dependent fashion; namely, swollen and/or rounding cells emerged within a couple of hours after combination treatment, marking the initial stage in the process leading to the destruction of the biofilms. We could not find any difference among the 3 fluoroquinolones with regard to their synergistic effects when administered with fosfomycin. The combination treatment of fosfomycin and fluoroquinolones with highly potent antipseudomonal activities was effective in eradicating sessile cells of P. aeruginosa in the biofilm and promises to be beneficial against biofilm-associated infectious diseases.