In vivo effects of human dialyzable leukocyte lysate: III. Modulation of the spleen cell proliferative response to antigen by components of leukocyte dialysates and an initial characterization of an ampliative nucleoside

The augmentative effects of isolated components of human dialyzable leukocyte lysates upon the proliferative response to antigen were investigated. Sequential Sephadex G-25 and Bio-Gel P-4 chromatography separated five distinct fractions which, 24 hr after injection into Keyhole limpet hemacyanin (KLH)-sensitive mice, either augmented or suppressed the in vitro spleen cell proliferative response to KLH. An amplifier molecule was isolated from one of the augmentative fractions by high-pressure, reverse-phase liquid chromatography. Preliminary structural analysis of the amplifier component indicated a nucleoside structure, similar to—but possibly distinct from—thymidine.     

Fanconi anemia mutation causes cellular susceptibility to ambient oxygen.

The gene defect causing the Fanconi anemia (FA) phenotype appears to be expressed at the cellular level, since FA fibroblasts show a protracted course of explant outgrowth, a diminished in vitro life span, and very poor cloning. We show that exposure of FA fibroblasts to hypoxic (5% v/v oxygen) culture conditions restores their growth in vitro to near normal. Exposure to elevated oxygen tension (35% v/v) causes accumulations of FA cells in the S and G2/M phases of the cell cycle that are in significant excess of those seen in heterozygote and control strains. In the absence of evidence for defective cytoplasmatic radical scavenging systems, these observations suggest increased nuclear susceptibility to ambient oxygen as cause of the FA cellular phenotype.     

Fluorescence photobleaching analysis of nuclear transport: dynamic evidence for auxiliary channels in detergent-treated nuclei

Nuclear transport experiments were performed on isolated rat liver nuclei to examine the permeability of membrane and detergent-free peripheral nuclear lamina. The transport of 64K molecular weight fluorescent-derivatized dextrans was measured by using the technique of fluorescence redistribution after photobleaching. Results of these experiments provide evidence for transport pathways that appear to be functionally distinct from nuclear pore complex channels. The suggestion is made that these supplemental pathways are embedded in the peripheral nuclear lamina and are normally masked by the inner nuclear membrane.     

Enhanced sensitivity to naltrexone is associated with an up-regulation in GABA receptor function.

Rats were made sensitive to the effects of the opioid antagonist naltrexone by treating them once weekly with cumulative doses of the drug (1, 3, 10, 30 and 100 mg/kg). Sensitization was monitored by measuring salivation following naltrexone administration. During the first week of treatment, no salivation was noted following any dose of naltrexone. Over a period of 8 weeks, however, increasing amounts of salivation were noted, with the most salivation occurring at the higher doses. Animals treated for 8 weeks with saline never salivated following injections. Following the development of sensitivity to naltrexone, the rats were sacrificed and their brains were assayed for GABA receptor function. GABA-stimulated chloride uptake, a measure of GABA receptor function, was unchanged in the cortex, but was increased in the cerebellum. These results suggest that the effects of naltrexone on cerebellar GABA receptors may be involved in the development of enhanced sensitivity to opioid antagonists.