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Biomedical subjects

W C Gordon

Publications and source records attributed to W C Gordon.

53 records · Page 3Linked to original sources

Selective facilitation of memory attributes by strychnine.

In two experiments, the effects of strychnine on the specific memory attributes of prior discrimination training were assessed in terms of subjects' performance under various discrimination reversal conditions. Mice were trained in a discrimination task with two redundant relevant cues. Immediately after their last training trial, subjects were administered an intraperitoneal injection of either strychnine (1.0 mg/kg) or saline. When both training cues were reversed (Experiment 1), strychnine treated subjects were observed to exhibit greater performance decrements than saline-treated subjects upon initial exposure to reversal conditions, suggesting that strychnine had enhanced the memory of a relatively specific stimulus-response association. When subjects were tested under partial cue-reveraal conditions (Experiment 2) strychnine treated animals exhibited treater utilization of one of the redundant relevant stimuli than the other, while saline-treated animals exhibited no preference.

Animals↗

Effector cell stimulation-inhibition of in vitro lymphoma cell DNA synthesis and correlation with in vivo antitumor response.

DNA synthesis by murine lymphoma cells was stimulated up to 20-fold in vitro by syngeneic or allogeneic peritoneal cells (PEC) and peripheral blood lymphocytes, as measured by [3H]thymidine incorporation in a 44-hr assay. The increase in DNA synthesis correlated with an increase in tumor cell number in the cultures. The adherent PEC population was responsible for most of the enhancement. This effect was abrogated by pretreating the adherent cells with the metabolic inhibitors iodoacetamide, KCN, NaF, and dinitrophenol, or with glutaraldehyde, or by heating at 56 degrees. Pretreatment with mitomycin C did not eliminate the stimulatory effect. PEC supernatants did not enhance tumor growth, but effector-to-target cell proximity was shown to be necessary for stimulation. PEC from tumor-immunized mice also stimulated tumor target cell growth, but to a consistently smaller degree than did nonimmune PEC. This immune inhibition correlated with in vivo survival of mice to live tumor challenge and with ability of effector cells to increase life-span in adoptive immunity tests. Differential production of thymidine by normal and immune PEC appeared not to be a factor in these assays. Fractionation of PEC showed that the immune nonadherent cells were inhibitory in vitro and were able to increase survival time in adoptive immunity tests. On the other hand, the adherent PEC from immune mice either inhibited, stimulated, or had no effect on tumor cell DNA synthesis, compared with nonimmune adherent PEC, thus exhibiting no correlation with the immune status of the donor. In one example, administration of the macrophage activator lipopolysaccharide to mice resulted in PEC that were inhibitory in the in vitro assay, although the agent did not produce in vivo immunity. The inhibition of tumor DNA synthesis assay, with unfractionated PEC, exhibited a consistent correlation with the immune status of the host when mice were sensitized to lymphoma cells. However, the variable influence of the adherent PEC population on tumor growth reduced or nullified the immune inhibitory effect in a few cases.

Animals↗

Immunogenicity of modified tumor cells in syngenic hosts.

Modified tumor cells were used to immunize three murine hosts against syngenic ascitic lymphomas: C3H-6C3HED, BALB/c-P1798, and DBA/2-L1210. When the host was capable of a significant immune response against the malignant cells during progressive tumor growth (e.g., C3H vs. 6C3HED), protective immunization against a larger challenge tumor dose was achieved after fewer vaccinations. Lipopolysaccharide (LPS) enhanced host response to iodoacetamide (IAd) modified P1798 and L1210 so as to confer resistance after fewer immunizations with these weakly antigenic tumors. Similarities among the three systems were also seen. Modified cells may be stored at 4 degrees C several weeks and are effective when 107-108 are given i.p.; resistance appears maximal about one week after vaccination. In immunotherapy trials, C3H mice implanted with 5 x 104 6C3HED cells and treated at least four times with IAd-6C3HED demonstrated a 25% cure rate. A model was presented for evaluating parameters of response to immunotherapy in conjunction with chemotherapy. Cell-mediated immunity in resistant mice was demonstrated by inhibition of DNA synthesis in cultures of lymphoma cells and sensitized peritoneal cells (PEC) compared to that with nonimmune PEC. This assay system may also provide an opportunity for examining the hypothesis of immunostimulation of tumor growth in vitro. Humoral response to modified cells was established by membrane immunofluorescence. Although anti-6C3HED and anti-L1210 appear specific, anti-P1798 antiserum reacts with BALB/c thymocytes and murine fetal antigen.

Animals↗

Multiple Forms and Intracellular Localization of Uridine Diphosphate Glucose Pyrophosphorylase in Avena sativa.

Uridine diphosphate glucose pyrophosphorylase was isolated separately from Avena sativa leaves, roots, and etiolated coleoptiles and purified by ammonium sulfate fractionation, DEAE-Sephadex chromatography and polyacrylamide gel electrophoresis. There was no difference in the enzyme from the different tissue types with respect to properties exhibited during the purification procedure. A small portion of the enzyme from all three sources was found to be particulate when homogenized in aqueous sucrose media. Characterization of the particulate form by discontinuous sucrose density gradient showed the enzyme to be located at two different densities, one of which corresponded to chloroplasts in the leaves and plastids in the coleoptiles and roots. Homogenization and fractionation of the oat leaves using the nonaqueous media, hexane, and carbon tetrachloride, resulted in 50 to 60% of the enzyme being associated with chloroplasts and the remainder being associated with other membranous material. These data indicate that the enzyme from oat leaves, roots, and etiolated coleoptiles has multiple intracellular locations, and it is suggested that compartmentation of this enzyme may be a mechanism for regulation of uridine diphosphate glucose metabolism in oats.

Journal Article↗

Phosphorylated and nucleotide sugar metabolism in relation to cell wall production in Avena coleoptiles treated with fluroride and peroxyacetyl nitrate.

Coleoptile sections of Avena sativa L. were pretreated with sodium fluoride or peroxyacetyl nitrate at levels which inhibit auxin-induced growth but did not affect glucose uptake or CO(2) production when postincubated for 30 minutes in a (14)C-glucose medium without auxin. Labeling of metabolites involved in cell wall synthesis was measured. Peroxyacetyl nitrate decreased labeling, and it was concluded that the pool size of uridine di-phosphoglucose, sucrose, and cell wall polysaccharides decreased compared to control. The changes suggest that peroxyacetyl nitrate inactivated sucrose and cell wall synthesizing enzymes including cellulose synthetase and decreased cell growth by inhibiting production of cell wall constituents. Fluoride treatment had no effect on production of cell wall polysaccharides, with or without indoleacetic acid stimulation of growth. The only change after fluoride treatment was a decrease in uridine diphosphoglucose during incubation without indoleacetic acid, a decrease that disappeared when indoleacetic acid was present. It was concluded that some other aspect of cell wall metabolism, not determined here, was involved in fluoride-induced inhibition of growth.

Journal Article↗

Effect of Serenoa repens extract (Permixon) on estradiol/testosterone-induced experimental prostate enlargement in the rat.

The effect of the lipidosterolic extract of Serenoa repens (LSESR) on experimental prostate enlargement was investigated in three groups of rats: shams treated with LSESR (sham rats), castrated animals treated with estradiol and testosterone (castrated rats), castrated animals treated with estradiol/testosterone and treated with LSESR (castrated and treated rats). Following three months of continuous hormonal treatment, the weight of prostates in estradiol/testosterone-treated castrated rats was significantly increased in comparison with sham-operated rats. Such an increase started rapidly, reached a maximum by 30 days and remained at a plateau or slightly declined thereafter. The increase of prostate total weight induced by the hormone treatment was inhibited by administration of LSESR. Indeed, the weight was significantly lower at day 60 and day 90 for the dorsal and lateral regions of the prostate. The weight of the ventral region of the prostate was significantly lower after 30 and 60 days treatment with LSESR. These results demonstrate that administering LSESR to hormone-treated castrated rats inhibits the increase in prostate wet weight. This effect of LSESR may explain the beneficial effect of this extract in human benign prostatic hypertrophy.

Androgen Antagonists↗

Alterations in rabbit retina lipid metabolism induced by detachment. Decreased incorporation of [3H]DHA into phospholipids.

BACKGROUND: Docosahexaenoic acid (22:6n-3, DHA) is found in high concentration in phospholipids from retinal membranes, and is essential for their function. This study investigated the effect of in vivo retinal detachment on in vitro lipid metabolism using [3H]DHA. METHODS: Rabbit retina was detached from the retinal pigment epithelium by injecting physiological saline into the subretinal space of the eye. Retinal samples from control (non-operated) and sham (operated, no detachment) animals, and from attached and detached retinal areas from the same eye, were incubated in vitro with [3H]DHA for 4 hours, and then prepared for biochemical and autoradiographic analysis. RESULTS: In control and sham retinas, [3H]DHA was preferentially esterified into phospholipids (82%) with low labeling of free fatty acids (FFA) (5%). In samples from detached areas of the retina, a higher proportion of [3H]DHA was recovered in the FFA pool (up to 30%) and its esterification was shunted into triacylglycerol, thereby reducing the formation of [3H]DHA-phospholipids. Changes were sustained through 48 hours of postdetachment. High labeling of inner segments and synaptic terminals was observed autoradiographically in control retinas, while in detached retinas, clusters of labeling were detected in the neural retina, and eventually within the photoreceptor layer. CONCLUSION: Retinal detachment induces longlasting changes in lipid metabolism which are reflected in lower labeling of [3H]DHA-phospholipids. Metabolic changes, sustained through 48 hours, may lead to inadequate synthesis/turnover of phospholipids, among them, those containing DHA, possibly resulting in defective disc membrane assembly with subsequent deterioration of visual cells.

Animals↗

Facilitation of the long term memory store with strychnine: a reexamination.

Contrary to previous findings, some recent studies have reported that several daily injections of strychnine, beginning 24 hr after learning, facilitates subsequent retention. The present paper reports 3 studies using mice which suggest that strychnine has no effect on retention when the learning-injection interval is 24 hr. This absence of an effect was found using a range of strychnine doses. Furthermore, the absence of the facilitation effect was found not to be due to any failure of animals to learn prior to injection or to the fact that all animals performed asymptotically on the retention test.

Animals↗

Rapid screening method for deoxynivalenol in agricultural commodities by fluorescent minicolumn.

A rapid screening procedure based on the selective adsorption of deoxynivalenol (DON) from extracts of wheat and corn has been developed. DON is extracted from the sample with acetonitrile-water (85 + 15) and partially purified on a preparative minicolumn. Solvent is evaporated and the residue is dissolved in toluene-acetone (95 + 5) and chromatographed on a novel detector minicolumn which selectively adsorbs DON. A blue fluorescence is produced when the column is heated 5 min at 100 degrees C. The procedure is capable of detecting DON at greater than or equal to 500 ng/g. Forty-three wheat samples, contaminated with DON at 60-6300 ng/g, were assayed by gas chromatography-mass spectroscopy (GC-MS) of the heptafluorobutyryl derivative of DON and by the selective adsorption procedure. Comparison of results showed 91% agreement between data from the 2 methods. Selective adsorption assays were positive for all samples that were greater than or equal to 500 ng/g by GC-MS (no false negatives) and were negative for 85% of samples less than 500 ng/g (4/27 false positives). These four samples contained greater than 200 ng/g by GC-MS. Samples of wheat (64), corn (23), soybeans (8), and sorghum (6) were extracted and extracts were assayed by thin-layer chromatography and the selective adsorption procedure. Selective adsorption assays agreed with TLC results.

Chromatography, Thin Layer↗

Childhood psychosis and 24-h rhythms: A behavioral and psychophysiological analysis.

Three investigations were performed to examine behavioral and physiological variation with respect to rhythmicity in psychotic children. Case report I observed periodicity in certain stereo-typed behaviors, and provided data on extinction of self-stimulation and self-injurious behavior for a 72 h period. Case report II monitored psychophysiological reaction in an orienting response paradigm. Results indicated significant changes as a function of time of day. Study I indicated differences in amplitude of the temperature rhythm between normal controls and the psychotic group. The results of these investigations are discussed in terms of their potential for etiological and diagnostic research. Further, specific treatment implications are presented.

Arousal↗

Experimental models and their use in studies of diabetic retinal microangiopathy.

Diabetes produces dramatic changes in retinal microvasculature, triggering endothelial cell proliferation and microaneurysms. Capillaries become weakened, releasing blood into vitreal and retinal spaces. Photoreceptors become occluded and separated from the choriocapillaris, resulting in visual acuity decline, detachment and cell death. Several models have been developed that have proved useful for the study of this disease, resulting in a better understanding of the processes involved. Streptozotocin treatment affects the pancreatic beta cells, rapidly reducing them until insulin is no longer synthesized in sufficient amounts. The galactosemic model shifts metabolism away from glucose, increasing aldose reductase and retinal polyol metabolism. Finally, two weeks of cycled oxygen from high to low tension every 24 hours, followed by return to room air, triggers microangiogenesis in developing retinas. Use of these models, separately or in combination, as well as electroretinographic analysis, has begun to reveal the events taking place as diabetic retinopathy progresses. Endothelial cells become separated from pericytes as basement membranes thicken, and vascular endothelial growth factor increases, triggering their proliferation. Finally, early changes occurring within photoreceptors can now be studied.

Animals↗