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Biomedical subjects

W F White

Publications and source records attributed to W F White.

At least 55 records · Page 3Linked to original sources
PubMed1984

Ascorbic acid supplementation and five year survival rates in women with early breast cancer.

The effect of long term ascorbic acid (AA) supplementation (3g per day) on 27 women with early breast cancer has been investigated. For comparison a similar but limited study was carried out in patients with benign breast disease. The responses of leucocyte levels of AA to supplementation provided some evidence to suggest that the metabolism and utilisation of the vitamin may be different in these patients. In addition longitudinal measurements of urinary hydroxyproline/creatinine (OHPro/Cr) ratio were carried out in these patients. The long term ingestion of AA did not appear to affect the prognosis of the disease in the early breast cancer group. Similar 5 year survival rates were seen in the unsupplemented and supplemented cancer groups.

Adult↗
PubMed1983

Isoguvacine binding, uptake, and release: relation to the GABA system.

Isoguvacine (1,2,3,6-tetrahydropyridine-4-carboxylic acid) is a GABA (gamma-aminobutyric acid) agonist with limited conformational flexibility. In these studies we investigated the binding, uptake, and release of [3H] isoguvacine by use of tissue preparations of rat CNS, comparing the results with similar studies of [3H]GABA. The results from these investigations indicate that isoguvacine binds to membrane preparations of rat forebrain with pharmacological characteristics similar to the post-synaptic GABA recognition site; that it is transported into synaptosomal preparations by an uptake system similar to the high-affinity GABA uptake system; and that recently accumulated isoguvacine is released in a Ca2+-dependent manner and by heteroexchange with external GABA. The ability of isoguvacine and gamma-hydroxybutyric acid to decrease the K+-stimulated Ca2+-dependent release process was also investigated. The results indicate that isoguvacine interactions have many of the biochemical features of GABA synaptic function, isoguvacine being, however, less potent than GABA.

3-O-Methylglucose↗
PubMed1983

Etazolate (SQ20009): electrophysiology and effects on [3H]flunitrazepam binding in cultured cortical neurons.

The actions of etazolate (SQ20009) on cultured cortical neurons have been examined in electrophysiological experiments and in receptor binding studies. Etazolate (0.3 to 100 microM) prolongs the duration of spontaneously occurring IPSPs. Higher concentrations of etazolate produce an increase in membrane chloride conductance, an effect which is picrotoxinin and bicuculline sensitive. Etazolate potentiates the response to exogenously applied GABA and acts synergistically with diazepam to enhance GABA-mediated conductance. Etazolate does not increase glycine-mediated conductance changes. Etazolate increases [3H]flunitrazepam binding and stimulates the GABA enhancement of [3H]flunitrazepam binding. In addition, GABA stimulates the etazolate enhancement of [3H]flunitrazepam binding. The etazolate-mediated increases in binding are Cl- dependent and picrotoxinin and bicuculline sensitive. The dose response relationships for etazolate-mediated effects are similar in physiological experiments and in binding studies. These data suggest that etazolate interacts with the postsynaptic GABA receptor complex at a site distinct from either the GABA recognition site or the benzodiazepine binding site to enhance GABA-mediated inhibition and to increase benzodiazepine binding.

Animals↗
PubMed1982

Aminoglutethimide therapy for advanced carcinoma of the prostate.

The results of aminoglutethimide treatment of 12 patients with advanced progressive metastatic carcinoma of the prostate are reported. As judged by performance status and analgesic requirements, there were subjective improvements in 75% of the group and side effects were minimal. No consistent objective improvements were observed but decrease in plasma androstenedione and testosterone was associated with subjective improvement in most responders. Mean survival of patients following introduction of aminoglutethimide was 6.5 months. Aminoglutethimide "medical adrenalectomy" appears safe and effective in management of advanced carcinoma of the prostate.

Aged↗
PubMed1981

Benzodiazepine binding and interactions with the GABA receptor complex in living cultures of rat cerebral cortex.

Benzodiazepines bind to living cultures of dissociated rat cerebral cortex. This binding is saturable, and kinetic analyses indicate that the binding is to a single class on sites with kinetic constants very close to those obtained using neuronal membrane preparations. The efficacy of a number of benzodiazepines, xanthine derivatives and other drugs in competition experiments is similar to that seen in neuronal membrane preparations, and suggests that the benzodiazepine binding site studied in these investigations is the same as that found in neuronal membrane preparations and believed to be the pharmacologically active benzodiazepine binding site. GABA agonists increase the binding of benzodiazepines, and this increase has the same order of efficacy as their ability to hyperpolarize the neurons when applied at known concentrations with muscimol greater than GABA greater than THIP. At high concentrations THIP potentials benzodiazepine binding to the same level as GABA. Diazepam increases the ability of both GABA and THIP to hyperpolarize the neurons as well as the amplitude of spontaneous IPSPS which, in this system, are GABA-mediated. The competitive GABA antagonist bicuculline methiodide slightly decreased benzodiazepine binding and also antagonized the increase due to GABA. The non-competitive GABA antagonist picrotoxinin had no effect on benzodiazepine binding but did antagonize the GABA-induced increase in benzodiazepine binding. Replacement of Cl- in the incubation medium by acetate, which does not permeate the GABA-mediated Cl-- ionophore, increases benzodiazepine binding, and GABA no longer increases the binding. Picrotoxinin decreases the increase in benzodiazepine binding is Cl--free media, and this decrease is blocked by GABA. These results are discussed in terms of interactions at the GABA receptor complex consisting of a GABA recognition site, a benzodiazepine recognition site, a picrotoxinin recognition site, and a Cl- ionophore.

Animals↗
PubMed1980

Biochemical correlates of GABA function in rat cortical neurons in culture.

Serial biochemical studies of a rat cortical tissue culture system in which synapses regularly form showed that gamma-aminobutyric acid (GABA) is present in the cultures and increases with their maturation. The tissue GABA concentration in mature cultures is similar to that of adult rat cortex in vivo. The synthetic enzyme, glutamate decarboxylase, also increases with age as does high affinity GABA uptake. GABA uptake was blocked by L-2,4-diaminobutyrate (DABA) and had the properties of neuronal GABA uptake. Specific release by depolarizing media of both exogenous [3H]GABA and GABA synthesized from D-[U-14C]glucose was demonstrated. The GABA released by high potassium media had higher specific activity and a greater contribution from glucose (as compared to acetate) than GABA found in the medium in the absence of depolarization. Calcium dependency of evoked GABA release could be shown only after pretreatment of cultures with ethyleneglycol-bis-(beta-aminoethyl ether)-N,N'-tetraacetic acid or EGTA. Synaptosomes may exhibit greater calcium dependence of evoked transmitter release than intact cells in culture because their intracellular calcium stores are depleted during preparation. Glycine uptake by the cultures was much less in amount than was GABA uptake, and specific release of glycine could not be demonstrated. Specific binding of both a GABA agonist ([3H]muscimol) and an antagonist ([3H]bicuculline) was shown by membranes prepared from the cultures. By contrast, when [3H]muscimol binding to intact cells was studied, essentially all binding was sodium dependent and had the properties of GABA uptake binding. We conclude that the use of [3H]muscimol for receptor studies is valid only after the elimination of GABA uptake systems. Biochemical data from these studies support the concept that GABA is the transmitter for many cortical synapses. Glycine and taurine are not likely to be transmitters in these cortical cultures. When considered together with physiological data from the preceding paper, we have satisfied Werman's criteria (see ref. 36) for accepting GABA as the major inhibitory transmitter in the cortical culture system.

4-Aminobutyrate Transaminase↗
PubMed1980

Identification of GABA neurons in rat cortical cultures by GABA uptake autoradiography.

Autoradiographic studies of rat cortical cultures were conducted with tritiated transmitters and related drugs. Autoradiographs prepared from cultures incubated in [3H]GABA showed selective labeling: dense accumulations of silver grains over the somas and all processes of approximately 30-50% of the neuronal population, few grains over the non-neuronal cells. This labeling was blocked by diaminobutyric acid (DABA) and sodium-free media but not by beta-alanine and thus has the characteristics of GABA uptake in other neuronal systems. There were no obvious differences in the size, shape, number of processes or distribution in the culture between neurons which accumulated GABA and those which did not. Similar cultures incubated in either [3H]glycine or [3H]glutamate and processed by autoradiography resulted in a much different distribution of silver grains than that seen for [3H]GABA. Following incubation in [3H]glycine, silver grains were distributed uniformly over all cells in the culture, both neuronal and non-neuronal. This distribution suggests a metabolic and not a neurotransmitter role for glycine in the cultures, as would be expected of neuronal cells derived from cerebral cortex. Glutamate incubations resulted in the appearance of silver grains over only the non-neuronal cells with very few over the neuronal population. Autoradiograms were also prepared following incubation in the potent GABA receptor agonist [3H]muscimol. These autoradiograms were indistinguishable from those obtained following [3H]GABA incubation. Thus, a finite population of neurons was densely labeled, the labeling was blocked by the GABA uptake inhibitors DABA, nipecotic acid, guvacine and Na+-free media, while substances which interact with the GABA receptor, bicuculline methiodide, THIP, isoguvacine and the noncompetitive antagonist, picrotoxin, were without effect. These results demonstrate that the affinity of muscimol for the GABA uptake site far outweighs its affinity for the GABA receptor site in autoradiographic experiments where intact cells are employed, presumably because its binding to receptors is fleeting. Therefore, muscimol autoradiography may not be informative about GABA receptor localization. These autoradiographic studies suggest that nearly half the neurons in our culture system are GABA neurons but disclosed no morphological handle for GABA neurons.

Animals↗
PubMed1979

Analysis of short-term plasticity at the perforant path-granule cell synapse.

Short-term plasticity was investigated at the perforant path-granule cell synapse in the hippocampal slice preparation. A successive decrement in the amplitude of the extracellular EPSP was obtained at all stimulus frequencies above 0.05 Hz. This effect of repetitive stimulation has previously been shown to fulfill the requirements for habituation processes. If each stimulus within an habituation train was followed by a second identical test stimulus the response to the test stimulus was larger than that to the paired conditioning stimulus. This short-term plasticity has been called paired pulse potentiation. The test response potentiated only with respect to the paired conditioning response and not with respect to previous test responses. Neither form of plasticity appeared to result from changes in the amplitude of the afferent fiber volley. Both habituation and paired pulse potentiation result from an interaction of at least three changes in the efficacy of transmission after a conditioning stimulus: (1) an initial depression, (2) an intermediate relative potentiation and (3) a late depression which decays slowly. Paired pulse potentiation could be demonstrated only if the interpair interval corresponded to the period of maximal late depression and the interstimulus interval to the period of relative potentiation. The amplitudes of intermediate relative potentiation and late depression (and inhibition of transmission by 2-amino-4-phosphonobutyric acid (APB)) were inversely related to the control response amplitude. This relationship likely derives from nonlinear stimulation of postsynaptic ionic currents at higher stimulus intensities. In contrast, the initial depression increased with response amplitude. This is consistent with a mechanism dependent on the postsynaptic membrane potential, such as refractoriness to succeeding stimuli. When the response amplitudes in the presence and absence of 2.5 mM APB were equalized by adjusting the stimulus intensity, no difference was found in the magnitude of either form of plasticity. Since APB probably inhibits transmission at this site through competitive antagonism at the postsynaptic receptor, this observation suggests that habituation and paired pulse potentiation are generated presynaptically.

Action Potentials↗
PubMed1979

The effect of acidic amino acid antagonists on synaptic transmission in the hippocampal formation in vitro.

The effects on synaptic efficacy of the putative acidic amino acid antagonists, 2-amino-4-phosphonobutyric acid (APB), 2-amino-3-phosphonopropionic acid (APP), 1-hydroxy-3-amino-pyrrolidone-2 (HA-966) and glutamic acid diethyl ester (GDEE), were tested by bath application to the hippocampal slice preparation. On the basis of previous work, we hypothesized that APB, HA-966 and GDEE might antagonize synaptic responses to either glutamate or aspartate, but APP should antagonize only synaptic responses to aspartate. APB and HA-966 reduced the amplitude of the extracellular EPSP recorded during stimulation of the perforant path fibers, but APP and GDEE were without effect. APB, APP and HA-966, but not GDEE, consistently inhibited transmission at Schaffer collateral and commissural synapses. The mossy fiber evoked extracellular EPSP was unaffected by these agents. At the concentrations used in this study (usually 2.5 mM) none of these drugs affected the amplitude of presynaptic fiber potentials or antidromic responses, indicating that they probably acted at synapses. The spontaneous activity of hippocampal pyramidal cells, but not of dentate granule cells, increased in the presence of 2.5 mM APB. The amplitude of the population spike generated by Schaffer commissural stimulation initially increased following introduction of APB into the medium and then declined in parallel with the extracellular EPSP. In addition, APB reduced the duration of recurrent inhibition during the period when pyramidal cell firing was enhanced. These results can be explained by an antagonism at the synapse between pyramidal cell and inhibitory interneuron.

Afferent Pathways↗
PubMed1978

Prolongation and enhancement of serum methotrexate concentrations by probenecid.

The disappearance of methotrexate (MTX) from the serum after an intravenous bolus injection and intravenous infusion was studied over 24 hours in eight and four patients respectively. Probenecid given at the same time as the bolus injection delayed the disappearance of MTX from the serum and resulted in enhanced concentrations throughout the 24 hours studied. At 24 hours the mean concentration was four times higher than in patients not given probenecid. Overall serum concentrations were even greater than those in patients who had received MTX by intravenous infusion. We suggest that smaller doses of MTX may be given and treatment costs thereby reduced if probenecid is given in addition.

Adult↗
PubMed1978

Self-concept correlates in academic placement of secondary school students.

In a large school system in the Southeastern United States 26% of the eighth grade students in the lower distribution of scores on a standardized test in reading and mathematics were assigned to vocational education courses and a career education program. One of the school counselors administered a self-concept inventory, the Me Scale (Yeatts & Morrison, 1974), to a randomized group of 43 students who were in the lower 26% of scores. The same inventory was administered to 91 randomly selected students in the upper distribution of scores. Significant differences were noted for one of five factors in the Me Scale. Lower achieving students perceived themselves as more capable in manual dexterity than higher achieving students.

Achievement↗