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Biomedical subjects

E J Davis

Publications and source records attributed to E J Davis.

At least 19 recordsLinked to original sources
PubMed1996

Stem-completion priming in Alzheimer's disease: the importance of target word articulation.

Stem-completion priming performance in patients with Alzheimer's type dementia (DAT) was explored in three experiments in which both the standard repetition priming effect and a novel indirect form of priming, cohort priming, were measured. In the first experiment, in which study stimuli were words, both priming effects were found to be markedly attenuated in the DAT group. In the second experiment, the study stimuli were specially constructed nonwords, and it was found that cohort priming was present at normal levels in the DAT group. In a third experiment we tested the specific hypothesis that the requirement to overtly articulate target stimuli during the study phase was critical for the appearance of normal cohort priming in the DAT group in Experiment 2, and also for the normal levels of repetition priming which have been reported in some published studies. Two encoding conditions were compared, one in which subjects simply had to read aloud the target words and a second in which subjects were required to make evaluative (pleasantness) ratings for each of the target words (identical to that used in Experiment 1). Stem-completion priming performance following the latter condition was significantly attenuated in the DAT group relative to a healthy control group, but following the "read aloud" encoding condition, normal levels of repetition and cohort priming were observed. It is suggested that the most fruitful approach to understanding the performance of DAT subjects on lexical repetition priming tasks will involve a detailed analysis of language functions and how they interact with other, possibly mnemonic, processes in the generation of primed responses.

Aged↗
PubMed1994

Excess membrane cholesterol is not responsible for metabolic and bioenergetic changes in AS-30D hepatoma mitochondria.

Using mitochondria isolated from normal rat liver and AS-30D hepatoma in addition to cholesterol-enriched mitochondria, we have evaluated the ability of membrane cholesterol to induce changes in mitochondrial function, specifically, the preferential export of citrate (i.e., truncation of the Krebs cycle). Two in vitro cholesterol-enrichment procedures failed to produce mitochondria with any physiologically significant increases in free membrane cholesterol. Alternatively, male Wistar rats were maintained on a 2% cholesterol diet to elevate mitochondrial cholesterol. This treatment resulted in liver mitochondria which contained 70% of the cholesterol levels found in AS-30D hepatoma mitochondria, yet only minor metabolic and bioenergetic alterations. Subfractionation of the various mitochondrial preparations revealed that cholesterol was located primarily in outer membranes of both the cholesterol-enriched and AS-30D preparations. We therefore conclude that an increase in membrane cholesterol is not sufficient to induce "truncation" of the citric acid cycle or any other mitochondrial abnormality in tumor cells.

Animals↗
PubMed1994

Cellular forms and functions of brain microglia.

Consistent with the recent characterization of microglial cells as macrophages, an overall picture for the unique function of these cells in CNS tissue has developed. The microglia are derived from blood monocytes that migrate into the tissue during fetal development and subsequently remain after complete formation of the blood-brain barrier. These monocytes give rise to the ramified microglia of adult tissue through the developmental intermediate of amoeboid microglia. Ramified microglia appear uniquely adapted in contrast to other tissue macrophages based on their stability or lack of turnover and mitotic capability. The ramified cells, while usually downregulated, can convert into active macrophages termed reactive microglia; this conversion appears to occur nonspecifically in response to any injury. Further, reactive microglial cells can fuse to form giant multinucleated cells during viral infections. Each microglia cell form possesses a characteristic morphology and differing functional state with regard to macrophage activity. In their role as tissue macrophages, microglia are involved in immune responses, tissue transplantation, and AIDS dementia complex, as well as many other neurological mechanisms and diseases.

Animals↗
PubMed1993

Oxidation of pyruvate, malate, citrate, and cytosolic reducing equivalents by AS-30D hepatoma mitochondria.

Mitochondria isolated from normal rat liver and AS-30D hepatoma were concurrently evaluated with regard to their bioenergetic and metabolic properties. AS-30D mitochondria oxidized many NAD-linked respiratory substrates at rates 1.5-4 times faster than those from liver, a fact which contributes to their diminished membrane depolarization on conversion from state 4 to state 3 respiration. AS-30D mitochondria exhibited no signs of a "truncated" Krebs cycle, nor did they oxidize malate preferentially based upon its origin in the cytosol or the mitochondrial matrix. In addition, beta-oxidation in AS-30D mitochondria was not sufficient to suppress respiratory CO2 production and induce pyruvate carboxylation to the extent observed in liver. Finally, AS-30D mitochondria were able to oxidize externally generated NADH in a reconstituted system, but in a manner independent of the transmembrane electrical potential (delta psi), suggesting that the malate-aspartate shuttle is not operable in vivo. This fact may necessitate the adaptations tumor cells make to reoxidize cytosolic NADH through glycolysis even in the presence of adequate oxygen.

Aconitate Hydratase↗
PubMed1993

Cognitive function during moderate hypoxaemia.

The effect of hypoxaemia (mean SpO2 78%) on cognitive function was measured in two groups of twelve normal subjects. A series of psychometric tests was administered to each subject in the same sequence and consisted of the Reitan trail-making test, a digit symbol substitution test, a visuospatial orientation test and the simple unprepared reaction-time test. Psychomotor performance was assessed in a double-blind manner while the subjects were breathing first air and then either air or a hypoxic mixture. While there was improvement in time for the trail-making test during a repeat study breathing air, there was significant deterioration of time to completion of the test in conditions of hypoxia. A significant learning effect in the orientation test was seen in the control group but this did not occur in hypoxic subjects. Hypoxaemia was shown to cause a significant impairment of simple unprepared reaction time compared with controls. All the changes in cognitive function were small and there were no subjective differences in the air or hypoxic groups. The usefulness of the Reitan trail-making and the simple unprepared reaction-time test in the assessment of psychomotor performance deficit under conditions of hypoxaemia has been demonstrated by this study in normal subjects. It was concluded that a mean oxygen saturation of 78% caused only minor changes in cognitive function in normal subjects.

Adult↗
PubMed1993

Wilson's disease and catatonia.

A 12-year-old Indian boy presented to a psychiatric unit with catatonia. He was subsequently diagnosed to have Wilson's disease. Symptoms improved on treatment with penicillamine, zinc sulphate, and benzodiazepines.

Catatonia↗
PubMed1992

Tardive dyskinesia and type II schizophrenia.

Cognitive impairment, negative and positive symptoms, primitive release reflexes, and age/temporal disorientation were assessed in 20 male patients meeting the DSM-III-R criteria for chronic schizophrenia and Schooler & Kane's criteria for TD. The control group comprised 20 age-matched male chronic schizophrenic patients without TD. Significant associations were found between TD, cognitive impairment, some negative symptoms, and formal thought disorder. These associations were independent of other illness and treatment variables. The severity of TD correlated significantly with that of cognitive impairment.

Age Factors↗
PubMed1991

An assessment of the role of proton leaks in the mechanistic stoichiometry of oxidative phosphorylation.

Rat liver mitochondria were incubated in the presence of varying concentrations of ATP, followed by ADP to initiate phosphorylation. Analysis of phosphorylation to oxygen ratios (P/O) was carried out with varied initial phosphorylation potentials (or ATP/ADP ratios). Rates of phosphorylation and respiration and magnitude of membrane potential (delta psi) were measured. The results are discussed in the framework of P/total O and P/"extra" O ratios in determination of the mechanistic P/O ratio. It is concluded that the former underestimates, and the latter overestimates the mechanistic P/O ratio.

Adenosine Diphosphate↗
PubMed1991

Control of reversible intracellular transfer of reducing potential.

Isolated rat liver mitochondria were incubated in the presence of a reconstituted malate-aspartate shuttle under carboxylating conditions in the presence of glutamate, octanoyl-carnitine and pyruvate, or a preset lactate/pyruvate ratio. The respiration and attendant energy state were varied with soluble F1-ATPase. Under these conditions reducing equivalents are exported due to pyruvate carboxylation. This was shown by lactate production from pyruvate and by a substantial increase in the lactate/pyruvate ratio. This led to a competition between malate export and energy-driven malate cycling via the malate-aspartate shuttle, resulting in a lowered redox segregation of the NAD systems between the mitochondrial and extramitochondrial spaces. If pyruvate carboxylation was blocked, this egress of reducing equivalents was also blocked, leading to an elevated value of redox segregation, delta G(redox) (in kJ) = -5.7 log(NAD+/NADHout)/(NAD+/NADHin) being then equal to approximately one-half of the membrane potential, in accordance with electrogenic glutamate/aspartate exchange. Reconstitution of malate-pyruvate cycling led to a further kinetic decrease in the original malate-aspartate shuttle-driven value of delta G(redox). Therefore, the value of segregation of reducing potential between mitochondria and cytosol caused by glutamate/aspartate exchange can be diminished kinetically by processes exporting reducing equivalents from mitochondria, such as pyruvate carboxylation and pyruvate cycling.

Animals↗
PubMed1989

Purification and characterization of methylmalonate-semialdehyde dehydrogenase from rat liver. Identity to malonate-semialdehyde dehydrogenase.

Methylmalonate semialdehyde dehydrogenase was purified from rat liver in order to define the distal portion of valine catabolism and related pathways in mammals. The purified enzyme is active with malonate semialdehyde and consumes both stereoisomers of methylmalonate semialdehyde, implicating a single semialdehyde dehydrogenase in the catabolism of valine, thymine, and compounds catabolized by way of beta-alanine. The oxidation of malonate and methylmalonate semialdehydes by this enzyme is CoA-dependent, the products being acetyl-CoA and propionyl-CoA, respectively. Expected activity with ethylmalonate semialdehyde as substrate was not found. Methylmalonate semialdehyde dehydrogenase was separated on DEAE-Sephacel into two isoforms which differ in mobility during nondenaturing polyacrylamide gel electrophoresis. The two forms are immunologically cross-reactive and exhibit the same N-terminal sequence, suggesting that one form is the product of the other. The monomer molecular mass, determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, was 58 kDa. The native molecular mass, estimated by gel filtration, was 250 kDa, suggesting a tetrameric structure.

Aldehyde Oxidoreductases↗
PubMed1989

Force-flow and back-pressure relationships in mitochondrial energy transduction: an examination of extended state 3-state 4 transitions.

Liver mitochondria were incubated through extended State 3-State 4 transitions (B. Chance and G. N. Williams (1955) J. Biol. Chem. 217, 409-423) in the presence of high concentrations of adenine nucleotides and in presence and absence of a protonophore. In the terminal phase of these transitions (the region of respiratory control), (a) there was a proportional relationship between the phosphorylation potential and membrane potential (delta psi); and (b) the rate of phosphorylation (Jp) was proportionately and inversely related to the back-pressure of delta psi (reflective of proton-motive force (delta p); (c) when phosphorylation was limited by the magnitude of delta psi in the presence of increasing [protonophore], Jp was proportionately and directly related to delta psi. The slopes of these two dependencies (a and c) were approximately equal, but opposite in sign. Protonophore or ADP, added separately, decreased delta psi but the extent of decrease in delta psi by ADP added after increasing amounts of protonophore decreased in a manner proportional to Jp. These data are in all respects consistent with bulk-phase delta p being the central intermediate driving (or suppressing) the phosphorylation reaction.

Adenine Nucleotides↗
PubMed1989

Heart mitochondria metabolize 3-methylthiopropionate to CO2 and methanethiol.

3-Methylthiopropionate (MTP) stimulates respiration of substrate-depleted heart mitochondria. This is blocked by uncouplers and by malonate. With the use of methyl-14C- and uniformly 14C-labeled MTP, it was found that methanethiol and CO2 are reaction products. The methyl carbon was not significantly oxidized. This study, together with a recent report [P. W. D. Scislowski et al. (1987) Biochem. J. 247, 35-40], demonstrates the existence of a transsulfuration independent pathway of methionine metabolism by muscle, and that the complete pathway following the initial transamination is a mitochondrial process. The data suggest that MTP is oxidized via acetyl-CoA.

Animals↗
PubMed1987

Methionine metabolism by rat muscle and other tissues. Occurrence of a new carnitine intermediate.

Perfused rat hindquarter preparations were shown to incorporate radioactivity from [U-14C]methionine into citrate-cycle intermediates, lactate, alanine, glutamate, glutamine and CO2. During perfusion, large amounts of methionine were also oxidized to methionine sulphoxide. The capacity for transamination of methionine or its oxo analogue, 4-methylthio-2-oxobutyrate, by muscle extracts was demonstrated. Rat skeletal muscle, heart, liver and kidney mitochondria, when incubated with the latter plus radiolabelled carnitine, formed a newly identified carnitine derivative, 3-methylthiopropionylcarnitine. It is concluded that the capacity for oxidation of methionine by a trans-sulphuration-independent pathway occurs in several mammalian tissues. The extent of inter-organ handling of intermediates in this pathway(s) is discussed.

Acyltransferases↗
PubMed1986

The involvement of pyruvate cycling in the metabolism of aspartate and glycerate by the perfused rat kidney.

The metabolism of glycerate and aspartate was investigated in perfused rat kidneys. The major pathway active for aspartate metabolism and NH3 production was found to include transamination, and not the purine nucleotide cycle. Pyruvate cycling was identified as a means by which reducing potential is generated in the cytosol for glucose and lactate production from these substrates. Inhibition of mitochondrial pyruvate transport caused an inhibition of glucose production, accumulation of lactate and pyruvate in the perfusate, and a decrease in the [lactate]/[pyruvate] ratio in kidneys perfused with aspartate. These data indicate a role of mitochondrial pyruvate transport in the provision of cytosolic reducing potential. With either aspartate or glycerate, 3-mercaptopicolinic acid (3-MPA) suppressed glucose synthesis and caused accumulation of malate plus fumarate within the kidney. Glucose production from glycerate was much less sensitive to the presence of 3-MPA than was glucose production from aspartate, illustrating a phosphoenolpyruvate carboxykinase (PEPCK)-independent pathway for the cycling of pyruvate. In aspartate-perfused kidneys, the presence of 3-MPA, at concentrations that completely blocked glucose accumulation in the perfusate, did not affect the rate of NH3 production and had only a minor effect on the rate of aspartate uptake. These data allow for an estimation of the rate of pyruvate formation from aspartate of about 1 mumol/min per kidney under conditions of complete PEPCK inhibition. Thus a PEPCK-independent pathway is operative for amino acid oxidation and pyruvate formation in perfused kidneys. The NADP-linked, but not the NAD-linked, 'malic' enzyme activity of the kidney cortex was found to be sufficient to catalyse this estimated rate of pyruvate formation.

Aminooxyacetic Acid↗