Focal osteoporotic bone marrow defect.
Explore the source record for details and available documents.
Adipose Tissue↗
Biomedical subjects
D F Wilson
Publications and source records attributed to D F Wilson.
Substrate dependence of metabolic state and coronary flow in perfused rat heart.
The effect of substrate source on the regulation of energy metabolism and coronary flow was studied in isolated perfused rat hearts. Compared with glucose-perfused hearts, those perfused at the same work load with palmitate or acetate demonstrated increases (P less than 0.01) in O2 consumption of 16 and 18%, respectively, and increases (P less than 0.01) in coronary flow of 30 and 32%, respectively. Parallel substrate-related changes occurred in the levels of high-energy phosphate compounds: tissue creatine, ADP free, and inorganic phosphate (Pi) were significantly decreased, leading to increases (P less than 0.01) in [creatine phosphate]/[creatine] and [ATP]free/[ADP]free[Pi]. These changes were accompanied by increased reduction of intramitochondrial pyridine nucleotides. Omitting orthophosphate from perfusate lowered intracellular Pi and modified cardiac function, but substrate-related differences were similar to those in Pi containing media. Differences in intracellular pH among substrates were observed, which may contribute in some instances to differences in energy metabolism and coronary flow. When work load was altered in glucose- and acetate-perfused hearts, both O2 consumption and coronary flow were linearly related to cytosolic [ATP]free/[ADP]free[Pi], and slopes of regression lines were similar for both substrates. These correlations support the view that [ATP]free/[ADP]free[Pi] is a major determinant of O2 consumption by cardiac cells and of coronary flow.
Acetates↗
Middle fossa surgery. Report of 153 cases.
The principal indications for the middle cranial fossa approach to the petrous apex and internal auditory canal are section of the vestibular nerves in vertigo, management of lesions of the labyrinthine segment of the facial nerve, and removal of mass lesions of the internal auditory canal. We report 153 cases of pathosis of the temporal bone and related structures for which this approach was used.
Cranial Nerve Neoplasms↗
Spontaneous nasopharyngeal malignancies in the common marmoset.
Explore the source record for details and available documents.
Animals↗
Effect of oxygen concentration on cellular metabolism.
Experimental evidence is presented that mitochondrial oxidative phosphorylation is dependent on oxygen concentration in its physiologic range both in vivo and in vitro. Mitochondrial oxidative phosphorylation is considered to act as a tissue oxygen sensor important for controlling local vascular resistance.
Adenosine Diphosphate↗
Amino acid neurotransmitters in the CNS: effect of thiopental.
Thiopental, a thiobarbiturate which partitions prefentially into the hydrophobic environment, inhibited transport of amino acid neurotransmitters, GABA, aspartate and glutamate, and of biogenic amine, dopamine, across the synaptosomal membrane. At a given protein and thiopental concentration GABA transport was more sensitive to the barbiturate than were the movements of aspartate and glutamate although the uptake of each amino acid was inhibited essentially to the same extent as was its K+-stimulated release. By contrast, inhibition of dopamine uptake was larger than that of its release. Thiopental also inhibited the release of amino acid neurotransmitters caused by anaerobiosis. It is suggested that the barbiturate modifies the properties of the synaptosomal lipids and/or hydrophobic segments of proteins and thereby, simultaneously and independently, affects various membrane functions. The equal inhibition of uptake and release of amino acid neurotransmitters is consistent with the postulate that their transport occurs through the reversible membrane carriers which function efficiently in both the inward and outward directions.
Amino Acids↗
Relationship of the intra- and extramitochondrial adenine nucleotide ratios during synthesis of phosphoenolpyruvate using extramitochondrial ATP.
Mitochondria prepared from the livers of guinea pig, chicken, and pigeon all actively synthesize phosphoenolpyruvate from oxalacetate and GTP, utilizing phosphoenolpyruvate carboxykinase. It was previously shown (Wilson, D. F., Erecińska, M., and Schramm, V. L. (1983). J. Biol. Chem. 258, 10464-10473) that phosphoenolpyruvate carboxykinase is freely reversible and that, in conjunction with nucleoside diphosphate kinase and malate dehydrogenase, which are also present in the mitochondria, it can be used to measure the intramitochondrial [ATPfree]/[ADPfree]. In this study, synthesis of phosphoenolpyruvate by guinea pig liver mitochondria was studied under conditions for which the only source of GTP was extramitochondrial ATP via adenine nucleotide translocase and nucleoside diphosphate kinase (the mitochondria were treated with rotenone, oligomycin, uncoupler, and fluorocitrate). When the extramitochondrial [ATP]/[ADP] was greater than the intramitochondrial [ATPfree]/[ADPfree] calculated from the phosphoenolpyruvate carboxykinase reaction, there was net synthesis of phosphoenolpyruvate, but when it was less, there was net disappearance of phosphoenolpyruvate. Thus, the intramitochondrial [ATPfree]/[ADPfree] was equal to the extramitochondrial value at the point of reversal of the phosphoenolpyruvate carboxykinase reaction. This equality of the intra- and extramitochondrial adenine nucleotide ratios occurred with a measured mitochondrial membrane potential of approximately -36 mV, whereas in the previous experiments, equality was observed for conditions in which the measured membrane potential was -111 to -125 mV. Thus, adenine nucleotide translocation was not dependent on the transmembrane electrical potential and must, therefore, have occurred by electroneutral exchange.
Adenosine Diphosphate↗
Neurotransmitter amino acids in the CNS. I. Regional changes in amino acid levels in rat brain during ischemia and reperfusion.
The levels of amino acids in 6 regions of the brain (cortex, hippocampus, striatum, diencephalon, stem and cerebellum) were determined during an ischemic insult of 30 min and after recovery periods of up to 10 h. The results were analyzed in two groups: putative neurotransmitters (GABA, aspartate, glutamate, taurine, glycine and alanine) and non-neurotransmitters. In the neurotransmitter group, it was found that at the end of 30 min ischemia the levels of aspartate and glutamate slightly decreased whereas those of GABA and alanine rose substantially. The amounts of glycine and taurine remained unchanged. In 30 min after the ischemic insult, there were much larger decreases in aspartate and glutamate and increases in GABA and alanine with no change in glycine and taurine. At 2 h recovery the levels of the neurotransmitter amino acids had almost returned to control values and were fully recovered by 10 h after ischemia. It is postulated that glutamate and aspartate are released during ischemia into the extracellular space and subsequently 'washed-out' into the blood during the reperfusion. Release of GABA, if it occurs, is however, compensated by increase in its synthesis and decrease in its degradation under anaerobic conditions, both of which contribute to the rise in its steady-state level. In the non-transmitter category, increases were seen in amino acids present normally in very small concentrations; tyrosine, lysine, leucine and 3 hydrophobic amino acids: valine, methionine and phenylalanine, which were most pronounced at 2 h after ischemia. It is suggested that the rise in the levels of these molecules is the consequence of stimulation of protein breakdown caused by activation of intracellular proteases by calcium and H+ during the ischemic episode. Regional variations in the patterns of changes were small although in the ischemic models used the brainstem seemed to be least affected.
Alanine↗
Neurotransmitter amino acids in the CNS. II. Some changes in amino acid levels in rat brain synaptosomes during and after in vitro anoxia and simulated ischemia.
The effects of in vitro anoxia and membrane depolarization by veratridine on the uptake and release of amino acids were investigated in suspensions of synaptosomes isolated from the forebrains of rats. It was observed that GABA, aspartate and glutamate were released from synaptosomes in anaerobic conditions and upon addition of veratridine in a time-dependent manner. The release of the two latter amino acids was faster and more pronounced than that of GABA. The other amino acids were not affected in any systematic way by either condition. Re-introduction of oxygen or addition of tetrodotoxin to veratridine-treated synaptosomes resulted in the re-uptake of GABA, aspartate and glutamate, which was much faster and more complete for GABA than for the acidic amino acids, especially at acid pH values. The amounts of aspartate and glutamate in the incubation mixture remained constant during all the manipulations whereas that of GABA increased by about 30% during anaerobiosis, in agreement with the results obtained during in vivo ischemia. It is postulated that synaptosomes which utilize glutamate and aspartate as neurotransmitters are more damaged by anoxia and depolarization with veratridine than the population which utilizes GABA. These observations may explain reports that those neurons which are thought to receive major glutamatergic input are particularly sensitive to the lack of oxygen.
Amino Acids↗
The effect of thiol reagents on GABA transport in rat brain synaptosomes.
The nature of gamma-aminobutyric acid (GABA) transport has been investigated in preparations of rat brain synaptosomes using a number of thiol reagents with varying membrane permeabilities. N-Ethylmaleimide, p-chloromercuribenzoate and p-chloromercuriphenylsulfonate effectively inhibited GABA transport in both directions (i.e., uptake and release) whereas 5,5'-dithiobis-2-nitrobenzoate, mercaptopropionate and N- nitroethylenediamine were much less effective, or ineffective, even at millimolar concentrations. For each of the thiol reagents, the inhibition profile for GABA uptake was approximately the same as that for its release. The effectiveness of the reagents indicates that there is an external, reactable SH-group on the transporter, that the thiol reagent must be somewhat lipophilic for it to react with the SH-group(s), and that the same synaptosomal transport system is responsible for both uptake and release of GABA.
4-Chloromercuribenzenesulfonate↗
Dependence of gluconeogenesis, urea synthesis, and energy metabolism of hepatocytes on intracellular pH.
The relationship of intracellular pH to extracellular pH has been measured in suspensions of isolated hepatocytes at 25 degrees C. The internal pH was found to be a linear function of external pH and it changed by 0.45 pH unit per 1.0 unit change in external pH. The internal [H+] was equal to the external [H+] at approximately pH 7.1. Gluconeogenesis, urea synthesis, and oxidative phosphorylation showed different dependencies on the intracellular pH. Gluconeogenesis was the most sensitive to changes in [H+] and it declined by 80% when the intracellular pH decreased from 7.1 to 6.9. Urea synthesis was less pH-dependent, decreasing by about 30% for the same change in the intracellular [H+] whereas respiratory rate showed very little dependence on pH at this temperature. Intracellular [ATP]/[ADP] decreased linearly from 8.5 to 1.5 as the intracellular pH increased from 6.8 to 7.6, while intracellular [Pi] was essentially constant at 3.2 nmol/mg of cells, wet weight. Cytochrome c became more reduced with increasing intracellular pH, from less than 10% at pH 6.8 to 35% at pH 7.7. The calculated free energy of hydrolysis of ATP was nearly independent of pH as was the free energy of electron transfer from the intramitochondrial NAD couple (calculated from the [acetoacetate]/[3-OH-butyrate] ratio) to cytochrome c.
Animals↗
Oxygen dependence of cellular metabolism: the effect of O2 tension on gluconeogenesis and urea synthesis in isolated rat hepatocytes.
The dependencies of gluconeogenesis and urea synthesis on oxygen concentration were measured in suspensions of isolated rat hepatocytes and compared with the O2 dependence of cellular energy supply (reduction of cytochrome c, respiratory rate, mitochondrial [NAD+]/[NADH], lactate production, and [ATP]/[ADP] [Pi]). As the oxygen concentration was decreased, production of both glucose and urea declined; the changes were observable at 20 microM oxygen and below, with the apparent Km values for both processes of near 5 microM. The similar dependence of gluconeogenesis and urea synthesis on oxygen concentration indicates that the two pathways have equal access to the cellular ATP supply, i.e., there is no evidence that either pathway is preferentially turned off to spare ATP for the other. The cellular energy state had an oxygen dependence similar to that of glucose and urea synthesis. It is suggested that the behavior of gluconeogenesis and urea production is a reflection of homeostatic regulation of cellular metabolism which is designed to respond to changes in [ATP]/[ADP][Pi].
3-Hydroxybutyric Acid↗
Mitochondrial oxidative phosphorylation: tissue oxygen sensor for regulation of coronary flow.
The observation that mitochondrial oxidative phosphorylation in vivo is dependent on oxygen tension throughout the physiological range (Wilson et al., 1979a , 1979b ) has made this metabolic pathway the most probable candidate for the tissue oxygen sensor in the regulation of local blood flow. We have utilized the oxygen dependent regulatory system for coronary blood flow to examine this possibility. Alterations in coronary flow were induced by: 1. Varied work load; 2. Infusion of Amytal (an inhibitor of mitochondrial respiration); 3. Infusion of DNP; 4. Hypoxia. Increased work load caused increased coronary flow with no decrease in effluent oxygen tension while Amytal infusion and hypoxia caused vasodilation with increased and decreased O2 tension respectively. This indicates that oxygen tension per se cannot be responsible for the observed vasodilation. Tissue energy metabolism was evaluated by measuring metabolite levels in hearts which were freeze-clamped in each state of perfusion. In all four methods of vasodilation, a decrease in cellular energy state ratio ([ATP]f/[ADP]f[Pi]) expressed as the calculated ratio of free adenine nucleotides, was observed for conditions which increased flow. Systematic variation of work load, Amytal or DNP concentration resulted in quantitatively the same correlation between tissue [ATP]f/[ADP]f[Pi] and coronary flow. It is concluded that mitochondrial oxidative phosphorylation is the oxygen sensor for the regulation of coronary blood flow by tissue oxygen tension. Infusion of adenosine, a known coronary vasodilator, induced vasodilation which was completely blocked by theophylline.(ABSTRACT TRUNCATED AT 250 WORDS)
2,4-Dinitrophenol↗
Dependence of cellular metabolism and local oxygen delivery on oxygen tension.
Explore the source record for details and available documents.
Animals↗
Oral inverted ductal papilloma.
Explore the source record for details and available documents.
Epithelium↗
Papillary cystadenoma-like hyperplasia of the lip.
Explore the source record for details and available documents.
Cystadenoma↗
Effects of kainic acid in rat brain synaptosomes: the involvement of calcium.
The effects of kainic acid were investigated in preparations of rat brain synaptosomes. It was found that kainic acid inhibited competitively the uptake of D-[3H]aspartate, with a Ki of approximately 0.3 mM. Kainic acid also caused release of two excitatory amino acid neurotransmitters, aspartate and glutamate, in a time- and concentration-dependent manner, but had no effect on the content of gamma-aminobutyric acid. Concomitant with the release of aspartate and glutamate, depolarization of the synaptosomal membrane and an increase in intracellular calcium were observed, with no measurable change in the concentration of internal sodium ions. The increase in intrasynaptosomal calcium and decrease in transmembrane electrical potential were prevented by the addition of glutamate, whereas the kainate-induced release of radioactive aspartate was substantially inhibited by lowering the concentration of calcium in the external medium. It is postulated that kainic acid reacts with a class of glutamate receptors located in a subpopulation of synaptosomes, presumably derived from the glutamatergic and aspartatergic neuronal pathways, which possesses high-affinity uptake system(s) for glutamate and/or aspartate. Activation of these receptors causes opening of calcium channels, influx of calcium into the synaptosomes, and depolarization of the synaptosomal plasma membrane with consequent release of amino acid neurotransmitters.
Animals↗
Surgicel: its fate following implantation.
Surgicel, a local haemostatic gauze, is claimed to consist of oxidised regenerated cellulose. It is a polyanion, the functional unit of which is termed polyanhydroglucuronic acid. The ability of tissues to absorb Surgicel and its inherent haemostatic properties have been extensively investigated. This study was undertaken a) to determine the time required for absorption of Surgicel from implantation sites in the chest wall muscles of rats, and b) to establish mechanisms for its removal. Data derived from sequential uronic acid assays, histochemistry using the stain alcian blue, and transmission electron microscopy of implanted Surgicel were interpreted to reveal that Surgicel consists of at least two active components. These are a soluble uronic acid component which is lost after 6 h, and a fibrous component which persists. The latter material resembles Surgicel in the electron microscope and is still evident at the implantation site at 48 h post-implantation. Moreover, Surgicel can be characterized in vitro into at least two components according to its solubility under dissociative salt conditions (4M guanidinium chloride). A residual fibrous material could then be hydrolysed with 0.3N sodium hydroxide. We postulate that the absorption of the former salt soluble uronate in vivo is by early degradation and/or systemic clearance, whilst removal of the fibrous material requires phagocytosis.
Absorption↗