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Biomedical subjects

G F Mason

Publications and source records attributed to G F Mason.

42 records · Page 3Linked to original sources

Direct measurement of brain glucose concentrations in humans by 13C NMR spectroscopy.

Glucose is the main fuel for energy metabolism in the normal human brain. It is generally assumed that glucose transport into the brain is not rate-limiting for metabolism. Since brain glucose concentrations cannot be determined directly by radiotracer techniques, we used 13C NMR spectroscopy after infusing enriched D-[1-13C]glucose to measure brain glucose concentrations at euglycemia and at hyperglycemia (range, 4.5-12.1 mM) in six healthy children (13-16 years old). Brain glucose concentrations averaged 1.0 +/- 0.1 mumol/ml at euglycemia (4.7 +/- 0.3 mM plasma) and 1.8-2.7 mumol/ml at hyperglycemia (7.3-12.1 mM plasma). Michaelis-Menten parameters of transport were calculated to be Kt = 6.2 +/- 1.7 mM and Tmax = 1.2 +/- 0.1 mumol/g.min from the relationship between plasma and brain glucose concentrations. The brain glucose concentrations and transport constants are consistent with transport not being rate-limiting for resting brain metabolism at plasma levels greater than 3 mM.

Adolescent↗

NMR determination of the TCA cycle rate and alpha-ketoglutarate/glutamate exchange rate in rat brain.

A mathematical model of cerebral glucose metabolism was developed to analyze the isotopic labeling of carbon atoms C4 and C3 of glutamate following an intravenous infusion of [1-13C]glucose. The model consists of a series of coupled metabolic pools representing glucose, glycolytic intermediates, tricarboxylic acid (TCA) cycle intermediates, glutamate, aspartate, and glutamine. Based on the rate of 13C isotopic labeling of glutamate C4 measured in a previous study, the TCA cycle rate in rat brain was determined to be 1.58 +/- 0.41 mumol min-1 g-1 (mean +/- SD, n = 5). Analysis of the difference between the rates of isotopic enrichment of glutamate C4 and C3 permitted the rate of exchange between alpha-ketoglutarate (alpha-KG) and glutamate to be assessed in vivo. In rat brain, the exchange rate between alpha-KG and glutamate is between 89 +/- 35 and 126 +/- 22 times faster than the TCA cycle rate (mean +/- SD, n = 4). The sensitivity of the calculated value of the TCA cycle rate to other metabolic fluxes and to concentrations of glycolytic and TCA cycle intermediates was tested and found to be small.

Animals↗

NMR determination of intracerebral glucose concentration and transport kinetics in rat brain.

The concentration of intracerebral glucose as a function of plasma glucose concentration was measured in rats by 13C NMR spectroscopy. Measurements were made in 20-60 min periods during the infusion of [1-13C]D-glucose, when intracerebral and plasma glucose levels were at steady state. Intracerebral glucose was found to vary from 0.7 to 19 mumol g-1 wet weight as the steady-state plasma glucose concentration was varied from 3 to 62 mM. A symmetric Michaelis-Menten model was fit to the brain and plasma glucose data with and without an unsaturable component, yielding the transport parameters Km, Vmax, and Kd. If it is assumed that all transport is saturable (Kd = 0), then Km = 13.9 +/- 2.7 mM and Vmax/Vgly = 5.8 +/- 0.8, where Vgly is the rate of brain glucose consumption. If an unsaturable component of transport is included, the transport parameters are Km = 9.2 +/- 4.7 mM, Vmax/Vgly = 5.3 +/- 1.5, and Kd/Vgly = 0.0088 +/- 0.0075 ml mumol-1. It was not possible to distinguish between the cases of Kd = 0 and Kd greater than 0, because the goodness of fit was similar for both. However, the results in both cases indicate that the unidirectional rate of glucose influx exceeds the glycolytic rate in the basal state by 2.4-fold and as a result should not be rate limiting for normal glucose utilization.

Animals↗

Achiasmate meiosis and centromere shift in Eusimulium aureum (Diptera-Simuliidae).

Light and electronmicroscope studies indicate that Eusimulium aureum (n equals 2 metacentrics) is male-achiasmate. Supporting evidence for achiasmate meiosis includes lack of recombination between, I) widely separated differential segments of X and Y chromosomes and 2) linked autosomal inversions. In sibling C, chromosome II exists in an alternate "neoacrocentric" form interpreted as originating through the three-break shift of a small segment including centromere and nucleolar organizer. Male-achiasmate meiosis appears to be a prerequisite for the establishment of rearrangements that include large displacements of the centromere. This suggestion is supported by a correlation between achiasmate male meiosis and the fixation of gross pericentric changes in a number of other black fly species.

Animals↗