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Biomedical subjects

L Sokoloff

Publications and source records attributed to L Sokoloff.

At least 235 records · Page 13Linked to original sources
PubMed1979

Osmotic opening of the blood-brain barrier and local cerebral glucose utilization.

The effects of osmotic opening of the blood-brain barrier (BBB) on local cerebral glucose utilization (LCGU) were studied in rats with the carbon 14-deoxyglucose method. The BBB was opened to Evans blue dye by unilateral carotid artery perfusion with hypertonic mannitol solution. (14C)-Deoxyglucose was injected 15 minutes or two to three hours later. Osmotic opening of the BBB resulted in focal areas of intense LCGU in affected areas of the perfused hemisphere. In the contralateral hemisphere, glucose utilization was diminished, especially in cerebral cortical areas. The effects were reversible. LCGU was normal in both hemispheres when permeability to Evans blue returned to normal two to three hours after carotid artery perfusion. In 3 of 5 experiments the administration of high doses of intravenous diazepam immediately following carotid artery perfusion with mannitol prevented an increase in LCGU in the perfused hemisphere but did not prevent lowering of LCGU in the contralateral hemisphere. Increased LCGU following osmotic opening of the BBB was not accompanied by a rise in local cerebral blood flow as measured by the iodoantipyrine method. Blood flow was, in fact, significantly decreased.

Animals↗
PubMed1979

Tomographic measurement of local cerebral glucose metabolic rate in humans with (F-18)2-fluoro-2-deoxy-D-glucose: validation of method.

Tracer techniques and quantitative autoradiographic and tissue counting models for measurement of metabolic rates were combined with positron computed tomography (PCT) and (F-18)2-fluoro-2-deoxy-D-glucose (FDG) for the measurement of local cerebral metabolic rate for glucose (LCMRGlc) in humans. A three-compartment model, which incorporates hydrolysis of FDG-6-PO4 to FDG, was developed for the measure of kinetic constants and calculation of LCMRGlc. Our model is an extension of that developed by Sokoloff et al. Although small, hydrolysis of FDG-6-PO4 was found to be significant. A PCT system, the ECAT, was used to determine the rate constants, lumped constant, and stability of the model in human beings. The data indicate that cerebral FDG-6-PO4 in humans increases for about 90 minutes, plateaus, and then slowly decreases. After 10 minutes, cerebral blood FDG activity levels were found to be a minor fraction of tissue activity. Precursor pool turnover rate, distribution volumes, and red blood cell-plasma concentration ratios were determined. Reproducibility (precision) of LCMRGlc measurements (approximate 2 cm2 regions) was +/- 5.5% over a 5-hour period. The replacement of arterial blood sampling with venous sampling was validated.

Animals↗
PubMed1979

Mapping of local cerebral functional activity by measurement of local cerebral glucose utilization with [14C]deoxyglucose.

A method has been developed to measure the rates of glucose utilization in the individual structural and functional components of the central nervous system. It can be applied to conscious as well as anaesthetized animals. The method is based on the use of [14C]deoxyglucose as a tracer for glucose consumption. [14C]Deoxyglucose-6-phosphate accumulates in the tissue in a mathematically definable relationship to the rate of the tissue's glucose utilization. The [14C]deoxyglucose-6-phosphate concentrations in the various tissues of the nervous system are measured by a quantitative autoradiographic technique. The autoradiographs themselves are pictorial representations of the relative rates of glucose consumption in these tissues. Application of this method to rats and monkeys in various states of altered function demonstrates a clear and close relationship between the local levels of functional activity and energy metabolism. The method appears to be useful for mapping functional neural pathways on the basis of evoked metabolic responses (Plum, Gjedde and Samson, 1976).

Animals↗
PubMed1979

The [18F]fluorodeoxyglucose method for the measurement of local cerebral glucose utilization in man.

A method has been developed to measure local glucose consumption in the various structures of the brain in man with three-dimensional resolution. [18F]-2-deoxy-2-fluoro-D-glucose is used as a tracer for the exchange of glucose between plasma and brain and its phosphorylation by hexokinase in the tissue. A mathematical model and derived operational equation are used which enable local cerebral glucose consumption to be calculated in terms of the following measurable variables. An intravenous bolus of [18F]-2-deoxy-2-fluoro-D-glucose is given and the arterial specific activity monitored for a predetermined period of from 30 to 120 minutes. Starting at 30 minutes, the activity in a series of sections through the brain is determined with three-dimensional resolution by an emission tomographic scanner. The method was used to measure local cerebral glucose consumption in two normal volunteers. The values in gray matter structures range from 5.79 mg/100 g per minute in the cerebellar cortex to 10.27 in the visual cortex, whereas, in white matter structures, the values range from 3.64 mg/100 g per minute in the corpus callosum to 4.22 in the occipital lobe. Average values for gray matter, white matter, and whole brain metabolic rates, calculated as a weighted average based on the approximate volume of each structure, are 8.05, 3.80, and 5.90 mg/100 g per minute, respectively. The value of 5.9 mg/100 g per minute compares favorably with values previously reported.

Adult↗
PubMed1978

Functional plasticity in the immature striate cortex of the monkey shown by the [14C]deoxyglucose method.

Autoradiographic representation of the local rates of cerebral glucose utilization and local cerebral functional activity by means of the [14C]deoxyglucose technique reveals the existence of the ocular dominance columns in the striate cortex of the monkey in the first day of life. In contrast to the stability of these columns in more mature brain, monocular deprivation for 3 months from the first day of life results in their complete disappearance and a reversion of the autoradiographic pattern to that seen in animals with normal binocular vision. These results are consistent with a reorganization of the representation of the visual fields of the two eyes in the striate cortex and provide additional evidence of the plasticity of the striate cortex of the monkey in early life.

Animals↗
PubMed1978

Local cerebral energy metabolism: its relationships to local functional activity and blood flow.

The results of studies with the [14C] deoxyglucose technique unequivocally establish that local functional activity in cerebral tissues is, as in other tissues, closely coupled to the local rate of energy metabolism. Stimulation of local functional activity increases the local rate of glucose utilization; reduced functional activity depresses it. Local cerebral blood flow is normally distributed among the cerebral structures in almost exact proportion to their rates of glucose utilization and it changes together with local glucose consumption in response to altered local functional activity. These results demonstrate that the level of functional activity in the structural and functional components of the central nervous system regulates the local rate of energy metabolism, and local blood flow is adjusted to the local metabolic demand.

Animals↗
PubMed1978

Local cerebral glucose utilization in the normal conscious macaque monkey.

The [14C]deoxyglucose method for quantitative determination of local cerebral glucose utilization was extended to the macaque monkey. The necessary constants required by its operational equation were evaluated. The lumped constant, measured in 7 normal conscious monkeys, was found to equal 0.344 (SEM, +/- 0.036). The rate constants were also estimated and found to be very similar to those obtained previously in the rat. With these essential constants evaluated, the method was applied to normal conscious monkeys. Local cerebral glucose utilization was found to vary marked throughout the brain but to fall within two distributions, a higher one in gray matter and lower one in white matter. In general, the values fell in a range to be expected from previous measurements of average energy metabolism in the brain as a whole. The values were considerably lower than those observed previously in the conscious rat. Marked heterogeneity of rates of glucose utilization were observed in a number of anatomical structures. In some cases the patterns of heterogeneity were consistent with known histological cytoarchitecture; in others the heterogeneity did not conform with known cytoarchitectural features but corresponded to patterns previously demonstrated by electrophysiological techniques. Many of the regions of the cerebral cortex showed columnar patterns of distribution of higher and lower rates of glucose utilization. These may be a metabolic reflection of the columnar organization of function within the cerebral cortex.

Animals↗
PubMed1978

Occult osteomalacia in American (U.S.A.) patients with fracture of the hip.

Low-grade osteomalacia, detectable only by quantitative histological measurement, was present in eight of 31 femoral heads from normocalcemia American patients having intracapsular fracture of the hip. The histological changes were of a much lower degree than those observed in overt clinical osteomalacia. Further, regional differences between the osteoid content of the proximal femur and iliac crest were demonstrated in 13 age-matched controls. In these, the osteoid content of the femoral bone averaged only 30% of that in the iliac crest.

Aged↗
PubMed1978

Local cerebral glucose uptake in awake and halothane-anesthetized primates.

Local glucose consumption within specific brain structures in awake and halothane-anesthetized primates was studied using a quantitative autoradiographic technique for glucose (14C-deoxyglucose). In both awake and anesthetized animals, significant heterogeneity (one-way analysis of variance) in uptake of glucose was found in the cortex, subcortical grey matter, and brainstem nuclei. No significant variability was found for any of the white matter areas sampled under either experimental condition. Halothane produced significant decreases in glucose metabolic rates in the occipital cortex, brainstem nuclei, cerebellar cortex, cerebellar white matter, and anterior commissure, compared with the awake state. The greatest decrease in cerebral metabolic rate was found in the occipital lobes of halothaneanesthetized animals. Results of this study suggest that neurophysiologic and behavioral changes that occur with anesthetic agents can, for the first time, be correlated with alterations in local cerebral glucose metabolism.

Anesthesia, Inhalation↗
PubMed1978

Measurement of local cerebral blood flow with iodo [14C] antipyrine.

The autoradiographic diffusible tracer technique for the measurement of local cerebral blood flow was originally designed for use with the radioactive, inert gas 131I-labeled trifluoroiodomethane and is applicable only with tracers that exhibit unrestricted diffusion through the blood-brain barrier. Because of the technical problems associated with the use of gaseous tracers, a suitable nonvolatile tracer has been sought. [14C] Antipyrine has been used previously and found to be unsuitable because of limitations in its diffusion through the blood-brain barrier. An analogue of [14C]antipyrine, iodo [14C]antipyrine, exhibits higher partition coefficients than [14C]antipyrine between nonpolar solvents and water and might, therefore, be expected to diffuse more freely through the barrier. Its use as the tracer in the local blood flow technique leads to values considerably above those obtained with [14C]antipyrine in the rat and cat and essentially the same as those obtained with the gas trifluoro[131I]iodomethane in the cat. Iodo[14C]antipyrine appears, therefore, to be a satisfactory nonvolatile tracer for the measurement of local cerebral blood flow.

Animals↗
PubMed1978

The effect of chondrocyte growth factor on membrane transport by articular chondrocytes in monolayer culture.

Chondrocyte growth factor (CGF), a contaminant of pituitary glycoprotein hormones, stimulates growth of cultured lapine articular chondrocytes while depressing SO4-proteoglycan synthesis. To study its effect on membrane transport, NIH-bTSH and two other preparations with comparable CGF activity were employed. In early log phase (36 hr) cultures CGF (64 microgram/ml) did not alter thymidine (dThd) uptake during the first 5 min. By 15 min however, TCA-precipitable dThd was 4-fold greater than in controls while the TCA-soluble fraction remained the same. CGF increased deoxy-glucose (DG) uptake in 36-hr old cultures. At 66 hr, CGF reduced DG transport. The transport of cycloleucine (CL) and aminoisobutyric acid (AIB) was reduced by CGF in 36 and 66-hr old cultures. There was a dose dependency between CGF concentration, the lowered uptake of DG, CL and AIB, and cell protein content. The effect of CGF on DG transport and dThd incorporation into DNA was not immediate but required prior exposure of the cells to CGF. CGF did not alter DG transport in rabbit or mouse fibrocytes or Chang liver cells. This and the reported finding that pituitary fibroblast growth factor (FGF), increases amino acid transport in other cells suggests that the biological specificity of CGF may not be identical to that of FGF.

Aminoisobutyric Acids↗