Metastases and spinal cord compression.
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Epidural Space↗
Biomedical subjects
G C Newman
Publications and source records attributed to G C Newman.
Preservation of hippocampal brain slices with in vivo or in vitro hypothermia.
Hippocampal brain slices show CA1 injury similar to that seen after global ischemia in vivo. Cooling rats to 31 degrees C prior to sacrifice or cooling slices to 21 degrees C for 45 min increased the percentage of normal CA1 pyramidal cells after 5 h in vitro from 30% to over 80%. Brain slices also show a unique, consistent injury in dentate which is lessened by transient cooling to 21 degrees C but not by cooling the animal.
Analysis of Variance↗
Analysis of in vitro glucose utilization in a circadian pacemaker model.
An in vitro glucose utilization method, based upon 14C-2-deoxyglucose kinetics in brain slices, has been used to study circadian rhythms in hypothalamic slices containing the suprachiasmatic nucleus (SCN). Spontaneous SCN metabolic activity in vitro is similar to that observed in vivo with higher metabolic rates in subjective daytime and lower rates during subjective night. However, in vitro SCN metabolic activity during late subjective day is above that seen when glucose utilization is measured in vivo, suggesting that an inhibitory influence normally active in vivo is lost during slice isolation. Incubation of slices containing SCN in the presence of TTX exposes a TTX-insensitive component of metabolic activity in early subjective day, supporting prior suggestions that glucose utilization by the circadian oscillator continues in the absence of Na(+)-dependent action potentials. Studies with high Mg2+ concentrations are consistent with the hypothesis that most metabolic activity above the basal level observed with the glucose utilization method is related to synaptic activity. Pharmacological studies of the SCN brain slice model with radiotracers offer potential for analysis of both circadian rhythmicity and neural regulation.
Animals↗
Ischemic brain slice glucose utilization: effects of slice thickness, acidosis, and K+.
Brain slices of varying thickness were used to modify retention of metabolic products in an in vitro model of ischemia. Past and present results reveal increased anaerobic glycolysis in 660-microns slices with accumulation of lactate as slice thickness reaches 1,000 microns. Brain slice glucose utilization and lactate content were measured in buffers of various extracellular K+ levels and pH in 540-, 660-, and 1,000-microns slices. Acidosis suppresses glucose utilization at all slice thicknesses without affecting tissue lactate. Studies of 2-deoxyglucose metabolites establish that the suppression of glucose utilization by acidosis is due entirely to inhibition of glucose phosphorylation without any effect on glucose uptake into tissue. The inhibition is reversible after 45 min at pH 6.1. The experiments with acidosis also suggest that persistent energy demands continue to stimulate phosphofructokinase despite the low pH so that glycolysis continues, with potential for injury. Increasing K+ increases glucose utilization and tissue lactate at all three thicknesses. Correlations of glucose utilization with lactate accumulation support the possibility that high K+ may exert a dual influence on the tissue metabolism, not only stimulating glucose utilization by inducing depolarization but also by influencing the removal of metabolic products.
Animals↗
Kinetic model of 2-deoxyglucose metabolism using brain slices.
A six-compartment, nine-parameter kinetic model of 2-deoxyglucose (2DG) metabolism, which includes bidirectional tissue transport, phosphorylation, two-step dephosphorylation, phosphoisomerization, and conjugation to UDP and macromolecules, has been derived. Data for analysis were obtained from 540- and 1,000-microns-thick hippocampal and hypothalamic brain slices, which were incubated in buffer containing [14C]2DG, frozen, extracted with perchlorate, and separated on anion-exchange columns. Solutions of the equations of the model were fit to the data by means of nonlinear least-squares analysis. These studies suggest that dephosphorylation is adequately described by a single reaction so that the model reduces to eight parameters. The in vitro rate constants for transport, phosphorylation, and dephosphorylation are very similar to prior in vivo results. The phosphoisomerization rate constant is similar to dephosphorylation, so glycosylated macromolecules slowly accumulate and gradually assume larger relative importance as other compounds disappear more rapidly. Rate constants for 540-microns slices from hypothalamus and hippocampus are similar, while 1,000-microns slices have smaller tissue transport constants and larger phosphorylation constants. The rate equation for glucose utilization of this model is relatively insensitive to uncertainties regarding the rate constants. Including later metabolic components in kinetic models improves the calculations of glucose utilization with long isotope exposures.
Algorithms↗
Glucose utilization of ischemic hippocampal slices.
Hippocampal brain slices that were 1000 mu thick were prepared from Sprague-Dawley rats and studied using in vitro glucose utilization under well-oxygenated conditions or after a 15 min anoxic insult produced with a nitrogen atmosphere. Autoradiography reveals that glucose utilization is increased in CA1 and CA3 stratum radiatum of 1000 mu slices, even with full oxygenation, compared to the same regions in 540 mu slices. Following anoxia, there is an initial addition increase in stratum oriens of CA1 and CA3 glucose utilization that is followed by a decline in glucose utilization in all slice regions within an hour of the insult. Because increased glucose utilization is apparent at the slice surfaces as well as at the interior, it is suggested that thick brain slices are a model of brain ischemia, not just hypoxia.
Animals↗
Two augmentative communication systems for speechless disabled patients.
Patients may be rendered speechless because of many conditions, including cancer surgery, stroke, cerebral palsy, cervical cord and head trauma, neuromuscular paralysis, and intubation for respiratory failure. These same conditions may also be associated with decreased use of the hands, so that writing and other nonverbal forms of communication are also impaired. Lack of communication can frustrate the patient, the family, and health care personnel; increase the patient's isolation; and lead to poor patient cooperation, thus impeding progress in therapy and producing secondary psychiatric disturbances. Two communication programs that use a Commodore 64 computer are described in this paper. One communication program uses the alphabet and the other is based on the international Morse code. These programs are easy to use and inexpensive to establish, and they accommodate any switching device.
Communication Devices for People with Disabilities↗
Thick brain slices model the ischemic penumbra.
Hypothalamic brain slices, varying in thickness from 400 mu to 1,000 mu, were assessed by studying 2-deoxyglucose (2DG) metabolism, lactate accumulation, inulin spaces, and morphology at the light and ultrastructural levels. Evidence of increased glycolytic flux due to anaerobic metabolism is found at thickness greater than 600 mu in association with a progressive increase in the inulin-exclusion space. The metabolic profiles, as a function of depth into the slices, reveal that 700-mu slices function in a manner similar to 540-mu slices at the surfaces, but with a core of increased 2DG phosphorylation at the slice center. In contrast, the 1,000-mu slices show significant reduction of 2DG and increases in 2DG6P relative to the 540-mu slices at the slice surface as well as in the slice interior, suggesting impaired transport of 2DG into cells and spread of ischemic injury from the slice interior to the slice surface. Despite these metabolic changes, only minor morphologic changes of ischemic injury were found at the center of thicker slices, and in vitro glucose utilization of 1000-mu slices remained constant for up to 15 h. These three slice thicknesses should provide a useful model for studying the neurochemistry and neuropharmacology of the ischemic penumbra.
Animals↗
Brain slice glucose utilization.
The metabolism of 2-deoxyglucose has been studied in 540 micron and 1,000 micron hypothalamic brain slices. Slice 2-deoxyglucose (2DG) and 2-deoxyglucose-6-phosphate (2DG6P) levels were measured after tissue homogenization and perchloric acid extraction. By analyzing the uptake and washout kinetics with nonlinear least-squares methods, we have determined the rate constants for three-, four-, or five-parameter kinetic models and obtained a value for the in vitro lumped constant (LC). The kinetic analysis reveals a small, slowly decaying, 2DG component that is not predicted by any of the models. If this component is treated as a separate, parallel compartment, then the four- and five-parameter models are essentially equivalent. To compare our data to prior in vivo data, we combined 2DG and 2DG6P to produce Ci*, the total slice radioactivity, and analyzed the first 45 min of uptake. These data were fit best by a three-parameter model and the slowly decaying pool was not identified. Calculation of glucose utilization from total tissue radioactivity, measured by whole slice homogenization and by image analysis of autoradiograms, showed excellent correlation between the two methods. Image analysis of radioactivity in the suprachiasmatic nucleus, which is present in these slices, revealed a spontaneous diurnal variation in in vitro glucose utilization in close quantitative agreement with prior in vivo measurements. The kinetic analysis of the 1,000 micron slice was qualitatively similar to that of the 540 micron slice but revealed an increase in the LC and a large decrease in k1 as well as the expected large increase in the hexokinase rate constant, k3. Overall, in vitro glucose utilization increased by about 60%. These results are consistent with our prior studies of the 1,000 micron slice and support our interpretation that the 1,000 micron slice is an excellent in vitro model for brain ischemia without infarction.
Animals↗
Effects of calcium ions on glucose utilization in the rat suprachiasmatic nucleus in vitro.
The role of calcium ions in maintenance of the circadian rhythm in glucose utilization in the suprachiasmatic nucleus (SCN) of the hypothalamus was investigated in vitro in a rat hypothalamic slice preparation using the 2-deoxyglucose (2-DG) method. In normal Krebs solution, 2-DG uptake of adult and embryonic day 22 rat SCN was higher in subjective day than in subjective night. In calcium-free Krebs solution, however, 2-DG uptake of adult and embryonic SCN was low in both subjective day and night periods. These results indicate that the SCN rhythm in metabolic activity is dependent on calcium ions in both adult and embryonic rats. Since immunohistochemical and ultrastructural analysis of synapse formation has shown very few synapses in the SCN of embryonic day 22 rats, it is suggested that the development and maintenance of the circadian rhythm in metabolism demonstrated by the 2-DG method depends on intracellular calcium-mediated events rather than synaptic transmission.
Animals↗
Rhythm of suprachiasmatic nucleus 2-deoxyglucose uptake in vitro.
Using a hypothalamic slice preparation containing the suprachiasmatic nucleus (SCN) and measurement of 2-deoxy[14C]glucose (2-DG) uptake by autoradiography, we have demonstrated that, after 1 h in vitro, 2-DG uptake into the SCN is proportional to the rate of glucose utilization present in vivo at the corresponding subjective time of day and that, during an 8-h incubation in vitro, the SCN is capable of spontaneously changing its metabolic rate.
Animals↗
Treatment of progressive supranuclear palsy with tricyclic antidepressants.
After a single patient with progressive supranuclear palsy (PSP) improved when given amitriptyline, we compared the effects of amitriptyline, desipramine, and placebo on the symptoms and signs of four patients with PSP in a double-blind, double-crossover manner. There was good correlation between the use of tricyclic agents and symptomatic improvement, although all patients remained disabled. Amitriptyline produced better overall improvement, whereas desipramine preferentially improved apraxia of eyelid opening.
Aged↗
Diabetes mellitus updated: standards of quality care in office and hospital practice.
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Acidosis↗
Structural studies on phophatidylcholine-cholesterol mixed vesicles.
The homogeneous, single-walled phosphatidylcholine-cholesterol mixed vesicles were prepared by ultrasonic irradiation of egg phosphatidylcholine in the presence of various amounts of cholesterol in solution at 4 degrees under a nitrogen atmosphere followed by molecular sieve chromatography on a Sepharose 4B column. Physicochemical studies performed on these systems invluding sedimentation velocity, diffusion, partial specific volume, intrinsic viscosity, and trapped volume measurements allowed estimation of the weight-average vesicle weight, the vesicle shape, and bilayer membrane thickness of the binary mixture of phosphatidylcholine and cholesterol. Vesicle hydration was calculated using two different methods and the agreement between them was excellent up to cholesterol concentration of 0.32 mole fraction. It was observed that the structural parameters change slowly with increasing cholesterol content up to around 0.3 mole fraction and a relatively abrupt structural alteration occurs above this cholesterol content. This abrupt structural change is consistent with the asymmetrical distribution of lipid composition between the inner and outer bilayer face.
Binding Sites↗