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Biomedical subjects

G C Newman

Publications and source records attributed to G C Newman.

33 records · Page 2Linked to original sources
PubMed1989

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↗
PubMed1989

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1987

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↗
PubMed1986

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↗
PubMed1985

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↗
PubMed1975

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↗
PubMedDate not supplied

Effects of dextran on hippocampal brain slice water, extracellular space, calcium kinetics and histology.

Hippocampal brain slices are valuable models for studying brain function but are compromised by several artifacts, including significant water gain and histologic injury, which occur under certain incubation conditions. Addition of colloid to Krebs-Ringer buffer (K-R) has been shown to eliminate water gain but has not achieved widespread acceptance. We confirm prior observations that dextran and PEG lessen the increase in slice mass during incubation in a dose-dependent manner with no water gain occurring at 4% concentrations. However, we also observe that addition of colloid to standard K-R induces severe neuronal pyknosis. Fortunately, the pyknosis can be eliminated by reduction in buffer osmolarity through adjustment of NaCl, producing markedly improved slice histology in dextran buffer, especially in the CA3 and CA4 regions of the hippocampus which are severely injured when incubated submerged in K-R at 37 degrees C. Extracellular space markers are not affected by either colloid. The volume of distribution for 45Ca is much larger in dextran buffers than in K-R and variability of 45Ca kinetics is also reduced. In the presence of dextran, hypoxia induces significant slice water gain, a relatively selective histologic injury and an alteration of tissue Ca2+ kinetics. Use of dextran buffers may eliminate many troubling brain slice artifacts.

Animals↗
PubMedDate not supplied

Phenytoin-induced hyperglycaemia may confound rat cerebroprotection models.

1. The anticonvulsant phenytoin (PHT) has been used with variable success in animal models of cerebral ischaemia. Although PHT has been reported to alter glucose regulation in man, this potential effect has been largely ignored in animals. Because hyperglycaemia strongly influences the outcome of cerebral ischaemia, we sought to systematically delineate the effects of PHT on serum glucose in several rat strains. 2. We studied the PHT dose-response curve for serum PHT and glucose concentrations and several physiological variables. Phenytoin induces a significant, concentration-dependent hyperglycaemia, even in the ranges commonly used for humans and in animal models. 3. Hypothermia of several degrees was observed during PHT administration, but no hypotension or bradycardia was found. 4. Both hyperglycaemia and hypothermia must be considered when PHT is studied as a neuroprotective agent in animal models.

Animals↗
PubMedDate not supplied

Optimizing dynamic T2* MR imaging for measurement of cerebral blood flow using infusions for cerebral blood volume.

We describe an approach to measuring cerebral blood flow (CBF) based on independent measurements of cerebral blood volume (CBV) and mean transit time (MTT) with calculation of CBF by using the central volume theorem: CBF = CBV / MTT. This permits optimization of the individual acquisitions and analyses. In particular, measurement of CBV during contrast infusion, rather than simultaneously with MTT from a single bolus, yields values more consistent with those of other methods.

Adult↗