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Biomedical subjects

M E Rice

Publications and source records attributed to M E Rice.

At least 55 records · Page 3Linked to original sources

Direct monitoring of dopamine and 5-HT release in substantia nigra and ventral tegmental area in vitro.

Fast-scan cyclic voltammetry with carbon fibre microelectrodes was used to detect endogenous dopamine (DA) and 5-hydroxytryptamine (5-HT) release from three distinct regions of guinea-pig mid-brain in vitro: rostral and caudal substantia nigra (SN) and the ventral tegmental area (VTA). Previous electrophysiological studies have demonstrated that cells of the caudal SN and the VTA have similar characteristics, whereas cells in the rostral SN have distinctly different properties. In the present study, we confirmed that each region has tyrosine hydroxylase-positive neurons and determined, using high-performance liquid chromatography, that DA levels were similar in rostral and caudal SN, but lower in SN than in VTA. In each region, application of veratrine, which was shown by intracellular recordings to have a reversible depolarising action, evoked a signal attributable to DA and distinguishable from that of 5-HT. Release signals were monitored every 250 ms with a spatial resolution of less than 50 microns.l DA release was calcium-dependent and was not detectable in a catecholamine-poor area such as the cerebellum, or in mid-brain tissue pre-treated with reserpine. Within the normal mid-brain, the amount of DA released was correlated with tissue content in that it was higher in the VTA than in either region of SN. It is concluded that DA released from somato-dendritic parts of mid-brain neurons exhibits site-specific variation. This is the first report of direct monitoring of DA and 5-HT release from these regions with in situ electrodes and demonstrates the utility of fast-scan cyclic voltammetry to investigate the mechanisms and possible non-classical functions of somato-dendritic DA release.

Animals↗

Psychopathy as a taxon: evidence that psychopaths are a discrete class.

Taxometric analyses were applied to the construct of psychopathy (as measured by the Psychopathy Checklist) and to several variables reflecting antisocial childhood, adult criminality, and criminal recidivism. Subjects were 653 serious offenders assessed or treated in a maximum-security institution. Results supported the existence of a taxon underlying psychopathy. Childhood problem behaviors provided convergent evidence for the existence of the taxon. Adult criminal history variables were continuously distributed and were insufficient in themselves to detect the taxon.

Adolescent↗

Ascorbic acid, but not glutathione, is taken up by brain slices and preserves cell morphology.

1. We have determined the ascorbic acid (ascorbate) and glutathione (GSH) content of cortical and hippocampal slices from rat brain after prolonged (6h) incubation and have correlated these levels with the histological quality of the slices. Ascorbate and GSH levels in control and sliced tissue were determined by high performance liquid chromatography (HPLC) with electrochemical detection. Cell morphology of incubated slices was compared with that of intact tissue in cresyl violet stained tissue sections. 2. Roughly 70% of tissue ascorbate and GSH was lost from slices during incubation in vitro. Normal in vivo levels of ascorbate (2-3 mumol g-1 tissue wet weight) could be maintained by including 200-400 microM ascorbate (typical extracellular concentration) in the incubation media. By contrast, the loss of GSH could not be prevented by incubation with GSH. 3. The morphology of cells in hippocampal slices incubated under conditions that maintained ascorbate content and compartmentalization were similar to those of intact tissue. Ascorbate protected pyramidal cells in CA1 and CA3 regions of the hippocampus from the degeneration that was seen in slices incubated in ascorbate-free media. 4. These data suggest that loss of endogenous antioxidants may be a major factor in neuronal loss in vitro and support the notion that ascorbate is an endogenous neuroprotective agent.

Animals↗

Origin of the apparent tissue conductivity in the molecular and granular layers of the in vitro turtle cerebellum and the interpretation of current source-density analysis.

1. We determined the origin of the apparent tissue conductivity (sigma 2) of the turtle cerebellum in vitro. 2. Application of a current with a known current density (J) along the longitudinal axis of a conductivity cell produced an electric field in the cerebellum suspended in the cell. The measured electric field (E) perpendicular to the cerebellar surface indicated a significant inhomogeneity in sigma a (= J/E) with a major discontinuity between the molecular layer (0.25 +/- 0.05 S/m, mean +/- SD) and granular layers (0.15 +/- 0.03 S/m) (n = 39). 3. This inhomogeneity was more pronounced after anoxic depolarization. The value of sigma a decreased to 0.11 +/- 0.03 and 0.040 +/- 0.008 S/m in the molecular and granular layers, respectively. The ratio of sigma a S in the two layers increased from 1.67 in the normoxic condition to 2.75 after anoxic depolarization. 4. This difference in sigma a across the two layers was present within the range of frequencies (DC to 10 kHz) studied where the phase of sigma a was small (less than +/- 2 degrees) and therefore sigma a was ohmic. 5. The inhomogeneity in sigma a was in part due to an inhomogeneity in the extracellular conductivity (sigma e) as determined from the extracellular diffusion of ionophoresed tetramethylammonium. Like sigma a, the value of sigma e was also higher in the molecular layer (0.165 S/m) than in the granular layer (0.097 S/m). The inhomogeneity in sigma e was due to a smaller tortuosity and a larger extracellular volume fraction in the molecular layer compared with the granular layer. 6. sigma a was, however, consistently higher, by approximately 50%, than sigma e. A core conductor model of the cerebellum indicated that these discrepancies between sigma a and sigma e were attributable to additional conductivity produced by a passage of the longitudinal applied current through the intracellular space of Purkinje cells and ependymal glial cells, with the glial compartment playing the dominant role. Cells with a long process and a short space constant such as the ependymal glia evidently enhance the effective "extracellular" conductivity by serving as intracellular conduits for the applied current. The result implies that the effective sigma e may be larger than sigma e for neuronally generated currents in the turtle cerebellum because the space constant for Purkinje cells is several times greater than that for the ependymal glia and consequently Purkinje cell-generated currents travel over a long distance relative to the space constant of glial cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Extracellular dopamine concentration in the retina of the clawed frog, Xenopus laevis.

Dopamine reaches targets in the outer retina of the clawed frog (Xenopus laevis) by diffusion from a network of dopaminergic cells and processes located predominantly at the junction of inner nuclear and inner plexiform layers. We obtained values for the steady-state release, uptake, and extracellular concentration of dopamine in the retina by a combination of HPLC (with electrochemical detection), scintillation spectroscopy, and fast-scan cyclic voltammetry. Vitreal concentrations of dopamine varied from 564 +/- 109 nM in light-adapted eyes near the time of subjective dawn to 156 +/- 12 nM in dark-adapted eyes. The data are consistent with a simple model for steady-state dopamine diffusion from an appropriately sited thin-sheet source. This model was used to generate a profile of extracellular dopamine concentration as a function of retinal depth. The model predicted an increase in the dopamine concentration from the vitreous to the layer of dopaminergic cells, remaining constant from that layer to the distal tips of the photoreceptors. This prediction was borne out by comparing fast-scan voltammetric measures of dopamine at the distal tips of the receptors with the vitreal concentrations determined by HPLC using electrochemical detection.

Animals↗

Transient extracellular volume reduction in neural lobe of rat hypophysis in response to neural stalk stimulation in vitro and its relationship to extracellular potassium.

1. Using ion-sensitive microelectrodes, a transient reduction in the local volume of neural lobe extracellular space was found to accompany the elevation in extracellular potassium induced by stimulation of the neural stalk. The volume decrease and potassium increase had similar stimulus-response curves when stimulus frequency was varied from 1 to 40 Hz, with maximal response at 20 Hz. The curves for stimulus duration diverged, as a near maximal potassium response was reached in 4-16 s with a 20-Hz stimulus, while the extracellular volume decrease was maximal at 64 s. 2. The volume decrease, but not the potassium increase, was strongly inhibited by lowering bath temperature and moderately inhibited by furosemide and by lowering extracellular chloride concentration. Both the volume and the potassium response were enhanced by ouabain. 3. In conclusion, shrinkage of the local extracellular space in neural lobe during nerve activity is mediated by a metabolically active process which is only partially dependent upon extracellular chloride concentration and anion-cation co-transport, but is relatively independent of Na(+)-K+ pump activity. A transient shrinkage in extracellular space during increased neurohypophysial nerve activity would be expected to play a role in hormone diffusion, ion buffering, and extracellular current flow.

Animals↗

Anisotropic and heterogeneous diffusion in the turtle cerebellum: implications for volume transmission.

1. Measurements of extracellular diffusion properties were made in three orthogonal axes of the molecular and granular layers of the isolated turtle cerebellum with the use of iontophoresis of tetramethylammonium (TMA+) combined with ion-selective microelectrodes. 2. Diffusion in the extracellular space of the molecular layer was anisotropic, that is, there was a different value for the tortuosity factor, lambda i, associated with each axis of that layer. The x- and y-axes lay in the plane parallel to the pial surface of this lissencephalic cerebellum with the x-axis in the direction of the parallel fibers. The z-axis was perpendicular this plane. The tortuosity values were lambda x = 1.44 +/- 0.01, lambda y = 1.95 +/- 0.02, and lambda z = 1.58 +/- 0.01 (mean +/- SE). By contrast, the granular layer was isotropic with a single tortuosity value, lambda Gr = 1.77 +/- 0.01. 3. These data confirm the applicability of appropriately extended Fickian equations to describe diffusion in anisotropic porous media, including brain tissue. 4. Heterogeneity between the molecular and granular layer was revealed by a striking difference in extracellular volume fraction, alpha, for each layer. In the molecular layer alpha = 0.31 +/- 0.01, whereas in the granular layer alpha = 0.22 +/- 0.01. 5. Volume fraction and tortuosity affected the time course and amplitude of extracellular TMA+ concentration after iontophoresis. This was modeled by the use of the average parameters determined experimentally, and the nonspherical pattern of diffusion in the molecular layer was compared with the spherical distribution in the granular layer and agarose gel by computing isoconcentration ellipsoids. 6. One functional consequence of these results was demonstrated by measuring local changes in [K+]o and [Ca2+]o after microiontophoresis of a cerebellar transmitter, glutamate. The ratios of ion shifts in the x- and y-axes in the granular layer were close to unity, with a ratio of 1.04 +/- 0.08 for the rise in [K+]o and 1.03 +/- 0.17 for the decrease in [Ca2+]o. In contrast, ion shifts in the molecular layer had an x:y ratio of 1.44 +/- 0.14 for the rise in [K+]o and 2.10 +/- 0.42 for the decrease in [Ca2+]o. 7. These data demonstrate that the structure of cellular aggregates can channel the migration of substances in the extracellular microenvironment, and this could be a mechanism for volume transmission of chemical signals. For example, the preferred diffusion direction of glutamate along the parallel fibers would help constrain an incoming excitatory stimulus to stay "on-beam."

Animals↗

Anoxia-resistant turtle brain maintains ascorbic acid content in vitro.

The isolated turtle brain maintains intra- and extracellular concentrations of ascorbate when incubated in ascorbate-free physiological saline for as long as 24 h. After incubation for 1 h, total tissue content of ascorbate in the turtle cerebellum was the same as in unincubated controls. After 20-24 h, tissue ascorbate content remained at 65% of control levels, while extracellular ascorbate concentration, measured with carbon fiber voltammetric microelectrodes, was 56% of the initial value. For an intermediate incubation period of 6 h, reduced ascorbate content was maintained at about 80% of control levels, regardless of whether incubation was under normal conditions or in the absence of glucose or oxygen. By contrast, only 4% of the ascorbate content of guinea pig brain slices remained after a 6 h incubation. Maintenance of high levels of ascorbate by the anoxia-resistant turtle brain could be an important factor in the amelioration of oxidative injury in this tissue. Inclusion of ascorbate in media used for in vitro studies of mammalian brain tissue is recommended.

Animals↗

Extracellular alkaline-acid pH shifts evoked by iontophoresis of glutamate and aspartate in turtle cerebellum.

The effect of glutamate and aspartate iontophoresis on extracellular pH was investigated in the turtle cerebellum in vitro. Both amino acids produced a rapid alkaline transient, typically followed by a prolonged acidification. These responses could be evoked in all layers of the cerebellum. Transition from bicarbonate to N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid-buffered media amplified the pH shifts. Similar alkaline-acid transients could be evoked in the molecular layer by electrical stimulation of the parallel fibers or the ipsilateral peduncle, or by superfusion of glutamate or aspartate. However, no alkaline shifts were evoked in the granular layer by either parallel fiber or peduncle stimulation. In contrast, the iontophoretically induced alkaline shifts were largest in the granular layer. Compared with the stimulus-evoked alkalinizations, the iontophoretic alkaline shifts were relatively insensitive to Mn2+ or Cd2+. These data suggest that the activity-dependent alkalinization of brain extracellular space is generated by a bicarbonate-independent mechanism related to excitatory synaptic transmission. The results are consistent with a flux of hydrogen ions through cationic channels, but do not support a direct role for voltage-dependent Ca2+ channels. In view of the sensitivity of ion channels to changes in external pH, and the magnitude of the amino acid-induced pH shifts, these results indicate that extracellular pH could play an important modulatory role in excitatory synaptic transmission.

Animals↗

Sexual recidivism among child molesters released from a maximum security psychiatric institution.

The recidivism of 136 extrafamilial child molesters who had received phallometric assessment in a maximum security psychiatric institution from 1972 to 1983 was determined over an average 6.3-year follow-up. Fifty had participated in behavioral treatment to alter inappropriate sexual age preferences. Thirty-one percent of the subjects were convicted of a new sex offense, 43% committed a violent or sexual offense, and 58% were arrested for some offense or returned to the institution. Subjects convicted of a new sex offense had previously committed more sex offenses, had been admitted to correctional institutions more frequently, were more likely to have been diagnosed as personality disordered, were more likely to have never married, and had shown more inappropriate sexual preferences in initial phallometric assessment than those who had not. Behavioral treatment did not affect recidivism.

Adult↗

Extracellular volume decreases while cell volume is maintained by ion uptake in rat brain during acute hypernatremia.

1. Regulation of brain extracellular and intracellular water content, regarded as volume, and electrolytes in response to 90 min of hypernatremia has been studied in the cerebral cortex of rats under urethane anaesthetic. 2. Total tissue electrolytes and water were partitioned between extracellular and intracellular compartments based on measurements made in two series of experiments. In one, tissue samples were collected and analysed for total water, Na+, K+ and Cl-. In the other, tissue extracellular volume fraction, [Na+] and [K+] were measured in situ using ion-selective microelectrodes. 3. Osmotically induced water loss from cerebral cortex was less than that predicted for ideal osmotic behaviour, revealing a degree of volume regulation, and this regulation was associated with net tissue uptake of Na+, Cl- and K+. 4. Total water content was 3.77 g H2O (g dry weight)-1 in control cortex and this decreased by 7% after 30 min of hypernatremia and then remained relatively stable at this value. Control extracellular water content, based on an extracellular volume fraction of 0.18, was 0.88 g H2O (g dry weight)-1. Control intracellular water content, estimated as the difference between total and extracellular water contents, was 2.89 g H2O (g dry weight)-1. After 30 min of hypernatremia, extracellular water content decreased by an average of 27% but intracellular water did not change. This indicates selective regulation of cell volume. By 90 min the extracellular water content had decreased by 47% and the loss in extracellular water content appeared to be accompanied by a roughly equivalent increase in intracellular water content. The intracellular volume increase, however, was not statistically significant. The tortuosity of the extracellular space averaged 1.57 and increased to 1.65 during the hypernatremia. 5. Brain extracellular fluid and plasma [Na+] were roughly equal in control tissue. Both increased by 30 mu equiv (g H2O)-1 as a result of the hypernatremia, although extracellular [Na+] lagged behind the plasma value during much of the first 60 min of hypernatremia. Extracellular [K+] was homeostatically regulated at 3 mu equiv (g H2O)-1 independent of changes in plasma electrolytes. 6. Estimates of extracellular and intracellular ion content (mu equiv (g dry weight)-1) indicate that extracellular Na+, Cl- and K+ content decreased during hypernatremia, by 32, 21 and 42% respectively, whereas intracellular ion content increased by 100, 169 and 5% respectively. 7. It is concluded that during acute hypernatremia the extracellular space decreases in volume through the loss of water and electrolytes while the intracellular compartment maintains its water content and gains electrolytes.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Diffusion characteristics and extracellular volume fraction during normoxia and hypoxia in slices of rat neostriatum.

1. Diffusion properties of submerged, superfused slices from the rat neostriatum were measured by quantitative analysis of concentration-time profiles of tetramethylammonium (TMA+) introduced by iontophoresis. TMA+ was sensed at an ion-selective microelectrode (ISM) positioned 100-150 microns from the source pipette. Slice viability was assessed from the extracellular field potentials evoked by intrastriatal electrical stimulation. 2. Under normoxic conditions the extracellular volume fraction (alpha) was 0.21 (range 0.18-0.24), and the tortuosity (lambda) was 1.54, in slices with good field potentials. In slices with poor field potentials, alpha was 0.09-0.16. Extraction of correct alpha and lambda in the slice required evaluation of nonspecific uptake, k', which was 1 x 10(-2) s-1. 3. Slices were made hypoxic by superfusing physiological saline equilibrated with 95% N2-5% CO2 for 10-30 min. Synaptic components of field potentials were inhibited after 3-4 min in hypoxic media. In some experiments extracellular K+ concentration [( K+]o) was monitored with ISMs. During hypoxia, [K+]o rose from an average baseline of 5.1 mM to 7-10 mM. After reoxygenation, [K+]o transiently fell below the original level. 4. The average value for alpha during hypoxia was 0.13 (a 38% decrease), which was significantly different from control (P less than 0.001) and increased progressively during hypoxic exposure. In contrast, tortuosity and k' were unchanged by this treatment. 5. These data represent the first characterization of the diffusion properties of the rat striatal slice and of changes in extracellular volume fraction during hypoxia in a brain slice preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

An empirical approach to classification and treatment planning for psychiatric inpatients.

Treatment efforts for psychiatric patients traditionally are organized according to diagnosis, length of stay, age, and level of management difficulty. The current study, prompted by an attempt to reorganize services for 178 patients at a regional psychiatric hospital, examined the incidence of 72 problems exhibited either in the community prior to admission or within the institution. Factor and cluster analyses were used to identify clinically important subgroups of patients. Implications of the results for institutional organization also are discussed.

Activities of Daily Living↗

Glutamate- and aspartate-induced extracellular potassium and calcium shifts and their relation to those of kainate, quisqualate and N-methyl-D-aspartate in the isolated turtle cerebellum.

Ion-selective microelectrodes can be used to evaluate the characteristics and laminar distribution of excitatory amino acid agonist-induced K+ and Ca2+ shifts in the extracellular environment of brain cells. This report describes the pattern of K+ increases and Ca2+ decreases elicited by glutamate and aspartate at 100 microns intervals in the isolated turtle cerebellum. These responses were compared to ion shifts evoked by kainate, quisqualate and N-methyl-D-aspartate. Glutamate and aspartate produced indistinguishable laminar patterns of ion shifts, with the greatest [K+]o and [Ca2+]o shifts in the granular layer. The average maximum granular and molecular layer increases in [K+]o were, respectively, 130% and 24% larger than the increase in the Purkinje cell layer. Kainate-induced increases in [K+]o also followed this granular greater than molecular greater than Purkinje cell layer pattern; however, the corresponding [Ca2+]o decreases were smaller and more variable. Quisqualate-evoked ion shifts in the molecular layer closely mimicked the shape of glutamate- and aspartate-induced responses. In the granular layer, however, quisqualate caused little ion change during iontophoresis followed by large [K+]o and [Ca+]o shifts after the end of the pulse. The minimal ion shifts induced during quisqualate application in the granular layer gave this agonist the distinction of being the only agent tested to have its greatest direct effect in the molecular layer. N-Methyl-D-aspartate caused large, two-phase [K+]o and [Ca2+]o shifts in the granular layer, only small [K+]o rises in the Purkinje cell and ventral molecular layers, and no response in the dorsal molecular layer. The lack of similarity between glutamate- and aspartate-induced ion shifts in the granular layer and those of any one agonist demonstrate the mixed agonist action of glutamate and aspartate in the cerebellum. These studies provide new information about the dynamics of excitatory amino acid receptor activation that is complementary to autoradiographic receptor mapping data and to single cell electrophysiological studies.

Amino Acids↗

Reversible accumulation of plant suspension cell cultures in g(1) phase and subsequent synchronous traverse of the cell cycle.

The induction of DNA synthesis in Datura innoxia Mill. cell cultures was determined by flow cytometry. A large fraction of the total population of cells traversed the cell cycle in synchrony when exposed to fresh medium. One hour after transfer to fresh medium, 37% of the cells were found in the process of DNA synthesis. After 24 hours of culture, 66% of the cells had accumulated in G(2) phase, and underwent cell division simultaneously. Only 10% of the cells remained in G(0) or G(1). Transfer of cells into a medium, 80% (v/v) of which was conditioned by a sister culture for 2 days, was adequate to inhibit this simultaneous traverse of the cell cycle. A large proportion of dividing cells could be arrested at the G(0) + G(1)/S boundary by exposure to 10 millimolar hydroxyurea (HU) for 12 to 24 hours. Inhibition of DNA synthesis by HU was reversible, and when resuspended into fresh culture medium synchronized cells resumed the cell cycle. Consequently, a large fraction of the cell population could be obtained in the G(2) phase. However, reversal of G(1) arrested cells was not complete and a fraction of cells did not initiate DNA synthesis. Seventy-four percent of the cells simultaneously reached 4C DNA content whereas the frequency of cells which remained in G(0) + G(1) phase was approximately 17%. Incorporation of radioactive precursors into DNA and proteins identified a population of nondividing cells which represents the fraction of cells in G(0). The frequency of cells entering G(0) was 11% at each generation. Our results indicate that almost 100% of the population of dividing cells synchronously traversed the cell cycle following suspension in fresh medium.

Journal Article↗