The Mississippi Recovering Physicians Program.
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Biomedical subjects
Publications and source records attributed to G D Carr.
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We initiated a biosystematic study of a recently discovered population of Calycadenia pauciflora in order to evaluate its cytogenetic relationship to previously characterized chromosome races of that species. Cytogenetic analyses of six or more artificially produced individuals of each of the five possible interracial hybrid combinations indicated that the new race (designated Wurlitzer) is differentiated from the other races (Elegans, Healdsburg, Pauciflora, Ramulosa, and Tehama) by the equivalent of 2-4 reciprocal chromosome translocations and in one instance apparently a pericentric inversion. Mean pollen stainability in the hybrids ranged from 13 to 26%. The floral and vegetative features of the new race are very similar to those of races Pauciflora, Ramulosa, and Tehama of C. pauciflora. We ascribe the apparent lack of single-step cytogenetic events in the evolution of the races of C. pauciflora to one or more of the following: (1) (in some cases) the occurrence of saltational chromosome reorganization; (2) extinction of or failure to detect intermediate populations in C. pauciflora; and (3) an insufficient consideration of the possibility of the existence of intermediate races in the closely related species, C. fremontii. We conclude that the C. fremontii-C. pauciflora alliance is one of the most complex and potentially instructive examples of diploid chromosome evolution in plants.
Chromosome numbers and other cytogenetic data were determined from microsporocytes in 316 collections including 13 tribes of Compositae, mostly from Africa, Australia, Mexico, Central America, and South America. First reports are provided for 66 species and the genera Cassinia (2n ≈ 14(II)), Feldstonia (2n = 11(II)), Gochnatia (2n ≈ 23(II)), and Pseudoconyza (n = 10). In addition, new chromosome numbers are established at the generic level in Acourtia, Calea, Craspedia, Gnaphalium, Helipterum, Liabum, Leucheria, Smallanthus, Trixis, and Viguiera and at the specific level in 13 additional species.
Although cognitive impairment is commonly associated with Parkinson's disease, the relative importance of cortical and subcortical pathologic changes to the development of dementia is controversial. Characteristic abnormalities in cortical glucose metabolism have been reported previously in Alzheimer's disease, a disease in which cortical changes predominate. We measured cerebral glucose metabolism with positron emission tomography in 20 control subjects and in 14 patients with PD with mental status ranging from normal to severely demented to determine whether changes in cortical glucose metabolism occur in early PD and whether the degree and pattern of metabolic change relate to the severity of dementia. The patients were divided into demented and nondemented groups according to the results of neuropsychological assessment. Age-adjusted covariance analyses were performed, since the age distribution varied between groups. The nondemented patients with PD showed widespread cortical glucose hypometabolism without any selective temporoparietal defects. The pattern of glucose hypometabolism seen in the demented patients with PD resembled that described in patients with Alzheimer's disease; ie, there was a global decrease in glucose metabolism, with more severe abnormalities observed in the temporoparietal regions.
Chloroplast DNA restriction-site comparisons were made among 24 species of the Hawaiian silversword alliance (Argyroxiphium, Dubautia, and Wilkesia) and 7 species of North American perennial tarweeds in Adenothamnus, Madia, Raillardella, and Raillardiopsis (Asteraceae-Madiinae). These data and results from intergeneric hybridization indicated surprisingly close genetic affinity of the monophyletic Hawaiian group to two diploid species of montane perennial herbs in California, Madia bolanderi and Raillardiopsis muirii. Of 117 restriction-site mutations shared among a subset of two or more accessions, more than one-fifth (25 mutations) separated the silversword alliance, M. bolanderi, and Raillardiopsis from Adenothamnus and Raillardella. An additional 10 mutations distinguished the silversword alliance, M. bolanderi, and R. muirii from Adenothamnus, Raillardella, and Raillardiopsis scabrida. Phylogenetic analyses of these data and production of vigorous hybrids of the combinations Dubautia laevigata x R. muirii and (Dubautia knudsenii x Dubautia laxa) x M. bolanderi reinforce and refine Carlquist's hypothesis [Carlquist, S. (1959) Aliso 4, 171-236] that the Hawaiian silversword alliance arose from American tarweeds. Ultimate origin of silversword alliance chloroplast DNA from within the Californian-endemic paraphyletic genus Raillardiopsis was supported with high bootstrap confidence. Geologic considerations and the distribution of sporophytic self-incompatibility among these species demonstrate that the tarweed ancestor of the silverswords overcame (i) a dispersal barrier of at least 3900 km of open ocean and (ii) the breeding barrier of self-incompatibility.
Characteristic regional patterns of decreased cerebral glucose metabolism (rCMRG) have been described in a variety of neurodegenerative conditions associated with dementia. The present study was undertaken to determine whether the metabolic pattern in Parkinson's disease is altered by the presence of impaired cognitive function. Glucose metabolism was measured with positron emission tomography in 6 patients with Parkinson's disease and dementia (PDD), 8 patients with Parkinson's disease and normal cognition (PD), and 6 patients with Alzheimer's disease (AD). All AD patients subsequently had the diagnosis proven neuropathologically at autopsy. Correlation coefficients of the metabolic rates across 32 regions of interest were calculated between each pair of patients. Q-component analysis of the correlation matrix showed that the AD and PD groups formed two distinct clusters and that the PDD group had a metabolic pattern which was similar to that of the AD group. Comparison of standardized rCMRG values showed that the PDD group differed from the PD group in having significantly lower relative rCMRG in the left perirolandic and bilateral angular gyrus regions. There were no significant differences between the PDD and AD groups. These results suggest a similar pattern of cortical dysfunction in both Alzheimer's disease and in Parkinson's disease/dementia.
The conditioned place preference (CPP) paradigm is used widely as a measure of a drug's rewarding properties. The present study examined whether the CPP produced by amphetamine is dependent on the locomotor stimulation that is produced by the drug. An earlier study (Swerdlow and Koob 1984) found that interfering with locomotor stimulation using restraint during the drug treatment blocked CPP. The present study examined whether this effect of restraint was indeed due to restriction of locomotion or was due to restraint maintaining the stimulus novelty of the CPP apparatus. The first experiment showed that novelty of the apparatus itself was a potent factor in the CPP paradigm and was capable of producing a place preference. The second experiment showed that restraint alone could produce a CPP, as would be expected if it maintained stimulus novelty of the apparatus. It also showed that although a CPP to amphetamine could be blocked by restraining the animals during drug treatment, prior habituation to the apparatus to reduce stimulus novelty before treatment negated the effect of restraint on amphetamine CPP. These results indicate that rats can demonstrate a CPP produced by amphetamine even when their activity is restrained. This suggests that the drug's rewarding properties are not dependent on locomotor stimulation.
Systemic injections of amphetamine result in profound changes in the behavior of animals in an open field. There is an increase in activity, certain species-typical behaviors are produced, and there is a tendency for any elicited behavior to be repeated in a stereotyped way. The present study examined the contributions of dopamine terminal regions to these effects in rats by microinjecting amphetamine directly into one of six discrete sites (medial frontal cortex, nucleus accumbens, anteromedial caudate nucleus, ventrolateral caudate nucleus, amygdala, or the region surrounding the area postrema) and making detailed behavioral observations. This data was compared with the behavior of systemically injected rats that were also observed in the open field. An observer recorded the occurrence of twelve categories of behavior and recorded photocell beam interruptions during five post-injection observation periods. The results confirmed and extended previous accounts of the behavior of systemically injected rats, adding increased snout contact with the environment as an additional effect of amphetamine. Intracranial injections produced changes in activity level from several of the injection sites but there was no increase in the species-typical behaviors associated with stereotypy. Changes in the occurrence of some recorded behaviors were produced by injections into most of the sites and these data are presented in detail.
Disruption of neural activity within the basal ganglia of experimental animals causes selective learning deficits in tasks requiring switching between response strategies. These data along with reports of both general and specific intellectual impairment in patients with neurodegenerative disorders such as Parkinson's disease, appear to support the theory of cognitive functions of the basal ganglia. Recent studies have failed to confirm general cognitive or memory deficits in parkinsonian patients, but have identified deficiencies in devising and executing certain cognitive strategies. Following the lead of theorists such as Squire and Mishkin, this brief review emphasizes the distinction between procedural and declarative knowledge and examines the possible role of the basal ganglia in the acquisition and retention of procedural knowledge.
Amphetamine has rewarding properties in some behavioral paradigms, such as self-administration and conditioned place preference (CPP), but an aversive component is also apparent when the drug is tested with the conditioned taste aversion (CTA) paradigm. The present study was an attempt to determine the neuroanatomical substrates of the drug's rewarding and aversive effects. Previous evidence suggested that amphetamine's stimulation of activity in dopaminergic synapses is critical for both effects. Amphetamine was therefore micro-injected bilaterally (10 micrograms/0.5 microliter per side) into six different dopaminergic sites, each in a different group of animals: the medial prefrontal cortex, nucleus accumbens, anteromedial caudate nucleus, lateroventral caudate nucleus, amygdala, and the region subjacent to the area postrema (AP region). The effects of these injections in both the taste and place conditioning paradigms were examined in separate experiments. Of the six sites, a significant CPP was observed only with accumbens injections and a significant CTA was observed only with AP region injections. It was concluded that the accumbens plays a primary role in mediating the rewarding effects of amphetamine and that the AP region plays a primary role in mediating the CTA. This constitutes an anatomical disassociation of amphetamine's rewarding and aversive effects. The differential associative bias of place-reward and taste-aversion learning apparent in the results is discussed.
Systemic injections of amphetamine produce both anorexia and adipsia. Evidence suggests that it is the stimulation of activity by the drug in both noradrenergic and dopaminergic synapses that mediate these effects. The present study examined the contributions of dopamine terminal regions to these effects in rats by microinjecting amphetamine directly into one of six discrete sites (medial frontal cortex, nucleus accumbens, anteromedial caudate nucleus, ventrolateral caudate nucleus, amygdala, or the region surrounding the area postrema) and observing the effects of the injections on eating or drinking. The rats were mildly deprived of either food or water and following microinjection of either amphetamine or saline, were given access to food or water. Injections of amphetamine into either the nucleus accumbens or amygdala caused both anorexia and adipsia but no effects were observed from the other sites. It is suggested that the amphetamine's action on these two sites contributes to the anorexia and adipsia that are observed after systemic injection of the drug. Possible behavioral mechanisms for the effects are discussed.
The conditioned place preference method for measuring the affective properties of reinforcing events was studied using treatments of known affective value. The size of the place aversion observed increased with dose when the reinforcer was injections of lithium chloride. The size of the place preference observed increased with concentration when the reinforcer was drinking sucrose solutions. However, when the reinforcer was solutions of saccharin (that were consumed in the same amounts as the sucrose solutions) no place preferences were observed. This finding was explained in terms of the dual reinforcement hypothesis [20] which postulates that although sucrose and saccharin both have positive affective properties (based on their tastes) only sucrose has memory improving properties (based on its post-ingestive action). It was therefore proposed that conditioned place preferences depend on the activation of both affective and memory improving processes. This hypothesis was confirmed by the observation of place preferences with a saccharin solution as the reinforcer when the pairing trials were followed by non-contingent, post-pairing injections of glucose or amphetamine (both of which are known to improve memory). Therefore, behavior in the place preference method depends upon both the affective and the memory improving properties of the reinforcers under test.
This study examined the possibility that amphetamine-induced stereotypy and facilitation of memory consolidation are both mediated by amphetamine's stimulation of dopaminergic activity in the caudate nucleus. In the first experiment, rats were given pairings of a tone and a shock followed by SC amphetamine (2 mg/kg). The amount of stereotypy and increased locomotor activity produced by the injection were measured immediately. Retention of the tone-shock association was evaluated 48 h later by observing the ability of the tone to suppress drinking. The degree of retention was significantly correlated with the amount of stereotypy but not with the amount of locomotion previously measured. In the second experiment, amphetamine was microinjected into the caudate nucleus (10 micrograms/microliters) and its ability to produce the same three behavioral effects was examined. These injections produced increased stereotypy and improved retention, but no increase in locomotion. The correlation of memory facilitation with stereotypy and the fact that both were produced by intracaudate amphetamine suggest that they may be mediated by the same neuropharmacological substrate, namely amphetamine-induced release of dopamine in the caudate.
Rats received injections of d-amphetamine sulphate (10 micrograms in 0.5 ul) in nucleus accumbens and were placed into one of two (randomly assigned) distinctive environments. The next day the rats were placed into the other environment and received either a saline injection or no treatment. This procedure was repeated six times. When the rats were allowed a free choice between the two environments they showed a significant preference for the one that had been paired with amphetamine. This finding suggests that amphetamine-stimulated release of dopamine in nucleus accumbens can increase the incentive value of neutral stimuli with which it is paired. When the same procedure was carried out with a group of rats that received amphetamine injections in the dorsolateral caudate nucleus, no preference for the side paired with the drug was evident. This suggests that there is functional differentiation between different parts of the dopaminergic terminal system.