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Biomedical subjects

J L Price

Publications and source records attributed to J L Price.

At least 55 records · Page 3Linked to original sources

Subgenual prefrontal cortex abnormalities in mood disorders.

Pathological disturbances of mood may follow a 'bipolar' course, in which normal moods alternate with both depression and mania, or a 'unipolar' course, in which only depression occurs. Both bipolar and unipolar disorders can be heritable illnesses associated with neurochemical, neuroendocrine and autonomic abnormalities. The neurobiological basis for these abnormalities has not been established. Using positron emission tomographic (PET) images of cerebral blood flow and rate of glucose metabolism to measure brain activity, we have now localized an area of abnormally decreased activity in the prefrontal cortex ventral to the genu of the corpus callosum in both familial bipolar depressives and familial unipolar depressives. This decrement in activity was at least partly explained by a corresponding reduction in cortical volume, as magnetic resonance imaging (MRI) demonstrated reductions in the mean grey matter volume in the same area of 39 and 48% in the bipolar and unipolar samples, respectively. This region has previously been implicated in the mediation of emotional and autonomic responses to socially significant or provocative stimuli, and in the modulation of the neurotransmitter systems targeted by antidepressant drugs.

Adult↗

Transabdominal cervico-isthmic cerclage in the management of cervical incompetence.

The use of transabdominal cervico-isthmic cerclage is described in 13 patients with a diagnosis of cervical incompetence. The patients were recruited from seven Scottish Maternity Units over a period of 10 years. The 13 patients have had a successful pregnancy in 86.6% of pregnancies with this procedure compared with a success rate of 16% in their previous pregnancies. In carefully selected cases transabdominal cervico-isthmic cerclage is a worthwhile procedure in patients with cervical incompetence when the cervix is so damaged that it would be impossible to insert a vaginal suture or when a vaginal suture has previously failed.

Adult↗

Protein synthesis inhibitors delay transneuronal death in the piriform cortex of young adult rats.

It has been demonstrated that apoptotic cell death is an active process that is dependent on RNA and protein synthesis. The question remains as to whether neuronal death in adult, mammalian brains can also be demonstrated in vivo to be dependent on protein synthesis. To address this question we have analysed transneuronal death in the piriform (olfactory) cortex. Following unilateral olfactory bulb ablation in young adult rats, layer IIa of the piriform cortex undergoes rapid degeneration, that commences 12 h after ablation and that is almost complete at 48 h. In order to block protein synthesis, three to six subcutaneous injections of the short acting protein synthesis inhibitor anisomycin, were given at 2 h intervals beginning just before the ablation of the olfactory bulb. In other cases a single injection of the long acting protein synthesis inhibitor emetine were made intracerebrally just before or after olfactory bulb ablation. The number of dying cells was then counted in sections through the rostrocaudal extent of the piriform cortex. Both anisomycin and emetine injections markedly reduced the number of pyknotic cells in layer IIa of the piriform cortex after olfactory bulb ablation. The effect of anisomycin was dose-dependent, near lethal doses leading to an almost complete absence of cell death (six injections of 100 mg/kg). As the doses of anisomycin were reduced, more dying cells were observed. Emetine was only effective at near lethal doses (10 mg/kg) and showed a greater capacity to reduce the levels of cell death when injected into structures near the piriform cortex (e.g., accumbens nucleus) than when injected into more distant structures. To further confirm that the cell death observed was due to apoptosis, we analysed sections by tunel staining to demonstrate DNA fragmentation. We found that tunel-positive cells were also always pyknotic, one of the landmarks of apoptosis. The appearance of pyknotic cells labelled by the tunel method demonstrated that the dying cells in the piriform cortex did indeed undergo apoptosis.

Animals↗

Insights into the molecular mechanisms of temperature compensation from the Drosophila period and timeless mutants.

The relative constancy of the circadian period over a wide range of temperatures is a general property of circadian rhythms. Insights into the molecular mechanisms of temperature compensation are emerging from genetic and molecular genetic studies of the period (per) and timeless (tim) genes in Drosophila. These genes encode proteins that are thought to be part of a negative feedback cycle, which results in circadian oscillations of both per and tim mRNA, as well as a complex of the two proteins. Complex formation is temporally regulated and apparently necessary for nuclear localization of both per and tim proteins. While insights into the roles of per and tim in temperature compensation have been intriguing, they have also been somewhat perplexing. For instance, the interaction of wild-type per peptides is relatively insensitive to temperature in the yeast two-hybrid assay or in assays employing in-vitro-translated peptides, while the interaction of perL mutant peptides is reduced at a high temperature. Apparently, the perL mutation increases an intramolecular interaction between different parts of the per peptide in these assays, and this interaction reduces the amount of per homodimer. On the other hand, the same assays show that the intermolecular interaction between the per and tim peptides is reduced at a high temperature by the perL mutation; this reduction does not require the competing intramolecular interaction. Despite this difference, in all of the experiments employing these assays the perL mutation has rendered per-per and per-tim peptide interactions sensitive to high temperature, so it is likely that one or both of these reduced interactions contribute to the longer circadian periods at high temperature in perL mutant flies. However, the timSL and perS mutations, as well as deletion of the Thr-Gly repeats from per, affect temperature compensation but have not been shown to affect these molecular interactions of per and tim. Finally, a recent report of oscillating per and tim proteins in the cytoplasm (rather than the nuclei) of silk moth neurons may suggest an alternative mechanism for per and tim function in these cells.

Animals↗

Empowerment as a source of healing: redefining the art of nursing management.

Empowerment amounts to a social process of recognizing, promoting and enhancing staff nurse abilities to meet self needs, solve their own problems and mobilize the necessary resources to gain mastery over their own professional lives. Healing, to be made whole, is a process of getting in touch with that which is impeding our realization of wholeness. Empowerment as a source of organizational healing conveys the message that in order to realize wholeness, nurses are dependent upon personal and organizational resources. As nurses learn multiple ways to interact with the work environment, they find the path to a wholeness that incorporates physical, emotional, intellectual, and spiritual aspects of themselves. As the value of wholeness is realized individually, interactions with the environment spontaneously manifest these attributes and the message permeates the nursing community. As the nursing community is empowered, it is increasingly able to empower the individual. This expanding energy can result in a synergistic pattern that brings phenomena together, and interrelates them, creating a new and greater whole from the disparate, seemingly conflicting parts. When nurses as individuals and groups are able and willing (empowered) to invest energy to that which impacts their lives so that they can move toward wholeness (heal), positive energy exponentially intensifies and permeates the environment to envelop all.

Decision Making, Organizational↗

Connectional networks within the orbital and medial prefrontal cortex of macaque monkeys.

The intrinsic cortico-cortical connections within the orbital and medial prefrontal cortex (OMPFC) were demonstrated with retrograde and anterograde tracers injected into each of the architectonic areas that constitute this region. Although many of the connections linked neighboring areas, others selectively connected relatively distant areas. Most, but not all, of the connections were reciprocal. Altogether, the connections formed at least two distinct networks within the OMPFC. The "orbital" prefrontal network linked most of the areas within the orbital cortex, with very few connections to medial prefrontal areas. Areas Iam, Iapm, Ial, 12l, 12m, and 12r in the caudal and lateral parts of the orbital cortex (which received inputs from several sensory modalities) had convergent connections with areas 13l, 13m, and 13b in the central orbital cortex, with further connections to the rostral orbital area 11l. For the connections between areas Iapm, Iam, Ial, 13m, 13l, and 11l, rostrally directed fibers arose mainly in layer V, whereas caudally directed fibers originated mainly in layer III. The "medial" prefrontal network selectively involved medial areas 14r, 14c, 24, 25, 32, and 10m, rostral orbital areas 10o and 11m, and agranular insular area Iai in the posterior orbital cortex. Two orbital areas, 13a and 12o, had substantial connections to both networks and may serve as points of interaction between them; otherwise there were relatively few interconnections. The two networks also had distinct connections with other cortical regions, with limbic structures, and with the mediodorsal thalamic nucleus. Their role in guidance of affective behaviour is discussed.

Animals↗

Profound loss of layer II entorhinal cortex neurons occurs in very mild Alzheimer's disease.

The entorhinal cortex (EC) plays a crucial role as a gateway connecting the neocortex and the hippocampal formation. Layer II of the EC gives rise to the perforant pathway, the major source of the excitatory input to the hippocampus, and layer IV receives a major hippocampal efferent projection. The EC is affected severely in Alzheimer disease (AD), likely contributing to memory impairment. We applied stereological principles of neuron counting to determine whether neuronal loss occurs in the EC in the very early stages of AD. We studied 20 individuals who at death had a Clinical Dementia Rating (CDR) score of 0 (cognitively normal), 0.5 (very mild), 1 (mild), or 3 (severe cognitive impairment). Lamina-specific neuronal counts were carried out on sections representing the entire EC. In the cognitively normal (CDR = 0) individuals, there were approximately 650,000 neurons in layer II, 1 million neurons in layer IV, and 7 million neurons in the entire EC. The number of neurons remained constant between 60 and 90 years of age. The group with the mildest clinically detectable dementia (CDR = 0.5), all of whom had sufficient neurofibrillary tangles (NFTs) and senile plaques for the neuropathological diagnosis of AD, had 32% fewer EC neurons than controls. Decreases in individual lamina were even more dramatic, with the number of neurons in layer II decreasing by 60% and in layer IV by 40% compared with controls. In the severe dementia cases (CDR = 3), the number of neurons in layer II decreased by approximately 90%, and the number of neurons in layer IV decreased by approximately 70% compared with controls. Neuronal number in AD was inversely proportional to NFT formation and neuritic plaques, but was not related significantly to diffuse plaques or to total plaques. These results support the conclusion that a marked decrement of layer II neurons distinguishes even very mild AD from nondemented aging.

Aged↗

Visual and auditory information as determinants of primacy effects.

Recent research has demonstrated that auditory and visual information have similar mnemonic properties. The relative influence of verbal, auditory, and visual stimulus materials on the primacy effect in free recall was studied. Significant primacy effects were obtained when either verbal or auditory-input stimuli were presented. However, primacy effects were suppressed when pictorial materials were used, principally because of elevation of recall for midlist and later elements. Instructions to use visual mental imagery at encoding suppressed primacy effects for verbal materials, but not for auditory materials, indicating that although auditory information processing is probably similar to phonological processing within working memory, auditory processing may share cognitive resources with visuospatial processing. Results are shown to be predictable and interpretable within the item-specific/relational information distinction of Hunt and Einstein (e.g., 1981), and within the working-memory theory of Baddeley (e.g., 1986).

Adolescent↗

Cerebral amyloid deposition and diffuse plaques in "normal" aging: Evidence for presymptomatic and very mild Alzheimer's disease.

The presence of senile plaques in the neocortex of apparently nondemented elderly persons often is accepted as part of "normal" aging. Alternatively, because cerebral deposition of beta-amyloid may be a key mechanism in the development of Alzheimer's disease (AD), the presence of beta-amyloid-containing plaques may represent very early AD. To examine the relationships of cognitively normal aging, very mild dementia of the Alzheimer type, and the presence of neocortical senile plaques, we performed clinicopathologic correlation in 21 longitudinally studied healthy elderly subjects (84.5 +/- 6.6 years old at death). Nine subjects had strikingly high plaque densities in the neocortex; two of these subjects died of head injury before which there was no evidence of cognitive impairment. The other seven subjects with high plaque densities had clinical evidence for very mild cognitive impairment (Clinical Dementia Rating score of 0.5) at some time during their course and mildly impaired psychometric performance at last assessment before death. The remaining 12 subjects had no clinical or psychometric impairment and had few or no neocortical AD lesions. These results suggest that senile plaques may not be part of normal aging but instead represent presymptomatic or unrecognized early symptomatic AD. The high density of senile plaques (predominately of the diffuse subtype) in the cortex of subjects just at the threshold of detectable dementia is consistent with the hypothesis that beta-amyloid deposition is an initial pathogenetic event in the development of AD.

Aged↗

Limbic connections of the orbital and medial prefrontal cortex in macaque monkeys.

Previous studies have shown that the orbital and medial prefrontal cortex (OMPFC) is extensively connected with medial temporal and cingulate limbic structures. In this study, the organization of these projections was defined in relation to architectonic areas within the OMPFC. All of the limbic structures were substantially connected with the following posterior and medial orbital areas: the posteromedial, medial, intermediate, and lateral agranular insular areas (Iapm, Iam, Iai, and Ial, respectively) and areas 11m, 13a, 13b, 14c and 14r. In contrast, lateral orbital areas 12o, 12m, and 12l and medial wall areas 24a,b and 32 were primarily connected with the amygdala, the temporal pole, and the cingulate cortex. Data were not obtained on the posteroventral medial wall. Three distinct projections were recognized from the basal amygdaloid nucleus: 1) The dorsal part projected to area 12l; 2) the ventromedial part projected to most areas in the posterior and medial orbital cortex except for area Iai, 12o, 13a, and 14c; and 3) the ventrolateral part projected to orbital areas 12o, Iai, 13a, 14c, and to the medial wall areas. The accessory basal and lateral amygdaloid nuclei projected most strongly to areas in the posterior and medial orbital cortex. The medial, anterior cortical, and central amygdaloid nuclei and the periamygdaloid cortex were connected with the posterior orbital areas. The projection from the hippocampus originated from the rostral subiculum and terminated in the medial orbital areas. The same region was reciprocally connected with the anteromedial nucleus of the thalamus, which received input from the rostral subiculum. The parahippocampal cortical areas (including the temporal polar, entorhinal, perirhinal, and posterior parahippocampal cortices) were primarily connected with posterior and medial orbital areas, with some projections to the dorsal part of the medial wall. The rostral cingulate cortex sent fibers to the medial wall, to the medial orbital areas, and to lateral areas 12o, 12r, and Iai. The posterior cingulate gyrus, including the caudomedial lobule, was especially strongly connected with area 11m.

Amygdala↗

Sensory and premotor connections of the orbital and medial prefrontal cortex of macaque monkeys.

Sensory and premotor inputs to the orbital and medial prefrontal cortex (OMPFC) were studied with retrograde axonal tracers. Restricted areas of the lateral and posterior orbital cortex had specific connections with visual-, somatosensory-, olfactory-, gustatory-, and visceral-related structures. More medial areas received few direct sensory inputs. Within the lateral and posterior orbital cortex, area 12l received a substantial projection from visual areas in the inferior temporal cortex (TE). Area 12m received somatosensory input from face, digit, or forelimb regions in the opercular part of area 1-2, in area 7b, in the second somatosensory area (SII), and in the anterior infraparietal area (AIP). Areas 13m and 13l also received a projection from the opercular part of areas 1-2 and 3b. The posteromedial and lateral agranular insular areas (Iapm and Ial, respectively) received fibers from the ventral part of the parvicellular division of the ventroposterior medial nucleus of the thalamus (VPMpc) that may represent a visceral afferent system. The dorsal part of VPMpc projected to the adjacent gustatory cortex. These restricted inputs from several sensory modalities and the convergent corticocortical connections to orbital areas 13l and 13m suggest a network related to feeding. The OMPFC was also connected to premotor cortex in ventral area 6 (areas 6va and 6vb), in cingulate area 24c, and probably in the supplementary eye field. Area 6va projected to area 12m, whereas a region of area 6vb projected to area 13l. The region of the supplementary eye field projected to areas 12l, 12o, and 12r. Area Ial received fibers from area 24c. Lighter and more diffuse projections also reached wider areas of the OMPFC. For example, injections in several orbital areas labeled a few cells scattered through the anterior part of area TE and the superior temporal gyrus. There was also a projection to the intermediate agranular insular area (Iai) and to areas 13a and 12o from the apparently multimodal areas in the superior temporal sulcus and gyrus.

Animals↗

Suppression of PERIOD protein abundance and circadian cycling by the Drosophila clock mutation timeless.

The timeless mutation (tim) leads to loss of circadian behavioral rhythms in Drosophila melanogaster. The effects of tim on rhythmicity involve interactions with period (per), a second essential clock gene, as the tim mutation suppresses circadian oscillations of per transcription and blocks nuclear localization of a PER reporter protein. In the present study it was found that the tim mutant constitutively produces a low level of PER protein that is comparable with that produced late in the day by wild-type flies. In addition, it was shown that tim suppresses circadian cycling of PER protein abundance and circadian regulation of PER phosphorylation. Transfer of wild-type flies to constant light also suppressed cycling of PER abundance and phosphorylation and produced constitutively low levels of PER. In the tim mutant there was no additional effect of constant light on PER. These results suggest that constant light and the tim mutation produce related changes in the underlying biological clock. We further suggest that the multiple effects of tim are due to a primary effect on per expression at the posttranscriptional level. The effects of tim on behavioral rhythms and per RNA cycling are therefore likely to involve effects on PER protein through previously proposed feedback mechanisms.

Animals↗

Thalamocortical synapses between axons from the mediodorsal thalamic nucleus and pyramidal cells in the prelimbic cortex of the rat.

A combined anterograde axonal degeneration and Golgi electron microscopic (Golgi-EM) study was undertaken to identify thalamocortical synaptic connections between axon terminals from the mediodorsal thalamic nucleus (MD) and pyramidal cells in layers III and V of the agranular prelimbic cortex in the rat. The morphological characteristics of thalamocortical synapses from MD were also examined by labeling axon terminals with anterograde transport of wheat germ agglutinin-horseradish peroxidase (WGA-HRP). WGA-HRP labeled axon terminals from MD to the prelimbic cortex were small in size (0.5-1 microns in diameter), contained round synaptic vesicles, and formed axospinous synapses with asymmetrical membrane thickenings. With Golgi-EM methods, gold-toned apical dendrites in layer III were analyzed by reconstruction of serial ultrathin sections. Following lesions in the thalamus, degenerating thalamocortical axon terminals formed asymmetrical contacts exclusively on dendritic spines of the identified apical dendrites. More thalamocortical synapses were found on apical dendrites of layer V pyramidal cells than on apical dendrites of layer III pyramidal cells. In addition to thalamocortical synapses, a very few unlabeled symmetrical synapses were found on apical dendrites and somata of pyramidal cells, but they were not quantified and their sources are unknown.

Animals↗

Are competing intermolecular and intramolecular interactions of PERIOD protein important for the regulation of circadian rhythms in Drosophila?

Genetic analysis is revealing molecular components of circadian rhythms. The gene products of the period gene in Drosophila and the frequency gene in Neurospora oscillate with a circadian rhythm. A recent paper (1) has shown that the PERIOD protein can undergo both intermolecular and intramolecular interactions in vitro. The effects of temperature and two period mutations on these molecular interactions were compared to the effects of the mutations and temperature on the in vivo period length of circadian rhythms. The results suggest that the molecular interactions may compete to maintain a rhythm with a constant period over a wide temperature range.

Animals↗

Relational and item-specific information as determinants of category superiority effects.

Recent studies have shown that the category superiority effect--the mnemonic effect of grouping items by category--pertains largely to verbal rather than pictorial stimuli, suggesting that the category superiority effect may depend primarily upon the relative availability of relational and item-specific information in a given stimulus situation. This hypothesis was tested in two experiments, in which the level of item-specific information available per stimulus item was systematically diminished through the reduction of presentation time. This manipulation resulted in the systematic creation of significant category superiority effects for pictorial stimuli. Effects were reversed for verbal materials: They decreased with diminished presentation time. In a second experiment, the complexity of category structure was also shown to influence the category superiority effect. The category superiority effect varied predictably with manipulations of verbal and nonverbal stimulus materials, consistent with current theory concerning the processing of item-specific and relational information.

Acoustic Stimulation↗

Architectonic subdivision of the orbital and medial prefrontal cortex in the macaque monkey.

The orbital and medial prefrontal cortex (OMPFC) of macaque monkeys is a large but little understood region of the cerebral cortex. In this study the architectonic structure of the OMPFC was analyzed with nine histochemical and immunohistochemical stains in 32 individuals of three macaque species. The stains included Nissl, myelin, acetylcholinesterase, Timm, and selenide stains and immunohistochemical stains for parvalbumin, calbindin, a nonphosphorylated neurofilament epitope (with the SMI-32 antibody), and a membrane-bound glycoprotein (with the 8b3 antibody). In addition to patterns of cell bodies and myelinated fibers, these techniques allow the visualization of markers related to metabolism, synapses, and neurotransmitters. A cortical area was defined as distinct if it was differentiated in at least three different stains and, as described in later papers, possessed a distinct set of connections. Twenty-two areas were recognized in the OMPFC. Walker's areas 10, 11, 12, 13, and 14 [J. Comp. Neurol. (1940) 73:59-86] have been subdivided into areas 10m, 10o, 11m, 11l, 12r, 12l, 12m, 12o, 13m, 13l, 13a, 13b, 14r, and 14c. On the medial wall, areas 32, 25, and 24a,b,c have been delineated, in addition to area 10m. The agranular insula also has been recognized to extend onto the posterior orbital surface and has been subdivided into medial, intermediate, lateral, posteromedial, and posterolateral agranular insula areas. The OMPFC, therefore, resembles other areas of primate cortex, such as the posterior parietal and temporal cortices, where a large number of relatively small, structurally and connectionally distinct areas have been recognized. Just as the area-specific neurophysiological properties of these parietotemporal areas underlie broader regional functions such as visuospatial analysis, it is likely that the many small areas of the OMPFC also make differential contributions to the general mnemonic, sensory, and affective functions of this region.

Acetylcholinesterase↗