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Biomedical subjects

M Davis

Publications and source records attributed to M Davis.

At least 163 records · Page 9Linked to original sources
PubMed1998

Experiences of ethnic minority faculty employed in predominantly white schools of nursing.

This qualitative study describes the bicultural experience of ten ethnic minority faculty employed in predominately white baccalaureate and higher degree nursing programs in the Southeastern section of the United States. Seven themes emerged from the data: (a) appraising, (b) proving, (c) fitting-in, (d) defending, (e) distancing, (f) being invisible, and (g) mentoring to describe their experience. Results also provided support for the authors' generated Bicultural Systems Model which evaluates why and to what extent a particular transaction or series of transactions between the person and the environment is perceived as stressful. The general perception among participants was that they were not fully accepted in the academic setting of predominately white nursing programs. As a result, some faculty were expending energy trying to convince others of their legitimacy; while others were choosing to distance themselves from the academic setting and white colleagues. This study indicates a need for dialogue between white and ethnic minority faculty to facilitate adoption of strategies that reduce the negative effects of the bicultural phenomenon.

Adaptation, Psychological↗
PubMed1997

Repeated stress, like vasopressin, sensitizes the excitatory effects of corticotropin releasing factor on the acoustic startle reflex.

In the rat, evidence now suggests a neurotransmitter function for the neuropeptides arginine vasopressin (AVP) and corticotropin releasing factor (CRF), implicating them in various autonomic, behavioral, and neuroendocrine responses to stress. Repeated AVP/CRF release in the pituitary portal circulation, due to stress, sensitizes and potentiates the release of ACTH from the anterior pituitary. Using a neuroanatomically well-defined behavior, the acoustic startle reflex in the rat, we sought to determine whether an interaction between AVP, CRF and stress might also occur centrally as measured by increased behavioral sensitivity to AVP or CRF given directly into the brain. The first experiment tested whether repeated intraventricular (i.c.v.) infusion of AVP would lead to an increase in the excitatory effect of a subthreshold dose of AVP on the acoustic startle reflex when infused 48 h later. Different groups of rats were infused with various doses of AVP (0.3, 3, or 30 ng) or vehicle on Day 1 and tested for startle over the next 60 min. On Day 2, 48 h later, all animals were infused with a single dose of AVP (300 pg) and tested for startle. Infusion of AVP on Day 1 did not increase startle consistently at any dose, but did lead to a sensitized excitatory effect of AVP on startle on Day 2 which was non-monotonically related to the dose of AVP given on Day 1. Experiment 2 tested whether AVP on Day 1 would sensitize the excitatory effects on startle of CRF given i.c.v. on Day 2. Different groups of rats were infused i.c.v. with various doses of AVP (10, 30, 100, 300 pg) or vehicle on Day 1. On Day 2, 48 h later, all rats were infused with a subthreshold dose of CRF (0.25 microg). Infusion of AVP on Day 1 led to a sensitized excitatory effect of CRF on startle on Day 2 which was non-monotonically related to the dose of AVP given on Day 1. In experiment 3, we tested whether footshocks given on Day 1 would sensitize the excitatory effect of CRF on startle tested 48 h later. Different groups were given footshocks (0.2, 0.4, 0.8, 1.6 mA) on Day 1. On Day 2, 48 h later, all rats were infused with a subthreshold dose of CRF (0.25 microg). Footshocks given on Day 1 led to a sensitized excitatory effect of CRF on startle on Day 2 which was non-monotonically related to the intensity of footshock on Day 1. Taken together, these results suggest that an interaction between AVP, CRF and stress may occur centrally, consistent with other studies showing similar interactions peripherally. This may provide a model system for analyzing how prior stress leads to enhanced behavioral reactions to subsequent stressors and a mechanism to explain dysregulation of the stress response.

Acoustic Stimulation↗
PubMed1997

Evidence of contextual fear after lesions of the hippocampus: a disruption of freezing but not fear-potentiated startle.

The roles of the dorsal hippocampus and the central nucleus of the amygdala in the expression of contextual fear were assessed using two measures of conditioned fear: freezing and fear-potentiated startle. A discriminable context conditioning paradigm was developed that demonstrated both conditioned freezing and fear-potentiated startle in a context paired previously with foot shock, relative to a context in which foot shock had never been presented. Post-training lesions of the central nucleus of the amygdala completely blocked both contextual freezing and fear-potentiated startle. Post-training lesions of the dorsal hippocampus attenuated contextual freezing, consistent with previous reports in the literature; however, these same lesions had no effect on fear-potentiated startle, suggesting preserved contextual fear. These results suggest that lesions of the hippocampus disrupt the freezing response but not contextual fear itself.

Acoustic Stimulation↗
PubMed1997

Double dissociation between the involvement of the bed nucleus of the stria terminalis and the central nucleus of the amygdala in startle increases produced by conditioned versus unconditioned fear.

The amplitude of the acoustic startle response is reliably enhanced when elicited in the presence of bright light (light-enhanced startle) or in the presence of cues previously paired with shock (fear-potentiated startle). Light-enhanced startle appears to reflect an unconditioned response to an anxiogenic stimulus, whereas fear-potentiated startle reflects a conditioned response to a fear-eliciting stimulus. We examine the involvement of the basolateral nucleus of the amygdala, the central nucleus of the amygdala, and the bed nucleus of the stria terminalis in both phenomena. Immediately before light-enhanced or fear-potentiated startle testing, rats received intracranial infusions of the AMPA receptor antagonist 2, 3-dihydroxy-6-nitro-7-sulphamoylbenzo(F)-quinoxaline (3 microg) or PBS. Infusions into the central nucleus of the amygdala blocked fear-potentiated but not light-enhanced startle, and infusions into the bed nucleus of the stria terminalis blocked light-enhanced but not fear-potentiated startle. Infusions into the basolateral amygdala disrupted both phenomena. These findings indicate that the neuroanatomical substrates of fear-potentiated and light-enhanced startle, and perhaps more generally of conditioned and unconditioned fear, may be anatomically dissociated.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1997

Amygdala and bed nucleus of the stria terminalis: differential roles in fear and anxiety measured with the acoustic startle reflex.

Neural stimuli associated with traumatic events can readily become conditioned so as to reinstate the memory of the original trauma. These conditioned fear responses can last a lifetime and may be especially resistant to extinction. A large amount of data from many different laboratories indicate that the amygdala plays a crucial role in conditioned fear. The amygdala receives information from all sensory modalities and projects to a variety of hypothalamic and brainstem target areas known to be critically involved in specific signs that are used to define fear and anxiety. Electrical stimulation of the amygdala elicits a pattern of behaviours that mimic natural or conditioned states of fear. Lesions of the amygdala block innate or conditioned fear and local infusion of drugs into the amygdala have anxiolytic effects in several behavioural tests. Excitatory amino acid receptors in the amygdala are critical for the acquisition, expression and extinction of conditioned fear.

Amygdala↗
PubMed1997

Anxiogenic effects of high illumination levels assessed with the acoustic startle response in rats.

Previous studies have shown that the amplitude of the acoustic startle reflex is increased by the presentation of aversive stimuli. In the present study, the amplitude of acoustic startle in rats was increased by exposure to high illumination levels. The effect was directly related to the intensity (0, 8, 70, and 700 footlamberts) of illumination (experiment I); was blocked by the anxiolytic compound buspirone (experiment II); and showed little or no habituation with repeated testing (experiment III). These results suggest that the elevation of startle amplitude by light may reflect an unconditioned anxiogenic effect of high illumination levels. The possible utility of this phenomenon as an animal model of anxiety is discussed.

Acoustic Stimulation↗
PubMed1997

Darkness facilitates the acoustic startle reflex in humans.

The effects of darkness on startle reactivity and prepulse inhibition were investigated in two studies with 25 subjects participating in each study. Acoustic startle stimuli that were or were not preceded by an acoustic prepulse were delivered in alternating periods of complete darkness or light. In both studies, darkness significantly increased the magnitude of startle but did not affect prepulse inhibition (PPI). The PPI results suggest that darkness did not increase attention to the auditory modality, so that the startle facilitation in the dark probably did not result from an attentional process. The increased startle in the dark was significantly correlated with the intensity of subjects' fear of the dark as children based on retrospective rating scales. It is hypothesized that the startle facilitation in the dark results from a change in affect rather than from a change in attention.

Acoustic Stimulation↗
PubMed1997

Role of the septum in the excitatory effect of corticotropin-releasing hormone on the acoustic startle reflex.

Intracerebroventricular administration of corticotropin-releasing hormone (CRH) elicits a constellation of behavioral, autonomic, and endocrinological changes typically observed in stress. One of the behavioral changes after intracerebroventricular CRH is a profound increase of startle amplitude (CRH-enhanced startle). The present study examined the role of the septum in CRH-enhanced startle. The septum has direct and indirect connections to the amygdala and inhibits the amygdala. Electrophysiological data show that CRH in the septum is inhibitory. Therefore, it has been hypothesized that intracerebroventricular CRH inhibits the septum, which in turn disinhibits the amygdala, resulting in a constellation of changes via activation of amygdala efferent targets. In testing this hypothesis, it was found that electrolytic lesions of the medial septum, but not the lateral septum, blocked CRH-enhanced startle. However, fiber-sparing chemical lesions of the medial septum did not block CRH-enhanced startle, suggesting that the blockade seen with the electrolytic lesions was caused by damage to fibers of passage. A major fiber bundle passing through the medial septum is the fornix, the primary efferent pathway for the hippocampus. Fimbria transection blocked CRH-enhanced startle almost completely, whereas the large electrolytic lesions of the dorsal hippocampus did not block CRH-enhanced startle. Taken together, these data suggest that perhaps the ventral hippocampus and its efferent target areas, which communicate via the fimbria, may be critically involved in CRH-enhanced startle.

Acoustic Stimulation↗
PubMed1997

Role of the hippocampus, the bed nucleus of the stria terminalis, and the amygdala in the excitatory effect of corticotropin-releasing hormone on the acoustic startle reflex.

Previously, we demonstrated that transection of the fimbria/fornix blocked the excitatory effect of corticotropin-releasing hormone (CRH) on startle (CRH-enhanced startle), suggesting that the hippocampus and its efferent target areas that communicate via the fimbria may be critically involved in CRH-enhanced startle. The bed nucleus of the stria terminalis (BNST) receives direct projections from the ventral hippocampus via the fimbria/fornix. Therefore, the role of the ventral hippocampus, the BNST, and the amygdala in CRH-enhanced startle was investigated. NMDA lesions of the BNST completely blocked CRH-enhanced startle, whereas chemical lesions of the ventral hippocampus and the amygdala failed to block CRH-enhanced startle. However, the same amygdala-lesioned animals showed a complete blockade of fear-potentiated startle, a conditioned fear response sensitive to manipulations of the amygdala. In contrast, BNST-lesioned rats had normal fear-potentiated startle. This indicates a double dissociation between the BNST and the amygdala in two different paradigms that enhance startle amplitude. Microinfusions of CRH into the BNST, but not into the ventral hippocampus, mimicked intracerebroventricular CRH effects. Furthermore, infusion of a CRH antagonist into the BNST blocked CRH-enhanced startle in a dose-dependent manner. Control studies showed that this blockade did not result from either leakage of the antagonist into the ventricular system or a local anesthetic effect caused by infusion of the antagonist into the BNST. The present studies strongly suggest that CRH in the CSF can activate the BNST, which could lead to activation of brainstem and hypothalamic BNST target areas involved in anxiety and stress responses.

Acoustic Stimulation↗
PubMed1997

Second-order fear conditioning prevented by blocking NMDA receptors in amygdala.

Antagonists of NMDA (N-methyl-D-aspartate)-type glutamate receptors disrupt several forms of learning. Although this might indicate that NMDA-receptor-mediated processes are critical for synaptic plasticity, there may be other mechanisms by which NMDA-receptor antagonism could interfere with learning. For instance, fear conditioning would be blocked by microinfusion of the NMDA-receptor antagonist AP5 (D,L-2-amino-5-phosphonovalerate) into the basolateral amygdala if AP5 inhibited routine synaptic transmission, thereby reducing the ability of stimuli to activate amygdala neurons. In second-order fear conditioning, the reinforcer is a fear-eliciting conditioned stimulus rather than an unconditioned stimulus. Expression of conditioned fear is amygdala-dependent and so provides a behavioural assessment of the ability of the reinforcer to activate amygdala neurons in the presence of AP5. We report here that intra-amygdala AP5 actually enhances expression of conditioned fear to the conditioned stimulus that provides the reinforcement signal for second-order conditioning. Nevertheless, acquisition of second-order fear conditioning is completely blocked. Our findings strongly support the view that NMDA receptors are critically involved in synaptic plasticity.

2-Amino-5-phosphonovalerate↗
PubMed1997

Empirical free energy calculations: a blind test and further improvements to the method.

Empirical Gibbs functions estimate free energies of non-covalent reactions (deltaG) from atomic coordinates of reaction products (e.g. antibody-antigen complexes). The function previously developed by us has four terms that quantify the effects of hydrophobic, electrostatic and entropy changes (conformational, association) upon complexation. The function was used to calculate delta deltaG of ten lysozyme mutants affecting the stability of the HyHEL-10 antibody-lysozyme complex. The mutants were computer-modeled from the X-ray structure of the wild-type, and free energy calculations produced a correlation coefficient of 0.5 with the experimental delta deltaG data (average absolute error +/-3 kcal). The following changes were then introduced into the Gibbs function: (1) the hydrophobic force was made proportional to the molecular surface, as calculated by the GEPOL93 algorithm, with the scaling constant of 70 cal/mol/A2; (2) calculation of the electrostatics of binding was carried out by the finite difference Poisson-Boltzmann algorithm, which employed uniform grid charging, dielectric boundary smoothing and charge anti-aliasing; and (3) side-chain conformational entropy was estimated from the CONGEN sampling of torsional degrees of freedom. In the new calculations, correlation with experimental data improved to 0.6 or 0.8 if a single outlying mutant, K96M, was neglected. Analysis of the errors remaining in our calculations indicated that molecular mechanics-based modeling of the mutants, rather than the form of our amended Gibbs function, was the main factor limiting the accuracy of the free energy estimates.

Animals↗
PubMed1997

Enhancement by an ampakine of memory encoding in humans.

Acentrally active drug that enhances AMPA receptor-mediated currents was tested for its effects on memory in humans. Evidence for a positive influence on encoding was obtained in four tests: (i) visual associations, (ii) recognition of odors, (iii) acquisition of a visuospatial maze, and (iv) location and identity of playing cards. The drug did not improve scores in a task requiring cued recall of verbal information. The selectivity of drug effects on memory was confirmed using tests of visual recognition, motor performance, and general intellectual functioning. These results suggest that positive modulators of AMPA receptors selectively improve at least some aspects of memory.

Adult↗
PubMed1997

Loss of heterozygosity at the alpha-inhibin locus on chromosome 2q is not a feature of human granulosa cell tumors.

The alpha-inhibin gene has been shown in knockout mouse models to be a suppressor of granulosa tumorigenesis in the mouse. To determine if alpha-inhibin has the same function in humans, we have assessed the frequency of loss of heterozygosity (LOH) of the alpha-inhibin gene locus on chromosome 2q in 17 human granulosa cell tumors and 36 epithelial ovarian cancers. LOH was detected in 12 of 36 (33.3%) epithelial tumors but in only 1 of 17 (6%) granulosa cell tumors. These data suggest that in contrast to the suggestions from the mouse model alpha-inhibin does not function as a granulosa cell tumor suppressor gene in the human. Furthermore, analysis of the TP53 gene in the granulosa cell tumors failed to detect either LOH or point mutations, indicating that they have a developmental pathway distinct from that of epithelial ovarian tumors.

Adult↗
PubMed1997

Selective impairments of mitochondrial respiratory chain activity during aging and ischemic brain damage.

Cumulative oxidative damage to mitochondrial deoxyribonucleic acid (DNA) with subsequent defects in oxidative phosphorylation may reduce the capacity of the aging brain to cope with metabolic stress. This may contribute to the age related increase in cerebral infarct size that has been documented following permanent middle cerebral artery occlusion (MCAO) in the rat. This hypothesis was evaluated by assessing mitochondrial respiratory chain complex activity in both ischemic and non ischemic brain tissue of adult (10 month) and aged (28 month) male Wistar rats, six hours after occlusion of the left middle cerebral artery. Aging was associated with a significant decline in cerebral mitochondrial function with impairment of the activities of complexes I. II and IV. The individual respiratory chain complexes also exhibited selective vulnerability to a focal cerebral ischemic lesion, with significant impairment of complex I activity in the lesioned hemisphere of both age groups. The age related decline in complex I activity may be important in the enhanced susceptibility of the aging brain to ischemic neuronal damage.

Aging↗
PubMed1997

The effect of non-competitive N-methyl-D-aspartate receptor antagonism on cerebral oedema and cerebral infarct size in the aging ischaemic brain.

Although vulnerability to ischemic neuronal injury is enhanced with age, the aging brain may be less amenable to neuroprotection as a result of quantitative and qualitative changes in the NMDA receptor. In addition, the elderly may be less tolerant of adverse effects of neuroprotective drugs and this might ultimately limit therapeutic potential in human stroke. However, antagonism of the excitotoxic effects of glutamate by parenteral administration of the non competitive NMDA antagonist magnesium has been well tolerated and has shown to be neuroprotective in young animal models of stroke and head injury. We therefore evaluated the potential of magnesium chloride to reduce ischemic neuronal injury in aged rodents subjected to permanent occlusion of the middle cerebral artery. Treatment with magnesium chloride induced hypotension and hyperglycaemia in both adult and aged rats and did not reduce ischemic neuronal injury or cerebral edema. However, despite these adverse haemodynamic and biochemical effects, which may augment cerebral infarct size, ischemic damage was not exacerbated in the treated groups, suggesting that magnesium has the potential to salvage penumbral neurons and that inotropic support and maintenance of normoglycaemia may permit realisation of its neuroprotective potential. This may have important implications for future clinical stroke trials.

Aging↗
PubMed1997

The transition to adulthood for youth who have serious emotional disturbance: developmental transition and young adult outcomes.

This article reviews studies that depict the developmental transition from adolescence to young adulthood of persons who have experienced serious emotional disturbance (SED) as children or adolescents. The literature demonstrates that their plight in young adulthood is grave. Youth with SED enter the transition phase delayed in their developmental maturation and face additional challenges relative to their nondisabled peers. As a group, they are undereducated, underemployed, and have limited social supports. Homelessness, criminal activity, and drug use are prevalent. This article defines the transitional youth population, describes the developmental tasks of transition, and summarizes the results of longitudinal studies that have tracked functional outcomes of transitional youth into young adulthood. The discussion focuses on the relevance of these findings to service provision.

Adolescent↗
PubMed1997

Anti-arthritic activity of hydroxamic acid-based pseudopeptide inhibitors of matrix metalloproteinases and TNF alpha processing.

OBJECTIVE AND DESIGN: The effects of two hydroxamate inhibitors of metalloproteinase and tumor necrosis factor alpha (TNF alpha) processing on endotoxin-induced plasma TNF alpha and arthritic lesions in adjuvant-induced arthritic (AA) rats were determined. MATERIAL AND TREATMENT: BB-1101 and BB-1433 were administered orally twice daily to AA Lewis rats with an established disease (days 13 to 22). AA rats (day 16) or normal rats were injected with bacterial endotoxin and plasma levels of TNF alpha were also determined. METHODS: Hindpaw swelling was measured plethysmographically. Bone degradation was determined by radiography and bone mineral densitometry. TNF alpha was quantified using a sandwich ELISA. RESULTS: The hydroxamic-acid pseudopeptides inhibited plasma. TNF alpha levels in vivo and significantly reduced swelling and bone degradation of the tibiotarsal joints of AA rats in the range of 10-50 mg/kg given orally (p < 0.01 by Student's t-test). CONCLUSIONS: Thus, these novel compounds offer a new disease modifying therapy for arthritis and the results also suggest that inhibition of TNF alpha production may contribute, at least in part, to their anti-arthritic activity.

Animals↗