Search PubMed⌕ Search

Biomedical subjects

B Adams

Publications and source records attributed to B Adams.

At least 55 records · Page 3Linked to original sources
PubMed1998

G-Protein-dependent facilitation of neuronal alpha1A, alpha1B, and alpha1E Ca channels.

Modulation of neuronal voltage-gated Ca channels has important implications for synaptic function. To investigate the mechanisms of Ca channel modulation, we compared the G-protein-dependent facilitation of three neuronal Ca channels. alpha1A, alpha1B, or alpha1E subunits were transiently coexpressed with alpha2-deltab and beta3 subunits in HEK293 cells, and whole-cell currents were recorded. After intracellular dialysis with GTPgammaS, strongly depolarized conditioning pulses facilitated currents mediated by each Ca channel type. The magnitude of facilitation depended on current density, with low-density currents being most strongly facilitated and high-density currents often lacking facilitation. Facilitating depolarizations speeded channel activation approximately 1.7-fold for alpha1A and alpha1B and increased current amplitudes by the same proportion, demonstrating equivalent facilitation of G-protein-inhibited alpha1A and alpha1B channels. Inactivation typically obscured facilitation of alpha1E current amplitudes, but the activation kinetics of alpha1E currents showed consistent and pronounced G-protein-dependent facilitation. The onset and decay of facilitation had the same kinetics for alpha1A, alpha1B, and alpha1E, suggesting that Gbeta gamma dimers dissociate from and reassociate with these Ca channels at very similar rates. To investigate the structural basis for N-type Ca channel modulation, we expressed a mutant of alpha1B missing large segments of the II-III loop and C terminus. This deletion mutant exhibited undiminished G-protein-dependent facilitation, demonstrating that a Gbeta gamma interaction site recently identified within the C terminus of alpha1E is not required for modulation of alpha1B.

Calcium Channels↗
PubMed1998

Corticolimbic dopamine neurotransmission is temporally dissociated from the cognitive and locomotor effects of phencyclidine.

The behavioral syndrome produced by phencyclidine (PCP) and its analog ketamine represents a pharmacological model for some aspects of schizophrenia. Despite the multifaceted properties of these drugs, the main mechanism for their psychotomimetic and cognitive-impairing effects has been thought heretofore to involve the corticolimbic dopamine system. The present study examined the temporal relationship between alterations in corticolimbic dopamine and glutamate neurotransmission and two dopamine-dependent behavioral effects of PCP in the rodent that have relevance to the clinical phenomenology, namely, impairment of working memory, which is used to model the frontal lobe deficits associated with schizophrenia, and hyperlocomotion, which is used as a predictor of the propensity of a drug to elicit or exacerbate psychosis. PCP increased dopamine and glutamate efflux in the prefrontal cortex and nucleus accumbens, as measured by microdialysis. The increase in dopamine in both regions remained elevated well above baseline 2.5 hr after the injection, at which time the experiment was terminated. However, locomotor activity returned to baseline in <2 hr after injection. Furthermore, impaired performance in a discrete trial delayed alternation task, a rodent working memory task, was only evident up to 60 min after PCP injection; animals tested 80 min after injection, when cortical dopamine release was elevated at 300% of baseline, did not exhibit impaired performance. These findings indicate that activation of dopamine neurotransmission is not sufficient to sustain PCP-induced locomotion and impairment of working memory. Thus, effects of PCP, including a glutamatergic hyperstimulation, may be necessary to account for the psychotomimetic and cognitive-impairing effects of this drug.

Animals↗
PubMed1998

X-ray Holography for Structural Imaging.

X-ray atomic resolution holography is a new method for direct evaluation of three-dimensional electron density distribution in solids. The practical implementation of the multiple-energy technique on a synchrotron radiation source as well as image reconstruction from the experimental data are described. Holograms at several different energies were processed together to suppress twin images and artifacts from long-range-order effects in the experimental data sets. Reconstructed images of copper atoms in Cu(2)O crystals are presented.

Journal Article↗
PubMed1998

Molecular cloning, sequencing, and phylogenetic relationships of a new potyvirus: sugarcane streak mosaic virus, and a reevaluation of the classification of the potyviridae.

The nucleic acid of a serologically distinct potyvirus, originally isolated out of sugar cane from Pakistan, was reverse transcribed and the 3' terminal 2000 bp was PCR amplified, cloned, and sequenced. Phylogenetic comparisons of viruses representing each genus of the Potyviridae show that the Pakistani isolate is most closely related to the rymoviruses wheat streak mosaic virus (WSMV) and brome streak mosaic virus. We therefore propose that this new virus species be named sugar cane streak mosaic virus to reflect its similarity to WSMV. The phylogenetic data also show that the genus Rymovirus contains at least two unique evolutionary lineages. Thus the current taxonomy, based on transmission vector, is paraphyletic. We present an analysis of the taxonomic relationships among members of the family and propose a classification that both resolves the paraphyly and more accurately represents the evolutionary history of the Potyviridae.

Amino Acid Sequence↗
PubMed1997

Long-term potentiation trains induce mossy fiber sprouting.

It has been shown that both amygdaloid and hippocampal kindling induce sprouting of the mossy fibers in the dentate gyrus. In this study, we investigated whether non-epileptogenic stimulation could also induce mossy fiber sprouting. Long-term potentiation (LTP) was induced in the dentate gyrus by the application of brief, high frequency trains to the perforant path. The potentiating stimulation was applied each day for 10 days, and the tissue was prepared for Timm labelling 7 days later. Sprouting was significantly increased in the LTP group compared to the implanted control rats. These results suggest that mossy fiber sprouting is not damage-induced and is dependent on neuronal activation.

Animals↗
PubMed1997

Nerve growth factor accelerates seizure development, enhances mossy fiber sprouting, and attenuates seizure-induced decreases in neuronal density in the kindling model of epilepsy.

Recurrent seizure activity induced during kindling has been reported to produce a functional synaptic reorganization of the mossy fibers in the hippocampus. To date, it is unclear whether this kindling-induced growth is secondary to decreases in hilar neuron density, which are presumed to reflect hilar neuronal cell loss, or whether it is related specifically to an activation-dependent plasticity. We recently demonstrated that blocking nerve growth factor (NGF) biological activity retards seizure development and inhibits the sprouting of mossy fibers. We now demonstrate that intraventricular administration of NGF itself accelerates the progression of kindling epileptogenesis, increases mossy fiber sprouting in the CA3 region and in the inner molecular layer (IML), but reduces seizure-induced decreases in hilar cell density. These findings provide support for a role of NGF in kindling and kindling-induced mossy fiber sprouting. In addition, the results dissociate this form of epileptogenesis from hilar cell loss or decreases in hilar cell density attributable to increases in hilar area, thereby supporting seizure-induced mossy fiber sprouting as being primarily attributable to the combined effects of neuronal activation and the activation-induced upregulation of growth factors.

Animals↗
PubMed1997

Activation of glutamatergic neurotransmission by ketamine: a novel step in the pathway from NMDA receptor blockade to dopaminergic and cognitive disruptions associated with the prefrontal cortex.

Subanesthetic doses of ketamine, a noncompetitive NMDA receptor antagonist, impair prefrontal cortex (PFC) function in the rat and produce symptoms in humans similar to those observed in schizophrenia and dissociative states, including impaired performance of frontal lobe-sensitive tests. Several lines of evidence suggest that ketamine may impair PFC function in part by interacting with dopamine neurotransmission in this region. This study sought to determine the mechanism by which ketamine may disrupt dopaminergic neurotransmission in, and cognitive functions associated with, the PFC. A thorough dose-response study using microdialysis in conscious rats indicated that low doses of ketamine (10, 20, and 30 mg/kg) increase glutamate outflow in the PFC, suggesting that at these doses ketamine may increase glutamatergic neurotransmission in the PFC at non-NMDA glutamate receptors. An anesthetic dose of ketamine (200 mg/kg) decreased, and an intermediate dose of 50 mg/kg did not affect, glutamate levels. Ketamine, at 30 mg/kg, also increased the release of dopamine in the PFC. This increase was blocked by intra-PFC application of the AMPA/kainate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione CNQX. Furthermore, ketamine-induced activation of dopamine release and impairment of spatial delayed alternation in the rodent, a PFC-sensitive cognitive task, was ameliorated by systemic pretreatment with AMPA/kainate receptor antagonist LY293558. These findings suggest that ketamine may disrupt dopaminergic neurotransmission in the PFC as well as cognitive functions associated with this region, in part, by increasing the release of glutamate, thereby stimulating postsynaptic non-NMDA glutamate receptors.

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

Structural regions of the cardiac Ca channel alpha subunit involved in Ca-dependent inactivation.

We investigated the molecular basis for Ca-dependent inactivation of the cardiac L-type Ca channel. Transfection of HEK293 cells with the wild-type alpha or its 3' deletion mutant (alpha) produced channels that exhibited prominent Ca-dependent inactivation. To identify structural regions of alpha involved in this process, we analyzed chimeric alpha subunits in which one of the major intracellular domains of alpha was replaced by the corresponding region from the skeletal muscle alpha subunit (which lacks Ca-dependent inactivation). Replacing the NH terminus or the III-IV loop of alpha with its counterpart from alpha had no appreciable effect on Ca channel inactivation. In contrast, replacing the I-II loop of alpha with the corresponding region from alpha dramatically slowed the inactivation of Ba currents while preserving Ca-dependent inactivation. A similar but less pronounced result was obtained with a II-III loop chimera. These results suggest that the I-II and II-III loops of alpha may participate in the mechanism of Ca-dependent inactivation. Replacing the final 80% of the COOH terminus of alpha with the corresponding region from alpha completely eliminated Ca-dependent inactivation without affecting inactivation of Ba currents. Significantly, Ca-dependent inactivation was restored to this chimera by deleting a nonconserved, 211-amino acid segment from the end of the COOH terminus. These results suggest that the distal COOH terminus of alpha can block Ca-dependent inactivation, possibly by interacting with other proteins or other regions of the Ca channel. Our findings suggest that structural determinants of Ca-dependent inactivation are distributed among several major cytoplasmic domains of alpha.

Amino Acid Sequence↗
PubMed1997

Guantanamo Bay, Cuba 1996: psychiatric services to Cuban migrants in the final days of Operation Sea Signal.

Conditions during the final days of Operation Sea Signal in Guantanamo Bay, Cuba, presented a unique challenge for the U.S. Naval Hospital psychiatry/mental health team. The team was charged with evaluation and treatment of Cuban migrants and with determining suitability for immigration to the United States. Degradation of social support networks appeared to be a factor in the course of psychiatric symptoms. The cases of two Cuban migrant males presenting with psychiatric disorders in the final month of the operation illustrate the complexities of the operation's psychiatric mission. Our focus was on behavioral interventions and social supports rather than definitive pharmacologic management of the underlying psychiatric disorders. Suggestions for management of similar missions in the future are provided.

Adult↗
PubMed1996

The role of the C-terminal lysine in the hinge bending mechanism of yeast phosphoglycerate kinase.

Treatment of yeast phosphoglycerate kinase (PGK) with trypsin results in a fourfold increase in the Vmax of this enzyme, without affecting the Km. This activation is shown to be due to the removal of the C-terminal lysine residue. The C-terminal sequence folds back over the N-terminal domain and contacts the extreme N-terminal sequence which folds onto the C-terminal domain, thus making many of the inter-domain contacts in this two domain protein. Previous studies have shown that this C-terminal region is important in mediating the conformational changes required during catalysis by yeast PGK. Observation of the three-dimensional structure of this enzyme suggests that removal of the C-terminal lysine residue will strengthen the interaction between K5 and E413. This indicates that this salt bridge stabilises the enzyme in the higher activity form, while the presence of K415 reduces the strength of that interaction.

Enzyme Activation↗
PubMed1996

Melatonin efficacy in aviation missions requiring rapid deployment and night operations.

BACKGROUND: The rapid deployment of Army aviation personnel across time zones, combined with missions beginning immediately upon arrival, results in desynchronization of physiological and cognitive performance rhythms. Implementation of effective countermeasures enhances safety, health, well-being, and mission completion. The naturally occurring hormone melatonin has been suggested as an effective counter measure for jet lag and shift lag because of its influence on the human circadian timing system and its hypnotic properties. METHODS: The efficacy of melatonin (10 mg) in maintaining stable sleep/wake cycles of Army aircrews was tested during a training mission involving rapid deployment to the Middle East and night operations. Cognitive performance was tested before and after travel; activity rhythms were recorded continuously for 13 d. RESULTS: Melatonin treatment advanced both bedtimes and rise times (2-3 h) and maintained sleep durations between 7-8 h. Placebo treatment was mostly associated with longer advances in rise times than bedtimes resulting in shorter sleep durations (5-7 h). Upon awakening, the melatonin group exhibited significantly fewer errors (mean: 7.45) than the placebo group (mean: 14.50) in a dual-task vigilance test. CONCLUSION: Melatonin can be a useful treatment for the prevention of sleep disruptions and cognitive degradation, even in uncontrolled sleeping environments characteristic of military deployments.

Adult↗