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D Davidson

Publications and source records attributed to D Davidson.

At least 109 records · Page 6Linked to original sources

Ondansetron alters human alcohol intoxication.

There is considerable evidence that serotonin-3 (5-HT3) receptor antagonists modulate some of the behavioral effects of alcohol, and may decrease alcohol consumption. To better clarify the mechanism of action of 5-HT3 antagonists on these behaviors, we investigated the effects of the 5-HT3 antagonist, ondansetron, on several subjective and objective measures of alcohol intoxication in social drinkers. Twelve nonalcoholic, social drinkers received either 8 mg ondansetron, p.o., or placebo during one of two test sessions in a crossover, double-blind protocol. Both conditions were followed by a standard, intoxicating dose of alcohol. Subjective and objective measures of intoxication including mood, physical sensations, performance changes, and alcohol pharmacokinetics were determined. To control for ondansetron effects, 10 additional subjects received either ondansetron or placebo, followed by a nonintoxicating, "placebo" dose of alcohol during a second crossover double-blind protocol. Ondansetron was found to augment certain stimulant, sedative, and discriminant effects of alcohol, without affecting psychomotor performance or alcohol pharmacokinetics. Ondansetron had minimal effects on subjects receiving placebo alcohol. These data suggest that the reductions in alcohol consumption observed in animals and humans treated with ondansetron may be mediated by increases in subjective intoxication, and/or increases in the aversive effects of alcohol.

Adult↗

Association of tyrosine protein kinase Zap-70 with the protooncogene product p120c-cbl in T lymphocytes.

Accumulating data show that the tyrosine protein kinase Zap-70 plays an essential role in T cell receptor-mediated signal transduction. However, the model of action, as well as the physiologically relevant substrates of Zap-70, have not been determined. We have attempted to identify a 120-kD tyrosine-phosphorylated protein (p120) that associates with Zap-70 in activated T lymphocytes. The results of our analyses showed that p120 is largely encoded by the c-cbl protooncogene. Furthermore, the association of Zap-70 with c-Cbl was shown to be induced by T cell receptor stimulation, implying that it required posttranslational modification of one or both of these products. FynT, but not Lck, also associated with c-Cbl in activated T cells. Finally, using a heterologous system, it was demonstrated that the ability of Zap-70 to cause tyrosine phosphorylation of p120c-cbl was dependent on Lck- or FynT-mediated signals. As c-Cbl can associate with several other signaling molecules, it may couple Zap-70 to downstream effectors during T cell activation.

Animals↗

The effects of decision characteristics on children's selective search of predecisional information.

In the present research, an information-board procedure was used to examine second and fifth grade children's selective search of predecisional information. Several conditions were used to facilitate children's selective search of information, including putting decisions within meaningful contexts (i.e., stories), increasing the perceptual salience of some of the dimensions on the information boards, and constraining the amount of time and the amount of information children could take when searching predecisional information. It was found that both second and fifth graders' predecisional search became more selective when the perceptual salience of some of the dimensions was increased. Children also became more selective in their searching over successive decisions. In contrast, the information constraint resulted in less selective searching, and less choosing of the best alternative for both second and fifth grader, whereas the time pressure decreased second but not fifth graders' selectivity in searching. Thus, without sufficient mastery of a search strategy, children may resort to using less sophisticated strategies, particularly under time and information pressures. These results are discussed in terms how the development of selective search and attentional strategies may impact both predecisional search behavior and the quality of children's decisions.

Attention↗

Complementary tissue-specific expression of LIF and LIF-receptor mRNAs in early mouse embryogenesis.

The maintenance of pluripotential embryonic stem (ES) cells is dependent on the cytokine LIF. This report documents the mRNA expression profiles of LIF and the two components of the LIF-receptor complex, LIF-R and gp130, during early mouse embryogenesis. These mRNAs were undetectable in 1- or 2-cell embryos, but all were present by the blastocyst stage. LIF transcripts were localised in the differentiated trophectoderm, and were absent from the pluripotential inner cell mass. In contrast, LIF-R mRNA was found in the inner cell mass but not in the trophectoderm. This complementary pattern of expression is suggestive of a paracrine coupling between stem cells and differentiated progeny at the earliest stage of mammalian development. After implantation, transcripts for all components were down-regulated in the embryo. High levels of LIF-R and gp130 mRNAs were observed in the deciduum, however. These dynamic, tissue-specific expression patterns are consistent with regulatory roles for LIF or related cytokines, both in the maintenance of pluripotency in the mouse embryo, and in development of the foeto-maternal interface.

Animals↗

Mutation of putative branchpoint consensus sequences in plant introns reduces splicing efficiency.

Intron lariat formation between the 5' end of an intron and a branchpoint adenosine is a fundamental aspect of the first step in animal and yeast nuclear pre-mRNA splicing. Despite similarities in intron sequence requirements and the components of splicing, differences exist between the splicing of plant and vertebrate introns. The identification of AU-rich sequences as major functional elements in plant introns and the demonstration that a branchpoint consensus sequence was not required for splicing have led to the suggestion that the transition from AU-rich intron to GC-rich exon is a major potential signal by which plant pre-mRNA splice sites are recognized. The role of putative branchpoint sequences as an internal signal in plant intron recognition/definition has been re-examined. Single nucleotide mutations in putative branchpoint adenosines contained within CUNAN sequences in four different plant introns all significantly reduced splicing efficiency. These results provide the most direct evidence to date for preferred branchpoint sequences being required for the efficient splicing of at least some plant introns in addition to the important role played by AU sequences in dicot intron recognition. The observed patterns of 3' splice site selection in the introns studied are consistent with the scanning model described for animal intron 3' splice site selection. It is suggested that, despite the clear importance of AU sequences for plant intron splicing, the fundamental processes of splice site selection and splicing in plants are similar to those in animals.

Amylases↗

After the shooting stops: follow-up on victims of an assault rifle attack.

OBJECTIVE: To determine long-term medical, social, and psychological outcome of survivors of a multiple-shooting mass casualty disaster. DESIGN: A case-study review was performed 42 months after injury involving chart reviews and patient interviews. PARTICIPANTS: Survivors of a multiple shooting. MAIN OUTCOME MEASURES: The need for primary operative treatment, subsequent operations, and medical treatment related to the injuries, current work status, and psychological impact of injury was determined. RESULTS: Thirteen patients required operation initially; 12 are long-term survivors. Eight have returned to work. Most of the victims reported experiencing psychological and emotional problems. CONCLUSIONS: Despite a well-functioning trauma system that maximized survival from devastating injury, considerable long-term morbidity and disability persists. Efforts at prevention of mass casualties seem to be the only potential solution.

Bone and Bones↗

Effects of naloxone on limited-access ethanol drinking in rats.

The hypothesis that naloxone (NAL) decreases oral ethanol intake in rats by inducing a conditioned taste aversion (CTA) to ethanol was investigated. Rats were trained to drink 8% ethanol (v/v) on a 1-hr limited-access schedule. They received 4 days of intraperitoneal injections of 10 mg/kg of NAL, 10 min before limited-access (-10MIN group), immediately after limited-access (1HR group), or 3 hr after limited-access (3HR). Ethanol intake decreased in the -10MIN and 1HR groups during the injection period and on the postinjection day. In experiment 2, rats received 4 days of NAL injections when ethanol was not available (pre-exposure), and then the paradigm was repeated. In this experiment, there was no suppression of ethanol intake for any group on the postinjection day. The decrease in ethanol intake during injections observed for the 1HR in experiment 1 and the sustained suppression postinjection was interpreted as a CTA. Pre-exposure in experiment 2 abolished the CTA. Differences in the pattern ethanol intake for the -10MIN and 3HR groups during the experiments, however, suggest that a CTA is not the sole mechanism underlying NAL's suppressant effects on ethanol intake. In conclusion, in rats both the dose of NAL and the relative timing of NAL injections and ethanol drinking effect subsequent NAL suppression of ethanol intake.

Alcohol Drinking↗

Naltrexone increases the latency to drink alcohol in social drinkers.

We investigated the effects of naltrexone (NTX) on alcohol drinking, urge to drink alcohol, and alcohol-induced sensations and mood states in social drinkers consuming alcohol ad libitum in a cocktail bar. Sixteen college-age men and women participated in a double-blind, placebo-controlled, within-subjects, cross-over study. Subjects were tested during each of three drug conditions: NTX, 50 mg/ day, po; inactive placebo; and no drug. Each treatment condition lasted 8 to 11 days. Small groups of subjects consumed alcohol ad libitum during three 2-hr evening drinking sessions, separated by approximately-2 weeks. NTX treatment significantly increased the latency (time in seconds) to first sip the first (p < 0.05) and second alcoholic beverages consumed (p < 0.01). Moreover, the mean blood alcohol concentration at the end of the session was significantly lower when subjects were treated with NTX (p < 0.05). No differences were found on self-report urge to drink alcohol. Subjects reported more fatigue and tension on the Profile of Mood States (p < 0.05), before drinking, and increases in nausea on the Alcohol Sensation Scale (p < 0.05) when treated with NTX. The increase in the latency to sip the first and second alcoholic beverages may reflect the capacity of NTX to block urge for alcohol elicited from external cues (before consuming alcohol), as well as urge for alcohol after priming from ingested alcohol. Thus, the effectiveness of NTX for reducing drinking behaviors of alcoholics may be partially caused by anticraving properties of NTX.

Adult↗

The faces of Medicaid.

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American Hospital Association↗

Identification of Rlk, a novel protein tyrosine kinase with predominant expression in the T cell lineage.

The control of phosphorylation by protein tyrosine kinases represents an important regulatory mechanism in T cell growth, function, and differentiation. We have identified a 62-kDa murine protein tyrosine kinase predominantly expressed within the T cell lineage, which we have termed Rlk (for Resting lymphocyte kinase). rlk mRNA was found to be expressed in the fetal thymus as early as day 13 of embryonic development as well as in adult thymus and mature resting peripheral T cells. The sequence of rlk showed that it is most closely related to the subfamily of cytoplasmic tyrosine kinases that includes the Btk, Itk, and Tec proteins. However, Rlk differs from these kinases by virtue of its unique aminoterminal domain, which lacks a region of pleckstrin homology common to the other members of this protein subfamily. Examination of rlk abundance within different T cell subpopulations revealed preferential expression in Th1 relative to Th2 T cell clones, suggesting a possible role in signal transduction pathways that selectively regulate cytokine production in mature CD4+ T cell subsets. Rlk thus represents a novel cytoplasmic tyrosine kinase with potential functions in intrathymic T cell development and mature T cell signaling.

Amino Acid Sequence↗