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Biomedical subjects

R J Davidson

Publications and source records attributed to R J Davidson.

At least 73 records · Page 4Linked to original sources
PubMed1996

Quantitation of mafosfamide-resistant pre-colony-forming units in allogeneic bone marrow transplantation: relationship with rate of engraftment and evidence for long-lasting reduction in stem cell numbers.

Current assays of human committed-stem cells are of limited value in predicting the rate of engraftment or in assessing the integrity of the stem cell pool after allogeneic bone marrow (BM) transplantation (BMT). We have used a limiting dilution assay of mafosfamide-resistant progenitors (pre-colony-forming units [CFU]), which are ancestral to committed progenitors such as CFU-granulocyte-macrophage (GM) to analyze the kinetics of myeloid engraftment after BMT and to assess the size of the stem cell pool at intervals up to 66 months thereafter. In 24 patients transplanted for chronic myeloid leukemia in chronic phase (eight with matched unrelated donors and 16 with sibling donors), the rate of neutrophil engraftment correlated strongly with the number of pre-CFU transfused per kilogram recipient body weight (r = .7, P < .005) but not with CFU-GM per kilogram or nucleated cells per kilogram. In 25 patients studied 6 to 66 months after allogeneic BMT, the mean number of pre-CFU in the marrow was 3.1/10(5) mononuclear cells (MNC) (median, 3.47; range, 0.4 to 23.3), compared with 24.7/10(5) MNC (median, 27.3; range, 4.2 to 180) in 25 normal subjects. CFU-GM were also reduced in these patients, but with considerable overlap into the normal range (mean +/- SD: 54 +/- 45.6 per 10(5) MNC; normal, 129 +/- 61.6). Low pre-CFU but not low CFU-GM levels were associated with reduced peripheral blood white blood cell counts in post-BMT patients. Pre-CFU and CFU-GM levels were not related to the interval posttransplant and remained low for up to 66 months. We conclude that the pre-CFU assay measures a population of stem/progenitor cells that are important in the kinetics of engraftment after allogeneic BMT. Our data suggest that pre-CFU levels may remain low for some years after BMT in humans.

Antineoplastic Agents↗
PubMed1996

A new method for aversive Pavlovian conditioning of heart rate in rhesus monkeys.

Aversive Pavlovian conditioning is an important tool used to investigate neurobiological mechanisms underlying the acquisition and expression of fear. Most studies have used nonprimate species employing electrical shock as the unconditioned stimulus (US). Although important advances have been made in understanding the neural substrates of conditioned fear, the extent to which these findings apply to primates is unclear. Research in primates has not progressed because of the lack of a conditioning paradigm that does not use shock. Therefore, we developed a method that uses a US consisting of a loud noise coupled with a stream of compressed air aimed at the face to aversively condition heart rate response in rhesus monkeys. With this US, rhesus monkeys rapidly acquire a conditioned bradycardia. The availability of an easy, reliable, and efficient method of aversive conditioning that does not require electrical shock, will facilitate studies investigating neurobiological mechanisms underlying the acquisition and expression of fear in primates.

Animals↗
PubMed1996

Individual differences in repressive-defensiveness predict basal salivary cortisol levels.

Prior studies assessing the relation between negative affective traits and cortisol have yielded inconsistent results. Two studies assessed the relation between individual differences in repressive-defensiveness and basal salivary cortisol levels. Experiment 1 assessed midafternoon salivary cortisol levels in men classified as repressors, high-anxious, or low-anxious. In Experiment 2, more rigorous controls were applied as salivary cortisol levels in women and men were assessed at 3 times of day on 3 separate days. In both studies, as hypothesized, repressors and high-anxious participants demonstrated higher basal cortisol levels than low-anxious participants. These findings suggest that both heightened distress and the inhibition of distress may be independently linked to relative elevations in cortisol. Also discussed is the possible mediational role of individual differences in responsivity to, or mobilization for, uncertainty or change.

Adolescent↗
PubMed1995

Affective neuroscience: the emergence of a discipline.

This past year has seen significant advances in our understanding of the physiology of emotion. Attention continues to focus on the amygdala and its interconnections with prefrontal cortical regions. New evidence underscores the importance of lateralization for emotion. There are also new findings on the physiological predictors of individual differences in emotional behavior and experience, and on the role of autonomic arousal in emotional memory.

Animals↗
PubMed1995

Development of multiple-antibiotic-resistant (Mar) mutants of Pseudomonas aeruginosa after serial exposure to fluoroquinolones.

Laboratory-derived fluoroquinolone-resistant mutants were created by serially passaging wild-type Pseudomonas aeruginosa on fluoroquinolone-containing agar to obtain high-level fluoroquinolone resistance (e.g., ciprofloxacin MIC of 1,024 micrograms/ml). With increases of 4- to 32-fold in MICs of fluoroquinolones, these organisms demonstrated (relative to wild-type) normal morphology, resistance to fluoroquinolones only, no change in fluoroquinolone uptake, and no change in lipopolysaccharide profiles or outer membrane protein profiles. Complementation with wild-type Escherichia coli gyrA restored fluoroquinolone susceptibility, suggesting that these were gyrA mutants. After 4- to 32-fold increases in fluoroquinolone MICs (with continued passage on fluoroquinolone-containing agar) isolates demonstrated altered morphology, a multiple-antibiotic-resistant (Mar) phenotype (including cross-resistance to beta-lactams, chloramphenicol, and tetracycline), reduced fluoroquinolone uptake and altered outer membrane proteins (reductions in the 25- and 38-kDa bands as well as several bands in the 43- to 66-kDa region). Complementation with wild-type E. coli gyrA partially reduced the level of fluoroquinolone resistance by approximately 8- to 32-fold, suggesting that these mutants displayed both gyrA and non-gyrA mutations.

Anti-Infective Agents↗
PubMed1994

Frontal brain activation in repressors and nonrepressors.

We assessed whether resting anterior asymmetry would discriminate individual differences in repressive-defensive coping styles. In 2 sessions, resting electroencephalogram was recorded from female adults during 8 60-s baselines. Subjects were classified as repressors or nonrepressors on the basis of scores on the Marlowe-Crowne Social Desirability Scale (MC), the State-Trait Anxiety Inventory (STAI), and the Beck Depression Inventory (BDI). In midfrontal and lateral frontal sites, repressors demonstrated relative left hemisphere activation when compared with other groups. The MC, but not the STAI or the BDI, contributed unique variance to frontal asymmetry. Relative left frontal activation may be linked to a self-enhancing regulatory style that promotes lowered risk for psychopathology.

Adaptation, Psychological↗
PubMed1994

Reward fails to alter response bias in depression.

Several different models postulate that depression is associated with decreased approach-related behavior. Relatively little has been done to date to specifically investigate this issue. In the present study, a signal-detection analysis was used to examine the response biases of dysphoric and nondysphoric female undergraduates during 3 payoff conditions: neutral, reward, and punishment. As predicted, the dysphoric subjects had a smaller change in bias from the neutral to the reward condition compared with the nondysphoric group. The 2 groups did not differ during the neutral and punishment conditions. These findings are consistent with the hypothesis that the left frontal hypoactivation observed in depression reflects a deficit in approach-related behavior.

Adult↗
PubMed1994

How and why do the two cerebral hemispheres interact?

Research on the anatomical bases of interhemispheric interaction, including individual differences in corpus callosum (CC) anatomy, is reviewed. These anatomical findings form the basis for the discussion of two major themes. The first considers interhemispheric transfer time (IHTT) and related issues. These include varieties of IHTT and possible directional asymmetries of IHTT. Evidence suggests that pathological variations in IHTT may have cognitive consequences. The second involves conditions under which interhemispheric interaction is necessary and beneficial. The data suggest that when both hemispheres have some competence at a difficult task, there is a benefit to interhemispheric interaction. The role of the CC in the dynamic distribution of attention may be particularly relevant to this advantage. Throughout the article reference is made to individual differences and developmental changes associated with interhemispheric interaction.

Animals↗
PubMed1994

Postantibiotic effect in Pseudomonas aeruginosa following single and multiple aminoglycoside exposures in vitro.

The effect of single and multiple 2-h aminoglycoside exposures on the duration of the postantibiotic effect (PAE) and bacterial killing were investigated using a reference strain (ATCC 27853) and four clinical isolates of Pseudomonas aeruginosa. Concentration-dependent PAE and bacterial killing were demonstrated following single exposures to amikacin, gentamicin or tobramycin. Cultures were also repeatedly exposed to peak aminoglycoside concentration simulating traditional (three times a day) and once daily dosing regimens. Aminoglycoside re-exposures every 8 h at the original culture MIC produced significant, successive reductions in PAE (P < 0.05) and bacterial killing (P < 0.01) coincident with increases in culture MICs. Identical experiments re-exposing cultures to their predetermined, induced MICs demonstrated similar to significantly longer PAEs (P < 0.05) than those observed following first exposure. Multiple gentamicin or tobramycin exposures at 8 mg/L (traditional peak) every 8 h or 24 mg/L (once daily peak) once every 24 h both showed significant reductions in PAE (P < 0.05) and bacterial killing (P < 0.05) on repeated dosing. However, the once-daily high peak concentration exposure demonstrated significantly longer PAEs and greater bacterial killing both initially and upon re-exposure compared with the 8-hourly exposure. In addition, the once daily dosing regimen maintained substantially larger aminoglycoside concentration/MIC ratios. We conclude that multiple exposure of P. aeruginosa in-vitro, to aminoglycosides at the intervals tested, reduces the PAE and bacterial killing and increases the MICs.

Aminoglycosides↗
PubMed1994

The accumulation of fluoroquinolones in Staphylococcus aureus during the postantibiotic effect.

The accumulation of radiolabelled pefloxacin, norfloxacin, and lomefloxacin was determined in Staphylococcus aureus during log phase growth, the postantibiotic effect (PAE), and at 1, 4 and 6 h post PAE. Uptake in actively growing cells was consistent with a non-saturable passive diffusion process. The addition of metabolic inhibitors significantly increased accumulation consistent with the presence of an energy dependent efflux system. Accumulation of all three fluoroquinolones in PAE phase cells was significantly increased compared to that which occurred in actively growing cells. In contrast to cells in the log phase, addition of metabolic inhibitors to PAE phase cells did not result in a significant increase in drug accumulation. Uptake kinetics 1 h and 4 h post PAE were similar to those found during the PAE phase. Organisms required 6 h after the end of the PAE phase before normal uptake kinetics of fluoroquinolones resumed.

Anti-Infective Agents↗
PubMed1994

Once-daily aminoglycoside dosing assessed by MIC reversion time with Pseudomonas aeruginosa.

A novel, in vitro, pharmacodynamic comparison of single and divided daily dosing regimens of aminoglycosides is described. Experiments were conducted to evaluate the impact of gentamicin and tobramycin concentration on the time required for the MICs for five Pseudomonas aeruginosa strains to revert to their original values (MIC reversion time [MRT]) following single and multiple 2-h aminoglycoside exposures to 8 and 24 mg/liter. Single 2-h aminoglycoside exposures to 8 mg/liter produced culture MRTs (gentamicin, 21.5 +/- 4.0 h; tobramycin, 22.3 +/- 2.8 h) that were significantly (P < 0.05) shorter than those measured following identical exposures to 24 mg/liter (gentamicin, 28.9 +/- 3.8 h; tobramycin, 26.8 +/- 3.1 h). However, three sequential 2-h exposures to 8 mg/liter, one exposure every 8 h, produced MRTs following the third exposure (gentamicin, 68.1 +/- 5.2 h; tobramycin, 77.8 +/- 7.8 h) that were significantly longer (P < 0.005) than those determined following three 2-h exposures to 24 mg/liter, one exposure every 24 h (gentamicin, 36.1 +/- 3.0 h; tobramycin, 34.5 +/- 3.0 h). In addition, the once-daily exposure regimen to 24 mg/liter consistently produced cultures with significantly (P < 0.005) higher aminoglycoside concentration/MIC ratios compared with those for cultures reexposed to 8 mg/liter once every 8 h. These data support the concept of once-daily aminoglycoside dosing.

Anti-Bacterial Agents↗
PubMed1994

Antisense BCR-ABL oligomers cause non-specific inhibition of chronic myeloid leukemia cell lines.

We have examined the effects of antisense oligomers (AOs) of various lengths, sequences and chemistry on the proliferation of eight different cell lines, five derived from patients with chronic myelogenous leukemia (CML) and three from other sources. In general, phosphodiester AOs were inactive, presumably due to degradation by nucleases present in fetal calf serum. Both BA2 and B3A2 phosphorothiolate AOs (but not corresponding sense oligomers) significantly inhibited the proliferation of three CML cell lines (BV173, LAMA84, and KYO1), but the effect was independent of the type of breakpoint expressed by each cell line, suggesting that the inhibition was sequence dependent but not sequence specific. The CML cell lines tested showed different sensitivities to inhibition of proliferation by AOs--lines with defective expression of the normal ABL protooncogene (e.g. BV173) were more readily inhibited than lines with a normal ABL message (e.g. K562). We conclude that further studies are necessary to delineate the precise mechanism(s) by which CML cell proliferation is inhibited by AOs.

Base Sequence↗
PubMed1993

Lateralized response to diazepam predicts temperamental style in rhesus monkeys.

Based on previous findings in humans and rhesus monkeys suggesting that diazepam has asymmetrical effects on frontal lobe activity and other literature supporting a role for the benzodiazepine system in the mediation of individual differences in anxiety and fearfulness, the relation between asymmetrical changes in scalp-recorded regional brain activity in response to diazepam and the temperamental dimension of behavioral inhibition indexed by freezing time in 9 rhesus monkeys was examined. Animals showed greater relative left-sided frontal activation in response to diazepam compared with the preceding baseline. The magnitude of this shift was strongly correlated with an aggregate measure of freezing time (r = .82). The implications of these findings for understanding the role of regional differences in the benzodiazepine system in mediating individual differences in fearfulness are discussed.

Animals↗
PubMed1993

Guidelines for the recording and quantitative analysis of electroencephalographic activity in research contexts.

Developments in technologic and analytical procedures applied to the study of brain electrical activity have intensified interest in this modality as a means of examining brain function. The impact of these new developments on traditional methods of acquiring and analyzing electroencephalographic activity requires evaluation. Ultimately, the integration of the old with the new must result in an accepted standardized methodology to be used in these investigations. In this paper, basic procedures and recent developments involved in the recording and analysis of brain electrical activity are discussed and recommendations are made, with emphasis on psychophysiological applications of these procedures.

Action Potentials↗
PubMed1993

Frontal brain asymmetry and emotional reactivity: a biological substrate of affective style.

Individuals differ dramatically in the quality and intensity of their response to affectively evocative stimuli. On the basis of prior theory and research, we hypothesized that these individual differences are related to variation in activation of the left and right frontal brain regions. We recorded baseline brain electrical activity from subjects on two occasions 3 weeks apart. Immediately following the second recording, subjects were exposed to brief positive and negative emotional film clips. For subjects whose frontal asymmetry was stable across the 3-week period, greater left frontal activation was associated with reports of more intense positive affect in response to the positive films, whereas greater right frontal activation was associated with more intense reports of negative affect in response to the negative film clips. The methodological and theoretical implications of these data are discussed.

Adolescent↗
PubMed1993

In vitro postantibiotic effects following multiple exposures of cefotaxime, ciprofloxacin, and gentamicin against Escherichia coli in pooled human cerebrospinal fluid and Mueller-Hinton broth.

Multiple exposures with cefotaxime in either Mueller-Hinton broth or cerebrospinal fluid had no effect on killing or the duration of postantibiotic effect (PAE) in Escherichia coli strains tested. However, upon multiple exposures in Mueller-Hinton broth, ciprofloxacin and gentamicin PAEs significantly decreased with a concomitant reduction in bacterial killing. A reduction in bacterial killing following multiple ciprofloxacin and gentamicin exposures was also seen with cerebrospinal fluid; however, the PAE was maintained.

Cefotaxime↗