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Biomedical subjects

J A Nagel

Publications and source records attributed to J A Nagel.

12 recordsLinked to original sources

Quantitative comparison of shear-dependent Staphylococcus aureus adhesion to three polyurethane ionomer analogs with distinct surface properties.

Bacterial adhesion is a central step in infection on biomaterial surfaces; however, the relation between biomaterial surface properties and adhesion remains poorly understood. To quantitatively determine the relationship among polyurethane surface properties, protein coating, and adhesion, we have compared attachment and detachment kinetics of Staphylococcus aureus on three different novel polyurethanes with different protein coatings. Rate constants for attachment or detachment were measured as a function of shear rate in a well-defined laminar flow field. The tested polyurethanes included a relatively hydrophobic-base polyether urethane and hydrophilic anionomer and cationomer analogs of the base material. Materials were tested bare, or coated with human fibrinogen, plasma, or albumin. The results suggest that the presence of fibrinogen or plasma greatly enhance the attachment rate constants and decrease the detachment rate constants on all materials. The most extreme differences among the different materials were observed on the bare materials, with the base polyurethane being most resistant to both attachment and detachment. However, except for a reduced attachment rate constant on the plasma-coated sulfonated polyurethane, few differences in the rate constants were observed among protein-coated materials, suggesting the primary role of surface properties is masked by the presence of the adsorbed protein layer.

Bacterial Adhesion↗

Bacterial adhesion to polyurethane surfaces in the presence of pre-adsorbed high molecular weight kininogen.

The factors which affect the adherence of a bacteria cell to the surface of a biomaterial include the surface chemistry of the cell and material, as well as the composition of the adsorbed protein layer when the biomaterial is exposed to circulating blood. In an effort to better understand the mechanisms by which bacteria adhere to such surfaces, and specifically to determine the effects of high molecular weight kininogen on bacterial adhesion, experiments were performed in which the attachment of Staphylococcus aureus was directly observed on glass and on a series of functionalized polyurethanes. These surfaces had been pre-adsorbed with various concentrations of high molecular weight kininogen and fibrinogen. Attachment was observed using a radial flow chamber, in which shear stress varied inversely with radial distance. Protein adsorption studies were also performed using 125I labeled fibrinogen to investigate the relationship between surface chemistry, protein adsorption, and bacterial attachment. Bacterial attachment was significantly decreased when the glass surface was pre-adsorbed with high molecular weight kininogen--either alone, or following adsorption of fibrinogen. High molecular weight kininogen thus exhibited anti-adhesive effects. On polyurethane surfaces pre-adsorbed with fibrinogen, kininogen, and albumin, the highest bacterial attachment was found on the base polyurethane, while significant decreases were seen on the hydrophilic polyurethanes. In addition, it was found that the surface with the least bacterial attachment and fibrinogen deposition was the polyurethane with pendant phosphonate groups.

Adsorption↗

Quantitative comparison of clumping factor- and coagulase-mediated Staphylococcus aureus adhesion to surface-bound fibrinogen under flow.

The contributions of clumping factor and coagulase in mediating Staphylococcus aureus adhesion to surface-adsorbed fibrinogen have been quantified by using a new methodology and analysis. The attachment or detachment kinetics of bacteria were directly observed in a radial flow chamber with a well-defined laminar flow field and a spatially varying shear rate and were quantified by recursively scanning the chamber surface and counting cells via automated video microscopy and image analysis with a motorized stage and focus control. Intrinsic rate constants for attachment or detachment were estimated as functions of shear rate for the wild-type Newman strain of S. aureus and for mutants lacking clumping factor, coagulase, or both proteins on surfaces coated with plasma, fibrinogen, or albumin. Clumping factor, but not coagulase, increased the probability of attachment and decreased the probability of detachment of S. aureus on plasma-coated surfaces; however, both clumping factor and, to a lesser extent, coagulase increased the probability of attachment on the purified-fibrinogen-coated surface. All mutants were resistant to detachment on the purified-fibrinogen-coated surface, suggesting the possibility of an additional adhesion mechanism which was independent of coagulase or clumping factor and effective only for fully attached cells. Together, these results suggest that the presence of clumping factor plays the primary role in enhancing adhesion to surfaces with adsorbed fibrinogen, not only by enhancing the probability of cell attachment but also by increasing the strength of the resulting adhesion.

Bacterial Adhesion↗

Enhanced inhibitory avoidance learning produced by post-trial injections of substance P into the basal forebrain.

The effects of injections of the neuropeptide substance P or the GABA agonist muscimol on performance of a step-down inhibitory avoidance task were examined. Immediately after the training trial, rats with chronically implanted cannulas were injected with 100 or 10 ng of substance P or 500 or 50 ng of muscimol into the region of the nucleus basalis magnocellularis. Control groups included vehicle-injected rats, a sham-operated group, a substance P 5-h delay group, and a substance P no-footshock group. Rats injected with 100 ng of substance P exhibited longer step-down latencies when tested 24 h later than did vehicle-injected rats. The retention latencies for rats in the substance P 5-h delay group did not differ from those of vehicle-injected animals, indicating that proactive effects on performance were not responsible for the effect. In contrast to injections of SP, injections of 500 or 50 ng of muscimol disrupted performance. However, in the absence of a delayed-injection control group, proactive effects cannot be ruled out.

Animals↗

Asymmetries of brain dopamine metabolism related to conditioned paw usage in the rat.

Concentrations of dopamine, serotonin, and some of their metabolites were analyzed by means of high-performance liquid chromatography in brain samples obtained from rats operantly conditioned to use one paw for water-reinforced lever pressing. In the first experiment, the side of paw usage was determined by physical constraint (forced-handedness condition), whereas in the second experiment the side of paw usage was not restricted (paw-preference condition). Differences in dopamine metabolism were detected between brain samples from the hemispheres located ipsi- and contralaterally to the side of paw usage. A higher dopamine metabolism (indicated by higher metabolite/transmitter ratios) was found in the amygdala ipsilateral to the paw used both under the forced-handedness and paw-preference condition. A higher level of dopamine in the contralateral septum was found in rats sacrificed immediately after 15 min of forced-handedness and an ipsilateral increase was found in rats analyzed 2 h after performance of this task. In addition, a higher dopamine metabolism in the ventral striatum, dorsal striatum, and amygdala was found in the forced-handedness and yoked controls groups than in rats analyzed 2 h after lever pressing. In the second experiment, rats in the paw preference group had a lower dopamine metabolism in the ventral and dorsal striatum, septum, and substantia nigra than did their yoked controls. These results show that changes in dopamine metabolism during conditioned lever pressing can be asymmetrical with respect to the side of paw usage, indicating that the dopamine neurons in the two brain hemispheres are asymmetrically involved in such behavioral tasks.

3,4-Dihydroxyphenylacetic Acid↗

Eye tracking dysfunction in Alzheimer-type dementia.

Performance on visual tracking tasks was measured in groups of Alzheimer-type dementia, pseudodementia of depression, and elderly normal controls. Smooth pursuit tracking errors were identified by counting the number of catch-up saccades required to compensate for failure of the smooth pursuit system. The group with Alzheimer-type dementia had significantly worse (p less than 0.0001) smooth pursuit tracking than either pseudodementia subjects or elderly normal controls. A strong correlation (r = 0.74, p less than 0.005) was found in Alzheimer patients between severity of visual tracking abnormality and severity of dementia.

Aged↗

Variables affecting eye tracking performance.

The effect of age and gender on eye tracking performance was studied in normal healthy subjects. Two measures of tracking performance, phase corrected cross-correlation coefficients and number of catch-up saccades were determined. The cross-correlation measures revealed a differential effect with the elderly men demonstrating significantly better tracking performance than elderly women. An aging effect was found in women and an aging trend in men using the catch-up saccade measure. Other variables influencing tracking performance, in addition to age and sex, were target speed and type of measure. Recognition of this differential effect largely explains the existing controversy as to whether age or sex variables influence tracking performance.

Age Factors↗

Mild cold exposure increases survival in rats with medial preoptic lesions.

High mortality rate in rats with large medial preoptic lesions discourage their use in studies of brain function. However, virtually all such animals (six out of seven) survived indefinitely if kept at an ambient temperature of 15 degrees C for 2 hours before and 10 to 12 hours after the lesions were made. Although these rats appeared otherwise healthy, they could not maintain normal both temperatures in short-term cold tests. In contrast, five of the nine rats kept at 25 degrees C died within 10 hours after the operation, and three more died within 5 days. Rats kept at 25 degrees C had a much higher incidence of cardiac arrhythmias than did rats kept at 15 degrees C, which may be responsible for their higher moratlity rates.

Animals↗

Persistent depression of rearing behavior in rats after extensive septal lesions.

Extensive septal lesions produced a persistent (76 days) reduction in rearing behavior which was not directly attributable to altered deprivation states, emotionality, activity levels, or competing behaviors and which occurred in familiar as well as various novel testing environments. Changes in visual, olfactory, or conspecific stimuli ameliorated or had no effect on the lesion effect. The results indicate that the septal area is importantly involved in normal rearing behavior and that lesion-induced alterations in responsiveness to some forms of stimulation may play a modulatory role in reduced rearing. It is also suggested that the septal area may constitute a portion of a neural system responsible for the initiation of this form of response.

Animals↗

Facilitation of tunnel maze performance by systemic injection of the neurokinin substance P.

The effect of peripheral injections of substance P (SP) on performance in two different configurations of an automated tunnel maze was examined in three experiments. In two experiments, the effect of pretrial SP injections (10-1000 micrograms/kg) on performance in the hexagonal and radial maze configuration of an automated tunnel maze was investigated. In the hexagonal maze, which measures activity, exploratory efficiency, habituation, and perimeter walking, injection of SP affected perimeter walking only. In the radial maze, SP produced a facilitation of measures of efficiency and long-term and short-term memory without affecting activity. In the third experiment, the effect of pre- and posttrial injections of SP (50 or 500 micrograms/kg) on performance in the radial maze configuration was tested. Again, pretrial injections of 500 micrograms of SP facilitated performance with respect to measures of efficiency and short- and long-term memory; 50 micrograms produced a weaker effect. Virtually no effect was seen with posttrial injections.

Animals↗