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J M Walker

Publications and source records attributed to J M Walker.

At least 109 records · Page 6Linked to original sources
PubMed1994

Regional variation in the ratio of sigma 1 to sigma 2 binding in rat brain.

In vitro binding experiments were performed to determine whether known subtypes of the putative sigma receptor exhibit a differential distribution across brain regions and species. Rat brains were dissected into nine regions, pooled, and used to prepare membranes for ligand binding studies. Whole guinea pig brains were prepared in an identical manner for comparison to rat. sigma 1 Receptors were labeled with [3H](+)-pentazocine. sigma 2 Receptors were labeled with [3H]1,3-di-o-tolylguanidine (DTG) in the presence of 1 microM dextrallorphan to mask sigma 1 sites. Non-specific binding was determined in the presence of 10 microM haloperidol. Filtration and scintillation spectroscopy provided the binding values. The experiment revealed marked variation in the ratio of sigma 2 to sigma 1 binding across brain regions ranging from a low of 1.63 in the hindbrain to 3.51 in the cerebellum, that result mainly differences in the density of the receptors. Scatchard analysis on membranes derived from the hindbrain and cortex suggested that the effects were due primarily to regional differences in densities of receptor subtypes rather than different affinities. Guinea pig brain showed a marked preponderance of sigma 1 receptors with a ratio (sigma 2/sigma 1) of 0.67. These findings demonstrate that sigma 1 and sigma 2 receptors are differentially distributed in rat brain.

Animals↗
PubMed1994

Effects of sigma ligands on rat cerebellar Purkinje neuron firing: an iontophoretic study.

The electrophysiological responses of rat cerebellar Purkinje neurons to selective sigma ligands applied iontophoretically was examined in urethane anesthetized male Sprague-Dawley rats. 1,3-Di-o-tolylguanidine (DTG), dextrallorphan (DEX), (+)-pentazocine((+)-PENT), (+)-3-(3-Hydroxyphenyl)-N-propylpiperidine ((+)-3-PPP), and the novel diamine BD1008, were ejected from multibarrel pipettes onto individual Purkinje cells. In some neurons, cell firing was inhibited following ejections of all compounds. These inhibitory effects were dose dependent and occurred without changes in spike amplitude or duration, thus ruling out local anesthetic effects as a mechanism. (+)-3-PPP and DEX increased firing rate in 27% and 14% (n = 15, n = 14, respectively) of cells studied. The results of this study indicate that sigma ligands significantly alter the spontaneous firing of Purkinje neurons, consistent with previous work suggesting motor effects of sigma ligands via the rubro-cerebellar circuitry.

Animals↗
PubMed1994

Cardiovascular performance and core temperature during transurethral prostatectomy.

Hemodynamic performance and core temperature were recorded during transurethral prostatectomy in 52 patients who were stratified according to cardiac symptom score and then randomized to undergo standard (31) or isothermic (21) transurethral prostatectomy. During the standard procedure ambient temperature (21C) irrigant was used, while during isothermic prostatectomy warmed irrigant at 38C was used to prevent heat loss from the bladder, and a warming blanket and humidifying filter were used to decrease cutaneous and respiratory heat loss. Core temperature decreased by a mean of 0.8C (95% confidence interval -0.9 to -0.7) during standard transurethral prostatectomy and by 0.27C (-0.4 to -0.15) during the isothermic procedure. The standard prostatectomy group showed a significant hemodynamic response consisting of increased mean arterial pressure (p < 0.0002), increased index of systemic vascular resistance (p < 0.0001), bradycardia (p < 0.02), and decreased Doppler indexes of stroke volume (p < 0.005) and cardiac output (p < 0.001). The isothermic transurethral prostatectomy group was hemodynamically stable. These differences between the groups suggest that rapid central cooling exerted a significant effect on perioperative hemodynamic performance during transurethral prostatectomy.

Aged↗
PubMed1994

Preconditioning in isolated superfused rabbit papillary muscles.

Preconditioning has only been demonstrated in arterially perfused myocardium. Our aim was to develop a model of preconditioning in isolated, superfused, isometrically contracting rabbit right ventricular papillary muscle. This would eventually allow us to evaluate isolated human muscles. Papillary muscles were suspended in an organ bath, superfused with oxygenated Tyrode solution, and field stimulated at 1 Hz. Muscles were assigned either to control or to preconditioning groups. Preconditioning was induced with 3 min of rapid pacing (3 Hz) with substrate-free hypoxic buffer and was followed by 15 min of reoxygenation with substrate. Subsequently, both groups were exposed to 45 min of substrate-free hypoxia followed by 120 min of reoxygenation with substrate. Preconditioning protected the myocardium with better recovery of developed force (50.6 +/- 6.7 vs. 27.4 +/- 4.2% of baseline developed force, P < 0.01). This effect could be blocked by 8-(p-sulfophenyl)theophylline (SPT) given during preconditioning at a dose that did not increase hypoxic damage in controls (percent developed force compared to baseline: preconditioned muscles + SPT = 30.9 +/- 2.8% and control muscles + SPT = 27.1 +/- 2.3%). In addition, pretreatment with (-)N6(2-phenylisopropyl)adenosine similarly protected the myocardium (49.5 +/- 5.5% recovery, P < 0.01). We conclude that isolated superfused muscles can be preconditioned. This preconditioning does not depend on coronary flow and involves activation of adenosine receptors.

Animals↗
PubMed1994

Myocardial protection after whole body heat stress in the rabbit is dependent on metabolic substrate and is related to the amount of the inducible 70-kD heat stress protein.

The aims of this study were to examine the effects of whole body heat stress and subsequent stress protein induction on glycolytic metabolism, mitochondrial metabolism, and calcium handling within the heart. The effect of heat stress on glycolytic and mitochondrial pathways was examined by measuring contractile performance in the presence of glucose and pyruvate, respectively. Calcium handling was assessed using force-interval relationships. Right ventricular papillary muscles taken from heat-stressed and control rabbit hearts were superfused with Kreb's solution containing either glucose or pyruvate and rendered hypoxic for 30 min. After reoxygenation, the greatest recovery of contractile function occurred in the heat-stressed muscles with pyruvate as substrate; there was, however, no difference in the force-interval relationship between the groups. The degree of contractile recovery was related to the content of the inducible 70-kD but not the 65-kD, heat stress protein. This study suggests that heat stress enhances the ability of rabbit papillary muscle to use pyruvate, but not glucose, after reoxygenation, and that the differences seen in contractility may be secondary to induction of the 72-kD stress protein.

Animals↗
PubMed1994

Adaptations during the stance phase of gait for simulated flexion contractures at the knee.

Adaptations in the stance phase of gait to knee flexion contractures simulated by a knee-ankle-foot orthosis were studied in 20 healthy women (mean age: 25 +/- 3.6 years). Stride characteristics, joint postures, floor reactions, and indwelling electromyographic activity of the lower gluteus maximus, vastus lateralis, long head of the biceps femoris, and soleus muscles were measured during walking with the orthosis, with and without contracture simulation. Simulated knee flexion contracture resulted in decreased stride length and velocity and increased forefoot weight bearing and flexion posture in stance. Increases were also seen in magnitude and/or duration of flexion floor reaction torques and gluteus maximus, vastus lateralis, and soleus muscle activity. The addition of a restriction of plantar flexion resulted in a further decrease in velocity and stride length and a small increase in hip extension posture. These results show that knee flexion contractures, simulated in healthy subjects, cause a decrease in gait function with a simultaneous increase in muscular demand.

Adaptation, Physiological↗
PubMed1994

Informatics for nurse managers: integrating clinical expertise, business applications, and technology.

Nurse managers must become familiar with computers, information systems, and nursing informatics in order to be competitive in the future. Knowledge and skills for identifying critical data elements, organizing the data into information, and presenting it for decision making can be learned through formal and informal education. After learning to use computers and to apply nursing informatics, nurse managers will be equipped to make more relevant, data-driven management decisions. This article describes how nurse managers can identify business applications relevant to management, learn how to use them, and put nursing informatics to work in very practical ways.

Clinical Competence↗
PubMed1993

Antinociceptive actions of cannabinoids following intraventricular administration in rats.

Intraventricular administration of 5 or 20 micrograms of the cannabinoids WIN55,212-2 and CP-55,940 markedly reduced rat's responses to noxious thermal stimuli in the tail-flick test; no significant effect was found at 1 micrograms. The dose-response curves were steep and monotonic, the onset was rapid, and the effect lasted about an hour at the highest dose. In contrast to their antinociceptive actions, WIN55,212-2 and CP-55,940 failed to alter the latency of righting reflexes at the highest dose, suggesting that motor impairment did not cause the decreased responsiveness to the thermal stimulus. Finally, an assessment of the biodistribution of intraventricularly administered [3H]WIN55,212-2 in brain and spinal cord at the time of maximal antinociception revealed that the drug was confined to the brain. The levels of [3H]WIN55,212-2 found in S3-S4, the location of the spinal mechanisms for tail-flick, were below the limit of detectability. Together, these findings provide direct evidence that the antinociceptive effects of cannabinoids are mediated, at least in part, by their actions in the brain.

Analgesics↗
PubMed1993

Sigma binding parameters in developing rats predict behavioral efficacy of a sigma ligand.

The relationship between sigma binding and the behavioral efficacy of a selective sigma ligand was examined in rats of varying ages (30, 45, 60, 75, 90, and 150 days old). Scatchard analyses of the binding of the sigma radioligand [3H]1,3-di-o-tolylguanidine ([3H]DTG) to brain membranes revealed significant age-related differences in binding to both crude synaptosomal and microsomal fractions. The functional significance of these developmental changes in sigma ligand binding was studied by determining the postural effects of rubral microinjections of DTG in age-matched littermates of rats used in the binding studies. The degree of dystonia produced by a single dose of DTG was significantly correlated with the amount of [3H]DTG bound to rat brain synaptosomal membranes at low but not at high concentrations. No significant correlation between binding to the microsomal fraction and drug efficacy was observed. These experimental results were in good agreement with predicted amounts bound as estimated from a Scatchard analysis of the data. The results suggest that sigma binding sites found in brain synaptosomal membranes are functional receptors involved in the control of movement and posture.

Animals↗