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Biomedical subjects

J M Walker

Publications and source records attributed to J M Walker.

At least 163 records · Page 9Linked to original sources
PubMed1990

Inhibitory effects of the kappa opiate U50,488 in the substantia nigra pars reticulata.

The effect of the selective kappa opiate agonist U50,488 on the firing rate of neurons of the substantia nigra pars reticulata (SNR) was investigated in a series of extracellular single unit recording experiments in rats. Intravenous administration of U50,488 produced a dose-related decrease in the spontaneous firing rate of SNR neurons, an effect that was reversed by naloxone in most cases. Iontophoretic application of the kappa agonist also inhibited the firing of SNR neurons, indicating a direct action of U50,488 in the SNR. U50,488 was particularly effective in inhibiting a local group of SNR neurons that exhibit increased firing in response to mechanical pressure. In separate experiments, it was determined that these pressure sensitive neurons (1) include nigrotectal and nigrothalamic cells, (2) are responsive to mild as well as painful levels of pressure, and (3) are not responsive to light flashes. This group of neurons may be a primary target of naturally occurring kappa selective opioids of the prodynorphinergic striatonigral pathway.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1990

Differential activation of protein kinase C isozymes by short chain phosphatidylserines and phosphatidylcholines.

To investigate the importance of the physical state of phospholipids for activation of protein kinase C, we have used short chain phospholipids, which, depending on their concentration, can exist as either monomers or micelles. We previously reported that short chain phosphatidylcholines (PC) can activate protein kinase C at concentrations that correlate with the critical micelle concentration of the activating lipid (Walker, J. M., and Sando, J. J. (1988) J. Biol. Chem. 263, 4537-4540). We have now expanded this work to short chain phosphatidylserine (PS) systems in order to examine the role of Ca2(+)-phospholipid interactions in the activation process. Short chain PS were synthesized from corresponding PC and purified by reverse-phase high pressure liquid chromatography. Use of the short chain system has revealed significant differences in the activation of type II and type III protein kinase C isozymes. The type II isozyme required Ca2+ in the presence of long chain PS vesicles; in the presence of the short chain phospholipid micelles (PC or PS), most of the activity was Ca2+ independent. Addition of diacylglycerol caused a small increase in type II activity in all phospholipid systems. In contrast, type III protein kinase C was Ca(+)-dependent in all of the lipid systems. The concentration of Ca2+ required to activate type III protein kinase C was independent of the phospholipid type despite large differences in the ability of these lipids to bind Ca2+. This isozyme required diacylglycerol only in the PC micelle system or with vesicles composed of long chain saturated PS. The presence of short chain PS micelles or long chain PS with unsaturated fatty acyl chains rendered this Ca2(+)-dependent protein kinase C virtually diacylglycerol independent. These results are consistent with a model in which type II protein kinase C requires Ca2+ primarily for membrane association, a requirement which is bypassed with the micelle system, whereas type III protein kinase C has an additional Ca2+ requirement for activity that does not involve Ca2(+)-phospholipid interactions.

Animals↗
PubMed1990

Metabolites of haloperidol display preferential activity at sigma receptors compared to dopamine D-2 receptors.

Haloperidol bound with equal affinity to sigma and dopamine D-2 receptors (KI = 2.8 nM). Compared to haloperidol, its carbonyl-reduced metabolite bound to sigma receptors with nearly equal affinity. However, reduced haloperidol bound to dopamine receptors with 85-fold lower affinity compared to haloperidol (KI = 239 nM). The chlorophenyl-hydroxy-piperidine metabolite of haloperidol lacked affinity for dopamine receptors, but bound with moderate affinity to sigma receptors (KI = 326 nM). The carboxylic acid metabolite lacked affinity for either receptor. Like haloperidol, (+)-pentazocine, and 1,3-di-o-tolylguanidine, reduced haloperidol potently inhibited the phosphoinositide response to muscarinic agonists in rat brain synaptoneurosomes, an assay which monitors sigma agonist activity. This metabolite also produced a dystonic alteration of head position in rats when microinjected into the red nucleus. However, unlike observations with haloperidol and other sigma ligands, this effect was associated with pathological changes in the red nucleus. Therefore, it cannot be attributed to sigma receptor interactions with certainty. These findings suggest that administration of haloperidol results initially in effects mediated through both dopamine and sigma receptors, but as metabolism proceeds the sigma actions would be expected to decline at a significantly slower rate than the dopaminergic actions.

Animals↗
PubMed1990

A human metallothionein pseudogene containing AG/CT repetitive elements.

A lambda phage recombinant clone, 25 S, which contains a 15.5-kb EcoRI human genomic DNA fragment, has been characterized. Restriction mapping and Southern blot hybridization indicated a 3.0-kb HindIII fragment containing metallothionein (MT)-like sequences. Several interesting features were found upon comparison of this nucleotide sequence with that of other human MT genes: (1) sequences representing the 5' regulatory region, the 5' untranslated region, and the first exon are not contained in the 3.0-kb HindIII fragment; (2) the coding sequence of the second exon (amino acids 10-31 encoding a portion of the beta-domain of the MT protein) has 11 amino acid changes out of a total of 21, whereas, the third exon (amino acids 32-61, representing the complete alpha-domain of the MT protein) has only 4 amino acid substitutions; however, all cysteine residues are conserved; (3) this MT-like gene retains intron sequences and processing signals; (4) Southern blot analysis of human genomic DNA indicated this MT-like gene is located on a 10.5-kb EcoRI genomic DNA fragment; and (5) unusual AG/CT-rich repetitive elements are located within the second intron and upstream of the second exon of this MT-like gene. This gene is not expressed in response to metal induction in two human cell lines, as shown by northern blot analyses. Based on these observations, this MT-like gene represents a unique nonprocessed pseudogene of the human MT multigene family.

Amino Acid Sequence↗
PubMed1990

Effects of U50,488H on locomotor activity in the hamster.

Two experiments investigated the effects of the specific kappa opiate agonist, U50,488 on locomotor activity in the golden Syrian hamster. In Experiment 1, the effects of U50,488 were found to be dose-related, with a 1 mg/kg dose eliciting hyperactivity and a 10 mg/kg dose eliciting hypoactivity. In Experiment 2, the dual effects of U50,488 on locomotor activity were shown to be naloxone (1 mg/kg) reversible. It is suggested that the effects of U50,488 on activity are consistent with the reported dual opposing influences of kappa agonists in the substantia nigra pars compacta and pars reticulata.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1990

Drug specificity of pharmacological dystonia.

Three (+)-benzomorphans that bind to sigma receptors produced dystonia in a dose-related manner when microinjected into the red nucleus of rats. Two lines of evidence suggest that these effects were related to the sigma-binding properties of the compounds. First, the behavioral potency of the (+)-benzomorphans and other active sigma compounds correlated highly with their affinities for [3H]1,3-di-o-tolylguanidine-labelled sigma receptors in the rat brain (r = .94). Second, similar intrarubral injections of non-sigma ligands were without effect: various vehicles, a structurally related (+)-opiate with no affinity for sigma receptors, and selective dopaminergic and serotonergic compounds failed to significantly alter the normal posture of rats. The only ligand in this study that binds with high affinity to sigma receptors, but failed to elicit torsional head movements was (+)-[3-(3-hydroxyphenyl)-N-(1-propyl)piperidine] [(+)-3PPP], a ligand with mixed activity at sigma and dopamine receptors. Since (+)-3PPP failed to produce an effect on its own and also failed to attenuate the dystonia produced by another sigma ligand (DTG), it may interact with a non-sigma mechanism or with a different sigma receptor type from the other compounds.

Animals↗
PubMed1990

The effect of foot-shock on the noxious-evoked activity of neurons in the rostral ventral medulla.

The effect of foot-shock on the noxious-evoked activity of rostral ventral medulla (RVM) neurons was investigated in anesthetized rats. Neurons were first classified as on-cells if they fired faster during noxious pinch or as off-cells if they fired slower. Exposure to a 20 Hz squarewave at 2.5 or 3.5 mA administered for two minutes decreased the noxious-evoked responses of both cell types: on-cells showed a reduced increase in firing, while off-cells showed a reduced decrease in firing. The results indicate that stress-induced analgesia is accompanied by alterations in the activity of on- and off-cells.

Action Potentials↗
PubMed1990

The nursing management of elderly patients with pain in the community: study and recommendations.

This study is designed to identify factors which influence quality of life for elderly people suffering from painful conditions. It is based upon a theoretical model of control in which mood state is used as the indicator of coping. One hundred and ninety elderly patients took part in semi-structured interviews about their pain and coping experiences, and data were also collected from their nurses in the community. Multivariate statistical analysis revealed that the key determinants of mood were having regrets about the past, being occupied, perceived level of pain control, additional personal problems (notably bereavement) and feeling informed about the painful condition. Active personal coping strategies were identified as more therapeutic than passive strategies. Nurses' data revealed that pain complaints were associated with perceived exaggeration. Few nurses used formal pain assessment. Recommendations for the management of persistent pain in the community are given.

Adaptation, Psychological↗
PubMed1990

Permanent transvenous pacing after a Mustard procedure.

We report the case of a 20-year-old man born with transposition of the great arteries who underwent emergency balloon septostomy and subsequently a Mustard procedure. When aged 20 years, he had several syncopal attacks due to sinoatrial disease for which he was simply and successfully paced transvenously in VVI mode.

Adult↗
PubMed1990

Urinary growth hormone excretion as a screening test for growth hormone deficiency.

Overnight urinary growth hormone secretion was measured by an immunoradiometric assay incorporating commercially available reagents, in 41 normal prepubertal school-children from three age groups: 3-5 years, 6-7 years, and 9-10 years. There was no significant difference between the groups expressing the results as total microU/specimen and so they have been combined to provide a prepubertal reference range of 2.25-10.50 microU/night. Prepubertal children with growth hormone deficiency who had not been receiving growth hormone treatment for two days had overnight urinary growth hormone concentrations well below this range. Urinary growth hormone was assayed in 49 children undergoing investigation for short stature with conventional provocative testing, and those shown to have growth hormone deficiency had correspondingly low overnight urinary growth hormone concentrations. There was, in addition, a strong correlation between overnight urinary growth hormone concentrations and peak serum response to provocation. This simple urine assay may provide a useful screening test for growth hormone deficiency.

Adolescent↗
PubMed1990

Dipyridamole magnetic resonance imaging: a comparison with thallium-201 emission tomography.

Limitation of space and motion artefact make magnetic resonance imaging during dynamic exercise difficult. Pharmacological stress with dipyridamole can be used as an alternative to exercise for thallium scanning. Forty patients with a history of angina and an abnormal exercise electrocardiogram were studied by dipyridamole thallium myocardial perfusion tomography and dipyridamole magnetic resonance wall motion imaging with a cine gradient refocused sequence. Images for both scans were obtained in the oblique horizontal and vertical long axis and short axis planes before and after pharmacological stress with dipyridamole. The myocardium was divided into nine segments for direct comparison of perfusion with wall motion. Segments were assessed visually into grades--normal, hypokinesis or reduced perfusion, and akinesis or very reduced perfusion. After dipyridamole there were reversible wall motion abnormalities in 24 (62%) of 39 patients with coronary artery disease and 24 (67%) of 36 patients with reversible thallium defects. The site of wall motion deterioration was always the site of a reversible thallium defect. Thallium defects affecting more than two segments were always associated with wall motion deterioration but most single segment thallium defects were undetected by magnetic resonance imaging. There was a significant correlation between detection of wall motion abnormality, the angiographic severity of coronary artery disease, and the induction of chest pain by dipyridamole. There were no significant differences in ventricular volume or ejection fraction changes after dipyridamole between the groups with and without detectable reversible wall motion changes but the normalised magnetic resonance signal intensity of the abnormally moving segments was significantly less than the signal intensity of the normal segments. In nine patients the change was apparent visually and it was maximal in the subendocardial region. Magnetic resonance imaging of reversible wall motion abnormalities in patients with coronary artery disease is feasible during pharmacological stress with dipyridamole and may be associated with a reduced magnetic resonance signal. The failure to show wall motion abnormalities in all cases of reversible thallium defects may be because the defect was small or because dipyridamole caused perfusion defects in the absence of myocardial ischaemia.

Adult↗
PubMed1990

Effect of an unrestricted knee-ankle-foot orthosis on the stance phase of gait in healthy persons.

Twenty healthy women (mean age: 25 +/- 3.6 years) were studied for postural adaptations produced when walking with unrestricted knee-ankle-foot orthoses. Stride characteristics, motion, floor reaction forces and their torques, and indwelling electromyographic activity of the lower gluteus maximus, as well as the long head of the biceps femoris, vastus lateralis, and soleus muscles were all measured during barefoot and orthosis walking. Wearing a knee-ankle-foot orthosis increased stride length and decreased cadence and stance duration. The subjects walked in slightly more plantar flexion, knee flexion, and hip flexion, while increasing the duration of the corresponding floor reaction torques, resulting in an activity increase of the vastus lateralis, soleus, and biceps femoris muscles. These results, obtained in healthy subjects, show a definite effect of an unrestricted knee-ankle-foot orthosis on gait.

Adult↗
PubMed1990

Conditions for the extraction of protease-free LMG proteins from calf thymus.

Calf thymus LMG proteins are known to be susceptible to a wide variety of chromatin-associated proteases. We have investigated the use of different inhibitors to protect LMG chromosomal proteins from proteolytic degradation. In this work we have developed a preparative method for the extraction of LMG proteins from purified chromatin which provides an LMG protein extract devoid of proteolytic activity.

Animals↗