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Biomedical subjects

J M Walker

Publications and source records attributed to J M Walker.

At least 55 records · Page 3Linked to original sources
PubMed1999

Intrathecal cannabinoid administration suppresses noxious stimulus-evoked Fos protein-like immunoreactivity in rat spinal cord: comparison with morphine.

AIM: To determine whether cannabinoids suppress noxious stimulus-evoked Fos protein-like immunoreactivity (FLI) through direct actions at the spinal level. METHODS: Rats were implanted with intrathecal (ith) catheters at least one week prior to evaluation in the formalin test. Effects of the cannabinoid agonist, CP55,940 (80 micrograms ith) on formalin pain and FLI in rat spinal cord were compared with that of the prototypic narcotic analgesic, morphine (20 micrograms ith). CP55,940 suppressed pain behavior and FLI induced by intraplantar formalin. The cannabinoid suppressed Fos in the neck region of the dorsal horn and in the ventral horn, but not in the nucleus proprius. The efficacy of the cannabinoid in suppressing FLI in these laminae and pain behavior was comparable to morphine administered via the same route. However, only morphine suppressed FLI in the superficial dorsal horn relative to vehicle treatment. CONCLUSION: Cannabinoids suppress nociceptive processing, in part, through actions at the spinal level. However, morphine showed greater potency and efficacy than CP55,940 in suppressing formalin-induced FLI following spinal administration.

Analgesics↗
PubMed1998

Evidence for a role of endogenous cannabinoids in the modulation of acute and tonic pain sensitivity.

The competitive CB1 receptor antagonist SR141716A was used to test the hypothesis that endogenous cannabinoids modulate tonic pain sensitivity. Pretreatment with the antagonist significantly enhanced the response to a chemical nociceptive stimulus in the formalin test. Postreatment with the antagonist 5 min following the induction of tonic pain produced hyperalgesia during the tonic phase only. These findings suggest that endogenous cannabinoids serve naturally to modulate the maintenance of pain following repeated noxious stimulation.

Acute Disease↗
PubMed1998

Cannabinoid modulation of wide dynamic range neurons in the lumbar dorsal horn of the rat by spinally administered WIN55,212-2.

The effects of spinally administered cannabinoids on nociceptive responses of wide dynamic range (WDR) neurons in the lumbar spinal cord were investigated in urethane-anesthetized rats. Noxious thermal stimulation was applied with a Peltier device to regions of the ipsilateral hindpaw corresponding to the receptive fields of isolated neurons. WIN55,212-2 (100 microg, i.t.), applied topically on the dorsal spinal surface, suppressed noxious heat-evoked activity in spinal WDR neurons. By contrast, responsiveness was unchanged following administration of either vehicle or WIN55,212-3, the receptor-inactive enantiomer. WIN55,212-2, administered intrathecally to separate rats, produced antinociceptive effects in the tail-flick test with a time course and efficacy that paralleled the suppression of noxious heat-evoked activity. These results suggest that cannabinoid modulation of spinal nociceptive processing involves direct actions in the spinal dorsal horn and is related to the antinociceptive effects of intrathecally administered cannabinoids.

Animals↗
PubMed1998

Fatty acid amide hydrolase is located preferentially in large neurons in the rat central nervous system as revealed by immunohistochemistry.

The distribution in the rat brain of fatty acid amide hydrolase (FAAH) an enzyme that catalyzes the hydrolysis of the endogenous cannabinoid anandamide was studied by immunohistochemistry. An immunopurified, polyclonal antibody to the C terminal region of FAAH was used in these studies. The large principal neurons, such as pyramidal cells in the cerebral cortex, the pyramidal cells the hippocampus, Purkinje cells in the cerebellar cortex and the mitral cells in the olfactory bulb, showed the strongest FAAH immunoreactivity. These FAAH-containing principal neurons except the mitral cells in the olfactory bulb are in close proximity with cannabinoid CB1 receptors as revealed by our previous immunohistochemical study. Moderately or lightly stained FAAH-containing neurons were also found in the amygdala, the basal ganglia, the deep cerebellar nuclei, the ventral posterior nuclei of the thalamus, the optic layer and the intermediate white layer of the superior colliculus and the red nucleus in the midbrain, and motor neurons of the spinal cord. These data demonstrate that FAAH is heterogeneously distributed and this distribution exhibits considerable, although not complete, overlap with the distribution of cannabinoid CB1 receptors in rat brain.

Amidohydrolases↗
PubMed1998

Local effects of cannabinoids on spontaneous activity and evoked inhibition in the globus pallidus.

The globus pallidus has been identified as a site of action for the motor effects of cannabinoids. A previous report from this laboratory demonstrated that systemic administration of the potent and selective cannabinoid receptor agonist (R)-(+)-[2,3-dihydro-5-methyl-3-[(4-morpholinyl) methyl]pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl] (1-napthalenyl) methanone (WIN 55,212-2) inhibits rat pallidal neurons and reverses the inhibition of pallidal activity produced by electrical stimulation of the striatum. The current study used in vivo single unit electrophysiology/micropressure ejection to investigate whether the effects of cannabinoids on spontaneous activity and evoked inhibition in the globus pallidus are locally mediated. Micropressure ejection of either WIN 55,212-2 or CP 55,940 into the globus pallidus inhibited spontaneous activity in the globus pallidus. Local administration of the cannabinoid receptor antagonist, N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazo le-carboxamide (SR141716A), did not produce an effect on its own but blocked the effect of WIN 55,212-2 on spontaneous activity of pallidal neurons. The decrease in pallidal activity produced by WIN 55,212-2 was not blocked by coadministration of bicuculline, suggesting this effect is independent of GABA(A) receptors. Micropressure ejection of cannabinoids into the globus pallidus did not reverse the inhibitory effect of striatal stimulation in the globus pallidus. Taken together, these findings suggest that pallidal cannabinoid receptors mediate an inhibition of spontaneous activity in the globus pallidus.

Animals↗
PubMed1998

Cannabinoid effects in basal ganglia in a rat model of Parkinson's disease.

Cannabinoid receptors in the brain are highly concentrated in the basal ganglia, which is in accordance with their well known effects on motor behavior. In this study, rats with 6-hydroxydopamine lesions of the nigrostriatal pathway were implanted with cannulae in the striatum, globus pallidus and substantia nigra. The effect of unilateral infusion of the potent cannabinoid agonist CP55,940 on turning behavior was studied for each structure. Lesioned animals responded to intrapallidal and intrastriatal administration of the cannabinoid in a manner that was similar to that of unlesioned animals. However, lesioned animals showed greater contralateral turning in response to the cannabinoid infusions in the substantia nigra than unlesioned animals.

Animals↗
PubMed1998

Ipsilateral turning behavior induced by unilateral microinjections of a cannabinoid into the rat subthalamic nucleus.

The subthalamic nucleus contains cannabinoid receptors and cannabinoid receptor mRNA. However, the role of cannabinoid receptors in this nucleus has not been examined. In order to investigate the functional role of cannabinoid receptors in the rat subthalamic nucleus, turning activity was observed following unilateral microinjection of the synthetic cannabinoid CP 55,940. CP 55,940 (10 microg) induced ipsilateral turning. This effect was blocked by coadministration of the cannabinoid receptor antagonist SR141716A (5 microg). These results suggest that cannabinoid receptors in the subthalamic nucleus mediate an inhibition of motor activity.

Animals↗
PubMed1998

Cannabinoid receptor-mediated inhibition of the rat tail-flick reflex after microinjection into the rostral ventromedial medulla.

Systemic administration of cannabinoids produce profound antinociception in rodents. The purpose of this study was to examine the contribution of the rostral ventromedial medulla (RVM) to cannabinoid-mediated inhibition of the tail-flick reflex. Rats received direct injections of two selective cannabinoid agonists, WIN55,212-2 and HU210, into the RVM. Both compounds significantly elevated tail-flick latencies by over 50%. WIN55,212-3, the inactive enantiomer, was without effect. Furthermore, co-administration of the selective cannabinoid receptor antagonist, SR141716A greatly attenuated the antinociception produced by HU210. Finally, injections of WIN55,212-2 outside the region of the RVM did not affect tail-flick latencies. These results demonstrate that the cannabinoid receptor system participates in the descending control of nociception and raise the possibility that actions of endogenous cannabinoids in the RVM may modulate nociceptive responsiveness.

Analgesics↗
PubMed1998

Effects of intrapallidal cannabinoids on rotational behavior in rats: interactions with the dopaminergic system.

The effect of unilateral intrapallidal cannabinoid receptor stimulation on rotational behavior in rats was explored. The potent cannabinoid agonist CP55,940 (5 microg/0.5 microl) induced ipsilateral turning when microinjected unilaterally into the globus pallidus. The D2 dopamine agonist quinpirole reversed this ipsilateral rotation but failed to affect motor behavior on its own. Finally, the D1 dopamine agonist SKF 82958 inhibited movement when administered into the globus pallidus, and this effect was not additive with CP55,940.

Animals↗
PubMed1998

Effects of intrastriatal cannabinoids on rotational behavior in rats: interactions with the dopaminergic system.

The effect of unilateral intrastriatal cannabinoid receptor stimulation on rotational behavior in rats was explored. The potent cannabinoid agonist CP 55,940 (5 microg/0.5 microl) induced contralateral turning when microinjected unilaterally into the striatum. The D2 dopamine agonist quinpirole reversed this contralateral rotation but failed to affect motor behavior on its own. Finally, the D1 dopamine agonist SKF 82958 inhibited movement when administered into the striatum and this inhibition was reversed by co-administration of the cannabinoid agonist. Surprisingly, microinjections of the cannabinoid agonist into the striatum induced movement through activation of the striatonigral pathway and/or inhibition of the striatopallidal pathway, while the D1 dopamine agonist produced the opposite effect.

Animals↗
PubMed1998

Curricular content on urinary incontinence in entry-level physical therapy programmes in three countries.

BACKGROUND AND PURPOSE: Urinary incontinence (UI) is a significant psychological, social and healthcare problem across the lifespan. Although there is evidence of physical therapy (PT) efficacy, no literature was located pertaining to UI in PT curricula. The aim was to compare curricular content on UI (of non-neuropathic origin) in PT programmes in Canada, the UK and the USA. The study subjects were PT educators in entry-level programmes. METHODS: All Canadian PT programmes (13) were surveyed. Stratification was used to make random samples of PT programmes: 50% of UK (13/26) and 50% of USA (69/136). A questionnaire was used to obtain information on: degree level, programme length, specific courses, time allotted, UI topics, teaching method(s), the professional teaching patients with UI and reasons for non-inclusion in the study. One follow-up letter was sent. Results are presented as frequencies and percentages. RESULTS: Overall, the response rate was 62.8%; country response rates were: Canada 92.3%; UK 76.9% and USA 53.6%. UI was taught in 80% of Canadian, 90% of UK (which gave the most time to teaching on UI: 70% > 60 minutes) and 78.4% of USA PT programmes. Kegel exercises were taught in all three countries (> 81.1%) and electrical stimulation in > 65%. Theory only was the primary method of teaching in all countries (> 64.9%). Physical therapists were reported to have a major role in treating patients with UI (Canada > 75%; UK 100%; USA 70.3%). CONCLUSIONS: With Kegel exercises and electrical stimulation taught in two-thirds of all programmes physical therapy graduates may have some knowledge of UI management. However, for the UK and USA programmes data are from only 38.5% and 27% respectively. As the common method of teaching on UI was by theory only, graduating physical therapists may lack the clinical skills to apply assessment and treatment techniques.

Canada↗
PubMed1998

An antiviral protein from Bougainvillea spectabilis roots; purification and characterisation.

An antiviral protein active against mechanical transmission of tomato spotted wilt virus was identified in the root tissues of Bougainvillea spectabilis Willd. Bougainvillea Antiviral Protein I (BAP I) was purified to apparent homogeneity from the roots of Bougainvillea by ammonium sulphate precipitation, CM- and DEAE-Sepharose chromatography and reverse phase HPLC. BAP I is a highly basic protein (pI value > 8.6) with an Mr of 28,000. The N-terminal sequence of BAP I showed homology with other plant antiviral proteins. Preliminary tests suggest that purified BAP I is capable of interfering with in vitro protein synthesis.

Amino Acid Sequence↗
PubMed1998

Immunohistochemical distribution of cannabinoid CB1 receptors in the rat central nervous system.

Immunohistochemical distribution of cannabinoid receptors in the adult rat brain was studied using specific purified antibodies against the amino-terminus of the CB1 receptor. Our results generally agree well with the previous studies using CB1 receptor autoradiography and messenger RNA in situ hybridization. However, because of its greater resolution, immunohistochemistry allowed identification of particular neuronal cells and fibers that possess cannabinoid receptors. CB1-like immunoreactivity was found in axons, cell bodies and dendrites, where it appeared as puncta in somata and processes. Both intensely and moderately or lightly stained neurons were observed. The intensely stained neurons were dispersed and only occur in cortical structures including hippocampal formation and olfactory bulb. Moderately or lightly stained neurons were found in caudate-putamen and amygdala. In the hippocampal formation only intensely stained neurons were observed. The cell bodies of pyramidal neurons in CA1 and CA3 fields appeared to be unstained but surrounded by a dense plexus of immunoreactive fibers. The granule cells in the dentate area were also immunonegative. Many intensely stained neurons were located at the base of the granule cell layer. CB1-like immunoreactive neurons and fibers were also found in the somatosensory, cingulate, perirhinal, entorhinal and piriform cortices, in claustrum, amygdaloid nuclei, nucleus accumbens and septum. Beaded immunoreactive fibers were detected in periaqueductal gray, nucleus tractus solitarius, spinal trigeminal tract and nucleus, dorsal horn and lamina X of the spinal cord. A triangular cap-like mass of immunoreactivity was found to surround the basal part of the Purkinje cell body in the cerebellum. Only small, lightly stained cells were found in the molecular layer in the cerebellum close to the Purkinje cell layer. The CB1 receptor is widely distributed in the forebrain and has a more restricted distribution in the hindbrain and the spinal cord. It appears to be expressed on cell bodies, dendrites and axons. According to the location and morphology, many, but not all, CB1-like immunoreactive neurons appear to be GABAergic. Therefore, cannabinoids and cannabinoid receptors may play a role in modulating GABAergic neurons.

Animals↗
PubMed1998

Prolonging the delayed phase of myocardial protection: repetitive adenosine A1 receptor activation maintains rabbit myocardium in a preconditioned state.

OBJECTIVES: This study was designed to examine whether the myocardium can be maintained in a protected state by extending the delayed phase of cardioprotection with chronic, intermittent adenosine A1 receptor activation. BACKGROUND: Several recent studies have explored the temporal characteristics of the protective effects of ischemic preconditioning. Two distinct phases of myocardial protection have been described: the short-lived immediate phase, or "classic" preconditioning, and the delayed phase, or "second window of protection" (SWOP). Previous studies have examined the potential for extending the duration of classic preconditioning by repeated application of the preconditioning stimulus. Pretreatment with either multiple episodes of ischemia or continuous infusion of a selective adenosine A1 receptor agonist, 2-chloro-N6-cyclopentyladenosine (CCPA), resulted in attenuation of the protective effects of preconditioning, implying downregulation of the receptors involved in triggering classic preconditioning. METHODS: Male New Zealand White rabbits were treated with repeated intravenous boluses of CCPA, 100 microg/kg body weight, or 0.9% saline at 48-h intervals. Forty-eight hours after the fifth dose (day 10), the animals were anesthetized and subjected to 30 min of coronary occlusion, followed by 120 min of reperfusion. Infarct size was determined as a percentage of myocardial risk volume using tetrazolium staining. To further explore whether the rabbits had developed tolerance to the effects of adenosine A1 receptor activation, a subgroup of animals were treated with a further bolus of CCPA, 100 microg/kg, at the end of the reperfusion period, and the hemodynamic response was monitored for 10 min before excision of the heart. RESULTS: Pretreatment with intermittent doses of CCPA resulted in a 42% reduction in the infarct to risk ratio compared with vehicle pretreatment (26.6+/-3.7% vs. 45.9+/-5.5%, p < 0.01). Furthermore, CCPA treatment at the end of reperfusion resulted in identical hypotension and bradycardia in both groups. CONCLUSIONS: We conclude that rabbits can be maintained in a protected state against myocardial infarction by repeated activation of adenosine A1 receptors, with no evidence of tachyphylaxis to the infarct-limiting or hemodynamic effects of CCPA. This finding suggests that adenosine A1 receptor activation may hold promise as a new approach to long-term cardioprotection.

Adenosine↗
PubMed1998

Pathomechanics and classification of cartilage lesions, facilitation of repair.

Joint forces have a high potential to promote degenerative changes in articular cartilage. Researchers have not yet developed a material that simulates natural articular cartilage, and replacement procedures have finite lives. In all patients, regardless of diagnostic category, the impact of rehabilitative procedures on the integrity and health of articular cartilage should be a consideration. In this paper, I will review why articular cartilage breaks down, how cartilage lesions are classified in vitro and in vivo, as well as cartilage's capacity for repair and repair enhancement. The primary focus will be on processes and procedures that impact physical therapy. Review sources included common computer-based search instruments and literature in all languages. This research showed that most studies have been conducted on animals, which differ in important respects from humans. Such studies, however, provide guidelines for physical therapists. Unloading and overloading are detrimental to articular cartilage. Research indicates value in controlled, progressive regimes that alternate load and non-load conditions.

Animals↗
PubMed1997

Cloning and sequencing of aspartate aminotransferase from Thermus aquaticus YT1.

A 39-base oligonucleotide "guessmer" probe, based on partial N-terminal sequence analysis of the aspartate aminotransferase purified from Thermus aquaticus strain YT1, was used to screen a genomic library prepared from T. aquaticus DNA. A 1842 bp DNA fragment was isolated that proved to contain the coding sequence for the aspartate aminotransferase. The gene is 1152 bases long and codes for a protein of 383 amino acid residues. The amino acid sequence obtained showed 88.7%, 45.1% and 32.9% identity of sequence with those of thermostable aspartate aminotransferases from T. thermophilus, Bacillus YM2, and Sulfolobus solfataricus, respectively. It showed 39.1% identity with one of the gene products tentatively identified as aspartate aminotransferase from the methanogenic archaebacterium Methanococcus jannaschii. Neither the amino acid compositions nor the aligned amino acid sequences provides any obvious clue as to the origin of thermal stability in this group of enzymes.

Amino Acid Sequence↗