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J M Walker

Publications and source records attributed to J M Walker.

At least 91 records · Page 5Linked to original sources
PubMed1996

Suppression of noxious stimulus-evoked expression of Fos protein-like immunoreactivity in rat spinal cord by a selective cannabinoid agonist.

In rats, cannabinoids inhibit behavioral responses to noxious stimulation with a potency and efficacy similar to that of morphine. However, because cannabinoids depress motor function, it has not been possible to state beyond any doubt that these effects were related to a dampening of noxious sensory input. Therefore, c-fos immunocytochemistry was used to explore the possibility that cannabinoids reduce behavioral responses to noxious stimuli by decreasing spinal processing of nociceptive inputs. Rats received systemic injections of the potent and selective cannabinoid agonist WIN 55,212-2, the receptor-inactive enantiomer WIN 55,212-3 or vehicle prior to observations in a model of tonic pain, the formalin test. As demonstrated previously, plantar injections of formalin led to lifting and licking of the injected paw, with two peaks of activity occurring at 5 and 30 min after injection. The cannabinoid agonist suppressed these pain responses and produced a reduction in mobility. Immunocytochemical processing of sections with an antibody to the Fos protein revealed that the cannabinoid markedly suppressed pain-evoked c-fos expression in the superficial and neck regions of the spinal dorsal horn, but not in the nucleus proprius. Decreased expression of c-fos also occurred in the ventral horn. The specificity of this effect and its probable mediation by cannabinoid receptors are suggested by three findings: (i) the suppression by the drug of both behavioral and immunocytochemical responses to pain was dose-dependent; (ii) neither the behavioral nor the immunocytochemical response to the noxious stimulus was significantly affected by the receptor-inactive enantiomer of the agonist; (iii) animals rendered tolerant to cannabinoids by repeated injections of the agonist showed reduced responses to the drug. These findings suggest that cannabinoids inhibit the spinal processing of nociceptive stimuli and support the notion that endogenous cannabinoids may act naturally to modify pain trnasmission within the central nervous system.

Animals↗
PubMed1996

The amino-terminus of phytochrome A contains two distinct functional domains.

The N-terminus of phytochrome A is important for the structural integrity and biological activity of the photoreceptor. Mutational analysis of the N-terminus by two different strategies created two distinct photoreceptors, one inactive and the other hyperactive when expressed in transgenic tobacco, suggesting that this region has multiple functional domains. To identify critical residues within this N-terminal region, a series of smaller deletions of oat phytochrome A were created, designated NB (delta49-62), NC (delta6-47), ND (delta7-21), NE (delta2-5), and NF (delta6-12), and compared with a previously characterized deletion mutant NA (delta7-69) and full-length oat phytochrome A. Using photochemical properties as a measure of chromoprotein structure, it was found that the region between residues 13 and 62 was important for the spectral integrity of the photoreceptor. These deletion mutants were also biologically inactive when expressed in both mature tobacco plants and seedlings grown under continuous far-red or red light. In contrast, deletion of the serine-rich region between residues 6 and 12 did not alter the photochemical properties but did produce a hyperactive photoreceptor, indicating this region may be involved in down-regulating phytochrome A activity. The data show that the N-terminus of phytochrome A contains two functional domains, one necessary for conformational stability and biological activity (residues 13-62), and the other involved in attenuating phytochrome responses (residues 6-12).

Amino Acid Sequence↗
PubMed1996

Systemic sclerosis associated with right ventricular cardiomyopathy.

Systemic sclerosis is an uncommon multisystem disorder of unknown aetiology which predominantly affects the skin. Cardiac involvement, which is far more common than was originally realized, may affect any part of the heart but most frequently affects the left ventricular myocardium. Right ventricular dysfunction is usually associated with pulmonary vascular disease. We report a case of systemic sclerosis associated with right ventricular cardiomyopathy in whom pulmonary artery pressures were normal.

Adult↗
PubMed1995

Physical withdrawal in rats tolerant to delta 9-tetrahydrocannabinol precipitated by a cannabinoid receptor antagonist.

Tolerance to delta 9-tetrahydrocannabinol (delta 9-THC) was produced in rats by twice daily injections (15 mg/kg i.p.) for 6.5 days. Administration of the cannabinoid antagonist SR141716A (i.p. or i.c.v.) induced a profound precipitated withdrawal syndrome in delta 9-THC-tolerant animals. The syndrome was characterized by a disorganized pattern of constantly changing brief sequences of motor behavior. Autonomic signs were not evident. THC-tolerant animals that were treated with vehicle remained quiet throughout the observation period.

Animals↗
PubMed1995

Effects of a cannabinoid on spontaneous and evoked neuronal activity in the substantia nigra pars reticulata.

Single unit electrophysiology was used to explore the role of cannabinoid receptors in the substantia nigra pars reticulata. Intravenous and intraperitoneal injections of the potent and selective synthetic cannabinoid (R)-(+)-[2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]pyrrolo[1,2,3- de]-1,4-benzoxazin-6-yl](1-naphthalenyl) methanone (WIN 55,212-2) produced modest but significant increases in the spontaneous firing rate of neurons in the substantia nigra pars reticulata. In a second set of experiments, WIN 55,212-2 (up to 1.0 mg/kg i.v.) antagonized the inhibition of firing produced in the substantia nigra pars reticulata by electrical stimulation of the striatum. The pharmacological specificity of this effect was demonstrated using the inactive enantiomer WIN 55,212-3. The possibility that WIN 55,212-2 exerts its effects by regulating gamma-aminobutyric acid (GABA) release from striatonigral fibers was suggested by the observation that bicuculline (up to 0.5 mg/kg i.v.) reversed the effect of striatal stimulation. It thus appears that cannabinoid receptors on striatonigral neuron terminals may regulate movement by disinhibiting the activity of substantia nigra pars reticulata neurons, perhaps by inhibiting the release of GABA into the substantia nigra pars reticulata.

Analgesics↗
PubMed1995

Stimulation of rat striatal tyrosine hydroxylase activity following intranigral administration of sigma receptor ligands.

The effects of sigma ligands on turning behavior and striatal tyrosine hydroxylase activity were determined following microinjection of two chemically dissimilar sigma ligands into the rat substantia nigra. Striatal tyrosine hydroxylase activity was monitored by measuring the amount of 3,4-dihydroxyphenylalanine (DOPA) formed following inhibition of DOPA decarboxylase activity with m-hydroxybenzylhydrazine (NSD-1015). The sigma ligands, 1,3-di-o-tolylguanidine (DTG) and (-)-deoxy-N-benzylnormetazocine, produced a significant increase both in contralateral turning and in tyrosine hydroxylase activity. The DTG-induced increase in tyrosine hydroxylase activity was not antagonized by intranigral injection of the NMDA receptor antagonist, 3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid (CPP). CPP alone produced significant contralateral turning that was not accompanied by an increase in striatal tyrosine hydroxylase activity, indicating that turning per se is not sufficient to activate striatal tyrosine hydroxylase. The DTG-induced increase in tyrosine hydroxylase activity was antagonized by general anesthetics such as halothane and chloral hydrate. These results indicate that occupancy of sigma receptors in the substantia nigra is associated with an activation of dopamine formation in dopaminergic terminals in the striatum and support the concept that sigma activity in the substantia nigra produces an activation of dopamine-mediated responses in the striatum.

Animals↗
PubMed1995

Ni2+ inhibition induces asymmetry in axonemal functioning and bend initiation of bull sperm.

Bull sperm extracted with 0.1% Triton X-100 can be reactivated to full motility with 0.33 mM Mg-ATP (sperm models). When motile sperm models are treated with 0.66 mM NiSO4, spontaneous motility is lost. During the transition to motility arrest, the beat becomes progressively more asymmetric, finally arresting at one extreme of the beat cycle. After spontaneous motility has been lost, the flagellum retains the ability to respond to mechanical stimulation. If a microprobe is used to bend the flagellum in the direction opposite to its own prevailing curvature and released, the recoil is rapid and overshoots the equilibrium position. When the same flagellum is manipulated in the opposite direction (into a tighter bend of the existing curve), the recoil is slower and does not exceed the initial bend. If a microprobe is used to carefully bend the whole flagellum into a curve, the flagellum will resume continuous beating, but only if the imposed bend is in the direction opposite the natural curvature. The reinstated beating activity (mechanical reactivation) is sustained as long as the flagellum is held by the microprobe. The rate of change of the shear angle in these mechanically reactivated, Ni(2+)-inhibited sperm suggests an impaired rate of sliding on one side of the axoneme compared to similarly restrained control sperm. It appears that Ni2+ has a selective inhibitory effect on the dynein arms that bend the flagellum in one direction. Furthermore, the remaining functional arms activate only when the flagellum is bent in the direction opposing their own action.

Animals↗
PubMed1995

An examination of the central sites of action of cannabinoid-induced antinociception in the rat.

Microinjections of low doses of the potent and selective cannabinoids WIN 55,212-2 and CP 55,940 into the lateral ventricle produce long-lasting reduction in sensitivity to noxious thermal stimuli (1). To determine the central distribution of ventricularly administered WIN 55,212-2, we microinjected an analgesic dose of the drug with [3H]WIN 55,212-2. At the peak time of antinociception, the radiolabeled drug was confined to periventricular sites throughout the brain. The contribution of particular periventricular structures to the antinociceptive effect was evaluated using intracerebral microinjection techniques and the tail-flick test. Guide cannulae were implanted above the following periventricular structures: the medial septal area, lateral habenlua, perihypothalamic area, arcuate nucleus of the hypothalamus, dorsal raphe nucleus and the dorsolateral and ventrolateral aspects of the periaqueductal gray. Microinjections of WIN 55,212-2 (5 micrograms/0.5 microliter) into the medial septal area, lateral habenula, perihypothalamic area, arcuate nucleus, and ventrolateral periaqueductal gray did not significantly affect tail-flick latencies. By contrast, microinjections of WIN 55,212-2 into the dorsolateral periaqueductal gray and the dorsal raphe significantly elevated tail-flick latencies. The results of this study indicate that at least two periventricular structures within the brain are involved in cannabinoid antinociception.

Analgesics↗
PubMed1995

Inhibition of noxious stimulus-evoked activity of spinal cord dorsal horn neurons by the cannabinoid WIN 55,212-2.

The effects of a potent synthetic cannabinoid WIN 55,212-2 on nociceptive responses of wide dynamic range (WDR) neurons in the lumbar spinal cord were investigated in anesthetized rats. WDR neurons were identified by their responses to innocuous brushing and to a range of pressure stimuli from innocuous to noxious. Noxious pressure was applied to regions of the ipsilateral hind paw corresponding to the receptive field of the neuron. WIN 55,212-2 (125 micrograms/kg and 250 micrograms/kg, i.v.) produced a profound inhibition of firing evoked by the noxious pressure stimulus. By contrast, the cannabinoid did not alter the evoked activity of non-nociceptive neurons in response to non-noxious levels of stimulation. Treatment with either vehicle or the inactive enantiomer WIN 55,212-3 (250 micrograms/kg) failed to alter noxious stimulus-evoked activity of WDR neurons. These data provide direct evidence for cannabinoid-mediated inhibition of pain neurotransmission in the spinal dorsal horn. The site of action for these effects remains to be determined.

Analgesics↗
PubMed1995

Probability of failure of orthodontic brackets bonded with different cementing agents.

OBJECTIVES: The aim of this study was to compare the maximum loads at failure and the probability of failure of three glass ionomer cements and a composite cement bonding orthodontic brackets to human premolar teeth. METHODS: The cements studied included a conventional glass ionomer cement, two resin-modified glass ionomer cements and a composite cement. The roots of 200 human premolar teeth were embedded in acrylic resin and the buccal enamel surface of the crown prepared as required. Each cement used to bond the bracket to the enamel was weighted, and light-cured where required. The specimens were stored for 10 min or 24 h at 37 degrees C and 100% humidity. A tensile shear force was applied via a wire loop placed under the wings of the bracket. The maximum load at failure was noted and subjected to Weibull analysis to compare probabilities of survival for each cement. The data obtained was also analyzed using a Kruskal-Wallis test followed by comparison of the groups using Mann-Whitney tests. RESULTS: Comparison of the loads at failure revealed that the composite cement was significantly stronger than the glass ionomer cements at 10 min and 24 h (p<0.05). Weibull analysis of the results gave values for the Weibull moduli and probabilities of survival for an orthodontic bracket under a given load for each cement at 10 min and 24 h. SIGNIFICANCE: . Glass ionomer cements give a number of clinically significant advantages over composite cement in the retention of brackets. The resin-modified glass ionomer cements tested had a higher probability of survival than the conventional cement tested at 24 h. However, further improvements in their early bond strength would be clinically beneficial.

Bisphenol A-Glycidyl Methacrylate↗
PubMed1995

The experience of labour: a perspective from those receiving care in a midwife-led unit.

AIM: to elucidate the experience of labour for those receiving any aspect of care in a midwife-led unit. PARTICIPANTS: a total of 32 women and six partners who were interviewed during the postnatal period, either prior to discharge from the unit or between three and five months following delivery. METHOD: in-depth focused interviews were taped, transcribed, and analysed using a grounded theory approach to identify common categories of experience. FINDINGS: the core category to emerge was the balance of perceived control and perceived support. Sub-categories included feeling informed, having options and choices, a supportive environment and someone to trust and give confidence. Continuity of care was found not to be an option for those whose care was transferred during pregnancy or labour. CONCLUSIONS: staffing levels which provide immediate access to the support of the midwife throughout labour enhance personal control. Those with the greatest need for support and continuity of care and carer are among those least likely to receive it.

Female↗
PubMed1995

Preconditioning in isolated superfused human muscle.

Studies in isolated superfused rabbit papillary muscles indicate that preconditioning (PC) is not confined to arterially perfused myocardium. In the present study PC of isolated human right atrial trabeculae was investigated avoiding the problems of invasive experimentation in patients. Atrial trabeculae were suspended in an organ bath, superfused with Tyrode's solution and field stimulated at 1 Hz. After stabilization, muscles were randomly allocated to five groups (n = 8 per group). Control (C) muscles had no additional treatment. PC was induced by 3 min rapid pacing at 3 Hz with hypoxic substrate-free buffer, followed by reoxygenation with substrate for 12 min. In two additional groups 8-p-sulfophenyltheophylline (SPT) was added to the superfusate either during stabilization in controls (C+SPT) or during preconditioning (PC+SPT). In the final group, R-phenyl-isopropyl adenosine (R-PIA) was added to the superfusate for 5 min to see whether or not this could substitute for preconditioning. All muscles were then exposed to 90 min hypoxia with no substrate and pacing at 3 Hz, followed by 120 min reoxygenation at 1 Hz. Recovery of developed tension was significantly improved by PC 46.5 +/- 2.4% v 24.6 +/- 2.3% in controls) and this protective effect was blocked by the addition of SPT without adversely affecting controls (recovery in PC+SPT, 25.8 +/- 4.1% and C+SPT, 22.7 +/- 2.9%). R-PIA protected the muscles to a similar extent as PC (43.8 +/- 1.9%). These data provide evidence for the involvement of adenosine in preconditioning in human myocardium.

Adenosine↗
PubMed1995

Office management of common sleep-wake disorders.

The prevalence of sleep disorders manifest as insomnia and fatigue of excessive daytime sleepiness in the general population; office practice is high. Poor quality sleep may pose a significant health risk for not only the patient but society in general. Sensitivity for potentially serious sleep disorders should be coupled with an organized approach to diagnosis and therapy. Differentiation of the principal complaint into insomnia versus hypersomnia and determination of duration are the key elements. Office-based management of the most common sleep-wake disorders and current diagnostic testing standards are discussed.

Aged↗
PubMed1995

Statistics.

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Assertiveness↗
PubMed1995

Cardiac effects of growth hormone in short normal children: results after four years of treatment.

Growth hormone excess is known to have adverse effects on the heart. The long term cardiac effects of growth hormone given to short normal children as part of a prospective randomised controlled trial of growth hormone treatment (Genotropin 30 IU/m2/week v no treatment) were therefore investigated. Echocardiographic findings are presented for 28 children who have been followed up for a minimum of four years. At the outset, the treated (n = 15) and untreated groups (n = 13) did not differ for any anthropometric or echocardiographic parameter. Their mean (SD) age at onset was 7.8 (0.5) years. After four years of treatment mean height SD score increased from -2.4 to -1.2 compared with no change (-2.5) in the untreated group. Left ventricular posterior wall and septal thickness and left ventricular shortening fraction did not differ between the groups, but a tendency towards increased left ventricular mass was seen in the treatment group (93 v 73 g). No such differential was observed after indexing left ventricular mass for body surface area (79 v 71 g/m2) or lean body mass (3.15 v 3.05 g/kg). It is concluded that prolonged growth hormone treatment does not cause important changes to the heart. A tendency towards increased left ventricular mass simply reflects the increase in lean body mass during treatment.

Anthropometry↗
PubMed1995

How do the clinical findings in patients with pericardial effusions influence the success of aspiration?

OBJECTIVE: To identify features associated with success or failure of aspiration of pericardial effusion. METHOD: A retrospective analysis of 36 drainage procedures in 30 patients with pericardial effusion was performed using patient records and echocardiograms. RESULTS: Unsuccessful aspiration was associated with pericardial loculation but not with the seniority of the operator or the size and position of the effusion. Pericardiocentesis relieved symptoms of breathlessness in 21 of 26 patients who had a pericardial effusion suspected of causing dyspnoea. These 21 patients had few clinical or echocardiographic signs of classic tamponade. CONCLUSION: The paucity of abnormal physical or echocardiographic signs of tamponade in breathless patients with pericardial effusion does not exclude symptomatic benefit being derived from pericardiocentesis. Pericardial aspiration is safe in appropriate hands, although aspiration of loculated effusions may not be as successful as aspiration of non-loculated effusions.

Adolescent↗
PubMed1995

Assessment of magnetic resonance velocity mapping of global ventricular function during dobutamine infusion in coronary artery disease.

BACKGROUND: Magnetic resonance imaging (MRI) is a versatile technique for examination of the cardiovascular system but only recently has assessment of myocardial ischaemia in coronary artery disease (CAD) become possible, for example by demonstrating abnormalities of regional ventricular contraction during stress. Global ventricular function during stress was assessed by MRI of aortic flow, which has not been previously attempted. DESIGN: Variables measured by MRI reflecting the effect of ischaemia on global ventricular function during dobutamine stress were correlated with thallium-201 myocardial perfusion tomography. PATIENTS: 10 normal controls and 25 patients with CAD. SETTING: Tertiary cardiac referral centre. METHODS: Novel MRI sequences and analysis systems were used to measure the following variables during staged dobutamine infusion to 20 micrograms/kg/min: stroke volume, cardiac output, cardiac power output, peak flow, peak flow acceleration, aortic back flow, and flow wave velocity. Heart rate, blood pressure, double product, and maximum tolerated dobutamine dose were also measured. Multiple regression analysis was used to compare changes during stress with 201TI tomography. RESULTS: All parameters except for stroke volume and diastolic blood pressure increased in the controls. In the patients with CAD a significant relation was shown between the extent of reversible ischaemia and the change in peak flow acceleration (P < 0.00001), peak flow (P = 0.002), cardiac power output (P = 0.036), maximum dobutamine dose (P = 0.039), and systolic blood pressure (P = 0.04). Peak flow acceleration accounted for 58.4% of the variation in reversible ischaemia, and after allowing for this, only cardiac power output remained independently predictive adding a further 4.2% to the model (adjusted r2 = 0.626). A decrease in peak flow acceleration with an increase in dobutamine infusion indicated moderate or severe ischaemia (chi 2 = 10.2, P = 0.017). CONCLUSION: MRI may be used to assess variables of aortic flow during stress, which includes acceleration with high temporal resolution. Peak flow acceleration was the most sensitive indicator of the effect of ischaemia on global ventricular function.

Adult↗