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Biomedical subjects

J M Walker

Publications and source records attributed to J M Walker.

At least 127 records · Page 7Linked to original sources
PubMed1993

Increases in rat striatal extracellular dopamine and vacuous chewing produced by two sigma receptor ligands.

The present studies were carried out to analyze the neurochemical and behavioral effects of peripheral sigma ligand administration in the rat. Based upon previous studies which showed an increase in turning behavior following unilateral intranigral administration of sigma ligands, we determined the effects of two sigma ligands, 1,3-di-o-tolylguanidine (DTG) and (+)-pentazocine, on extracellular dopamine levels in the rat striatum. Dopamine levels were monitored via microdialysis in awake freely moving animals following i.p. injection of the ligands. Both DTG (1 and 3 mg/kg) and (+)-pentazocine (10 mg/kg) produced a significant (30-50%) increase in extracellular dopamine. Given the relatively high concentration of sigma receptors in brain nuclei involved in facial and mouth movements, we have also determined the effects of the two sigma ligands on facial movements. Both ligands produced a significant increase in vacuous chewing movements, suggesting that studies on the consequences of sigma receptor activation may have relevance to animal models of human dystonia and/or dyskinesia.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

A comparison of (-)-deoxybenzomorphans devoid of opiate activity with their dextrorotatory phenolic counterparts suggests role of sigma 2 receptors in motor function.

Three novel benzomorphans, (+)-N-benzylnormetazocine, (-)-deoxy-N-benzylnormetazocine, and (-)-deoxypentazocine were tested for their ability to produce circling behavior in rats following intranigral microinjections. Dose studies revealed the following rank order of potency: (-)-deoxypentazocine > (-)-deoxy-N-benzylnormetazocine > (+)-N-benzylnormetazocine. This rank order approximates that for affinities for sigma 2 receptors but not sigma 1 receptors. It is very unlikely that the effects of the (-)-deoxybenzomorphans were mediated by opiate receptors for the following reasons: (1) consistent with the known requirement for the phenolic hydroxyl group for opiate activity, both (-)-deoxy compounds showed very low affinity for opiate receptors; (2) naloxone (4 micrograms) co-administered with (-)-deoxy-N-benzylnormetazocine failed to reduce its efficacy; (3) both (-)-deoxy compounds failed to produce marked analgesic effects in the tail flick test following systemic injections of 20 mg/kg s.c. These finding suggest that sigma 2 receptors mediate the motor effects of sigma ligands in rats.

Animals↗
PubMed1993

Attenuation by heat stress of a submaximal calcium paradox in the rabbit heart.

Heat stress limits the injury associated with myocardial ischaemia and reperfusion, an effect previously attributed to enhanced endogenous anti-oxidant activity. We examined the influence of heat stress on the calcium paradox, an injury in which oxidant stress is not thought to play a major role. Twenty-four hours following sham or true heat stress, rabbits were re-anaesthetized and hearts either removed for stress protein analysis (n = 8), or Langendorff-perfused (n = 20) and subjected to a calcium paradox. Ten minutes following calcium repletion (Ca2+ = 1.3 mM), left ventricular developed pressure was better preserved in heat stress vs control hearts (38.3 +/- 5.0 vs 18.8 +/- 4.1 mmHg, respectively, P = 0.003) whilst contracture, measured by left ventricular end-diastolic pressure, was diminished (21.6 +/- 4.7 vs 39.9 +/- 5.2 mmHg, respectively, P = 0.02). Creatine phosphokinase release at 1 min was less in heat stress vs control hearts (10.6 +/- 8.6 vs 86.4 +/- 33.7 U/min/g, respectively, P = 0.01). The myocardial content of the 72 kDa stress protein was elevated eight-fold in heat stress vs control hearts (2.8 +/- 0.2 vs 0.4 +/- 0.1 U, respectively, P = 0.01). This study suggests that some portion of the stress protein response represents a form of cardiac adaptation capable of limiting myocyte injury independent of antioxidant mechanisms.

Animals↗
PubMed1993

Nurses' perceptions of patients' feelings about breast surgery.

This qualitative study was designed to gain insight into nurses' perceptions of patients' feelings and needs with specific reference to breast surgery. A grounded theory approach was adopted, based on in-depth, unstructured interviews with eight trained nurses working on surgical wards in a district general hospital. It emerged that the informants believed breast surgery patients to be very vulnerable and to be suffering from extreme stress and trauma. Patients were thought to lack knowledge regarding their treatment and condition. The nurses thought it to be their moral and professional duty to act as advocates for the patient and the family. Imposed restrictions on their advocacy role were found to cause a sense of frustration and powerlessness which appeared to be compounded by the nurses' perceived lack of counselling skills and the absence of a readily available counsellor or specialist nurse. Recommendations for improvements in the care of patients undergoing breast surgery are based upon these findings.

Adult↗
PubMed1993

A single five minute period of rapid atrial pacing fails to limit infarct size in the in situ rabbit heart.

OBJECTIVE: Rapid pacing has been shown to precondition the dog heart against ischaemic dysrhythmia. The aim of this study was to determine whether rapid pacing could also limit infarct size. METHODS: Rabbits (n = 5) were rapidly paced via the left atrium at 420-480 beats.min-1. Five min of rapid pacing and 10 min of recovery in sinus rhythm were followed by 45 min of regional ischaemia and 120 min of reperfusion. Control rabbits (n = 9) were treated identically without prior rapid pacing. Infarct size was determined in both groups using tetrazolium and expressed as a percentage of the area at risk demarcated by fluorescent microspheres. In a separate series of experiments, rapidly paced Langendorff perfused rabbit hearts (n = 9) were used to determine coronary flow under perfusion conditions designed to simulate the in vivo situation during rapid pacing. RESULTS: Rapid pacing caused a fall in systolic pressure from 91.4(SEM 4.5) to 47.0(5.9) mm Hg (p < 0.01) and diastolic pressure from 67.2(2.9) to 23.6(3.2) mm Hg (p < 0.01). Both recovered within 30 s of cessation of pacing. During rapid pacing the action potential duration shortened from 192(13) to 128(5) ms (p = 0.01) and developed electrical alternans (n = 4). Following rapid pacing the ECG showed either ST depression or T wave inversion (n = 4). Despite these profound changes, rapid pacing did not reduce infarct size v control [52.7(4.6)% v 60.8(9.1)% of the area at risk, respectively]. The in vitro experiments estimated that rapid pacing would result in a reduction in coronary flow to 44% of that in sinus rhythm without a significant rise in lactate efflux. CONCLUSIONS: In our model, pretreatment with rapid pacing fails to reduce infarct size. The most likely reason for this is that rapid pacing at a rate of 480 beats.min-1 does not cause myocardial ischaemia of sufficient severity to trigger the preconditioning response.

Action Potentials↗
PubMed1993

Carboxy-terminal deletion analysis of oat phytochrome A reveals the presence of separate domains required for structure and biological activity.

A series of seven carboxy-terminal deletion mutants of oat phytochrome A were stably expressed in transgenic tobacco to localize phytochrome domains involved in chromophore attachment, spectral integrity, photoreversibility between the red light (Pr)- and far-red light (Pfr)-absorbing forms, dimerization, and biological activity. Amino acids necessary for chromophore attachment in vivo were localized to the amino-terminal 398 residues because mutant proteins this small had covalently bound chromophore. Deletion mutants from the carboxy terminus to residue 653 were spectrally indistinguishable from the full-length chromoprotein. In contrast, further truncation to residue 399 resulted in a chromoprotein with a bleached Pfr absorbance spectrum, Pr and Pfr absorbance maxima shifted toward shorter wavelengths, and reduced Pfr to Pr phototransformation efficiency. Thus, residues between 399 ad 652 are required for spectral integrity but are not essential for chromophore attachment. The sequence(s) between residues 919 and 1093 appears to be necessary for dimerization. Carboxy-terminal mutants containing this region behaved as dimers under nondenaturing conditions in vitro, whereas truncations without this region behaved as monomers. None of the plants expressing high levels of deletion mutants lacking the 35 carboxy-terminal amino acids displayed the light-exaggerated phenotype characteristic of plants expressing biologically active phytochrome A, even when the truncated phytochromes were expressed at levels 6- to 15-fold greater than that effective for the full-length chromoprotein. Collectively, these data show that the phytochrome protein contains several separable carboxy-terminal domains required for structure/function and identify a domain within 35 residues of the carboxy terminus that is critical for the biological activity of the photoreceptor in vivo.

Base Sequence↗
PubMed1993

False aneurysm of the pulmonary artery associated with cardiac catheterisation.

A false aneurysm of the pulmonary artery developed in a 59 year old woman as a complication of right-sided cardiac catheterisation. This rare, life-threatening condition was successfully treated with coil embolisation of the feeding artery. Cardiologists and intensive care doctors should be aware of the possibility of the formation of false aneurysms of the pulmonary artery after Swan-Ganz and other right heart catheterisation. Appropriate therapy could be life-saving.

Aneurysm, False↗
PubMed1993

Cardiac stress protein elevation 24 hours after brief ischemia or heat stress is associated with resistance to myocardial infarction.

BACKGROUND: To test the hypothesis that the heat shock response is associated with myocardial salvage, the heat stress protein (HSP) content of cardiac tissue was increased by either ischemic or thermal stress. METHODS AND RESULTS: Rabbits were divided into four groups. Ischemic pretreatment (n = 15) comprised four 5-minute episodes of coronary ligation separated by 10 minutes of reperfusion. The corresponding control group (n = 21) underwent surgical preparation without coronary ligation. Thermal pretreatment (n = 16) involved whole-body temperature elevation to 42 degrees C for 15 minutes; corresponding controls (n = 15) were treated with anesthetic alone. Twenty-four hours later, hearts were removed for HSP estimation or infarct size assessment after a 30-minute coronary ligation. Myocardial HSP72 content assessed by Western blotting was elevated by both ischemic and thermal pretreatments (2.5 +/- 0.2 units, n = 4, and 2.8 +/- 0.3 units, n = 4, mean +/- SEM; P = NS, respectively) compared with the corresponding control groups (1.0 +/- 0.3, n = 4, P < or = .01 and 0.3 +/- 0.1, n = 4, P < or = .01, respectively). HSP60 was preferentially elevated by ischemic pretreatment. After a 30-minute coronary occlusion and 120 minutes of reperfusion, ischemic and thermal pretreatments limited infarct size as a percentage of the volume at risk by 28.8 +/- 5.2% vs 52.0 +/- 5.2%, P < or = .01 and 32.8 +/- 3.8% vs 56.9 +/- 6.5%, P < or = .01, respectively. CONCLUSIONS: Myocardial stress protein induced by either sublethal thermal or ischemic injury is associated with myocardial salvage. Our findings suggest that stress protein elevation, rather than the nonspecific effects of thermal or ischemic stress, may be responsible for the myocardial protection seen in this model. Our observations may have important implications regarding myocardial adaptation to brief periods of ischemia.

Animals↗
PubMed1993

An evaluation of a rinse procedure using sodium bicarbonate and hydrogen peroxide on the recovery of bacteria from broiler carcasses.

A patent entitled "Reduction of Bacteria Count on Poultry Being Processed into Food at a Poultry Processing Plant" (U.S. Patent No. 4,683,618) claimed that a three-step rinse process using sodium bicarbonate and hydrogen peroxide solutions would remove bacteria from the surface of broiler carcasses. In three replicate trials, 40 broilers were obtained postchill from a commercial processing plant. Broilers (n = 20) were treated according to the patent by spraying the inside and outside surfaces of each carcass with a 2% NaHCO3 solution for 5 s and rinsing with water, repeating, spraying with a 3% H2O2 solution for 5 s, and rinsing a final time with water. Controls (n = 20) were treated identically except that in each of the rinse steps tap water was used in place of the test solutions. Whole carcass rinses were conducted and total aerobic plate counts (TPC) and impedance detection times (DT) were determined after 1 h and 7 days at 4 C. The NaHCO3 + H2O2 treatment resulted in no significant difference in TPC at 1 h post-treatment but did result in lower TPC after 7 days and greater DT at both 1 h and 7 days. The procedure was effective in reducing the recovery of bacteria at 7 days post-treatment by .3 log10 but was not effective in removing the bacteria to the extent implied in the patient. Based on previous studies using H2O2, these results are not unexpected, but commercial applicability remains questionable based on actual reduction levels.

Analysis of Variance↗
PubMed1993

Global myocardial ischemia protects the myocardium from subsequent regional ischemia.

Many investigators use in vitro models of global ischemia to examine the effects of preconditioning, often with recovery of contractile function as the end-point. Such models are relevant to myocardial protection during cardiac surgery. However, there is still debate as to whether preconditioning preserves ventricular contraction secondary to limitation of infarction or by a direct effect on stunning. Since infarct size is the original end-point against which protection by preconditioning is measured, our aims were, first, to validate global ischemic preconditioning by measuring infarct size after subsequent regional ischemia and, second, to correlate limitation of infarct size with mechanical function. After stabilization, seven isolated buffer perfused rabbit hearts were subjected to 5 minutes of global "no-flow" ischemia followed by 10 minutes of reperfusion ("global preconditioning"). Seven control hearts were allowed to stabilize for an additional 15 minutes at constant flow. Subsequently, regional ischemia was induced in both groups for 45 minutes followed by 2 hours of reperfusion. Left ventricular and coronary perfusion pressures were measured throughout. Myocardial infarct size was measured using triphenyltetrazolium staining and expressed as a percentage of the area at risk outlined with fluorescent microspheres. The ratio of infarct to risk zone was reduced from 47.6 +/- 7.3% in control hearts to 16.4 +/- 5.4% (p = 0.005) in preconditioned hearts, confirming the efficacy of global preconditioning. In addition, preconditioning led to a better preservation of systolic function, which correlated significantly with limitation of infarct size (r = 0.75, p = 0.002). Global preconditioning may account for the successful use of cross-clamp fibrillation during cardiac surgery.

Animals↗
PubMed1993

Purification of aspartate aminotransferase from Thermus aquaticus.

A method is described for the purification of the enzyme aspartate aminotransferase from the thermophile Thermus aquaticus. The enzyme has been characterized with respect to its molecular weight on SDS PAGE and by amino acid analysis. Attempts to obtain N-terminal sequence data was unsuccessful, presumably due to a blocked N-terminus. The purified enzyme has been shown to be highly thermostable, having a half life of inactivation of about 6 hours at 100 degrees C, and to have a temperature optimum greater than 95 degrees C.

Amino Acids↗
PubMed1992

Effects of 1,3-di-o-tolylguanidine (DTG), a sigma ligand, on local cerebral glucose utilization in rat brain.

The 2-deoxy-D-[1-14C]glucose ([14C]DG) method was used to examine the effects of the relatively selective sigma ligand 1,3-di-o-tolylguanidine (DTG) on cerebral metabolism in freely moving rats. Each animal received an i.p. injection of DTG (0.2, 1, or 5 mg/kg) or normal saline 20 min prior to the infusion of [14C]DG. DTG induced dose-dependent changes in local cerebral glucose utilization (LCGU) in several motor and limbic structures. Most structures showed increases in LCGU, with a maximum effect at 1 mg/kg. The most profound increases in LCGU were observed in brain regions that are rich in sigma receptors. These included cerebellar and related nuclei (interpositus, lateral and medial cerebellar n., vestibular n., olivary n.), ambiguus n., superior colliculus (superior layers), hippocampus (CA2, CA3, DG), n. basalis of Meynert interpeduncular n., and the substantia nigra pars compacta and pars reticulata. No significant decreases in glucose utilization were observed at any dose. Although the areas affected by DTG are similar to those previously reported for other sigma ligands, future studies employing a range of doses for additional selective sigma ligands must be carried out in order to confirm whether these changes in LCGU were sigma-mediated.

Animals↗
PubMed1992

Magnetic resonance imaging during dobutamine stress in coronary artery disease.

Cine magnetic resonance imaging (MRI) provides a tomographic method of assessing regional ventricular function in any desired plane. It has not been possible to obtain adequate images during dynamic exercise, and this has limited its value in patients with coronary artery disease (CAD). Therefore, an infusion of dobutamine was used to study 25 patients with exertional chest pain and abnormal exercise electrocardiograms. Areas of abnormal wall motion were compared with areas of abnormal myocardial perfusion imaged by dobutamine thallium emission tomography and with coronary arteriography. Twenty-two patients had significant CAD. Twenty-one (96%) of these patients had reversible myocardial ischemia shown by dobutamine thallium tomography, and 20 (91%) had reversible wall motion abnormalities shown by dobutamine MRI. Comparison of abnormal segments of perfusion and wall motion showed 96% agreement at rest, 90% agreement during stress, and 91% agreement for the assessment of functional reversibility. The normalized magnetic resonance signal intensity of the ischemic segments showed a small but significant reduction when compared with that of normal segments (-67 units [9.2%]; p less than 0.05). Dobutamine infusion was well-tolerated, despite causing chest discomfort in 24 patients (96%). Nine patients (36%) developed a minor dysrhythmia that was usually ventricular premature complexes, but this did not limit infusion, and other side effects were mild. The short plasma half-life of dobutamine makes it ideal as a stress agent for imaging techniques (such as MRI), and these results suggest that it is more effective in the provocation of wall motion abnormalities than is dipyridamole in patients with CAD.

Adult↗
PubMed1992

Phytochrome requires the 6-kDa N-terminal domain for full biological activity.

Phytochrome is a red/far-red-absorbing photoreceptor that controls many aspects of plant photomorphogenesis. Because proteolytic removal of approximately 6 kDa from the N terminus of 124-kDa oat phytochrome substantially alters many physicochemical properties of the chromoprotein, it has been proposed that the N terminus is required for biological activity. Here we test this hypothesis by comparing tobacco plants expressing full-length oat phytochrome (FL) with plants expressing a 118-kDa oat phytochrome lacking amino acids 7-69 (NA phytochrome). NA phytochrome, like its FL counterpart, exists as a homodimer in solution, is capable of covalently binding chromophore to form a red/far-red-photoreversible product, and is rapidly degraded in vivo after photoconversion to the far-red-absorbing form. However, like proteolytically degraded phytochrome missing the N terminus, the absorption maxima of the red- and far-red-light-absorbing forms of NA phytochrome are blue shifted relative to the maxima of the FL chromoprotein, and the rate of dark reversion of the far-red- to red-light-absorbing form is substantially increased. Tobacco plants producing high levels of NA phytochrome do not exhibit the light-exaggerated phenotype characteristic of FL phytochrome overexpression. By comparison of phytochrome-dose-phenotype-response curves generated by using a series of transgenic lines expressing various levels of FL or NA phytochrome, we demonstrate that NA phytochrome has less than 1/5th the biological activity of FL phytochrome expressed in tobacco. Furthermore, the shape of the dose-response curve for plants expressing FL phytochrome indicates that there is a sharp transition between phenotypically normal and abnormal plants over a relatively narrow range of phytochrome content, demonstrating that precise control of phytochrome levels is critical to photomorphogenesis.

Amino Acid Sequence↗
PubMed1992

Autoradiographic distribution of [3H](+)-pentazocine and [3H]1,3-di-o-tolylguanidine (DTG) binding sites in guinea pig brain: a comparative study.

Binding studies suggested the selectivity of (+)-pentazocine for sigma receptors, and subsequent synthesis and testing of [3H](+)-pentazocine confirmed its high potency and selectivity for sigma sites. Newer data have demonstrated the selectivity of (+)-pentazocine for a subtype of the sigma receptor called sigma-1. Based on these findings, the distribution of [3H](+)-pentazocine binding sites in the guinea pig brain was examined using in vitro autoradiography. [3H](+)-Pentazocine binding was high in the cingulate cortex, dorsal diagonal band, periaqueductal gray, cerebellum and cranial nerve nuclei. It was relatively low in the nucleus accumbens, neocortical areas and caudate nucleus. A significant correlation was found between the binding of [3H](+)-pentazocine and [3H]1,3-di-o-tolylguanidine, a selective sigma ligand across brain regions. However, certain nuclei exhibited markedly different ratios of binding of the two ligands. Since DTG is not selective for the sigma subtypes, while (+)-pentazocine is selective for the sigma-1 type, the data are suggestive of relative differences in the distributions of sigma-1 and sigma-2 sites.

Animals↗
PubMed1992

Haemodynamic evidence for cardiac stress during transurethral prostatectomy.

OBJECTIVE: To compare haemodynamic performance during transurethral prostatectomy and non-endoscopic control procedures similar in duration and surgical trauma. DESIGN: Controlled comparative study. SETTING: London teaching hospital. PATIENTS: 33 men aged 50-85 years in American Society of Anesthesiologists risk groups I and II undergoing transurethral prostatectomy (20), herniorrhaphy (eight), or testicular exploration (five). MAIN OUTCOME MEASURES: Percentage change from baseline in mean arterial pressure, heart rate, Doppler indices of stroke volume and cardiac output, and index of systemic vascular resistance, and change from baseline in core temperature. RESULTS: In the control group mean arterial pressure fell to 11% (95% confidence interval -17% to -5%) below baseline at two minutes into surgery and remained below baseline; there were no other overall changes in haemodynamic variables and the core temperature was stable. During transurethral prostatectomy mean arterial pressure increased by 16% (5% to 27%) at the two minute recording and remained raised throughout. Bradycardia reached -7% (-14% to 1%) by the end of the procedure. Doppler indices of stroke volume fell progressively to 15% (-24% to -6%) below baseline at the end of the procedure, and the index of cardiac output fell to 21% (-32% to -10%) below baseline by the end of the procedure. The index of systemic vascular resistance was increased by 28% (17% to 38%) at two minutes, and by 46.8% (28% to 66%) at the end of the procedure. Core temperature fell by a mean of 0.8 (-1.0 to -0.6) degrees C. Significant differences existed between the two groups in summary measures of mean arterial pressure (p less than 0.05), Doppler indices of stroke volume (p less than 0.005) and cardiac output (p less than 0.005), index of systemic vascular resistance (p less than 0.0005), and core temperature (p less than 0.0001). CONCLUSIONS: Important haemodynamic disturbances were identified during routine apparently uneventful transurethral prostatectomy but not during control procedures. These responses may be related to the rapid central cooling observed during transurethral prostatectomy and require further study.

Aged↗
PubMed1992

Involvement of the nigrotectal and nigrothalamic pathways in kappa opioid-induced circling.

The relationship between kappa opioid-induced movement and output stations of the substantia nigra pars reticulata (SNpr) was examined using the rodent circling model. Contralateral rotation produced by intranigral microinjection of the kappa opiate U50,488 was lower in animals with ibotenic acid lesions of either the ipsilateral ventromedial thalamus or superior colliculus than in control animals without lesions. These results suggest that endogenous kappa opioids in the SNpr may influence movement through actions on the nigrothalamic and nigrotectal pathways. In contrast, animals with ipsilateral lesions of the striatum showed an increase in circling relative to controls, possibly due to kappa receptor supersensitivity in the SNpr.

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