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Biomedical subjects

J M Walker

Publications and source records attributed to J M Walker.

At least 19 recordsLinked to original sources
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↗
PubMed1992

Coxiella burneti endocarditis in a patient with positive chlamydial serology.

A 41-year-old man who habitually slept in a car park presented with a culture-negative endocarditis. Serological tests indicated infection with both Coxiella burneti and Chlamydia psittaci. He was treated with doxycycline and clindamycin and required aortic valve replacement. Culture of the excised value for both agents was negative but electron microscopy was suggestive of coxiella endocarditis.

Adult↗
PubMed1992

The sacroiliac joint: a critical review.

Clinicians continue to focus attention on the sacroiliac joint (SIJ) as one cause of low back pain. Considerable literature now exists to support the contention that symptoms arise from the sacroiliac region. In the last couple of decades, studies with quantitative data, often using sophisticated methods, have added to our knowledge from earlier descriptive reports of SIJ morphology and motion. The unique morphology of the SIJ, together with its location, makes study of the SIJ complex. All reported studies have limitations such as small sample size or lack of randomization or methodology. The purpose of this article is to review the literature to determine the support for current beliefs, opinions, and theories on joint morphology, life-span changes, and motion. Clinicians should provide well-documented clinical case-study series if we are to understand what occurs with treatments designed to affect the SIJ.

Biomechanical Phenomena↗
PubMed1992

Transtracheal oxygen, nasal CPAP and nasal oxygen in five patients with obstructive sleep apnea.

The effect of transtracheal oxygen administration by means of a 9-French (2.7 mm) percutaneous catheter was assessed in five patients with severe obstructive sleep apnea. We hypothesized that the delivery of oxygen below the site of airway obstruction should reduce the arterial oxygen desaturation during apneas and hypopneas, thereby increasing respiratory stability. Standard sleep and respiratory measurements were recorded in these subjects with all-night polysomnography on nonconsecutive nights during four experimental conditions: room air (BL), nasal continuous positive airway pressure (CPAP), nasal O2 (NC O2), and transtracheal O2 (TT O2). In three of these subjects, room air was infused (TT RA) at flow rates comparable to TT O2. Compared with baseline room air measurements, TT O2 not only significantly increased the SaO2 nadir from 70.4 percent to 89.7 percent (p less than 0.01), but it also reduced the frequency of sleep apnea/hypopnea from 64.6 to 26.2/h sleep (p less than 0.01). NC O2 ameliorated desaturation during apnea/hypopnea (mean SaO2 nadir, 86.2 percent; p less than .01) but did not significantly alter frequency (59.0/h sleep). Nasal CPAP was the most effective means of reducing sleep apnea/hypopnea (13.8/h sleep) but did not abolish desaturations when apneas occurred (mean SaO2 nadir, 80.0 percent). Compared with oxygen, transtracheal infusion of room air appeared to be somewhat effective; however, the small number of studies with TT RA precluded statistical analysis. We believe that TT O2 is superior to NC O2 for some patients with obstructive sleep apnea because continuous oxygen flow below the site of airway obstruction more reliably prevents alveolar hypoxia and respiration is stabilized. Infusion of air or oxygen through the tracheal catheter flow may also increase mean airway pressure and reduce obstructive apnea similar to nasal CPAP. We conclude that TT O2 may be an effective alternative mode of therapy for some patients with severe sleep apnea/hypopnea when nasal CPAP is not tolerated or when combined oxygen and nasal CPAP are required.

Adult↗
PubMed1992

Characterization of the enantiomers of cis-N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1- pyrrolidinyl)cyclohexylamine (BD737 and BD738): novel compounds with high affinity, selectivity and biological efficacy at sigma receptors.

A novel class of compounds with very high affinity and selectivity for sigma receptors has been discovered. BD614 [(+/-)-cis-N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1- pyrrolidinyl)cyclohexylamine] and its optically pure 1S,2R-(-)-[BD737] and 1R,2S-(+)-[BD738]enantiomers bound to sigma receptors of guinea pig brain with Ki = 2.0 +/- 0.4, 1.3 +/- 0.3 and 6 +/- 3 nM, respectively. These compounds exhibited little or no affinity for dopamine-D2, kappa opiate or phencyclidine receptors and displayed high biological efficacy in assays of sigma receptor function, ability to produce alterations in motor behavior and inhibition of the muscarinic cholinergic phosphoinositide response. Microinjection of BD614 into the rat red nucleus or substantia nigra produced a dose-dependent alteration in head position and contralateral circling, respectively. BD614, BD737 and BD738 inhibited stimulation of inositol phosphate production by carbachol or oxotremorine-M in a dose-dependent manner. Thus, N-substituted cis-2-(1-pyrrolidinyl)cyclohexylamines may prove useful in studies of sigma receptor structure and function.

Analgesics↗
PubMed1991

Dobutamine thallium myocardial perfusion tomography.

Dobutamine has favorable properties for the pharmacologic manipulation of myocardial oxygen demand in the provocation of ischemia during the investigation of coronary artery disease. The value of dobutamine infusion for thallium myocardial perfusion tomography was assessed in 50 patients with exertional chest pain undergoing coronary arteriography. Dobutamine was infused in 5-min stages at incremental rates from 5 to 20 micrograms/kg per min or until limited by symptoms. The myocardium was divided into nine segments for analysis of perfusion. Thirty-nine of 40 patients with coronary artery disease had a reversible perfusion defect demonstrated by dobutamine thallium tomography (sensitivity 97%) and 8 of 10 patients with normal coronary arteries had normal myocardial perfusion (specificity 80%). These values were significantly better than the sensitivity and specificity of exercise electrocardiography (78% and 44%, respectively; p less than 0.01). There was a significant relation between the mean number of segments with abnormal perfusion and the number of diseased coronary vessels (0.6, 2.6, 4.4 and 6 segments in zero-, one-, two- and three-vessel disease, respectively; p less than 0.001). There was also a significant relation between the maximal tolerated dose of dobutamine and the treadmill exercise time (r = 0.56, p less than 0.001), but a wide range of exercise times was achieved in the 15- and 20-micrograms/kg per min groups, principally because of exercise limitation by noncardiac symptoms. Dobutamine infusion was well tolerated in all patients, including six with asthma. There were no significant arrhythmias or limiting symptoms other than chest pain.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Inhibition of rubral neurons by noxious and non-noxious pressure.

The role of the red nucleus (RN) in nociception was investigated in this study. Extracellular recordings from spontaneously active RN neurons were conducted in the rat while noxious pressure was delivered to the hindpaws or tail. Cells in the RN were predominantly inhibited by the stimuli. The units were most responsive when noxious pressure was applied to the contralateral hindpaw. Furthermore, more cells in the magnocellular division of the RN responded to the stimuli than cells in the parvocellular division. Delivery of a graded pressure stimulus to the contralateral hindpaw revealed 4 cell types in the RN: non-responsive cells; cells only responsive during the early, non-noxious portion of the stimulus; cells only responsive during the later, noxious portion of the stimulus; and cells that showed an initial response during the non-noxious part of the stimulus and a second, later response during the noxious portion of the stimulus. To further examine the putative role of the RN in nociception, oxotremorine, gamma-aminobutyric acid (GABA), serotonin, glutamate, and morphine were unilaterally microinjected into the RN and the responses of the animals in the tail flick test were assessed. Only morphine produced a significant antinociception in the animals following intrarubral microinjection. However, it is unclear whether this alteration was mediated through the RN because an antinociception of equal magnitude could be elicited from the reticular formation surrounding the RN and lesions of the RN did not alter the antinociception produced by systemic administration of morphine. Although other explanations cannot be ruled out, it appears that the RN may be involved in coordinating the motor response to pain rather than modulating sensory transmission.

Animals↗
PubMed1991

Purification of cloned trypanosomal calmodulin and preliminary NMR studies.

Cloned trypanosomal calmodulin was expressed in Escherichia coli and purified to homogeneity using hydrophobic interaction chromatography on phenyl-Sepharose. The purified protein was subjected to NMR analysis which allows detailed changes to be observed when, firstly, calcium, and secondly, the drug calmidazolium bind. These spectral changes are the result of conformational changes in the protein and proximity effects due to the drug.

Amino Acid Sequence↗
PubMed1991

Concomitant sensitization of amphetamine-induced behavioral stimulation and in vivo dopamine release from rat caudate nucleus.

Rats were treated twice daily either with saline or d-amphetamine (5 mg/kg) for 5 days. When challenged approximately 15 days later with an injection of 0.5 mg/kg amphetamine, the chronic amphetamine animals showed (1) an augmented release of dopamine in the caudate nucleus in vivo and (2) an increase in stereotyped behavior compared to the chronic saline animals. These results suggest that an increase in dopamine release from the caudate may contribute to amphetamine-induced behavioral sensitization.

Animals↗