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Biomedical subjects

S J Taylor

Publications and source records attributed to S J Taylor.

At least 91 records · Page 5Linked to original sources
PubMed1992

In vivo occupancy of histamine H3 receptors by thioperamide and (R)-alpha-methylhistamine measured using histamine turnover and an ex vivo labeling technique.

In the brain, the H3 type of histamine receptor has a pre-synaptic autoreceptor inhibitory role which regulates neuronal release and synthesis of histamine. To examine the interaction of the selective H3 receptor antagonist thioperamide with H3 receptors in the brain in vivo, we have used a functional and non-functional measurement of H3 receptor occupancy. In three species (rat, guinea-pig and mouse) peripheral administration of thioperamide caused dose-related increases in histamine turnover in the cerebral cortex (whole brain was examined in the mouse) and, in the same tissues, inhibited the ex vivo binding of the selective H3 receptor agonist [3H](R)-alpha-methylhistamine ([3H]-RAMH). The peak effect of thioperamide to inhibit ex vivo binding of [3H]RAMH was observed approximately 30 min after i.p. administration, whilst the maximum increase in histamine turnover did not occur until after at least 100 min. At a pretreatment time of 30 min, the ED50 of thioperamide to inhibit ex vivo binding of [3H]RAMH binding in the rat, guinea-pig and mouse brain was found to be 2.0 +/- 0.2, 4.8 +/- 0.6 and 2.6 +/- 0.3 mg/kg (mean +/- SEM, N = 4), respectively. We have also examined the effect of peripheral administration of RAMH on ex vivo binding of [3H]RAMH in rat cortex. Qualitatively and quantitatively similar results to those of thioperamide were observed following i.p. administration of RAMH to rats (ED50 = 3.9 +/- 0.4 mg/kg, mean +/- SEM, N = 4). An effect of RAMH on histamine turnover in rat cortex could not be determined as this compound displayed significant cross-reactivity with the antibodies used in the radioimmunoassay to measure histamine and telemethylhistamine. These data indicate that, following peripheral administration, both thioperamide and RAMH penetrate the brain where they can subsequently interact with H3 receptors. It would appear that binding of thioperamide to H3 receptors is linked with a concomitant increase in histamine turnover in the brain. In conclusion, the ex vivo binding technique, particularly when coupled with measurement of histamine turnover, should provide a valuable means for investigating the ability of any peripherally administered compound to cross the blood-brain barrier and subsequently interact with histamine H3 receptors.

Animals↗
PubMed1992

Regulation of phosphoinositide and phosphatidylcholine phospholipases by G proteins.

Two G proteins that regulate phosphoinositide phospholipase C in liver plasma membranes have been purified to homogeneity in both the heterotrimeric and dissociated forms. The heterotrimers contain a 42 kDa or 43 kDa alpha subunit and a 35 kDa beta subunit. The alpha subunits are not ADP-ribosylated by pertussis toxin and are closely related immunologically to members of the recently identified Gq class of G proteins. The specific phosphoinositide phospholipase C isozyme that responds to the G proteins has been determined to the beta 1 isozyme. GTP analogues stimulate phosphatidylcholine hydrolysis in rat liver plasma membranes. The nucleotide specificity and Mg2+ dependency of the response indicate that it is mediated by a G protein. Phosphatidic acid, diacylglycerol, choline and phosphorylcholine are the products, indicating that both phospholipase D and C activities are involved. Activation of phospholipase D is also indicated by the enhanced production of phosphatidyl-ethanol in the presence of ethanol.

Animals↗
PubMed1992

c-Src and mitosis.

The transforming potential and by inference the physiological function of the proto-oncoprotein pp60c-src closely correlate with the level of its protein tyrosine kinase activity. We have investigated the cell cycle-dependent regulation of this activity using mouse fibroblasts overexpressing chicken or mouse pp60c-src as a model system. During mitosis pp60c-src becomes phosphorylated at specific serine and threonine residues by p34cdc2. At the same time its tyrosine kinase activity, assayed in vitro, is increased approximately twofold and accessibility of its SH2 domain for binding relevant phosphotyrosine-containing ligands increases by about 15-fold. A kinase-defective mutant of pp60c-src exhibits a substantial (50-70%) decrease in phosphorylation at Tyr527 during mitosis. Phosphorylation of this residue negatively regulates kinase activity. Indirect evidence indicates a lesser decrease in wild-type pp60c-src Tyr527 phosphorylation during mitosis. Coordinate mutation of the mitosis-specific phosphorylation (MSP) sites in kinase-defective pp60c-src greatly reduces, though does not abolish, its mitosis-specific tyrosine dephosphorylation. Similarly, coordinate mutation of the three MSP sites in chicken pp60c-src or the corresponding two sites in mouse pp60c-src does not completely block mitotic stimulation of kinase activity. Thus, additional events beyond p34cdc2-mediated phosphorylation are involved in cell-cycle dependent regulation of pp60c-src activity. This is also suggested by the stimulation of pp60c-src kinase activity and decrease in phosphorylation of Tyr527 observed following treatment of fibroblasts with okadaic acid, a potent inhibitor of types 1 and 2A serine/threonine phosphatases. The potential role of cell cycle-dependent regulation of phosphatases and kinases acting on the regulatory tyrosine residue of pp60c-src is discussed.

Animals↗
PubMed1992

Cafeteria benefits in the NHS?

Choice of benefits in addition to (or as an alternative to part of) base pay. Lessons from the USA. How much applies to the NHS in the UK? Discusses some examples and describes a process of devising such a scheme. Concludes that there is a need to consider such a scheme in relation to an organizations's labour market and culture. Is it appropriate? Or are there better ways to the same results?

Community Participation↗
PubMed1992

Further thoughts on the reward of health care assistants.

Discusses the need to view HDAs in a multiskilled generic context, irrespective of function (for reward purposes). Suggests three groups (direct care, indirect care and support). Mentions assimilation, then some NHS examples. Refers to a previous article in Health Manpower Management, Vol. 18 No. 1 and updates a Table therein. Mentions surveying the local labour market. Suggests a possible logical route, then an alternative scenario. Concludes that there is no one route to local variations, but there is a common need to separate NVQ-competence training, skill-mix and reward issues first--then link all together into one overall strategy comprising all component parts.

Allied Health Personnel↗
PubMed1992

Characterization of histamine-H3 receptors controlling non-adrenergic non-cholinergic contractions of the guinea-pig isolated ileum.

1. In the presence of atropine, mepyramine and ranitidine, electric field stimulation of the guinea-pig isolated ileum longitudinal muscle-myenteric plexus preparation resulted in a two component non-adrenergic non-cholinergic contraction. The initial contraction had a duration of approximately 1 s whereas the second contraction lasted approximately 10 s. The second contraction was completely inhibited by tetrodotoxin (0.2 x 10(-6) M) with minimal effect on the initial contraction. Phentolamine (3 x 10(-6) M), propranolol (3 x 10(-6) M) and hexamethonium (10(-4) M), did not significantly reduce either component of the contractile response. 2. The neurokinin NK1 receptor antagonists, GR82334 and GR71251, produced concentration-related (EC50 = 564 and 173 nM respectively) inhibitions of the second contraction with no effect on the initial contraction. The neurokinin NK2 receptor antagonists MEN 10207 and Ac-Leu-Asp-Gln-Trp-Phe-Gly-NH2 (R 396), 1 x 10(-9)-10(-5) M, were without effect on either component of the contractile response. 3. Concentration-related inhibitions of the second contraction, with no effect on the initial contraction, were observed after inclusion of the histamine H3 receptor agonists (R)-alpha-methylhistamine (pD2 = 7.6), N alpha-methylhistamine (pD2 = 7.7) and N alpha,N alpha-dimethylhistamine (pD2 = 6.3). Histamine also inhibited the second contraction (pD2 = 6.2) in a concentration-related manner but produced a lower maximum inhibitory effect than the other agonists tested. 4. Inclusion of the H3 receptor antagonists, thioperamide, burimamide, impromidine and phenylbutanoylhistamine, caused parallel concentration-related rightward shifts in the concentration-response curve to (R)-alpha-methylhistamine. In each case, Schild analysis of these data gave slopes not significantly different from unity. Antagonist affinity values for thioperamide (pA2 = 8.2), burimamide (pA2 = 7.0) and impromidine (pA2 = 7.0) were consistent with values obtained in other assays of the H3 receptor. However, phenylbutanoylhistamine (pA2 = 5.8) and betahistine (pKB < 4) had affinities more than ten fold lower than values obtained in other assays of the H3 receptor.5. Exposure of the tissues to N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (10-6 M) for 7-30min followed by extensive washing, had no effect on basal contractions, but produced a rightward shift in the concentration-response curves to (R-alpha-methylhistamine, Nalpha"-methylhistamine, Nalpha",Nalpha-dimethylhistamine and histamine. This treatment also resulted in a decrease in the maximum inhibitory response obtainable. Apparent agonist affinity (pKD) values of 7.01, 7.06, 6.09 and 6.13 were estimated for (R)-alpha-methylhistamine, Nalpha-methylhistamine, Nalpha',Nalpha"-dimethylhistamine and histamine respectively.6. In conclusion, pharmacological analysis has revealed that histamine H3 receptors in the guinea-pig ileum modulate the release of non-adrenergic non-cholinergic neurotransmitters, one of which is probably substance P. In addition we have identified N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline as an irreversible antagonist at H3 receptors and have used this compound to estimate apparent affinity values of agonists at H3 receptors in this preparation.

Adrenergic alpha-Antagonists↗
PubMed1991

Two alpha subunits of the Gq class of G proteins stimulate phosphoinositide phospholipase C-beta 1 activity.

Two G protein alpha subunits were detected in preparations of GTP gamma S-dependent, phosphoinositide-specific phospholipase C-activating proteins from bovine liver membranes. Partial resolution of the two alpha subunits, of molecular mass 42 and 43 kDa, was achieved by Mono Q chromatography. Quantitation of the levels of each alpha subunit and reconstitution assays demonstrated that each possessed stimulatory activity towards the beta 1 isozyme of phospholipase C. Immunoblot analysis showed that the 42 kDa protein was immunologically related to alpha q, whereas the 43 kDa protein was related to alpha 11, another member of the Gq class. The data thus show that two different alpha subunits of the Gq class of G proteins stimulate phospholipase C-beta 1 Activity.

Animals↗
PubMed1991

Activation of the beta 1 isozyme of phospholipase C by alpha subunits of the Gq class of G proteins.

Many hormones, neurotransmitters and growth factors, on binding to G protein-coupled receptors or receptors possessing tyrosine kinase activity, increase intracellular levels of the second messengers inositol 1,4,5-trisphosphate and 1,2-diacylglycerol. This is due to activation of phosphoinositide-specific phospholipase(s) C (PLC), the isozymes of which are classified into groups, alpha, beta, gamma and delta. The beta, gamma and delta groups themselves contain PLC isozymes which have both common and unique structural domains. Only the gamma 1 isozyme has been implicated in a signal transduction mechanism. This involves association with, and tyrosine phosphorylation by, the ligand-bound epidermal growth factor and platelet-derived growth factor receptors, probably by means of the PLC-gamma 1-specific src homology (SH2) domain. Because EGF receptor-mediated tyrosine phosphorylation of PLC-gamma 1 stimulates catalytic activity in vitro and G proteins have been implicated in the activation of PLC, we investigated which PLC isozymes are subject to G protein regulation. We have purified an activated G protein alpha subunit that stimulates partially purified phospholipase C and now report that this G protein specifically activates the beta 1 isozyme, but not the gamma 1 and delta 1 isozymes of phospholipase C. We also show that this protein is related to the Gq class of G protein alpha subunits.

Animals↗
PubMed1991

A survey of wheelchair seating problems of the institutionalized elderly.

This study attempted to define and quantify the need for appropriate seating for elderly nursing home residents. A questionnaire was administered to 200 randomly selected nonambulatory elderly residents living in six Memphis area nursing homes. The study results supported previous findings that many nursing home residents have seating and mobility problems. Of the 139 wheelchair users analyzed, 112 (80%) experienced at least one problem related to discomfort, hindered mobility, or poor posture. Thirty-four percent of the residents had at least one problem considered to be severe. In most cases our respondents' seating and mobility problems could have been solved by the tailored application of presently available technologies.

Aged↗
PubMed1991

Effect of general anaesthesia on the pharynx.

Conventional lateral radiography was used in 18 elderly male patients to investigate the changes induced by general anaesthesia in the upper airway. The effect of tongue traction under anaesthesia was studied similarly in another 11 patients. Following induction of anaesthesia, there were highly significant approximations to the posterior pharyngeal wall of the soft palate (median change 1.3 mm, 95% confidence interval (Cl) 0.3-2.6 mm; P = 0.006), tongue base (mean change 6.5 mm, 95% Cl 5.3-7.7 mm; P less than 0.001) and epiglottis (mean change 3.8 mm, 95% Cl 3.1-4.5 mm; P less than 0.001). Apparent radiographic occlusion of the airway occurred most consistently at the level of the soft palate (17 of 18 patients), sometimes at the level of the epiglottis (four patients), but the tongue base did not touch the posterior pharyngeal wall in any patient. Traction on the tongue failed to clear the nasopharyngeal obstruction. Attempted inspiration under anaesthesia caused major secondary collapse of the pharynx, with multiple sites of obstruction, similar to that found in obstructive sleep apnoea.

Aged↗
PubMed1991

Airway obstruction associated with the use of the Guedel airway.

Soft tissue lateral neck radiography was used in 22 male patients older than 60 yr, to determine the cause of pharyngeal airway obstruction during anaesthesia, before and after insertion of a Guedel airway. In six of the patients, the airway was radiologically and clinically clear with the head in the neutral position. Nine patients showed obstruction of the airway by a "shelf" of tongue, but seven were cleared clinically by dorsiflexion at the atlanto-occipital joint, and the remaining two by the Esmarch-Heiberg manoeuvre. In four of the 22 patients, the Guedel airway was lodged in the vallecula in the neutral position. This was cleared clinically by dorsiflexion at the atlanto-occipital joint in all these patients. In three patients the Guedel airway was obstructed by the epiglottis, but this was cleared by dorsiflexion at the atlanto-occipital joint in two; in the third patient, the Guedel airway slipped into the vallecula after dorsiflexion at the atlanto-occipital joint and remained there despite the Esmarch-Heiberg manoeuvre. There was only one instance in 66 trials of a clinically obstructed airway without an apparent radiological cause. However, there were 10 instances in 66 trials of a clinically clear airway with an apparent radiological cause for obstruction.

Aged↗
PubMed1991

Prescription and positioning: evaluating the physically disabled individual for wheelchair seating.

Within the past 10 years, technology has provided members of the seating team with new approaches in dealing with severely physically disabled children and adults. Positioning is often the first step in overall provision of technical aids. Before physically disabled individuals can operate augmentative communication devices, computer keyboards or other assistive or rehabilitative devices, they should be provided with the optimum seated posture from which to operate. The proximal stability provided by a therapeutically designed seating system will enhance motor potential. Presently, there are many approaches to providing dynamic seating. A thorough evaluation, with input from all team members including the client and his family is necessary to define clearly the goals for the seating device. Once these goals are defined, the team can investigate the possible technical solutions. Thorough ongoing re-evaluation and follow-up of both the client's needs and the possible technical solutions will ensure that persons with physical disabilities will be in the best possible posture to perform the tasks of daily living.

Activities of Daily Living↗
PubMed1991

Radiological study of the Laryngeal Mask.

Lateral soft-tissue radiography was used to determine the location of the Laryngeal Mask (LM) in relation to the larynx and surrounding structures in 24 elderly male patients undergoing general anaesthesia. In a majority of cases (16 of 24) the epiglottis was within the cuff of the mask but without causing discernable airway obstruction in any case. One case of backfolding of the cuff occurred, and there was one case of gross misplacement (also clinically undetected). Supplementary information was obtained in 13 patients by the use of fibre-optic endoscopy, via the lumen of the LM, confirming the inclusion of the epiglottis within the mask and demonstrating a characteristic distortion by the LM of the normal laryngeal anatomy. It is concluded that inclusion of the epiglottis within the LM is commonplace, and misplacements may occur without clinical evidence of a compromised airway.

Anesthesiology↗