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Biomedical subjects

J Dawson

Publications and source records attributed to J Dawson.

At least 163 records · Page 9Linked to original sources

Decrease of cellular ATP by dihexanoylglycerol may limit responses to protein kinase C activation.

1,2-sn-Dihexanoylglycerol (HHG) reduced the ATP content of HL-60 cells. This concentration-related (10-100 microM) effect reached a maximum of over 90%, was enantiomerically specific and not accompanied by release of lactate dehydrogenase. Oleoylacetylglycerols (3-100 microM) had no effect on ATP levels while phorbol dibutyrate (PDBu, 0.01-1 microM) decreased ATP content of HL-60 cells by up to 40%. Responses stimulated by HHG became limited as the concentration was increased above 10 microM, this being manifest as either a low maximum response compared to PDBu (superoxide release) or a bell-shaped concentration-effect curve (degranulation). HHG (30-100 microM) inhibited PDBu-stimulated superoxide release, this inhibition being enantiomerically specific. It is probable that the effect of HHG on ATP content impairs cellular responses mediated through protein kinase C activation.

Adenosine Triphosphate↗

Actions of non-steroidal anti-inflammatory drugs on equine leucocyte movement in vitro.

The direct effects of four non-steroidal anti-inflammatory drugs (NSAIDs) on equine polymorphonuclear (PMN) and mononuclear (MN) leucocyte movement were investigated using two in vitro assay systems. The Boyden chamber microfilter technique measures both chemokinetic and chemotactic locomotion, and the agarose microdroplet assay measures solely chemokinesis. Zymosan-activated plasma (ZAP) and the synthetic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) were used as standard chemoattractants for PMN and MN leucocytes, respectively. The actions of six concentrations of each NSAID, indomethacin (50 microM-10 mM), phenylbutazone (10 microM-1 mM), oxyphenbutazone (2.5 microM-500 microM) and flunixin (0.1 microM-50 microM), in suppressing cell movement induced by ZAP and FMLP were investigated. All four drugs exerted inhibitory effects on induced movement of both cell types in the Boyden chamber assay, usually in a concentration-dependent manner, although oxyphenbutazone action on PMN cells occurred only at the highest concentration tested. Significant inhibition of PMN and MN cell locomotion was produced by indomethacin, flunixin and oxyphenbutazone, and inhibition of PMN movement by phenylbutazone occurred in the agarose microdroplet assay. Flunixin was the most potent of the four drugs investigated in both assay systems. The findings may be of importance to the use of phenylbutazone and flunixin as NSAIDs in equine medicine, since the concentrations used were similar to concentrations of both drugs and the phenylbutazone metabolite oxyphenbutazone previously reported to occur in equine plasma and inflammatory exudate.

Animals↗

Computer-aided medical ethics.

This paper describes COMET, the first 'expert' computer system to incorporate a comprehensive set of the rules of law and medical ethics relating to consent to medical treatment.

Computer Systems↗

The activation of carrageenan air pouch inflammation by silica and its effects on cartilage degradation.

We have examined the effects of carrageenan inflammation activated by silica particles on implanted femoral-head cartilage. The injection of silica particles modifies the inflammatory response, inducing a prolonged polymorphonuclear leucocyte infiltration and low exudate volume. This modification in the inflammatory response resulted in an accelerated loss of proteoglycan by the implanted femoral heads. Examination of exudate interleukin 1 (IL-1) concentrations directly by a lymphocyte-activating assay and indirectly by measuring the acute-phase response indicated that the increased loss was not due to increased levels of IL-1. High levels of lactate dehydrogenase would suggest that the increase cartilage breakdown is due to dying polymorphonuclear leucocytes releasing their intracellular enzymes. It is concluded that injection of silica together with carrageenan produces a pathological environment similar to that seen in human septic arthritis.

Animals↗

Influence of chemotactic agents on the locomotion of equine polymorphonuclear and mononuclear leucocytes.

Subpopulations of equine leucocytes, polymorphonuclear and mononuclear cells, were separated from whole blood on a discontinuous Percoll gradient and used in studies of chemokinesis and chemotaxis. Polymorphonuclear cells responded to the chemo-attractant properties of zymosan-activated plasma in Boyden chamber and agarose microdroplet assays but they responded only slightly (Boyden chamber) or not at all (agarose microdroplet) to the peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP). Equine mononuclear cell movement was increased by FMLP in both assay systems and these cells also responded to zymosan activated plasma in the Boyden chamber assay but not in the agarose microdroplet. It is concluded that factors controlling equine polymorphonuclear and mononuclear cell movements into inflammatory exudates may differ.

Animals↗

Inhibition of phorbol ester stimulated superoxide production by 1-oleoyl-2-acetyl-sn-glycerol (OAG); fact or artefact?

OAG-stimulated superoxide (O2) production by HL-60 granulocytes showed enantiomeric specificity but reached a maximum of only 5% of that produced by either phorbol myristate acetate (PMA) or phorbol dibutyrate (PDBu). At 10-100 microM, OAG displaced specifically-bound [3H]PDBu from intact HL-60 cells by only 25%, suggesting limited cell penetration. OAG (10-100 microM) also inhibited PDBu-stimulated O2 production by 25%; this inhibition was enantiomerically specific. However, at a lower concentration (3 microM), both enantiomers of OAG fully blocked O2 production stimulated by PMA (0.5 microM). This inhibition is probably artefactual, due to the hydrophobic PMA physically associating with OAG in the extracellular fluid.

Animals↗

Easeful death.

Explore the source record for details and available documents.

Attitude of Health Personnel↗

Procedures for manufacturing double-barrelled ion-sensitive microelectrodes employing liquid sensors.

Liquid ion-sensitive/selective sensors are available for most inorganic ions of physiological and biochemical importance. In order to measure intracellular ionic activities in relatively small cells, it is advisable to manufacture and use double-barrelled microelectrodes. Procedures for making two types of double-barrelled ion-sensitive microelectrode are described in detail. Such microelectrodes have been used successfully to measure intracellular K+, Cl- and Na+ activities in retinal horizontal cells of fish and body-wall muscles of insect larvae.

Animals↗

Jejunal mucosal enzyme activities, regulatory peptides and organelle pathology of the enteropathy of common variable immunodeficiency.

Jejunal biopsies from six patients having the small bowel enteropathy associated with common variable immunodeficiency have been subjected to analytical subcellular fractionation and enzymic and regulatory peptide microassay to define the organelle pathology of this syndrome. Compared with normal subjects, the immunodeficient patients had decreased activities of the three brush border enzymes: alkaline phosphatase, gamma-glutamyl transferase and alpha-glucosidase. The other organelle marker enzyme activities and all the regulatory peptide concentrations did not differ from the controls. Density gradient experiments showed a complete loss of particulate beta-glucosidase (lactase) with activity entirely located in the cytosol. The integrity of other organelles was normal. These data indicate that the enteropathy of common variable immunodeficiency is associated with abnormalities in the jejunal brush border analogous to those present in tropical malabsorption syndrome.

Adult↗

A randomized controlled trial of variceal compression as an adjunct to endoscopic variceal sclerosis.

Endoscopic variceal sclerosis is effective at eradicating oesophageal varices and prolonging survival, but early rebleeding before varices have been obliterated remains a problem. A randomized controlled trial was therefore conducted to determine whether more rapid variceal obliteration and hence a lower morbidity and mortality in the first month could be achieved by compressing the varices after the first injection of sclerosant. Forty patients bleeding from previously untreated varices were studied. There was no demonstrable benefit from post-sclerosis variceal compression in terms of early death from rebleeding (compression, 3 of 19; no compression, 3 of 21 in the first month), total number of patients rebleeding (compression, 5 of 19; no compression, 6 of 21 in the first month), or speed of variceal obliteration (percentage of variceal columns obliterated at 1 month: compression, 13%; no compression, 26%). This study shows that post-sclerosis variceal compression by means of the Williams overtube and Sengstaken tamponade does not improve the efficacy of endoscopic variceal sclerosis.

Clinical Trials as Topic↗

Is chloride depletion an important contributing cause of death in infants with bronchopulmonary dysplasia?

A retrospective analysis of infants with bronchopulmonary dysplasia requiring prolonged hospitalization (greater than 100 days) was carried out to determine those factors associated with fatal outcome. Twenty-three infants made up the study population. Eleven infants died and 12 survived (survivors). No differences were noted between the groups regarding ventilator requirement, radiographic changes, and medication use (digoxin, aldactazide), except for furosemide which was used twice as frequently in the group of infants who died v the group of infants who survived (P less than .001). Differences noted between the groups included moderate hypochloremia (chloride less than 80 mEq/L) in all 11 infants who died v six of 12 survivors, severe hypochloremia (chloride less than 70 mEq/L) in the nine of 11 infants who died v two of 12 survivors, metabolic alkalosis (pH greater than 7.45) in nine of 11 infants who died v three of 12 survivors, hypertension (systolic BP greater than 113 mm Hg) in eight of 11 infants who died v one of 12 survivors, decrease in head growth in ten of the 11 infants who died v one of the 12 survivors; these differences were all significant (P less than .001). The metabolic alkalosis and head growth changes appear to be related to the hypochloremia. The data suggest that chloride deficiency may be an important contributing factor in the genesis of poor outcome in infants with bronchopulmonary dysplasia and that close attention to chloride supplementation might influence outcome.

Acid-Base Imbalance↗

The peripheral vascular effects of nifedipine in Raynaud's syndrome associated with scleroderma: a double blind crossover study.

The effectiveness of nifedipine in the treatment of Raynaud's syndrome was assessed in 16 patients with systemic sclerosis or a variant of this condition. Changes in finger and forearm blood flow (venous occlusion plethysmography), skin temperature and digital systolic pressure were measured both during the acute period and after a 2-week treatment. Subjective assessment of efficacy was based on patient diary data. Finger blood flow increased significantly both during the acute period and after 2 weeks of nifedipine therapy compared to placebo (P less than 0.05). Digital skin temperature also increased during the study period (P less than 0.01). Forearm blood flow and digital systolic pressure did not change. Nifedipine significantly reduced the frequency (P less than 0.05), duration (P less than 0.05) and severity (P less than 0.01) of attacks. Eleven out of the sixteen patients experienced side effects while on nifedipine. These results suggest that nifedipine is of benefit in the treatment of Raynaud's syndrome in patients with systemic sclerosis over a short time course.

Adolescent↗