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Biomedical subjects

W A Scott

Publications and source records attributed to W A Scott.

At least 127 records · Page 7Linked to original sources
PubMed1981

Depletion of glutathione selectively inhibits synthesis of leukotriene C by macrophages.

We have examined the role of glutathione synthesis and intracellular glutathione content in the formation of leukotriene C (LTC) by mouse peritoneal macrophages. For this purpose, we utilized the drug buthionine sulfoximine (BSO), a specific inhibitor of glutathione synthesis. Thirty minutes after the addition of BSO (200 microM) to macrophage cultures, when glutathione synthesis was inhibited approximately 80%, the cells responded to a zymosan challenge with a normal release of LTC. During this period, intracellular glutathione stores were not significantly depleted. Cells exposed to BSO for 2 hr or more exhibited marked decreases in glutathione levels and a progressive inhibition of LTC synthesis. After exposure to BSO for 16 hr, intracellular glutathione was undetectable, and no LTC was synthesized by the cells. Treatment of macrophages with BSO for 16 hr had no effect on cell viability, phagocytosis, total release of arachidonic acid, or prostaglandin synthesis. However, an increased synthesis of hydroxyicosatetraenoic acids in BSO-treated cells compensated for the diminished production of LTC. We conclude that BSO produces a specific, time-dependent inhibition of LTC synthesis as a result of intracellular glutathione depletion. This is consistent with a biosynthetic pathway for LTC in which glutathione is a direct precursor of this arachidonic acid metabolite.

Animals↗
PubMed1981

Distribution of DNase I-sensitive sites in simian virus 40 nucleoprotein complexes from disrupted virus particles.

Nucleoprotein complexes (core particles) released from simian virus 40 (SV40) virions were compared with similar complexes (SV40 chromatin) extracted from nuclei of infected cells. Core particles were sensitive to cleavage by DNase I at about the same enzyme concentration required to cleave SV40 chromatin. DNase I preferentially cleaved SV40 chromatin adjacent to the viral origin of replication; however, cleavage of core particles occurred with much less selectivity. The difference between these nucleoproteins was not due to a structural alteration induced by the virion disruption procedure, since SV40 chromatin retained its pattern of DNase I-sensitive sites when subjected top this treatment. On the other hand, core particles did not acquire the nuclease-sensitive feature typical of SV40 chromatin when they were exposed to infected cell nuclei and the Triton X-100-EDTA extraction procedure. Hence, the nuclease-sensitive feature was lost or altered during the normal process of virion assembly and maturation.

Chromatin↗
PubMed1981

Mortality of nickel workers: experience of men working with metallic nickel.

The mortality of men employed in a plant manufacturing nickel alloys from metallic nickel and other metals has been examined. The plant has operated since May 1953, and 1925 men were identified who had been employed in the operating areas at the plant, other than as members of the staff, for a total of five or more years, excluding breaks. Analysis of samples of air obtained from personal samplers showed that since 1975 most of the men are likely to have been exposed to average concentrations of nickel of between 0.5 and 0.9 mg Ni/m3. All but 22 (1.1%) of the men were successfully traced to 1 April 1978 or until they died or emigrated. One hundred and seventeen had died. The numbers of deaths observed from cancers of respiratory and other sites, other respiratory disease, ischaemic heart disease, and other causes of death were compared with the numbers expected from national and local mortality rates. No evidence of the existence of any occupational hazard was obtained. The number of deaths from lung cancer (15) in men employed for five years or more is small. At 98% of the number expected at local rates it is statistically compatible with risks of between 0.5 and 2.2 times "normal."

England↗
PubMed1981

Benzbromarone therapy in hyperuricaemia.

A series of patients with hyperuricaemia associated with rheumatic symptoms were treated with Benzbromarone (Minuric) and followed over a period of 5 months. Each patient was assessed clinically and biochemically before and at regular monthly intervals during the trial. All patients showed a marked reduction in serum uric acid levels and a significant increase in urinary uric acid elimination rates. Some degree of clinical improvement was noted in most patients and the drug was well tolerated throughout the study. Two patients were withdrawn during the trial; one because of diarrhoea, probably due to benzbromarone and the other because of lack of efficacy.

Adult↗
PubMed1980

Dynamics of leukotriene C production by macrophages.

A method for the radiochemical assay of LTC production by mouse peritoneal macrophages in vitro is presented. The method involves labeling macrophages in culture with [5,6,8,9,11,12,14,15-3H]20:4 followed by stimulation of arachidonic acid (20:4) release under the experimental conditions desired. Radiolabeled leukotriene C (LTC) is recovered from the culture medium by extraction and silicic acid chromatography in 40% yield with full retention of biological activity. Because this LTC is radiochemically pure, the quantity of LTC release may be estimated from the amount of radioactivity in the sample. Use of the radioassay to study parameters affecting LTC synthesis by macrophages indicated that the time course of LTC synthesis and its relationship to the dose of a phagocytic stimulus (zymosan) were very similar to those of prostaglandin (PG) release. LTC release was also similar to that of PG in that lower levels of both metabolites were produced by Corynebacterium parvum-elicited macrophages than by resident cells. Finally, LTC release was stimulated in response to a challenge with antigen-antibody complexes, but lower maximal levels were attained than those with zymosan. The data presented here are consistent with the hypothesis that challenge of macrophages with a phagocytic stimulus leads to the release of 20:4 by an inducible phospholipase. Cyclooxygenase and lipoxygenase then compete for the released 20:4, leading to the production of PG, hydroxyeicosatetraenoic acids, and LTC.

Animals↗
PubMed1980

Regulation of arachidonic acid metabolites in macrophages.

The lipids of mouse peritoneal macrophages contain high levels (25 mole percent) of esterified arachidonic acid (20:4). Following in vitro exposure to unopsonized zymosan, these cells synthesize and release oxygenated products of 20:4. Maximal levels of zymosan ingestion promote the release of 40-50% of the 20:4 content of cultures without loss of viabilitiy. Release of radiolabel from macrophages prelabeled with [3H]20:4 provides a quantitative measure for the synthesis of 20:4-derived products. Approximately 67% of the released 20:4 is recovered as prostaglandins (PG) (51% PGE and 16% 6-oxo-PGF1 alpha) and the remainder as apolar products tentatively identified as hydroxy-eicosatetraenoic acids. The kinetics of synthesis are comparable for both sets of products. A detailed examination of PGE synthesis indicated the PGE levels rise in parallel with phagocytosis during a continuous exposure of macrophages to zymosan. The concentration of particles determines the initial rate of PGE release, but the time-course of synthesis is finite (approximately 60 min), regardless of the zymosan dose. These observations are compatible with the notion that phagocytosis results in a burst of PG synthesis, the size of which is determined by the phagocytic stimulus. This is supported by the finding that secondary challenges of zymosan promote new rounds of PG synthesis by macrophages.

Animals↗
PubMed1980

Plasma membrane of Entamoeba histolytica.

Axenically propagated Entamoeba histolytica (HK9:NIH strain) were employed as starting material for the isoation of plasma membrane by a novel procedure. In the absence of known enzymatic markers, the externally disposed polypeptides of intact amoebae were iodinated and the incorporated label used to monitor membrane separation and recovery. 12 major plasma membrane polypeptides (12 x 10(3)-200 x 10(3) mol wt) were labeled and separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Each of these was a glycoprotein. Preincubation of amoebae with concanavalin A stabilized the plasma membranes as large sheets, facilitating its separation by low-speed centrifugation. Dissociation of the lectin with alpha-methyl mannoside, followed by additional homogenization led to vesiculation and further purification. The isolated plasma membrane was recovered in high yield (28%) and enriched 30-fold in terms of incorporated iodide. All iodinated surface glycoproteins of the intact organism were present in the plasma membrane fraction. A Ca++-dependent ATPase was enriched in the plasma membrane to a similar extent, but over one-half of the total activity was associated with internal, unlabeled membranes, suggesting a dual localization of this activity. The isolated plasma membrane was enriched in cholesterol and had a cholesterol:molar ratio of 0.87. It also contained larger amounts of an unusual phospholipid--ceramide aminoethyl phosphonate--a phospholipase-resistant species.

Acid Phosphatase↗
PubMed1980

Ataxia and spinal cord degeneration in llama, wildebeeste and camel.

Clinical and pathological findings from instances of ataxia in a group of wildebeeste (Connochaetes taurinus), two llamas (Llama glama) and one Arabian camel (Camelus dromedarius) are presented. Clinically, all the affected animals showed a non-febrile, progressive ataxia. Neuropathologically, Wallerian degeneration was diffuse in the spinal cord of the camel and llamas but was focal in the wildebeeste. Degeneration was present in the cervical dorsal roots in the wildebeeste and in the ventral nerve roots at all levels of the cord in the llamas. Peripheral nerve were affected in all the species. The possible roles of copper deficiency and plant poisons in the aetiology of the condition are discussed.

Animals↗
PubMed1980

Prostaglandin synthesis by macrophages requires a specific receptor-ligand interaction.

The ingestion of particles by macrophages leads to the prompt induction of prostaglandin (PG) synthesis. We have now dissected the endocytic process and examined the requirements of prostaglandin E (PGE) synthesis for particle attachment, membrane interiorization, and phagosome-lysosome fusion. Macrophages that were loaded with the polyanion dextran sulfate and exhibited a greater than 99% inhibition of phagosome-lysosome fusion produced normal amounts of PGE upon challenge with zymosan. Inhibition of membrane interiorization with cytochalasin D was similarly ineffective in blocking PGE synthesis. The addition of large numbers of unmodified polystyrene latex beads, which were readily ingested by macrophages, failed to stimulate PGE synthesis. However, when macrophages were challenged with latex beads coated with immune complexes, an increased synthesis of PGE resulted. No response occurred if the complex was prepared with the F(ab')2 fragment of IgG. Similar results occurred when nonphagocytizable Sephadex beads coated with immune complexes were employed. We conclude that particle binding to the Fc receptor of the macrophage plasma membrane is a sufficient stimulus for PGE synthesis.

Animals↗
PubMed1980

Mouse peritoneal macrophages release leukotriene C in response to a phagocytic stimulus.

Mouse peritoneal macrophages that had ingested zymosan particles released a polar metabolite of arachidonic acid possessing slow-reacting substance activity in the guinea pig ileum assay. The metabolite was purified by solvent extraction, Sephadex G-25 column chromatography. The purified metabolite absorbed light at 280 nm and contained a free amino group. When macrophages were preincubated overnight with [3H]arachidonic acid, [35H]cysteine, or [14C]glutamic acid, each radiolabel was incorporated into the compound. Direct amino acid analysis revealed glycine, glutamic acid, and cysteine at molar ratios of 0.97:1.00:0.82. The above data were consistent with the structure of leukotriene C, an adduct of arachidonic acid and glutaathione. Quantification of the leukotriene C based on incorporation of [3H]arachidonic acid or amino acid analysis indicated that 6 X 10(7) macrophages (3.6 mg of cell protein) released 7.5 nmol after a maximal phagocytic stimulus. The purified leukotriene C had a slow reacting substance activity of 11,500 units/nmol (1 unit has the activity of 5 ng of histamine in a guinea pig ileum contraction assay).

Amino Acids↗
PubMed1980

Asymptomatic hyperuricaemia and its early treatment.

Sixteen patients with asymptomatic hyperuricaemia were treated with "Citro-Soda', an urinary alkanlinizing agent, in a dose of 4 g four times daily for one month. Ten of the sixteen patients exhibited a meaningful reduction in serum uric acid (greater than 15%). No adverse effects were noted and various haematological and urinary tests were all normal. 'Citro-Soda' could, therefore, be considered a useful and well-tolerated adjunct in the treatment of hyperuricaemia.

Bicarbonates↗