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Biomedical subjects

G D Gray

Publications and source records attributed to G D Gray.

At least 37 records · Page 2Linked to original sources
PubMed1992

Parasitological and immunological responses of genetically resistant Merino sheep on pastures contaminated with parasitic nematodes.

One hundred and twenty lambs were grazed continuously from weaning until 9 months of age on 12 plots contaminated with larvae of three nematode species (Haemonchus contortus, Trichostrongylus colubriformis and Ostertagia circumcincta). The lambs were sired by either a genetically resistant ram or susceptible rams (determined by the response of previous progeny to artificial H. contortus infection). Half the resistant and half the susceptible lambs were given strategic anthelmintic treatment and the remainder remained untreated. Faecal egg counts and blood packed cell volume were measured frequently in all animals. One and 5 months after weaning, two lambs from each plot were slaughtered, and worm burdens and larval establishment rates of the three species of nematode were estimated. At the second slaughter, leukotriene levels and larval migration inhibitory (LMI) activity were measured in mucus collected from the small intestine. The dominant species in all faecal samples and the gastrointestinal tract was T. colubriformis. Lambs of the resistant genotype had lower faecal worm egg counts, lower worm burdens and higher levels of resistance to larval establishment. There were no differences in larval migration inhibition (LMI) activity, but resistant lambs had higher levels of the leukotriene LTC4/D4/E4. Further, the resistant genotype, identified on responsiveness to artificial infections with H. contortus, was more resistant to infections of three important species acquired naturally from contaminated pastures. All these genetic differences were maintained while the lambs were subject to strategic anthelmintic treatment.

Animals↗
PubMed1988

The effect of immunosuppression with dexamethasone on Haemonchus contortus infections in genetically resistant merino sheep.

The effect of immunosuppression with the glucocorticosteroid, dexamethasone, on the susceptibility to Haemonchus contortus infection of a highly resistant Merino genotype was investigated. Higher faecal egg counts, larger worm burdens and heavier worms were recorded in immunosuppressed wethers. The characteristic globule leucocyte infiltrate in the abomasum of resistant wethers (12-month-old castrated males) was absent in immunosuppressed animals. Treatment with dexamethasone abolished differences between resistant and susceptible genotypes in faecal egg counts, worm weights, thymus weights and globule leucocyte responses to infection with H. contortus. These results suggest that an immunological basis underlies the high level of resistance to infection in the resistant genotype.

Animals↗
PubMed1987

Genetic resistance to haemonchosis in sheep.

Parasitic nematodes cause huge economic losses to the domestic livestock industry. Control requires skilled farm management and heavy use of anthelmintics, but breeding for resistant animals has long been held a possibility. For about 20 years after World War ll, the genetics of association between sheep breeds and Haemonchus contortus - the main parasite of importance in sheep - was studied in the USA and Europe. Since the early 1970s, however, such studies have received greater emphasis in Australia, where anthelmintic resistance has become widespread. In this article, Douglas Gray discusses the background to breeding programmes for resistance to hoemonchosis - paying homage to the 'Golden Ram', a Merino believed to have carried a single major gene for immunological resistance to Haemonchus and Trichostrongylus.

Journal Article↗
PubMed1986

Feline polymorphonuclear leukocytes respond chemotactically to leukotriene B4 and activated serum but not to F-Met-Leu-Phe.

The chemotactic response of feline polymorphonuclear leukocytes (PMNs) to three types of chemoattractants was studied. Feline PMNs responded to leukotriene B4 as well as to agarose-activated autologous and homologous serum. However, no response was obtained to N-formylmethionylleucylphenylalanine (FMLP), and four similar peptides that activate the FMLP receptor (N-formylnorleucylleucylphenylalanine, N-formylmethionylphenylalanine, methionylleucylphenylalanine, and pepstatin). Thus, feline PMNs are similar to equine, porcine, bovine and canine PMNs which also do not respond chemotactically to these peptides.

Animals↗
PubMed1986

The role of cyclooxygenase and lipoxygenase pathways in the adhesive interaction between bovine polymorphonuclear leukocytes and bovine endothelial cells.

The effects of arachidonic acid metabolites, analogues and cyclooxygenase/lipoxygenase inhibitors were tested on an "in vitro" bovine model of endothelial cell (EC)-polymorphonuclear leukocyte (PMN) adhesion. Arachidonic acid blocked adhesion at 10(-5)M, a dose which also induced aggregation of PMN. Lower doses did not affect either EC-PMN adhesion or PMN aggregation. Various cyclooxygenase pathway metabolites were inactive in the EC-PMN adhesion assay, with the exception of prostaglandin A2 and prostaglandin B2 which significantly suppressed adhesion at 10(-5)M. Of the synthetic analogs tested, 6 alpha-carbaprostacyclin I2, (5Z)-9 beta-ethynyl-calcium salt (U-64,567E) was inhibitory at 10(-5)M. The cyclooxygenase inhibitors acetylsalicylic acid, indomethacin and ibuprofen were inactive. Products of the lipoxygenase pathways, leukotriene B4 (LTB4), 5-hydroxyeicosatetraenoic acid (5-HETE) and 15-hydroperoxyeicosatetraenoic acid (15-HPETE) exhibited variable inhibitory activity at 10(-5)M only. Paradoxical effects were observed with the putative lipoxygenase inhibitors 4,7,10,13-eicosatetraynoic acid (4,7,10,13 ETYA), 5,8,11,14-eicosatetraynoic acid (5,8,11,14 ETYA) and nordihydroguairetic acid (NDGA), which also suppressed EC-PMN adhesion at 10(-5)M. The dual cyclooxygenase-lipoxygenase inhibitor, BW755C was inactive. Bovine PMNs did not respond chemotactically to LTB4 although they were able to synthesize the 5-lipoxygenase products LTB4 and 5-HETE.

Adhesiveness↗
PubMed1986

Countergradients of nonchemotactic ligands for N-formylmethionylleucylphenylalanine (FMLP) receptors promote FMLP-induced chemotaxis.

Using the under-agarose chemotaxis assay, addition of compounds known to inhibit chemotaxis of leukocytes toward N-f-Met-Leu-Phe (FMLP) was made to the first well in a line of three wells, leukocytes to the middle well, and a slight excess of FMLP to the third well. The compounds included rifampin, fusidic acid, carbobenzoxy Phe-Met, phenylbutazone, sulfinpyrazone, sulfasalazine, and sulfapyridine. The countergradients created in this system markedly stimulated, not inhibited, locomotion toward FMLP. These results, based on functional responses, confirm data using radiolabeled FMLP and support the hypothesis that these compounds are nonchemotactic ligands for FMLP receptors.

Binding, Competitive↗
PubMed1986

Antibiotic binding to human polymorphonuclear neutrophils, mouse leukemia L1210 cells and mouse thymocytes.

This report describes a system in which antibiotics could be compared for binding to different mammalian cells. These included functional phagocytes (human polymorphonuclear neutrophils; PMNs), non-phagocytic lymphocytes (mouse thymocytes), and non-functional leukocytes (mouse leukemia L1210 cells). When antibiotics bound to PMNs, they bound about the same to L1210 cells but much less to thymocytes. Combining these data with previous data, the ranking of cells that bound the greatest amount of antibiotics was: PMNs = L1210 cells = blood mononuclear leukocytes greater than thymocytes greater than erythrocytes. Thus, antibiotics bind differentially and not indiscriminately to mammalian cells.

Animals↗
PubMed1984

A simple system for studying antibiotic binding to leukocytes.

Studies on the interaction between antibiotics and polymorphonuclear leukocytes (PMLs) usually require the availability of radiolabeled antibiotic, that the antibiotic kill intraleukocyte pathogens, or that the antibiotic affect some function of the leukocyte. The system described here does not have the requirements above but depends instead upon anti-staphylococci activity. The key features of the system are that, following incubation, extracellular antibiotic was removed from PMLs by centrifugation, contact between Staphylococcus aureus 502A and the phagocyte-antibiotic complex was assured by centrifugation at 4 degrees C in 96 well tissue culture dishes, phagocytosis was induced by incubation at 37 degrees C, and assessment of surviving bacteria was accomplished by collecting [3H]thymidine labeled bacteria using a cell harvester. Antibiotics that were active in this system included naphthalenic ansamycins (rifamycins and streptovaricins ), lincosaminides ( clindamycins and pirlimycins ), coumarins (novobiocin), erythromycin, tetracycline, tyrocidine and paulomycin .

Anti-Bacterial Agents↗
PubMed1983

Suppression of primary and secondary antibody responses and inhibition of antigen priming during Babesia microti infections in mice.

The antibody response to sheep red blood cells (SRBC) has been measured in C57Bl mice infected with the intra-erythrocytic piroplasm Babesia microti. The primary antibody response is severely reduced or abolished when antigen is administered at the time of maximum parasitaemia. The secondary antibody response of infected mice, which had been primed with SRBC, is reduced but retains the characteristics of a secondary response. Mice injected with SRBC at maximum parasitaemia failed to become primed to that antigen: these mice gave a primary antibody response to a second injection of SRBC given after the infection had become sub-patent. B. microti, therefore, can completely prevent the induction of memory, but only partially inhibit the expression of memory.

Animals↗
PubMed1983

Rifampin affects polymorphonuclear leukocyte interactions with bacterial and synthetic chemotaxins but not interactions with serum-derived chemotaxins.

Three independent experimental approaches support the hypothesis that rifampin competes for receptors on polymorphonuclear leukocytes (PMLs) with small peptide chemoattractants, e.g., N-formylmethionylleucylphenylalanine (FMLP), but not with serum-derived chemoattractants (C5a). First, rifampin inhibited chemotaxis induced with FMLP but reversed the immobilization of PMLs that occurred at high FMLP concentrations. Second, rifampin competed with radiolabeled FMLP for binding sites on PMLs and displaced already-bound radiolabeled FMLP. Third, rifampin blocked and reversed the bipolar shape changes induced in PMLs by FMLP. These effects occurred at concentrations attained during rifampin therapy and were not due to rifampin toxicity. In contrast, no effect of rifampin was observed on serum-derived chemoattractants (C5a) in any of the three systems. The evidence suggests, therefore, that rifampin is a ligand for FMLP-type receptors on PMLs.

Binding, Competitive↗
PubMed1983

Hormonal changes and sexual function in aging men.

A cross-sectional study on 220 men, aged 41-93 yr, was conducted to determine whether age-related changes in circulating pituitary and gonadal hormone levels are related to quantitatively assessed changes in sexuality over this age span. The conclusion of most previous studies, that total and free plasma testosterone (T) levels decline with advancing age as gonadotropins increase, was corroborated. These changes were found to roughly parallel a decline in sexual function affecting the level of sexual activity, libido, and potency measures. PRL and estradiol did not change with age, and the age-related decline in free T was greater than that in total T. Decreases in free T and increases in LH manifested significant, but small, correlations with sexual hypofunction. Behavioral variables were also clearly related to LH and to the ratio of free T to LH and estradiol. The data also suggested that aging and hormonal changes were more strongly related to sexual activity and nocturnal erections that to libido (enjoyment, drive, and thoughts). Partial correlation procedures demonstrated that diseases and drugs were not responsible for the hormone-behavior relationships. Declining androgen levels, reduced sexual activity, and decreased sexual interest thus appear to be related sequelae of the aging process in men. Hormonal factors do not completely account for age-related changes in sexuality, although the full explanation of these changes must include a consideration of hormonal factors.

Adult↗
PubMed1983

MIC values do not predict the intraphagocytic killing of Staphylococcus aureus by naphthalenic ansamycins.

Ten naphthalenic ansamycins were compared for their ability to kill extracellular or phagocytosed Staphylococcus aureus 502A. These included rifamycins, streptovaricins and tolypomycin Y. Although the compounds differed markedly in killing extracellular S. aureus, there was surprisingly little difference between them in assisting human leukocytes to kill phagocytosed S. aureus. In fact, when compared to rifampin, some ansamycins that were less effective in killing extracellular bacteria were more effective in killing phagocytosed bacteria. These data, together with an analysis of structure and activity, suggested that a specific transport mechanism might be involved. First considered was a vitamin K transport mechanism. Indeed warfarin, a vitamin K antagonist, blocked the ability of rifampin to kill phagocytosed S. aureus, as did the coumarins, novobiocin and coumarin-3-carboxylic acid. However, direct evidence for a vitamin K transport mechanism could not be obtained using vitamin K preparations. The fused phenolic, bicyclic system common to all of these ansamycins was tentatively considered to be the portion necessary for phagocyte penetration.

Anti-Bacterial Agents↗
PubMed1983

Relapsed parasitaemia following chemotherapy of chronic T. brucei infections in mice and its relation to cerebral trypanosomes.

Mice infected with Trypanosoma brucei can be easily cured using the available trypanocidal drugs, provided treatment is given soon after the infection; however, if infection is allowed to continue for some time then it is extremely difficult to obtain a permanent cure, and after an aparasitaemic period the infection eventually relapses. It has been shown that a relatively small number of infective trypanosomes in the brain have escaped the action of the drug and these are able to replicate and eventually they re-establish a circulating parasitaemia. The number of infective trypanosomes remaining after chemotherapy varied according to the stabilate of T. brucei, but using the stabilate T. brucei GVR 35 there were up to, 5,000 infective trypanosomes 2 days after treatment, and this rapidly increased up to 50,000 trypanosomes at 7 days. Infected mice on histological examination exhibited a mild meningitis and this was exacerbated by Berenil therapy and 7 days posttreatment the mice had an acute meningoencephalitis. It would appear that if the infective trypanosomes are completely eliminated from the brain this exacerbated reaction does not occur. It has been found that combined treatment of chronic T. brucei infections with either diminazene aceturate or suramin followed by 5-substituted nitroimidazoles at appropriate dose levels will completely eliminate the infective trypanosomes from the brain and the mice are permanently cured.

Animals↗
PubMed1982

The possible use of Trypanosoma musculi infection in mice as a screening test for potential Trypanosoma cruzi-active drugs.

The ability of a range of trypanocidal drugs, including a number known to be active in Trypanosoma cruzi infections were tested against Trypanosoma musculi infections in the mouse. The ability of these drugs, particularly in their ability to eliminate the "cryptic phase" of T. musculi infections remaining in the kidneys, was investigated and their activity against this phase of T. musculi largely paralleled their known activity against T. cruzi infections. It is suggested that this could be used as a preliminary screening test for potential T. cruzi-active drugs.

Animals↗