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Biomedical subjects

L Drummond

Publications and source records attributed to L Drummond.

At least 19 recordsLinked to original sources
PubMed1996

Stressor-induced alterations of the splenic plaque-forming cell response: strain differences and modification by propranolol.

The effects of stressor application on the splenic plaque-forming cell (PFC) response was assessed in two strains of mice: the BALB/cByJ strain, which is highly responsive to stressors; and the more hardy DBA/2J strain. Both strains exhibited a peak PFC response 120 h following administration of sheep red blood cells (SRBC; 5 x 106 cells). Stressor exposure reduced the immune response; however, the appearance of such an outcome was dependent upon the time at which the stressor was applied relative to SRBC inoculation. In DBA/2J mice, foot-shock applied either immediately after SRBC inoculation or at the time of the peak immune response (120 h) resulted in suppression of the PFC response. In BALB/cByJ mice, both stressor severities provoked an immunosuppression when applied 120 h after inoculation, but when applied 96 h after immunization only foot-shock reduced the PFC response. At other intervals, the stressors were without effect. Pretreatment with the beta-norepinephrine antagonist propranolol precluded the immunosuppression elicited by a stressor applied 96 h after inoculation, but did not affect the reduction of the PFC response elicited by a stressor applied 120 h after inoculation. It is suggested that several factors may contribute to stressor-provoked alterations of the immune response, and that the contribution of these factors vary over the course of an immune response being mounted.

Adrenergic beta-Antagonists↗
PubMed1992

The metabolism of 1,6-dinitropyrene in rat hepatocytes.

This paper reports investigations using hepatocytes to study the metabolism and DNA binding of the environmental contaminant, 1,6-dinitropyrene. Since 1,6-dinitropyrene is not believed to be mutagenic per se, metabolites were synthesized and the metabolism of 1,6-dinitropyrene was subsequently studied in rat hepatocytes. The mode of activation of dinitropyrenes is reduction of one of the nitro groups. Nitroreduction has been shown previously to be oxygen sensitive and therefore the effect of oxygen on the metabolic pattern and DNA binding was investigated by comparing results from aerobic and anaerobic conditions. The binding of [14C]1,6-dinitropyrene equivalents to rat hepatocyte DNA was increased by 15% in the presence of oxygen. Although there was little difference in the rate of 1,6-dinitropyrene metabolism, with or without O2, there was a difference in the metabolic pattern. Under anaerobic conditions there was an increase in the level of the terminal reduction product 1-amino-6-nitropyrene.

Animals↗
PubMed1990

The stereoselectivity of 1,2-phenylethanediol and mandelic acid metabolism and disposition in the rat.

1. The steps involved in determining the chirality of the mandelic acid excreted by rats after administration of ethylbenzene and styrene were investigated by studying the fate of racemic, (R)- and (s)1,2-phenylethanediol, a precursor of mandelic acid. These investigations indicate the occurrence of two alternative routes of metabolism for 1,2-phenylethanediol, one involving retention of configuration and the other resulting in the loss of the chiral centre. 2. The stereoselectivity of the disposition of mandelic acid was investigated; rats were dosed with mandelic acid either as the racemate or as the individual enantiomers, G.1.c.-mass spectrometry and h.p.l.c. were used to determine the enantiomers of mandelic acid. 3. There were at least two routes by which mandelic acid could be metabolized and/or excreted; there is a stereoselective pathway in rat for (s)-mandelic acid, which gives rise to phenylglyoxylic acid. 4. The chiral inversion of (s)-mandelic acid to (R)-mandelic acid is reported; although this has been observed in bacteria it has not previously been observed in mammals. 5. The extent to which mandelic acid is metabolized to phenylglyoxylic acid is dependent on the enantiomeric composition of the mandelic acid administered. There is no evidence to indicate significant ketone-alcohol conversion, that is phenylglyoxylic acid is not significantly reduced to mandelic acid in vivo.

Animals↗
PubMed1989

The metabolism of ethylbenzene and styrene to mandelic acid: stereochemical considerations.

1. The stereochemistry of mandelic acid, produced as a major urinary metabolite of ethylbenzene and styrene in rat and man has been investigated. Although these solvents are both achiral they are metabolized to chiral metabolites, via a series of chiral intermediates. 2. Analytical methods (g.l.c.-mass spectrometry, h.p.l.c. and 19F-n.m.r.) have been developed for the determination of the enantiomeric composition of mandelic acid in urine. 3. These methods have been applied to the study of the metabolic stereochemistry of ethylbenzene and styrene in rats dosed orally (100 mg/kg body weight) and in human volunteers exposed to atmospheres containing these solvents at the upper limits prescribed for workplaces by the UK Health and Safety Executive (100 ppm in air). 4. Results show that whereas only the R-enantiomer of mandelic acid was excreted after ethylbenzene exposure, the mandelic acid formed from styrene was essentially racemic. In three workers occupationally exposed to styrene, ratios of R to S isomers of 1.16, 1.27 and 1.14 were found. A synthetic R/S mixture of mandelic acid had an R/S ratio of 1.03. 5. The implications of these findings for the biological monitoring of workers occupationally exposed to stryrene and/or ethylbenzene are discussed.

Animals↗
PubMed1988

Biological monitoring of workers exposed to benzene in the coke oven industry.

Workers in the coke oven industry are potentially exposed to low concentrations of benzene. There is a need to establish a well validated biological monitoring procedure for low level benzene exposure. The use of breath and blood benzene and urinary phenol has been explored in conjunction with personal monitoring data. At exposures of about 1 ppm benzene, urinary phenol is of no value as an indicator of uptake/exposure. Benzene in blood was measured by head space gas chromatography but the concentrations were only just above the detection limit. The determination of breath benzene collected before the next shift is non-specific in the case of smokers. The most useful monitor at low concentrations appears to be breath benzene measured at the end-of-shift.

Adult↗
PubMed1988

Plasma gamma-hexachlorocyclohexane concentrations in forestry workers exposed to lindane.

Plasma gamma-hexachlorocyclohexane (gamma-HCH) and three urinary trichlorophenols were measured in forestry workers who were engaged in planting seedlings treated with gamma-HCH. These two procedures were assessed as potential biological monitoring methods and the data were compared with reported clinical symptoms. The measurement of plasma gamma-HCH was considered to be a feasible and valid monitoring method for use in routine practice and is a useful indicator of gamma-HCH absorption. The data were used to illustrate the need to be vigilant about personal hygiene and the efficacy of protective clothing. Plasma gamma-HCH concentrations above 70 nmol/l were measured in two workers which coincided with persistent non-specific clinical symptoms. Trichlorophenols were identified in urine but the extensive and variable metabolism of gamma-HCH makes this approach less suitable for biological monitoring.

Agriculture↗
PubMed1986

Development of increased serum immunoblot reactivity against a 45,000-dalton polypeptide of Treponema pallidum (Nichols) correlates with establishment of chancre immunity in syphilitic rabbits.

Rabbits developed chancre immunity 5.0 to 7.5 weeks after intradermal infection with 10(3) Treponema pallidum (Nichols). The serological response against T. pallidum antigen during this 2.5-week period was examined by Western immunoblotting. Sera from rabbits infected for 5.0 weeks contained antibodies against 7 of 13 major T. pallidum immunogens, with strongest binding detected against a polypeptide of Mr 47,000. By 7.5 weeks of infection, syphilitic rabbit sera recognized 10 of 13 antigens; the most evident increase in serological reactivity was directed against a polypeptide of Mr 45,000, suggesting that the development of a strong serological response against this polypeptide correlated with the onset of chancre immunity.

Animals↗
PubMed1986

Secondary lesions in rabbits experimentally infected with Treponema pallidum.

Thirty rabbits infected with 10(3) of either Nichols or Melbourne 1 strains of Treponema pallidum were observed for the development of secondary lesions, which appeared outside areas inoculated with viable treponemes. More rabbits infected with Melbourne 1 strain (eight of 15 rabbits) than were infected with the Nichols reference strain (three of 15 rabbits) developed secondary lesions. The mean (SD) incubation periods of secondary lesions were 52 (8) days for rabbits infected with Melbourne 1 and 56 (4) days for rabbits infected with Nichols strain. These mean incubation periods did not correlate with appreciably increased concentrations of immune complexes or glycosaminoglycans in the serum of infected rabbits.

Animals↗
PubMed1984

Polyanions in syphilis: evidence that glycoproteins and macromolecules resembling glycosaminoglycans are synthesised by host tissues in response to infection with Treponema pallidum.

We investigated by means of radiolabelled precursors the source and nature of the polyanionic macromolecules present in rabbit tissues during active syphilis infection. Previous studies indicated that Treponema pallidum itself does not synthesise glycosaminoglycans, at least in vitro. In replicate experiments on unilaterally infected rabbits, tissue from the orchitic testis incorporated two to three times more 35S-sulphate and 3H-glucosamine (on a wet weight basis) than tissue from the non-orchitic contralateral testis. Incorporation of 35S-sulphate was independent of the number of viable T pallidum organisms present in the infested tissue, which suggested that incorporation represented biosynthesis by the host and not the treponeme. Testes from syphilitic rabbits two days after treatment with high doses (100 mg/kg) of penicillin incorporated less 35S-sulphate than untreated infected testes, but more than normal uninfected rabbit testes. This suggests that active syphilitic infection was necessary for maximum biosynthesis of the macromolecule(s) by host tissue. Hydrodynamic profiles showed incorporation of radiolabelled precursors into two distinct fractions of different sizes, which may represent a proteoglycan and a sulphated glycoprotein. Alcian blue staining of syphilitic testes at or after peak orchitis showed focal deposition of newly synthesised polyanionic components during peak orchitis and a more generalised fibrosis in testes after peak orchitis.

Alcian Blue↗
PubMed1983

The role of respiratory protection on increased survival of Treponema pallidum (Nichols) when cocultivated with mammalian cells in vitro.

The ability of mammalian cells in tissue culture to protect against oxygen toxicity for Treponema pallidum was examined. Addition of catalase to the incubation medium enhanced T. pallidum survival when co-incubation was carried out under aerobic conditions. When co-incubation was carried out under 3% oxygen, catalase had no enhancing effect on survival despite the fact it was still highly stimulatory when T. pallidum was incubated under 3% oxygen in the same medium with no tissue culture cells present. Inactivation of the catalase present endogenously in the mammalian cells by the addition of the catalase inhibitor 3-amino-1,2,4-triazole largely eliminated the enhancing effect of mammalian cells on the survival of T. pallidum under 3% oxygen. Increasing the oxygen consumption of the host mammalian cells with 0.1 mM 2,4-dinitrophenol enhanced T. pallidum under both aerobic and microaerobic conditions; a much greater effect was seen under aerobic conditions. The results indicated that mammalian cells offer significant protection against toxic oxygen reduction products for T. pallidum in vitro under microaerobic conditions.

2,4-Dinitrophenol↗
PubMed1983

Changes in brain ATPases in rats fed on chlordane mixed with iron-sufficient and deficient diet.

The in vivo effects of chlordane on brain Na+-K+, oligomycin-sensitive (O.S) and oligomycin-insensitive (O.I) Mg2+ ATPases in rats were investigated. The rats were fed on 0, 25, 50 and 100 ppm chlordane mixed with iron-sufficient (I.S) and deficient (I.D) diets for 12 weeks. The enzyme activities were determined in the brain P2 fraction of rats at the end of 4, 8 and 12 weeks after treatment. Na+-K+ ATPase activity was reduced in a dose-dependent and time-dependent manner in rats fed on chlordane mixed with I.S and I.D diets. The reduction in the enzyme activity was more pronounced in the rats fed on chlordane mixed with I.D diet as compared to those fed on I.S diet. The brain O.S Mg2+ ATPase was also reduced in rats receiving chlordane. The reduction of O.S Mg2+ ATPase was higher than Na+-K+ ATPase. However, the O.I Mg2+ ATPase activity in rats fed on chlordane was not altered at any dose level. These results indicate that the rat brain ATPases may be particularly sensitive to chlordane.

Adenosine Triphosphatases↗
PubMed1980

Effect of cadmium on ATPase activities in rats fed on iron-deficient and sufficient diets.

Male Sprague-Dawley rats were fed on different levels of cadmium mixed with purified diets containing iron or no iron for 8 weeks. The body weight gain, tissue weights, hemoglobin, hematocrit, liver and brain ATPase were measured at 2, 4 and 8 weeks after feeding. The hemoglobin and hematocrit values were the same in all rats fed on cadmium. The rats fed on iron-deficient diets mixed with cadmium showed a significant decrease in body weight gain. However, the rats receiving only the 100 ppm of cadmium in iron-sufficient diet showed a significant decrease in body weight gain. There were no significant changes in the weights of thymus, spleen, kidney, heart, brain and testes. However, the liver weights were decreased in the highest treatment of cadmium but the liver weight/body ratios were uneffected. Na+-K+ activated ATPase activity in brains of rats fed on cadmium were significantly decreased at 2, 4 and 8 weeks of treatment. The decrease was more pronounced in rats fed on iron-deficient diets. Oligomycin-sensitive (Mitochondrial) Mg2+ ATPase activity was also significantly decreased in liver and brain tissues of rats fed on cadmium. Oligomycin-insensitive Mg2+ ATPase activity, however, was not altered in any tissues tested. It appears that cadmium may be interfering with energy (ATP) production and utilization processes in rat brain and liver tissues.

Adenosine Triphosphatases↗
PubMed1979

Cobalt induced changes in immune response and adenosine triphosphatase activities in rats.

The immuno-biochemical effects of cobaltous chloride in rats receiving iron-sufficient and deficient diets were investigated. Rats receiving 100 ppm or more cobalt showed a significant reduction in thymus and body weights along with a marked decrease in hemoglobin, hematocrit, sheep agglutinins and plaque forming cells. These effects were more pronounced in rats receiving cobalt mixed with iron-deficient diet than those fed on iron-sufficient diet. The Na+-K+ and mitochondrial (Oligomycin-sensitive) Mg2+ATPase activities in brain and liver of rats fed with iron-deficient diets were decreased significantly. However, the ATPase activities in these tissues from rats fed with cobalt mixed with iron-sufficient diets were not altered.

Adenosine Triphosphatases↗
PubMed1979

Inhibition of rat hepatic microsomal cytochrome P-450 system by cobaltous chloride and reversal of inhibition by iron in vivo.

The effects of preexposure of rats to cobaltous chloride (CO) mixed in iron-sufficient (I.S) and -deficient (I.D) diets on hepatic microsomal electron transfer system was investigated. Male Sprague-Dawley rats were fed for 4 weeks on I.D diets mixed with 0, 100 and 200 ppm CO. At the end of 4 weeks three rats from each group were transferred to I.S diets mixed with the same amount of CO. Liver microsomal NADPH - Cytochrome C reductase, NADPH - dehydrogenase, cytochrome P-450 and aniline binding were determined in both batches of rats. The rats receiving CO in the I.D diets showed a 35, 60, 75 and 40% decrease in NADPH - Cyt. C reductase, dehydrogenase, Cyt. P-450 and aniline binding respectively. The rats transferred from I.D diet to I.S diet showed a complete recovery of the inhibition of the microsomal electron transfer system. The rats receiving 200 ppm mixed with I.S diets did not show any changes in any biochemical parameter measured.

Aniline Compounds↗