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A L Foster

Publications and source records attributed to A L Foster.

11 recordsLinked to original sources

Mineral surfaces and bioavailability of heavy metals: a molecular-scale perspective.

There is a continual influx of heavy metal contaminants and pollutants into the biosphere from both natural and anthropogenic sources. A complex variety of abiotic and biotic processes affects their speciation and distribution, including adsorption onto and desorption from mineral surfaces, incorporation in precipitates or coprecipitates, release through the dissolution of minerals, and interactions with plants and microbes. Some of these processes can effectively isolate heavy metals from the biosphere, whereas others cause their release or transformation to different species that may be more (or less) bioavailable and/or toxic to organisms. Here we focus on abiotic adsorption and precipitation or coprecipitation processes involving the common heavy metal contaminant lead and the metalloids arsenic and selenium in mine tailings and contaminated soils. We have used extremely intense x-rays from synchrotron sources and a structure-sensitive method known as x-ray absorption fine structure (XAFS) spectroscopy to determine the molecular-level speciation of these elements at concentrations of 50 to several thousand ppm in the contaminated environmental samples as well as in synthetic sorption samples. Our XAFS studies of As and Pb in the mine tailings show that up to 50% of these contaminants in the samples studied may be present as adsorbed species on mineral surfaces, which makes them potentially more bioavailable than when present in sparingly soluble solid phases. Our XAFS studies of Se(VI) sorption on Fe2+-containing sulfates show that this element undergoes redox reactions that transform it into less bioavailable and less toxic species. This type of information on molecular-level speciation of heavy metal and metalloid contaminants in various environmental settings is needed to prioritize remediation efforts and to assess their potential hazard to humans and other organisms.

Journal Article↗

Penicillamine and penicillin can generate antigenic determinants on rat peritoneal cells in vitro.

Conjugation of the protein-reactive drugs D-penicillamine (PA) and benzylpenicillin (BP) to immune cells to generate drug-derived antigenic determinants has been implicated in drug-induced allergies and autoimmunity. We have therefore developed an in vitro system to demonstrate and characterize the formation of cellular antigens by these drugs. Binding of PA and BP to rat peritoneal exudate cells was detected by a cell ELISA, employing rabbit antisera specific for each drug, and an indicator system employing a second antibody coupled to biotin-streptavidin-beta-galactosidase. For both drugs, binding was detected over the concentration range 125-1000 micrograms/ml. PA bound cells rapidly (maximum binding within 10 min), whereas BP bound relatively slowly (maximum binding occurring later than 4 hr). A possible role for intracellular processing and cellular metabolic activity in the generation of these drug-derived antigenic determinants was examined. Pretreatment of the cells with the fixative paraformaldehyde significantly enhanced binding of PA but not BP. Treatment of cells with the lysosomotropic agents ammonium chloride or chloroquine, or with the metabolic inactivator sodium azide, did not affect the binding of either drug compared with untreated control cells. However, treatment with the oxidising agent copper sulphate, or the cellular activator phorbol myristate acetate, did significantly enhance binding of both drugs to the cells. Therefore, binding of PA and BP to the cell surface appears not to require an intracellular processing event to generate a recognizable antigenic determinant, but is enhanced by treatments that stimulate oxidative processes.

Animals↗

A rat model of captopril immunogenicity.

Following chronic administration of the protein-reactive sulphydryl drug captopril (CP) to rats, an IgG antibody response to CP-derived antigen was detected by ELISA in rats administered the free drug at doses of 270 mumol/kg (i.p. and i.m.) and 27 mumol/kg (i.p.). The antibody response was slow to develop, requiring three series of four daily injections at one-monthly intervals before CP-specific serum IgG was apparent. The IgG antibody recognized CP-ovalbumin but not ovalbumin, and was inhibited by CP in protein-conjugated form, and by free CP and CP-disulphide, thus confirming specificity for a CP-derived antigenic determinant. A drug-induced non-drug-specific IgG response directed against human serum albumin was also observed after chronic high dose CP treatment. No IgG anti-DNA, IgM anti-CP nor IgM anti-HSA responses were seen following chronic drug administration. These studies show that CP, like the model reactive metabolite dinitrofluorobenzene, but unlike other protein-reactive drugs such as D-penicillamine and benzylpenicillin, is immunogenic in the rat. The findings also suggest the possibility that anti-CP antibodies reported in man may be drug-induced, rather than naturally occurring.

Animals↗

Drug-protein conjugates--XV. A study of the disposition of D-penicillamine in the rat and its relationship to immunogenicity.

The disposition of [14C]D-penicillamine (PA) was investigated in vitro and in vivo with male Wistar rats. Irreversible binding of [14C]PA to isolated rat plasma proteins in vitro reached a maximum of 20.6% of total radioactivity at 6 hr. Irreversibly bound [14C]PA could be dissociated with dithiothreitol, demonstrating that conjugation was via disulphide linkage. Three hours after i.v. administration of [14C]PA (27 mumol/kg) to rats 100% of plasma radioactivity was irreversibly bound, representing approximately 3.5% of the dose. Further studies on the disposition of PA-plasma protein conjugates showed that dissociation occurred readily in vivo: the plasma half-life of the conjugate was approximately 3 hr. Free [14C]PA was the major urinary metabolite after administration of both free and conjugated drug. These studies show that the disposition of PA is similar to that reported for the structurally related sulphydryl drug captopril (CP). Free PA (340 mumol/kg and 3.4 mmol/kg) administered i.p. and i.m. daily for 4 days at one monthly intervals, and also PA-KLH conjugate (100 micrograms/rat) administered by single i.p. injection at monthly intervals with and without Freund's complete adjuvant, failed to induce PA-specific IgG or IgM antibody responses detectable by ELISA. In contrast, CP (270 mumol/kg), administered by the same protocol as free PA, induced a CP-specific IgG antibody response after the third series of monthly injections. These data suggest that the difference in immunogenicity between PA and CP arises from a difference in the intrinsic immunogenicity of the haptens, rather than from their disposition.

Animals↗

A specific enzyme-linked immunosorbent assay for definition of the IgG antibody response to disulphide-conjugated D-penicillamine in the rabbit.

An enzyme-linked immunosorbent assay (ELISA) has been developed for unambiguous detection of antibodies against the sulphydryl drug D-penicillamine (PA) and its disulphide-conjugated metabolites. Disulphide-linked PA human serum albumin (PA-HSA) conjugates for use as coating antigens were prepared by a range of procedures employing oxidation with either potassium ferricyanide (0.1 M) or cupric sulphate (5 ppm). A satisfactory degree of conjugation was achieved by both oxidative procedures. Hapten density and antigenicity were increased when urea-denatured rather than non-denatured HSA was used. In 2 out of 3 rabbits, a specific IgG anti-PA response was detected following monthly injection of PA keyhole limpet haemocyanin (PA-KLH) in Freund's complete adjuvant. In the third rabbit, any anti-PA activity was obscured by a high level of binding to HSA. The anti-PA response was slow to develop in the 2 responder rabbits (requiring four injections) and was of low intensity (antibody titres less than 6,000). In contrast, the IgG antibody response to the structurally related drug captopril (CP), administered under identical conditions, was rapid in onset and of greater intensity (titres greater than 6,000 after one injection of CP-KLH). The hapten specificity of the IgG anti-PA-HSA antisera was defined by ELISA inhibition assays. Binding of IgG to PA-HSA was inhibited by PA, PA disulphide, PA cysteine and disulphide-linked PA-HSA conjugates, but not by PA acetone (thiazolidine ring-linked PA), CP, or unconjugated HSA. The inhibitory preparations were inactive in unrelated ELISAs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Changes in marital sexual relationship following treatment for sexual dysfunctioning.

Ten couples treated for sexual dysfunctional problems were administered the Sexual Compatibility Test before and after treatment. Significant changes between before-and-after testing were found on all subscales, on the major scales, and on dysfunctional scores. Changes occurred in amount of sexual communication, amount of sexual activity, level of sexual pleasure, and the ability to perceive accurately a mate's sexual preferences and pleasures. The group means of test scores for before-and-after testing were computed and the significance of the differences presented. No significant differences were found for a control group. Group profiles of the treatment group were presented. The impact of the observed changes upon the lives of the treatment couples was discussed.

Adult↗

Natural Systems.

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Journal Article↗