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Biomedical subjects

A D Jones

Publications and source records attributed to A D Jones.

At least 109 records · Page 6Linked to original sources
PubMed1990

Isolation and identification of a pyrrolic glutathione conjugate metabolite of the pyrrolizidine alkaloid monocrotaline.

This report describes the isolation and identification of a monocrotaline-derived, glutathione-conjugated pyrrole obtained from the bile of male Sprague-Dawley rats. Bile obtained from rats given an intravenous bolus of 14C-monocrotaline was fractionated using a series of chromatographic separations. Initial purification with cholestyramine resin removed bile acid and pigment contaminants. Subsequent anion exchange and reversed-phase HPLC separations yielded several fractions that contained the 14C label and tested positive for pyrroles using Ehrlich's reagent. These fractions were analyzed using fast-atom-bombardment tandem mass spectrometry (FAB MS/MS). In addition to glutathione-conjugated dehydroretronecine, at least one other pyrrole present had similar ionic properties. The latter was not present in amounts sufficient for positive identification.

Animals↗
PubMed1990

Contrasting bronchoalveolar leukocyte responses in rats inhaling coal mine dust, quartz, or titanium dioxide: effects of coal rank, airborne mass concentration, and cessation of exposure.

The aim of this study was to determine the bronchoalveolar leukocyte response to airborne coal mine dust; quartz and titanium dioxide were used as positive and negative controls, respectively. Groups of rats were exposed to airborne mass concentrations of 10 and 50 mg/m3 of the dusts for 7 hr/day, 5 days/week and their bronchoalveolar space was lavaged at time points between 2 and 75 days of exposure, to assess the leukocyte response. This study revealed time-dependent and airborne mass concentration-dependent recruitment of neutrophils and macrophages into the bronchoalveolar region with coal mine dust inhalation but no real difference in the magnitude of the response between coal mine dusts from collieries mining coal of different rank and quartz content although the maximum quartz content in the dusts used was 6%. The inflammatory response was much less than that produced by quartz, at similar airborne mass concentrations, and more than that produced by titanium dioxide which was, in general, a poor inflammogen in the rat lung. Groups of rats were exposed to the airborne dusts for 32 or 75 days, then removed from the exposure chambers, and allowed to recover by breathing room air for a further 64 days. During this recovery period there was marked progression of the leukocyte response with quartz and persistence of the response with coal mine dust. Chronic recruitment of leukocytes to the lungs of individuals inhaling coal mine dust is likely to be an important factor in the development of coal workers' pneumoconiosis.

Administration, Inhalation↗
PubMed1990

Bioavailability of folates in selected foods incorporated into amino acid-based diets fed to rats.

Two experiments were conducted to determine the feasibility of using a folate depletion/repletion protocol with rats fed an amino acid-based diet to measure the bioavailability of food folate. Growth, liver folate and serum folate of depleted rats that were fed test foods incorporated into a folate-free, amino acid-based diet were standardized against similar responses of rats fed known amounts of folic acid incorporated into the same diet. Bioavailability of folate of cooked broccoli, refried beans and orange juice concentrate in experiment 1 was 80-89, 113 and 62%, respectively, based on growth response; in experiment 2, values for cooked and raw broccoli, cooked cabbage and cantaloupe were 95, 103, 74 and 81%, respectively. The results demonstrate that in addition to serum and liver folate concentrations, growth may be a useful response criterion to evaluate the bioavailability of folates in foods. Further research is needed to determine the relevance of these bioavailability estimates to human nutrition.

Amino Acids↗
PubMed1989

Steroid induced exocytosis: the human sperm acrosome reaction.

By a combination of organic precipitation and high pressure liquid chromatography, human sperm acrosome reaction inducing activity has been purified from the fluid aspirated from preovulatory human ovarian follicles and identified as 4-pregnen-3,20-dione (progesterone) and 4-pregnen-17 alpha-ol-3,20-dione (17 alpha-hydroxyprogesterone). It is argued that progesterone is present at the site of fertilization of placental mammals in concentrations sufficient for activity, and hence provides a mechanism of inducing the acrosome reaction, an exocytotic event, in vivo.

17-alpha-Hydroxyprogesterone↗
PubMed1989

Use of deuterium labelled glucose in evaluating the pathway of hepatic glycogen synthesis.

Deuterium labelled glucose has been used to study the pathway of hepatic glycogen synthesis during the fasted-refed transition in rats. Deuterium enrichment of liver glycogen was determined using nuclear magnetic resonance as well as mass spectroscopy. Sixty minutes after oral administration of deuterated glucose to fasted rats, the portal vein blood was fully enriched with deuterated glucose. Despite this, less than half of the glucose molecules incorporated into liver glycogen contained deuterium. The loss of deuterium label from glucose is consistent with hepatic glycogen synthesis by an indirect pathway requiring prior metabolism of glucose. The use of deuterium labelled glucose may prove to be a useful probe to study hepatic glycogen metabolism. Its use may also find application in the study of liver glycogen metabolism in humans by a noninvasive means.

Animals↗
PubMed1989

Metabolism of N-nitroso-1,3-thiazolidine in the rat.

[2-14C]N-nitroso-1,3-thiazolidine (125 mg/kg body weight) administered by gavage to rats was excreted mostly (81% of the dose) in the urine with a smaller amount (7%) in respired air. The major metabolite in the urine (77.2%) was 2-hydroxy-1,3-thiazolidine and minor quantities of the isomers 4- and 5-hydroxy-1,3-thiazolidine were also detected. The presence of hydroxy-1,3-thiazolidine, determined using mass spectrometry and high-performance liquid chromatography, indicated that alpha-hydroxylation and denitrosation are major metabolic pathways of N-nitroso-1,3-thiazolidine. Analysis of the non-acidic urine extract with gas chromatography-mass spectrometry (GC-MS) using untreated on-column injection and heated split injection gave differing results. Compounds detected using the latter technique may have been artefacts formed by pyrolysis in the heated injection port. Analysis of the metabolites by direct probe mass spectrometry (unheated) and Fourier transform infra-red spectroscopy supported the results seen with on-column GC-MS.

Animals↗
PubMed1989

Accumulation of mixed mineral dusts in the lungs of rats during chronic inhalation exposure.

The effects of mixed dust exposure on pulmonary clearance during chronic exposure has been investigated using rats exposed to combinations of toxic and relatively nontoxic dusts: quartz (at respirable dust concentrations of 1 and 10 mg/m3) plus titanium dioxide (at 30 and 20 mg/m3, respectively), and amosite asbestos (2.5 mg/m3) plus titanium dioxide (15 mg/m3). The rats were exposed for 5 days per week, and for up to 16 weeks (for quartz) or up to 32 weeks (for asbestos). The lung burdens were compared with previously published results for exposure to single dusts under the same exposure regimens. The main feature of all these comparisons was the absence of significant differences between the lung burdens (at 3, 10, and 38 days postexposure) for single-dust and mixed-dust exposures. There was, however, some reduction in the postexposure clearance (as shown by the lung burdens at 94, 150, and 260 days postexposure) of titanium dioxide which appeared to be due to the presence of quartz in the lung. For the quartz plus titanium dioxide experiments, the lymph nodes were dissected and analyzed separately. These results showed that transfer to lymph nodes accounted for most of the postexposure clearance for titanium dioxide, and almost all for the quartz.

Animals↗
PubMed1989

Vitamin A concentrations in liver determined by isotope dilution assay with tetradeuterated vitamin A and by biopsy in generally healthy adult humans.

The vitamin A status in 11 generally healthy surgical patients was estimated by measuring the dilution of a 45-mg oral dose of tetradeuterated retinyl acetate (99% pure). After purification of retinol by high-performance liquid chromatography, the ratio of 2H4-retinol:1H-retinol in plasma was measured by gas chromatography-mass spectrometry. On the basis of the observed ratios of [2H4]retinol:[1H]retinol over 19-47 d, the total body reserves and liver concentrations of vitamin A were calculated. Liver biopsy samples taken at surgery were directly analyzed for vitamin A. The correlation coefficient between calculated and measured liver vitamin A concentrations for 10 of the subjects was 0.88, and the Spearman's rank correlation coefficient was 0.95 (p less than 0.002). Thus, total body reserves of vitamin A in humans can be estimated validly in the marginal and satisfactory ranges by a benign, relatively noninvasive procedure.

Adult↗
PubMed1988

Gas chromatography of retinol and alpha-tocopherol without derivatization.

An improved gas chromatographic method for the analysis of retinol and alpha-tocopherol in biological samples is described. The use of cold on-column injection in combination with wall coated open tubular column gas chromatography eliminates thermal decomposition of vitamin A and yields efficient separations of fat-soluble vitamins (A, D2, D3, and E) without derivatization. Peak tailing was judged to be minimal. Vitamins were quantified by flame ionization detection responses down to 3.5 ng injected, and their identities were confirmed using gas chromatography-mass spectrometry. Extracts of biological samples were saponified, and sterols were removed using digitonin-impregnated celite chromatography before analysis by gas chromatography and gas chromatography-mass spectrometry. Recoveries of vitamins from a test diet ranged from 89 to 103%.

Animals↗
PubMed1988

Determination of pyrrolizidine alkaloid metabolites from mouse liver microsomes using tandem mass spectrometry and gas chromatography/mass spectrometry.

The rapid and sensitive identification and quantification of important pyrrolizidine alkaloid metabolites using tandem mass spectrometry (MS/MS) and gas chromatography/mass spectrometry (GC/MS) is described. Identifications of N-oxide and hydrolytic metabolites of the pyrrolizidine alkaloids senecionine and monocrotaline in extracts of mouse hepatic microsomal incubations were accomplished by comparing collisionally activated decomposition/mass-analyzed ion kinetic energy spectra of specific ions from microsomal extracts with spectra obtained from synthetic standards of suspected metabolites. Trace amounts of the toxic metabolite dihydropyrrolizine (DHP) were observed by GC/MS of trimethylsilyl (TMS) derivatives, but the amounts present in hepatic microsomal extracts were below the MS/MS limit of detection. Quantitative determinations of senecionine N-oxide were performed by fast atom bombardment MS/MS. Suppression of N-oxide ionization by other substances in the extracts was judged to be minimal. The TMS derivatives of the metabolites senecic acid, monocrotalic acid and DHP were quantified using capillary GC/MS. Results from the study demonstrate that the relative contributions of the three major pathways of pyrrolizidine alkaloid metabolism (N-oxidation, hydrolysis and oxidation to pyrrolic compounds) can be assessed using a single analytical instrument and minimal sample preparation.

Animals↗
PubMed1988

Obstetric management and outcome related to maternal characteristics.

Presented are the results of a logit analysis of the variations in birth management and outcome, other than birth weight, associated with socioeconomic and physical maternal characteristics at a London teaching hospital. Previous studies have not attempted to discriminate rigorously between the effects of correlated explanatory variables. Logit analysis overcomes this problem by systematically measuring the independent effect of each maternal characteristic on each type of management and outcome, holding the effects of all other maternal characteristics constant. The results show that, in quantitative terms, parity and age have the greatest effects on both management and birth outcome. Stature is also an important factor for certain types of management, and ethnicity, occupation, and prenatal class attendance have some significant effects. In contrast to the literature on the determinants of birth weight, the smoking habit of the mother had no significant effect when all other factors were controlled for.

Adult↗
PubMed1988

Oxidative metabolism of dihomogammalinolenic acid by guinea pig epidermis: evidence of generation of anti-inflammatory products.

Reports that vegetable oils which contain gamma-linolenic acid (18:3n-6) may exert beneficial effects on cutaneous disorders prompted us to investigate whether epidermis possesses the ability to transform dihomogammalinolenic acid (20:3n-6), the epidermal elongase product of 18:3n-6, into oxidative metabolites with anti-inflammatory potential. Incubations of [1-14C]20:3n-6 with the 105,000 g particulate (microsomal) fraction from guinea pig epidermal homogenate resulted in the formation of the 1-series prostaglandin PGE1. The identity of this product was confirmed by argentation thin-layer chromatography (TLC), reverse phase-HPLC, and conversion with alkali treatment to PGB1. Incubations of [1-14C]20:3n-6 with the 105,000 g supernatant (cytosolic) fraction from guinea pig epidermal homogenate resulted in the formation of the 15-lipoxygenase product 15-hydroxy-8, 11, 13-eicosatrienoic acid (15-OH-20:3n6). The identity of this product was confirmed by normal phase-HPLC and gas chromatography/mass spectrometry (GC/MS). Thus, data from these studies indicate the capacity of enzymes in the microsomal and cytosolic fractions of guinea pig epidermal homogenates to transform 20:3n-6 to the eicosanoids PGE1 and 15-OH 20:3n-6, products which reportedly have anti-inflammatory properties. The in vivo significance of these findings remains to be explored.

8,11,14-Eicosatrienoic Acid↗
PubMed1988

Species differences in the hepatic microsomal metabolism of the pyrrolizidine alkaloid senecionine.

1. The comparative metabolism of the pyrrolizidine alkaloid (PA) senecionine was studied in vitro in incubations of rat, guinea pig, cow, horse, and sheep hepatic microsomes. 2. Levels of the toxic pyrrolic metabolite 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP) were higher from guinea pig incubations (39.9 nmol/mg protein) than from other species (range 0.07 to 7.5 nmol/mg); results disagree with prior studies which used nonspecific techniques and suggest that the guinea pig's resistance to certain PAs may be due to resistance to pyrrole toxicity rather than low pyrrole formation. 3. Minor differences in senecionine N-oxidation and hydrolysis existed between the various species.

Animals↗
PubMed1988

Quantification of Indole-3-Acetic Acid in Dark-Grown Seedlings of the Diageotropica and Epinastic Mutants of Tomato (Lycopersicon esculentum Mill.).

Endogenous indoleacetic acid (IAA) levels were examined in 7-day-old, dark-grown tomato seedlings (Lycopersicon esculentum Mill. cv VFN8), and in two single-gene mutants, Epinastic and diageotropica. Gas chromatography-mass spectrometry was employed to quantify IAA using (13)C(6)-[benzene ring]indoleacetic acid as internal standard. IAA concentrations ranged from 89 to 134 nanograms per gram dry weight and were not significantly different for the three genotypes. Ethylene over-production by dark-grown Epi seedlings is not likely to result from increased IAA. Assuming similar recovery percentages for each genotype, indole-3-ethanol, a purported storage form of IAA, was identified by GC-MS and found to be more prevalent in the parent tomato, VFN8, with only trace amounts observed in Epi. No IEt was detected by high performance liquid chromatography/fluorescence in dgt (detection limit >100 picograms).

Journal Article↗
PubMed1988

Potential contribution of mild pepsin treatment at pH4 to the viral safety of human immunoglobulin products.

Different manufacturers use several different processes for the production of intravenous immunoglobulin. Several manufacturers include a production step where the immunoglobulin is treated with low levels of pepsin at pH 4. A series of experiments were undertaken to assess whether or not pH 4/pepsin treatment could inactivate a range of test viruses. Acid-labile viruses such as vaccinia, herpes simplex, mumps and Semliki Forest virus were found to be susceptible to pH 4/pepsin treatment whereas poliovirus type 2, an acid-stable virus, was completely resistant to this treatment. In immunoglobulin preparations, viral contaminants are likely to be present as antibody/virus complexes and such complexing was found to help protect the test viruses from inactivation by pH 4/pepsin treatment. Despite this protection, at least 99% of the test inoculum of two susceptible viruses (vaccinia and herpes simplex) was found to be inactivated after treatment and the subsequent dissociation of virus/antibody complexes. It is concluded that pH 4/pepsin treatment may contribute to the safety of intravenous IgG by inactivating potential viral contaminants.

Antibodies, Viral↗