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Biomedical subjects

A B Jones

Publications and source records attributed to A B Jones.

At least 91 records · Page 5Linked to original sources
PubMed1972

Brain amine concentrations after monoamine oxidase inhibitor administration.

The concentrations of 5-hydroxytryptamine (5HT), noradrenaline, and dopamine were estimated post mortem in brain stem, hypothalamus, and caudate nucleus in 33 patients who had been treated with isocarboxazid, clorgyline, or tranylcypromine and 11 controls. Similar and highly significant increases in 5HT and noradrenaline concentration occurred with all three drugs. The distribution was unimodal, but about a quarter of the patients showed only a small increase in brain amines. Tranylcypromine seemed to have a significantly greater effect on dopamine in caudate nucleus and hypothalamus compared with isocarboxazid and clorgyline. In the doses used chlorpromazine did not reduce the amine concentrations. Four patients with Parkinson's syndrome had low concentrations of dopamine in caudate nucleus in spite of monoamine oxidase inhibitor administration.

Aged↗
PubMed1970

Inhibition of hormone-sensitive adenyl cyclase by phenothiazines.

Chlorpromazine (3 x 10(-4)M) prevents the stimulation of adenyl cyclase activity in thyroid membranes produced by thyrotropin and prostaglandin, ACTH stimulation of adenyl cyclase in adrenal tissue, and glucagon- and epinephrine-stimulation of adenyl cyclase activity in liver. Baseline activity is unaffected. Parathyroid hormone stimulation of kidney preparations was not inhibited under these conditions. At chlorpromazine concentrations >3 x 10(-4)M F(-)-stimulated cyclase activity of thyroid and adrenal tissue was increased. Other phenothiazines, trifluoperazine, and prochlorperazine, have similar effects on thyrotropin and F(-)-stimulated cyclase activity of thyroid. Na(+)- K(+)-dependent ATPase of thyroid is also inhibited by chlorpromazine. Since thymol causes a similar dissociation of hormone- and F(-)-stimulated adenyl cyclase, it is concluded that the surface properties of these agents best account for their effects on adenyl cyclase.

Adenine Nucleotides↗
PubMedDate not supplied

A compact multichamber gas inhalation exposure system for mice.

A multi-unit, dynamic flow, inhalation exposure system which is capable of accommodating 12 mice per unit has been described. Components of the system include a mixing board, one or more glass distributing tubes, and detachable glass chamber tubes. The flow of a specified concentration of test gas exits from the mixing board, enters a distributing tube, and is then distributed equally to 12 chamber tubes housing one mouse each. Advantages includes quick equilibration time (10 min), relatively low flow rates (20 l/min per distributing tube), ease of disassembly for cleaning, compact size, modest expense and minimal temperature, pressure and physico-chemical effects.

Ammonia↗
PubMedDate not supplied

DNA adducts in human and patas monkey maternal and fetal tissues induced by platinum drug chemotherapy.

Platinum-DNA adducts in placenta and blood from a woman exposed to 200 mg/m2 of cis-diamminedichloroplatinum(II) (cisplatin) and 300 mg/m2 diamminecyclobutanedicarboxylatoplatinum(II) (carboplatin) for ovarian cancer have been documented by cisplatin-DNA enzyme-linked immunosorbent assay (ELISA) and atomic absorbance spectrometry (AAS). A patas monkey model was used to investigate transplacentally induced cisplatin-DNA damage in fetal tissues. During the last trimester of gestation, 5 patas monkeys were given multiple doses of cisplatin to mimic human ovarian cancer treatment. In spite of careful choice of dose and treatment conditions, cumulative toxicity occurred in monkeys given doses comparable on a mg/m2 basis to those received by the human. A total dose of 12 mg/m2 (0.625 mg/kg body weight), given in the last trimester, supported fetal viability, and multiple tissues, taken by cesarean section, were examined in the fetal monkeys. By cisplatin-DNA ELISA and AAS, maternal tissues from the monkey receiving the highest dose contained approximately twice as much DNA damage as the fetal tissues. A similar relationship was observed when we compared DNA adduct formation in fetal liver and biopsies of liver taken from the monkey dams at cesarean delivery. In all of the monkey pairs studied there were very significant levels of DNA damage in the placenta, and high adduct levels in brains of fetuses that survived treatment. Thus, cisplatin does cross the placenta in the patas monkey. These observations imply that the human fetus, for which the total maternal dose was approximately 5.4 mg platinum drug/kg body weight, may also have sustained some DNA damage.

Adult↗
PubMedDate not supplied

Transplacental cisplatin exposure induces persistent fetal mitochondrial and genomic DNA damage in patas monkeys.

A previous attempt to model transplacental cisplatin exposure and genotoxicity employed several pregnant Erythrocebus patas monkeys; most of the animals were exposed near the end of gestation and cisplatin-DNA adduct analyses included only genomic DNA. Here, both genomic and mitochondrial DNA adduct formation have been determined in fetuses from two pregnant monkeys exposed at the end of the second trimester of gestation. Multiple fetal tissues were obtained after doses of 0.315 mg cisplatin/kg body weight (5.3 mg/m2 total) on days 101 and 106 of gestation. Cesarean sections were performed 24 h after exposure and 27 d after exposure. Cisplatin genomic (g)-DNA adducts were observed in fetal adrenal, brain, heart, kidney, liver, skin, spleen, and thymus. When placentas from the two animals were divided into four concentric regions at increasing distances from the umbilical cord, and g-DNA was assayed, cisplatin DNA adduct levels were similar in all four regions. Mitochondrial (mt)-DNA adducts were higher than g-DNA adducts in maternal liver and fetal liver, brain and kidney, suggesting that the mitochondria may constitute a particular target for cisplatin genotoxicity. The study demonstrates significant fetal genotoxicity in g-DNA and mt-DNA of patas monkeys exposed to cisplatin in utero, suggesting that similarly exposed human fetuses may also sustain drug-induced DNA damage.

Animals↗
PubMedDate not supplied

Release of bovine serum albumin from preformed porous microspheres of poly(L-lactic acid).

Preformed porous microspheres of poly(L-lactic acid) (Accurel have been shown to sustain the release of highly water soluble solutes, like dextran and mannitol, for a time period of more than 4 months. The purpose of this investigation was to mechanistically characterize the release of a model protein, bovine serum albumin (BSA), from these highly porous microspheres. The microspheres were loaded with [14C]BSA in three different concentrations of 0.06, 0.26 and 0.59% w/w. The rate of release of [14C]BSA from microspheres was correlated to media ([3H]PBS) uptake. The release of BSA showed a biphasic pattern; an initial rapid release, followed by a sustained release. The initial burst of BSA was found to be inversely proportional to BSA loading and highly correlated to water penetration. The sustained release phase was independent of water penetration kinetics. Washing the microspheres did not remove either the surface bound BSA or the BSA incorporated in the microsphere matrix, indicating the tight binding of BSA to highly porous microspheres. Furthermore, addition of a surfactant induced a dramatic increase in the amount of BSA released, suggesting that the release is controlled by the surface binding of BSA to the polymer. Also, the release rate of BSA beyond the initial burst was found to be much slower than for the lower MW macromolecules like dextran at a similar level. The data from the present work suggests the BSA-polymer interaction to be a major contributing factor in explaining the overall BSA release kinetics.

Animals↗
PubMedDate not supplied

Spectrophotometric evaluation of carboxyhemoglobin in blood of mice after exposure to marijuana or tobacco smoke in a modified Walton horizontal smoke exposure machine.

Carboxyhemoglobin (COHb) values were determined in mice exposed to varying amounts of marijuana and tobacco cigarette smoke utilizing a spectrophotometric technique. Mice were exposed to smoke inhalation in a modified Walton horizontal smoke exposure machine, whereby rodents can be exposed to multiples of 1-min smoke exposure cycles. Smoke exposure was intermittent; during the first 30 sec of each 1-min cycle, the subjects were exposed to smoke diluted either 1:10 or 1:5 with air. During the second half of the cycle the animals were given fresh air. There was a positive linear relationship between COHb values obtained and the number of puffs of marijuana smoke administered via either 2, 4, 6, or 8 "puffs" of marijuana smoke. COHb levels in plasma did not increase in animals given multiple 8-puff episodes of smoke daily as long as a 60-min period was interposed between smoking episodes. COHb values in mice exposed to tobacco smoke were significantly higher than those in mice receiving equal numbers of exposures to marijuana smoke. Mean COHb values of mice receiving 8 consecutive puffs of marijuana smoke were 18.6 and 22.0% saturation, but CO was rapidly cleared from the blood. This rapid clearance suggests that the binding affinity of CO for mouse hemoglobin may be be weaker than that of human hemoglobin. Mice similarly exposed to 6 or 8 puffs of tobacco smoke had mean COHb values of 24.6 and 28.5% saturation, respectively. No acute lethal effects were observed in mice receiving multiple daily episodes of 8 puffs per episode of marijuana smoke, whereas mice exposed to a single 8-puff episode of tobacco smoke suffered about 50% acute lethal effects.

Animals↗
PubMedDate not supplied

Cross-reactivity of selected compounds in the Abbott TDx cannabinoid assay.

Immunoassay procedures, both enzyme immunoassay and radioimmunoassay, continue to be widely used to screen samples for recent marijuana use by analyzing the urine samples for 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid (11-nor-delta 9-THC-9-COOH) (the major urinary metabolite of delta 9-tetrahydrocannabinol [delta 9-THC]). Using commercially available immunoassay reagents, the cross-reactivity of the antiserum utilized in Abbott's TDx cannabinoid assay (a fluorescence polarization immunoassay) was evaluated. This cross-reactivity was evaluated against a group of cannabinoids and noncannabinoid phenolic constituents of Cannabis, some cannabinoid metabolites, and other agents that appear in normal urine samples. In general, the antiserum was equally reactive toward 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid, its glucuronide, and the corresponding delta 8-isomer, which was the acid moiety utilized in standards and controls of the assay prior to January, 1990. Reduced binding to the antiserum was observed with hydroxylated derivatives of delta 9- and delta 8-THC, and the other cannabinoids, in general, exhibited limited binding potentials toward the antibody. For the noncannabinoid constituents, no binding was observed at the highest concentrations evaluated (40 mg/L).

Antibody Specificity↗
PubMedDate not supplied

Analysis of the major metabolite of delta 9-tetrahydrocannabinol in urine II. A HPLC procedure.

A high performance liquid chromatographic (HPLC) procedure was developed for the analysis of 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid in urine. Hydrolyzed urine samples were cleaned up using Bond-Elut columns. 11-Nor-cannabinol-9-carboxylic acid was used as internal standard. The analysis was carried out using a C8 reversed-phase column with acetonitrile:50 mM phosphoric acid (65:35) as the solvent. Detection was done by ultraviolet detector at 214 nm. The minimum detectable level of 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid was 25 ng/mL.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

Analysis of the major metabolite of delta 9-tetrahydrocannabinol in urine. III. A GC/ECD procedure.

A gas chromatographic/electron capture detection procedure was developed for the analysis of 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid in urine. Hydrolyzed urine samples (1 mL or less) were extracted by a simple acid-base partitioning step. The extracted metabolite was derivatized with pentafluorobenzyl bromide in a biphasic system using benzyl tributylammonium hydroxide as a phase transfer catalyst. 11-Nor-cannabinol-9-carboxylic acid was used as internal standard. A linear relationship was observed between the peak height ratio of the metabolite/internal standard and the concentration of the metabolite (r = 0.9996), and between the peak height and concentration of the metabolite (r = 0.9995). Concentration of 5 ng/mL of metabolite in urine resulted in a peak-to-noise ratio of 4:1; however, concentrations down to 1 to 2 ng/mL could be determined. The procedure has many advantages over currently available methods, of which sensitivity and speed are the most important.

Chromatography, Gas↗
PubMedDate not supplied

Analysis of the major metabolite of delta 9-tetrahydrocannabinol in urine. IV. A comparison of five methods.

Urine samples from 29 subjects were simultaneously analyzed for 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid by five previously published methods. The procedures employed were radioimmunoassay (RIA), enzyme immunoassay (EIA), high performance liquid chromatography (HPLC), gas chromatography with electron capture detector (GC/ECD), and gas chromatography/mass spectrometry (GC/MS). A comparison of the results showed significant correlations between the results obtained by HPLC, GC/ECD, and GC/MS procedures. As anticipated, quantitation by any of these procedures resulted in lower values than those obtained by either of the immunoassays.

Chromatography, Gas↗