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Biomedical subjects

J Carson

Publications and source records attributed to J Carson.

At least 91 records · Page 5Linked to original sources
PubMed1988

Effect of tolmetin glycine amide (McN-4366), a prodrug of tolmetin sodium, on adjuvant arthritis in the rat.

The glycine amide of tolmetin sodium (TGA) functions as a prodrug and was demonstrated to be more potent than the parent compound as an inhibitor of developing and established adjuvant arthritis in the female Lewis rat. In contrast, the glycine amide of indomethacin was less potent than indomethacin. The superiority of TGA relative to tolmetin sodium in alleviating this condition was demonstrated by inhibition of paw swelling and reduction of the degenerative bone changes that are associated with the progression of this chronic animal model of rheumatoid arthritis in humans. These properties were not evident when equimolar mixtures of tolmetin sodium and glycine were administered concurrently. Pharmacokinetic analyses revealed that TGA was absorbed completely and hydrolyzed to tolmetin in the female adjuvant arthritic rat. The combined effects of absorption, distribution and hydrolysis of TGA produced lower peak plasma tolmetin levels than an equivalent dose of tolmetin sodium, but plasma concentrations were sustained for a longer period of time contributing to an apparent increase in potency. Furthermore, TGA displayed a decreased propensity to cause gastrointestinal irritation compared to tolmetin sodium. Several additional amino acid amides of tolmetin were similar to the glycine amide in exhibiting increased potency and reduced gastrointestinal toxicity in comparison to equivalent doses of tolmetin sodium.

Animals↗
PubMed1986

Cholinergic function and memory: extensive inhibition of choline acetyltransferase fails to impair radial maze performance in rats.

The present study investigated the effects of a potent inhibitor of choline acetyltransferase (ChAT), BW813U, on the choice accuracy of rats in the radial arm maze. BW813U (100 mg/kg, IP) produced a rapid (within 1 hour) and substantial decrease in ChAT activity throughout the brain, ranging from 66% (hippocampus) to 80% (caudate nucleus) that lasted up to 5 days. A single injection (50 mg/kg, IP) into rats with lesions (using ibotenic acid) in the nucleus basalis magnocellularis and medial septal area, decreased ChAT activity by 75% and 60% in the cortex and hippocampus, respectively. Lesioned and unlesioned rats were trained on the radial arm maze until they reached a criterion level of performance. Each rat then received an injection of BW813U (50 or 100 mg/kg, IP). Choice accuracy was not impaired at any time following the injection. The lack of effect on performance may be due to 2 possible factors: The radial maze retention paradigm chosen may not be sufficiently difficult, or the decrease in acetylcholine production was not sufficient to affect behavior. Compensation by non-cholinergic neural systems might account for the insensitivity of the rats to significant cholinergic depletion.

Animals↗
PubMed1985

Exercised induced asthma in young male asthmatics with symptoms, and in remission.

A treadmill exercise test was carried out on 154 male subjects aged 15-25 years who gave a history of mild asthma in childhood, and on 31 similarly aged control subjects. The results were expressed as an exercise lability index, (ELI), based on measurement of FEV. The mean ELI of the control group was 7.6%, range 2.9-12.2% and a positive result in the asthma subjects was an ELI greater than 15%. Seventy five of the asthma subjects were found to have been asymptomatic for a year or more (group 1) and, in 15 of them (20%) the test was positive. The remaining 79 were currently symptomatic, or had been symptomatic within a year (group 2), and in 52 of these (66%), the test was positive. The difference between the two results was significant, p greater than or equal to 0.001. We believe this observation suggests that exercise induced asthma (EIA) cannot be demonstrated in the majority of asthmatics who are in remission.

Adolescent↗
PubMed1985

Selection bias in clinical trials.

Of 90 patients with intermediate or high-grade sarcoma eligible for a randomized trial of adjuvant doxorubicin (Adriamycin, Adria Laboratories, Columbus, Ohio), 48 were not entered: 24 (27%) by physician's choice and 24 refused randomization. Sixty-five percent of lower stage patients were randomized compared with 37% of those with higher stage (P = .02). Patients with extremity lesions were more frequently offered participation in the study (P = .07). Patients with lower stage lesions accepted randomization more readily than those with higher stage lesions (P = .01). As predicted by the higher stage and percentage of central lesions, the disease-free survival of nonrandomized patients was inferior to that of randomized patients (P = .15). Thus, patients at high risk appeared to avoid randomization and adjuvant doxorubicin in this trial, resulting in an inferior disease-free survival for the nonrandomized control group. Important questions generally require randomized trials that reliably determine relative treatment differences. If, however, the patients in a clinical trial are not representative of the entire patient population because of patient and physician selection biases, the generalizability of the results to the entire patient population may be compromised. For example, the prognosis of the general population cannot necessarily be inferred from the selected group in the study. In this study, the randomized and nonrandomized series yielded differing conclusions regarding treatment efficacy, even when an adjustment was made for known prognostic facts.

Clinical Trials as Topic↗
PubMed1985

Quantitative measurement of myocardial blood flow with oxygen-15 water and positron computed tomography: an assessment of potential and problems.

An in vivo measurement technique using 15O water and positron CT for quantitation of myocardial blood flow (MBF) was investigated. A closed-chest dog model and NeuroECAT scanner were used in the study. The in vivo technique involves i.v. infusion of 15O water for a duration of 2-3 min. Oxygen-15 water radioactivity in myocardium was imaged with a NeuroECAT scanner for 10 min, starting at the time of tracer infusion. A separate scan following inhalation of 15O CO was obtained to label the blood pool and to help remove the contribution of radioactivity in the blood pool during the 15O water scans. The integrated projection technique was used for calculating MBF. The quantitative microsphere technique for measurement of MBF was performed along with the 15O water study to provide reference values, with which the MBF values by the in vivo technique was compared. Results of 12 experimental runs (in seven animals) show the in vivo technique with 15O water and positron CT can give quantitative flow images of myocardium. The in vivo positron CT measurement was found to correlate well (r = 0.93) with the in vitro values (by microspheres) over the flow range of 40 to 150 ml/min/100 g.

Animals↗
PubMed1985

Phaeoannellomyces and the Phaeococcomycetaceae, new dematiaceous blastomycete taxa.

Phaeoannellomyces McGinnis et Schell gen. nov., which is based upon P. elegans McGinnis et Schell sp. nov., is proposed for dematiaceous yeasts which produce percurrently proliferating conidiogenous cells. Cladosporium werneckii Horta is transferred to Phaeoannellomyces as P. werneckii (Horta) McGinnis et Schell comb. nov. because the most stable and distinctive synanamorph produced by this fungus consists of annellidic yeast cells. The Phaeococcomycetaceae McGinnis et Schell fam. nov. is proposed in the class Blastomycetes, division Fungi Imperfecti for the dematiaceous yeast genera Phaeoannellomyces and Phaeococcomyces de Hoog.

Mitosporic Fungi↗
PubMed1984

The heparin-binding site of antithrombin III. Identification of a critical tryptophan in the amino acid sequence.

Chemical modification of a single tryptophan residue in antithrombin III with dimethyl(2-hydroxy-5-nitrobenzyl)sulfonium bromide blocks heparin binding and the heparin-enhanced inhibition of thrombin without altering the heparin-independent rate of thrombin inhibition (Blackburn, M. N., and Sibley, C. C. (1980) J. Biol. Chem. 255, 824-826). The labeled protein was reduced and carboxymethylated and then cleaved with cyanogen bromide. The peptide containing the hydroxynitrobenzyl-labeled tryptophan was isolated by gel filtration and ion exchange chromatography. Amino acid analysis of the labeled peptide indicates that it corresponds to residues 21 through 89 of human antithrombin III. The site of labeling corresponds to Trp 49, which is located within the disulfide-stabilized loops near the NH2-terminal end of the antithrombin III molecule.

Amino Acid Sequence↗
PubMed1983

Quantitative measurement of local cerebral blood flow in humans by positron computed tomography and 15O-water.

A noninvasive method that employs 15O-water and positron-computed tomography (PCT) was used to measure quantitative local cerebral blood flow (lCBF) in man. 15O-Water (about 30-50 mCi) was introduced through a single-breath inhalation of 15O-carbon dioxide or through an intravenous bolus injection of 15O-water. A sequence of five 2-min PCT scans was initiated at the time of tracer administration. A series of 15-20 blood samples (1 ml each) was withdrawn from the radial artery of the subject over a period of 10 min. Oxygen-15 radioactivities in the blood samples were immediately counted in a well counter to give an input function, which together with the projection data collected by PCT were processed to provide images of 1CBF and local water distribution volume. The method was found to be convenient to use and gave good-quality images of 1CBF. Quantitative values of 1CBF in images were 59 +/- 11 and 20 +/- 4 ml/min/100 g for gray and white matter, respectively, with a gray-to-white matter ratio of 2.93 and a global flow value of 42 +/- 8 ml/min/100 g. Distribution volume of water was 0.85 +/- 0.03, 0.76 +/- 0.03, and 0.81 +/- 0.02 ml/g respectively, for gray matter, white matter, and whole brain.

Adult↗
PubMed1982

Hyperbilirubinemia in Inuit neonates.

A prospective study was undertaken to determine if Inuit and Caucasian neonates have different patterns of physiologic jaundice. Daily blood samples obtained by heel pricks of Inuit and Caucasian neonates born at the Churchill (Man.) Health Centre were assayed for the total serum bilirubin concentration. The mean peak bilirubin level in the Inuit group was significantly higher than that in the Caucasian group (8.76 v. 6.04 mg/dl [150 v. 103 mumol/l]) and occurred later (on day 3 rather than day 2). Of the Caucasian neonates, those who were breast-fed in hospital had a significantly higher (P less than 0.05) mean peak bilirubin level than those who were not, and among all the neonates who were not breast-fed in hospital the Inuit had a significantly higher mean peak bilirubin level than the Caucasians (7.98 v. 3.64 mg/dl [136 v. 62 mumol/l]). These findings indicate that factors other than breastfeeding, some of which may be genetic, are responsible for the higher and later peak in the serum bilirubin concentration in Inuit neonates.

Bilirubin↗
PubMed1982

A simple method for the handling and orientation of small specimens for electron microscopy.

Cyanoacrylic glue (Eastman 910) was used to affix small pieces of nasal scrapings to lens paper immediately before fixation in the glutaraldehyde. The lens paper not only served to hold specimens together so that they were not lost during tissue processing, but also functioned as a 'landmark' for the specimens, so that specimens could be oriented in a specific manner during embedding and subsequent sectioning.

Adhesives↗