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Biomedical subjects

J W Daniel

Publications and source records attributed to J W Daniel.

53 records · Page 3Linked to original sources

The metabolism of arylazoisoxazolones by rats and dogs.

1. When rats were given a single oral dose of the lipid-soluble fungicide 4-(2-chlorophenylhydrazono)-3-methyl[4-(14)C]isoxazol-5-one ([(14)C]drazoxolon), about 75% of the label was excreted in the urine and 13% in the faeces in 96hr. An additional 7% of the radioactivity was recovered as (14)CO(2) in 48hr. 2. About 8% of the label was excreted by rats in the bile in 0-24hr. and an additional 6% was excreted by the same route in 24-48hr. 3. When dogs were given a single oral dose of [(14)C]drazoxolon about 35% of the label was excreted in the urine and a similar amount was excreted in the faeces in 96hr. 4. The major metabolites in the urine of the rat and the dog were identified as 2-(2-chloro-4-hydroxyphenylhydrazono)acetoacetic acid (dog, 14%), the corresponding ether glucosiduronic acid (dog, 12%; rat, 13%) and ester sulphate (rat, 65%). 5. When rats were given a single oral dose of 3-methyl-4-([U-(14)C]phenylhydrazono)isoxazol-5-one about 75% of the label was excreted in the urine and 15% in the faeces in 96hr. The major metabolite in the urine was identified as the ester sulphate conjugate of 2-(4-hydroxyphenylhydrazono)-acetoacetic acid. 6. Reduction of the azo link was of minor quantitative significance. 7. These results are discussed in their relation to species differences in the toxicity of these compounds.

Acetoacetates↗

The metabolism of 3,5-di-tert.-butyl-4-hydroxytoluene in the rat and in man.

1. The major metabolites of 3,5-di-tert.-butyl-4-hydroxytoluene (BHT) in the rat are 3,5-di-tert.-butyl-4-hydroxybenzoic acid (BHT-acid), both free (9% of the dose) and as a glucuronide (15%), and S-(3,5-di-tert.-butyl-4-hydroxybenzyl)-N-acetylcysteine. 2. The mercapturic acid does not appear to derive from the usually accepted enzyme mechanism, and may involve a non-enzymic reaction between BHT free radical and cysteine. 3. The ester glucuronide and mercapturic acid found in rat urine are also the major metabolites in rat bile and must be responsible for the enterohepatic circulation. 4. Free BHT-acid is the main component in rat faeces. 5. In man, BHT-acid, free and conjugated, is a minor component in urine, and the mercapturic acid is virtually absent. The bulk of the radioactivity is excreted as the ether-insoluble glucuronide of a metabolite in which the ring methyl group and one tert.-butyl methyl group are oxidized to carboxyl groups, and a methyl group on the other tert.-butyl group is also oxidized, probably to an aldehyde group. 6. These differences in metabolism by the rat and by man are sufficient to account for the difference in excretion by the two species.

Animals↗

Methionine metabolism of the myxomycete Physarum polycephalum.

Daniel, John W. (University of Wisconsin, Madison), and Karlee Babcock. Methionine metabolism of the myxomycete Physarum polycephalum. J. Bacteriol. 92:1028-1035. 1966.-Previous studies have shown that Physarum polycephalum requires exogenous methionine for growth, but not cysteine, folic acid, or vitamin B(12). Methionine can also serve as the sole source of sulfur for all cellular requirements, without limiting the growth rate. S-methyl-l-cysteine, 2-hydroxy-4-methiol butyric acid, S-adenosyl-l-methionine, and methionine peptides were the only compounds supporting growth, when substituted for methionine. Other methionine analogues, methyl donors in combination with homocysteine, and intermediates of the cystathionine pathway were not active. Ethionine and S-ethyl cysteine were good methionine antagonists. This myxomycete is apparently unable to synthesize the methyl or S-methyl group, although it still appears able to transmethylate, at least from S-methyl cysteine, and probably from S-adenosyl methionine, which can also serve as a source of adenine.

Adenine↗

A biochemical basis for the radiosensitizing and cytotoxic effects of chlorpromazine hydrochloride in vitro and in vivo.

There have been many investigations on the radiosensitizing and cytotoxic effects of chlorpromazine, both in vitro and in vivo. We have extended the studies to include the chemotherapeutic effect of chlorpromazine on lymphosarcoma and on a mammary adenocarcinoma arising spontaneously in breeding female CBA mice. Chlorpromazine was ineffective in the former tumor but enhanced the longevity of tumor-bearing mice in the latter case. The drug was also observed to potentiate the hyperthermic killing of L5178Y cells and inhibit cellular oxygen utilization by cultured mammalian cells. The possible mechanisms involved are discussed.

Animals↗

Aspergillosis of the central nervous system.

The authors report an unusual case involving a 38 year-old man who developed a intracranial abscess caused by Aspergillus of the parietal lobe. Cerebral aspergilloma of an initial pulmonary origin developed in a patient with "Fungus Ball" secondary to tuberculosis sequelae. The diagnosis was made through the isolation of Aspergillus from the secretion of the brain abscesses. The patient was treated with drainage of the abscesses and Amphotericin B. He presented a progressive regression of the radiological images (brain and pulmonary) over a period of 55 days. This report emphasizes the importance of combined anti-fungal therapy and surgical resection as a treatment for cerebral aspergilloma. Furthermore, an early initiation of therapy should improve the prognosis in such cases.

Adult↗

Metabolic aspects of antioxidants and preservatives.

The use of chemical preservatives serves to ensure the nutritional adequacy, palatability and safety of processed foods and beverages. The toxicity of some of the more ubiquitous antimicrobial agents (sorbic acid, p-hydroxybenzoates, sulphur dioxide) and antioxidants (propyl gallate, butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT] is reviewed together with the role of metabolic data in assessing the 'safety-in-use' of these and other food-additives.

Animals↗