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G A Reed

Publications and source records attributed to G A Reed.

At least 37 records · Page 2Linked to original sources
PubMed1984

Prostaglandin H synthase-dependent co-oxygenation of (+/-)-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene in hamster trachea and human bronchus explants.

The role of prostaglandin H synthase (PHS) in the metabolism of 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BP-7,8-diol) has been examined in short-term explant cultures of hamster and human tracheobronchial tissues. Labeled BP-7,8-diol was incubated with the explants in the presence and absence of the PHS substrate arachidonic acid (20:4) and the PHS inhibitor indomethacin. The addition of 10 microM to 200 microM 20:4 to incubations of hamster trachea with 5 microM BP-7,8-diol caused significant increases in the formation of 7r,8t-dihydroxy-9t,10t-epoxy-7,8,9,10-tetrahydrobenzo[ a]pyrene (anti-BPDE). These increases were not seen when 1 microM or 20 microM BP-7,8-diol was employed. The stimulation of anti-BPDE formation was observed after incubations of from 1 to 48 h. This stimulation was inhibited to the basal level by 20 microM indomethacin, supporting the role of PHS in the response. No effect of 20:4 was seen on the uptake of BP-7,8-diol by the tracheas or on the formation of water-soluble metabolites. Significant increases in covalent binding of BP-7,8-diol metabolites to DNA of the tracheal epithelium were also elicited by the addition of 20:4, however these increases were not well correlated quantitatively with the increases in anti-BPDE formation. H.p.l.c. profiles of deoxynucleoside adducts from basal and 20:4-stimulated incubations were qualitatively identical. Far greater variability of metabolism was seen in human bronchus explants, but 20:4-dependent increases in anti-BPDE formation could be demonstrated in those tissues as well. Inhibition of this stimulation by indomethacin was either absent or incomplete. This variation in the effect of indomethacin was explained by the examination of the products of 20:4 metabolism by the two tissues. Hamster trachea produced almost exclusively PHS metabolites whereas human bronchus yielded predominantly products of lipoxygenases, enzymes insensitive to indomethacin. In conclusion, this study indicates that co-oxygenation of chemical carcinogens can occur in hamster and human tracheobronchial tissues. The concentration-dependence observed with BP-7,8-diol, however, suggests that this pathway is of minor importance in the activation of BP in these tissues.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1982

Metabolism and activation of 7,8-dihydrobenzo[a]pyrene during prostaglandin biosynthesis. Intermediacy of a bay-region epoxide.

A Tween 20-solubilized preparation of prostaglandin endoperoxide synthase has been shown to metabolize 7,8-dihydrobenzo[a]pyrene (H2BP) to a form highly mutagenic to Salmonella typhimurium strain TA98. The arachidonic acid-dependent metabolism of H2BP by microsomal and purified prostaglandin endoperoxide synthase has been studied and the products identified. A spectral investigation of the metabolism indicated the bay-region double bond as the primary site of metabolism. Radiolabeled H2BP was synthesized and incubated with the enzyme preparations and the metabolites were separated by reverse phase high performance liquid chromatography and quantitated by liquid scintillation counting. Radioactive products were characterized by co-chromatography with chemically synthesized standards, UV-visible spectra, and mass spectrometry of acetate derivatives. The major polar products were determined to be trans- and cis-9,10-dihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene and 7,8,9,10-tetrahydrobenzo[a]pyrene-9-one in a ratio of 1:1.2:0.4. The inclusion of 5 mM 3,3,3-trichloropropene-1,2-oxide, an epoxide hydrolase inhibitor, produced the same products but in a ratio of 1:2.3:1.2. Incubations with purified prostaglandin endoperoxide synthase yielded the three products in a ratio of 1:2.8:0.7. The major nonpolar product was identified as benzo[a]pyrene. The polar products of metabolism, the effects of 3,3,3-trichloropropene-1,2-oxide on their distribution, and the detection of a mutagenic intermediate support the conclusion that H2BP is co-oxygenated during prostaglandin biosynthesis to 9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene.

Animals↗
PubMed1982

Antipsychotic drugs and involuntarily committed patients.

This summer, the U.S. Supreme Court wil rule on whether an involuntarily committed mental patient has a legal right to refuse antipsychotic drugs. In this article, two federal appellate decisions that may influence that decision are reviewed. The appellate decisions suggest that patients have a right to refuse treatment except in circumstances where there is an overriding state interest.

Antipsychotic Agents↗
PubMed1980

Assessment of recovery of arm control in hemiplegic stroke patients. 2. Comparison of arm function tests and pursuit tracking in relation to clinical recovery.

In a preliminary study, return of arm function in hemiplegic patients has been assessed for periods up to 64 weeks after stroke using two methods of testing. The first method concerns the performance of simple motor tasks involving the arm and hand. The second method is a pursuit tracking task using elbow movements. Patients were divided into two groups depending on whether they scored above 80% (Group I) or below 80% (Group II) on the first method at 16 weeks after stroke. When the two arm assessment methods were compared with clinical assessments for all the patients, general agreement was shown. Among Group I patients there was also significant agreement between the assessments; among Group II patients the agreement was poor. The two arm assessment methods, however, showed mutual agreement. In conclusion, both arm assessments provide a general prediction of the recovery of movement control of patients following stroke.

Aged↗
PubMed1979

Peroxidatic oxidation of benzo[a]pyrene and prostaglandin biosynthesis.

The arachidonic acid dependent oxidation of benzo[a]pyrene to a mixture of 3,6-, 1,6-, and 6,12-quinones has been studied by using enzyme preparations from sheep seminal vesicles. Maximal oxidation is observed at 100 microM benzo[a]pyrene and 150 microM arachidonic acid. The arachidonic acid dependent oxidation is peroxidatic and utilizes prostaglandin G2 (PGG2), generated in situ from arachidonate, as the hydroperoxide substrate. 15-Hydroperoxy-5,8,11,13-eicosatetraenoic acid is equivalent to PGG2 as a hydroperoxide substrate, but hydrogen peroxide, cumene hydroperoxide, and tert-butyl hydroperoxide are much poorer substrates. Arachidonic acid dependent benzo[a]pyrene oxidation by microsomal and solubilized enzyme preparations is markedly.

Animals↗