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Biomedical subjects

W S Johnson

Publications and source records attributed to W S Johnson.

10 recordsLinked to original sources

Inhibition of 2,3-oxidosqualene cyclases.

Monocyclic and tricyclic compounds possessing a nitrogen atom situated at a position corresponding to the carbenium ion of high energy intermediates or transition states involved during cyclization of 2,3-oxidosqualene to tetra- and pentacyclic triterpenes have been synthesized. These compounds were tested as inhibitors of 2,3-oxidosqualene cycloartenol, lanosterol-, and beta(alpha)-amyrin-cyclases in vitro and in vivo, and their affinity was compared to that of formerly synthesized 8-aza-bicyclic compounds [Taton et al. (1986) Biochem. Biophys. Res. Commun. 138, 764-770]. A monocyclic N-alkyl-hydroxypiperidine was shown to be the strongest inhibitor of the series upon cycloartenol-cyclase (I50 = 1 microM) from maize embryos but was much less effective on the beta(alpha)-amyrin-cyclases from Rubus fruticosus suspension cultures or pea cotyledons. In contrast, 13-aza-tricyclic derivatives displayed little inhibition on 2,3-oxidosqualene cycloartenol-, lanosterol-, and beta(alpha)-amyrin-cyclases. The obtained data exemplify the differences existing in the cyclization process between cycloartenol- (lanosterol-) cyclases on one hand and beta(alpha)-amyrin-cyclases on the other. The results are discussed with respect to current mechanisms postulated for 2,3-oxidosqualene cyclization. Because of its activity in vivo and in vitro the monocyclic N-alkyl-hydroxypiperidine appears to be a potent and promising tool to study sterol biosynthesis regulation.

Animals

Cyanide poisoning successfully treated without 'therapeutic methemoglobin levels'.

A 24-year-old woman ingested an unknown amount of potassium cyanide in a suicide attempt. Coma and metabolic acidosis developed. Administration of the Lilly Cyanide Antidote kit (Eli Lilly and Co, Indianapolis) resulted in prompt resolution of symptoms and full recovery. Whole blood cyanide level was 13 micrograms/mL approximately one hour after ingestion. The highest measured methemoglobin level after sodium nitrite administration was 9.2%, demonstrating that attaining a "therapeutic methemoglobin level" of 25% is unnecessary to insure a satisfactory clinical outcome. Because severe hypotension or excessive methemoglobinemia can be caused by the sodium nitrite component of the Lilly kit, only enough to produce an acceptable clinical response should be administered.

Acidosis

Effects of polyvinyl chloride ingestion by dogs.

Polyvinyl chloride (PVC) acrylic thermoplastic sheeting was fed to 6 dogs to determine whether ingestion during periods of normal transit of military working dogs would be toxic and thus affect the safety of this material for construction of shipping containers. The test dogs were fed PVC acrylic (0.125 g/kg of body weight; by gelatin capsule) twice each day for 5 days: for 2 dogs, the test material was in a shredded form; for 2 dogs, the material was diced; and for 2 dogs, it was powdered. Two other dogs were used as controls. Dogs were observed for clinical signs, and feed consumption and body weights were recorded. Blood and urine samples were examined. All animals were necropsied approximately 10 days after the feeding was stopped. Clinical or pathologic indication of a toxic effect of PVC was not seen within the time limits of the study.

Animals

Morbidity and mortality in pseudopolycythaemia.

A follow-up of 35 patients with pseudopolycythaemia showed that symptoms, high packed-cell volumes, and low plasma volumes persisted in most patients. The death-rate in these patients was six times greater than expected. Patients with pseudopolycythaemia are often regarded as having a good prognosis; however, this view should be revised in the light of these findings.

Adult