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Biomedical subjects

L MacKenzie

Publications and source records attributed to L MacKenzie.

22 records · Page 2Linked to original sources

Effects of chronic LHRH agonist treatment on the endometrium and ovaries of the stumptailed macaque.

Eight stumptailed macaques were injected daily with 5 or 20 micrograms D-Ser(But)6des Gly luteinizing hormone releasing hormone ethylamide (LHRH agonist) for approximately one year in order to prevent ovulation. On the last day of treatment (7 monkeys) or during the mid-luteal phase of the first cycle after treatment (1 monkey), a laparotomy was performed. Uterine size was slightly smaller (P less than 0.01) than in controls with normal cycles (n = 6). A full thickness wedge of anterior uterine wall was excised and examined histologically. Five of the agonist-treated monkeys had endometrium consistent with an atropic or resting proliferative pattern, but in 2 the appearance varied from early proliferative to marked secretory. All appeared entirely benign. The remaining animal studied in the luteal phase after stopping treatment exhibited a normal secretory endometrium. Ovaries from 2 of the LHRH agonist-treated animals were also studied histologically and found to consist of follicles at various stages of maturation. The occurrence of endometrial activity in 2 of the 8 LHRH agonist-treated monkeys stresses the need for careful endometrial assessment during clinical trials involving repeated administration of LHRH agonists in women.

Animals↗

9-Octadecynoic acid: a novel DNA binding agent.

A novel bioassay was developed to permit the identification of cytotoxic natural principles that bind to DNA. A hexane extract of Schoepfia californica cytotoxic to cultured KB cells displayed much less cytotoxic potential when the culture medium contained exogenously added calf thymus DNA. Fractionation of the extract afforded a purified principle shown to be 9-octadecynoic acid, an 18-carbon, unbranched acetylenic fatty acid. 9-Octadecynoic acid had an apparent DNA dissociation constant of 1.8 mM; it inhibited topoisomerase I mediated DNA filter binding but did not inhibit the DNA topoisomerase I mediated relaxation of a supercoiled plasmid DNA. The fatty acid was weakly inhibitory to DNA polymerase alpha. 9-Octadecynoic acid possesses none of the structural characteristics of known DNA binding molecules and may bind to DNA by some novel mechanism.

Adenosine Triphosphate↗