John S. Evans

Antitumor Activity of 1-β-D-Arabinofuranosylcytosine Hydrochloride

Summary 1-β-D-Arabinofuranosylcytosine hydrochloride has been shown to be active against recently transplanted and established Sarcoma 180, Ehrlich carcinoma and L-1210 leukemia in mice. This nucleoside was inactive at the same dose per kilogram of body weight in tumor-bearing rats.

THE REVERSAL OF CYTOSINE ARABINOSIDE ACTIVITY IN VIVO BY DEOXYCYTIDINE.

Abstract The reversal of 1-β- d -arabinofuranosylcytosine (cytosine arabinoside) activity by deoxycytidine, which has been shown in cell culture by Renis and Johnson (Bact. Proc.45, 140, 1962) and Chu and Fischer (Biochem. Pharmacol.11, 432, 1962), was demonstrated in mice in three tumor systems. Reversal of activity was shown in two ascites systems (L5178Y and Ehrlich carcinoma) and in one solid tumor system (T-4 lymphoma). Preliminary studies showed that in certain tumor systems the availability of deoxycytidine may be one of the limiting factors in tumor growth.

Radioimmunoassay for Glyburide in Human Serum

Abstract A radioimnunoassay (RIA) has been developed to measure nanogram amounts of drug-related materials in human serum, after oral administration of 1.25, 2.5, 3.75 or 5.0 mg glyburide, G, Micronase®, (Micronase® is the registered trademark of The Upjohn Company for 1-[[p-[2-(5-chloro-o-anisamido)ethyl]phenyl]-sulfonyl] 3-cyclohexylurea). Of the compounds tested, only the known hydroxy metabolites of G cross-reacted significantly. Using 20 μl specimens, containing 25.6 ng G/ml serum, the within-day and between-day coefficients of variation for the assay were 3.47% and 3.18%, respectively. Recoveries were quantitative (100.6%). In normal human volunteers, peak serum drug concentrations were observed at 4.3 ± 1.4 hrs (S.D., M = 32). After single oral doses

Manufacture of antithymocyte globulin (ATGAM) for clinical trials.

Methods are described for preparing large amounts of horse anti-human thymocyte globulin (ATG, ATGAM; The Upjohn Company) for clinical use. These methods have been used since 1968 to provide material for clinical trials. Characteristics of 40 lots of ATG are summarized.

SYNERGISM OF THE ANTINEOPLASTIC ACTIVITY OF CYTOSINE ARABINOSIDE BY PORFIROMYCIN.

Abstract When mice bearing ascitic L5178Y or L1210 lymphoblasts were treated with a combination of 1-β- d -arabinofuranosylcytosine (cytosine arabinoside) and porfiromycin, the median survival time and the number of survivors were increased. The combination is most effective when treatment is started within 24 hr after implanting the leukemie cells. The synergistic effect is noted only when the dosage level of the cytosine arabinoside component of the combination is optimal. The same synergistic effects were noted when the combination of mitomycin C and cytosine arabinoside was used.

Difference in Response of Certain Strains of Rats to Augmentative Gonadotropic Effect

Summary A marked difference in the sensitivity of three different strains of rats to the synergistic action of certain gonadotropic hormones has been shown. The three strains, Sprague-Dawley, Wistar and Sherman, give comparable responses to the gonadotropins of pituitary, pregnant mare serum and pregnancy urine when administered singly. Only the Sprague-Dawley and Wistar strains show any augmentative response when purified pituitary follicle-stimulating hormone is given in combination with either chorionic gonadotropin (prolan) or pregnant mare serum hormone.

Development of Complement Fixing Antibodies to Parenterally Administered DEAE Sephadex in Rabbits

Summary Complement binding antibodies were induced readily in rabbits by multiple injections of dextran or DEAE dextran. Antisera to DEAE dextran cross reacted with dextran, and preliminary evidence indicates that antisera to dextran also cross reacts with DEAE dextran and DEAE Sephadex. In contrast, complement binding antibodies to DEAE Sephadex developed very slowly. Low titers were observed only after multiple subcutaneous and intravenous doses of the antigen with complete Freunds adjuvant and in saline over a 3-month period.

Augmentation of the Pregnant Mare Serum Gonadotropic Effect

Summary An augmentative effect was observed when pregnant mare serum gonadotropin was administered in combination with a pituitary follicle-stimulating preparation. On the other hand, the addition of chorionic gonadotropin under the same experimental conditions, did not potentiate the gonadotropic effect of the pregnant mare serum preparations.