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Biomedical subjects

R K Johnson

Publications and source records attributed to R K Johnson.

At least 271 records · Page 15Linked to original sources
PubMed1971

Nailplasty.

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Cosmetics↗
PubMed1970

Hepatic drug-metabolizing enzyme activity in rats pretreated with (-)-emetine or (plus or minus)-2,3-dehydroemetine.

1. Pretreatment of female rats with (-)-emetine or (+/-)-2,3-dehydroemetine (at 18mumol/kg body wt. for 24h) prolongs the hexobarbital-induced sleeping-time of the treated animals. 2. This effect is not observed on pretreating animals with other compounds closely related to (-)-emetine, such as (-)-isoemetine or (+)-O-methylpsychotrine. 3. Liver microsomal drug-metabolizing enzyme activity in vitro as measured by N-demethylation of aminopyrine and azo-reduction of Neoprontosil is inhibited in rats pretreated with (-)-emetine or with (+/-)-2,3-dehydroemetine. 4. These inhibitory effects on drug metabolism in vitro are not observed in corresponding experiments involving pretreatment of rats with (-)-isoemetine or (+)-O-methylpsychotrine. 5. Co-administration of emetine or 2,3-dehydroemetine and sodium phenobarbital or 1,1-dichloro-2-o-chlorophenyl-2-p-chlorophenylethane to rats abolishes or greatly diminishes the stimulation of drug-metabolizing enzyme activity in vitro usually obtained by the administration of phenobarbital or 1,1-dichloro-2-o-chlorophenyl-2-p-chlorophenylethane alone. 6. Further, in rats pretreated with sodium phenobarbital and subsequently injected with emetine or 2,3-dehydroemetine the pre-stimulated drug-metabolizing enzyme activity in vitro is diminished. 7. The inhibitory effects on drug-metabolizing enzyme activity after pretreatment with (-)-emetine or (+/-)-2,3-dehydroemetine do not appear to be related to NADPH generation.

Aminopyrine↗
PubMedDate not supplied

Influence of WR 2721 on the efficacy of radiotherapy and chemotherapy of murine tumors.

The effect of WR 2721 on the response of tumors to radiation, antineoplastic alkylating drugs, and DNA binding agents was evaluated and compared to the degree of normal tissue protection provided by WR 2721 against these agents. WR 2721 administered to mice bearing P388 leukemia or Lewis lung carcinoma was found to reduce the radiosensitivity of the leukemia and lung tumor by dose modifying factors of 1.4 and 1.3, respectively. WR 2721 protected bone marrow, intestine, and skin from radiation by factors of 1.9, 1.5, and 1.8. WR 2721 protected mice from the lethality of cyclophosphamide by a factor of only 1.2 whereas protection from melphalan toxicity was more dramatic with a dose modifying factor of 1.6. In chemotherapy studies of established M5076 ovarian tumor, the combination of WR 2721 plus cyclophosphamide was equivalent in activity to cyclophosphamide alone. WR 2721 did not modify the antitumor activity of melphalan in early Lewis lung carcinoma but did decrease the antileukemic effects of this agent by a factor of 2.6 indicating tumor protection greater than host protection in the leukemia. The antitumor activity of the DNA binding agents etoposide (VP16--213) and mitoxantrone against systemic P388 leukemia was not diminished by WR 2721, while a substantial increase in host toxicity was noted for the combinations. The protective effects of WR 2721 against radiation and drug damage were, therefore, not entirely selective for normal tissues. In some cases the degree of tumor protection can be similar to, or greater than, normal tissue protection.

Amifostine↗
PubMedDate not supplied

Evaluation of radiosensitizers in combination with chemotherapeutic agents in solid tumors.

The electron-affinic compounds misonidazole (MISO), metronidazole (MET), desmethylmisonidazole (DMM), and CB1954 were shown to enhance the activity of alkylating agents in M5076 ovarian tumor. MISO, MET, and DMM enhanced the antitumor activity of cyclophosphamide by factors of 1.7, 1.5, and 1.7, respectively. MIS, MET, and CB1954 enhanced the antitumor activity of melphalan by factors of 2.2, 2.4, and 1.8, respectively. MISO also enhanced the antitumor activity of mitomycin C by a factor of 2.0. MISO did not enhance the activity of chlorozotocin given as a single dose and only slightly enhanced the antitumor activity of this agent when the combination was given on a q4D x 3 schedule. MISO administered 1 hr prior to the antimetabolite 5-FU on a q7D x 3 schedule was no more effective than 5-FU alone against colon carcinoma 38. MISO given simultaneously with or 1 hr after 5-FU strongly inhibited the antitumor activity of 5-FU in this tumor. Data obtained in this study indicate that several radiation sensitizers including three nitroimidazoles and a dinitrobenzamide can enhance the antineoplastic activity of alkylating agents. The degree of enhancement in the M5076 tumor appears to be independent of the electron affinity of the sensitizer. Enhancement was observed with relatively ineffective as well as highly active alkylating agents.

Animals↗
PubMedDate not supplied

Inhibition of topoisomerase I function by nitidine and fagaronine.

The benzophenanthridine alkaloids nitidine and fagaronine were characterized as inhibitors of topoisomerase I function. In common with the antitumor agent camptothecin, both nitidine and fagaronine stabilized the covalent binary complex formed between calf thymus topoisomerase I and DNA. The effects of these compounds were readily apparent at 0.15-0.3 microM concentrations. Both nitidine and fagaronine inhibited the topoisomerase I-mediated relaxation of supercoiled pSP64 plasmid DNA more effectively than camptothecin; unlike camptothecin, both of these benzophenanthridine alkaloids also bound directly to and mediated the unwinding of B-form DNA. Nitidine and fagaronine were also studied in comparison with camptothecin to determine the sequence specificity of DNA breaks produced from a 32P-end-labeled duplex in the presence of topoisomerase I. All three compounds produced very similar cleavage patterns. The specificity of nitidine and fagaronine for inhibiting topoisomerase I function was studied by measuring the effects of the compounds on the unknotting of P4 DNA by calf thymus topoisomerase II. Moderate inhibition of topoisomerase II-mediated unknotting was obtained, but only in the presence of high (i.e., 40 microM) concentrations of nitidine and fagaronine. In comparison, doxorubicin inhibited topoisomerase II to the same extent as nitidine and fagaronine when it was employed at 2.5 microM concentration and was strongly inhibitory when employed at 10 microM concentration.

Alkaloids↗