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Biomedical subjects

R K Johnson

Publications and source records attributed to R K Johnson.

At least 235 records · Page 13Linked to original sources
PubMed1978

Biochemical parameters of resistance of an adriamycin-resistant subline of P388 leukemia to emetine, an inhibitor of protein synthesis.

The effects of emetine on protein and DNA synthesis in vitro and in vivo were compared in P388 leukemia cells (P388/S) and in an adriamycin-resistant subline of P388 leukemia (P388/ADR), which was completely cross-resistant in vivo to emetine. In P388/ADR cells in vitro no apparent resistance to emetine was found; no difference in cytotoxicity was evident in P388/S or P388/ADR cells exposed to emetine in vitro for 1 or 6 hours. Protein and DNA synthesis was inhibited to a similar extent in P388/S and P388/ADR cells at equivalent concentrations of the drug. However, inhibition of protein synthesis by emetine in P388/ADR cells was more reversible than in P388/S cells when the cells were exposed to emetine and subsequently incubated in drug-free medium for 1 hour prior to addition of labeled L-leucine. Differences between P388/S and P388/ADR cells were evident in vivo. The duration of inhibition (greater than 90%) of protein and DNA synthesis in P388/ADR cells was about 8 hours compared to 24 hours in P388/S cells following administration of a therapeutic dose of 25 mg emetine/kg to tumor-bearing mice. The level of radioactivity in the P388/ADR cells 24 hours after in vivo administration of the emetine analog, (+/-)-[3'-14C]2,3-dehydroemetine, was only 26% of that in P388/S cells. This evidence suggests that the resistance of P388/ADR to emetine is due to decreased retention of the drug.

Animals↗
PubMed1978

In vivo characteristics of resistance and cross-resistance of an adriamycin-resistant subline of P388 leukemia.

A subline of P388 leukemia resistant to adriamycin (P388/ADR) was developed by exposure to the drug in vivo. Resistance to adriamycin proved to be a stable characteristic of P388/ADR. There was no significant inhibition of nucleic acid synthesis in P388/ADR cells in vivo following a dose of 10 mg/kg of adriamycin in contrast to a prolonged and complete inhibition, particularly of DNA synthesis, observed in parental sensitive P388 leukemia cells. P388/ADR proved to be completely cross-resistant to a spectrum of anthracycline derivatives. Cross-resistance was observed to nonanthracycline DNA intercalating agents (with the exception of anthramycin), to agents which interfere with mitotic spindle function, and to antineoplastic inhibitors of protein biosynthesis (with the exception of bruceantin). P388/ADR was sensitive to antimetabolites and alkylating agents. Cross-resistance was also observed to several agents (ICRF-159, a terephthalanilide, taxol, lymphosarcin, bouvardin, and a crude extract of Ervatamia hyneana) whose mechanisms of action have not yet been clearly defined. This observation has proved useful in providing a lead for determination of mechanism of action of some of these drugs. The pattern of cross-resistance of a subline of P388 leukemia resistant to daunorubicin, though not studied extensively, appears to be similar to that of P388/ADR.

Animals↗
PubMed1977

A systematic study of the oblique retinacular ligament of the human finger: its structure and function.

A dissection of 14 preserved and two fresh human hands, a total of 64 fingers, all from different individuals, showed the oblique retinacular ligament to vary incompleteness and to be functionally present in only 40 to 50% of the specimens, except for the ulnar side of the ring finger where it was present in over 90%. When present, it was made taut by flexion of the distal phalanx, regardless of the postition of the proximal interphalangeal joint. Excision of the ligament when present or in its absence in these fingers, did not alter the coordinated motion of the interphalangeal joints produced by traction on the extrinsic flexors and the lateral bands. In absence of the ligament, a constant finding was the presence of a proximally located osteocapsular ligament which became taut on extension of the proximal interphalangeal joint.

Female↗
PubMed1977

A facile method of purification of neocarzinostatin, an antitumor protein.

A three-step column chromatographic method for the purification of neocarzinostatin (NCS) from a crude preparation was described. The purified material was homogeneous by acrylamide gel electrophoresis, isoelectric focusing, amino terminal analysis, and immunologic criteria. Purified NCS was 40 times as active in the inhibition of growth of Sarcina lutea and twice as active against CCRF-CEM human leukemia cells in vitro as was the starting material. When assayed against P388 and L1210 mouse leukemias in vivo, the purified material showed a median increase in life-span of 119 and 72%, respectively.

Amino Acids↗
PubMed1977

Decreased retention of actinomycin D as the basis for cross-resistance in anthracycline-resistant sublines of P388 leukemia.

Sublines of P388 leukemia resistant to Adriamycin and daunorubicin were cross-resistant to actinomycin D in vivo and in vitro. The Adriamycin-resistant cell line was 1000-fold resistant to actinomycin D on 1-hr exposure in vitro and 370-fold resistant when exposed to the drug for 16 hr. The immediate binding of radioactive actinomycin D to sensitive and resistant cells was similar, and the uptake of the drug by the resistant cells was only about 27% less than the rate of uptake by sensitive cells. There was a dramatic difference in efflux of drug from sensitive and resistant sublines. Equivalent cytotoxicity of actinomycin D for the sensitive and resistant sublines was obtained at concentrations of the drug that resulted in approximately equivalent levels of net retention of actinomycin D (retained drug minus background levels of immediate binding of the drug to the cells). Incubation of cells in the presence of actinomycin D plus either Tween 80 or acridine orange incresed the rate of uptake and the percentage of actinomycin D retained by the resistant cells on short-term assays but did not reverse the resistance. It is concluded that these tumors must retain appreciable concentrations of actinomycin D for several hr in order to be killed. The anthracycline-resistant sublines are cross-resistant to actinomycin D by virtue of their inability to retain the drug.

Acridines↗
PubMed1976

The pronator quadratus in motions and in stabilization of the radius and ulna at the distal radioulnar joint.

Based upon the findings of dissections of 15 forearms and clinical observations in patients with disturbed architecture of the distal radioulnar joint, the pronator quadratus was found to be composed of two heads. A superficial head originated from the ulna and passed transversely to its insertion into the radius. It averaged 5.1 cm. in length, 4.5 cm. in width, 0.2 cm. in thickness, with a cross-sectional area of 0.95 cm.2 and a contractile volume of 2.6 cm.3. The deep head ran obliquely from a more proximal origin on the ulna to a distal insertion on the radius, with an average length of 4.0 cm., average width of 3.2 cm., and a thickness of 0.4 cm. Its average cross-sectional area was 1.64 cm.2 and its contractile volume 2.5 cm.3. A group of fibers occasionally was noted deep to both heads, running at right angles to them and paralleling the direction of the fibers of the interosseous membrane. The superficial head initiates pronation while the deep head coapts the joint surfaces and stabilizes the joint.

Adult↗
PubMed1976

Effects of Corynebacterium parvum alone and in combination with adriamycin in experimental tumor systems.

Corynebacterium parvum (C. parvum) was used in antitumor tests against four murine tumor models in B6D2F1 mice. The C. parvum was effective at all doses and schedules tested against P388 leukemia, B16 melanoma, and Lewis lung carcinoma but was ineffective against L1210 leukemia. Combination immunochemotherapy of P388 leukemia and Lewis lung carcinoma with C. parvum and adriamycin was better than either regimen alone in increasing the lifespan of mice with tumors. The results show that the effects of C. parvum are due to nonspecific stimulation of the host rather than direct cytotoxic action on tumor cells. C. parvum protected the mice when given before as well as after tumor challenge. In vitro 51Cr-release assay showed that the peritoneal cells were cytotoxic to P388 tumor cells but spleen cells were not. While the C. parvum was effective against P388 in conventional mice, it was ineffective against P388 growing in athymic (nude) mice. Thus, the antitumor effect in this tumor system is T-cell dependent.

Adjuvants, Immunologic↗