PubMed · 491089
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Y Miura. 1979-06-29. [Colony-forming cells].. https://pubmed.ncbi.nlm.nih.gov/491089/
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Killing curves of Pseudomonas aeruginosa were performed in an in vitro system simulating in-vivo gentamicin kinetics, i.e. decay of the antibiotic concentration with a 2.1 h halflife time. Minimal inhibitory concentrations (MIC) of gentamicin killed 99.999% of the initial Pseudomonas inoculum whereas 99.99% were killed at a continuously falling gentamicin concentration (starting from the MIC level) in the same period of time. Regrowth of persistent germs occurred only after 6 hours in cultures exposed to falling gentamicin concentrations, and after 8 hours in cultures kept at the MIC. Thus, a postulated superiority of gentamicin infusions over intermittent gentamicin therapy could not be demonstrated in vitro. Intervals between bolus injections of gentamicin should probably not be longer than 6 hours.
The time-course of DNA repair after gamma irradiation was measured in HeLa cells at various temperatures. Unscheduled DNA synthesis was estimated by incorporation of 3H-thymidine in presence of hydroxyurea. To detect the ligase reaction, the number of single strand breaks (SSB) was determined by centrifugation in alcaline sucrose as well as by hydroxylapatite chromatography after partial denaturation. In addition, the temperature dependence of DNA polymerase and DNase reaction in cell-free systems were measured. These data were compared with the reduction of colony-forming ability of the cells caused by gamma irradiation and following repair at various temperatures. All steps of repair proceed faster at 41--43 degrees than at 37 degrees but cells are most resistant to gamma irradiation at 37 degrees. We therefore assume that the DNA repair process at 42 degrees is faster but more error prone than at 37 degrees.
Human interferon from normal diploid fibroblasts, purified by sequential chromatography on concanavalin A-agarose and phenyl-sepharose, was administered parenterally in 4 subjects. Fever, marked skin hypersensitivity reactions and suppression of marrow stem cells (estimated by the count of myeloid colony-forming cells), side-effects common for less purified fibroblast and leukocyte interferons, were absent. Purified fibroblast interferon retained antiviral and immunomodulatory activity, evidenced by reduction of the blastogenic response of peripheral lymphocytes and decrease of hepatitis B virus markers in a patient with chronic hepatitis B infection treated with this substance.