CS-514, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase: tissue-selective inhibition of sterol synthesis and hypolipidemic effect on various animal species.

CS-514 is a tissue-selective inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, a key enzyme in cholesterol synthesis. For the microsomal enzyme from rat liver, the mode of inhibition is competitive with respect to hydroxymethylglutaryl-CoA, and the Ki value is 2.3 X 10(-9) M.

Radiation-induced alterations in binding of concanavalin A to cells and in their susceptibility to agglutination.

Cell susceptibility to agglutination mediated by a plant lectin, concanavalin A (Con A), and the binding capacity of Con A to cells following gamma-irradiation have been examined in mouse myeloid leukaemia cells cultured in suspension. Irradiation caused an immediate decrease in the amount of Con A bound to the cell surface, whereas susceptibility of irradiated cells to agglutination by Con A was unchanged when compared to that of the unirradiated cells. Post-irradiation incubation of cells at 37 degrees C resulted in a temporary, more than 1.

Increase in the frequency of gamma-ray induced chromosomal aberrations in mammalian cells by post-treatment with novobiocin.

The effect of novobiocin (an inhibitor of DNA topoisomerase and polymerase) on the frequency of chromosomal aberrations was examined in Chinese hamster V79 cells irradiated with gamma-rays in the plateau phase of growth and subcultured in the presence of novobiocin until the first mitosis after irradiation. Novobiocin alone affected cell survival, DNA synthesis and the mitotic frequency of unirradiated cells in a dose-dependent manner, without causing any significant increase in the frequency of chromosome- or chromatid-type aberrations. The frequency of chromosome-type aberrations induced by gamma-radiation was not influenced by novobiocin at 200 microM, but the frequency of chromosome deletions (but not rings and dicentrics) showed a two-fold increase when 300 microM novobiocin was present.

Effect of pulsing electromagnetic fields on DNA synthesis in mammalian cells in culture.

DNA synthesis in Chinese hamster V79 cells was significantly enhanced when they were exposed to weak, pulsing electromagnetic fields generated by specific combinations of the pulse width (25 microseconds), frequency (10, 100 Hz) and magnetic intensity (2 X 10(-5), 8 X 10(-5) T). Conversely the DNA synthesis of cells in the fields at 4 X 10(-4) T was repressed to 80% of that in controls not exposed to the fields.

Microdosimetric considerations of effects of heavy ions on microorganisms.

An estimation of dose around the trajectory of an ion has been made by use of Tabata and Ito's energy deposition algorithm for electrons which takes into account transmission coefficient. The result of the calculation, as well as Butts and Katz's dose, is successfully applied to the interpretation of inactivation cross sections of vegetative cells of E. coli Bs-1, and E.

Device of anoxic chamber system and repair of potentially lethal damage of anoxic cells in vitro.

In order to study radiation responses of anoxic plateau phase cells in vitro, an air-tight anoxic chamber was devised in which Chinese hamster V-79 or Swiss mouse NIH3T3 cells were deoxygenated by replacing the air with saturatedly humidified N2 gas. The cells as adhered on the culture plate, which was contained in the anoxic chamber, were x-irradiated. The deoxygenated condition in the anoxic chamber was maintained as long as necessary.

Effect of novobiocin on the frequencies of chromatid-type aberrations and sister-chromatid exchanges following gamma-irradiation.

The effect of novobiocin on the frequencies of chromatid-type aberrations and SCEs was examined in Chinese hamster V79 cells which were exposed to gamma-rays and post-treated with novobiocin. While no chromatid aberrations were induced in the unirradiated cells by novobiocin, the frequency of SCEs was slightly increased by treatment with novobiocin alone. Irradiation of G2 cells produced multiple chromatid-type aberrations and post-treatment of the irradiated cells with novobiocin resulted in a significant increase of the aberrations, including chromatid gaps and breaks.

Changes in nuclease sensitivity of mammalian cells after irradiation with 60Co gamma-rays.

Changes in sensitivity of mouse BALB/c 3T3 cells in the plateau phase to digestion with micrococcal nuclease were examined following gamma-irradiation. Immediately after irradiation, cell nuclei were more sensitive to micrococcal nuclease compared to unirradiated nuclei. However, there were no detectable changes in length of basic repeating subunits of 182 base pairs of DNA, which include the nucleosome cores consisting of approximately 140 base pairs of DNA, which When the cells were incubated at 37 degrees following irradiation, the sensitivity of cell nuclei to the nuclease first increased then decreased, reaching a similar level to unirradiated nuclei 6 h after irradiation.

Differential recovery from potentially lethal damage in normal human lung fibroblasts after irradiation with 60Co gamma-rays and accelerated N-ion beam.

PLD recovery after irradiation with accelerated N-ion was examined and compared with that after irradiation with 60Co gamma-rays in normal human lung fibroblasts (IMR-90). No shoulder region was observed in the survival curve of the cells after N-ion irradiation. Ratios of D0 values before and after a 6-hour incubation in plateau phase were 1.

Two active forms of valyl-tRNA synthetase from Bacillus subtilis: alteration related to the early stages of sporulation.

Two enzymatically active forms, E-I and E-II, of valyl-tRNA synthetase [EC 6.1.1.

Membrane distribution and adsorptive endocytosis by C3b receptors on human polymorphonuclear leukocytes.

C3b receptors on human polymorphonuclear leukocytes (PMN) were nonrandomly distributed in small clusters on the plasma membranes of these cells when assessed by indirect immunofluorescence at 0 degree C using monospecific rabbit Fab' or F(ab')2 anti-C3b receptor and tetramethylrhodamine isothiocyanate (TRITC)-conjugated goat IgG anti-F(ab')2. When PMN were incubated with the bivalent anti-C3b receptor at 37 rather than at 0 degree C, almost no immunofluorescence was observed, which indicates that the C3b receptor-F(ab')2 complexes had been rendered inaccessible to TRITC-IgG anti-F(ab')2. Endocytosis of the anti-C3b receptor ligand was quantitated by measuring the binding 131I-IgG anti-F(ab')2 by PMN that had previously taken up 125I-F(ab')2 anti-C3b receptor at 0 and at 37 degree C, respectively.

A new method of urea removal using urease and expanded polytetrafluoroethylene membrane.

A new method for urea removal using a gas membrane is introduced along with some preliminary results. The membrane used was expanded polytetrafluoroethylene (E-PTFE) which is highly permeable to gaseous substances, while at the same time it is highly resistant to water permeation. In in vitro experiments using 10 mmol/L ammonia solution it was revealed that the single-pass reduction rate was approximately 95% at 30 degrees C at a flow rate of 200 ml/min.