Mina Levy

Amino acid requirements of normal and malignant human cells in tissue culture.

Abstract Three tissue culture cell lines deriving from normal human tissue (liver, conjunctiva, and intestine) and two lines deriving from human cancer [KB (nasopharynx), and J-111 (monocytic leukemia)] have been examined with respect to their amino acid requirements in comparison with those of a HeLa cell and a mouse fibroblast. With the possible exception of tryptophan, all seven cell lines required the same amino acids (arginine, cystine, glutamine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tyrosine, valine); and in the absence of any one of these 12, cytopathogenic changes developed which culminated in the death of the cell. The provision of non-essential amino acids, purines, pyrimidines, and NH 4 + had a glutamine-sparing effect, but did not eliminate the need for this amino acid. Extremely high and nonphysiological concentrations of glutamic acid (20 mM ) did, however, substitute for glutamine. It is not yet clear whether tryptophan is similarly essential for survival and growth, or whether it is merely growth stimulatory for some of the five cell lines here studied. The concentration of the individual amino acids necessary for optimum growth varied somewhat among the six strains; but there were not significant or consistent differences in this respect between the lines deriving from normal and from malignant tissues.

Effect of Prior Immunization on Bactericidal Action of Penicillin in vivo

Summary and Conclusions In the group A streptococcal infection of mice here studied, and under the conditions of the present experiments, the presence of a significant degree of immunity had no effect on the direct bactericidal action of penicillin. This proceeded at the same rate in the immunized animals as in control mice simultaneously inoculated, and continued for the same period of time. The difference in the 2 groups lay in the course of the infection after penicillin had fallen to ineffective levels. In non-immune mice, the surviving bacteria regularly grew out to cause a fatal infection. In the partially immunized animals, however, a small fraction of the normally curative dose of penicillin sufficed to reduce the bacterial population to levels which could be handled by the host defenses. Those surviving bacteria gradually disappeared in the course of 24-48 hours, after penicillin itself was no longer operative, and the animals survived. Under the conditions of this experiment, the host defenses and the bactericidal action of penicillin proceeded independently of each other, but were mutually supplementary in effecting cure in the partially immunized animals. The choice of a group A streptococcal infection was perhaps unfortunate. The resistance to reinfection in the immunized animals probably reflects enhanced phagocytosis; and in the present experiments, there was no pronounced cellular infiltration at the focus of infection at the time of treatment with penicillin. It would be of interest to carry out similar studies under conditions closer to those usually operative in the natural infection of man, with the cellular host defenses already mobilized at the focus of infection. It would be of interest also to determine, in infections caused by organisms susceptible to the bactericidal action of antibodies and complement, whether the presence of such antibodies modifies the therapeutic action of penicillin and other antibiotics.