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Biomedical subjects

H EAGLE

Publications and source records attributed to H EAGLE.

At least 55 records · Page 3Linked to original sources
PubMed1955

The minimum vitamin requirements of the L and HeLa cells in tissue culture, the production of specific vitamin deficiencies, and their cure.

SEVEN VITAMINS HAVE TO DATE PROVED ESSENTIAL FOR THE SURVIVAL AND MULTIPLICATION OF A MOUSE FIBROBLAST (STRAIN L) AND A HUMAN CARCINOMA CELL (STRAIN HELA) IN TISSUE CULTURE: choline, folic acid, nicotinamide, pantothenic acid, pyridoxal, riboflavin, and thiamin. It was necessary to cultivate the cells for 5 to 15 days in a medium lacking the specific vitamin before the deficiency became apparent in the cessation of multiplication and the development of specific cytopathogenic effects. In their early stages these changes could be reversed by the addition of the missing vitamin, an in vitro, "cure" of a vitamin deficiency. The maximally effective concentrations were in the range 10(7) to 10(8) gm. per ml. The probability that additional vitamins not demonstrably essential under the conditions of the present experiments are nevertheless required for survival and growth is discussed in the text.

Animals↗
PubMed1955

The specific amino acid requirements of a human carcinoma cell (Stain HeLa) in tissue culture.

The amino acid requirements of a human uterine carcinoma cell (HeLa strain) have been defined. The 12 compounds previously found to be essential for the growth of a mouse fibroblast proved similarly essential for this human epithelial cell. They included arginine, cyst(e)ine, histidine, and tyrosine, in addition to the eight amino acids required for nitrogen balance in man (isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine). Only the L-amino acids were active; the D-enantiomorphs had no demonstrable effect at physiologic concentrations. The minimum concentrations required for survival and limited growth varied from 0.003 microM per ml. for L-tryptophan, to 0.1 microM per ml. for L-lysine. The concentrations permitting optimum growth similarly varied from 0.01 microM per ml. for tryptophan, to 0.1 microM per ml. for leucine, isoleucine, threonine, lysine, and valine. The latter optimum concentrations of the individual amino acids were closely correlated with their serum levels. With at least six of the amino acids, high concentrations, in the range 1 to 10 microM per ml., caused a definite growth inhibition. In the absence of a single essential amino acid, degenerative changes occurred in the cells, culminating in their death and dissolution. In the early stages, however, these degenerative changes could be reversed by the restoration of the missing component.

Amino Acids↗
PubMed1955

Antibiotics.

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Anti-Bacterial Agents↗
PubMed1954

The binding of penicillin in relation to its cytotoxic action. II. The reactivity with penicillin of resistant variants of streptococci, pneumococci, and staphylococci.

1. In a previous study, the differing sensitivity of bacterial strains as they occur in nature appeared to be correlated with their correspondingly differing reactivity with penicillin. Presumably, the over-all reactivity of the cell with penicillin paralleled that of the vulnerable cell component(s). However, when penicillin-resistant variants of these strains (Streptococcus pyogenes, Micrococcus pyogenes, Diplococcus pneumoniae, and Streptococcus faecalis) were produced by serial passage through increasing concentrations of antibiotic, this correlation between resistance and the ability of the cell to bind penicillin was no longer apparent. Some resistant variants bound more penicillin than the parent, sensitive cell (Streptococcus faecalis, Micrococcus pyogenes), some were unchanged in their reactivity (Diplococcus pneumoniae, Micrococcus pyogenes), and some bound less (Streptococcus pyogenes, Micrococcus pyogenes). One resistant variant of Micrococcus pyogenes at first showed enhanced reactivity with penicillin; on continued passage through antibiotic, there was a further increase in resistance, but now associated with a significantly decreased reactivity. In the case of Diplococcus pneumoniae, a resistant variant at first reacted normally with penicillin; on continued passage in antibiotic, its binding affinity for penicillin gradually decreased, but with no associated further increase in resistance. 2. The reactivity with penicillin of cell-free sonic extracts of the resistant variants paralleled that of the intact organisms. Permeability considerations therefore did not seem involved in the increased resistance produced by serial passage in antibiotic. 3. The penicillin-resistant variants did not have an enhanced capacity to degrade the free intracellular antibiotic. 4. Possible alternative explanations are discussed in the text.

Anti-Bacterial Agents↗
PubMed1954

The binding of penicillin in relation to its cytotoxic action. III. The binding of penicillin by mammalian cells in tissue culture (HeLa and L strains).

1. (a) Mammalian cells in tissue culture (mouse fibroblasts and malignant human uterine epithelium) did not concentrate penicillin from the culture medium. Even at low concentrations, the cellular accumulation was usually less than that in the surrounding fluid, and most of it was removed by washing. The radioactive material in such eluates was actively bactericidal, and was presumably in large part unchanged penicillin. (b) Penicilloic acid, produced by the action of penicillinase, was bound to the same (limited) extent as the active antibiotic. In both these respects mammalian cells behaved like naturally penicillin-resistant bacteria, and unlike such penicillin-sensitive bacteria as Streptococcus pyogenes or Diplococcus pneumoniae. 2. Cell-free sonic extracts of the L strain had the same limited reactivity with penicillin as the intact cells. The relatively minute amounts bound by the cells are therefore not due to their impermeability, but instead reflect the inherently low reactivity of the cellular constituents with penicillin. 3. It is suggested that the relative non-toxicity of penicillin for the mammalian host, and for mammalian cells in tissue culture, may be related to this low order of reactivity with the antibiotic.

Animals↗
PubMed1954

The binding of penicillin in relation to its cytotoxic action. I. Correlation between the penicillin sensitivity and combining activity of intact bacteria and cell-free extracts.

1. Bacteria exposed to C(14)- or S(35)-labelled penicillin bound and concentrated the antibiotic. The amount bound from low concentrations (0.001 to 0.01 microg. per ml.) was related to the penicillin sensitivity of the strain; and highly sensitive organisms such as Streptococcus pyogenes concentrated the antibiotic as much as 200-fold. The material bound by highly sensitive strains from these low concentrations of penicillin was removed to only a minor extent by washing. Penicillin inactivated with penicillinase, by hot H(2)SO(4) or by cold HCl was not similarly concentrated. 2. Despite wide differences in their sensitivity to penicillin, at equieffective (LD(99.9)) levels, four of the five strains here studied had bound comparable amounts of antibiotic. That lethal intracellular concentration averaged 1.7 to 4 microg. per gm., and 1600 to 3300 molecules per cell. 3. Bacteria in the logarithmic phase of growth, "resting" organisms, and cell-free sonic extracts, had roughly the same reactivity with penicillin. The differences in the amount of penicillin bound by bacteria of varying sensitivity therefore do not rest on differences in the permeability of the cell. 4. Escherichia coli (K12)-inactivated penicillin within the cell; and that inactivation adequately explains its low binding affinity, and its relative resistance. The other species here studied inactivated the diffusible cellular penicillin to only a minor degree, and not enough to explain the differences in their penicillin-sensitivity. The working hypothesis is suggested that their varying sensitivity is instead determined by differences in the reactivity of vital cell components with the antibiotic. 5. At high concentrations of antibiotic (1 to 1000 microg. per ml.), there was non-specific binding by all the cell strains and cell extracts here studied, unrelated to their sensitivity, and masking the specific differences in reactivity noted at low concentrations. At these high levels, penicilloic acid was bound to the same degree as the active antibiotic.

Anti-Bacterial Agents↗
PubMed1954

Drug resistance.

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Bacteria↗