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Biomedical subjects

H E ALEXANDER

Publications and source records attributed to H E ALEXANDER.

At least 37 records · Page 2Linked to original sources
PubMed1954

Studies on the nature of hemophilus influenzae cells susceptible to heritable changes by desoxyribonucleic acids.

In E. influenzae the highly specific desoxyribonucleic acids (DNA's) which play the role of heredity determinants of type specificity and SM resistance, have induced these traits in only a small proportion of the population exposed to their action. The evidence suggests that this small proportion, "the susceptible cells" possess a property or substance needed by the DNA in order to induce an heritable change. The size of the small proportion of susceptible cells can be influenced significantly by a number of factors; when all the factors now to be listed are operating the frequency has not exceeded 1:1000. The Type of Origin of Recipient Cells.-Type a exhibits the lowest frequency, about 1:10,000,000, and type d the highest, approximately 1 per 1000 cells exposed. This type-specific property which controls the frequency of susceptible cells is an inherited trait; repeated change to a heterologous type shows no influence on the incidence of these cells. Concentration of DNA.-Within certain limits increase in the concentration of DNA controlling streptomycin resistance can increase the size of the proportion of cells in which streptomycin resistance can be induced. However, increases in concentrations greater than 10(-1) microg. per ml. have not induced streptomycin resistance in a higher proportion of cells. Phase of Growth Cycle.-Predictable fluctuations in frequency of induced heritable changes have been demonstrated in both Rb and Rd populations during growth. There is no evidence that susceptible cells reproduce their kind; they emerge in all experiments when the population reaches the end of the logarithmic period and a density of 2 to 4 x 10(8) cells per ml. In the early logarithmic phase it is difficult to demonstrate the presence of susceptible cells. The peak frequency of susceptible cells occurs in the early stationary phase of the growth cycle. Thereafter, the decline in frequency is a gradual one. The data suggest that in a given population the same cells are susceptible to a number of different type-specific DNA's and the DNA controlling SM resistance. Comparison of Frequency of Cells Susceptible to Different DNA's.-In a given population the frequency of cells susceptible to different type-specific DNA's and the DNA controlling streptomycin resistance is not significantly different. Competition between Type-Specific DNA's-The data suggest that DNA's of types a, b, and c compete for the same cells in Rd populations. When Rd populations are exposed simultaneously to 2 of these 3 DNA's in different concentrations the proportion which each type contributes to the total type-specific cells induced is closely correlated with the concentration of the corresponding DNA. Exclusion of DNA's.-Induction of one type specificity or streptomycin resistance can be completely prevented in a population containing susceptible cells by previous exposure for 15 minutes to a 1000-fold higher concentration of another type-specific DNA.

DNA↗
PubMed1953

Induction of streptomycin resistance in sensitive Hemophilus influenzae by extracts containing desoxyribonucleic acid from resistant Hemophilus influenzae.

Resistance to streptomycin, of a degree exceeding 1000 microg. per ml., has been induced in sensitive strains of Hemophilus influenzae by exposure for 10 minutes to desoxyribonucleic acid-containing extracts isolated from a strain of type b Hemophilus influenzae which had emerged resistant to 1000 microg. of streptomycin per ml. DNA is essential for the process which brings out this change; the reaction can be prevented by destruction of the DNA with crystalline desoxyribonuclease.The resistant trait which is created in this way is heritable. The nature of the process which induces resistance is similar in all respects to the reaction which induces heritable changes in type specificity of H. influenzae. These results offer another example of the gene-like action of highly specific DNA's. The pattern of resistance brought out in a bacterial population exposed to the DNA-containing, resistance-inducing extract, is similar to that which occurs when emergence of resistance of H. influenzae to streptomycin follows the selection by streptomycin of spontaneously occurring resistant mutants. The change in a bacterial cell from average susceptibility to streptomycin to resistance to 1000 microg. of streptomycin per ml. can occur in a single step.

DNA↗
PubMed1953

In vitro production of new types of hemophilus influenzae.

Two new types of Hemophilus influenzae, Sab and Sad have been produced in vitro. Each exhibits the presence of the type specific polysaccharides of 2 types of E. influenzae within the same cell. In Sab the polysaccharides of types a and b have been demonstrated and in Sad those which characterize types a and d. The Sab and Sad traits are inherited. Sab was produced by the action of DNA-containing extract isolated from type a on either type b cells or Rb cells (non-encapsulated non-type-specific cells derived from type b). Sad cells were formed as a result of the action of the DNA-containing extract isolated from type d on cells intermediate between Rab and Sab cells. DNA-containing extracts isolated from Sab cells have induced the Sab trait in Rd cells with predictable regularity. Evidence has been presented that the hereditary determinant of Sab cells is a new genetic substance with new functions. Therefore, the interaction of the DNA-containing substance from cells of one genetic type with living cells of a genetically different type has produced what appears to be a new individual which differs from each of the cells contributing the differing genetic traits but has at least one trait in common with each. Sab cells derived presumably from a single cell show the appearance of type b cells sometime during the first 7 generations.

B-Lymphocytes↗
PubMed1953

Transformation of type specificity of meningococci; change in heritable type induced by type-specific extracts containing desoxyribonucleic acid.

Heritable type-specific traits have been induced in meningococcus populations by exposure to desoxyribonucleic acid (DNA)-containing extracts derived from meningococcus cells of the type desired. The DNA has been shown to be an essential component of the transforming extract. As in the H. influenzae system, the reaction between the susceptible cell and the DNA responsible for the heritable change requires less than 15 minutes. Only a minute proportion of the total cells exposed to the DNA extracts for a short time are susceptible to the change; but in the growth and reproduction of bacteria susceptible cells appear with fairly predictable frequency. Type I specific traits have been induced in populations of RIIa and SIIa cells. Type IIa specificity has been induced in RIIa cells.

DNA↗
PubMed1953

Studies on the chemistry of the transforming activity. I. Resistance to physical and chemical agents.

The transforming principles of Hemophilus influenzae have been purified by a new method including fractional extraction. The active molecule behaves in these extractions like the bulk of the DNA preparation. The minimal amount of DNA necessary for transformation appeared to be of the same order of magnitude as the amount of DNA in a single cell. Quantitative study has been made of the resistance of transforming activity to various agents. When subjected to heat, the temperature at which the activity starts to decrease corresponds rather closely to the temperature at which the viscosity of the bulk of the DNA preparations starts to decrease. Similar correspondence was found when the transforming principle was subjected to pH changes. This is further evidence that the behavior of the active molecules is similar to the behavior of the average DNA molecule of the preparation. The activity is reduced by exposure to low ionic strength and by dehydration. Desoxyribonuclease in concentrations less than 10(-4) gamma/cc. is able to destroy the activity; a lag period during which the activity but not the viscosity decreases has been observed. NaNO(2) at pH 5.3, HCHO and 10(-5)M Fe(++) reduce or destroy the activity; the importance of intact amino groups in the DNA molecule for the activity is discussed. Several protein-denaturing, sterilizing, and mutagenic agents have been found to have no effect on the transforming activity.

DNA↗