Search PubMed⌕ Search

Biomedical subjects

F L HORSFALL

Publications and source records attributed to F L HORSFALL.

At least 19 recordsLinked to original sources
PubMed1963

CURRENT CONCEPTS OF CANCER.

Because the cancerous change in cells appears to be a permanent alteration, handed on to daughter cells through innumerable divisions, it seems probable that it reflects an abnormality in the transfer of information from cell to daughter cells. Transfer of information in cells is believed to depend on their genetic apparatus, and transfer of abnormal information implies that the genetic apparatus is not functioning normally. Abnormalities in genetic material, whether induced by ionizing radiation, chemical compounds or viruses, would, if reproduced at cell division, reappear in daughter cells. If such abnormalities lead to cancerous change in cells, any one of these primary incitants might be effective. Under such circumstances, the nature of the primary incitant may not be the most important question, and definition of the nature of the abnormality in the genetic material may become the central problem. It may ultimately be feasible to explain the cancerous change in cells in chemical terms and to find that it represents a molecular disease which takes its origin from the emergence of abnormal nucleotide sequences in the genetic material. In biological terms this would correspond with an induced mutation which is heritable at the level of the somatic cell.

Base Sequence↗
PubMed1961

Dr. Leo WADE.

Explore the source record for details and available documents.

History, 20th Century↗
PubMed1955

Reproduction of influenza viruses; quantitative investigations with particle enumeration procedures on the dynamics of influenza A and B virus reproduction.

Influenza A and B virus reproduction in the allantoic membrane of the intact chicken embryo was studied quantitatively with particle enumeration procedures. Virus particles were enumerated on the basis of two independent properties; capacity to infect and to cause hemagglutination. The infective property of influenza B virus (Lee) was even more unstable than that of influenza A virus (PR8). Inactivation occurred at a constant logarithmic rate which was independent of the concentration of particles and corresponded with first order reaction kinetics. In allantoic fluid at 35 degrees C. either in vitro or in vivo, Lee virus had a half-life for infectivity of only 85 minutes. In contrast, the hemagglutinating property, like that of PR8, was relatively stable and was not appreciably affected by 12 hours at 35 degrees C. On the basis that the number of non-infective particles is equal to the number of hemagglutinating particles minus the number of infective particles and that the number of cells lining the allnatoic membrane is 1.8 x 10(7), the effects of various particle-cell ratios on the reproductive process were analyzed. Adsorption of infective and non-infective Lee particles occurred at the same logarithmic rate, i.e. about 50 per cent in 72 minutes, and the rate was nearly independent of the particle-cell ratio up to a value of 55. The adsorption capacity of an allantoic cell was at least 44 Lee or 89 PR8 particles. The interval before new particles appeared in the allantoic fluid increased as the particle-cell ratio was decreased with both Lee and PR8. At ratios of 0.2 or less, the appearance time for infective particles was nearly identical to that for hemagglutinating particles with both viruses. At ratios of about 1.0, the "latent period" in the allantoic membrane per se was computed to be 150 to 160 minutes for both Lee and PR8. The number of particles, both infective and hemagglutinating, increased at a constant logarithmic rate for 6 hours or more after the adsorptive period. With Lee virus, at a particle-cell ratio of 5 or less, the doubling time was constant and had a value of 43 minutes. The dynamics of the logarithmic increase period suggest that reproduction corresponds to an autocatalytic reaction in which the rate is proportional to the amount of material produced. When the particle-cell ratio was increased to 10 or more, either with infective or non-infective (inactivated at 35 degrees C. or 22 degrees C.) particles, the doubling time increased to 65 minutes. Comparable effects from high ratios were found with PR8. Non-infective particles accumulated at a rapid rate after the interval of constant logarithmic increase regardless of the particle-cell ratio. This accumulation was even more striking with Lee than with PR8 as was expected because of the shorter half-life of the infective property. With both viruses at particle-cell ratios of 4 or more, a large proportion of the particles were non-infective within a few hours after new particles appeared. At particle-cell ratios of 0.2 or less, the maximal yield was relatively constant, i.e., about 900 to 1400 hemagglutinating particles per cell with Lee and 500 to 900 with PR8. However, even with very low ratios, i.e. 0.001 or less, it was not possible to obtain more than about 160 infective particles per cell with either virus regardless of the interval. As was expected, the lower the ratio, the longer was the interval before maximal yields were produced. At ratios of about 10, the maximal yield was reduced by 50 per cent or more with both viruses. Comparable reductions in yield were obtained whether the high particle-cell ratio was due to infective or non-infective (inactivated at 35 degrees C. or 22 degrees C.) particles. These findings indicate that there is a critical particle-cell ratio above which alterations appear in the dynamics of reproduction of influenza viruses. This ratio has a value of approximately 3. The observed alterations in the reproductive process are discussed in relation to the hypothesis that adsorption of 3 or more infective or non-infective particles per cell induces cell damage.

Animals↗
PubMed1954

On the reproduction of influenza virus; quantitative studies with procedures which enumerate infective and hemagglutinating virus particles.

Procedures which make possible the enumeration of both infective and hemagglutinating influenza A virus particles have been developed and used in a quantitative investigation on the reproduction of the agent. Infective particles were found to be highly unstable and their half-life was only 147 minutes in allantoic fluid at 35 degrees C. both in vitro and in vivo. The instability of infective particles provides an explanation for the rapid accumulation of non-infective particles which retained the hemagglutinating property. The number of non-infective (N) particles was determined from the difference between the number of hemagglutinating (H) particles and the number of infective (I) particles as indicated by the relation: [N] = [H]- [1]. When the half-life of infective particles was taken into account, both infective and hemagglutinating particles were found to disappear from the allantoic fluid; i.e., were adsorbed by the allantoic membrane, at the same logarithmic rate after inoculation. Inoculation of any number of particles up to 3 x 10(7) was followed by a constant and progressive decrease in the proportion of unadsorbed particles from 0 to 4 hours. Approximately 20 per cent of particles were unadsorbed at 2 hours and about 5 per cent at 4 hours. Inoculation of 3 x 10(8) or more particles led to a larger proportion of unadsorbed particles at 4 hours. The maximum number of particles adsorbed was computed to be about 1.6 x 10(9). The concentration of both infective and hemagglutinating particles increased rapidly in the allantoic fluid after 4 hours when any number of infective particles up to 3 x 10(7) was inoculated. With such inocula, the rate of increase during the logarithmic period was constant and the time to double the concentration of infective or hemagglutinating particles was 46 minutes. With larger inocula, i.e. 3 x 10(8) particles, the concentrations of infective and hemagglutinating particles did not increase until after 8 hours and the rate of increase was much slower. The time to double the concentration of either then became 92 minutes. The number of infective particles was approximately equal to the number of hemagglutinating particles during the logarithmic increase period when any number of infective particles up to 3 x 10(6) was inoculated and no more than 10(6) non-infective particles were included in the inoculum. This finding was taken to indicate that all or almost all particles produced and released under these conditions were infective. That such particles became inactivated rapidly and led to the accumulation of an increasing number of non-infective particles after the logarithmic period can be explained by the short half-life of infective particles. The number of infective particles was no larger than one-tenth the number of hemagglutinating particles during the logarithmic increase period after 3 x 10(7) or more infective particles had been inoculated or when smaller inocula were used which also contained 3 x 10(7) or more non-infective particles. Non-infective particles prepared in vitro at 35 degrees or 22 degrees C. were as effective as those which accumulated in vivo in diminishing the proportion of infective particles in the yield. The extent of the reduction in the proportion of infective particles was directly related to the number of non-infective particles included in the inoculum. The yield of hemagglutinating particles was diminished when the inoculum contained 3 x 10(7) or more non-infective particles. The rate of increase was reduced so that the time to double the concentration became 92 minutes when the inoculum contained 3 x 10(8) non-infective particles. It appears from these findings that the single condition which will lead to the emergence of non-infective particles during the logarithmic period is a high initial particle-cell ratio. Because non-infective particles are equally as effective as infective particles in producing this result, it seems probable that the appearance of non-infective but hemagglutinating particles is not a necessary accompaniment of the reproductive process.

Germ Cells↗
PubMed1954

Disruption of influenza virus; properties of degradation products of the virus particle.

1. The hemagglutinating capacity, enzymic activity, and infectivity of several influenza viruses were destroyed by repeated freezing and thawing of dialyzed allantoic fluids containing them. 2. Influenza virus degraded by freezing and thawing, by treatment with 5 M urea, or by heating at 65 degrees C. still combined with homologous antibody and was demonstrable by blocking of the hemagglutination-inhibition and virus neutralization reactions. 3. After 50 cycles of freezing and thawing, much of the blocking antigen activity was not sedimented by centrifugation at 120,000 g for 2 hours, and electron microscopy showed complete disruption of the virus particles. So called soluble blocking antigen was obtained from four strains of influenza A, the Lee strain of influenza B, mumps, and Newcastle disease viruses. 4. Soluble blocking antigens from influenza A viruses were highly strain-specific; gave little or no reaction in complement-fixation tests; stimulated but little antibody production in rabbits and did not induce immunity in mice; caused reactivation of infective virus in neutral mixtures of homologous virus and immune serum. 5. Repeatedly frozen and thawed influenza virus preparations did not interfere with the propagation of infective virus in the allantoic sac. The blocking antigen activity they contained was precipitated by half saturated ammonium sulfate, destroyed by trypsin, chymotrypsin, or heating at 56 degrees C. for 30 minutes, but was unaffected by desoxyribonuclease or ribonuclease. 6. These findings are in accord with the view that soluble blocking antigen obtained from influenza virus particles on disruption by repeated freezing and thawing is protein in nature and represents the essential antigenic material of the intact virus.

Animals↗