Tumor Viruses

Beard, J. W.; Sharp, D. G.; Eckert, Edward A.

doi:10.1016/s0065-3527(08)60635-1

Cited by 44 publications

(10 citation statements)

References 102 publications

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“…However, the curves for groups given relatively small doses may be discontinuous as shown in the inset of Fig. 2 (Bryan & Beard, 1940;Cavalli & Magni, 1947;McKee, Rake, Donovick & Jambor, 1949;Beard, Sharp & Eckert, 1955: the latter discuss the treatment of these distributions). This implies that at a varying time after inoculation, which is related to the size of the dose, the hosts then surviving take longer to respond than would have been expected from the behaviour of those which had already responded.…”

Section: Discussionmentioning

confidence: 98%

The growth of micro-organismsin vivowith particular reference to the relation between dose and latent period

Meynell

1958

J. Hyg.

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The growth of Salmonella typhimurium in mice was studied by performing viable counts on pooled viscera and, in the case of fatally infected mice, by determining the relation between size of dose and mean death time. The results suggested that this system conformed to a general model which postulates (a) that the organisms causing the response (death in the present experiments) increase in vivo at a rate which is constant for all doses, and (b) that the response is certain to occur when their number reaches a constant figure. It follows that logarithm of dose (for doses > 1 ED50) should be linearly related to mean latent period (the interval between inoculation and response). A search of the literature showed that this relation was observed in many reported infective systems.The interpretation of the observations on partially resistant mice (LD50 = 102.5−106 organisms) was not straightforward for the hypothesis of independent action (Meynell & Stocker, 1957) states that only a random fraction of the inoculum usually initiates each response. Multiplication of this fraction is considered to cause a reduction in host resistance so that other organisms surviving in vivo began to increase in numbers and to contribute to the fatal infection. The observations showed that this could well occur as (i) the counts on all mice, whether fatally infected or not, increased exponentially for 2–3 days after inoculation; (ii) the growth curves of fatally infected mice showed exponential increase of the whole inoculum as postulated; and (iii) the length of the death time was found to be determined by the growth of the whole inoculum and not by the predicted random fraction. The viable count per fatally infected mouse at the time of death was approximately constant at 108.75 organisms. There was no evidence that the course of the infection was influenced by organisms which may have been killed in vivo as the requirements of the model were satisfied by the observed behaviour of the viable organisms alone. The rate of increase of organisms in a fatally infected animal was found to be less, the greater the LD50 of the host; which suggested that the degree of host resistance was determined by successive random events occurring after inoculation.The latent period/log dose curve provides a new test of the hypothesis of independent action, since this predicts that most responses to doses equal to or less than 1 ED50 are each initiated by only one inoculated organism. Hence, the latent period should become approximately constant at such doses. This was found to be so in the present experiments.The authors are grateful to the Medical Research Council for meeting part of the expenses of this work by a grant to G. G. M. They also wish to acknowledge the help of Dr W. R. Bryan, Dr B. Mandel, Dr D. B. W. Reid and Dr G. T. Stewart who provided unpublished data.

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Section: Discussionmentioning

confidence: 98%

The growth of micro-organismsin vivowith particular reference to the relation between dose and latent period

Meynell

1958

J. Hyg.

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“…While our data are not conclusive, future studies should examine the effects of different environmental temperatures on the efficiency of disease transmission and tumor development. The time lag for development of tumors caused by oncogenic viruses may also be influenced by infectious dose (Beard et al 1955). Presently we have no way to estimate the dose of infectious agent in our tumor extracts.…”

Section: Discussionmentioning

confidence: 99%

Experimental transmission of green turtle fibropapillomatosis using cell-free tumor extracts

et al. 1995

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Green turtle fibropapillomatosis (GTFP), characterized by multiple benign fibroepithelial tumors on the skin and eyes, has become a growing threat to green turtle Chelonja mydas populations worldwide. The cause of GTFP 1s unknown, but a viral etiology is suspected. This study investigated whether GTFP could be experimentally transmitted to young captive-reared green turtles using cell-free fibropapilloma extracts prepared from free-ranging turtles with spontaneous disease Turtles raised from eggs collected from 4 separate clutches in the wild were assigned to 4 expenmental groups and 1 control group. For each experiment a crude homogenate (33 % w/v) was prepared from fibropapillomas removed from a free-ranging turtle with spontaneous disease. The crude tumor homogenates were freeze-thawed and centrifuged to yield cell-free extracts that were used (both filtered and unaltered) for inoculation. Recipients were inoculated by intradermal injection or by scarification; control turtles were not treated but \yere housed with treated turtles. Fibropapillomas developed in all 12 turtles receiving 3 of the 4 tumor extracts, and were first detected between 15 and 43 wk post inoculation. Both filtered and unfiltered tumor extracts successfully induced tumor development. During the 10 and 12 mo monitoring periods. fibropapillomas did not develop in control turtles or in any turtles inoculated with the fourth tumor extract. Although 2 sets of experiments were performed 8 wk apart, most of the tumors in both sets became evident simultaneously after water temperatures rose Experimental tumors were h~stologically i n d~s -tinguishable from spontaneous fibropapillomas found In free-living turtles but lacked evidence of endoparasites. Scattered foci of epidermal degeneration were found in most sections of experimentally induced fibropapillomas and within some sections taken from donor turtles. Electron rnicroscopy revealed virus-like particles conforming in size, morphology, and intranuclear location with herpesvirus. Negativestaining electron microscopy of transmission-positive tumor extracts failed to demonstrate intact virus particles. This study demonstrates that the etiology of GTFP is an infectious filterable subcellular agent. The herpesvirus identified in this study is 1 possible candidate for the etiology of GTFP.

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“…Studies on the dose-response curves of bacterial and virus titrations have been extensively reviewed and discussed (Beard, Sharp & Eckert, 1955; Bryan, 1955; Isaacs, 1957;Lauffer & Price, 1945; Luria, 1940;Meynell & Stocker, 1957). In most infectivity titrations the log dose-probit response curves show a slope equal to or lower than 2 (Peto, 1953), this being approximately the slope of the first term of the Poisson distribution (the ' one-particle curve ').…”

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confidence: 99%

“…Deviations from the one-particle curve are attributed to variations in host susceptibility which cause a flattening of the curves. This is particularly evident with agents such as the tumour viruses where variation in host susceptibility greatly affects the slope of dose-response curves (Bryan, 1954;Beard et al 1955). With bacteriophages, on the other hand, where host susceptibility is uniform, agreement with the one-particle curve is good (Feemster & Wells, 1933; Luria, H .…”

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Dose-response Curves of Toxic and Infective Actions of Adenovirus in HeLa Cell Cultures

Pereira¹,

Kelly²

1957

Journal of General Microbiology

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The methods used for infectivity titrations of adenoviruses are based on the cytopathic action of these agents in tissue cultures. Titration techniques described by different workers vary in several respects but in most cases the results are based on quanta1 responses in cultures incubated for a given period. A relationship between virus dose and time of onset of cytopathic effect has been described (Rowe, Huebner, Gilmore, Parrott & Ward, 1953), and Kjellen (1956) developed a method of titration based on the latent period which precedes the cytopathic effect.In the course of repeated titrations of adenovirus preparations we observed a difference between the slopes of dose-response curves of titrations read after varying periods of incubation. These differences suggest that the early effect of adenoviruses in HeLa cell cultures is of the nature of a toxic action, whereas the late effect is a manifestation of the infective property of the virus resulting from the independent action of single infective units.Studies on the dose-response curves of bacterial and virus titrations have been extensively reviewed and discussed (Beard, Sharp

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Tumor Viruses

Cited by 44 publications

References 102 publications

The growth of micro-organismsin vivowith particular reference to the relation between dose and latent period

The growth of micro-organismsin vivowith particular reference to the relation between dose and latent period

Experimental transmission of green turtle fibropapillomatosis using cell-free tumor extracts

Dose-response Curves of Toxic and Infective Actions of Adenovirus in HeLa Cell Cultures

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