Enhancement of susceptibility to viruses in neoplastic tissues.
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Biomedical subjects
Publications and source records attributed to H KOPROWSKI.
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Detailed results are presented of primary immunizations of 387 persons with various courses of HEP Flury vaccine and of 54 persons with Harris- or Semple-type vaccines. Antibody response to HEP Flury vaccine was at least as rapid as that to the conventional type, but fell short in uniformity and level of response. The most promising course involved a 4-dose schedule, intradermal alone or combined with intramuscular, at 5-day intervals. A similar subcutaneous course of Semple vaccine yielded results completely equivalent to those of a 14-dose course of Harris vaccine. It is concluded that, although living, the HEP Flury virus does not multiply in man and that its lesser antigenic potency, as compared with Semple or Harris vaccines, is due to its relatively small content of viral antigen.Further evidence has been obtained that hyperimmune serum may exert a slight suppressive effect on active response, but the opinion is expressed that, with vaccines of full potency, this will not be of practical significance.Restimulation of immunity by a booster dose of HEP Flury vaccine was studied in 64 experimentally immunized persons and in 136 persons with history of previous Pasteur treatment. In both instances small intradermal inocula were as effective as larger intramuscular inocula in recalling pre-existing immunity.Study of recipients of Pasteur treatment indicated that antibody commonly persists for at least 5 years after a single course and for 15 or more years after re-treatment. It was also observed that the ability to respond to a booster of HEP Flury vaccine persists for at least 25 years. The response elicited by the booster is prompt and is usually at least equal to that resulting from a full primary course. The suggested conclusion is that previously treated persons need not receive more than a single booster on re-exposure, and that Pasteur treatment provides a solid basis for long-sustained immunity.
Further studies were made on groups of adult humans, previously unexposed to rabies and with no history of rabies vaccination, who were inoculated with different schedules of phenolized inactivated vaccine given subcutaneously and high egg passage (HEP) Flury strain vaccine given intradermally, with and without inoculation of antirabies serum. Serum specimens of the inoculated individuals were studied for antibody up to the 60th day after the first inoculation of the vaccines and serum. Studies were also made on the effect of "booster" doses of HEP Flury strain vaccine given 6 months after preparatory inoculations. The results can be summarized as follows:1. Fourteen daily inoculations of phenolized vaccine produced a superior antibody response to that obtained with 3 inoculations given 5 days apart.2. Three intradermal inoculations of HEP Flury vaccine given 5 days apart gave a low level of antibody response, but these individuals responded efficiently by producing antibody to a "booster" dose of the same vaccine given 6 months later.3. Administration of phenolized vaccine or of HEP Flury vaccine alone did not produce detectable antibody in most individuals until between the 10th and the 15th day after the first inoculation of the vaccine.4. Passive antibody following inoculation of antirabies serum persisted in some individuals for as long as 42 days. Two inoculations of serum administered 5 days apart did not give levels of antibody higher than those obtained with one inoculation.5. One inoculation of serum completely suppressed antibody response to 3 inoculations of Flury vaccine given intradermally 5 days apart, and also prevented the preparation of the individuals to respond to a later "booster" dose of this vaccine.6. Three inoculation of phenolized vaccine given 5 days apart acted efficiently in producing antibody by the 60th day. However, the interfering action of one and two inoculations of serum was clearly defined in this schedule.7. One inoculation of serum had no suppressive effect on the active antibody response to 14 daily doses of phenolized vaccine; two doses of serum given in the same combination definitely interfered with the production of an active antibody response.
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1. The cytological and cytochemical properties of the Ehrlich tetraploid and hyperdiploid, TA3 tetraploid and diploid, Krebs 2B, sarcoma 37, MC1M, 6C3HED and DBA lymphoma, and lymphoma #1 ascites tumors at a fixed interval after transplantation are described. 2. No qualitative differences were observed in the cytochemical properties of the nucleus, nucleolus, parachromatin, parachromatin bodies, large lipide globules, lipochondria, mitochondria, and cytoplasm of the tumor cells of the 10 neoplasms. 3. Quantitative differences were noted in the cells of the 10 neoplasms. These were reflected by variation in nuclear and cytoplasmic diameter, nucleolar mode, mitotic index, incidence of gross abnormalities of mitosis, karyorrhexis, multinucleated cells, accessory micronuclei, cell clumping, and in the number and size of the large lipide globules and lipochondria of the cells.
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Groups of adult humans, previously unexposed to rabies and with no history of rabies vaccination, were inoculated with different schedules of phenolized inactivated vaccine and Flury strain chicken-embryo vaccine, with or without one inoculation of hyperimmune serum. Serum specimens of the inoculated individuals were studied for antibody up to the 28th day following the first inoculation of the vaccines and serum. The results can be summarized as follows:1. Passive antibody appeared in the blood-stream within one day following inoculation of hyperimmune serum. The antibody persisted at a good level for at least 10 days, but dropped slightly by the 14th day and was present in most individuals at the 21st day.2. There was a tendency for the antibody levels at 21 and 28 days to be lower in the phenolized vaccine plus antiserum groups than in those groups which received phenolized vaccine alone.3. Seven or 12 daily inoculations of phenolized vaccine alone produced antibody in most instances by the 10th day and persisted generally through the 28th day.4. Daily inoculations of phenolized vaccine produced a superior antibody response to that derived from the same total amount of vaccine given as a single inoculation.5. A single inoculation intramuscularly of Flury strain chicken-embryo vaccine of high egg-passage did not produce detectable antibody.6. The group which received hyperimmune serum followed by 12 daily inoculations of phenolized vaccine showed early and persistent antibody throughout the entire period of test. The antibody levels were comparable to those recently observed in man treated effectively with antiserum-vaccine combination after severe exposure to rabies.(9)
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Sections of Ehrlich ascites tumor cells infected with anopheles A virus revealed particles in the cytoplasm, which were identified as the virus on the basis of their consistent size and internal structure; their high opacity in the electron beam after fixation with osmic acid; the localized occurrence, within a certain time interval following infection, of high concentrations of such particles within the cell; the absence of similar particles in uninoculated tumor cells and cells infected with other viruses, and the appearance of such particles in infected chorioallantoic membrane. The particles are spheroid, with a transparent 25 to 30 mmicro core, surrounded by an opaque complex shell 12 to 17 mmicro in thickness. Apparently "hollow," globular components of this shell have outer and inner diameters of approximately 12 mmicro and 5 to 7 mmicro respectively. The validity of an additional outer envelope is discussed. Particles are frequently embedded in a matrix, and their alignment and grouping are discussed. Markedly dense populations are found near nuclear concavities. Some infective changes in the cell are described, for example the formation of newly observed virus-induced necrotic regions.
Evidence is presented suggesting that anopheles A virus in the Ehrlich ascites tumor cell is harbored and propagated within the endoplasmic reticulum which in this system consists of an extensive canalicular network. The organization and differentiation of endoplasmic reticulum within the cell are described and the significance of such a location of virus is discussed.
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