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Biomedical subjects

P T Allen

Publications and source records attributed to P T Allen.

9 recordsLinked to original sources

Protection against 7, 12-dimethylbenz[a]anthracene-induced rat mammary carcinoma by infection with mouse xenotropic type C virus.

A single ip inoculation of female, outbred Sprague-Dawley rats with a viable mouse xenotropic type C virus significantly reduced the incidence and/or retarded the development of mammary carcinoma induced by 7, 12-dimethylbenz[a]anthracene administered orally 7 days after virus. Although infectious virus could not be isolated from organs of infected rats, high titers of circulating and tumor-associated antibodies were detected against the viral internal core protein p30, and a low-grade antibody response to intact virus or envelope glycoprotein was found. Moreover, a cell-mediated immune response, measured by lymphocyte transformation, was detected with the use of intact virus but not with p30 antigen. No immunity developed after a single inoculation of UV-inactivated virus. These data indicated that inoculation of adult individuals of heterologous species with viable xenotropic mouse type C virus resulted in the rapid disappearance of infectious virus from the recipient, followed by the development of both humoral and cellular immunity to virion constituents. These events led, by unknown mechanisms, to the effective retardation of chemical carcinogenesis when infection preceded carcinogen administration.

9,10-Dimethyl-1,2-benzanthracene

Influence of interferon on the synthesis of virus particles in oncornavirus carrier cell lines. IV. Relevance to the potential application of interferon in natural infectious diseases.

That interferon reduced the release of C-type oncornavirus particles by chronically infected mouse cells was shown by radiolabeling of the particles with uridine or amino acids and by determination of particle-associated reverse transcriptase. The number of released particles, as determined by direct electron microscopic enumeration, was reduced to a lesser extent. In contrast, interferon failed to affect the number of budding particles and caused a slight increase in the number of completed particles present in the microspace contiguous to the cell membranes. A working hypothesis is that, in the presence of interferon, C-type particle assembly and release are slowed but not arrested; sizable numbers of particles continue to be assembled and released. Some of these particles may be defective in one or more proteins, such as reverse transcriptase or proteins necessary for final release. These in vitro data justify speculation that, in vivo, interferon may be expected to reduce tissue damage due to antigen-antibody complex formation, but not damage due to sytolytic immune attack on cells carrying the antigens.

Animals

Differential sensitivity of Rauscher murine leukaemia virus (MuLV-R) to interferons in two interferon-responsive cell lines.

The effect of interferon on the replication of vesicular stomatitis virus (VSV) and type-C oncornavirus in two Balb/c mouse cell lines, JLS-V5 and JLS-V9R, infected with MuLV-R was examined. VSV replication was inhibited threefold (0-5 log10) in both cell lines by 10 to 20 units of interferon/ml. In JLS-V5 cells C-type virus yields, as measured by 3H-uridine incorporation and reverse transcriptase activity, were also reduced threefold by 10 to 20 units of interferon/ml. However, in JLS-V9R cells, C-type virus replication was refractory to interferon at concentrations up to 1 x 10(4) units/ml. Infectious C-type virus transmitted from JLS-V9R cells to Balb/3TS cells was as sensitive to interferon as virus transmitted from JLS-V5 cells, indicating that resistance of C-type virus in JLS-V9R cells is a feature of the cells rather than of the virus strain.

Animals

Evidence that detergent-reactivated interferons are not renatured.

The sedimentation rate of human leukocyte interferon (HLIF) reactivated from sodium dodecyl sulphate (SDS) solution was studied by glycerol gradient centrifugation and compared to that of native HLIF. Reactivated HLIF consistently sedimented faster than native HLIF, indicating that full recovery of antiviral activity does not require renaturation of the entire interferon molecule.

Animals

Effect of medium of lowered NaCl concentration on virus release and protein synthesis in cells infected with reticuloendotheliosis virus.

When cultures producing reticuloendotheliosis virus were incubated for 24 h in medium of lowered NaCl concentration, virus production was inhibited. The extent of inhibition increased as the salt concentration of the medium was decreased. The inhibition was rapidly reversed by replacement of low-salt medium with normal medium. During the first hour after the inhibited cultures were returned to normal medium, virus was released at an accelerated rate, making the total amount of virus released by inhibited and control cultures the same. After 1 h in normal medium, the rate of virus production in the previously inhibited cultures was the same as in the control cultures. Incubation of infected cells in low-salt medium resulted in a 60% decrease in the overall rate of protein synthesis. Although returning the cells to normal medium rapidly reversed the inhibition of virus production, it did not rapidly increase the rate of protein synthesis. These results suggest that host cell-directed protein synthesis is preferentially inhibited by the low-ionic-strength medium, whereas that required for virus production continues.

Animals

RNA-directed DNA polymerase activity of reticuloendotheliosis virus: characterization of the endogenous and exogenous reactions.

Reticuloendotheliosis virus (REV) contains an endogenously instructed, RNA-directed DNA polymerase activity. Both the endogenous and exogenous DNA polymerase activities exhibited up to 10-fold greater activity at the optimum concentration of manganous ion (0.025 mM for exogenous; 0.25 mM for endogenous) than at any concentration of magnesium ion. Antiserum to the DNA polymerase of an REV group virus (spleen necrosis virus) inhibited both endogenous and exogenous DNA polymerase activity of REV, whereas antiserum to the Rous sarcoma virus (Rous-associated virus-0) [RSV(RAV-0)]DNA polymerase did not. The DNA product of the endogenous reaction is associated with the high-molecular-weight RNA of REV and anneals with REV RNA but not with RNA from Rous sarcoma virus.

Antigens, Viral

Virus retrieval studies in human neoplasia.

Short- and long-term co-cultures of 49 cases of human osteosarcoma cells with bone marrow or peripheral blood cells of patients with different types of leukemia were studied. Morphological changes were observed in 7 of 13 long-term co-cultures resembling those induced by RNA tumor viruses. The changes were accompanied by appearance of cytoplasmic antigen as shown by fixed immunofluorescence test with sera from patients with osteosarcoma, leukemia, and of some apparently normal blood donors. Absorption with Forssman-like substances, whole human embryo cells or osteosarcoma cells demonstrated the reaction to be due to tumor antigen(s) in co-culture cells showing morphological changes. Electron microscopy showed a few type C virus particles in one co-culture. Cell-free filtrates of fluid from the transformed co-cultures induced morphological changes in 1 of 4 human embryo cultures. Uninoculated embryo cultures or those inoculated with filtrates from parental sarcoma or leukemia cultures showed no morphological changes. Human embryo cell cultures treated with fluid from parental leukemic bone marrow but not from parental sarcoma cultures showed appearance of cytoplasmic antigen by immunofluorescence test with sera of osteosarcoma and leukemia patients and of some apparently normal blood donors. Transformed human co-cultures showed the cytoplasmic antigen with 28 of 48 sera of osteosarcoma and leukemia patients tested, after absorption with Forssman-like material, human embryo, and mycoplasma suspensions. Fourteen of 49 sera of normal donors were also positive with the transformed co-cultures. Similar results were obtained in an earlier series of experiments with human embryonic cultures transformed by fluid from different osteosarcoma-leukemia co-cultures when examined by fixed immunofluorescence tests with sera of patients with osteosarcoma and leukemia. In 2 whole human embryo cell cultures showing morphological changes high molecular weight RNA was found, similar to that of RNA animal tumor viruses and in one of the cultures transient reverse transcriptase was detected.

Antigens, Viral