Herpes simplex virus neoplastic transformation.
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Biomedical subjects
Publications and source records attributed to F Deinhardt.
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Synovial cell lines were established from patients with rheumatoid arthritis (RA) and from normal human embryos. High levels of hyaluronic acid (HA) were produced by some RA cell lines, some of which were partially or completely resistant to infection with Newcastle disease virus (NDV), vesicular stomatitis virus (VSV), and rubella virus (RV). Normal fetal synovial cells lines were susceptible to NDV, VSV, and RV. Infection with virus became possible after treatment of RA cells with hyaluronidase to depolymerize HA, and HA prevented infection of normal synovial cells with VSV. These results provide evidence that HA and not chronic or latent viral infection is responsible for the lack of susceptibility of RA synovial cells to certain viruses.
Eight white-lipped marmosets immunized with BCG and 3 sham-immunized marmosets were studied after inoculation with Herpesvirus saimiri (HVS). BCG immunization had no significant influence on the incidence of infection by HVS, incidence of fatal malignant lymphoma, time of leukemia onset, development or titer of HVS antibodies, or average survival time. One BCG-immunized, HVS-infected marmoset failed to develop malignant lymphoma, whereas the remaining 10 HVS-infected marmosets died of malignant lymphoma. Prolonged survival occurred also in 1 marmoset immunized with BCG 100 days after HVS inoculation. The development and disappearance of lymphocyte reactivity to tuberculin were followed in 4 BCG-immunized marmosets.
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Several types of viral hepatitis may exist. Hepatitis A (MS-1 type) can be transmitted to marmosets and chimpanzees. Virus-like particles, which may be parvo- or enteroviruses and which have been demonstrated in feces of this type of hepatitis, do not share cross-reacting antigens with hepatitis B but do cross-react with fecal hepatitis A antigen. Hepatitis A (GB type), which also does not cross-react with hepatitis B, is not antigenically identical with MS-1; it can be transmitted to marmosets and it may be similar to non-type A/non-type B post-transfusion hepatitis. Hepatitits B does not cross-react either with HA particles, the faecal hepatitis type A antigen or with the MS-1 or GB strains; it can be transmitted to chimpanzees and rhesus monkeys but not to marmosets.
Transformation and induction of EBV-specified EBNA was studied in human umbilical cord-blood lymphocytes infected with EBV, HVS or HVA. Transformation of human umbilical umbilical cord-blood lymphocytes into continuous lymphoblastoid cell lines was successful with EBV derived from five of seven human or simian cell lines but not with HVS or HVA derived from simian lymphoblastoid cell lines. EBNA induction was studied using B95-8 virus for infection of lymphocytes; as early as 24 hours after infection, a few EBNA-positive cells were identified in 10 of 12 samples studied. Thereafter, the number of EBNA-positive cells increased progressively and by day 12, 50% of cells contained EBNA; after 18-20 days, approximately 85-90% of cells were EBNA-positive.
The response of cotton-topped (CT) or white-lipped (WL) marmosets, inoculated with material containing Epstein-Barr virus (EBV), was studied. Twenty-five marmosets inoculated with 10(6)-10(8) cells from human or simian EBV-carrying lymphoblastoid cell cultures developed no detectable clinical disease. Transitory antibody titres to VCA were detected in sera from several of these marmosets. Thirty-eight marmosets inoculated with P3 virus (10(9) particles) and seven marmosets inoculated with 10(5) infectious units of HR-1 virus likewise developed no recognizable clinical or haematological disease over several years of observation. Fourteen marmosets were inoculated with 10(2)-10(4) transforming units (TFU) of EBV strain B95-8; five of 11 animals inoculated with 10(3)-10(4) TFU of virus developed malignant lymphoma and died 31-110 days PI. Antibodies to one or more EBV-specified antigens were detected in sera from nine of the inoculated marmosets. EBV-carrying lymphoblastoid cell cultures were established from the spleen and lymph-nodes of one animal that died with malignant lymphoma and from another animal that died 19 days PI from undetermined causes.
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Reproductive performances of wild-caught and laboratory-born marmosets maintained in a paired-cage system were summarized. Wild-caught, white-lipped (WL) marmosets (Saguinus fuscicollis, S nigricollis) averaged 2.6 live births per pair per yr compared with 1.6 for cotton-topped (CT) marmosets (S oedipus); S fuscicollis illigeri pairs were the best producers. Of first and second generation laboratory-born animals, crossbred or hybrid WL pairs were the best producers; first generation pairs averaged 2.7 live births per pair per yr, comparable to the production of wild-caught WL pairs. In contrast, laboratory-born Sf illigeri pairs produced only 0.8 live births per pair per yr. No significant differences in reproductive performance were observed between first generation outbred vs inbred and between parent-reared vs hand-reared pairs. Based on limited data, the reproductive capabilities of wild-caught and laboratory-born Callithrix jacchus appeared superior to both WL and CT marmosets. Ten examples of marmoset models in biomedical research were discussed briefly.
Continuous lymphoblastoid cell cultures were established after transformation invitro with HVA of marmoset splenic or circulating lymphocytes. Transformation was achieved by co-cultivating lymphocytes with lethally X-irradiated, HVA-carrying cells (derived originally from tumour cells of a marmoset experimentally infected with HVA) or by infecting marmoset lymphocytes with cell-free virus. Tenty-eight continous cultures from 39 that underwent co-cultivation and two of four lymphocyte preparations infected with virus became transformed. Cultivation periods before transformation were in the range 17-32 days (co-cultivation) or 51-53 days (cell-free virus). HVA genome expression in transfromed cultures was demonstrated by:(1) recovery of small amounts of HVA from culture fluids; (2) ability of lymphoblasts to induce infectious centres after co-cultivation with permissive cells; and (3) observation of antigen-positive cells after staining with monospecific antiserum. Most cultures were composed of T lymphocytes: cells of 16 of 24 cultures formed rosettes with sheep erythrocytes and none of 30 possessed membrane Ig.
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