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Biomedical subjects

J H Pope

Publications and source records attributed to J H Pope.

At least 55 records · Page 3Linked to original sources

Search for human tumour viruses by transfection: uptake of melanoma and Epstein-Barr virus DNA by human cells.

In a model system, consistent transfection of chick embryo fibroblasts (CEF) by DNA from the XC cell line occurred, with recovery of infectious Rous sarcoma virus. The techniques were then applied in attempts to recover possible human tumour viruses. Even with various modifications of the XC technique, DNA from three human malignant melanoma cell lines failed to infect adult or foetal human fibroblasts, although melanoma DNA was taken up into nuclei of target cells. XC DNA did not transfect human foetal fibroblasts and melanoma DNA was ineffective in CEF. DNA from the Raji (Epstein-Barr virus non-producer) and QIMR-WIL (producer) lymphoblastoid cell lines did not transfect human cord blood lymphocytes or amnion cells. These broadly applicable techniques therefore failed to recover EB virus, the putative melanoma retrovirus, or other potential tumour virus.

Animals↗

Human malignant melanoma cell lines.

A series of 10 cell lines established from human malignant melanomas is described. The morphology varied but, in general, was epithelioid. Five produced visible melanin in culture but others produced melanin precursors. All lines were aneuploid and each had a distinctive human karyotype. One line appeared not to have the same sex as the patient but its karyotype was distinct from that of other lines.

Aneuploidy↗

Long-term T-cell-mediated immunity to Epstein-Barr virus in man. I. Complete regression of virus-induced transformation in cultures of seropositive donor leukocytes.

Peripheral blood mononuclear cells from donors of known serological status with respect to EB virus were exposed to the virus in vitro and then cultured at various cell concentrations. All cultures from nine seronegative adult and 12 foetal donors gave rise to cell lines following subculture 4 weeks post infection. In contrast, seropositive donor cultures seeded at the higher cell concentrations developed foci of proliferating EBNA-positive cells within the first 1--2 weeks but thereafter regressed completely and subcultures made after 4 weeks never gave rise to cell lines. Out of 18 seropositive donors tested, 15 showed regression in all cultures seeded at 10(6) cells/ml and above, and with the other three donors a proportion of replicate cultures regressed. T-cell depletion and reconstitution experiments showed that the effect was absolutely dependent upon the presence in the cultures of T cells from these seropositive donors. The results strongly suggest that the regression phenomenon is an in vitro expression of long-term T-cell-mediated immunity to EB virus which the large majority, if not all, infected individuals possess.

Adult↗

Inhibition of Epstein-Barr virus transformation: evidence for a block between EBNA production and cell proliferation.

Non-adherent lymphocyte populations prepared from donors with previous EBV infection transformed in the usual way in response to EBV. However, transformation was completely inhibited in the presence of adult but not fetal human fibroblasts. Such inhibition was associated with lymphocytes from donors with prior EBV infection, but not from those without, and there appears to be an immunological basis for inhibition. Inhibition was associated with production of EBNA and was reversible. Addition of adult fibroblasts to non-adherent lymphocytes up to 2-4 days after infection with EBV also resulted in inhibition of transformation. These results are interpreted as indicating that EBV transformation involves two recognizable phases, with an immunological block between EBNA production and cell proliferation.

Adult↗

Burkitt's lymphoma in Australia.

An Australian case of Burkitt's lymphoma is reported. The clinical features of large ovarian masses and subsequent bone marrow invasion, as well as the results of investigations related to the Epstein-Barr virus, were more consistent with the American than the African type of Burkitt's lymphoma. After a good initial response to cyclophosphamide and vincristine, the tumour rapidly became resistant to these and other therapeutic measures and the patient died 10 months after diagnosis.

Australia↗

Oncornavirus-like particles in malignant melanoma and control biopsies.

Tests for the presence of oncornavirus-like particles in human biopsies were made by the Spiegelman simultaneous assay for 70S RNA and RNA-dependent DNA polymerase and by detection of 600-900S particles, incorporating 3H-uridine, produced by cultured biopsy cells. Thirty-one malignant melanoma biopsies from 29 patients were studied. Using the simultaneous assay, evidence of virus-like particles was found in 15/26 (58%) of melanoma biopsies, 0/3 naevi pools, 1/4 samples of skin adjacent to melanoma, 0/3 samples of normal adult skin and 0/3 prepuces. The velocity sedimentation technique was shown to be a useful screening test for oncornaviruses in studies of two virus-producing mouse cell lines (TKL-5 and WEHI-22), and was positive with 7/9 melanoma biopsies. Overall, these results are compatible with the earlier findings of similar virus-like particles in malignant melanoma cell lines, but the exact nature of the particles remains to be defined.

Cell Line↗

Inhibition of EB virus transformation of non-adherent human lymphocytes by co-cultivation with adult fibroblasts.

Transformation of a special population of non-adherent human lymphocytes by EB virus (EBV) is reversibly inhibited by co-cultivation on adult human fibroblasts. Neither fluid from adult fibroblast cultures nor extracts of fibroblasts inhibited such transformation, and the growth of already transformed lymphocytes was not inhibited on adult fibroblasts. The EBV-associated nuclear antigen (EBNA) was detectable in inhibited cultures, with a maximum level of about 15% at 14 days after which it decreased gradually. Reversal of inhibition at 28 days, by either addition of phytohaemagglutinin or by removal of the lymphocytes from the adult fibroblasts, resulted in a prompt increase in the percentage of EBNA-positive cells and typical lymphoblastoid outgrowth. Transformation of EBV-infected non-adherent lymphocytes could be inhibited by the addition of adult fibroblasts up to 2-4 days after infection. The results indicate that, in the EBV-infection of non-adherent lymphocytes on adult fibroblasts, a block resulting in inhibition of transformation occurs between the production of EBNA and the onset of autonomous proliferation of the infected lymphocytes.

Adult↗

Reactivity of antibody in acute myeloid leukaemia with proliferation-associated nuclear antigen(s).

A reaction between antibody in leukaemic sera and nuclear antigen present in leukaemic cells was detected by means of an anticomplement immunofluorescence test. The antibody was found mainly in patients with myeloid leukaemia, particularly those with a high percentage of blast cells in their peripheral blood. The nuclear antigen(s), however, was present in various proportions of the circulating cells of almost all patients with leukaemia, lymphoma or infectious mononucleosis, as well as in phytohaemagglutinin-transformed blasts and proliferating cell lines. Thus, antibody appeared to be detecting a nuclear component associated with cell proliferation.

Antibody Specificity↗

EB Virus-associated nuclear antigen production and cell proliferation in adult peripheral blood leukocytes inoculated with the QIMR-WIL strain of EB virus.

A nuclear antigen, apparently the Epstein-Barr virus (EBV)-associated nuclear antigen (EBNA), was detected by anticomplement immunofluorescence (ACIF) tests in adult peripheral blood leukocytes infected with the QIMR-WIL strain of EBV. EBNA was not detectable at 24 h but appeared in about 11% of the cells by 3 days, and by 5 days up to 64% of the cells were positive. Proliferation of EBNA-positive cells at this stage was confirmed by autoradiography. There was a good correlation between the concentration of virus and the number of EBNA-positive cells in the first 5-7 days. The subsequent course of events was found to be influenced by the initial cell concentration and the time of subculture. EBNA production was delayed in cells infected with higher dilutions of virus but subsequently appeared in a high proportion of cells. Indirect immunofluorescence failed to detect viral capsid antigen (VCA) or early antigen (EA) by 10 days. The results show that EBV infection was abortive and that the critical events of viral transformation occurred within the first few days.

Antigens, Viral↗