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Biomedical subjects

J East

Publications and source records attributed to J East.

At least 37 records · Page 2Linked to original sources
PubMed1979

Azathioprine-induced lymphocytic neoplasms of NZB mice lack ecotropic murine leukaemia virus.

NZB mice injected intramuscularly throughout a 6-month period with the immunosuppressant azathioprine (Imuran) developed lymphocytic lymphomas 6--7 months after treatment was initiated. These malignancies were quite distinct from the reticulum-cell neoplasia which occurs spontaneously in the strain, and were readily transplantable to NZB or histocompatible BALB/c recipients. Xenotropic, but not ecotropic murine leukaemia virus (MuLV) was detected in leukaemic tissues of some donor and recipient NZBs when tested in vitro by co-cultivation with permissive cell lines, genome rescue, XC and viral polymerase assays. Virus filtrates prepared from donor leukaemic tissues were non-pathogenic when injected into newborn C3H mice. These results are evidence against a mandatory ecotropic MuLV genome in lymphocytic neoplasia.

Animals↗
PubMed1978

Longitudinal studies of chromosomal abnormalities and reticulum cell proliferation in New Zealand Black mice.

A longitudinal study of 40 New Zealand Black (NZB) mice and 20 BALB/c control animals was performed. A significant association was observed between the presence of acquired spleen-cell aneuploidy at some time during life and development of histological evidence of reticulum-cell neoplasia in individual animals. This finding is compatible with the hypothesis that aneuploid clones which arise in the spleens of aging NZBs are at least potentially neoplastic. However, no relationship between histologically neoplastic reticulum cell proliferation and aneuploidy was apparent in single splenic specimens obtained from NZB mice of various ages. This lack of association indicates that failure to detect chromosomal abnormalities on direct study of cells from a tumor cannot be taken as evidence that the neoplastic cells themselves lack such abnormalities.

Aneuploidy↗
PubMed1976

Transmission of auto-immune haemolytic anaemia and murine leukaemia virus in NZB-BALB/c hybrid mice.

When mated to normal BALB/c partners, male and female NZB mice transmitted auto-immune haemolytic anaemia to three generations of their hybrid progeny. Red cell auto-antibodies (positive Coombs tests) were detected, on average, 11 months later in the F1 hybrids than in the parental strain, and the course of the disease was protracted. In explicably, the auto-immune reactions then appeared progressively earlier in successive generations of both croses. The Coombs reactions of the F1 and F2 hybrids were often weak and inconsistent, while those of F3 offspring showed the strong and stable picture typical of NZB mice. The incidence of auto-immune disease in each generation, although similar in the reciprocal crosses, indicated that the pattern of inheritance was very complex. The hybrids did not develop the lymphoid type B reticulum cell neoplasia which characterizes auto-immune NZB mice. Instead, and irrespective of Coombs status, they had lymphocytic leukaemias, lung adenomas, hepatomas and type A reticulum cell neoplasms of the liver. Murine leukaemia virus was identified electronmicroscopically in F1 embryos, and in all the adults examined. It was also isolated from leukaemic spleen cells passaged briefly in vivo, and from malignant hepatic (reticulum) cells maintained in vitro. These isolated were leukaemogenic in newborn BALB/c, NZB, and F1 hybrid recipients, but did not induce or accelerate positive Coombs reactions. Only a small proportion of the hybrids had significant glomerulonephritis, and overt kidney disease was minimal. The lesions were not confined to Coombs-positive mice. Possible links between auto-immunity, malignancy, and virus infection in NZB mice are discussed in the light of these results.

Anemia, Hemolytic, Autoimmune↗
PubMed1976

Transmission of auto-immune haemolytic anaemia and murine leukaemia virus in F1 (BALB/c X NZB) hybrid mice derived by ovum transplantation.

F1(BALB/c X NZB)hybrid progeny derived by ovum transplantation were used to study the transmission of auto-immune haemolytic anaemia and murine leukaemia virus (MuLV) by male New Zealand black (NZB) mice. Fertilized ova, collected from the normal BALB/c partners 3 1/2 days after mating, were transferred to other, surrogate, BALB/c mothers, which then carried, delivered, and reared the hybrid young. This technical manoeuvre effectively closed the congenital transplacental route theoretically available to any infectious MuLV originating from the NZB father. Nevertheless, such progeny developed exactly the same profile of auto-immune haemolytic disease and the same range of diverse malignancies as their normally-derived F1(BALB/c X NZB) counterparts, and they carried type C MuLV particles readily detectable by electronmicroscopy. We concluded, therefore, that both the auto-immunity and virus were transmitted before placentation, presumably by the NZB male at fertilization, and probably as genetic information.

Anemia, Hemolytic, Autoimmune↗
PubMed1973

Chromosomal abnormalities in spleens of New Zealand black mice, a strain characterized by autoimmunity and malignancy.

Mosaicism of normal and chromosomally aberrant cells was detected in 14 of 20 spleens from adult New Zealand Black (NZB) mice reared under conventional conditions, a strain that spontaneously develops autoimmunity and lymphoreticular malignancy. No abnormalities were found in marrows from these same animals or in spleens from NZB mice younger than 3 months. The prevalence of chromosomal aberrations was significantly higher in spleens from NZB mice than in spleens from the two other strains studied-SJL/J, which has high frequency of reticulum cell neoplasia and paraproteinemia but no autoimmunity, and BALB/c, which has essentially no autoimmunity and only a low incidence of generalized lymphoid neoplasms and plasmacytomas in ageing animals. Causes for the chromosomal abnormalities in NZB mice are considered in terms of other features in these mice-immunoproliferation, autoimmunity, and the presence of murine leukemia ("C"-type) virus particles.

Age Factors↗
PubMed1972

Virus-associated immunopathology: animal models and implications for human disease. 1. Effects of viruses on the immune system, immune-complex diseases, and antibody-mediated immunologic injury.

The tissue damage caused by virus infection has been traditionally explained by the ability of viruses to multiply in cells and thereby injure or destroy them. Recent evidence suggests, however, that lesions may also be caused by the host's immune response to viral antigens and that the immune system itself may be perturbed by some viruses. This memorandum reviews recent developments in viral immunopathology, with special reference to animal model systems, and indicates the possible relevance of the new concepts and techniques for certain diseases of man. Certain viruses, notably the leukaemia viruses and some of those causing persistent infections, depress the host's ability to mount an antibody response to antigens, while other viruses may enhance the antibody response. Cell-mediated immunity may also be depressed. Another immunopathological manifestation of virus infection is immune-complex disease. When viruses or their antigens persist in the circulation they combine with specific antibody, and the resulting complexes lodge in various sites, especially the kidney. Further combination with complement leads to the release of tissue-damaging substances. A third condition associated with virus infection is antibody-mediated immunologic injury. Both oncogenic and non-oncogenic viruses frequently induce new antigens on the surface of the cells they invade. When antibody attaches to these antigens in the presence of complement, the cells are destroyed.

Animals↗
PubMed1972

Virus-associated immunopathology: animal models and implications for human disease. 2. Cell-mediated immunity, autoimmune diseases, genetics, and implications for clinical research.

Part 2 of this memorandum describes further mechanisms whereby the interaction of a virus with the host's immune system may lead to tissue damage. Cell-mediated immunity plays a vital role in promoting recovery from virus infections, but under some circumstances tissue damage may be caused by the reaction of immune cells with viral antigens. When mice are infected with lymphocytic choriomeningitis virus neonatally or as adults while receiving immunosuppressive drugs, widespread invasion of cells is seen but there is little overt disease. If, however, normal adults are infected or if immune cells are transfused into tolerant mice, cell injury and death follow. Viruses have long been suspected of contributing to the pathogenesis of autoimmune diseases. Antibodies directed against normal cell constituents have been reported in several virus infections. Viruses may conceivably unmask or release host antigens, alter host antigens and act as "helper determinants", or perhaps in other ways provoke immune responses against normal body constituents. The immunopathological manifestations caused by viruses may also be influenced by the host's genetic makeup. Certain observations indicate that, in addition to controlling susceptibility to virus infection, genetic factors partly determine the effectiveness of the immune response. The memorandum calls attention to the possible implications of these concepts and findings for clinical research. Some of the diseases of animals and man that serve as models for studies of virus-associated immunopathology are briefly described.

Anemia↗