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Biomedical subjects

M A Epstein

Publications and source records attributed to M A Epstein.

At least 145 records · Page 8Linked to original sources
PubMed1977

Further biological properties of the human syncytial virus.

Some biological properties of the human syncytial virus have been examined. A 13-day plaque assay in whole human embryo fibroblasts (HEF) has been developed using a liquid (growth medium) overlay. The plaques were 0.7-2 mm in diameter and often showed a clear central zone with irregular edges. Pretreatment of HEF monolayers with the polycation DEAE-dextran for either 30 min or 1 h was found to enhance plaque formation by a factor of from 2- to 7-fold. The plaque assay procedure required cell cultures undergoing active cell division. Adsorption kinetics and growth cycle studies in HEF indicated a relatively long adsorption period (3 h) and a relatively prolonged latent period of 24 h. Even under optimal conditions, virus yields were low and did not exceed 1 PFU per infected cell. Like other animal syncytium-forming 'foamy' viruses, the human virus induced both intranuclear and cytoplasmic antigens detectable by immmunofluorescence and was also markedly labile to freezing and thawing.

Adsorption↗
PubMed1977

Inhibition of the in vitro outgrowth of Epstein-Barr virus-transformed lymphocytes by thymus-dependent lymphocytes from infectious mononucleosis patients.

Known numbers of thymus-dependent (T) lymphocytes, obtained by positive selection from the blood of acute infectious mononucleosis (IM) patients and from control donors, were added to target cultures of foetal mononuclear cells within 0-7 days of exposure of the target cells to one of a range of doses of Epstein-Barr (EB) virus. The subsequent outgrowth of virus-transformed foetal cells was markedly inhibited by the presence in the cultures of IM-derived T cells, whilst similar numbers of T cells prepared either from cord blood or from adult donors seronegative for EB virus had little or no inhibitory effect. Target foetal cells treated with papain to remove any viral envelope material remaining on the cell surface after infection, were just as sensitive as untreated cells to the addition of IM-derived T cells. It is concluded that the inhibition cannot be mediated through recognition either of viral envelope structures on the surface of infected cells or of the antigenically related virus-determined membrane antigen, MA, but must depend upon recognition of the lymphocyte-detected membrane antigen, LYDMA. The regularity with which IM-derived T cells block the outgrowth of virus-transformed foetal cells suggests that LYDMA consistently appears on the surface of infected foetal cells before the establishment of transformed foci, but is unlikely to be directly associated with the cells' existing histocompatibility antigens.

Antigens, Viral↗
PubMed1976

Activation in vitro by BUdR of a productive EB virus infection in the epithelial cells of nasopharyngeal carcinoma.

Material from a nasopharyngeal carcinoma (NCP) has been passaged in athymic (nude) mice to eliminate non-malignant infiltrating cells. The human origin and derivation from NPC malignant epithelial cells of the nude mouse tumours have been confirmed by chromosome examination, electron microscopy showing desmosomes and keratin fibrils, and postive EB virus nuclear antigen (EBNA) testing. Samples of the mouse-grown tumours were cultured and pure monolayers of epithelial cells were obtained which still expressed EBNA and contained desmosomes and keratin; these cultures grew well for about 3 weeks. Extensive electron microscope searches failed to reveal herpes virus particles. In contrast, cultures treated with BUdR showed typical immature and mature herpes virus particles in epithelial, keratin-containing cells, and immunofluorescence tests for virus capsid antigen with a battery of human sera identified this agent as EB virus. EB virus has thus, for the first time, been activated in NPC epithelial cells and shown to be capable of replication in a cell type other than a primate B-lymphocyte.

Animals↗
PubMed1976

Morphological observations on the replication of herpesvirus saimiri in monkey kidney cell cultures.

Owl and African green monkey kidney cell cultures have been infected with 1 p.f.u./cell of herpesvirus saimiri and sample cultures have been taken for examination by electron microscopy at 3 to 6 hourly intervals over a period of 7 days; the experiments were repeated several times. The peculiarly slow replication cycle of Herpesvirus saimiri has enabled distinct cytoplasmic and nuclear phases in virus maturation to be clearly distinguished; the overall fine structural features were similar in both cell types. Immature particles were first detected in the nucleus and cytoplasm 63 h after infection. Thereafter, abundant cytoplasmic immature particles matured by budding through cytoplasmic membranes until about 100 h, whereas nuclear immature particles budded through the inner nuclear membrane or intranuclear invaginations of it later, from about 100 h until cytolysis was complete at 160 h. Morphological differences were also observed between particles budding at cytoplasmic membranes and the nuclear envelope. At the former site the membrane overlying the bud showed an electron opaque thickening which imparted to the mature particle an asymmetrical appearance. Such thickenings of the envelope were not observed in mature particles of nuclear origin. Unusual tubular and laminated nuclear structures were seen towards the end of the replicative cycle corresponding with the phase of nuclear virus maturation by budding; the morphology of the latter structures is described.

Animals↗
PubMed1976

Implications of a vaccine for the prevention of Epstein-Barr virus infection: ethical and logistic considerations.

Reasons are given for considering that there is sufficiently substantial indirect and circumstantial evidence linking Epstein-Barr (EB) virus to African Burkitt's lymphoma (BL) and nasopharyngeal carcinoma to call for a dynamic new approach to establish a causal role for the virus in these human cancers. It would seem that the only way to do this would be to develop a vaccine, vaccinate a population at risk in a high-tumor-incidence area, and subsequently follow the population for a consequential decrease in tumor incidence. Recent developments in the control of animal herpesvirus-induced malignant tumors by vaccines free of viral nucleic acid make it possible to envisage that a similar vaccine could be developed against EB virus without undue difficulty. Experiments showing the tumor-inducing ability of EB virus in South American subhuman primates have provided an in vivo laboratory system in which to test the safety and efficacy of the vaccine. Trial of the vaccine in human populations could be carried out by testing its ability to protect those at risk from primary EB virus infection accompanied by infectious mononucleosis. Although in world terms BL is not a major health problem, nevertheless African BL provides uniquely favorable conditions in which to test for a causative role for EB virus: high incidence areas are known, the peak tumor incidence is at the age of 5 or 6, and the effects of vaccination on tumor incidence could be assessed within a decade. Should a carcinogenic role for EB virus be demonstrated in African BL, a much longer term program would be called for to extend the vaccine control of infection to areas where EB virus is implicated in the induction of nasopharyngeal carcinoma. Although a high incidence of this tumor is confined to populations of Southern Chinese origin, the very large numbers of such people and the frequency of the tumor among them make this a substantial world health problem and, therefore, worth the cost and effort necessary to develop a vaccine giving life-long immunity and to conduct a program that will take more than a generation to give positive results.

Africa↗
PubMed1976

EB virus in the owl monkey (Aotus trivirgatus).

Owl monkeys (Aotus trivirgatus) were inoculated with EB (Epstein-Barr) virus-containing material or virion-free control material. One out of three animals given the virus died after 14 weeks with a reticuloproliferative disease compatible with malignant lymphoma. A cell line was established from an abnormal lymph node of the diseased monkey and was found by electronmicroscopy to carry a herpesvirus identified as EB virus by two types of immunofluorescence test, by its biological behavior and by nucleic acid hybridization studies. None of the inoculated animals developed heterophile antibodies, and only the diseased animal had an antibody response to EB virus. The findings were discussed in relation to a possible oncogenic capacity of EB virus in vivo.

Animals↗
PubMed1975

Pilot experiments with EB virus in owl monkeys (Aotus trivirgatus). III. Serological and biochemical findings in an animal with reticuloproliferative disease.

Nucleic acid hybridization with EB virus complementary RNA has demonstrated unequivocally that EB virus DNA is present in the cells of a continuous lymphoblastoid line established in culture from a pathological lymph node of an owl monkey with reticuloproliferative disease after inoculation with EB virus. There were 48 to 49 EB virus genome equivalents per cell. In addition, serological studies showed that the diseased owl monkey developed specific antibodies to EB virus capsid antigens. The antibodies were first detected by indirect immunofluorescence in serum sampled 13 weeks after inoculation, and were not found in sera from other animals without the disease. None of the monkeys developed heterophile antibodies. The significance of the biochemical and serological findings is discussed in relation to the nature of the reticuloproliferative disease and the possibility of tumour-induction by EB virus.

Animals↗
PubMed1975

Comparisons of surface markers on Herpesvirus-associated lymphoid cells of nonhuman primates and established human lymphoid cell lines.

Herpesvirus saimiri (HVS)-owl monkey lymphoid cells were found to have high levels of surface receptor for sheep erythrocytes and erythrocytes of 3 other species. These HVS-lymphoid cells lacked a receptor for modified complement. Lymphoid cells of one HVS-owl monkey line showed evidence for the presence of surface immunofluorescent staining with anti-kappa chain serum. Cells of an established HVS-marmoset lymphoid line had similar surface markers. Of 4 established human lymphoid cell lines, all lacked a receptor for sheep erythrocytes, 3 showed evidence for the presence of receptor for modified complement, and 3 showed immunofluorescent evidence for the presence on the surface of both heavy and light chain immunoglobulin. Preliminary data on an established Epstein-Barr virus (EBV)-owl monkey lymphoid cell line indicated a lack of receptor for sheep erythrocytes, presence of receptor for modified complement, and surface immunofluorescent staining with both anti-heavy and anti-light chain sera.

Animals↗
PubMed1975

The influence of electric fields red blood cells.

The effect of electric fields as related to red blood cell sizing techniques, hemolysis, mobility, and general behavior is examined. A review is made of the varying theories concerning these effects. In addition, the physical ramifications of electric field experimentation is viewed. Criticisms are made with regard to technique and lack of consideration for certain experimental variables.

Animals↗