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M A Epstein

Publications and source records attributed to M A Epstein.

At least 37 records · Page 2Linked to original sources
PubMed1988

Recombinant vaccinia virus expressing Epstein-Barr virus glycoprotein gp340 protects cottontop tamarins against EB virus-induced malignant lymphomas.

A strong association exists between Epstein-Barr (EB) virus and two human cancers, endemic Burkitt's lymphoma and nasopharyngeal carcinoma. In addition, the virus causes infectious mononucleosis [reviewed in Epstein and Achong, 1979, 1986] and more recently has been implicated in lymphomas arising in immunosuppressed individuals [Cleary et al., 1986]. The possibility of preventing or influencing the course of these diseases by vaccination has been advocated for a number of years [Epstein, 1976], especially in the case of undifferentiated nasopharyngeal carcinoma, which is the most common tumour of men in southern China and is prevalent in other specific regions; it therefore represents a major world cancer problem [Shanmugaratnam, 1971]. Two vaccinia virus strains were employed to make recombinants expressing the gene coding for the EB virus envelope glycoprotein, gp340, and were used to vaccinate cottontop tamarins. Protection against EB-virus-induced lymphoma was obtained in animals immunized with the laboratory (WR) strain recombinant but not with those recombinants derived from the vaccine (Wyeth) strain. Circulating antibodies to EB virus gp340 were not detected in any of the immunized animals.

Animals↗
PubMed1988

Effective dead space of differently shaped airways during high-frequency ventilation of a CO2-producing lung model.

A simple lung model is described which simulates the mechanical properties and CO2 production of the lungs of a small animal, and which can be used with high-frequency ventilators. The model was ventilated by a rotary-valve ventilator and the system was used to determine the increment in 'physiological' (Bohr) dead space produced at various ventilatory frequencies between 0.5 and 15 Hz by the insertion of various additional volumes and configurations of 'anatomical' dead space in its 'upper airway'. It was found that the insertion of a straight tube with an internal diameter similar to that of the ventilator outlet tube produced an increment in 'physiological' dead space that remained commensurate with the volume of the added tube at all combinations of the tube volume and ventilatory frequency. The insertion of similar volumes of dead space in the form of tubes with smoothly expanded central portions produced increments in 'physiological' dead space which were commensurate with the volume of the added tube only at the lowest frequencies, and actually became negative at higher frequencies and volumes. These findings provide further evidence that the volume and configuration of the external portion of a high-frequency ventilator system may be of at least as much importance in determining its efficiency as is the lung structure of the animal or patient being ventilated.

Animals↗
PubMed1987

The Florey lecture, 1986. Vaccine prevention of virus-induced human cancers.

Carcinogenic viruses have been discovered in numerous animal species over the last 80 years but their role in human cancer has only recently become an important issue. With EB virus involved with endemic Burkitt's lymphoma and undifferentiated nasopharyngeal carcinoma, hepatitis B virus with primary liver cancer, papilloma viruses with carcinoma of the cervix, and T-cell leukaemia virus with adult T leukaemia, 20-25% of all human cancer appears to have a virus component in its causation. By analogy with certain virus-induced animal cancers, vaccine prevention of infection should greatly reduce subsequent tumour development; vaccines against hepatitis B virus are already on trial for this purpose in populations at risk. Experiments are described in which an EB virus subunit vaccine consisting of the virus-determined membrane antigen glycoprotein molecule of molecular mass 340 kDa (MA gp340) has been prepared by two purification methods. Material from one of these has successfully protected cotton-top tamarins against a 100% lymphomagenic dose of challenge virus and investigations are under way to identify an immunogen, based on MA gp340, suitable for use in man. Genetically engineered bacterial, yeast, and mammalian cells expressing the gp340 gene are already available; this gene has also been inserted into vaccinia and varicella virus vectors. Powerful new adjuvants are also considered, together with future strategies for human vaccine studies.

Animals↗
PubMed1987

Volume estimation of symmetrical branching structures by resonance mode analysis.

An exact resonance condition is derived for rigid symmetric second-order bifurcating structures. In the low-frequency range, the resonance condition can be reduced into forms that facilitate volume estimation of bifurcating structures. Two such volume approximation techniques are presented: (1) a fundamental frequency method, in which the lowest resonant frequency is inversely proportional to the structure volume, and (2) an equivalent-length method, in which an equivalent length of two daughter branches is calculated for all branches distal to the first bifurcation. An experimental study to determine the resonance modes of seven bifurcating glass structures was performed. The volume estimates obtained by either method were in very close agreement with the true volumes.

Animals↗
PubMed1987

Munchausen syndrome by proxy: considerations in diagnosis and confirmation by video surveillance.

Munchausen syndrome by proxy is a form of abuse in which the child suffers from a factitious illness induced by a parent. A case report of an 18-month-old boy who suffered from intractable diarrhea because of the surreptitious administration of laxatives by his mother is presented. The evolution of this case is discussed, as are the legal and ethical considerations in the diagnosis of Munchausen syndrome by proxy.

Child Abuse↗
PubMed1986

Vaccination against Epstein-Barr virus: current progress and future strategies.

A vaccine derived from the high-molecular-weight glycoprotein (gp340) component of the Epstein-Barr (EB) virus membrane antigen conferred complete protection against a 100% lymphomagenic dose of EB virus in the cottontop tamarin, the animal of choice for experiments with EB virus. The membrane-antigen gene has already been cloned, and the development of a vaccine for use in man should now be possible. Such a vaccine could be tested first against infectious mononucleosis, because the effectiveness of vaccination would become evident in a relatively short time. Field trials against Burkitt's lymphoma and nasopharyngeal cancer could follow.

Animals↗
PubMed1986

Adenocarcinoma of the large bowel and colitis in captive cotton-top tamarins Saguinus o. oedipus.

The gross and microscopic appearance of large bowel adenocarcinoma in two young adult, captive-born cotton-top tamarins is described. A retrospective examination of sections of colons from other animals that had died in the colony revealed a high incidence of chronic colitis. The adenocarcinomas, which resembled those reported from colonies of this species in the U.S.A., are thought to be the first seen in Great Britain.

Adenocarcinoma↗
PubMed1986

Some criteria for laminar conditions during HFV.

Assessment of the type of flow regime-laminar, transitional or turbulent-present in the central airways during high-frequency ventilation (HFV) can assist in identification of the predominant gas transport mechanisms for a particular species and set of HFV conditions. In this study, we use published empirical relationships, developed to identify the initial change from oscillating laminar flow to oscillating turbulent flow in tubes, to derive the limiting relationships between a dimensionless stroke volume and the Womersley number for maintenance of laminar conditions. When used with morphometric lung models for man and dog, these limiting relationships predicted maximum stroke volumes at experimental frequencies that either exceeded or agreed within 20% with the stroke volumes reported for steady-state ventilation of humans and dogs using HFV. Based on these limiting relationships, stroke volume-frequency combinations reported to demarcate the decline of PaO2 and alveolar ventilation were associated with nonlaminar conditions. It is expected that this approach may be useful in selecting the stroke volume-frequency pairs for HFV when a specific type of flow regime is desired as well as for analysis of HFV data.

Animals↗
PubMed1986

The 1986 Walter Hubert lecture. Recent studies on a vaccine to prevent EB virus-associated cancers.

Epstein-Barr (EB) virus was discovered in 1964 (Epstein et al., 1964). In the decades since then an immense body of information has been accumulated on the virus and a great deal is now known about its general biological behaviour, its epidemiology, its molecular biology, the humoral and cellular immunological responses which it evokes, and about its relationship to human cancers. The fact that EB virus was thought from the outset to be a human tumour virus was no doubt responsible for the large number of laboratories in which it has been studied. Viruses causing tumours in animals have been known since early in the present century and affect frogs, fowl, rodents, rabbits, cats, cattle, monkeys and even fish (Klein, 1980). It was obvious that man could not be different in this respect and the finding of EB virus therefore promised to bring human tumours into line with those of other species.

Adult↗
PubMed1986

The abnormal cytotoxic T cell response to Epstein-Barr virus in rheumatoid arthritis is correlated with disease activity and occurs in other arthropathies.

The cytotoxic T cell response to Epstein-Barr virus as measured by the regression assay was found to be impaired in a group of patients with active rheumatoid arthritis (RA). When these patients responded clinically to treatment with sulphasalazine there was a concomitant increase in the strength of this virus specific T cell response. The suggestion of a correlation between disease activity and impairment in this immune response was borne out in studies of other groups of patients with RA. Thus six out of 10 hospitalised patients had abnormal regression compared with six out of 31 patients seen routinely as outpatients. Studies of patients with inflammatory arthropathies other than RA, however, also showed abnormal regression in four out of 16 patients. It is concluded that the impairment in the cytotoxic T cell response to Epstein-Barr virus in RA is influenced by disease activity, and that this abnormality is not a specific feature of rheumatoid disease.

Arthritis, Rheumatoid↗
PubMed1986

Not all potently neutralizing, vaccine-induced antibodies to Epstein-Barr virus ensure protection of susceptible experimental animals.

Cottontop tamarins have been immunized with a high molecular weight, Epstein-Barr (EB) virus membrane antigen (MA) glycoprotein (gp340) separated by monoclonal antibody immunoaffinity chromatography (MCABgp340). Specific antibody production was monitored by immunofluorescence, a highly sensitive enzyme-linked immunosorbent assay (ELISA), and virus neutralization tests, and was found to reach high titre after 4/5 inoculations. The animals were challenged with a 100% lymphomagenic dose of EB virus but despite possessing powerful neutralizing antibodies were not protected against tumour causation by the virus. This result contrasts with that of earlier experiments in which tamarins with neutralizing antibodies induced by gp340 prepared by a molecular weight-based method (MWgp340) were protected. The reasons for this difference in protection associated with vaccine molecules prepared in different ways are discussed together with the need for parameters other than neutralizing antibody for use in the assessment of subunit immunogens against EB virus.

Animals↗
PubMed1986

Disturbance of the Epstein-Barr virus-host balance in rheumatoid arthritis patients: a quantitative study.

Rheumatoid arthritis (RA), seronegative spondyloarthropathy (SA) and osteoarthritis (OA) patients receiving no steroid or disease-modifying therapy have been monitored, along with healthy controls, for their prevailing level of Epstein-Barr virus (EBV) infection using four independent indices of the EBV-host balance, levels of virus shedding in throat washings as measured by a cord-blood transformation assay of improved sensitivity, frequency of virus-infected B cells in the circulating blood as measured by the rate of 'spontaneous' transformation in limiting dilution cultures, antibody titres to viral antigens, and virus-specific cytotoxic T cell responsiveness as measured in the in vitro regression assay. All four parameters indicated significant disturbance of the virus-host balance accompanying RA, the range of values exhibited by RA patients as a group in each case extending beyond the normal control range in the direction of more active infection. However, observations with SA and OA patients suggested that such a disturbance may not be RA-specific.

Adult↗
PubMed1985

Individual tumors of multifocal EB virus-induced malignant lymphomas in tamarins arise from different B-cell clones.

Cotton-top tamarins were inoculated with sufficient Epstein-Barr virus to induce multiple tumors in each animal within 14 to 21 days. The tumors consisted of large-cell lymphomas that contained multiple copies of the Epstein-Barr virus genome and generated Epstein-Barr virus-carrying cell lines showing no detectable consistent chromosomal abnormality. Hybridization of tumor DNA with immunoglobulin gene probes revealed that each lymphoma was oligo- or monoclonal in origin and that individual tumors from the same animal arose from different B-cell clones. Thus the virus induced multiple transformation events in tamarins in vivo to cause malignant tumors resembling the Epstein-Barr virus-associated lymphomas of patients with organ transplants.

Animals↗
PubMed1985

Distinctions between endemic and sporadic forms of Epstein-Barr virus-positive Burkitt's lymphoma.

Tumour cell lines were established in vitro from 16 cases of Epstein-Barr (EB) virus genome-positive Burkitt's lymphoma (BL), 7 of "endemic" origin (i.e. from holoendemic malarial areas of Africa and of New Guinea) and 9 of "sporadic" origin (i.e. from outside such high-incidence areas). All the BL cell lines thus established were monoclonal by immunoglobulin isotype expression and displayed a characteristic chromosomal translocation, t(8:14) or t(8:22), confirming their malignant origin. Clear differences observed between the individual BL cell lines appeared to be related to their endemic or sporadic status. All 7 endemic cell lines began growth as a carpet of single cells, often with small, loose clumps appearing in later passage. Whilst 3 lines of sporadic origin displayed a similar pattern to the above, the majority of sporadic lines grew as large, tight clumps of cells from the first passage onwards. These differences in growth pattern were reflected by differences in cell surface phenotype, as defined in indirect immunofluorescence tests using a panel of monoclonal antibodies (MAbs) specific for B-lineage-associated antigens. BL cell lines could be classified into 3 separate groups on the basis of their reactivity with 6 particular antibodies (MHM6, AC2, Ki-1, Ki-24, J5 and 38.13). All 7 endemic BL cell lines and 2 of the 3 sporadic BL cell lines which began growth as single cells showed a group-I cell-surface phenotype (MHM6, AC2, Ki-1, Ki-24 negative; J5, 38.13 positive) in early passage. In contrast, all 6 sporadic BL cell lines which began growth in large clumps displayed a distinct group-II phenotype (MHM6, AC2, Ki-1 positive/negative; Ki-24, J5, 38.13 positive); in later passage most of these sporadic lines progressed to a group-III phenotype (MHM6, AC2, Ki-1, Ki-24 positive; J5, 38.13 negative) without loss of those immunoglobulin and chromosomal markers identifying the cells' malignant origin. These clear differences between endemic BL cell lines on the one hand and the majority of sporadic BL cell lines on the other suggest that endemic BL arises from a more restricted range of progenitor B cells than does the sporadic form of the disease.

Adult↗
PubMed1985

Large-scale purification of Epstein-Barr virus membrane antigen gp340 with a monoclonal antibody immunoabsorbent.

A purification method has been elaborated to isolate Epstein-Barr (EB) virus membrane antigen, gp340, in milligram amounts. The gp340 was prepared from detergent extracts of B95-8 cells by affinity chromatography with a monoclonal antibody immunoabsorbent. Bound material was eluted and the eluate, consisting of 50% gp340, was then fractionated by gel filtration. The final gp340 product was antigenically active and 95% pure. The purification method was found to be rapid and reproducible with no loss of the ability of the immunoabsorbent to retain gp340 after repeated elution. The procedure provides suitable material to permit the detailed structural analysis of gp340 necessary for both vaccine design and for the investigation of the role of gp340 in immunity to EB virus infection.

Antibodies, Monoclonal↗