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H Rabin

Publications and source records attributed to H Rabin.

At least 73 records · Page 4Linked to original sources

Selective stimulation and differentiation of early antigens in lymphoblastoid cell lines producing Epstein-Barr-like viruses.

Comparisons of early antigens (EA) of EBV-related lymphotropic herpes virus of Old World primates have proved difficult to accomplish because antigen levels are low in infected cells and the ratio of virus capsid antigen to EA is generally high. To overcome these difficulties, we have developed a procedure which combines antigen stimulation with inhibition of late virus functions and results in the selective stimulation of EA. Using this procedure, we have examined the EA of EBV, herpesvirus papio, h. pongo, and h. pan. The results show that the EA of these viruses are composed of both R (restricted) and D (diffuse) components and that the EA, while related, are distinguishable.

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Characteristics of cell lines established from Epstein-Barr virus induced marmoset tumors.

The inoculation of a cotton-topped marmoset with B95-8 strain of EBV resulted in the induction of a multifocal lymphoma and lymphoblastoid cell lines were established from liver, spleen and mesenteric lymph node tumors. The cell lines were remarkably similar to each other with respect to the presence of EBV and its expression, the surface properties of the cells and their stability, and the functional products of the cells. Karyotypic examination of the cell lines revealed the common loss of a single chromosome. The slight differences noted in karyotypes suggest some divergence from a tumor stem cell and imply a clonal origin. Thus, EBV-induced lymphomas in cotton-topped marmosets resemble Burkitt's lymphoma in man.

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Experimental infection of Callithrix Jacchus marmosets with Herpesvirus ateles, Herpesvirus saimiri, and Epstein Barr virus.

We inoculated common marmosets (Callithrix Jacchus) with Herpesvirus ateles (HVA), Herpesvirus saimiri (HVS), and Epstein-Barr virus (EBV). HVA-induced tumors contained several cell types, including giant cells reminiscent of the Sternberg-Reed cells observed in human Hodgkin's disease. HVS and EBV did not induce tumors, although HVS was present in lymphocytes and elicited a strong antibody response. EBV elicited only a variable antibody response. We feel that more common marmosets should be used to determine if the pathologic and immunologic lesions caused by HVA would be a suitable animal model for Hodgkin's disease and/or other malignant lymphomas of man. Inconsistency in the induction of tumors by EBV and HVS in common marmosets suggets that this species may be a different type of model for human cancer research than the cottontop marmoset, which is the most susceptible animal host for EBV and HVS oncogenesis.

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Spontaneous esophageal carcinoma and epithelial cell line of an adult rhesus monkey.

A continuous epithelial cell line, 816A, was established from a lymph node of an adult rhesus monkey with metastatic esophageal carcinoma. These cells are characterized by the presence of desmosomes and a markedly heteroploid karyotype. At a relatively early culture age, electron microscopy showed both budding and extracellular type C virus. Antigen reactive with antisera to Mason-Pfizer monkey virus was observed by complement-fixation. The level of this antigen decreased with increased culture age. To our knowledge, the 816A cells represent the only established simian or human cell line of esophageal carcinoma origin.

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Augmentation of the in vitro mitogenic response of owl monkey peripheral blood lymphocytes by levamisole and loss of this effect with the development of herpesvirus saimiri-induced lymphoma.

Levamisole (LMS) has been shown to be capable of enhancing the proliferative response of normal owl monkey peripheral blood lymphocytes (PBL) to PHA, and, to a lesser degree, of increasing the level of spontaneous DNA synthesis. With the development of herpesvirus saimiri-induced lymphoma, these stimulatory responses were lost. LMS was not capable of stimulating tumour cells to normal functions, or of reversing the disease-induced suppressed functions on normal cells.

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In vitro lymphocyte transformation by Epstein-Barr virus (EBV)-like viruses isolated from Old-World non-human primates.

EBV-like viruses and lymphoid cell lines have been isolated from baboons and an orangutan. The cell lines have properties of B- or undifferentiated lymphocytes and have antigens and DNA related to those of EBV. The baboon virus has a broad in vitro transformation host range among lymphocytes of Old-World simian species whereas the orangutan isolate has a narrower host range. Baboon and orangutan viruses as well as EBV have shown transforming activity for gibbon lymphocytes. Baboon virus is infectious for rhesus monkeys and baboons but has not induced neoplastic disease in these species.

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Transforming activity and antigenicity of an Epstein-Barr-like virus from lymphoblastoid cell lines of baboons with lymphoid disease.

Two lymphoblastoid cell lines were established from baboons with lymphoid disease. Cells of these lines were positive for complement and Fc receptors but lacked sheep cell receptors, theraby indicating B-cell origin. The cells contained antigens which cross-reacted with Epstein-Barr virus (EBV), viral capsid antigen (VCA), early antigen (EA) and membrane antigen (MA). Both lines released virus with in vitro transforming activity for lymphocytes of several primate species including humans. Cells of the original lines and transformed cells showed no staining for EB nuclear antigen (EBNA). The virus was neutralized by anti-MA positive baboon and human sera. Baboon virus and EBV had different but overlapping in vitro host-cell ranges.

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Antibody responses to membrane antigens in monkeys infected with Herpesvirus saimiri.

The antibody response to Herpesvirus saimiri (HSV)-induced membrane antigens (MA) was followed in HSV-infected owl monkeys using the membrane immunofluorescence (MF) and antibody-dependent lymphocyte cytotoxicity (ADLC) assays. These responses were correlated with the loss of T-cell responsiveness to general mitogens. Antibody titers to MA as determined by ADLC but not MF increased to remarkably high titers in those monkeys that developed malignant disease following virus infection, while remaining at relatively low and constant levels in those monkeys that developed a chronic virus infection in the absence of malignant disease. This disease-related antibody response pattern was paralleled by the loss of T-cell function in diseased animals. The development of leukemia in HVS-infected owl monkeys did not suppress the ability of peripheral blood lymphocytes to act as effector cells in the ADLC assay. The relationship of these immune response patterns to the development of malignant disease in this system is discussed.

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Characterization of a spontaneous undifferentiated carcinoma from an African green monkey (Cercopithecus aethiops).

An adult male African green monkey (Cercopithecus aethiops) with an undifferentiated carcinoma, probably originating from the nasal mucosa, was received from the Akron, Ohio zoo. Cultivation of this tumor in vitro resulted in a mixture of fibroblastic and epithelial cells which was subsequently separated using differential trypsinization. The neoplastic nature of the cultured epithelial cells was verified by their ability to transplant into athymic nude, or antithymocyte serum-treated mice, where poorly differentiated carcinomas were produced, and cultures of the tumors that arose in nude mice were morphologically similar to pretransplantation cultures. Early cultures showed a normal male karyotype characteristic of the species; however, in long-term cultures, a clearly defined, small submetacentric Y chromosome was not observed. Electron microscopic examination of tumor tissue and cultured tumor cells revealed desmosomes and the presence of cytoplasmic (keratin-type) fibrils, which tended to be organized around the nucleus. In addition to the keratin-type fibrils, the cultured tumor cells also contained a large amount of cytoplasmic inclusion material that may represent keratohyalin granules. There was no evidence of a viral association with tumor material or cultured cells. The cultures were susceptible to infection by vesicular stomatitis virus, Herpesvirus hominis type 1, and H. saimiri, but were resistant to the Epstein-Barr virus.

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Chronic Herpesvirus saimiri infection in an owl monkey.

An adult owl monkey (Aotus tricirgatus) used for immunologic studies of Herpesvirus saimiri (HVS) developed early, late, membrane, and neutralizing antibodies to HVS approximately 3 weeks after the beginning of the experiment. HVS was isolated by the cocultivation of peripheral blood for over 1 year. No clinical, gross, or histopathologic findings of malignancy were exhibited by the animal. The HVS isolate from the animal was indistinguishable biologically and serologically from the original HVS strain of Meléndez and from an isolate of an experimentally HVS-induced tumor. Inoculation of this isolate into 2 young white-lipped marmosets (Saguinus fuscicollis) produced typical malignant lymphoma and lymphocytic leukemia. Our findings suggested that the virus from the chronically infected animal was oncogenic and that host factors were primarily responsible for determining the disease manifestation of the virus infection. Another owl monkey chronically infected with HVS for over 2 years has remained asymptomatic.

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Virological studies of baboon (Papio hamadryas) lymphoma: isolation and characterization of foamyviruses.

In accordance with a memorandum of understanding in cancer research between scientists in the USSR and the USA, virological studies were performed on two baboons from the Russian colony at the Institute of Experimental Pathology and Therapy at Sukhumi where several cases of leukemia have been observed over the past few years. Foamyvirus isolations were made from lymphoid cells of both of these monkeys, one of which had a confirmed case of lymphoma. The isolates were similar to each other serologically and morphologically, possessed characteristics typical of foamyviruses, and cross-reacted to a low level with antibody to simian foamyvirus type 1.

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Pilot studies with human interferon in Herpesvirus saimiri-induced lymphoma in owl monkeys.

The nature of Herpesvirus saimiri-induced disease in owl monkeys is described with emphasis on those biological parameters useful in monitoring the disease. These parameters are lymphocyte response to general mitogens, lymphocyte-infective centers, and antibody to virus-associated early antigen. Human interferon was used in treating owl monkeys with virus-induced leukemia. In 2 animals evidence was obtained that suggested a positive antileukemic effect.

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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.

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Inhibition of the mitogenic response of normal peripheral lymphocytes by extracts or supernatant fluids of a Herpesvirus saimiri lymphoid tumor cell line.

A Herpesvirus saimiri-infected marmoset lymphoid cell line (MLC-1) was examined for the presence of soluble factors which might affect lymphocyte functions and, therefore, relate to the pathogenesis of lymphoma in vivo. MLC-1 cells, cell extracts, and culture fluids were shown to reduce the spontaneous deoxyribonucleic acid (DNA) synthesis of normal peripheral blood lymphocytes and to completely inhibit their response to phytohemagglutinin (PHA). Suppression of PHA response was demonstrated against a variety of human and nonhuman primate species, with 90 to 95% inhibition occurring at dilutions of extract as great as 1:5,120. Inhibition of this type was also demonstrated using extracts of two of five other lymphoblastoid cell lines tested. Physical-chemical characteristics of the active factor(s) revealed a non-sedimentable, non-dialyzable, trypsin-resistant molecule, which was stable at 56 C for 30 min but inactivated at 80 C for 30 min. The factor(s) also exerted an effect on some but not all established lymphoblastoid cell lines, where DNA, ribonucleic acid, and protein synthesis were all inhibited, with DNA synthesis being the most affected (95% suppression). Cellular respiration was not affected by the presence of the factor(s), and the inhibition of DNA synthesis was reversible after 24 h. Purified human interferon did not reduce the PHA response of normal owl monkey peripheral blood lymphocytes and was less effective against an established lymphoblastoid cell line than the MLC-1 extract. Antiviral activity was also demonstrated in the preparations and may represent interferon, which these cells are known to produce at low levels.

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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.

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