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Biomedical subjects

R H Neubauer

Publications and source records attributed to R H Neubauer.

At least 55 records · Page 3Linked to original sources
PubMed1977

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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PubMed1977

Fibrinolytic activity associated with established lymphoblastoid cell lines and fresh peripheral blood lymphocytes of human and nonhuman primate origin.

Established lymphoblastoid cell lines and normal peripheral blood lymphocytes were examined for their ability to induce fibrinolysis, a property associated with oncogenic transformation, using a 3H-fibrin plate technique. Fibrinolytic activity showed serum preferences with dog serum being most active. Most cell lines (14/18) induced greater than 40% release, while normal lymphocytes were generally less active. Only one cell line tested released plasminogen activator into the medium. No correlation was shown between fibrinolytic activity and growth in soft agar. Normal rhesus lymphocytes showed fibrinolytic activity in B cell-enriched populations with no evidence of interaction between B cells and T cells.

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PubMed1976

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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PubMed1976

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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PubMed1976

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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PubMed1975

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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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.

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PubMed1975

Spontaneous lymphoma associated with Herpesvirus saimiri in owl monkeys.

Two cases of lymphoma and one case of lymphoproliferative disease were found in a group of 7 owl monkeys imported into our colony as a single group. Herpesvirus saimiri (HVS) was isolated from the tumor cells of 1 lymphoma by cocultivation and from kidney cell cultures from the monkey with lymphoproliferative disease. Antibody to HVS was found in serum samples from 2 monkeys positive for HVS but not in the sera from the 4 clinically normal monkeys. Antibody to Epstein-Barr virus-infected cells was also found in the serum from the animal with lymphoma.

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PubMed1975

Infection of capuchin monkeys (Cebus albifrons) with Herpesvirus saimiri.

Herpesvirus saimiri (HVS) induced persistent, clinically inapparent infections of long-term duration in capuchin monkeys (Cebus albifrons). The infections were characterized by development of antibody to HVS-associated antigens and recovery of low levels of virus-genome-carrying lymphocytes in the peripheral blood. Peripheral lymphocyte counts remained in low-normal to normal ranges and no physical signs of lymphoma were evident. Prednisolone treatment caused immunosuppression in one monkey; this was accompanied by a progressive loss of humoral antibody to HVS-associated antigens, but neoplastic disease did not develop.

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PubMed1975

Depression in lymphocyte response to general mitogens by owl monkeys infected with Herpesvirus saimiri.

The effect of Herpesvirus saimiri (HVS) infection on the response of owl monkey lymphocytes to general mitogens was examined during the development of neoplastic disease. The reactivity of the lymphocytes was then correlated with the clinical condition of the infected monkeys and the content of virus rescued from the peripheral blood lymphocytes (PBL). Eight monkeys developed lymphoma which, in six monkeys, was accompanied by lymphocytic leukemia. All animals that died of HVS-induced neoplasia consistently showed a lack of mitogenic response to phytohemagglutinin and concanavalin A. The response to pokeweed mitogen, while always reduced, was generally less markedly affected than the response to the other two mitogens. Lymphocytes from five of the leukemic animals demonstrated an elevated level of spontaneous DNA synthesis in culture late in the disease. This increased spontaneous DNA synthesis tended to correlate with the rescue of HVS from the PBL as demonstrated by the infective center assay. Although mitogenic hyporesponsiveness corresponded with HVS rescue from PBL in six of nine monkeys, the impairment of normal lymphocyte responsiveness sometimes preceded virus recovery.

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PubMed1975

Evidence for suppressor cell activity associated with induction of Herpesvirus saimiri-induced lymphoma.

Peripheral blood lymphocytes (PBL) from Herpesvirus saimiri (HVS) infected owl monkeys lose their ability to respond to PHA during the development of lymphoma. In this study, five HVS-infected owl monkeys were examined for their ability to respond to PHA and to confer this loss of PHA reactivity to normal lymphocytes. Four of the monkeys developed HVS-induced disease and lost their ability to respond to PHA. Although less affected, reduced responses were also found with PWM. The animals which developed disease and suppressed PHA responses were found to be able to confer this loss of PHA reactivity to normal lymphocytes. One HVS-infected monkey did not develop disease or loss of PHA reactivity and did not confer a loss of PHA reactivity to normal lymphocytes. In the four affected monkeys, the conference of suppression to PHA was not accompanied by a concomitant reduction in response to PWM by the normal lymphocytes, demonstrating some specificity in the suppressor cell activity. Thus, the presence of suppressor cell activity appears to be associated with the inhibition of T-cell function and possibly the eventual development of lymphoma.

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PubMed1974

Stimulation of Herpesvirus saimiri expression in the absence of evidence for type C virus activation in a marmoset lymphoid cell line.

Nucleic acid base analogues were used to examine a Herpesvirus saimiri (HVS)-infected marmoset lymphoid cell line (MLC-1) for possible association with type C viruses. Synthetic templates poly(rA).d(pT)(10) and poly(dA).d(pT)(10) were used to detect RNA-directed DNA polymerase activity in 100-fold concentrated tissue culture fluids. HVS was monitored by immunofluorescence for early, late, and membrane antigens. MLC-1 cells were exposed to 30 mug of 5-bromo-2'-deoxyuridine (BUdR) per ml for 24 h and examined daily. Similar experiments used 5-iodo-2'-deoxyuridine (IUdR) (20 mug/ml) for 30 h or IUdR (20 mug/ml) for 3 days followed by 2% dimethyl sulfoxide for 4 days. Results of these experiments failed to show any type C virus-like polymerase; however, HVS expression was greatly stimulated. BUdR and IUdR enhanced expression of HVS-associated antigens five- to sevenfold, with maximal stimulation being observed 3 to 4 days after removal of the analogue. IUdR-dimethyl sulfoxide treatment was generally less effective. Although more cells showed HVS antigens, the treatments did not increase cell-free infectious virus. The data suggest that HVS-infected lymphoid cells can be stimulated to express virus in a manner similar to that of the Epstein-Barr virus in Burkitt's lymphoma cells. No evidence of type C virus was found in stimulated cultures.

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