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Biomedical subjects

W C Wallen

Publications and source records attributed to W C Wallen.

At least 19 recordsLinked to original sources

Brain tumors in owl monkeys inoculated with a human polyomavirus (JC virus).

Owl monkeys were inoculated intracerebrally, subcutaneously, and intravenously with JC, BK, or SV40 virus. Two of four adult owl monkeys inoculated with JC virus, a human polyomavirus, developed brain tumors at 16 and 25 months after inoculation, respectively. A grade 3 to grade 4 astrocytoma (resembling a human glioblastoma multiforme) was found in the left cerebral hemisphere and brainstem of one monkey. The second monkey developed a malignant tumor in the left cerebral hemisphere containing both glial and neuronal cell types. Impression smears prepared from unfixed tissue of this tumor showed cells that contained polyomavirus T antigen. Virion antigens were not detected. Tumor cells cultured in vitro also contained T antigen but were negative for virion antigen. Infectious virus was not isolated from extracts of this tumor.

Antibodies, Viral

Epstein-Barr virus infection following bone-marrow transplantation.

A 12-year-old patient with acute lymphoblastic leukemia received a bone-marrow transplant (BMT) from a matched sibling donor. Nine weeks prior to transplant the donor experienced Epstein-Barr virus (EBV)-induced infectious mononucleosis. The bone-marrow recipient was EBV-negative at the time of transplant; however, 4 weeks post transplant the recipient developed clinical symptoms of graft-verus-host disease (GVHD) coincident with serological evidence of acute EBV infection. In addition, a lymphoblastoid cell line positive for Epstein-Barr nuclear antigen was established from a bone-marrow sample obtained at the onset of symptoms compatible with GVHD. Sera obtained from the recipient over the ensuing 2 months showed the appearance of antibodies to specific EBV antigens consistent with a primary immune response to EBV infection. This association of acute EBV infection with symptoms of GVHD in a BMT recipient suggests a need for further investigation of the epidemiology of EBV infections in human bone-marrow transplantation and the relationship between EBV infection and GVHD.

Antibodies, Viral

Lymphocyte functions and subpopulation distribution in marmosets.

Marmoset lymphocytes were highly reactive to general mitogens, participate in direct cytotoxicity (purportedly mediated by T-cells) and particpate in an antibody dependent lymphocyte cytotoxicity assay (K-cell). The distribution of lymphocyte subpopulations among various species showed that the percent T-cells ranged from 46.4 to 66.6% in different species while complement receptor cells ranged from 10.3 to 19.0%. Surface immunoglobulin (SIg) stable B-cells ranged from 10.6 to 16.4% while the SIg labile L-cells ranged from 26.9 to 37.5%. A fourth receptor, Fc, was demonstrated on 23.7 to 31.7% of the marmoset lymphocytes.

Animals

Comparative studies on immunity to EBV-associated antigens in NPC patients in North America, Tunisia, France and Hong Kong.

This study compared the relative antibody titers to EBV-related antigens in patients with nasopharyngeal carcinoma (NPC) and controls from a high-incidence (Hong Kong), an intermediate incidence (Tunisia), and two low-incidence (France, North America) areas to determine which of several EBV antibodies best differentiated NPC patients from controls. Antibodies measured include anti-virus capsid antigen (VCA), anti-early antigen (EA), anti-soluble antigen by complement-fixation (CF) and antibody-dependent lymphocyte cytotoxicity (ADLC). A matched pair analysis showed that significantly more NPC patients had higher VCA and EA but not CF or ADLC antibody titers than their matched cancer controls. The comparison of geometric mean titers between NPC cases and controls was more than seven-fold (816 vs 11.5) for EA antibody and more than three-fold (359.7 vs 95.4) for VCA anti-body (p less than 0.01). A two-fold difference was seen for CF antibody to soluble antigens (27.3 vs 12.9, p less than 0.01) and a three-fold difference (2657.7 vs 870.9, p less than 0.05) was observed for ADLC. Our finding of significant differences between NPC patients from four countries and their matched controls suggest that if EBV is the etiological agent of NPC in Chinese, it is quite likely to cause the majority of NPC cases in other ethnic groups living in other countries as well.

Antibodies, Viral

Lymphocyte responses to EBV-associated antigens in infectious mononucleosis, and Hodgkin's and non-Hodgkin's lymphoma patients, with the leukocyte adherence inhibition assay.

The leukocyte adherence inhibition (LAI) assay was utilized as a test for cellular immunity to Epstein-Barr virus (EBV) antigens in 22 patients with infectious mononucleosis (IM), 47 patients with lymphoma, 101 carcinoma patients, and 84 subjects without cancer. Response to EB virion ("v") antigen was generally present at the time of diagnosis in the IM patients but the response to EB soluble ("S") antigen was delayed. An increased CMI response to "v" antigen was found in patients with IM, Hodgkin's disease and non-Hodgkin's lymphoma as compared to controls with and without cancer. Patients with Hodgkin's disease had depressed responses to the EBV-associated "S" antigen. The finding of increased LAI responses to "v" antigen in Hodgkin's disease patients with high EBV antibody titers conflicts with previous reports attributing high antibody responses against EBV to a generalized depressed cell-mediated immunity.

Antibodies, Viral

Detection of soluble antigen of Epstein-Barr virus by the enzyme-linked immunosorbent assay.

The enzym-linked immunosorbent assay (ELISA) was compared with the microcomplement-fixation test for sensitivity and reliability in detection of antibody to soluble antigen of Epstein-Barr virus. ELISA was found to be more sensitive (up to 160 times more antibody) in detecting levels of antibody than the complement-fixation assay. The ELISA test was shown also to be comparably reliable to the complement-fixation assay in detecting immunity to this antigen; only one false-positive response was found in tests of 21 sera. Because this assay is completely quantifiable, it provides an easy, rapid, and highly sensitive technique for the detection of antibody to antigen of Epstein-Barr virus.

Antibodies, Viral

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.

Animals

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.

Animals

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.

Animals

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.

Animals

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.

Animals

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