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Biomedical subjects

G R Armstrong

Publications and source records attributed to G R Armstrong.

At least 55 records · Page 3Linked to original sources

Fc receptor mediated immune regulation and gene expression.

Exogenous Fc receptors (FcR) have been demonstrated to either augment or inhibit endogenous FcR mediated immunity, immune regulation and gene expression. Other immune regulatory or modulator molecules, such as the H2 histocompatibility antigens, interferon, transfer factor and leukocyte chalones might involve association with or alter the synthesis or status of FcR, thus effecting regulation of immunity and/or gene expression. FcR provide a unique opportunity for eliciting the mechanisms and perhaps altering the immunity and/or gene expression which influence immune regulation, cellular differentiation, viral replication and malignant transformation.

Animals↗

Extraction of soluble antigens of Epstein-Barr virus, Herpesvirus salmirl, and Herpesvirus ateles with the use of glycine.

For extraction of soluble antigen from cells infected with Epstein-Barr virus, Herpesvirus salmirl, and H. ateles, 0.1 M glycine (pH 9.5) was used. This method yielded increased amounts of the antigen containing much less cell debris. Lymphoblastoid cells infected with Epstein-Barr virus could maintain up to 50% viability after the extraction procedure. These cells could be used again after an appropriate interval in culture. The usefulness of this technique is discussed.

Antigens, Viral↗

Neutralization of immune complex inhibition of antibody dependent cellular cytotoxicity in vitro by Staphylococcus-aureus protein A.

Staphylococcus-aureus protein A (SPA) incubated with sera containing immune complexes and effector cells increases antibody dependent cellular cytotoxicity (ADCC)and rosette formation. The enhanced ADCC and rosetting is due to SPA functioning as an IgG Fc cellular receptor. SPA binds to the Fc portion of Igg and has much greater affinity for immune complexes than free IgG. SPA bound immune complexes are blocked from attaching to the Fc cellular receptors via a competitive inhibition which neutralizes the inhibitory effect of these complexes on ADCC and rosette formation.

Animals↗

Augmentation and inhibition of delayed hypersensitivity by Staphylococcus aureus protein A.

The injection of Staphylococcus-aureus protein A into mice, previously exposed to an antigen (sheep red blood cells), is capable of augmenting or inhibiting a primary delayed hypersensitivity (DH) response. SPA enhances DH response to SRBC when given with a greater than optimal sensitizing dose of the antigen. At antigen doses optimal for eliciting DH to SRBC, SPA inhibited DH. A proposed mechanism for the action of Staphylococcus-aureus protein A is based upon the ability of the protein to function as a Fc cellular receptor, thus neutralizing the effect of antigen-antibody immune complexes on DH. The binding of protein A to the Fc portion of antigen-antibody immune complexes effectively prevents subsequent binding of these complexes to Fc cellular receptors, thus eliminating their participation as co-factors in inter-cellular immunological communication. The ability of protein A to both augment and inhibit DH suggests a role for relative concentrations of serum factors and/or cellular receptors in the regulation of a primary DH response.

Animals↗

Suppression of DNA synthesis in mitogen stimulated leukocytes with partial trypsin digests of Staphylococcus aureus protein A.

Staphylococcus aureus protein A (SPA) acts as a mitogen stimulating DNA synthesis and is not antagonistic to the mitogenic activity of other mitogens. The mitogenicity of SPA is due to the protein's multivalent Fc antibody receptors. Partial trypsin digestion of SPA yields monovalent Fc antibody receptors which are not mitogenic. Using a thymidine incorporation assay, results indicated that tryptic digests of SPA added to mouse splenic leukocytes 12 hours after stimulation with either concanavalin A, lipopolysaccaride or SPA suppressed the DNA synthesis normally elicited by these mitogens. SPA was digested with 1% trypsin at pH 8 for varying periods of time. As the digestion time increased from 0 to 60 minutes the mitogenicity of the SPA-trypsin digests decreased indicating cleavage from multivalent to monovalent SPA Fc antibody receptors. The decrease in mitogenicity of the SPA digests was directly associated with increased ability to inhibit DNA synthesis in mitogen stimulated leukocytes. A proposed mechanism for the inhibition of DNA synthesis suggests that SPA-monovalent Fc antibody receptors mimic cellular Fc receptor function thereby influencing cellular gene expression.

Animals↗

Athymic nude mice: induction of tumors containing Epstein-Barr virus using Burkitt's-related cell lines.

We studied tumor induction in athymic nude mice by D98/HR-1 cells, an epithelial somatic cell hybrid containing the Epstein-Barr virus (EBV) genome, and by the parental D98 and HR-1 cells. Groups of animals were inoculated with cells grown in culture, with cells from tumors induced by the cell lines, or with cells from lines derived from tumors. The tumors induced by D98/HR-1 cells were undifferentiated carcinomas; those induced by D98 cells were carcinomas and those induced by HR-1 cells were poorly differentiated lymphomas. Preliminary data suggest that the number of EBV genome equivalents was sharply reduced in cells from both D98/HR-1 and HR-1 tumors. Subsequent passage of tumor cells in vitro resulted in a partial recovery in the number of EBV genome equivalents in HR-1 cells and a complete recovery in D98/HR-1 cells. The reduction in the number of EBV genomes in the tumor cells suggests that in vitro passage can influence the number of EBV genomes in these cells.

Animals↗

Absence of horizontal transmission of herpesvirus saimiri between experimentally infected and noninfected owl monkeys.

We did not detect cell-free Herpesviurs saimiri (HVS) in the oropharyngeal secretions of owl monkeys with leukemia or lymphoma induced by this virus. These animals failed to transmit either virus or disease to their uninoculated cage-mates or room-mates. Comparison of oropharyngeal secretions of HVS from owl monkeys and squirrel monkeys may provide insight as to how human herpesviruses are maintained in the oropharynx.

Animals↗

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.

Animals↗

Xenotropic properties of an isolate from murine Rauscher leukemia virus in primates.

Murine Rauscher leukemia virus (MuRLV) from BALB/c plasma consisting of a mixture of an ecotropic and a xenotropic virus could be separated out by a selection process when propagated in human and simian cell cultures. This hypothesis is supported by obtaining consistently lower infectivity titers of human cell propagated RLV in human and simian cells as compared to MuRLV propagated in mouse cell cultures. Furthermore, RLV passaged in a simian cell culture failed to replicate in mouse cells, had a wide host range, was able to rescue Moloney sarcoma genome, possessed murine type C group-specific antigen, and was neutralized by anti-HRLV. Its reverse transcriptase was strongly inhibited by antiserum to MuRLV enzyme; however, antiserum to woolly monkey enzyme also inhibited (30%) its reverse transcriptase, suggesting some difference in antigenic properties. Inoculation of this virus in rhesus monkeys was inconclusive.

Animals↗

Some biological properties of herpesvirus saimiri from chronically infected monolayer and suspension cultures.

HVS-MEST cells, which are adherent, produced more infectious HVS at 37 degress C than at 33 degrees C. This was paralleled by the appearance of EA and LA in rounded cells and CF antigen in the cell cultures. In contrast, MLC-1 cells, which grow in suspension, produced hardly any infectious virus, but did produce more HVS S antigen than did the HVS-MEST cells. Production of S antigen in MLC-1 cells was augmented by treatment of the cells with BUDR. HVS-MEST cells could be superinfected with HVS, but MLC-1 cells were resistant to super-infection. The unpurified S antigens from both cell lines gave almost identical spectra when tested in CF against a battery of 10 owl and squirrel monkey sera. Thus, two cell lines have been described, one that produces infectious virus and S antigen, and another that produces more S antigen, but in the absence of any great amounts of infectious virus.

Antibodies, Viral↗