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R E Paque

Publications and source records attributed to R E Paque.

At least 37 records · Page 2Linked to original sources
PubMed1980

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National Institutes of Health (U.S.)↗
PubMed1979

Properties of coxsackievirus B3 variants which are amyocarditic or myocarditic for mice.

Inoculation of adolescent CD-1 mice with one variant of coxsackievirus B3 (CVB3m) results in induction of readily observable myocardial lesions, whereas inoculation of siblings with a second variant (CVB3o) results in little or no myocarditis. These variants could not be distinquished from each other on the basis of replication properties in HeLa cells or cardiac tissues in vivo, sensitivity to human interferon in HeLa cells, induction of interferon in the mouse, generation of detectable levels of defective-interfering particles in HeLa cells or in cardiac tissue in vivo, stimulation of serum-neutralizing antibody titers, nor in their rate of clearance by the spleen. Infectivity of CVB3o was slightly more heat labile at 34 degrees C than CVB3m. Little if any replication of either CVB3o or CVB3m occurred in either adherent or nonadherent populations of normal murine lymphoid cells. Cardiac tissues from mice inoculated with CVB3m but not CVBo contain new antigens that can inhibit migration of sensitized lymphocytes from CVB3m-immunized mice in an in vitro cell-migration-inhibition assay. However, the CVB3o variant was shown to have the genetic capability of inducing myocarditis if the mice were treated with cyclophosphamide prior to virus inoculation. These results suggest, in agreement with our previously published work, that induction of myocarditis by CVB3 requires destruction of myocytes by virus and subsequent stimulation of cell-mediated responses to new antigens produced in the myocardium during virus replication.

Animals↗
PubMed1979

Assessment of coxsackievirus B3 ts mutants for induction of myocarditis in a murine model.

Ten temperature-sensitive (ts) mutants isolated from a myocarditis-inducing wild-type (WT) coxsackievirus B3 parent did not induce myocarditis in adolescent CD-1 mice. An avirulent prototype ts mutant from one of the three complementation groups adsorbed to murine cardiac tissue, as did WT virus. Heart tissues from mice inoculated with WT virus contained 100- to 1,000-fold more virus than heart tissues from mice inoculated with any of the three prototype ts mutants. WT virus exhibited a greater capsid stability and a higher efficiency of replication at 37 degrees C than any of the three prototype ts mutants. All three prototype ts mutants induced less interferon in vivo than WT virus. Cell-mediated immune responses, assessed by the cell migration inhibition assay, were different in mice inoculated with WT virus when compared to ts 5 mutant virus. Peritoneal exudate cells from mice inoculated with WT but not ts 5 virus reacted specifically against antigens in WT virus HeLa cell lysates and antigens extracted with KCl from cardiac tissues of mice inoculated with WT virus. Cardiac tissues of mice inoculated with WT but not ts 5 virus contained KCl-extractable antigens which were able to specifically inhibit the migration of peritoneal exudate cells taken from mice immunized with WT virus. Therefore, ts 5 neither elicited a measurable cell-mediated immune response nor induced antigens in cardiac tissues which were immunoreactive with sensitized-(WT virus)-peritoneal exudate cells. Of 9 revertant viruses isolated from the 10 ts mutants, 5 showed covariance in ability to replicate at 39.5 degrees C and capacity for induction of myocarditis. Some revertants exhibited a reduced capsid thermostability compared to WT virus but yet retained the capacity for induction of myocarditis. The data suggest that induction of myocarditis by coxsackievirus B3 variants depends on a combination of several variables, including capsid stability, capacity for replication at 37 degrees C, and expression of the three identified genes. All three prototype ts mutants served as vaccine viruses in preventing myocarditis in adolescent mice subsequently challenged with WT virus. However, all three prototype ts mutants and their revertant variants retained partial to complete lethality in CD-1 neonates.

Animals↗
PubMed1979

Fractionation and immunologic assessment of KCl-extracted cardiac antigens in coxsackievirus B3 virus-induced myocarditis.

Hypertonic salt extracts prepared from the heart tissues of adolescent CD-1 mice were fractionated on Sephadex G-100 columns. Two separate fractions were obtained. Fraction I, containing the antigenic immunoreactive activity, was able to inhibit the migration of CVB3-PPD immune mouse peritoneal exudate cells (IMPEC) as well as PEC from mice infected with CVB3 virus alone. Fraction II did not have antigenic activity as assessed by the agarose droplet cell migration inhibition assay. As controls, Fraction I prepared from the livers of spleens of CVB3-infected CD-1 mice was unable to inhibit the migration of CVB3 IMPEC. Unimmunized or "normal" mouse peritoneal exudate cells (NMPEC) were not inhibited by Fraction I. Antibodies prepared against Fractions I and II were unable to neutralize CVB3m virus in the plaque reduction test, and polyacrylamide gel analysis revealed multiple bands in 10% SDS gels.

Animals↗
PubMed1978

Assessment of cell-mediated hypersensitivity against coxsackievirus B3 viral-induced myocarditis utilizing hypertonic salt extracts of cardiac tissue.

Hypertonic KCl extracts prepared from heart tissues of adolescent CD-1 mice inoculated with coxsackievirus B3 (CVB3) were tested for antigenicity in evaluating cell-mediated sensitivity to CVB3 virus utilizing the agarose droplet cell-migration-inhibition assay. Immune mouse peritoneal exudate cells (IMPEC) from mice immunized against CVB3 virus and Freund's complete adjuvant were specifically inhibited in the cell-migration-inhibition assay with graded doses of KCl-extracted antigen and purified protein derivative (PPD). Unimmunized for "normal" mouse peritoneal exudate cells (NMPEC) were not inhibited in the presence of the CVB3 KCl extracts. KCl heart extracts from mice inoculated with a cardiotropic strain of antigenically distinct mengovirus failed to inhibit CVB3 IMPEC, and noncardiac KCl extracts of liver and spleen from CVB3-inoculated mice also failed to inhibit cellular migration of CVB3 IMPEC. Reciprocal specificity experiments utilizing KCl-extracted antigens from mice infected with antigenically distinct cardiotropic mengovirus failed to inhibit cellular migration of IMPEC from mice immunized against the mengovirus. Serum-blocking power experiments indicate the antigenic KCl extracts failed to bind virus-neutralizing antibodies, indicating absence of detectable quantities of virion antigens. The results indicate that inoculation of mice with CVB3 virus results in the appearance of a new antigen(s) in cardiac tissue reacting with CVB3-IMPEC, but not with mengovirus IMPEC.

Animals↗
PubMed1976

Isolation and localization of RNA fractions able to transfer tumor-specific delayed hypersensitivity in vitro.

RNA fractions were prepared by sucrose density gradient centrifugation from hot-cold phenol, RNA-rich extracts of lymphoid tissues from strain 2 guinea pigs hyperimmunized to line 1 or line 10 tumors. Each RNA fraction was assessed for its ability to convert nonsensitized strain 2 peritoneal exudate cells to a state of specific sensitivity for line 1- or line 10-solubilized tumor antigens. An RNA fraction residing between the 4 S and 18 S peaks, designated as Fraction "B", transferred line 10 or line 1 sensitivity in 12 experiments. Twelve additional RNA extracts containing 2 subfractions prepared from RNA fraction B, designated as B1 and B2, also transferred line 1 or line 10 sensitivity in 14 experiments. Except for 3 experiments where the 4 S or 18 S material transferred tumor-specific sensitivity, RNA fractions corresponding to approximately 4 S, 18 S, 22 S, and 28 S were unable to transfer tumor-specific sensitivity to nonsensitized peritoneal exudate cells. Treatment of fraction B with RNase results in complete loss of ability to transfer immunobiological activity.

Animals↗
PubMed1975

Complete and apparently specif local tumor regression using syngeneic or xenogeneic "tumor-immune" RNA extracts.

Syngeneic and xenogeneic RNA-rich extracts of lymphoid tissues were used in an immunotherapeutic regimen to treat strain 2 guinea pigs that were given intradermal injections of a uniformly lethal dose (1 x 10(6)) of line 10 diethylnitrosamine-induced transplantable hepatoma cells. When 1 X 10(7) syngeneic nonsensitive peritoneal exudate cells, 2.5 mg RNA from line 10-immune strain 2 guinea pigs or line 10-immune Rhesus monkeys, and 1.0 mg of a line-10 tumor-specific antigen preparation were injected s.c. under the tumor cells injected 5 days previously, complete local tumor regression in all treated animals was observed. If either nonsensitive peritoneal exudate cells, RNA, or line 10 tumor-specific antigen was omitted, or if Escherichia coli RNA or RNA from animals sensitized to a different tumor (line 1) was used, little or no tumor regression was observed, suggesting that the action of the RNA may have resulted in an antitumor response specific for the noplasm being treated. The long-term tumor-free survival of all treated animals indicates that the action of the RNA is systemic, since metastases are known to occur frequently by the time our therapeutic regimen was given. Also, in testing the biological activity of the "tumor-immune" RNA in the in vitro cell-migration-inhibition assay, both the syngeneic and xenogeneic RNA extracts could transfer tumor-specific immunological sensitivity, as demonstrated by the elaboration of migration-inhibitory factor by the RNA-treated nonsensitive peritonial exudate cells in the presence of the line 10 tumor-specific antigen.

Animals↗
PubMed1975

Rosetting of antibody-sensitized tumor cells with anti-immunoglobulin antibody-coated erythrocytes by a new method for detecting antigens on cells.

Tumor cells were treated with rabbit antibody to tumor-associated cell surface antigens and tested with erythrocytes coated with antibody specific for the sensitizing rabbit immunoglobulin. The sensitized tumor cells formed rosettes with the indicator cells. By this method, we confirmed that line 1 and line 10 hepatoma cells (from two tumors independently induced by diethylnitrosamine in strain 2 guinea pigs) bear antigens not present on normal liver cells. We also confirmed that line 1 and line 10 cells bear antigenically different tumor-associated cell surface antigens. This method appears simpler than other serological methods for detecting tumor-associated cell surface antigens on tumor cells. Also, this method may be a general one for detecting and enumerating cells bearing surface antigens.

Animals↗