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Biomedical subjects

R P Messner

Publications and source records attributed to R P Messner.

At least 55 records · Page 3Linked to original sources
PubMed1986

Effects of lupus-inducing drugs on the B to Z transition of synthetic DNA.

Five drugs associated with systemic lupus erythematosus were studied for their effect on the salt-induced right-handed (B) to left-handed (Z) transition of poly(dG-me5dC) X poly(dG-me5dC). Using circular dichroism spectroscopy, procainamide and hydralazine were found to reduce the midpoint of B to Z transition from 0.8M NaCl to 0.5M NaCl and to increase the rate of this transition at 1M NaCl. Isoniazid and D-penicillamine had less effect on the midpoint of transition and practically no effect on the kinetics. N-acetyl procainamide (a structurally related control for procainamide) and L-canavanine had no effect. Procainamide caused slight reduction in the helix-coil transition (melting) temperature of calf thymus DNA. At a concentration of 1:1 (DNA phosphate:drug ratio), procainamide and hydralazine also caused the aggregation of calf thymus DNA. Since altered DNA conformations, such as Z-DNA, are more immunogenic, these results suggest that the induction or stabilization of Z-DNA by these drugs might be important in the pathogenesis of at least some cases of systemic lupus erythematosus.

Canavanine↗
PubMed1986

Anti-beta 2-microglobulin antibodies in systemic lupus erythematosus and ankylosing spondylitis: effects on in vitro lymphocyte function.

Antibodies to beta 2-microglobulin (anti-beta 2-mu) were isolated from sera of 6 patients with systemic lupus erythematosus (SLE) and 6 patients with ankylosing spondylitis (AS) by affinity chromatography on beta 2-mu-Sepharose. Specificity of the purified anti-beta 2-mu antibodies was demonstrated by immunofluorescent reactivity with cell surface beta 2-mu and by reactivity with purified beta 2-mu in ELISA. Anti-beta 2-mu from both SLE and AS patients inhibited Concanavalin A and phyto hemagglutinin induced proliferation of normal human peripheral blood lymphocytes (PBL) in a concentration dependent manner. High concentrations of anti-beta 2-mu inhibited pokeweed mitogen (PWM) induced PBL proliferation whereas lower concentrations enhanced the PWM response. Anti-beta 2-mu also inhibited E-rosette formation. The inhibition and enhancement of mitogen induced PBL proliferation and the inhibition of E-rosette formation were reversed when the antibodies were preincubated with purified beta 2-mu.

Antibodies↗
PubMed1985

In vitro production and scavenging of hydrogen peroxide by D-penicillamine. Relationship to copper availability.

The capacity of D-penicillamine (DP) to produce or scavenge hydrogen peroxide was investigated. DP added to copper produced H2O2. Greater production was observed with copper sulfate than with copper bound to ceruloplasmin. In contrast, DP in the absence of copper scavenged H2O2, as measured in a direct assay. Furthermore, DP or D-cysteine alone reversed H2O2-mediated inhibition of concanavalin A-stimulated mononuclear cell proliferation. These opposing immunomodulating properties of DP may be relevant to its toxic or therapeutic actions in rheumatoid arthritis.

Ceruloplasmin↗
PubMed1985

Pulmonary hypertension in systemic lupus erythematosus: effect of vasodilators on pulmonary hemodynamics.

Hemodynamic studies of the response of the pulmonary vasculature to vasodilator drugs were performed in 3 patients with systemic lupus and pulmonary hypertension. In one patient isoproterenol infusion produced a reduction in total pulmonary resistance, but increased pulmonary blood flow and pulmonary artery pressure. No significant change in pulmonary artery pressure or resistance was noted with nifedipine in any of the patients. One woman with associated pulmonary infiltrates improved symptomatically with high dose steroids.

Adult↗
PubMed1984

Inhibition of platelet aggregation by monoclonal antibody reactive with beta 2-microglobulin chain of HLA complex.

A mouse monoclonal antibody that reacts with beta 2-microglobulin, the light chain of class I major histocompatibility antigens, inhibited the second wave of human platelet aggregation induced by adenosine diphosphate and epinephrine and blocked aggregation and platelet protein phosphorylation induced by sodium arachidonate. Thrombin-induced platelet aggregation was inhibited at threshold concentrations but not at higher concentrations. The antibody also inhibited aggregation and secretion in response to thromboxane A2 or the stable endoperoxide analog, U46619. These results suggest that beta 2-microglobulin in the histocompatibility complex is intimately associated with transmission of the endoperoxide-thromboxane signal at the platelet membrane.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1984

Suppression of human lymphocyte mitogenesis mediated by phagocyte-released reactive oxygen species: comparative activities in normals and in chronic granulomatous disease.

Human blood monocytes and neutrophils stimulated in vitro with phorbol myristate acetate, N-formyl-L-methionyl-L-leucyl-L-phenylalanine, activated zymosan, or heat aggregated gamma-globulin were found to suppress lymphocyte mitogenic responses. In activated phagocyte-lymphocyte cocultures, both blast transformation and [3H]-thymidine incorporation were reduced while numbers of dead cells were increased, thus suggesting a cytolethal suppressive mechanism. Suppression was prevented by catalase but not by other oxygen radical scavengers nor by cyclooxygenase inhibitors, thus implicating H2O2 as the suppressive mediator. Activated monocytes and neutrophils but not lymphocytes released measurable quantities of H2O2 into cell supernatants. However, transfer of an inhibitory effect with these supernatants was not routinely achieved. Finally, as opposed to normals, lymphocyte blastogenesis in chronic granulomatous disease patients was not inhibited by their activated phagocytes. However, catalase -reversible suppression could be restored in cocultures of normal phagocytes and patient lymphocytes. In conclusion, these studies demonstrate a potentially important mechanism whereby activated phagocytes may alter lymphocyte reactivity.

Blood Bactericidal Activity↗
PubMed1984

Monoclonal antibody-induced murine hemolytic anemia.

A panel of 11 IgG monoclonal antierythrocyte antibodies was generated by fusing spleen and bone marrow cells from unimmunized New Zealand black mice with the nonsecreting murine plasmacytoma cell line P3.X63.NS1. The monoclonal antibodies were detected by indirect hemagglutination of unaltered erythrocytes from several strains of mice. Seven of the antibodies cross-reacted with rat erythrocytes, but none of the antibodies agglutinated erythrocytes from any other species tested. Seven of the monoclonal antibodies were also capable of fixing rabbit complement. In vivo studies utilizing these 11 IgG-secreting hybridomas were performed in syngeneic BALB/c mice. Mice injected with nine of the hybridomas showed positive direct antiglobulin test results but did not become anemic. In contrast, hybridoma 114, secreting an IgG3 antibody, and hybridoma 245, secreting an IgG1 antibody, were both capable of mediating an acute, rapidly fatal hemolytic anemia. Intraperitoneal injection of hybridomas 114 and 245 resulted in positive direct and indirect antiglobulin test results, decreased hematocrit level, and reticulocytosis 3 to 6 days after cell injection. The mice survived a mean of 8 days, and death was associated with severe anemia and spontaneous erythrocyte agglutination. Autopsy studies revealed hepatosplenomegaly, small mesenteric tumor (hybridoma) mass, and no ascites. The liver and spleens were characterized histologically by erythrophagocytosis, extramedullary hematopoiesis, and hemosiderin deposition. Acute hemolytic anemia in BALB/c mice mediated by hybridomas 114 and 245 represents a new animal model that can be used to further define the mechanisms of immune hemolytic disease.

Anemia, Hemolytic, Autoimmune↗
PubMed1983

Endogenous inhibition of autologous lymphocyte antibody-dependent cellular cytotoxicity.

Previous reports have indicated that prostaglandins can inhibit certain immune mechanisms, particularly mitogen responsiveness and cell-mediated cytotoxicity of virus-infected or tumor cells. In this study an endogenous self-inhibitory mechanism for antibody-dependent cellular cytotoxicity (ADCC) with normal human peripheral blood mononuclear cells is described. This inhibition could be abrogated by the prostaglandin synthetase inhibitor indomethacin or by removing nylon wool-adherent cells but not platelets. ADCC inhibition was restored by adding exogenous PGE1, PGE2, or supernatant fluid from cultured plastic-adherent mononuclear cells. In contrast, supernatant fluid from adherent mononuclear cells cultured with indomethacin was not inhibitory for ADCC. These results suggest that peripheral blood mononuclear cells contain adherent cells, probably monocytes, which produce prostaglandins that inhibit the ADCC effector activity of normal peripheral blood lymphocytes. This may explain, in part, the wide variability of ADCC effector cell activity that has been reported previously. Monocyte proportions and/or activity may have profound effects on tests of ADCC effector cell activity in various disease states.

Animals↗
PubMed1983

Urinary excretion of antinuclear antibodies.

The frequency of antinuclear antibodies (ANA), the immunoglobulin class of ANA and their specificity for known nuclear antigens were determined in 24-h urine collections from patients with systemic lupus erythematosus (SLE) and progressive systemic sclerosis (PSS). Sixteen % of SLE patients had detectable urine ANA by indirect immunofluorescence using mouse kidney substrate. A higher incidence, 32% of SLE and 28% of PSS patients, had detectable ANA in a titer greater than or equal to 1:16 using HEp-2 cell substrate. IgG ANA was the most frequent immunoglobulin class of antibodies present in the urine; 56% of SLE and 29% of PSS patients with urine ANA had more than one immunoglobulin class of antibodies. Antibodies to Sm, nRNP, SS-A and dsDNA were detected in SLE urine; antibodies to SS-A and centromere were detected in PSS urine. Urine ANA detected on mouse kidney substrate and urine dsDNA antibodies correlated with diffuse proliferative glomerulonephritis in patients with SLE. Sixty-two% of SLE patients with urine ANA had proteinuria. In the remaining SLE patients and in all the PSS patients with urine ANA however, protein excretion was normal. SDS-PAGE revealed heavy and light immunoglobulin molecules in both SLE and PSS patients with urine ANA. The intact immunoglobulin was shown to have ANA activity. ANA present in the urine of SLE and PSS patients with apparently normal renal function may be an early sign of altered glomerular capillary membrane permeability.

Adult↗
PubMed1981

Rapid semi-quantitative isolation of beta-2-microglobulin from urine.

A rapid semi-quantitative purification of beta 2-microglobulin from transplant urine relies on a batch absorption using hydroxylapatite-cellulose. Stepwise elution is followed by Sephadex G-150 gel permeation chromatography. Using this methodology, it is possible to process quickly and conveniently many liters of urine at bench scale, with yields exceeding 95% and overall purity greater than 97% beta 2-microglobulin.

Absorption↗
PubMed1981

Effect of physical stress on sensitivity of lymphocytes to inhibition by prostaglandin E2.

Physical stress is associated with depressed cellular immune function. We have found that lymphocytes from subjects undergoing either of 2 stressful events, cardiac surgery or childbirth, are more sensitive to inhibition by PGE2. For example, the concentration of PGE2 required for 50% inhibition of 3H-thymidine incorporation (ID50) into phytohemagglutinin-stimulated lymphocytes from patients undergoing cardiac surgery went from 1.5 X 10(-8) M on the day before surgery to 3 X 10(-9) M on the day after surgery. This increase in sensitivity to PGE2 was accompanied by a significantly decreased lymphocyte proliferative response (27 to 68% of control, depending on mitogen dose) and a 50% increase in the percentage of E rosette-positive cells with receptors for the Fc portion of IgG. The increased sensitivity to PGE and the depressed mitogen responses returned to preoperative values by day 10. The depressed mitogen responses of the postoperative patients were completely restored to normal by removal of glass-adherent cells before culture. In addition, the responses of the postoperative patients and the women in labor were partially restored by the addition of indomethacin, a prostaglandin synthetase inhibitor, to the cultures. Thus it would appear that physical stress causes lymphocytes to become more sensitive to prostaglandin E2, and the increased sensitivity to inhibition by this immunomodulator is responsible in part for the depressed cellular immune function after physical stress.

Cell Adhesion↗
PubMed1980

Lymphocytotoxic antibodies in systemic lupus erythematosus patients and their relatives: reactivity with the HLA antigenic molecular complex.

Lymphocytotoxic activity of sera from systemic lupus erythematosus (SLE) patients and their families was inhibited by 50% or more by preincubation of target cells with Fab2 fragments of xenoantisera against beta 2 microglobulin or the heavy chain of the HLA-A,B,C antigenic molecular complex. An antiHLA-DR xenoantiserum had less blocking effect on peripheral blood mononuclear cells but was effective at blocking reactivity of these sera against cultured B lymphoid cell lines. The repertoire of specificities in family members' sera differed from each other and their respective proband with respect to their reactions with cultured lymphoid cell lines. These data indicate that lymphocytotoxic antibodies (LCA) found in most patients with SLE and some of their relatives include a subpopulation with specificity for determinants present on major histocompatibility gene products. They also suggest that LCA in relatives represent a defect in immune regulation which allows expression of existing autoimmune potentials rather than immunization with a single "lupus" antigen.

Antibody Specificity↗