Cytolytic antibodies to murine lymphomas elicited by immunization with allogenic and syngenic tumors.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to F Milgrom.
Explore the source record for details and available documents.
Sera from patients who had received renal allografts were studied for the presence of circulating immune complexes by using platelet aggregation technique combined with density gradient centrifugation. A simple and highly reproducible modification of the platelet aggregation technique, employing the use of relatively small amounts of blood from pretested donors as the source for platelets, is described. Immune complexes were detected in post-transplantation sera from 3 out of 16 patients. The development of a persistent immune complex state as a consequence of grafting was concluded in one patient.
By means of mixed agglutination test and indirect immunofluorescence test, reactions of infectious mononucleosis sera with bone marrow cells were investigated. Positive reactions were observed with bovine, murine and rat bone marrow cells, but negative results were obtained with cells of monkeys and guinea pigs. Absorption studies demonstrated that the observed reactions are due to interaction of the Paul-Bunnell antigen on bone marrow cells with its corresponding antibodies in infectious mononucleosis sera. Whereas all cells of bovine bone marrow gave positive results, only 50% of murine or rat cells were positive and these cells were shown to be neutrophilic granulocytes. Evidence was also presented that the Paul-Bunnell antigen and Fc receptor are present, apart from each other, on murine neutrophilic granulocytes.
Sera and 5% PEG-precipitates from 20 patients with IMN, 18 with MPGN, 20 with SLE, 8 with anti-GBM disease and 17 with other varieties of glomerulonephritides, 19 patients with chronic liver or intestinal diseases, as well as those from 40 healthy adults, were tested by gel prcipitation for the presence of a ubiquitous tissue antigen (UTA) and/or its corresponding antibody, previously shown to be associated with renal disorders. The antigen was detected in sera of 5 patients with IMN, one with anit-GBM disease and one with SLE. Corresponding antibodies were present in sera of 2 patients with IMN. In 4 of 5 patients with IMN and UTA was only detected if the sera were first treated with PEG (mol. wt. 6,000) which induces precipitation of antigen-antibody complexes and other high molecular weight components in serum. The UTA was not detected in renal glomeruli by immunofluorescence. The possible significance of these findings in the pathogenesis of renal diseases is discussed.
A 22-year-old white male (L.V.) died of gram-negative septicemia complicating infectious mononucleosis (IM) that was associated with jaundice and oliguric renal failure. The kidney showed mesangial granular deposits of IgM and C3, mesangial electrondense deposits, and interstitial infiltrates of infiltrates of mononuclear cells, including atypical lymphocytes. Eluates obtained from kidney, spleen and liver contained Paul--Bunnell (PB) antibodies. Presence of PB antigens in these tissues was indicated by absorption of PB antibodies from IM sera, with the sediments resulting from tissue elutions. The IgM mesangial deposits were partially eluted with acid buffer at 56 degrees C and then reconstituted by incubation with IM sera or with immunoglobulins eluted from tissues of patient L.V. The presence in renal structures of PB antigens, IgM heterophile antibody, C3 and electron-dense deposits is consistent with the hypothesis that heterophile immune complexes were localized in the kidney and that they contribute in the pathogenisis of IM nephritis.
A procedure is described for detection of antibodies and antigens in 'immune complex' nephritis. Kidney tissue is minced, washed and sealed in a well of an agarose or agar plate. Separation of immune complexes is achieved by electrophoresis at 56 degrees. Afterwards, antibody is readily detected in reaction with a proper anti-IgG serum. Antigen is identified by its corresponding antibody, the reaction with which is, in some instances, strengthened by counterimmunoelectrophoresis.
Servlogical tests preformed on a patient with gold-induced nephropathy revealed a multitude of immunological phenomena preceding the onset of proteinuria. These included formtaion of tissue antibodies, rheumatoid factors and circulating immune complexes. An antigen sharing immunological determinants with DOC-extractable tissue antigens was released into circulation before and during proteinuria. Precipitating antibodies against this circulating antigen were found in one serum sample obtained 6 weeks before the complication was diagnosed. In this serum specimen, antibodies were also found which combined with saline extracts, DOC extracts containing the ubiquitous tissue antigen (UTA), and preparations obtained from various human organs by extraction at 100 degrees C followed by precipitation at 71% ethanol concentration (BE preparations). Most of the activities disappeared before the onset of proteinuria. The possible significance of these phenomena in the pathogenesis of nephropathy is discussed.
Explore the source record for details and available documents.
Precipitation tests using properly absorbed rabbit antisera revealed that PCA extracts of DMH-induced rat jejunal and colonic adenocarcinomas contain an antigen that is not detectable in extracts of normal rat tissue or other rat tumors. This rat tumor antigen was detected in extracts of normal rat colon by employing the much more sensitive procedure of tanned cell hemagglutination inhibition, however, the concentration of the antigen in tumor was about 250-fold higher than in normal colon. Similar to human CEA, the rat tumor antigen was found to be heat stable, contained glycoprotein, migrated as a beta-globulin, and appeared at a high concentration in fetal intestines, however, the rat tumor antigen was serologically distinct from human CEA.
Studies were performed on heterphile antibodies originally described by Hanganutziu and Deicher and referred to as H-D antibodies. It was confirmed that these antibodies appear as a result of injections of foreign species sera. They differ from Forssman antibodies by combining with bovine erythrocytes and from Paul-Bunnell antibodies by reacting with guinea-pig kidney. it was demonstrated that H-D antibodies react in double diffusion gel precipitation tests with: (1) crude extract of bovine erythrocyte stromata; (2) purified fraction of this extract devoid of Paul-Bunnell antigen; (3) whole bovine serum and sera of several other species; and (4) thermostable ethanol-insoluble freactions of serum and organs of oxen and several other species. These various antigenic preparations gave usually reactions of complete or partial identity with each other. In several instances, two or even three precipitation lines could be detected. H-D negative human erythrocytes became coated with H-D antigen upon simple incubation with H-D-positive sera. H-D antibodies were also detected in some pathological human sera without any indication that the patients had ever received injections of foreign species sera. Such antibodies were undistinguishable from H-D antibodies engendered by injections of foreign sera.
By means of double diffusion in gel reactions, "heterophile" antibodies were demonstrated in human renal transplantation sera. Of thirty-two recipients of renal allografts, 12 (37 per cent) had antibodies to extract of bovine erythrocyte stromata, and 5 (19 per cent) of 26 recipients produced antibodies to extract of sheep erythrocyte stromata. These antibodies became detectable 1-6 months after transplantation and persisted for several months or years. However, the strength of reactions given by individual serum samples from the same recipient varied considerably. Sera from the same recipient gave a reaction of identify, while sera from two different recipients frequently gave reactions of partial identity or nonidentity. The antibodies reacting with bovine stroma extract were distinct from those reacting with sheep stroma extract. Evidence was also presented that the heterophile antibodies in transplantation sera are different from Paul-Bunnell antibodies in infectious mononucleosis sera. Some of the HL-A typing sera were shown to contain antibodies against bovine stroma extract. The antigen recognized by these sera in the bovine stroma extract was not related to any HL-A specificity. Three of eight rabbits which received skin and renal allografts formed antibodies against bovine stroma extract. Absorption studies clearly demonstrated that these antibodies are directed against antigens present in the donor's, but not in the recipient's tissues.
Double diffusion tests in gel were employed for studies of reactions between infectious mononucleosis sera and extracts of bovine, sheep and equine erythrocyte stromata. The extracts were obtained by ultrasonication of stromata prepared from trypsin-digested erythrocytes. The reaction with bovine stroma extract was composed, in many instances, of two lines. A single line was observed in reactions with sheep and equine stroma extracts. This line merged into a reaction of partial or complete identy with one of the lines formed with bovine stroma extract. Evidence was obtained that some infectioous mononucleosis sera may contain heterophile (Paul-Bunnell) antibodies belonging to IgG class in addition to those of IgM nature.
Explore the source record for details and available documents.
Antibody titers to varicella-zoster (V-Z), herpes simplex (HSV) and vaccinia viruses were determined in sera collected in Buffalo, NY, from patients with multiple sclerosis (MS), patients with other diseases, and normal individuals. The mixed agglutination test employing cell cultures infected with one of the above viruses as a source of antigen was used to determine antibody titers. The geometric mean titer (GMT) for V-Z in 59 MS cases was significantly higher than that observed in patients with other diseases and in normal individuals. The GMT for vaccinia was also higher in MS patients but the difference was not as great as for V-Z. No difference was observed in the titer of antibodies for HSV. Similar results were obtained for 51 MS patients compared to healthy controls matched for sex and age. Higher antibody titers for V-Z and HSV were observed in cerebrospinal fluids from MS cases than in those from non-MS CNS patients in Baltimore, MD. Antibodies to V-Z, HSV and vaccinia were detected in washing fluids from brain homogenates of MS cases.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Reactions of murine myeloma cells with infectious mononucleosis sera were studied by means of cytolysis in agarose gel. Of 75 sera tested, 30 lysed IgM myeloma cells, MOPC-104E. The antibodies responsible for the lysis of the myeloma cells were shown to be different from Paul-Bunnell antibodies and other antibodies found in infectious mononucleosis sera. Three types of antibodies acting upon the myeloma cells were identified serologically on the basis of absorption experiments with bovine erythrocytes, theta-positive murine lymphoma cells and guinea pig kidney cells. Antibodies of the first group could be absorbed with none of these antigens, antibodies of the second group could be absorbed only with lymphoma cells, and antibodies of the third group could be absorbed with any of these three antigens. Evidence was presented that the antibodies under study combine with antigenic cell membrane components of a subpopulation of IgM-producing murine B cells.
Explore the source record for details and available documents.