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Biomedical subjects

F Milgrom

Publications and source records attributed to F Milgrom.

At least 73 records · Page 4Linked to original sources

Studies on Paul-Bunnell (P-B) antigen-antibody system. V. Immunoglobulin classes of P-B antibodies.

By means of enzyme immunoassay (EIA) with purified Paul-Bunnell (P-B) antigen of bovine erythrocytes and sera of infectious mononucleosis, P-B antibodies of IgG (92%), IgM (94%), IgA (77%), and IgE (64%) classes were demonstrated. Absorption and inhibition studies ascertained the P-B specificity of the antibodies of all four classes. Absorption of selected IM sera with sheep erythrocytes revealed the presence of both BS and B antibodies of P-B specificity in these sera. In three IM patients whose sequential serum samples were studied, P-B antibodies of all four classes appeared and reached their peaks within a few weeks after the onset of the disease, persisted for a month, and sharply declined thereafter.

Antibodies↗

Immunological studies on Kawasaki disease. I. Appearance of Hanganutziu-Deicher antibodies.

Sera of patients with Kawasaki disease were studied for heterophile antibodies by means of enzyme immunoassay (EIA) with enzyme conjugated antisera to human IgM, IgG, IgA and IgE. Antibodies of IgM (43%), IgG (3%), IgA (11%) and IgE (49%) classes were demonstrated that combined with high molecular weight glycoprotein (HMWGP) of bovine red blood cells (BRBC) one of the antigenic preparations of the Hanganutziu-Deicher (H-D) heterophile system. Studies on sequential sera of the patients revealed that HMWGP antibodies of IgM and IgE classes began to appear in the second week, reached their peaks in the third week of the disease and declined gradually thereafter. Absorption studies on the positive sera showed that the HMWGP antibody activities were abolished by BRBC, sheep red blood cells and guinea-pig kidney tissues, confirming H-D specificity of these antibodies. EIA inhibition studies showed that the antibody activity was inhibited by HMWGP and partially by asialo-HMWGP and NGNA ganglioside rich preparation of BRBC but not by purified Paul-Bunnell or Forssman antigens. These results indicate that the H-D antibodies under investigation consist of antibodies of two different specificities; one directed against asialo-HMWGP and the other NGNA ganglioside of BRBC. Circulating immune complexes (IC) were demonstrated in 23% of the patients by means of anti-antibody inhibition test. Evidence was presented that IC in the sera of five patients were composed of H-D (HMWGP) antigen and its corresponding antibodies.

Antibodies, Heterophile↗

Hyperacute renal allograft rejection in the rabbit. The role of platelet-activating factor and of cationic proteins derived from polymorphonuclear leukocytes and from platelets.

The macroscopic signs of rejection, the levels of circulating transplantation antibodies, the histologic and immunocytochemical aspects, and the levels of platelet-activating factor (PAF) present in the venous blood were studied in two groups of rabbits that had received renal allografts, one group presensitized with multiple skin grafts and a second group unsensitized, as well as in a third group of rabbits that had received renal autografts. All of the eight allografts hyperacutely rejected by presensitized recipients had deposits of rabbit IgG, IgM, and C3 along the endothelia of the vessels and massive intravascular accumulation of platelets (Pt) as soon as 5 minutes after revascularization. PAF release was detected in 2 to 10 minutes after revascularization and was present throughout most of the 60 minutes of observation. Sixty minutes after transplantation Pt and polymorphonuclear leukocytes (PMN) obliterated the vasculature and deposits of Pt- and PMN-derived cationic proteins were detected in the lumina and in the walls of the capillaries. Similar, but less severe, findings were observed in three of six renal allografts which had transient episodes of rejection after transplantation into presensitized recipients. In contrast, circulating transplantation antibodies, macroscopic signs of rejection, vascular immune deposits, release of PAF, and microvascular thrombosis were not detected in renal allografts transplanted into unsensitized recipients or in renal autografts. The results indicate that in hyperacute renal allograft rejection there is an immediate fixation of transplantation antibodies and complement of the recipient to endothelial antigens of the graft, local release of PAF, and massive accumulation, aggregation, and degranulation of Pt and PMN in the vasculature, resulting in a binding of Pt- and PMN-derived cationic proteins to the walls of the capillaries. It is conceivable that PAF release and Pt and PMN cationic proteins may contribute, together with other lysosomal enzymes, vasoconstriction, and coagulation, to the pathogenesis of antibody- and complement-mediated hyperacute graft injury.

Animals↗

Mixed agglutination with guinea pig tissue sediments for detection of heterophile antibodies.

Mixed agglutination (MA) test with sediments of guinea pig kidney (GPK) homogenates and indicator red blood cells of bovine (BRBC) or sheep (SRBC) origin was established for detection of human heterophile antibodies. By means of MA test with BRBC indicator cells, heterophile antibodies of Hanganutziu-Deicher (H-D) specificity were demonstrated in sera of patients with syphilis (20%), lepromatous leprosy (57%), infectious mononucleosis (45%), Chediak-Higashi syndrome (73%), Kawasaki disease (58%), multiple sclerosis (58%), and leukemias (13%), as well as in sera of subjects who received injections of foreign species sera (20%). Some but not all BRBC-positive sera gave positive MA tests when SRBC were employed as indicator cells. None of 13 multiple myeloma sera tested gave positive results. The incidence of positive reactions in normal human sera was 3%. Neutralization of H-D antibodies in representative pathologic sera by purified heterophile antigens showed that the antibodies under investigation were mostly directed against antigen(s) of high molecular weight glycoprotein, but not N-glycolyl-neuraminic acid (NGNA) ganglioside fraction of BRBC.

Agglutination Tests↗

Paul-Bunnell antigen in normal human tissues.

The BS antigen, the component of the Paul-Bunnell (P-B) antigen complex that is shared by bovine (BRBC) and sheep red blood cells (SRBC), was demonstrated in chloroform-methanol extracts from peripheral blood leukocytes of 4 of 26 healthy young individuals. One of the extracts formed a precipitation line with infectious mononucleosis (IM) sera, which merged into a reaction of identity with the corresponding line formed by the purified P-B antigen of BRBC. The BS antigen of the P-B complex was also demonstrated in tissue sediments of an apparently normal human kidney by means of mixed agglutination test with IM sera and trypsinized BRBC as the indicator. Results of this study suggest that the BS antigen is expressed in normal tissues of some individuals as an intracellular antigen, whereas in various pathologic conditions it is expressed as cell-surface antigen and/or appears in a soluble form in the patient's circulation.

Adult↗

Studies on Paul--Bunnell (P-B) antigen--antibody system. IV. Unresponsiveness to one of P-B antigens in infectious mononucleosis.

Sera of 198 patients with infectious mononucleosis (IM), which were obtained during the 3rd or 4th week of the disease, were studied for the presence of antibodies to BS and B antigens of the Paul--Bunnell (P-B) antigenic complex. Six of these IM patients had anti-B antibodies without or with very low-titer anti-BS antibodies and the remaining patients had both types of antibodies at high titers. These 6 IM patients would have been misdiagnosed as seronegative if the traditional P-B tests with sheep erythrocytes had been employed. BS antigen was demonstrated in a large amount in chloroform-methanol extracts of peripheral blood buffy coat and of erythrocytes obtained from 1 of the 6 patients during the 3rd week of the disease and right after recovery.

Adolescent↗

Studies on the Paul-Bunnell antigen-antibody system. III. Detection of a Paul-Bunnell-related antigen in syphilis and leprosy.

By means of double-diffusion precipitation tests in agarose gel with selected infectious mononucleosis (IM) sera, an antigen was detected in sera of patients with syphilis and leprosy. Of 378 syphilis sera tested 39 (10.3%) and of 36 leprosy sera 7 (19.4%) gave positive results. Sera of patients with various other diseases were negative. This antigen was demonstrable in sera of patients with both early and late syphilis and was shown to be unrelated to cardiolipin. Absorption studies of the IM sera with bovine and sheep erythrocytes and guinea pig tissues revealed that this antigen was identical with or closely related to the previously described B antigen of the Paul-Bunnel (P-B) antigenic complex and distinct from heterophile antigens of Hanganutziu-Deicher (H-D) and of Forssman specificity. However, 2 of 89 syphilis sera without the P-B antigen were shown to contain antigen(s) of H-D specificity. None of the syphilis or the leprosy sera contained P-B antibodies, but H-D antibodies were found in 13% of syphilis sera.

Animals↗

Dissociation of immune complexes in tissue sections by excess of antigen.

Immune complexes (IC) present in the glomeruli of rabbits with chronic serum sickness (CSS) and in patients with systemic lupus erythematosus (SLE), idiopathic membranous nephropathy (IMN), and acute poststreptococcal glomerulonephritis (PSGN) were analyzed by incubation with antigenic preparations. The efficacy of these preparations to dissolve IC was assayed by comparison of results of direct immunofluorescence tests performed with the kidney tissues before and after incubation with antigenic preparations. The FITC-conjugated antisera used in these tests were specific for IgG, C3, and-in the case of CSS-for the eliciting antigen, bovine serum albumin (BSA). During the acute proteinuric phase of CSS in rabbits, incubation of tissue sections with BSA alone led to complete dissolution of IC. In many rabbits with late phase proteinuria, however, tissues had to be incubated with both BSA and aggregated fraction II of rabbit serum. In all biopsy specimens from patients with IMN, and in some specimens from patients with PSGN and SLE, aggregated fraction II of human serum resulted in complete or incomplete dissolution of IC. On the other hand, incubation of tissues with excess DNA in SLE or with streptococcal antigens PSGN did not lead to dissolution of IC. These studies suggest significant participation of antibodies to aggregated immunoglobulins (i.e., rheumatoid factors or rheumatoid-like factors) in IC found in the above-mentioned diseases. Other antigen -antibody systems, however, may also contribute to the deposits in the glomerulonephritides studied.

Animals↗

Collagen-anti-collagen complexes in rheumatoid arthritis sera.

Immune complexes (IC) were detected in rheumatoid sera by means of anti-antibody (AA) neutralization tests. The sera with rheumatoid factor (RF) that did not agglutinate human Rh+ erythrocytes sensitized by incomplete Rh antibodies, Ripley, could be tested in an AA neutralization test without any further treatment. On the other hand, 'Ripley-positive' sera had to be treated with 2-mercaptoethanol or dithiothreitol in order to destroy RF. IC-containing sera were further studied for dispersion of IC by collagen. Surprisingly, roughly 50% of IC-containing sera were affected by collagen in that they lost AA-neutralizing activity completely or partially. Significantly, very similar results were obtained with collagen type I, collagen type II and denatured collagen type II. It was concluded that these sera contained IC formed by denatured collagen and its antibodies. Further experiments were devoted to the study of the effect of collagen on reactions of RF with Ripley-sensitized erythrocytes. In several sera, the addition of collagen eliminated the prozone. This was interpreted as deblocking of RF due to the dispersion of the blocking IC by an excess of collagen. In other sera, the addition of collagen seemed to remove or block RF. This blocking effect was interpreted as a neutralization of multispecific RF by collagen. An alternative explanation proposed that collagen formed IC with free anti-collagen antibodies and that these IC blocked the RF.

Antibodies, Anti-Idiotypic↗

Hanganutziu-Deicher antibodies in infectious mononucleosis and other diseases.

An enzyme immunoassay (EIA) was developed for the detection of heterophile, Hanganutziu-Deicher (H-D) antibodies in sera of patients with infectious mononucleosis (IM) and various other diseases. The EIA with a high m.w. glycoprotein (HMWGP) isolated from bovine erythrocyte stromata was shown to detect H-D antibodies directly, in spite of higher titers of Paul-Bunnell (P-B) antibodies in the IM sera. Absorption and inhibition studies of IM sera demonstrated H-D specificity of the antibodies combining with HMWGP in the EIA. The H-D antibodies were found in sera of 56% Caucasians and 27% of Japanese suffering from IM. The vast majority of the H-D antibodies in IM sera was of IgM class. Sera of patients with various other diseases also gave positive results: rheumatoid arthritis, 22%; syphilis, 19%; cancer of the gastrointestinal tract, 13%; and lepromatous leprosy 9.7%. The incidence of positive results in control sera from apparently healthy subjects was less than 4%. Results of this study confirmed our previous observation that whereas P-B antigens appear in immunogenic form in only IM, the H-D antigen is expressed as an immunogen in various diseases including IM.

Antibodies, Heterophile↗

IgG rheumatoid factor. Detection by enzyme immunoassay in rheumatoid arthritis and normal subjects.

IgG rheumatoid factors were demonstrated by enzyme immunoassay using, as antigen, goat antibodies to human serum albumin in the form of immune complexes. Elevated levels of IgG rheumatoid factor were noted in the majority of patients with seropositive rheumatoid arthritis but also relatively often in normal blood donors. Reactivity of IgG rheumatoid factor was in most instances inhibitable by IgG from various species, including man. Exceptionally, restricted specificity towards IgG from bovidae, was recognized.

Adult↗