Expression of heterophile Paul-Bunnell antigen on human lymphoid cell lines.
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Biomedical subjects
Publications and source records attributed to F Milgrom.
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Sera of patients with lepromatous leprosy were studied for the presence of a variety of antibodies and immune complexes (IC). The frequencies of heterophile, Hanganutziu-Deicher and Forssman antibodies were 61 and 43%, respectively, which were significantly higher than those in other diseases. The frequency of antibodies to cardiolipin was 89% and the frequency of rheumatoid factor was 34%. Circulating IC were demonstrated in 54% of the patients' sera by Raji-cell test and in 43% by anti-antibody inhibition test. Analyses of immunoglobulin classes of IC revealed that IgG was predominant in IC of patients with lepra reaction (LR) and IgM in patients without LR. Immune deposits were found in and between cells of dermis in skin biopsy specimens of patients with LR.
By means of mixed agglutination test with staphylococcal protein A indicator system, DRw antigens were studied on lymphocytes obtained from tonsils, peripheral blood and thymuses. Monospecific antisera to DRw 1, 2, 3, 6 and 7 which were preadsorbed with pooled platelets gave mixed agglutination titers of 300 or more against B cells of human tonsilar lymphocytes and peripheral blood lymphocytes. The DR phenotypes of human tonsilar lymphocytes and peripheral blood lymphocytes determined by mixed agglutination tests corresponded to those established by lymphocytotoxicity tests. Upon stimulation of thymocytes or T cells of peripheral blood lymphocytes by Con-A, DRw antigens became detectable by mixed agglutination tests. Simultaneous experiments on the stimulated T cells of peripheral blood lymphocytes by membrane fluorescence tests showed that 21-45% of the stimulated T cells possessed DRw antigens at a detectable level, while less than 2% of unstimulated cells were positive. These results indicated that DRw antigens are present in the subpopulation of T cells which may expand in the response to Con-A stimulation.
The serologically active moiety of an antigen detected occasionally in pathologic sera by double-diffusion gel precipitation tests, referred to in earlier studies as ubiquitous tissue antigen, was identified as a dextran composed predominantly, if not exclusively, of a(1 leads to 6)-linked glycopyranoses. By means of an enzyme immunoassay, dextran or dextran-like material, which inhibited the binding of antidextran serum to dextran, was detected in sera of several patients with various gastrointestinal (GI) diseases, especially GI ulcers (7/10), and also often in sera of aged people (9/21). However, 2 of 50 normal blood donor sera and a few sera from almost every disease group studied contained low quantities of dextran-like material. The levels of antidextran antibodies of the IgG class were also often elevated among patients with GI diseases and aged people as demonstrated by enzyme immunoassay with dextran T-500 as the solid phase antigen. OD values exceeding the mean plus 2.5 SD of 106 normal blood donor sera were recorded in ;69% of patients with gastric and duodenal ulcers, 40% with ulcerative colitis, 29% with Crohn's disease, 20% with colorectal carcinomas, and in 21% with rheumatoid arthritis. None of 23 children, but 9 of 23 aged people (35%) had elevated antibody levels. It is suggested that absorption of dextrans from food or their production by intestinal bacteria may be facilitated in various GI diseases.
The multiple nature of heterophile, Paul-Bunnel (P-B) antigen has been suggested by our previous studies as well as those of others. In the present study, two distinct antigens of P-B specificity were defined by means of hemagglutination and immunodiffusion tests in agarose gel; one antigen (BS) was shared by bovine (BRBC) and sheep red blood cells (SRBC) and another antigen (B) was limited to BRBC. Both anti-BS and anti-B antibodies were shown to be present in sera of 106 patients with infectious mono-nucleosis (IM) whereas they were virtually absent from the sera of the vast majority of patients with diseases other than IM and normal sera. Absorption and agglutination inhibition tests demonstrated the presence of BS and B antigens on horse erythrocytes. Goat erythrocytes were also shown to possess BS antigen, however, B antigen was found on erythrocytes of some but not all individual goats. By means of the previously established procedure, BS antigen was extracted from stromata of BRBC, SRBC and erythrocytes of horse and goat, and B antigen from BRBC and erythrocytes of some goats. BS and B antigens were also extracted from bovine lymphocytes and murine thymus and spleen tissues but not murine erythrocytes.
Peripheral blood lymphocytes from 51 multiple sclerosis (MS) patients and 23 healthy individuals were examined for their response to human myelin basic protein at three concentrations. Cells from active-MS patients responded in most cases with definitely enhanced blastogenic stimulation (BS), whereas those of the nonactive-MS patients or of patients in remission showed values of BS similar to or below those of the control group. Patients and control individuals were divided in two groups according to their age. The younger group included individuals from 20 to 40 years of age, the older those from 41 to 68 years. The lowest and highest values obtained using the three doses of basic protein was selected and the results compared. The higher values of BS and the greater frequency of active blood samples were observed in the younger than in the older active-MS patients. On the other hand, a larger number of samples obtained from the older patients showed the lowest values of BS. The relevance of age to the suppressor activity induced by the basic protein in the lymphocytes of MS patients is discussed.
Using an antibody reagent, an organ-specific antigen has been purified from human pancreas. Purification was achieved using ammonium sulfate and ethanol precipitations, concanavalin A-Sepharose affinity chromatography, anion-exchange chromatography and gel filtration. The antigen had a molecular weight of approximately 68,000 as determined by gel filtration, was not dissociated into subunits by sodium dodecyl sulfate, and did not bind to immobilized concanavalin A. The biological significance of this antigen in pancreatic cancer is being studied.
Preparations obtained by the chloroform-methanol extraction procedure from spleen tissues of patients with Hodgkin's disease, lymphomas, and leukemias, as well as from peripheral blood buffy coat of infectious mononucleosis (IM) patients were studied for the presence of 2 Paul-Bunnell (P-B) antigens; BS antigen shared by bovine red blood cells (BRBC) and sheep red blood cells (SRBC) and another, B antigen characteristic for BRBC. Both BS and B antigens were demonstrated by means of agglutination inhibition tests in over 40% of these extracts. None of the extracts from spleens, tonsils, and buffy coat of apparently normal human beings contained these antigens. P-B antigens of lymphoma-leukemia extracts were further purified by DEAE-Sephadex column chromatography. The purified fractions of some of these spleen extracts formed a precipitation line with IM sera, which merged into a reaction of identity with the lines formed by P-B antigens of BRBC. In studying various pathologic sera, B antigen was detected in sera of 28% of lymphoma-leukemia patients, 15% of patients with carcinomas of internal organs, and 3% of patients with systemic lupus erythematosus. On the other hand, BS antigen was found in only 3% of lymphoma-leukemia sera. These results confirmed our previous observations and indicated that both BS and B antigens are expressed as neoantigens on the patient's spleen cells as a result of pathologic processes in lymphoreticular malignancies.
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Four hundred and forty-nine syphilis sera, positive in VDRL and FTA-ABS tests, were studied for the presence of circulating immune complexes (CIC) by means of anti-antibody (AA) neutralization test. Ninety-three (20.7%) sera had demonstrable CIC. Subsequently, dispersion of CIC by saline suspension of cardiolipin and by extract of rabbit testicular syphiloma was examined. Of 40 CIC-containing sera tested with cardiolipin, dispersion of CIC was noted in 16 instances; of 32 CIC-containing sera examined with syphiloma extract, dispersion was noted in 16 cases. Significantly, CIC that showed definite dispersion by cardiolipin were not dispersed by syphiloma extract and vice versa. Some studies were also performed on lepromatous leprosy and SLE. None of 27 cIC-containing lepromatous leprosy sera were affected by cardiolipin, but in 2 of 9 CIC-containing SLE sera, cardiolipin dispersed the complexes. Cardiolipin-anti-cardiolipin complexes that neutralized AA were frequently observed when cardiolipin was added to sera containing its corresponding antibodies but not CIC. Similar reactions were noted between the syphiloma extract and anti-treponemal antibodies.
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The effect of prolonged immunization of mice with bovine serum albumin (BSA) on tumors elicited by injection of 3-methylcholanthrene was studied. The incidence of tumors and rate of tumor growth were higher in mice immunized with BSA than in control mice injected with syngeneic serum. The possibility of an immunosuppressive effect of the prolonged immunization with BSA is discussed.
Sera of Japanese patients with various diseases including patients with lympho-proliferative disease similar to infectious mononucleosis (IM) were studied for the presence of heterophile antibodies. Antibodies to sheep erythrocytes were demonstrated in 9 of 19 such patients whereas similar antibodies were found only in 28 of 3570 (0.8%) patients with various other diseases. Adsorption studies revealed that these antibodies in patients with IM-like syndrome are of Hangantziu-Deicher or Forssman nature. On the other hand, Paul-Bunnell antibody characteristic for IM in Caucasians was not demonstrated in Japanese suffering from IM-like syndrome.
Forty-seven patients with multiple sclerosis (MS), 21 subjects with neurological diseases other than MS (OND), 7 with miscellaneous disease (MD) and 21 healthy individuals (HI) were examined by the standard procedure of blast transformation for the in vitro response to mouse brain (MB), mouse kidney (MK) and mouse lung (ML) tissue extracts. Increased cellular response to MB was limited to the MS and OND groups, whereas high and low values of stimulation index to MK and ML were similarly observed in all groups of individuals examined. No correlation was found between the clinical activity of the MS patients and the in vitro response to MG. The possibility that low sensitivity of the technique and complexity of the antigenic composition of MS are determining factors in the results obtained in these studies is discussed.
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