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Biomedical subjects

S F Slovin

Publications and source records attributed to S F Slovin.

36 records · Page 2Linked to original sources
PubMed1984

Epstein--Barr virus nuclear antigen in a non-Hodgkin's lymphoma.

This paper describes the course of a patient with treated non-Hodgkin's lymphoma, which originally presented as a large nasopharyngeal mass. The tumor, though irradiated, recurred on two separate occasions in the right and left inguinal regions. At the time of tumor recurrence, markers were present which have been associated with past or recurrent Epstein-Barr virus (EBV) infection, namely, antibodies to the EBV viral capsid antigen (VCA) and the Epstein-Barr nuclear antigen (EBNA). EBNA was detected in approximately 10% of the neoplastic cells. An unusual immunoglobulin heavy and light chain switch within the tumor cells of the two separate inguinal node tumor recurrences was also observed. Whether EBV plays a role in the pathogenesis of lymphomas remains unclear.

Aged↗
PubMed1983

Antibodies to Epstein-Barr virus associated antigens in Pima Indians with and without rheumatoid arthritis.

We investigated anti-rheumatoid arthritis-associated nuclear antigens (RANA) and other anti-Epstein-Barr virus (EBV) antibodies in a uniquely controlled study in female Pima Indians of Arizona, an RA prone population. Four groups of age and sex-matched individuals were formulated: (1) individuals positive for rheumatoid factor (RF) who had clinical evidence of rheumatoid arthritis (RA); (2) individuals seropositive for RF, but without arthritis; (3) individuals seronegative for RF, but with various kinds of arthritis; (4) those seronegative without arthritis. The mean anti-RANA in the seropositive RA group was significantly above those of the other groups but the anti-VCA and anti-EBNA titers did not differ. The anti-RANA was shown to be independent of RF. Comparing the Pima Indians to Caucasians in La Jolla, we found the mean anti-RANA titers of the Pimas to be significantly higher than those of the Caucasians. This study thus establishes clearly that elevated anti-RANA titers are characteristics of this American Indian group, just as they are of Caucasian groups. The elevated anti-RANA titers in RA patients may represent a unique hyperresponsiveness to this antigen, since there is no consistency in the reported levels of antibodies to other EBV-related antigens.

Antibodies, Viral↗
PubMed1983

Analysis of cellular immune response to EBV by using cloned T cell lines.

Eight cloned T cell lines specific for Epstein Barr virus-transformed B lymphocytes were derived. In the presence of the autologous virus-infected B cells, the T cell lines show HLA-restricted cytotoxic activity and also secrete alpha-interferon in sufficient amounts to inhibit infection and transformation. Four of these clones showed restriction to a single HLA locus (two for A3, and two for B7) and three showed exquisite self-restriction lysing only autologous targets. These seven clones expressed the classical cell surface phenotype of cytotoxic T cells being T3, 8, 11, and la-positive and T4-negative. An eighth clone that lacked the T8 surface marker appeared to recognize both B7 and BW51. HLA restriction was confirmed: 1) by the ability of a monoclonal antibody against an HLA-A,B,C framework antigen (W6-32) to block the cytotoxicity; 2) the failure of the clones to lyse Daudi, an EBV-positive, HLA-A,B, C-negative cell line; and 3) successful competition of the cytotoxicity by autologous but not allogeneic cold targets. The cloned T cells do not kill EBV-negative targets such as autologous pokeweed mitogen blasts and cell lines including CEM and the natural killer cell target K562. The results suggest T cell clones may be generated against an EBV-associated membrane antigen on transformed B cells, perhaps equivalent to the lymphocyte-determined membrane antigen, and that the recognition is restricted by a single HLA determinant. We propose that single T cells can play multiple roles in controlling EBV infection in vitro and in vivo including the elimination of transformed cells by cytotoxicity and the prevention by secreted interferon of further re-infection and transformation.

Clone Cells↗
PubMed1982

Membrane antigen on Epstein--Barr virus-infected human B cells recognized by a monoclonal antibody.

This paper describes a monoclonal antibody (B532) that detects a membrane antigen present on greater than or equal to 95% of the B cells from lines carrying the Epstein-Barr virus (EBV) genome. Evidence suggesting that B532 is EBV-related was originally obtained by using a cell-binding radioassay with different cell line substrates. Immunofluorescence and cell-sorter analysis confirmed that the antigen was present in high density on all EBV-infected lymphoblastoid B-cell lines, but not on EBV-negative B-, T-, myeloid, or null cell lines. Isolated normal peripheral blood B and T lymphocytes and monocytes failed to bind B532. The monoclonal antibody did not inhibit in vitro EVB infection nor did it block the killing of EBV-infected targets by cytotoxic T lymphocytes. The cell surface antigen recognized by B532 was shown by immunoprecipitation to have a molecular weight of approximately 45,000.

Animals↗
PubMed1981

T lymphocyte-mediated cytotoxicity against autologous EBV-genome-bearing B cells.

We have stimulated human peripheral blood lymphocytes in vitro with autologous EBV-infected or noninfected B cells. A cytotoxic response was obtained only when virally infected cells were used. The activity of the effector cells was restricted by the major histocompatibility complex and was directed against EBV-genome-bearing targets. The highest cytolytic response was obtained when lymphocytes of individuals previously exposed to the virus (EBV-VCA positive) were used. Lymphocytes of noninfected donors (EBV-VCA negative) gave a low response; the relative frequency of their effector cells was at least 4-fold lower. Lymphocytes of newborns did not respond. The cytotoxic activity was mediated by T lymphocytes of the cytotoxic/suppressor subset, as determined by cytofluorographic analysis and antibody plus complement-mediated lysis, using monoclonal antibodies to human lymphocyte surface antigen.

Antibodies↗
PubMed1981

Discordant expression of 2 Epstein-Barr virus-associated antigens, EBNA and RANA, in man-rodent somatic cell hybrids.

The Epstein Barr nuclear antigen (EBNA) and the rheumatoid arthritis nuclear antigen (RANA) develop in human B lymphocytes that have been infected and transformed by Epstein Barr virus (EBV). Antibodies to RANA and EBNA are found only in individuals with prior exposure to EBV. The purpose of the present studies was to determine the relation of the 2 antigens to each other and to EBV genetic material, in human-rodent somatic cell hybrids. Cultured human B lymphoblastoid cells, Raji, Daudi, and RPMI 4098 were fused with thymidine kinase-deficient mouse or hamster fibroblasts. After selection and cloning in ouabain-HAT medium, the hybrid nature of the surviving cells was confirmed by isozyme analysis. The hybrid clones were analyzed for EBNA by anti-complement im,munofluorescence, and for RANA by anti-immunoglobulin immunofluorescence and immunodiffusion. The results showed that RANA and EBNA segregated entirely independently of each other in the hybrid clones. Two methods were used to detect the presence of EBV DNA sequences in the intracellular DNA of hybrid clones. The 1st method relied on the hybridization of labeled cRNA prepared from virion DNA with DNA from 8 hybrid clones affixed to nitrocellulose filters. The 2nd approach was to hybridize labeled intracellular DNA from 3 hybrid clones to Southern blots of cloned fragments of EBV DNA. These results suggested that the presence of EBV DNA was not sufficient for the expression of either antigen. One stable RANA-positive hybrid cell line contained at least 80% of the EBV genome in the absence of detectable EBNA.

Animals↗
PubMed1980

Changes in the expression of two Epstein-Barr virus-associated antigens, EBNA and RANA, during the cell cycle of transformed human B lymphoblasts.

Two methods of cell sychronization, density-dependent arrest and double thymidine block, were used to assign two Epstein-Barr virus-associated antigens to different parts of the growth cycle of the human B lymphblastoid cell lines, WI-L2 and Raji. The Epstein-Barr nuclear antigen (EBNA), as detected by anti-complement immunofluorescence, was maximally expressed during early S phase, decreased during the G2 and M phases, and was absent in early G1. In contrast, the rheumatoid arthritis nuclear antigen (RANA), as detected by anti-immunoglobulin immunofluorescence with a prototype serum form a patient with rheumatoid arthritis, was maximally expressed during early G1 phase, progressively decreased during S and early G2, and reappeared during late G2/M.

Antigens, Viral↗
PubMed1980

Evidence for the presence of receptors for C3 and IgG Fc on human synovial cells.

The presence of receptors for IgG Fc and fragments of C3 on primary cultures and cryostat sections of normal and rheumatoid synovial tissues was assessed. Significant proportions of large rounded cells with asteroid projections found in such cultures had receptors for both IgG Fc and fragments of C3. Moreover, Gram negative bacteria that had fixed complement, but not EAC, bound in a linear fashion on the superficial layers of synovial cryostat sections. On the basis of morphologic and histochemical criteria, the cultured cells bearing these receptors were tentatively determined to represent a subset of synovial lining cells. The possible role of such receptors on synovial lining cells in the pathogenesis of rheumatoid arthritis is discussed.

Arthritis, Rheumatoid↗
PubMed1980

Tumor directed antibody and carcinoembryonic antigen in the glomeruli of a patient with gastric carcinoma.

A patient dying of gastric carcinoma was one of a group of cancer patients examined for the presence of glomerular immune complex deposits not associated with the nephrotic syndrome. The deposits were distributed in the mesangial and subendothelial regions. This distribution is found in experimental animals with neoplasia and glomerulopathy as well as in over 30 per cent of humans with cancer. Immunofluorescence showed IgG and C3 in the patient's glomeruli. Carcinoembryonic antigen was identified in the patient's glomeruli by the immunoperoxidase staining method. An IgG antibody was eluted from the kidney and found to be reactive with the patient's tumor, as well as another patient's colonic carcinoma. This reactivity was blocked by preincubation of the tumor substrate with anticarcinoembryonic antigen. Thus, both a tumor associated antigen and a corresponding antibody were shown to be contained in the glomerular deposits. It is concluded that circulating immune complexes of high molecular weight containing carcinoembryonic antigen produced by the gastric carcinoma led to the formation of subendothelial deposits without significant renal damage. This is in contrast to the usual finding of membranous glomerulonephritis among cancer patient with the nephrotic syndrome and more closely resembles the animal models. Whereas tumor reactive antibodies can be found in the glomeruli of patients with cancer, a specific tumor associated antigen to which the antibody is reactive has only occasionally been demonstrated.

Adenocarcinoma↗
PubMed1980

Kawasaki disease in healthy young adult.

This report describes a 26-year-old woman who fulfills the criteria for the diagnosis of Kawasaki disease or mucocutaneous lymph node syndrome, an acute febrile illness that usually afflicts young children. The diagnosis is made in persons with fever lasting 5 or more days when four of the following criteria are met: bilateral injection of ocular conjunctivae; the involvement of the mucous membranes of the upper respiratory tract consisting of any combination of the following--redness and fissuring of lips; "strawberry tongue," or erythema of the pharynx; involvement of the peripheral extremities characterized in the early stages by an indurative erythematous rash of palms and soles followed by membranous desquamation; polymorphous nonvesicular truncal exanthem; and acute nonsuppurative enlargement of cervical lymph nodes. An added stipulation is that the illness must not be attributable to a known disease process.

Adult↗
PubMed1979

Antibodies to Epstein-Barr virus-determined antigens in normal subjects and in patients with seropositive rheumatoid arthritis.

Prior studies have shown that patients with seropositive rheumatoid arthritis (RA) have an increased frequency of precipitating antibody against a nuclear antigen, the RA nuclear antigen, detected in human B lymphoblastoid cell lines infected by Epstein-Barr virus. The present investigations demonstrate that patients with seropositive RA also have specifically elevated titers of antibodies to another, better-characterized Epstein-Barr virus-associated B cell antigen, the Epstein-Barr nuclear antigen, which is detected by anti-complement immunofluorescence. Titers of these two antibodies were not affected by absorption of rheumatoid factor from serum. Furthermore, patients with RA did not have elevated titers of antibodies against the Epstein-Barr virus capsid antigen or to three other species of human herpesviruses: herpes simplex type 1, varicella-zoster virus, and cytomegalovirus. In both normal individuals and RA patients there was a significant association between the presence of antibodies to RA nuclear antigen and the titers of antibody to Epstein-Barr nuclear antigen. Thus, normal subjects with antibody to RA nuclear antigen had titers of antibody to Epstein-Barr nuclear antigen equivalent to those of patients with RA and significantly higher than normal subjects lacking antibody to RA nuclear antigen. One interpretation of these results is that patients with seropositive RA derive from a larger population with enhanced immune responsiveness to B lymphocyte nuclear antigens determined by the Epstein-Barr virus.

Antibodies, Antinuclear↗
PubMed1977

Elution of tumor-directed antibody from kidneys of mammary tumor-bearing mice.

Immunoglobulin-containing eluates, prepared from kidneys of Paris RIII mammary tumor-bearing mice approximately 10 months old, were incubated with frozen sections of mouse mammary tumor and normal lactating mammary gland and examined by immunofluorescence. The eluates diffusely strained the tumor but did not stain the nonneoplastic lactating mammary gland. Mammary tumor and normal lactating mammary gland were both stained by an antiserum to mammary tumor virus (MuMTV). The euglobulin portion of the eluates, when fractionated on a Sephadex G-200 column, yielded an IgG fraction which was shown by immunodiffusion to react with Paris RIII mammary tumor extract and with anti-mouse globulin but not with nonneoplastic mouse tissue extracts. Since the lactating mammary glands of these animals contain MuMTV, the antibody-containing fraction eluted from the kidneys appeared to be tumor directed rather than virus directed.

Animals↗