Biomedical subjects

O Majdic

Publications and source records attributed to O Majdic.

At least 127 records · Page 7Linked to original sources

PubMed1986

Analysis of CD3-antibody-mediated inhibition of T-cell activation.

In this study the influence of a non-mitogenic anti-CD3 antibody on accessory cell-dependent antigen and mitogen-induced T-lymphocyte proliferation has been investigated. The antibody was found to completely inhibit PHA, Con A, PWM, and tetanus toxoid stimulation, with no effect on the proliferation induced by the calcium ionophore A23187. VIT3 completely abrogated the production of IL-2 by lectin-stimulated T cells. It had no effect, however, on the IL-2-dependent proliferation of preactivated T-cell blasts. In addition, the antibody was able to elevate free cytoplasmic Ca2+ levels within minutes after the addition to T cells. Detailed time kinetic analyses revealed that the time interval critical for inhibition was significantly dependent on the interaction between T cells and accessory cells. Under standard conditions, in the presence of 10% non-T cells as accessory cells 50% inhibition was still achieved when VIT3 was added to PHA-stimulated T cells as late as 8 hr after the onset of culture. Delayed addition or a decrease in the number of added accessory cells significantly prolonged this time period. Lectin-stimulated T cells can thus obviously be inhibited via CD3 as long as they have not received all signals including those delivered by accessory cells. Although the underlying mechanisms are not clear so far, the observation that VIT3 at the same time triggers an early cytoplasmic Ca2+ response might indicate that it thereby actively interferes with antigen and lectin-initiated activation processes.

Antibodies, Monoclonal↗

PubMed1986

[Lineage infidelity of leukemia cells].

We phenotyped 548 blast populations from patients with acute de novo leukemia with a panel of 27 monoclonal antibodies and an antiserum against the enzyme terminal deoxynucleotidyl-transferase (TdT). In 56 cases (10,2%) we found a marker profile consisting of both myeloid and lymphoid characteristics (biphenotypic) leukemia = interlineage infidelity). In 49 out of the 56 cases the blast populations were clearly related to the myeloid (n = 41) or the lymphatic (n = 8) system. In those blast populations only one characteristic of the other differentiation could be detected. However, in 7 cases more than one myeloid as well as lymphatic characteristics were found on the same blast cells. In 4 cases (0.7%) the immunological phenotyping indicated the presence of two separate blast populations. The occurrence of a stem cell leukemia, an abnormal derepression of a genome, a defect of the membrane synthesis and the existence of a normal counterpart are taken into consideration as a cause of an "atypical" marker profile.

Acute Disease↗

PubMed1985

[Immunologic phenotypes of germinal center cell tumors].

A panel of monoclonal antibodies applied to frozen sections of non-Hodgkin's lymphomas was used to establish clear-cut differences among the different entities of malignant lymphomas of germinal centre cell origin. 51 cases (18 centrocytic, 25 centroblastic-centrocytic and 8 centroblastic lymphomas) were included in this study. A clear-cut difference in the expression of the T65 antigen (Leu 1+) and the common acute lymphoblastic leukaemia antigen (CALLA) was found. Thus, centrocytic lymphomas predominantly expressed Leu 1, but not CALLA, whereas centroblastic-centrocytic lymphomas were always positive for CALLA, but not for the T65 antigen. Centroblastic lymphomas are virtually never positive with respect to either antibody. These findings suggest that, perhaps, two different phenotypes of centrocyte exist in centrocytic and centroblastic-centrocytic lymphomas.

Adult↗

PubMed1985

[Considerations on the therapeutic use of monoclonal antibodies].

The availability of monoclonal antibodies (MoAb) decisively improved and extended the analytical and diagnostic possibilities both in science and in clinical medicine. Monoclonal antibodies are also important tools for the isolation and purification of biologically active components. However, the therapeutic applications of monoclonal antibodies require manifold clarification. In this manuscript an attempt is made to present a short survey of the current stage of development in the therapeutic applications of MoAb and to discuss the foreseeable future in this research area. Possible fields of application, such as selective cell manipulation, drug targeting, detoxification by neutralization and/or immune clearance, specific antibody substitution are summarized and the negative and positive results so far achieved are discussed. Ex vivo therapy with monoclonal antibodies, which has already been used in a number of hospitals, is dealt with in detail. Problems already encountered, as well as anticipated in the course of the therapeutic implementation of monoclonal antibodies are discussed.

Antibodies, Monoclonal↗

PubMed1985

Quantitation of antibody uptake on A group erythrocytes using immunoautoradiography and monoclonal IgM anti-A.

The number of antibody molecules on individual erythrocytes was counted in A1, A2, A3 B and A group individuals using immunoautoradiography (IAR) and monoclonal IgM anti-A1. Quantitation was also done for A group pregnant women. The number of antibody molecules on different red cells of an individual varied widely. Gross variations were also noted in cells of different individuals from one and the same group. The mean values of the uptake of the number of antibody molecules showed the following range A1 greater than A2 greater than Ax greater than A3B. When compared to the average for total A1 adults, red cells of pregnant women and newborn infants showed a 10.7% and 19.7% reduction respectively, in antibody uptake. The mean number of antibody molecules per A1 adult red cells was 5.6 +/- 3 X 10(4), while A2 had 0.85 +/- 0.35 X 10(4) molecules, thus showing a significant quantitative variation.

ABO Blood-Group System↗

PubMed1985

Shared antigenic determinants between human hemopoietic cells and nervous tissues and tumors.

A panel of nine monoclonal antibodies raised against human hemopoietic cells was used for immunohistological labeling of frozen sections of human nervous tissues and tumors. Three antibodies showed a remarkably consistent labeling pattern when tested on 18 samples of normal or reactive tissue, on 31 neurogenic and 17 non-neurogenic tumors in an indirect immunofluorescence technique. VIM C6, an antibody recognizing cells of the granulocyte series, showed surface labeling of normal and reactive glial cells and of all types of glioma regardless of the grade of malignancy. VIT 13, an antibody recognizing activated T-cells, labeled the processes of normal, reactive, and neoplastic glia in a manner very similar to but not identical with glial fibrillary acidic protein (GFAP). VIB C5, an antibody recognizing B cells and granulocytes, showed surface labeling restricted to malignant cells (malignant gliomas and primitive neuroectodermal tumors) and fetal brain, thus recognizing, within the nervous system, an oncofetal antigen. Due to this operational specificity within the nervous system, some of the antibodies described here might have a role as diagnostic markers for CNS tumors. This study confirms and expands previous data that sharing of antigenic determinants by hemopoietic cells and nervous tissue or neurogenic tumors is common. However, the significance of such cross-recognition is still obscure. It is tempting to speculate that cross-reacting auto-antibodies might contribute to tissue damage in some immune-mediated neurologic diseases (myasthenia gravis, multiple sclerosis, CNS involvement in systemic lupus erythematosus) or to impairment of immunoregulation in multiple sclerosis or glioma patients. Furthermore, sharing of surface determinants might be responsible for the dual tissue tropism of some viruses, including the lymphotrophic virus (HTLV) in the encephalopathy of the acquired immune deficiency syndrome (AIDS).

Antibodies, Monoclonal↗

PubMed1985

Cross-reactivity between human hemopoietic cells and brain tumors as defined by monoclonal antibodies.

A battery of 24 monoclonal antibodies raised against human hemopoietic cells was tested in an indirect immunofluorescence technique on frozen sections of a variety of human neurogenic and non-neurogenic tumors. Twelve antibodies demonstrated some type of labeling of neurogenic tumors, frequently in patterns characteristic for benign and/or malignant gliomas and/or primitive neuroectodermal tumors (PNETs). Although also some cross-reactivity occurred in non-neurogenic tumors, the apparent operational specificity of some of our antibodies within the nervous system promises some aid in neuropathological tumor diagnosis; this was also demonstrated by combined use of some antibodies on smear preparations in which diagnosis by conventional stains was uncertain. This study confirms and expands previous data that sharing of antigenic determinants by hemopoietic cells and nervous system tumors is common. The significance of these cross-reactivities is at present a matter of speculation; cross-reacting autoantibodies might interfere with immune regulation in tumor patients, and an immune response might be initiated when glioma cells bearing Ia antigens present tumor-associated antigens to T cells.

Adolescent↗

PubMed1985

Kinetics of activation antigen expression by in vitro-stimulated human T lymphocytes.

In this study a panel of monoclonal antibodies was used to investigate the kinetics of the appearance of activation-linked surface determinants as well as cytoplasmic and nuclear determinants in human T cells following lectin stimulation. Well known activation markers, such as Ia/DR, transferrin receptor, IL-2 receptor, T10, and gp24, were compared and investigated together with the T13 structure, recently found in this laboratory. T13, not demonstrable on resting T cells, could be seen within 24 hr after lectin stimulation. Kinetics of the appearance were similar to IL-2 receptor and transferrin receptor expression. Ia/DR synthesis was investigated separately for each polypeptide and the cytoplasmic invariant gamma-chain expression could be demonstrated for the first time with a gamma-chain-specific monoclonal antibody VIC-Y1. Moreover, gamma-chain synthesis seems to precede alpha- and beta-chain occurrence in human T cells. In addition, data from quantitative studies on antigenic densities are presented.

Antibodies, Monoclonal↗

PubMed1985

Unexpected absence of a myeloid surface antigen (3-fucosyl-N-acetyllactosamine) in promyelocytic leukemia.

According to the criteria of the FAB classification we diagnosed acute promyelocytic leukemia in 19 out of 191 AML blast cell populations. The reaction pattern with the anti-myeloid monoclonal antibodies VIM2, MCS2 and MY9 and the MHC-class II antibody VID1 in all cases showed the characteristics which were expected from the normal granulopoiesis. The monoclonal antibody VIM-D5, which recognizes the myeloid cell surface structure 3-fucosyl-N-acetyllactosamine (3-FAL), was not reactive with the majority of promyelocytic blast cells, however. In 13 cases 3-FAL was not detectable and in 6 cases only low or moderate reactivity of VIM-D5 with blast cells was observed. The phenotype of leukemic promyelocytes thus differs from the majority of normal promyelocytes in this respect.

Antibodies, Monoclonal↗

PubMed1985

Cell lineage heterogeneity in blast crisis of chronic myeloid leukaemia.

Blast cells from 45 patients with chronic myeloid leukaemia in blast crisis (CML-BC) were immunologically phenotyped with a panel of 26 monoclonal antibodies and studied for terminal deoxynucleotidyl transferase (TdT) content. Out of 45 blast-populations, 28 showed a myeloid, 14 a lymphoid, two a mixed and one an unclassifiable marker profile. In contrast to acute myeloid leukaemia (AML), we found frequent involvement of the thrombopoietic and erythropoietic systems in myeloid CML-BC. Furthermore, the marker profile on blast cells in myeloid CML-BC was different from that seen in AML. The blast cells in lymphoid blast crises of CML displayed the same lymphoid marker profile as those in acute lymphoblastic leukaemia. In three of 16 patients who were serially tested, we observed phenotypic changes in the blast cell populations. In one patient the blasts changed from lymphoid to myeloid type while remaining TdT-positive; in another case the blasts switched from granulomonocytic TdT-negative to granulomonocytic TdT-positive. In the third patient erythroid precursor cells appeared as the disease progressed. The results indicate the capacity of blast populations in CML-patients during blast crisis to differentiate along several pathways.

Adolescent↗

PubMed1985

Monoclonal antibody to a 43 000 Mr surface protein of a human leukaemia cell line (THP-1) crossreacts with the fibroblast intermediate filament protein vimentin.

Monoclonal antibodies were produced against surface antigens of live cells from a human acute monocytic leukaemia cell line (THP-1). One clone, VIC-C2, when assayed by immunofluorescence microscopy, brightly stained the surface of THP-1 cells and the cytoplasm of Langerhans cells, fibroblasts and melanocytes in sections of human skin. The immunoreactive cytoplasmic structures were filamentous and resembled intermediate filaments. By double immunofluorescence microscopy using VIC-C2 and polyclonal antibodies to vimentin, the VIC-C2 antigen was shown to be located on intermediate filaments of cultured fibroblasts and to follow these filaments during various drug-induced rearrangements. As demonstrated by immunoprecipitation, antibody gel overlay and immunoblotting of two-dimensional polyacrylamide gels, VIC-C2 recognized two different antigens in extracts of THP-1 cells: one of Mr = 43 000 and pI = 7, the other of Mr = 57 000. In extracts from various cultured fibroblast cells only the 57 000 Mr antigen was detected. This 57 000 Mr protein was identified as vimentin by immunoblotting of rat glioma C6 cytoskeletons on two-dimensional gels. When vimentin was digested with chymotrypsin, only fragments containing parts of both helical rod pieces and the connecting non-helical spacer-region were strongly antigenic, whereas the helical rods alone were only weakly crossreactive. Moreover, immunoprecipitation revealed that VIC-C2 preferentially reacted with native compared to denatured vimentin.

Antibodies, Monoclonal↗

PubMed1985

Differences in the fine specificities of monoclonal (Class A) antibodies to human myeloid cells.

Among 13 monoclonal antibodies to human myelomonocytic cells, six could be assigned to a group designated Class A with the following properties: (a) they react almost exclusively with granulocytes among cells of the peripheral blood, (b) they resemble the previously described anti-granulocyte antibodies, VEP8 and VEP9, and the anti-mouse embryo, anti-SSEA-1, in their strong reactions with human meconium glycoproteins and ovarian cyst mucins of non-secretor type and (c) they recognize the carbohydrate antigen 3-fucosyl-N-acetyllactosamine (alpha 1----3fucosylated Type 2 blood group chains). The binding of these anti-myeloid antibodies is more strongly inhibited by lacto-N-fucopentaose III than by the trisaccharide-fucosyl-N-acetyllactosamine, in contrast to anti-SSEA-1 which is more strongly inhibited by the trisaccharide. These observations suggest that the myeloid Class A antibodies recognize additional determinants on the neolacto (Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4) backbone of the pentasaccharide which occurs on the glycoproteins and glycolipids of myeloid cells. However, no two of the anti-myeloid antibodies were identical in their inhibition patterns with the glycoproteins and the two oligosaccharides. They also differed in their cellular reactivities, for example, the proportion of cells in the K-562 cell line reacting with each antibody ranged from 15-57%.

Antibodies, Monoclonal↗

PubMed1985

5q- chromosome in acute leukemia with lymphoid morphology and expression of myeloid membrane determinants.

We present three patients, two children and one adult, with an unusual type of acute leukemia. Whereas the blast cells showed lymphoid morphology with correlating cytochemical staining, immunological phenotyping exhibited a pure myeloid in one patient and a biphenotypic membrane marker profile in the other two patients. Cytogenetic studies revealed a 5q- chromosome as a common marker and additional individual changes. Two of the patients who were treated according to acute lymphoblastic leukemia (ALL) therapy protocols died without remission five and four weeks after diagnosis, respectively. Despite relapsing several times, another patient survived for over eight years. These three patients seem to represent one new subgroup of leukemias that can only be distinguished from typical ALL by both determination of cell surface markers and cytogenetic analysis.

Aged↗

PubMed1985

Analysis of T cell activation with a non-mitogenic anti CD3 antibody and the phorbol ester TPA.

We used a non mitogenic anti CD3 antibody, termed VIT3, to study the signals required for the activation of normal resting T lymphocytes. Besides being not mitogenic, this antibody completely inhibits mitogen induced proliferative responses. In the presence of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), however, VIT3 induces DNA replication and cell proliferation comparable to PHA responses. In addition, T cells cultured with VIT3 plus TPA but not with VIT3 or TPA alone express high levels of interleukin 2 (IL-2) receptors and transferrin receptors. This co-stimulation appears to be accessory cell independent. Purified T cells respond equally well to VIT3 plus TPA as do unseparated mononuclear cells and addition of non-T cells has no enhancing effect. We conclude that the IgM antibody VIT3, although non-mitogenic by itself, still delivers a first and for the activation essential signal. In resting T cells this signal does not induce demonstrable anti-Tac antibody binding nor does it lead to a fully developed proliferative response in the presence of recombinant IL-2. Together with a second signal provided by TPA it serves, however, as a potent inducer of T cell growth.

Animals↗

PubMed1985

Lymphocytes of haemophilia patients treated with clotting factor concentrates display activation-linked cell-surface antigens.

Peripheral blood lymphocytes from 30 patients with haemophilia A were investigated for the expression of six activation-linked cell surface antigens as well as with regard to the relative proportions and total numbers of Leu-3a and Leu-2a positive cells. Twenty-nine of the haemophilia patients showed no clinical symptoms of immunodeficiency or infection whereas one patient presented the typical symptomatology of the acquired immunodeficiency syndrome (AIDS). The proportions and total numbers of circulating lymphocytes displaying Ia antigens, the p45 protein and/or the two recently defined surface antigens VIP-4 and VIP-5 were significantly increased in haemophilia patients when compared to healthy individuals of the same age group. No such increases could be observed for transferrin receptor and IL-2 receptor expression. After the observation of depressed helper/suppressor T-cell ratios in many haemophiliacs, the expression of activation linked surface antigens represents a further lymphocyte abnormality which resembles the findings in AIDS and its prodromal stages and can also be found in certain viral and parasitic diseases.

Acquired Immunodeficiency Syndrome↗

PubMed1985

Studies on differentiation of committed hemopoietic progenitor cells with monoclonal antibodies directed against myeloid differentiation antigens.

In the present study we evaluated the reactivity of monoclonal cytotoxic antibodies directed against myeloid differentiation antigens with hemopoietic precursor cells. VIM-D5 and VIM-2 inhibit the proliferation of clusters and colony formation after seven days of incubation. Day-14 CFU-GM are not affected by these antibodies. After complement-mediated cytolysis with VIM-2, the number of BFU-e was significantly reduced; however, this effect was largely abrogated by addition of leukocyte-conditioned medium to the cultures as an exogenous source of burst-promoting activity. Furthermore, the maturation of myeloid progenitor cells has been examined by delayed treatment with VIM-D5 and complement during the in vitro culture period. In these experiments a different maturation behavior of day-7 and day-14 CFU-GM was demonstrated. To study whether a cryptic carbohydrate structure is present on more immature CFU-GM, the effect of neuraminidase treatment of myeloid progenitor cells on reactivity with VIM-D5 was tested.

Antibodies, Monoclonal↗

PubMed1984

Evidence of HLA-DR antigen biosynthesis by human keratinocytes in disease.

As opposed to normal human skin where HLA-DR expression is restricted to the Langerhans cell (LC) population, HLA-DR, but not HLA-DS antigens can be readily detected on keratinocytes (KC) in certain disease states, i.e., cutaneous T cell lymphoma (CTCL), graft-vs-host disease (GVHD), and lichen planus (LP). To clarify the cellular origin of KC-bound HLA-DR antigens, we used a monoclonal antibody directed against determinants solely expressed on the cytoplasmic HLA-DR gamma chain (VIC-Y1) and observed that, by immunofluorescence, KC displaying HLA-DR alpha/beta complexes on their surface uniformly displayed cytoplasmic VIC-Y1 reactivity. In view of the crucial role of the gamma chain for HLA-DR biosynthesis, we conclude that HLA-DR antigens on KC are actively synthesized by these cells.

Epidermis↗

PubMed1984

M2, a novel myelomonocytic cell surface antigen and its distribution on leukemic cells.

The selectivity of a novel myelomonocytic cell surface antigen, designated M2, has been assessed in a series of 208 leukemias. The M2 antigen is defined by a monoclonal antibody (VIM-2) of the IgM class. Its expression within the normal hemopoietic system is restricted to myelomonocytic cells. Lymphocytes, erythrocytes, thrombocytes and their morphologically recognizable precursors are negative. Sixty of the 66 acute myeloblastic leukemias (= 91%) and 28 of the 30 myeloid blast crises of CML patients (= 93%) were M2-positive. As expected from our findings with normal myeloid cells, the myeloid cells found in stable phase of CML were also in all instances, M2-positive. Quite in contrast, lymphoid cells from patients with B-CLL, T-CLL, prolymphocytic leukemia, hairy-cell leukemia, lymphoblastic lymphoma, Sézary syndrome, from CML patients in lymphoid blast crisis and from the majority of patients with ALL, were completely M2-negative. Also negative were the blast cells of patients with acute megakaryoblastic leukemia and acute erythroleukemia. A direct comparison of M2 expression with the display of the 3-fucosyl-N-acetyllactosamine determinant, the structure recognized by most of the anti-myeloid monoclonal antibodies reported so far, shows that more AMLs are M2-positive and the proportion of M2-positive blast cells in individual AML samples is higher.

Antibodies, Monoclonal↗