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Biomedical subjects

O Majdic

Publications and source records attributed to O Majdic.

At least 145 records · Page 8Linked to original sources

Malignant histiocytosis with unusual features. Disseminated intravascular coagulation with severe hyperfibrinolysis, acute polyneuroradiculitis Guillain-Barré, and a unique chromosome abnormality.

The case of a 25-year-old man with the characteristic features of malignant histiocytosis (proliferation of abnormal histiocytic cells with erythrophagocytosis, hepatosplenomegaly, increased serum acid phosphatase, hypercalcemia, and bone pain) is reported. Chromosome studies revealed a near tetraploid karyotype with a pair of marker chromosomes. A few hours after initiation of chemotherapy with cyclophosphamide, Adriamycin (doxorubicin), vincristine, and prednisolone (CHOP regimen), the patient developed an acute ascending paralysis. Cerebrospinal fluid (CSF) findings were consistent with a diagnosis of Guillain-Barré Syndrome. On the next day, disseminated intravascular coagulation (DIC) with severe hyperfibrinolysis occurred. After intensive chemotherapy, complete remission could be achieved.

Adult↗

Monoclonal antibodies to human myelomonocyte differentiation antigens in the diagnosis of acute myeloid leukemia.

The immunological definition of malignant lymphatic cells has already been routinely applied by many laboratories over a number of years. Today it is clear and undisputed that the phenotypic data obtained in that way are often very useful and supporting. The immunological definition of non-lymphoid leukemias is not yet as far advanced. Additional surface markers for the recognition of poorly differentiated non-lymphoid cells are clearly needed. In this paper ten monoclonal antibodies to myeloid surface antigens are described. It is hoped that they are a useful addition to the presently available relatively small panel of well studied myeloid surface markers which are displayed by immature malignant blast cells.

Antibodies, Monoclonal↗

Diagnostic specificity of the monoclonal anti-CALLA antibody VIL-A1 in leukemia and malignant lymphoma.

VIL-A1 is an anti-CALLA antibody which binds efficiently and exclusively to CALLA positive cells. When the cell type specificity of VIL-A1 is studied in acute leukemias and lymphomas, results show that in those leukemias which could be characterized by cytochemical and morphological methods, VIL-A1 reactivity was specific for cells of lymphoid origin. It can therefore be assumed that VIL-A1 positive AUL cells (in this case 4 out of 9 patients) are also lymphoid in origin. In no case were AML blasts found to be positive with this antibody. Seventy-four per cent of the 88 ALL patients were positive (L1 + L2) whereas none in the L3 subgroup were positive, and 48% of CML patients in blastic crisis were positive. Of the low grade non-Hodgkin malignancies, only CB/CC was positive, distinguishing it from the CC type which was negative. Of the high grade lymphomas IB was found to be negative, while the others showed a heterogeneous picture which was not related to other immunological parameters.

Acute Disease↗

A human Ia cytoplasmic determinant located on multiple forms of invariant chain (gamma, gamma 2, gamma 3).

An antigenic determinant present in the cytoplasm, but not on the surface membrane of human Ia+ cells, is defined by a monoclonal antibody (VIC-Y1) and is shown by immunoprecipitation and by NEPHGE to be expressed by Ia oligomers. Immunoprecipitations of cellfree translates and of purified Ia subunits indicate that the VIC-Y1 determinant is located on the Ia gamma-(invariant) chain, as well as on two other related molecules, provisionally termed gamma 2 and gamma 3. Within our experimental conditions, the three forms of gamma-chains co-precipitate exclusively with Ia oligomers. As detected by VIC-Y1 and in the limits of our assays, gamma-chains could not be found at the cell surface; their tissue distribution, determined by cytoplasmic indirect immunofluorescence with VIC-Y1, closely resembles that of Ia antigens, with the possible exception of acute lymphatic leukemia cells (Ia+, gamma-chain-).

Animals↗

Exposure by desialylation of myeloid antigens on acute lymphoblastic leukemia cells.

The 3-fucosyl-N-acetyllactosamine structure, a sugar sequence contained in the human milk oligosaccharide lacto-N-fucopentaose III, is recognized by most of the granulocyte-specific monoclonal antibodies (MoAb) reported in the literature, including the six MoAb from our laboratory. Blast cells from patients with acute myeloblastic leukemia (AML) displayed a heterogeneous reaction pattern when they were exposed to MoAb against this moiety, and the proportion of reactive cells in individual cell samples was highly variable. The intensity of the reaction was strongly enhanced by neuraminidase treatment of AML blasts, and reactive structures were exposed on previously negative AML blast cells. Surprisingly, this granulocyte-associated antigen was exposed by desialylation not only on malignant myeloid precursor cells but also on common acute lymphoblastic leukemia cells. No such effect was seen when normal peripheral blood lymphocytes, lymphocytes from patients with chronic lymphatic leukemia, or blast cells from patients with B-cell acute lymphoblastic leukemia, acute erythroid leukemia, and acute megakaryoblastic leukemia were treated with neuraminidase.

Animals↗

Glycophorin A expression in malignant hematopoiesis.

Two hundred twenty-nine patients with hematopoietic malignancies were tested for reactivity with a monoclonal anti-human glycophorin A antibody. One hundred twenty-three of these cases were classified as acute leukemias of either the myeloid, lymphoid, erythroid, or undifferentiated type. The monoclonal antibody we used (VIE-G4) was obtained after immunization with a human thymocyte suspension. It selectively reacts with glycophorin A (GpA) and strongly binds to 40% of K-562 cells and all morphologically recognizable erythroid precursor cells. Apart from two cases with acute erythroid leukemia, this antibody reacted with none of the malignant cells in the 229 tested hematopoietic malignancies, including the 121 nonerythroid acute leukemias. This finding seems to contradict the earlier observations by L. Andersson and colleagues that a considerable proportion of acute leukemias express GpA on their surface. One reason for this discrepancy might be the fact that VIE-G4 detects only complete glycosylated GpA. If this is the sole explanation, this would mean that the poorly differentiated cells in these cases express incompletely glycosylated GpA.

Acute Disease↗

Distinct lymphoblastic and myeloblastic populations in TdT positive acute myeloblastic leukemia: evidence by double-fluorescence staining.

Double-immunofluorescent staining for the enzyme terminal deoxynucleotidyl transferase (TdT) as a marker of primitive lymphoblasts, and for the VIM-D5 antigen as a differentiation antigen of the myeloid system gave direct evidence for distinct lymphoblastic and myeloblastic populations (mixed leukemic cell populations) in seven patients with acute leukemia. The percentage of malignant TdT positive cells contributing to a leukemic cell bulk with unequivocal signs of myeloid origin was between 10 and 80%. A defect at the level of a common progenitor cell giving rise to both the TdT and the VIM-D5 positive blast cell population is discussed.

Antibodies, Monoclonal↗

Phenotypes of human large granular lymphocytes as defined by monoclonal antibodies.

Four monoclonal antibodies VEP8, VEP9, VIM-D5, VIB-C5 against antigens expressed on human mature myeloid cells (polymorphonuclear leukocytes [PMNL] and/or monocytes) as well as on immature cells in the bone marrow were tested for reactivity with cell preparations highly enriched for large granular lymphocytes (LGL). These cells are known to be the main effector cells responsible for natural killer (NK) cell activity in human peripheral blood. Using indirect membrane immunofluorescence (IMF), none of these antibodies showed any reactivity at all. In addition, LGL-enriched cell preparations were tested with the anti-lymphocyte monoclonal antibodies OKT6, anti-Leu1, anti-Leu2a, anti-Leu3a, and anti-human Lyt3, and also with OKM1 antibody. Significant reactivity was found with anti-Leu2a (59 +/- 8%), anti-Lyt3 (55 +/- 4%) and OKM1 (81 +/- 11%) antibodies, whereas T6, Leu1, and Leu3a antigens were less pronounced or missing on LGL. As a further approach, another monoclonal antibody, VEP13, which reacts with LGL, granulocytes but not monocytes and is therefore different in its specificity from OKM1 and OKT10, was used for identification of LGL. The coexpression of antigens as defined by the above-mentioned antibodies and OKT10 on VEP13+ cells was studied. Again, phenotypes similar to those observed on LGL enriched by Percoll gradient centrifugation were found: of VEP13+ cells 84 +/- 6% reacted with OKM1, 82 +/- 5% with OKT10, 52 +/- 17% with anti-human Lyt3, and 48 +/- 14% with anti-Leu2a, whereas VEP8, VEP9, VIM-D5, VIB-C5, T6, Leu1, Leu3a antigens were not expressed on VEP13+ cells. Taken together as an overall evaluation of phenotypic characteristics, our data indicate that LGL cannot be integrated into one of the known lymphocytic or myelomonocytic lineages. LGL show an intermediate phenotype depending possibly on varying differentiation or activation stages of haemopoietic cells. However, the possibility also exists that LGL belong to a separate, yet undefined cell lineage.

Antibodies, Monoclonal↗

Surface antigens defined by monoclonal antibodies as tumor markers in human leukemia.

The detection of surface-linked antigenic determinants by heteroantisera has greatly contributed to a better understanding of the heterogeneity of benign and malignant hematopoietic cells. The difficulties encountered in rendering these heteroantisera specific for a unique cell surface component have been a major drawback to a more rapid development of immunologic cell typing. With the introduction of hybridoma technology, it became possible to obtain monoclonal antibodies and markedly improve immunologic cell typing. We have, therefore, used this new technology for the production of monoclonal antibodies against human leukocyte surface antigens. This paper describes four cell type-specific monoclonal antibodies, which turned out to be very useful reagents in leukemia diagnosis. One of these antibodies, VIM-D5, is directed against a myeloid cell surface antigen. VIL-A1 is specific for the common acute leukemia associated antigen. VIB-C5 recognizes B-cell differentiation antigen and VIE-G4 is specific for glycophorin A, and thus detects erythroid precursor cells.

Antibodies, Monoclonal↗

[Diagnosis of leukemia with monoclonal antibodies].

The diagnosis and classification of leukaemic diseases is still primarily based on morphological and cytochemical criteria. Interpretational difficulties occur quite frequently, especially in acute leukaemias. Subjective morphological cell-type characterization--which is acquired only after many years of experience--is rather unsatisfactory in the long run. Therefore in order to obtain uniform results in all haematological areas, new methods are needed. In principle, immunological cell-type characterization represents an alternative method. By applying requisite antibodies practically any cell component can be demonstrated and quantitated. Up to recently the major obstacle to a more rapid development of immunological cell typing was the lack of specific antisera, but with the introduction of hybridoma technology it became possible to obtain monoclonal antibodies and thus, markedly improve immunological cell typing virtually overnight. We have, therefore, used this new technology for the production of monoclonal antibodies to human leucocyte antigens. This paper describes six of the cell-type specific monoclonal antibodies obtained, their suitability for diagnostic purposes and the classification of human leukaemias. With the help of these antibodies the majority of human leukaemias can now be typed. Without claiming completeness and in full awareness of the fact that a number of problems remain to be solved, we nevertheless believe that the presented data point to the possibilities opened up by this technology for leukaemia diagnosis in the future.

Animals↗

Comparison of currently available monoclonal antibodies with conventional markers for phenotyping of one hundred acute leukemias.

One hundred acute leukemia cell samples (89 ALL, 11 AMML) derived from children's bone marrow at diagnosis were typed for the reaction with 15 monoclonal antibodies (mAbs). Subdivision in ALL-subgroups was performed according to conventional markers. Only some mAbs like VIL-Al which is directed against the cALL-antigen, can substitute polyclonal rabbit antisera. Additional subclassifications became evident by the use of mAbs for T-cell differentiated ALL forms. However, unexpected negative reactions must be taken into account as observed for all T-directed mAbs with individual T-cell ALL samples.

Acute Disease↗

VIL-A1, a monoclonal antibody reactive with common acute lymphatic leukemia cells.

The VIL-A1 monoclonal antibody raised against Reh cells reacts with common acute lymphatic leukemia (CALL) cells but not with normal or malignant B or T lymphocytes. It also shows no binding to normal or malignant myeloid, monocytic or erythroid cells, nor does it react with thrombocytes. The antibody is of IgM class and lyses CALL cells very efficiently in the presence of rabbit but not human complement. Immunoprecipitation experiments followed by SDS-polyacrylamide gel electrophoresis under reducing conditions revealed that VIL-A1 defines a 95,000 mol. wt membrane protein. Approximately 40% of it binds to lens culinaris lectin. Capping experiments showed that the membrane component defined by VIL-A1 co-caps with the one recognized by another recently described monoclonal antibody to CALL cells (J5).

Antibodies, Monoclonal↗

In vitro effects of cyclosporin A (CSA) on human hemopoietic cell lines.

The sensitivity of 18 permanent hemopoietic cell lines to Cyclosporin A (CsA) was tested in a 3H-thymidine incorporation rate assay. Two human T cell lines (Molt4 and CEM) were significantly inhibited by a CsA concentration of 0.5 microgram/ml. Not affected at all or only inhibited by 10 to 20 times higher CsA concentrations were: three human B cell lines (4413a, Daudi, Raji), a monkey B cell line (B95-8), a mouse plasmocytoma line (X63-Ag8/653), a human non-B T cell line (Reh), four human myeloid lines (HL-60, ML-1, ML-2, ML-3), a human myelomonocytic line (Karpas 230), four human monoblastic lines (U 937, SU-DHL-1, THP-1, Karpas 241) and a human erythroid line (K 562). It therefore seems that among permanently growing hemopoietic cells a cell type specificity for T cells also exists.

Animals↗

Monoclonal antibodies to the structural glycoprotein of tick-borne encephalitis virus.

Hybridomas secreting antibodies to the structural glycoprotein of tick-borne encephalitis (TBE) virus were prepared by fusion of X63-Ag8/653 mouse myeloma cells with spleen cells from mice immunized with purified glycoprotein complexes of TBE virus. These antibodies were tested against 10 different TBE virus strains isolated in different European countries over a period of 26 years from different hosts. Quantitative evaluation of enzyme immunoassay results did not reveal any differences in reactivity among these strains, pointing further to the homogeneity of European TBE virus isolates, which has previously been inferred from results obtained by peptide mapping and competitive radioimmunoassay. Hybridomas defining three different antibody-combining sites (epitopes) on the glycoprotein of TBE virus were selected on the basis of cross-reactivity with another flavivirus. West Nile virus, as well as the ability to inhibit hemagglutination. Two epitopes were type specific, and the third was indistinguishably also present on West Nile virus. Hemagglutination was inhibited by monoclonal antibodies reacting with one of the type-specific epitopes as well as the cross-reactive determinant, which is apparently responsible for the broad cross-reactivity among different flaviviruses observed in hemagglutination inhibition tests with polyvalent immune sera.

Animals↗

Expression of a myeloid marker on TdT-positive acute lymphocytic leukemic cells: evidence by double-fluorescence staining.

The expression of a myeloid-specific antigen was detected on TdT-positive blast cell populations in two cases of childhood acute lymphocytic leukemia. Double-fluorescence staining by using the monoclonal antibody, VIM-D5, which is specific for cells of myeloid origin, in combination with TdT antiserum revealed that a distinct portion of the blast cells carried both markers. The finding represents the first direct demonstration of this specific biphenotype in leukemic cells and was interpreted as the abnormal expression of a myeloid antigen on lymphoid blast cells.

Animals↗

[In vitro testing of human lymphocytes (author's transl)].

The use of surface markers for the characterization of various lymphocyte subpopulation today belongs to the standard techniques of immunological laboratories. Recently, functional in vitro testing of human lymphocytes has met with increasing interest. In this paper some of the relevant in vitro test systems such as the lymphocyte stimulation test, the determination of the B cell differentiation capacity in vitro and the demonstration of suppressor cell activity are discussed. Apart from a discussion of the results obtained by these techniques in normal, healthy individuals, the applicability of these techniques for studies in patients is dealt with.

B-Lymphocytes↗