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M Schaadt

Publications and source records attributed to M Schaadt.

At least 37 records · Page 2Linked to original sources

[Clinical relevance of immune phenotyping of malignant lymphomas].

The characterization of malignant lymphomas with immunological methods (immunophenotyping) is gaining increasing importance in clinical hematology. Immunophenotyping is not only a basis of modern classifications of non-Hodgkin's lymphomas (e.g. the Kiel classification), it can also be helpful in the differentiation of lymphomas from epithelial or mesenchymal tumors. The immunological identification of subgroups of acute lymphocytic leukemia (c-ALL, T-ALL and B-ALL) bears significant meaning for differential therapy. Other applications of immunophenotyping of malignant lymphomas in the near future will be the demonstration of receptors for certain lymphokines (e.g. for therapy with interleukin-2 or tumor-necrosis-factor), the detection of specific cell surface antigens (for immunotherapy with monoclonal antibodies) and the demonstration of immunological markers for resistance to cytotoxic drugs. A general application of immunophenotyping of malignant lymphomas in clinical hematology will depend on a better standardization of the immunological reagents, a simplification of logistic problems and a significant reduction of the costs.

Antigens, Neoplasm↗

Phenotypic and genotypic analysis of Hodgkin's disease derived cell lines: histopathological and clinical implications.

Five Hodgkin's disease (HD) derived cell lines were established in vitro in our laboratory in the last seven years. Morphological, cytochemical, immunological and cytogenetic marker analysis demonstrated that the in vitro cells represent genotypically and phenotypically the in vivo Hodgkin (H) and Sternberg-Reed (SR) cells in biopsy specimens. The cultured cells resemble haematolymphoid cells at different stages of maturation. Four of the five continue to grow in vitro as suspension cells after more than 50 months. Four more in vitro HD-derived lines were described recently by several authors. A summary of the various marker characteristics of these in vitro lines is given as a synopsis of the phenotypic marker spectrum and is discussed in comparison with our own cell lines. There is a striking similarity between two of the newly established lines (CO, HDLM-2) and our lines whereas the two other in vitro established cultures seem to resemble cell species further along the line of maturation to B lymphocytes (DEV) and monocytes (SU-HD-1). Gene rearrangement experiments undertaken with the L428, L540, L591 and the CO cell line show that the L428 and 591 cells have undergone gene rearrangement, the L428 being compatible with the genotypic state of a pre-B cell; the L591 cells, similarly rearranged furthermore demonstrated functional light chain rearrangement, compatible with B-cell development. By cytogenetic analysis chromosome 7 was found to be affected in all our described lines. This chromosome appears to be particularly unstable and vulnerable in patients with HD, since all tested cell lines revealed multiple abnormalities of this chromosome, a finding which is in accordance with observations made by other investigators in HD-biopsy cells. Since similar structural changes or loss of chromosome 7 is a characteristic event in cases of secondary acute non-lymphocytic leukaemia, it is speculated that this form of secondary neoplasia could resemble the blast crisis, as observed in chronic myeloid leukaemia.

Cell Line↗

[Properties of Hodgkin cell lines. Possible significance for pathophysiology and clinical medicine].

In the last three years, five permanently in-vitro growing cell cultures with malignant properties were established from tumour material of patients with histologically confirmed Hodgkin's disease. Four cell lines have been maintained in culture. L 428 had identical characteristics in every respect with Hodgkin and Sternberg-Reed cells, tested in-vivo on biopsy tissue. The other lines--L 538, L 540 and L 591 - had certain characteristics of Hodgkin and Sternberg-Reed cells with a number of markers, but were not fully congruent. All lines reacted with a heterologous antiserum against L 428, which selectively cross-reacted with Hodgkin and Sternberg-Reed cells in fresh biopsies. Two sublines, L 428 KS and L 428 KSA, were established from L 428 by modifying the culture medium. Tests on L 428 KS cells with conventional methods and with monoclonal antibodies demonstrated that this line carried antigens of myeloid cells; however, it could not be definitely placed into any haematopoetic line. Conditioned medium of L 428 and its sublines showed CSF activity (colony-stimulating factor) and suppression of cell-mediated cytolysis.

Acid Phosphatase↗

Production of colony-stimulating factors by Hodgkin cell lines.

This work was performed with L 428, a cell line established in 1978 from a patient with Hodgkin's disease. These in vitro cells represent counterparts of in vivo Hodgkin and Sternberg-Reed cells. L 428 and its derived sublines produce a significant amount of colony-stimulating factor (CSF) compared to standard preparations of CSF (fetal liver conditioned medium). Hodgkin-cell-derived conditioned medium, tested in cord-blood assays and in semi-solid agar systems, induced myeloproliferation predominantly. Production of CSF is independent of fetal calf serum concentration in the cultures. L 428-conditioned medium could provide an excellent source for characterization and purification of granulocyte CSF.

Cell Line↗

Hodgkin's disease cell lines: characteristics and biological activities.

In the last 4 years we have established five long-term cultures from tumor material of Hodgkin's disease. The in vitro cells have malignant characteristics and represent the in vivo Hodgkin- and Sternberg-Reed-cells as shown by the identity of multiple properties. Common immunological, functional, and morphological assays did not characterize the in vitro cells as a known cell type of lymphoid, myeloid, or monocytoid tissue. The in vitro Hodgkin's disease cells are biologically active by producing factors involved in regulation and promotion of immunological response and granulopoiesis. The relevance of the findings for pathogenesis and clinical appearance of Hodgkin's disease is discussed.

Antibodies, Monoclonal↗

Translocation t(8;22) in peripheral lymphocytes and established lymphoid cell lines from a patient with Hodgkin's disease followed by acute lymphatic leukemia.

Cytogenetic studies on primary material and established cell lines of a patient with B-cell non-Hodgkin Lymphoma with leukemic presentation as secondary malignancy after Hodgkin's disease clearly revealed correspondent marker chromosomes in both culture systems. A translocation t(8;22) which has been described in some cases of non-endemic Burkitt's lymphoma as a variant of the translocation t(8;14) was found in all metaphases of the cell lines and in most of the cells of the primary material. In addition, structural aberrations involving chromosomes 1, 2, 3 and 11, as well as numerical deviations concerning chromosomes 2, 4, 7 and Y, could be observed. The cytogenetical findings are discussed in relation to clinical, immunological and cytochemical data.

Adult↗

Characteristics of Hodgkin's disease-derived cell lines.

In the last 3 years we were able to establish five long-term in vitro cell cultures from biopsy specimens taken preterminally from four patients with histologically proven Hodgkin's disease (nodular sclerosing type, clinical stage IVB). Four of the lines are continuously proliferating in vitro; one culture stopped growth for unknown reasons after 7 months. When culture conditions were modulated, the first culture, L 428, gave rise to two sublines: L 428 KS, after adaptation to calf serum, and L 428 KSA, permanently growing as an adherent monolayer line after treatment with a phorbol ester (12-O-tetradecanoylphorbol-13-acetate) for 3 weeks. Cell-marker analysis by conventional means (SIg, cIg, rosette formation, Epstein-barr virus reactivity, cytochemistry, phagocytosis, and lysozyme production) and with monoclonal antibodies directed against various human lymphoid, myeloid, and monocytoid antigens showed that the tested cell lines are clearly different from all hitherto described hematopoietic lines; they most likely represent a cell type resembling an early myeloid-monocytoid progenitor cell. Conditioned medium of the L 428 cells and its two sublines showed colony-stimulating factor activity and suppression of spontaneous cell-mediated cytolysis of L 428 KS and K 562 cells.

Adult↗

Hodgkin and sternberg-reed cell antigen(s) detected by an antiserum to a cell line (L428) derived from Hodgkin's disease.

Antisera to the cell line L428, derived from Hodgkin's disease, were raised in rabbits by injecting L428 cells intravenously and subcutaneously. The anti-L428 cell serum that did not react with HLA-DR was absorbed with tonsil cell plus acute myeloid leukemia cells or tonsil cells plus neutrophils, monocytes, and blood lymphocytes. Then it was tested for its ability to discriminate between L428 cells, Hodgkin and Sternberg-Reed cells, and various other cells. It was found that the anti L428 cell serum absorbed with tonsil cells plus acute myeloid leukemia cells stained only L428 cells, Hodgkin and Sternberg-Reed cells, and neutrophils. The anti L428 cell serum absorbed with tonsil cell plus neutrophils, monocytes, and blood lymphocytes reacted with L428 cells and Hodgkin and sternberg-Reed cells from 13 cases of Hodgkin's disease. It did not react with any other cell type present in the blood or in lymphoid tissue or with cells from five cases of non-Hodgkin's lymphoma. The absorbed anti-L428 cell serum also failed to stain Daudi and HRIK cell line cells. We conclude that the anti-L428 cell serum defines an antigen that is apparently restricted in expression to L428 cells and Hodgkin and Sternberg-Reed cells. This is a strong indication that the L428 cell line cells are derived from Hodgkin and Sternberg-Reed cells.

Antigens, Neoplasm↗

Sister chromatid exchange in lymphoma line and lymphoblastoid cell lines before and after heterotransplantation into nude mice.

The sister chromatid exchange (SCE) rates of cell lines derived from patients with different malignant and premalignant disease were studied before and after intracerebral inoculation into nude mice and were compared to the SCE frequencies of cell lines from healthy controls. Lymphoma lines characterized by chromosomal markers as well as chromosomally normal lymphoblastoid cell lines were used. The SCE frequencies of nude mouse tumor-derived cell lines did not show a homogeneous pattern. They were either as high as, or higher or lower than, the SCE levels of the original cell line. But all cell lines, karyotypically abnormal as well as normal, originating from patients with malignant and premalignant diseases, showed significantly higher SCE rates than the control lines from healthy donors.

Adult↗

Lymphoproliferation and heterotransplantation in nude mice: tumor cells in Hodgkin's disease.

In the last 3 years we were able to establish four long-term cultures from Hodgkin-derived material [pleural effusions (2), bone marrow (1), and peripheral blood (1)], consisting of cells which represent morphologic and cytochemical as well as cytogenetic features of their in vivo ancestors. Two of these cell lines are described in this paper. These two lines share the same features: non-B-T lymphocytes, non-macrophages, non myeloid cells, EBV genome negative, monoclonality, multiple numerical and structural chromosome aberrations, and tumor formation upon intracranial xenotransplantation in nude mice. The two remaining lines are being characterized at the moment. The common characteristics expressed synonymously in the two described lines suggest that the Hodgkin tumor cell does not seem to share the features of marker-carrying lymphocytes, macrophages, or myeloblasts. The cellular origin of these cells is not clear. The loss of cellular differential markers during the process of possible dedifferentiation is discussed.

Adult↗