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M Schaadt

Publications and source records attributed to M Schaadt.

51 records · Page 3Linked to original sources
PubMed1981

Correlation of chromosomal aberrations in a myeloma cell line with tumorigenicity in nude mice.

A human myeloma cell line (L 363) exhibiting several markers of malignancy including a 14q + chromosome marker was not tumorigenic in nude mice. Long-term cultivation in vitro resulted in new subclones with slight, well-defined chromosomal differences to the original line. Certain subclones turned out to have a growth advantage in vitro and became tumorigenic after transplantation in nude mice. A strong correlation between changes in the chromosome I constellation resulting in the threefold dose of long arm-material and the increased proliferative potential in both experimental systems was found.

Animals↗
PubMed1981

Hodgkin's disease: establishment and characterization of four in vitro cell lies.

Four in vitro cell lines (L 428, L 439, L 538, and L 540) were established from different materials of three patients with Hodgkin's disease: pleural effusions, peripheral blood, and bone marrow. The histological diagnosis was confirmed in all cases by several independent histologists. All four cell lines have been in culture for over 6 months up to over 3 years. The neoplastic nature of the culture cells is indicated by the demonstration of several structural and numeric chromosome abnormalities associated with a monoclonal pattern of marker chromosomes. EBV-specific antigens (EBNA, VCA) were not detected in either cell line. Ia-like antigens, receptors for human T cells, acid phosphatase, and acid esterase were showen to be present in the cultured cells. All cell lines lacked surface or cytoplasmic Ig, HTLA, receptors for C3b, C3d, IgG-Fc, mouse E or sheep E, and were devoid of lysozyme, peroxidase, and chloracetate esterase. The described features do not represent B cells, T cells, myeloid cells, monocytes, or macrophages. The morphology and the marker pattern of the culture cells, however, is identical with that of freshly obtained Hodgkin's (H)- and Sternberg-Reed (SR)-cells, except for the lack of CIg in the in vitro cells, which is explained by the culture conditions. Heterotransplantation in nude mice was achieved by intracranial inoculation and by s.c. transplantation of cultured cells embedded in a plasma clot. The described findings suggest that these cultured Hodgkin's cell lines are indeed derived from H and SR cells. The cellular origin of these cells is not clear, the loss of cellular differential markers during the process of possible dedifferentiation is discussed.

Adult↗
PubMed1981

Immunohistological analysis of Hodgkin's and Sternberg-reed cells: detection of a new antigen and evidence for selective IgG uptake in the absence of B cell, T cell and histiocytic markers.

To help clarify the origin and nature of Hodgkin's (H) and Sternberg-Reed (SR) cells, three different sets of experiments were performed. First, it was shown that cytoplasmic gamma, kappa, lambda occur not only in H and SR cells, but also in polymorphic tumor cells of epithelial, neurogenic, and lymphoid origin. Furthermore, human IgG that was injected i.v. into rats penetrated many rat liver cells, whereas injected human alpha 1-antitrypsin did not. Second, staining of frozen sections revealed that H and SR cells lack surface immunoglobulin and peripheral T-cell antigen. Third, an antiserum raised against the L 428 cell line (derived from Hodgkin's disease) and absorbed with human serum and normal cells did not react with any cells of tonsil tissue (lymphoid cells, histiocytes, and interdigitating reticulum cells), whereas it reacted strongly with the L 428 cell line cells and with H and SR cells of 10 different cases. In all ten cases, the antiserum stained the surface of H and SR cells; in two cases, it also stained the nucleoli and some chromatin spots in H and SR cells. The results obtained in these experiments indicate that H and SR cells are not closely related to lymphoid cells, histiocytes, or interdigitating reticulum cells. The findings also suggest that H and SR cells express one or more antigens that have not yet been detected on or in normal cells.

Animals↗
PubMed1980

Two neoplastic cell lines with unique features derived from Hodgkin's disease.

Two in vitro cell lines (L428, L439) were established from pleural effusions of two patients with Hodgkin's disease. The histological diagnosis was ascertained in both cases by two independent pathologists. The neoplastic nature of the culture cells is indicated by the demonstration of several structural and numerical chromosome abnormalities associated with a monoclonal pattern of marker chromosomes. Heterotransplantation in nude mice was achieved by intracranial inoculation and by subcutaneous transplantation of cultured cells embedded in a plasma clot. EBV-specific antigens (EBNA, VCA) were not detectable in either cell line. Ia-like antigens, receptors for T cells, acid phosphatase and acid esterase were shown to be present in the cultured cells. The L428 and L439 cell line lacked surface- or cytoplasmic Ig, HTLA, receptors for C3b, C3d, IgG-Fc, mouse E or sheep E, and were devoid of lysozyme, peroxidase and chloracetate esterase. These features do not correspond to those of B cells, T cells, myeloid cells, monocytes or macrophages; the morphology and the marker pattern of the culture cells, however, is identical with that of freshly obtained Hodgkin (H)- and Sternberg-Reed (SR)- cells, except for the lack of Clg in the in vitro cells, which is explained by the culture conditions. These findings suggest that the L428 and L439 cell lines are indeed derived from H- and SR-cells and offer the possibility of gaining new information upon the nature of Hodgkin's disease.

Adult↗
PubMed1980

A possible correlation between the degree of karyotype aberrations and the rate of sister chromatid exchanges in lymphoma lines.

The sister chromatid exchange (SCE) frequencies of six freshly established and two old cell lines derived from patients with lymphatic tumors or leukemia were compared to the SCE rates of lymphoblastoid cell lines of normal controls. All cell lines from malignant tumors displayed significantly higher SCE values than the control lines. In general, the SCE rates seem to be correlated to the number of chromosomal markers and the degree of karyotypic instability of each line.

Cell Line↗
PubMed1980

Determination of methotrexate in serum by a rapid, fully mechanized enzyme immunoassay (EMIT).

A homogeneous enzyme immunoassay for the determination of methotrexate in serum (EMIT, Syva Corp.) was fully mechanized by the use of an Eppendorf analyzer 5010. Coefficients of variation from day to day were in the range 2--16%. A comparison of the results obtained by EMIT and a radioimmunoassay (Methotrexate 125 I Radioimmunoassay Kit, Diagnostic Biochemistry Inc.) in a series of 50 samples from patients showed a good correlation between both methods. The specificity of the EMIT assay appeared to be adequate. The time required for the determination of about 20 patient samples by this procedure was only about 80 minutes. From our clinical experimence the EMIT assay appears to be well suited for routine monitoring of methotrexate serum concentrations above 0.1 mumol/1 during intrathecal and high dose methotrexate therapy.

Adult↗
PubMed1979

Sister chromatid exchange in cell lines from malignant lymphomas (lymphoma lines).

The frequency of sister chromatid exchanges (SCEs) was studied in cells from three freshly established lymphoma lines, derived from two patients with Hodgkin's disease and one patient with non-Hodgkin lymphoma. These values were compared to SCE rates found in cells from two long-established lymphoma lines (Raji and BJAB) and to those recorded in control cell lines of normal human donors. The highest SCE levels were demonstrated in the freshly established lymphoma lines, the lowest SCE values separated the lymphoblastoid cell lines from healthy controls, and the older lymphoma lines Raji and BJAB presented rates in between. The influences of BUDR concentration and of the duration of BUDR treatment on the frequency of SCEs were tested. Furthermore, the dependence of the SCE rate on the time interval between establishment of the cell line and its SCE investigation was considered. The connection between elevated SCE rates and the neoplastic nature of lymphoma lines is discussed.

Animals↗
PubMed1979

Intracranial heterotransplantation of human hematopoietic cells in nude mice.

A panel of established cell lines and many primary cell specimens from lymphomas and leukemias as well as from normal lymphatic tissues were tested for tumorigenicity by intracranial heterotransplantation in nude mice. Not only lymphoma and leukemia cell lines, but also lymphoblastoid cell lines, lacking markers of malignancy, were tumorigenic in the brains of nude mice. These findings indicate that tumorigenicity following intracranial heterotransplantation in nude mice cannot be used as proof for the malignant nature of established cell lines. Heterotraplantation of primary cell specimens yielded only a few tumor takes. When primary cells were infected with exogenous Epstein-Barr virus prior to the transplantation procedure, tumorigenicity could be significantly increased. Cytogenetic evaluation of tumors growing after intracranial transplantation of human hematopoietic cells showed, in some cases, a selection of cytogenetically aberrant cell clones.

Animals↗
PubMed1978

[Long term effects of splenectomy on the immune-status of Hodgkin's disease patients depending on the modality of treatment (author's transl)].

In a total group of 103 Hodgkin's disease patients the immune-status of splenectomized and non-splenectomized individuals is compared in subgroups characterized by the modality of treatment (RT, CT, RCT). The mitogenic stimulation of peripheral lymphocytes showed a decreased response of splenectomized patients in each therapy group. The percentage, but not the absolute number/mm3, of peripheral T-cells was reduced after splenectomy. Splenectomized patients, who received combined radiation and chemotherapy showed significantly lower IgM-levels than non-splenectomized patients after the same treatment. EBV-VCA-titers and skin-test-reactivity were not influenced by splenectomy.

Hodgkin Disease↗
PubMed1978

[Hodgkin's disease: effect of spenectomy on the immune status (author's transl)].

In 22 untreated Hodgkin's patients the following parameters were studied before and after splenectomy: the total WBC, lymphocytes, B- and T-cells and mitogenic stimulation of peripheral lymphocytes using autologous and control serum. The results were correlated to patient groups with favourable and unfavourable prognosis according to pathological stage, histology, spleen involvement and constitutional symptoms. 1. All Patients. Significant increase of the absolute number of peripheral lymphocytes and B-cells. Significant increase of the spontanous DNA synthesis in the presence of AB-control serum, but no change after mitogenic stimulation of peripheral lymphocytes. No change in the number of peripheral T-cells. 2. Patients with Favourable Prognosis. Significant increase of the absolute number of peripheral lymphocytes and B-cells. Significant increase of the spontanous DNA synthesis in the presence of AB-control-serum. Significant decrease of the T-cell function (PHA- and Con-A-stimulation in the presence of autologous serum). Significant decrease of the PHA-, Con-A- and PWM stimulation rate using control serum in the lymphocytic predominance and nodular sclerosis group. No change in the number of peripheral T-cells. 3. Patients with Unfavourable Prognosis. No change in the absolute number of B-cells, of the spontanous DNA-synthesis using autologous serum and of the PHA- and Con-A-stimulation. Significant increase of the EBV-induced blastogenesis in the mixed cellularity and lymphocytic depletion group.

Adolescent↗
PubMed1978

Long-term cultivation of plasma cell leukemia cells and autologous lymphoblasts (LCL) in vitro: a comparative study.

Two long-term cell lines were established in vitro from the peripheral blood of a patient with plasma cell leukemia: one line with plasma cell proliferation, the other with lymphoblastoid cell proliferation (LCL). The 9-month-old plasma cell line showed the typical morphology of plasmoblasts. The cells neither had B- nor T-lymphocyte characterisitics, were EBV negative, and showed aneuploidy with various marker chromosomes, including the 14 q+ marker. The cytogenetic findings indicate a monoclonal proliferation of the plasmacells. No tumor growth in thymusless nude mice could be induced upon intracranial inoculation with these cells. In contrast, the autologous LCL, cultured after addition of exogenous EBV, showed the characteristic markers of lymphoblastoid cells, with the typical morphology of pear- and handmirror-shaped lymphoblasts, growing in clumps. They had C3- and Fc-receptors, surface-Ig, E-rosette-negativity, a diploid karyotype, and EBV dependent macromolecule synthesis. They lymphoblastoid cells produced intracranial tumors in nude mice in 8 out of 8 attempts.

Adult↗
PubMedDate not supplied

Hodgkin's cell lines: characteristics and possible pathogenetic implications.

In the last four years we established five long term cultures from tumor material of Hodgkin's disease. The in vitro cells have malignant characteristics and represent the in vivo H- and SR-cells. Common immunological, functional and morphological assays did not characterize the in vitro cells to be a known cell type of lymphoid, myeloid or monocytoid tissue. The in vitro Hodgkin 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.

Cell Line↗
PubMedDate not supplied

Heterogeneous expression of proto-oncogenes in Hodgkin's disease derived cell lines.

The expression of 20 proto-oncogenes was analysed by Northern blotting in four cell lines derived from patients with Hodgkin's disease (L428, L540, CO and DEV) and compared to lymphoid and myeloid leukemia cell lines and normal hematopoietic cells. Expression of the proto-oncogenes c-myc, p53, c-jun, pim-1, lck, c-syn, c-raf and N-ras were detected in Hodgkin's disease derived cell lines and in normal hematopoietic cells. Transcripts of the proto-oncogene c-met were detected in the Hodgkin's derived cell lines L428 and L540 but not in the lymphoid or myeloid leukemia cell lines or in tonsil cells, peripheral blood mononuclear cells and granulocytes. Expression of the proto-oncogenes N-myc and lck were observed in the Hodgkin's derived cell line CO which express T cell receptor genes and in the T cell lines JM and CEM. L428 cells and CO cells expressed aberrant transcripts of the c-fes proto-oncogene. Thus Hodgkin's disease derived cell lines are heterogeneous in their expression pattern of proto-oncogenes, expressing normal and aberrant transcripts of proto-oncogenes which are not found in untransformed hematopoietic cells.

Blotting, Northern↗
PubMedDate not supplied

Intracranial transplantation of human hematopoietic cell lines in nude mice: a preclinical screening model for cytostatic drugs.

This study examines the suitability of the intracranial route of transplantation of human cell lines in nude mice for preclinical testing of cytostatic drugs. Tumours were generated by inoculation of human hematopoietic cell lines. Animals in which intramuscularly or intracranially transplanted human tumours developed were treated with cytostatic drugs. Three different cell line generated tumours (T-ALL L735, Hodgkin cell line L540 and Burkitt Lymphoma Line BJAB) were treated with four different drugs (CY, ADM, VCR, VP16). The data show a good correspondence between the results of treatment of intramuscularly and intracranially transplanted tumours. Thus intracranially transplanted tumour in nude mice are suitable for the testing of cytostatic drugs.

Animals↗