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Biomedical subjects

C Fonatsch

Publications and source records attributed to C Fonatsch.

At least 163 records · Page 9Linked to original sources
PubMed1985

Refinement of HLA gene mapping with induced B-cell line mutants.

The lymphoma cell line BJAB.B95.8.6 was gamma-irradiated to induce mutations of major histocompatibility complex (MHC) encoded genes. Cloned "wild-type" cells were phenotyped HLA-A1, A2, B13, B35, Bw4, Bw6, Cw4, DR5, DRw52, DQw1, DQw3, DPw2, DPw4, GLO1 1, PGM3 2-1, and ME1 0 and possessed two apparently normal chromosome 6s prior to mutagenesis. Loss mutants were selected 5 days after 3 Gy gamma-irradiation employing three complement-fixing monoclonal antibodies specific for HLA-A2 (TU101) and Bw4 (TU48, TU109). Fifteen independently arising mutants were isolated and cloned. Typing with monospecific alloantisera and cell-mediated lympholysis revealed the presence of HLA-A1, B35, Bw6, Cw4, DR5, DRw52, DQw3, and DPw4 specificities on all mutant clones. HLA-A2, B13, and Bw4 were absent. Mutants differed in their expression of class II antigens. One group retained DQw1 and DPw2, another was DQw1-, DPw2+, and a third was DQw1-, DPw2-. Karyotyping of the "wild-type" line and selected mutant clones showed that the loss of HLA specificities correlated with deletions which map the HLA-A and -B loci directly to the distal part of the 6p21.33 region and the class II genes to the region 6p21.33 (proximal) to 6p21.31 (distal) on the short arm of chromosome 6.

Antibodies, Monoclonal↗
PubMed1985

Monosomy 6 in a human lymphoma line induced by selection with a monoclonal antibody.

The human Epstein Barr Virus-superinfected B lymphoma cell line BJAB-B95.8.6 was mutagenized by gamma irradiation, and HLA mutants were selected with the HLA-Bw6-specific monoclonal antibody SFR8-B6. One of the mutants obtained, BM19, had lost one of the chromosomes 6 present in the wild type cells. Electrophoretic analysis of phosphoglucomutase isozyme PGM3 and erythrocyte glyoxalase 1 from both cells supports this conclusion. The HLA antigens expressed on BM19 were HLA-A2, B13, Bw4, C-, DR2 (questionable), DRw52 (weak) and DQw1. This constitutes one of the haplotypes of the wild type cells, the other (lost from BM19 cells) being HLA-A1, B35, Bw6, Cw4, DR5, DRw52 (strong) and DQw3. Possibilities to employ BM19 cells for the analysis of the major histocompatibility complex and other chromosome 6-encoded genes as well as their products are discussed.

Antibodies, Monoclonal↗
PubMed1985

Persistent Epstein-Barr virus infection associated with monosomy 7 or chromosome 3 abnormality in childhood myeloproliferative disorders.

This report deals with myeloproliferative disorders associated with chronic, persistent Epstein-Barr virus (EBV) infection and with monosomy 7 and aberrations concerning chromosomes 3 and 5. Altogether five children were affected, their age ranging from 1 to 4 years at time of clinical diagnosis. Principal symptoms were: hepatomegaly, splenomegaly, recurring upper respiratory tract infection and anaemia. The serum IgG level remained persistently increased. Anti EBV antibody concentrations were measured over a period of 9 months to 6 years, demonstrating persistently increased concentrations of IgG antibodies to viral capsid antigen (VCA) and against early antigen (EA). In three patients IgA antibodies were also studied and were found to be elevated. Within 2-5 years two children developed chronic myelomonocytic leukaemia from the chronic myeloproliferative syndrome. A third patient who initially was diagnosed as chronic myelomonocytic leukaemia developed acute leukaemia within a period of 12 months. A fourth patient with myeloproliferative syndrome went into spontaneous remission after an observation period of 2 years. A fifth patient, the only one with translocation t(3;5)(q27;q33), displayed symptoms and a clinical course that can best be characterized as juvenile chronic myelocytic leukaemia. The clinical, haematological, serological and cytogenetic findings may be related.

Child, Preschool↗
PubMed1985

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↗
PubMed1984

Heterochromatin and nucleolus organizer regions in cells of patients with malignant and premalignant lymphatic diseases.

Peripheral blood lymphocytes (short-term cultures) and permanent lymphoid cell lines (long-term cultures) of patients with Hodgkin disease (5), lymphoma (1), plasma cell leukemia (1), angioimmunoblastic lymphadenopathy (1), and infectious mononucleosis (3) were investigated for C-band variants and nucleolus organizer region (NOR)-activities by C-banding and silver-staining, and compared to those of healthy adults (5) and newborn children (3). Heterochromatin polymorphisms were found in malignant diseases (33%) as well as in controls (29%). In the lymphoma patients, heterochromatin of class 3 (Patil and Lubs 1977) was seen more frequently than in the controls (83%:57%). No marker C-band variants could be detected in any of the lymphatic diseases. There was no difference in the heterochromatin polymorphism between short-term cultures (predominantly T-cells) and long-term cultures (B-cells), and there was little but inconsistant difference in the NOR-activities. Silver-staining showed differences between healthy adults (8.8 AgNORs; SD:0.5) and newborn children (6.9; SD:0.4). In the lymphoma patients we found 8.3 (SD:0.7) AgNORs. Thus, using silver staining there was no detectable increase in the number of active NORs in cells of patients with malignant diseases as an expression of increased nucleolus activation in malignancies. The remarkably low NOR-activity in infectious mononucleosis (6.7; SD:1.0) may reflect an influence of acute virus infection (Epstein-Barr virus) on NOR-activity.

Adult↗
PubMed1983

[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↗
PubMed1983

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↗
PubMed1983

Frequency of fragile X chromosomes, fra(X), in lymphocytes in relation to blood storage time and culture techniques.

The fra(X) frequencies in metaphases of lymphocytes from seven male patients with X-linked mental retardation and macroorchidism were scored after use of different culture techniques and different times of blood storage. No statistically significant differences were found between the fra(X) rates of lymphocytes grown either in folic acid deficient medium (TC 199) or in medium containing folic acid as well as a folic acid antagonist (methotrexate: MTX, aminopterine: AP). With respect to the effect of the time interval between blood sampling and culture set-up, a statistically significant decrease in the fra(X) frequency was observed in all culture types after 4 or 7 days of blood storage.

Blood Preservation↗
PubMed1982

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↗
PubMed1982

[Fragile X chromosome and X-linked mental retardation (author's transl)].

In males affected by a special form of X-linked mental retardation a characteristic chromosomal abnormality can be demonstrated, - i.e. a fragile site on the long arm of the X chromosome, fra(X) (q27 or 28) (marker-X chromosome). Male carriers are physically normal, but in most cases show macroorchidism. The demonstration of the marker-X chromosome requires special cell culture conditions, above all a folic acid-deficient medium. The frequency of cells with fragile X chromosome varies interindividually, ranging from 2 to 50%. In female heterozygous carriers the number of cells with fra(X) decreases with age and cannot be demonstrated in some cases. Distribution and frequency of X-linked mental retardation with marker-X chromosome and macro-orchidism are discussed, as well as possibilities of prenatal diagnosis of this disorder.

Adolescent↗
PubMed1982

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↗
PubMed1981

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↗
PubMed1981

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↗