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Biomedical subjects

G Sieber

Publications and source records attributed to G Sieber.

At least 37 records · Page 2Linked to original sources
PubMed1984

T-ALL related to intermediate cortical/medullary thymocytes displaying functional and surface characteristics of suppressor T cells.

Leukemic cells of a patient with acute T-lymphoblastic leukemia (T-ALL) exhibiting the uncommon clinical feature of hypogammaglobulinemia were examined in terms of surface markers and immunologic functions. Employing various monoclonal reagents reacting with surface antigens present on T cells and additional conventional markers, it was shown that the patient's leukemic cells expressed a phenotypical profile (E-R+, TdT+, C3d-R-, OKT3-, T4-, T6(+), T 10+, T8++) corresponding to the intermediate stage between the cortical and medullary phase of normal thymocyte differentiation. Functionally, they were unable to respond to mitogens or to produce detectable amounts of immunoglobulins or to provide 'help' for allogeneic antibody production while they suppressed the immunoglobulin production of normal B cells by 76% in coculture experiments.

Adult↗
PubMed1984

Monoclonal antibodies recognizing T-cells (Leu 1) and transferrin receptor (OKT 9) crossreact with malignant B-cells of distinct differentiation stages.

The present study was carried out to determine the reactivity of Leu 1 and OKT 9 mouse monoclonal antibodies with B-cell samples obtained from 99 patients suffering from non-Hodgkin lymphomas of various B-type entities classified according to the Kiel-nomenclature. It could be demonstrated that both antibodies--previously known to display anti-T-cell reactivity--cross-react with several types of malignant B-cell. Leu 1 shows preference for membrane IgM and mouse erythrocyte receptor-bearing cells, whereas OKT 9 was expressed on malignant B-cells reflecting the terminal phase of B-cell ontogeny.

Antibodies, Monoclonal↗
PubMed1983

Heterogeneity of T-cell neoplasias as defined by monoclonal antibodies.

Surface marker studies were carried out on neoplastic cell samples (peripheral aspirates and skin biopsies) of 302 patients with non-Hodgkin lymphomas (221 patients) and acute lymphatic leukaemias (81 patients). In 11 patients with non-Hodgkin lymphomas (5%) and eight patients with acute lymphatic leukaemia (10%), the neoplastic cells possessed phenotypic characteristics of T cells. The investigations were carried out by means of an indirect immunofluorescence technique using a panel of monoclonal antibodies (OKT 3, 4, 6, 8, 9, 10; OKM 1; HNK 1 and VIL A 1). In addition, conventional markers (SIg, E-R 4 degrees, E-R 37 degrees, absorbed polyclonal rabbit antithymus and anti-TDT) were used. Our results, which show a pronounced phenotypic surface marker heterogeneity between the group of T-cell neoplasias, emphasize the diagnostic value of monoclonal antisera as compared to polyclonal reagents. Eleven different surface marker profiles were observed in the 19 patients investigated.

Adult↗
PubMed1983

Lymphocyte subsets in the peripheral blood of patients with multiple myeloma and benign monoclonal gammopathy.

A panel of monoclonal antibodies that identify various antigens present on T and B cells was used to characterize circulating blood lymphocyte subsets in multiple myeloma [(MM)--13 patients] and benign monoclonal gammopathy [(BMG)--5 patients]. In MM and BMG an increase in B cell proportions (BA 1 positive cells) was observed, whereas T cells (Lyt 3 positive cells) were reduced compared to normal controls. However, with respect to the T cell subset distribution, a marked diversity between MM and BMG was noted. This may help to differentiate BMG from MM. In MM a relative decrease in inducer/helper T cells (OKT 4 positive cells) and increase in suppressor/cytotoxic T cells (OKT 8 positive cells) as well as in NK/K T cells (Leu 7 positive cells) was observed. On the other hand, in BMG the relative T cell subset distribution was comparable to those seen in normal subjects.

Adult↗
PubMed1983

Evaluation of the circulating and splenic lymphocyte subpopulations in patients with non-Hodgkin lymphomas and Hodgkin's disease using monoclonal antibodies.

The number of B lymphocytes, T lymphocytes and their helper/inducer, cytotoxic/suppressor and NK/K subpopulations was measured in peripheral blood and spleen cell suspensions from patients with Hodgkin's disease (HD) in the active stage of the disease and in remission status, as well as in Non-Hodgkin lymphomas (NHL) in active stage of the disease. B lymphocytes were determined by direct immunofluorescence and T lymphocytes with the E rosette technique. Helper/inducer, cytotoxic/suppressor, and NK/K T lymphocytes were determined by indirect immunofluorescence with the monoclonal antibodies OKT4, OKT8 and Leu 7 (HNK1). In the same way, Lyt3 was used for determination of the total T lymphocytes. Whereas in peripheral blood of the NHL group an increase of B lymphocytes and a slight reduction of T lymphocytes could be observed, with normal distribution of the subpopulations, in patients with active HD as well as in those in remission, a marked absolute and relative decrease of T helper/inducer cells was found with normal cytotoxic/suppressor and NK/K proportion. In contrast to this, a significant increase of helper/inducer T lymphocytes with decreased cytotoxic/suppressor T proportion was found in spleen cell suspensions of patients with HD.

Adult↗
PubMed1983

Expanded T gamma cell populations with the morphology of large granular lymphocytes -- I. Immunological, clinical and morphological characterization.

Lymphocytes from two patients with T gamma cell proliferations displaying the morphology of large granular lymphocytes (LGL) were characterized in terms of cell marker phenotyping and immunologic functions. In both patients, the lymphocytes were positive for E-R, HuTLA, OKT5, OKT8, OKT11, OKM1, VEP13, Leu1, Leu2a, Lyt2 and Lyt3 and were negative for Tmu, Tar, SIg, BA1, BA2, EM-R, C3d-R, C3b-R, OKT6, OKT9, Leu3a, OKIa1 and TdT. In addition, investigations for T411, T811 and M522 in patient 1 yielded positive results. There were differences in the phenotype of the two patients with regard to the reactions with OKT3, OKT10 and VEP10. While, in patient 1, OKT3 was very pronounced and OKT10 and VEP10 were completely negative, OKT10 and VEP10 were very pronounced in patient 2, whereas OKT3 was positive only in a very small percentage of cells. Though the lymphocytes in both patients were potent effectors of NK and K functions (patient 2 more strongly than patient 1) and a noticeably reduced mitogen response was shown to PHA, Con A and zinc, patient 1 showed a distinct suppression of allogenic and autologous B cell response to transformation into ISC, coinciding with the clinical observation of a hypogammaglobulinemia; neither B cell suppression nor dysgammaglobulinemia was seen in patient 2. The results are discussed with regard to other comparable T gamma proliferations reported in the literature.

Aged↗
PubMed1983

Further evidence for T cell abnormalities in chronic lymphocytic leukaemia of the B cell type.

Functional properties were studied in the purified T cell fraction of patients with chronic lymphocytic leukaemia of the B cell type (B-CLL). This analysis included the evaluation of T suppressor activity when investigated patients' T cells were co-cultured together with allogenic normal B and OKT4 enriched T cells in the presence of pokeweed mitogen (PWM). The Ig secreting cells (ISC) were assessed in a reverse haemolytic plaque assay (RHPA). Antibody-dependent cytotoxicity (ADCC) and natural killer activity (NK) were determined in a 51Cr release assay. Furthermore, purified T cells reactive with the monoclonal antibody HNK1, known to recognize most effector cells in ADCC and NK, were enumerated using an indirect immunofluorescence. Our results revealed increased T suppressor cell activity and markedly deficient NK activity in peripheral blood lymphocytes (PBL), T cell and T gamma cell fractions from B-CLL patients, whereas ADCC potential was only increased in T cells and T gamma cells. Accordingly, T cells were recognized by HNK1 in greater numbers in B-CLL patients than in healthy subjects. Our data suggest that there may be a link between our findings and the hypogammaglobulinaemia as well as the increased incidence of second neoplasias reported in CLL.

Aged↗
PubMed1982

B-cell function in patients with chronic lymphocytic leukemia.

Using a reverse hemolytic protein A plaque assay, spontaneous and pokeweed mitogen (PWM)-induced immunoglobulin (Ig) secretion was determined in peripheral blood from 22 patients with B1-chronic lymphocytic leukemia (CLL), one patient with B2-CLL, and one patient with suppressor T-CLL. Diagnoses were established by cytological and histological criteria as well as several marker analyses. Lymphocytes from B1- and B2-CLL patients were unable to secrete Ig either spontaneously or after PWM stimulation. In T-CLL lymphocytes, spontaneous Ig secretion was suppressed very probably by the OKT-8-positive leukemic population, since, after cultivation with PWM, a normal Ig secretion could be demonstrated which was paralleled by a decrease in the OKT-8-positive cells. Cocultivation experiments with freshly isolated, unseparated lymphocytes from normal subjects and lymphocytes from patients were of no informational value, since isolated normal B-cells alone already showed a high rate of Ig secretion. However, coculture experiments with separated subpopulations after PWM stimulation revealed an intrinsic B-cell defect in lymphocytes from B1-CLL patients, whereas their T-lymphocytes were found to be normal helper cells.

Adult↗
PubMed1981

PWM-induced generation of immunoglobulin-secreting cells in patients with multiple myeloma.

The pokeweed-mitogen-induced transformation of B-lymphocytes into immunoglobulin-secreting cells was studied in vitro in 25 patients with multiple myeloma using a reverse hemolytic plaque assay. Fifteen patients showed a good response in generating immunoglobulin-secreting cells, whereas 10 patients showed a decreased B cell reactivity which was not due to intermittent melphalan/steroid therapy administered to 15 patients. Experiments with lymphocyte subpopulations demonstrated that the inability of some multiple-myeloma patients to generate immunoglobulin-secreting cells was always based on a defect in the B-cell subset. Co-culture experiments with lymphocytes from normal individuals and patients revealed a cell-mediated suppression in one case, whereas humoral suppressive factors in the patients' serum could not be observed using the reverse hemolytic plaque assay. Patients were classified into three groups: (a) patients with a normal B-cell function, (b) patients with a reversible, tumor-dependent suppression of B-cell reactivity and (c) patients in whom the normal B-cell population was replaced by non-reactive cells.

Adult↗
PubMed1981

Clinical and prognostic heterogeneity of non-Hodgkin lymphomas of high-grade malignancy.

Comparison of clinical data of 64 patients with centroblastic lymphoma, 55 patients with immunoblastic lymphoma and 31 patients with lymphoblastic lymphoma not only confirmed the original assumption of high-grade malignancy as proposed by the concept of the Kiel classification but also demonstrated distinct clinical differences, particularly between lymphoblastic lymphoma and the two other entities. Rapid lymph node enlargement as well as steep fall of survival curves within the first year after diagnosis were common characteristics. Bimodal age distribution, predominance of males and early generalization of disease were typical features of lymphoblastic lymphoma; elderly patients and patients with the unclassified subtypes of lymphoblastic lymphoma exhibited the worst prognosis. Whereas patients with centroblastic and immunoblastic lymphomas showed similar distribution of age, sex and initial stage of disease, patients with immunoblastic lymphoma presented more frequently with a reduced performance status and showed a poorer response to radio- and chemotherapy resulting in a worse prognosis discernible after the first year of follow-up. Generalization during course of the disease was significantly more frequent in immunoblastic than in centroblastic lymphoma.

Adolescent↗
PubMed1981

Impaired B-lymphocyte reactivity in patients with Hodgkin's disease and non-Hodgkin-lymphomas.

The generation of immunoglobulin-secreting cells upon stimulation with pokeweed mitogen was studied in patients with Hodgkin's Disease (HD) and non-Hodgkin lymphomas (NHL) using a reverse hemolytic plaque assay. The experiments revealed that the majority of the patients in both groups had greatly diminished responses of their peripheral B-lymphocytes. Whereas in NHL patients an intrinsic B-cell defect is the most likely explanation for the impaired B-cell reactivity, the situation in HD appears to be more complex. In some patients with an active stage of the disease, suppressor cells were found to cause the unresponsiveness: in other patients, an intrinsic B-cell defect as well as a defect of the T helper cells were responsible for the diminished responses. The results further suggest that the immune defect in patients with HD is reversible and can be corrected by therapy.

Adolescent↗
PubMed1980

Characteristics of immunoglobulin secretion in man evaluated by a reverse hemolytic plaque assay.

The kinetics of Pokeweed mitogen-induced transformation of human B-lymphocytes into immunoglobulin-secreting cells were examined in a reverse hemolytic plaque assay using protein A-coated sheep red blood cells as indicator cells. Peak responses occurred consistently after 6-8 days of incubation. After determination of the optimal experimental conditions the RHPA was found to be a reliable tool to estimate ISC in vitro; the technique was also found to be applicable for experiments surveying the B-cell response of an individual over a period of months. The PWM-induced transformation of B cells was absolutely T-cell-dependent. Other substances known as typical T-cell mitogens were also tested for polyclonal B-cell activation and some of them showed significant responses. Further experiments have shown that co-cultivation of non-HLA identical cells did not increase the number of plaques in unstimulated cultures whereas the addition of PWM leads to the generation of ISC within the expected range. These findings open a wide field of application of the RHPA in experimental and clinical immunology.

Animals↗
PubMed1980

Stimulation of human and mouse lymphocytes by ribosomal proteins.

Ribosomal 30S and 50S subunits as well as total proteins from the large subunit of E. coli ribosomes were found to be potent mitogens for both human adult and cord blood lymphocytes. On the other hand, the RNA fraction of the 50S subunit had only a weak stimulatory capacity suggesting that the protein moiety contains the stimulatory component. Experiments with lymphocyte subpopulations obtained by nylon wool filtration of E-rosette separation have shown that, in human, the main target cells are T lymphocytes. First experiments with mouse spleen cells indicate that, in mice, T and B lymphocytes can be stimulated by ribosomal proteins.

Adult↗
PubMed1979

Activation of human lymphocyte subpopulations by protein A from Staphylococcus aureus bacteria.

Cowan I strain Staphylococcus aureus bacteria were found to be mitogenic for human peripheral and cord blood lymphocytes. Experiments with lymphocyte supopulations otained by nylon wool filtration and/or E-rosette separation revealed that T-lymphocytes are the main target cells, whereas isolated B cells did not respond significantly. Further experiments suggested that B cells could be activated in the presence of mitomycin-treated T cells. Null cell-enriched lymphocyte suspensions could be stimulated by Con A but not by the bacteria or by PHA.

B-Lymphocytes↗