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Biomedical subjects

F Herrmann

Publications and source records attributed to F Herrmann.

At least 271 records · Page 15Linked to original sources

[Disorders of B cell activation in splenectomized patients].

Using a reverse hemolytic plaque assay as the effector system, we studied in vitro B-lymphocyte function in 12 patients after posttraumatic splenectomy as well as in 25 normal individuals. The time interval between the splenectomy and the immunological studies varied between 2 days and 7 years. Compared to normal individuals, the splenectomized patients had markedly elevated numbers of spontaneous immunoglobulin-secreting cells and severely decreased responses to the polyclonal activator pokeweed mitogen, indicating an in vivo polyclonal B-cell activation. A tendency towards normalization of these abnormalities, especially the high spontaneous ISC levels, could be observed during the time interval extending up to 7 years after splenectomy. In order to characterize the mechanism responsible for the altered immune response in splenectomized patients, in vitro experiments were performed with separated lymphocytes. These revealed an impaired T-helper cell capacity as well as an intrinsic B-cell defect. Marker analysis with monoclonal antibodies revealed normal proportions with the exception of OKT 4 positive and B 1 positive cells that identify T-helper/inducer and peripheral B-cells, respectively. We conclude that immune dysfunction in peripheral blood lymphocytes of splenectomized patients involves mainly the OKT 4 positive cell population.

Adult

Ph1 positive blast crisis of chronic myeloid leukaemia exhibiting features characteristic of early T blasts.

Leukaemic cells from a patient in the blast crisis of chronic myeloid leukaemia were subjected to a surface marker analysis using a panel of monoclonal antibodies recognizing differentiation antigens of myeloid (MY7, MY906, VIM D5, M phi P9), erythroid (VIE G4), megakaryocyte (AN51), T-lymphoid (WT1, 10.2, OKT3, OKT4, OKT6, OKT8, OKT11A) and B-lymphoid cells (B1, B2, Y29/55), common ALL-antigen (VILA1), non-lineage-restricted antigens (OKT9, OKT10), monomorphic HLA-DR determinants (7.2) as well as TdT. When the patient entered his first blast crisis, his blasts expressed a phenotype corresponding to an immature myeloid cell (7.2+, MY7+, My906+, VIM D5-). Ph1-chromosome-positive blasts from this patient's first relapse had completely changed their surface marker characteristics: they had become TdT-positive and exhibited surface features characteristic of early T blasts (WT1+, 10.2+, OKT9+, OKT10+, 7.2-, OKT6-). Together, these features provide evidence that myeloid cells may share a common precursor with T cells.

Adult

p69,71 antigen complex detected by monoclonal antibody Leu 1 in the identification of particular stages of malignant B-cell differentiation.

Lymphomatous cell samples from 86 patients with B-cell neoplasia (34 chronic lymphocytic leukaemia, 8 hairy-cell leukaemia, 5 prolymphocytic leukaemia, 20 immunocytic lymphoma, 9 centrocytic lymphoma, 3 centroblastic/centrocytic lymphoma, 3 lymphoblastic lymphoma, 1 plasma cell leukaemia and 3 plasmacytoma) were studied using the monoclonal antibody Leu 1, detecting a p69,71 antigen complex present on nearly all thymocytes, most (greater than 85%) peripheral T-lymphocytes as well as some malignant B-cells. Furthermore, we compared the reactivity of Leu 1-positive B-cells with those exhibiting conventional surface markers such as mouse-erythrocyte-receptor, FcIgG-receptor, C3b- or C3d-receptor and surface immunoglobulins of the various heavy- and light-chain types. Our results demonstrate a correlation between the expression of p69,71 antigen complex and distinct phenotypes revealed by conventional markers and underline the value of Leu 1 monoclonal antibody in the differential diagnosis of human B-cell neoplasia.

Antibodies, Monoclonal

Abnormalities of B-cell activation and immunoregulation in patients with Crohn's disease.

We have studied B-lymphocyte function in 39 patients with Crohn's disease and 35 normal individuals using a reverse haemolytic plaque assay as the effector system. Ten patients had active Crohn's disease, the others being in an inactive state of the disease. Compared with normal individuals, the Crohn's disease patients - especially those in the active state of the disease - had markedly raised numbers of spontaneous immunoglobulin secreting cells and severely decreased responses to the polyclonal activator pokeweed mitogen. The differences between the reactivity of patients with active disease and those with inactive disease were statistically significant. These findings indicate an in vivo polyclonal B-cell activation in Crohn's disease patients, possibly due to antigen(s) or infectious agent(s). In vitro experiments were performed with separated lymphocytes in order to characterise the mechanism responsible for the altered immune reactivity in Crohn's disease. These revealed an intrinsic B-cell defect as well as an impaired T-helper cell capacity in patients with Crohn's disease. Findings supporting the hypothesis of an increased suppressor activity in Crohn's disease patients could not be observed, and marker analyses revealed normal proportions with the exception of raised Leu 7 positive cells that mediate 'natural killer' and 'killer' cytolysis. We conclude that immune dysfunction in peripheral blood lymphocytes of Crohn's disease patients involves B-cells as well as T-helper cells.

Adult

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

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

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

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

Use of monoclonal antibodies as a diagnostic tool in human leukemia. I. Acute myeloid leukemia and acute phase of chronic myeloid leukemia.

Various monoclonal antibodies (mAbs) detecting certain different epitopes on myeloid cells (VIMD5, D5 D6, OKM1, Leu-M3, VIEG4, OKIa 1) have been used in combination with conventional markers (antihuman myeloid hetero-antiserum, FcIgG-receptors, C3d-receptors) to further define the phenotypic heterogeneity of myeloid leukemia. Subsequent leukemic samples from previously untreated patients with acute myeloid leukemia (AML) (51 adults, 24 children) and from nine adult patients in the acute phase of chronic myeloid leukemia (CML-BC) were studied. It was possible to demonstrate quantitative differences in the expression of antigens on the various leukemia subtypes which could be exploited for diagnosis. Furthermore our results revealed that there is a very close correlation between the different surface phenotypes and the types morphologically assessed according to FAB-criteria.

Adult

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

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

Dual expression of T and B cell markers in human B cell neoplasias.

Macrophage- and T-cell-depleted mononuclear cells from 36 patients with B cell lymphoma and 12 healthy individuals were investigated by indirect immunofluorescence with the monoclonal antibodies NEI-011 (7.2) and NEI-015 (10.2). The monoclonal antibody NEI-011 (7.2) recognized the Ia antigen and identified almost all B cells in the peripheral blood of healthy individuals. Furthermore, neoplastic B cells from all patients except those with plasma cell proliferation were found to react with this antibody. NEI-015 (10.2), a monoclonal antibody known to react with both T cells and B-CLL cells, did not react with normal circulating B cells. However, this antibody did identify neoplastic B cells except in cases of plasma cell proliferation and lymphoblastic lymphoma.

Antibodies, Monoclonal

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