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J Gerdes

Publications and source records attributed to J Gerdes.

At least 181 records · Page 10Linked to original sources

Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67.

The monoclonal antibody Ki-67 detects a nuclear antigen that is present only in proliferating cells. The aim of the present investigation was to clarify whether the Ki-67 nuclear antigen is restricted in its expression to certain phases of the cell cycle. All experiments consistently showed that the Ki-67 nuclear antigen is present in S, G2, and M phase, but is absent in G0. However, the results concerning Ki-67 antigen expression in G1 phase varied: cells passing the early events of mitogen triggered transition from G0 to G1, i.e., G1T and first G1A, lacked the Ki-67 nuclear antigen, whereas G1 cells after mitosis were constantly Ki-67-positive. This result suggests that after mitosis cells might not follow the same metabolic pathways as G0 cells do when entering G1 for the first time. Therefore, we suggest that the early stages of mitogen stimulation represent initial sequences of proliferation and not parts of the cell cycle. Because our data show that the Ki-67 nuclear antigen is present throughout the cell cycle, immunostaining with monoclonal antibody Ki-67 provides a reliable means of rapidly evaluating the growth fraction of normal and neoplastic human cell populations.

Animals↗

Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation.

The production of a mouse monoclonal antibody, Ki-67, is described. The Ki-67 antibody recognized a nuclear antigen present in proliferating cells, but absent in resting cells. Immunostainings with Ki-67 revealed nuclear reactivity in cells of germinal centres of cortical follicles, cortical thymocytes, neck cells of gastrointestinal mucosa, undifferentiated spermatogonia and cells of a number of human cell lines. The Ki-67 antibody did not react with cells known to be in a resting stage, such as lymphocytes, monocytes, parietal cells and Paneth's cells of gastrointestinal mucosa, hepatocytes, renal cells, mature sperm cells, brain cells, etc. Expression of the antigen recognized by Ki-67 could be induced in peripheral blood lymphocytes after stimulation with phytohaemagglutinin, whereas it disappeared from HL-60 cells stimulated with phorbol esters to differentiate into mature macrophages in a resting stage. These findings suggest that Ki-67 is directed against a nuclear antigen associated with cell proliferation. A first series of immunostainings of tumour biopsies indicated that Ki-67 may be a potent tool for easy and quick evaluation of the proportion of proliferating cells in a tumour.

Animals↗

Evidence for the origin of Hodgkin and Sternberg-Reed cells from a newly detected small cell population.

To clarify the origin of Hodgkin (H) and Sternberg-Reed (SR) cells, frozen sections of lymph nodes from 25 patients with Hodgkin's disease were immunostained with a large panel of monoclonal antibodies reactive with cells of lymphoid tissue and granulopoiesis. The results showed that (a) H and SR cells are devoid of markers specific to, or characteristic of B cells, macrophages, dendritic reticulum cells, or interdigitating reticulum cells, and (b) the vast majority of H and SR cells contain granulocyte-related antigens detectable with the monoclonal antibodies TU9 and 3C4, but constantly lack other granulocytic cell markers (such as peroxidase and chloroacetate esterase). Monoclonal antibodies raised against a Hodgkin's disease-derived cell line included one, Ki-l, that was found to be selectively reactive with H and SR cells and a minute, but distinct, cell population in normal lymphoid tissue and bone marrow. The latter hitherto unknown cell population appears to be the normal equivalent of H and SR cells.

Antibodies, Monoclonal↗

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↗

Human dendritic reticulum cells of lymphoid follicles: their antigenic profile and their identification as multinucleated giant cells.

The B-dependent areas of human lymphoid tissue contain non-lymphoid, non-phagocytic cells known as dendritic reticulum cells (DRC). These cells can be detected only very occasionally in routinely stained histologic sections. Recently we were able to overcome this limitation by preparing a monoclonal antibody, termed R 4/23, that reacts selectively with DRC. Thus by using an optimized immunoperoxidase method applied to frozen sections, it is possible to detect DRC in situ. To determine the antigenic profile of DRC, serial frozen sections of human tonsils were immunostained with R 4/23 and a large panel of other monoclonal antibodies or conventional antisera. In addition, touch imprints of tonsils and cytocentrifuge slides of cell suspensions with increased concentrations of DRC were immunostained with these reagents. DRC proved to be positive for mu, gamma, alpha, kappa and lambda chains, complement component C3b, C3b receptors, C3d receptors, HLA-A,B,C antigens, human Ia-like antigens, common ALL antigen (cALLa), and antigens that are characteristic of the monocyte/macrophage lineages. DRC did not express delta chains, T cell antigens, or antigens that are expressed on interdigitating reticulum cells (IDC) and Langerhans cells. DRC in touch imprints and suspensions prepared from hyperplastic tonsils were found to be giant cells often with 10 or more nuclei. In certain cases of follicular hyperplasia and of centroblastic-centrocytic lymphoma, DRC with several nuclei were also detectable in situ. These results show that (1) the phenotype of DRC differs from that of all other cell types in lymphoid tissue, (2) this phenotype most nearly resembles that of cells of the monocyte/macrophage series, thus suggesting that DRC are related to these cell lineages, and (3) DRC are multinucleated giant cells.

Antigens↗

The Epstein-Barr virus receptor is distinct from the C3 receptor.

Polyvalent serum directed against C3 receptors was employed in an attempt to block Epstein-Barr virus (EBV) binding to virus receptor-containing cell lines. The serum eliminated 90% of virus binding to Daudi and BJAB, lines which express only the C3d receptor. Raji and Ramos cells, which express the C3d, C3b and C3bi receptors, still adsorbed 70% of their virus capacity in the presence of excess antiserum. These effects were independent of the virus strain. In the light of previous reports, these data imply that, although the two receptors, EBV and C3d, are closely associated, the binding sites of EBV and complement are distinct. Additionally, an unusual EBV substrain-specific receptor found on U698 and P3HR-1/ASNP lines was shown to be independent of complement receptors.

Animals↗

Production of a monoclonal antibody reactive with human dendritic reticulum cells and its use in the immunohistological analysis of lymphoid tissue.

A murine monoclonal antibody (designated R4/23) which reacts strongly with human dendritic reticulum cells (DRC) is described. Immunoperoxidase staining of tissue cryostat sections revealed that this antibody reacts strongly with DRC in lymphoid follicles (both primary and secondary), and also weakly with marginal zone splenic B cells and with some peripheral follicular mantle B lymphocytes in lymph node cortical follicles. The value of antibody R4/23 is that it allows the distribution of DRC in reactive and neoplastic lymphoid tissue to be clearly delineated. Of particular interest is the fact that all cases of follicular lymphoma of germinal centre cell origin are consistently accompanied by a proliferation of DRC, even when the neoplasm is present in non-lymphoid tissue--for example, in the kidney. In contrast, DRC in B cell lymphomas of non-germinal centre origin are partially or totally obliterated.

Animals↗

Feature-positive effect in adults and attention to portion of stimulus array.

In three experiments, adult humans were tested in a feature-positive or feature-negative simultaneous symbol task. In Experiment 1, some persons focused on the correct side of the stimulus cards, whereas other persons focused on the not-correct side of the stimulus cards. The feature-positive group learned faster than the feature-negative group did in the correct side condition; the feature-negative group learned faster than the feature-positive group did in the not-correct side condition. In Experiments 2 and 3, all persons focused on both the correct and not-correct sides of the stimulus cards. Under these circumstances, feature-positive and feature-negative performances were comparable. These results indicated that the usual superiority of feature-positive over feature-negative learning results from a tendency to attend to only a portion of the stimulus array.

Attention↗

Identification of Hodgkin and Sternberg-reed cells as a unique cell type derived from a newly-detected small-cell population.

In this study the antigenic profile of Hodgkin (H) and Sternberg-Reed (SR) cells from cases of Hodgkin's disease was analysed using a large panel of monoclonal and polyclonal antibodies reactive with cells of lymphoid and haemotopoietic origin. The aim of this investigation was, firstly, to throw light on the origin of H and SR cells and, secondly, to determine whether there is any evidence to support recent suggestions that H and SR cells differ antigenically between different histological categories of Hodgkin's disease. Frozen sections (from 24 cases) and paraffin sections (83 cases) were stained by immunoenzymatic methods and the results compared with those obtained from staining a wide variety of reactive and neoplastic tissue samples (including examples of tuberculosis, sarcoidosis, malignant histiocytosis, histiocytosis X, osteomyelosclerosis and non-Hodgkin's lymphoma). The results revealed that H and SR cells of all types of Hodgkin's disease consistently lack markers found on null cells, B cells, T cells, cells of monocyte/macrophage series, interdigitating reticulum cells, dendritic reticulum cells and erythropoietic and thrombopoietic cells. However, H and SR cells constantly expressed an antigen detectable with the recently produced monoclonal antibody Ki-I. The vast majority of typical and lacunar type H and SR cells contained the granulocyte-related antigens detected by monoclonal antibodies TU5, TU6, TU9 and 3C4, whereas other more or less specific granulopoietic cell markers (such as peroxidase, chloroacetate esterade, lysozyme, cationic leukocyte antigen and OKMI) were consistently absent. H and SR cells in cases of nodular paragranuloma (nodular type of Hodgkin's disease with lymphocyte predominance) were not monotypic in light chain type (as has been previously reported), but rather contained chi and lambda chains within the same cells, as do typical and lacunar type H and SR cells. Immunostaining of normal and hyperplastic lymphoid tissue with the Ki-I antibody led to the detection of a new, as yet unidentified, small-cell population of unknown origin and function, which is present between, around, and within cortical follicles. It is concluded from these findings that H and SR cells constitute a unique cell type that differs in many properties from all other known cell types. Furthermore, H and SR cells of the various histological types of Hodgkin's disease are more closely related than previously believed. It is suggested that the hitherto unknown cell population detected with the monoclonal antibody Ki-I in normal lymphoid tissue is the normal equivalent of H and SR cells.

Antibodies, Monoclonal↗

Antisera with anti-pan C3 receptor reactivity which block complement C3b, C3bi and C3d receptors.

Antisera directed at human C3 receptors were prepared by 2 different methods. In method I rabbits were immunized with EAC coated with C3 receptors of tonsil cells (AC3RS type I). In method II rabbits were immunized with insoluble aggregates of tonsil membrane constituents containing significant amounts of C3 receptors. After appropriate absorptions both types of AC3RS showed a selective reactivity with those cells known to express C3 receptors. With the EAC rosette inhibition test it is demonstrated that both types of AC3RS contain antibodies against the binding sites of C3b, C3bi and C3d receptors. The antibody titer was consistently higher in AC3RS of type II.

Animals↗

Hodgkin and Sternberg-Reed cells contain antigens specific to late cells of granulopoiesis.

The results of a recent investigation, in which an antiserum specifically directed against Hodgkin (H) and Sternberg-Reed (SR) cells was prepared, indicated the existence of a granulocytic cell-specific antigen on H and SR cells. In the present study, a large series of biopsies from patients with Hodgkin's disease were subjected to immunostaining with monoclonal mouse antibodies raised against acute myelomonocytic leukemia (AMML) cells. Among seven hybrids that secreted antibodies showing reactivity to AMML cells but not to Daudi cells, there were three (TU5, TU6 and TU9) whose antibodies selectively stained formalin resistant antigens in cells of granulopoiesis. The strongest staining was found in the more mature cells; only a few promyelocytes stained very faintly with TU9, H and SR cells showed distinct staining for TU9 in 57 (76%) of the 75 tested cases of Hodgkin's disease, whereas TU5 and TU6-reactive H and SR cells were found in only 35 cases (47%). All cases of the nodular sclerosis type and almost all cases of the mixed cellularity type contained TU9-reactive H and SR cells, although the percentage varied from case to case. TU9-reactive H and SR cells were demonstrated in nine of 12 cases of the lymphocyte depletion type and in eight of 21 cases of the lymphocyte predominance type. The presence of granulocytic cell-specific antigens in H and SR cells in most of the cases of Hodgkin's disease suggest that (1) H and SR cells (including the lacunar cell variant) are not heterogeneous, but rather homogeneous in origin and nature, at least in a majority of cases, and (2) H and SR cells are more closely related to cells of the granulocytic cell lineage than to any other type of cell of the hemato-lymphoid system.

Antibodies, Monoclonal↗