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R Warnke

Publications and source records attributed to R Warnke.

At least 55 records · Page 3Linked to original sources
PubMed1984

Immunoglobulin gene rearrangements in hairy cell leukemia.

Studies of hairy cell leukemia have yielded conflicting data about the cell of origin in this disease. To investigate this issue, we have examined the state of immunoglobulin genes in the cells of 11 randomly selected spleens showing histologic involvement with hairy cell leukemia. DNA was extracted from splenic tissue samples and digested with restriction endonucleases. Following agarose gel electrophoresis and transfer to nitrocellulose filters or activated nylon membranes, splenic DNA was hybridized with radiolabeled DNA fragment probes specific for the constant regions of the immunoglobulin heavy chain and kappa and lambda light chain genes. Autoradiograms of the hybridized DNA in each case revealed rearrangements of a heavy chain gene and at least one light chain gene. In addition, immunophenotyping of cellular immunoglobulin polypeptides was carried out on frozen tissue sections from all but one case. In each case in which an immunoglobulin polypeptide could be detected, a rearrangement was present in the DNA of the corresponding immunoglobulin gene. These studies offer strong evidence for endogenous immunoglobulin synthesis in hairy cells and for the B lymphocytic character of this leukemia.

B-Lymphocytes↗
PubMed1984

Monoclonal antibody and enzymatic profiles of human malignant T-lymphoid cells and derived cell lines.

Recently, four distinct cell lines were established from patients whose malignancies had been defined by immunological and biochemical markers. Each patient had a distinct subtype of a T-cell cancer, and each possessed elevated adenosine deaminase and reduced nucleoside phosphorylase activity. Cell lines cultured in vitro possessed the same basic immunophenotype and biochemical enzyme activity as the patients' original malignant cells. In a direct comparison of the immunophenotype of the cell lines and the patients' malignant cells, full concordance existed for 48 of 52 paired antibody tests performed. However, when compared to the corresponding patient's sample, each cell line showed some minor changes in antigen expression or enzyme level. Antigen loss, de novo antigen expression, or elevated adenosine deaminase levels occurred in the cell lines, and these changes were stable on repeated analysis. While there was good general concordance between the patient's cancer and the established cell line, minor biological differences in the cell lines may reflect cellular maturation or subpopulation selection in vitro.

Adenosine Deaminase↗
PubMed1983

A single monoclonal antibody identifies T-cell lineage of childhood lymphoid malignancies.

Immunophenotyping studies with monoclonal antibodies have revealed the heterogeneity of childhood acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL). The lymphoid malignancies of T-cell lineage are particularly heterogeneous and, until now, no single monoclonal antibody has been found to identify all cases of T-ALL and T-NHL. A monoclonal antibody, 4H9, recognizes an antigen of 40,000 molecular weight on normal and malignant T cells. Thirty-six cases of childhood T-ALL and T-NHL were tested, and in all cases, the malignant blast cells were reactive with 4H9, whereas malignant cells from 61 cases of non-T ALL and NHL were not reactive with 4H9. Monoclonal antibody 4H9 is a sensitive and specific reagent for the identification of childhood T-cell ALL and NHL and should be extremely useful in immunophenotyping studies of lymphoid malignancies.

Antibodies, Monoclonal↗
PubMed1982

Histochemistry of Hodgkin's disease.

The histochemistry of Hodgkin's cells is controversial. Limited numbers and the variety of techniques used make comparisons difficulty. Acid phosphatase and nonspecific esterase have been the two enzymes most frequently tested because the presence of these enzymes has been thought to be characteristic of histiocytes. Despite the controversial results, these studies have frequently figured prominently in arguments about the cell of origin in Hodgkin's disease. Authors identifying the presence of acid phosphatase and nonspecific esterase have generally favored a mononuclear phagocyte origin; those with negative results have favored a lymphoid origin. We have evaluated a series of 21 cases of Hodgkin's disease using tissues embedded in plastic and tested for acid phosphatase and nonspecific esterase. We found that Hodgkin's cells were frequently positive for acid phosphatase (20 to 21 cases) and/or nonspecific esterase (18 of 21). The reactions are weak and sensitive to inhibition by processing procedures. The reaction patterns are unusual for lymphoid cells and histiocytes. The finding is similar to that seen in interdigitating reticulum cells, a specialized cell found in the paracortex of human lymph nodes.

Acid Phosphatase↗
PubMed1981

Studies of a human T lymphocyte antigen recognized by a monoclonal antibody.

A monoclonal antibody (designated L17F12) detects an antigen present on 95-100% of human peripheral T lymphocytes, the majority of thymocytes, and acute lymphocytic leukemia T cells but not B cells, B-cell lines, or monocytes. Examination of frozen tissue sections by the immunoperoxidase method revealed that the cells expressing this antigen were found predominantly in the medulla of thymus and in T-cell zones of lymph node and spleen. The antigen recognized by L17F12 was associated with a cell-surface glycoprotein of 67,000 daltons. L17F12 was used to isolate this molecule from human thymocytes, normal peripheral T cells, leukemic T cells, and T-cell lines. Expression of this antigen on normal T cells was not diminished by prolonged exposure in vitro to various T-cell stimuli. In the absence of complement, L17F12 bound to T cells without altering proliferative functions, thus enabling rapid purification of functionally intact T cells. In the presence of complement, L17F12 was cytolytic for T cells, providing the basis for depletion of T cells from heterogeneous populations. These data suggest that the monoclonal antibody L17F12 recognizes a specific T-cell differentiation protein. This antibody will be useful in studies of the human immune system.

Animals↗
PubMed1981

Suppression of endogenous avidin-binding activity in tissues and its relevance to biotin-avidin detection systems.

As biotin-avidin systems continue to be developed for applications involving single cells, cell suspensions, and especially tissue sections, the need arises for a method of blocking endogenous avidin-binding activity. One such method is described and its proposed mechanism is discussed. Utilizing this method, endogenous avidin-binding activity was detected and suppressed in selected human and murine tissues, thus facilitating the interpretation of specific immunohistochemical staining utilizing hybridoma monoclonal antibodies in a biotin-avidin-horseradish peroxidase detection system.

Animals↗
PubMed1980

Immunologic phenotype in 30 patients with diffuse large-cell lymphoma.

Frozen sections of 30 diffuse large-cell ("histiocytic") lymphomas that had arisen in both nodal and extranodal sites were stained with immunoglobulin light-chain and heavy-chain reagents, with nonoclonal antibodies to THAT HAD ARISEN IN BOTH NODAL AND EXTRANODAL SITES WERE STAINED WITH IMMUNOGLOBULIN LIGHT-CHAIN AND HEAVY-CHAIN REAGENTS, WITH MONOCLONAL ANTIBODIES TO T and B-cell antigens, and with an esterase marker for macrophages. Fourteen lymphomas expressed immunoglobulin light chains and were shown to be monoclonal; F(ab')2 fragments were sometimes necessary to demonstrate their monoclonal nature. Mu (IgM) was the most frequently expressed heavy chain, but in many patients other heavy chains were found. None of the lymphomas stained with T-cell antibodies or the esterase; 15 did not stain for immunoglobulin, but 13 of these 15 did express Ia antigen. These immunologic markers identified eight different phenotypes. Retrospective clinical analysis of the patients suggested that those who were immunoglobulin-positive had more advanced disease and shorter survival, but confirmation of the clinical relevance of immunologic phenotype will require prospective studies.

Adult↗
PubMed1980

Detection of T and B cell antigens hybridoma monoclonal antibodies: a biotin-avidin-horseradish peroxidase method.

Acetone-fixed frozen sections of reactive lymph node, spleen, three B cell lymphomas, and three T cell lymphomas were studied for the presence of Ia-like antigens and two T cell antigens. Detection of the binding of the hybridoma monoclonal antibodies to these antigens took advantage of the biotin-avidin interaction. The detection method employed a biotin conjugate of goat anti-mouse antibody and an avidin conjugate of horseradish peroxidase. B cell lymphoma cells stained for Ia. The cell lymphomas were shown to be heterogeneous for the expression of the two T cell antigens. these three antigens were generally not detectable after 10% formalin fixation of B-5 fixation. Detection of these antigens and the method employed should prove useful in the immunologic categorization of human lymphomas.

Animals↗
PubMed1979

Non-Hodgkin's lymphoma: a study of the evolution of the disease based upon 92 autopsied cases.

The evolution of the disease process in 92 patients with non-Hodgkin's lymphoma has been analyzed by comparing the initial histopathologic material with that obtained at autopsy. The distribution of lymphoma did not differ substantially among the subtypes, but the gross appearance of the lesions was different among certain subtypes, particularly between the "small cell" and "large cell" types. The diffuse lymphomas showed a remarkable constancy of subtype in the same patient, whereas the nodular lymphomas showed a high frequency of change to a diffuse pattern and/or a larger cell type. Diffuse histiocytic lymphomas with plasmacytoid features showed a striking propensity for involvement of the gastrointestinal tract. The occurrence and significance of bizarre pleomorphic giant cells, epithelioid histiocytes, a "starry-sky" pattern, erythrophagocytosis, hemosiderosis and extramedullary hematopoiesis are reported. All patients received anti-lymphomatous chemotherapy and/or radiotherapy. A second malignancy was observed in 8 patients. Thirteen patients showed no residual lymphoma at autopsy. The cause of death was considered to be related to lymphoma in all 92 patients; 67 had infections identified.

Adolescent↗
PubMed1979

A human thymus-leukemia antigen defined by hybridoma monoclonal antibodies.

A series of mouse hybridomas producing monoclonal antibodies against human acute lymphocytic leukemia (ALL) cells was generated and screened for tumor specificity. Among 1200 primary cultures, 60 produced an antibody that could distinguish between the immunizing leukemia cells and an isologous B lymphoblastoid cell line. Of these, two produced an antibody that detects an antigen expressed preferentially on ALL cells and on a subpopulation of normal cells found in the cortex of the thymus. Other normal human lymphoid cells from lymph nodes, spleen, bone marrow, and peripheral blood express only low levels of this antigen. High levels of this "thymus-leukemia" antigen were found on T-ALL cells, T-ALL-derived cell lines, and some "null" ALL cells. By contrast, B-cell leukemias, B lymphoblastoid cell lines, and normal and malignant myeloid cells contain either low or undetectable amounts of this antigen. The thymus-leukemia antigen has been isolated from the membranes of leukemia cells by detergent solubilization and subsequent immunoprecipitation with the monoclonal antibody. Preliminary biochemical characterization shows the antigen to be associated with a polypeptide of Mr approximately 28,000.

Antibody Specificity↗
PubMed1979

Alteration of immunoglobulin-bearing lymphoma cells by fixation.

Four large cell lymphomas known to be monoclonal B-cell proliferations were studied with immunofluorescent and immunohistochemical methods for the detection of kappa- and lambda-light chains. Frozen sections of lymphoma tissues as well as formalin and B-5-fixed tissues embedded in paraffin were studied. Both immunofluorescent and immunohistochemical methods gave similar results on frozen sections; however, a number of discrepancies were noted between the results obtained on fixed tissues and those obtained on frozen tissues. In an effort to identify a fixative which did not alter immunoglobulin (Ig), mouse lymph nodes were fixed in different fixatives before Ig detection; but all of the fixatives tested destroyed the Ig present on normal cortical B lymphocytes. Immunoglobulin-bearing normal and neoplastic lymphocytes are better detected on frozen sections than on paraffin sections after routine fixation.

Animals↗
PubMed1978

Exogenous immunoglobulin and the macrophage origin of Reed-Sternberg cells in Hodgkin's disease.

We studied Reed-Sternberg cells from 14 patients with Hodgkin's disease to learn whether they had monoclonal immunoglobulin synthesized by the cell or polyclonal immunoglobulin of external origin. Double-label immunofluorescence with F(ab')2 anti-serums to human light chains showed that cytoplasmic immunoglobulin of individual Reed-Sternberg cells is always polyclonal and usually associated with membrane-bound immunoglobulin of the same type. The predominant immunoglobulin was IgG; in one case IgM was also present. In vitro studies confirmed the internalization of exogenous IgG and phagocytosis of immune complexes by viable Reed-Sternberg cells. Their exclusion of trypan blue dye and lack of albumin and fibrinogen suggests relatively specific uptake of immunoglobulin, mediated by the Fc receptor or antigen (or antigens) associated with Hodgkin's disease at the cell membrane. Our studies support other recent evidence that the Reed-Sternberg cell is derived from a macrophage.

Adolescent↗
PubMed1978

Immunopathology of follicular lymphomas. A model of B-lymphocyte homing.

To investigate whether follicular lymphoma has a monoclonal origin, we stained frozen tissue sections from 22 afflicted patients for kappa and lambda light chains with an immunofluorescence technic. F(ab')2 antibody fragments were used to avoid binding by Fc receptors. In 20 cases the lymphoma nodules comprised a monoclonal population of immunoglobulin-producing cells. The nodules were usually surrounded by a normal, polyclonal population of B lymphocytes. Reactive lymphoid follicles were easily differentiated from lymphoma nodules on the basis of clonality. Eight cases contained multiple immunoglobulin heavy chains. All the lymphoma nodules in the same tissue or in multiple tissues in the same patient showed identical light-chain and heavy-chain staining even if different histologic subtypes were identified. Follicular lymphoma is the outgrowth of a single clone of immunoglobulin-bearing cells that retain the tissue-homing characteristics of B lymphocytes.

B-Lymphocytes↗
PubMed1978

The lymphoid system. Its normal architecture and the potential for understanding the system through the study of lymphoproliferative diseases.

This article presents a view of lymphoid tissue architecture as defined by the traffic of defined lymphoid cell classes. The compartmentalization of lymphocytes is discussed in reference to specific cell-cell interactions that occur in antigen-driven immune responses. Finally, the distribution of normal and neoplastic lymphocytes in humans is defined and compared with animal model systems.

Animals↗
PubMed1978

A study of lymphoproliferative diseases comparing immunofluorescence with immunohistochemistry.

Sections of lymph nodes from patients with lymphoproliferative disorders were stained by immunofluorescence and immunoperoxidase methods. Staining with anti-kappa and anti-lambda antibodies employed F(ab')2 fragments of purified antibodies to avoid binding via Fc receptors. Frozen-section immunofluorescence revealed that B-cell lymphomas were composed of monoclonal populations of Ig-bearing cells. With immunohistochemical technics, however, a significant number of B-cell lymphomas either did not stain for Ig or showed spurious staining. The possible reasons for lack of staining in some cases and spurious staining in others are discussed. As currently applied to lymphoproliferative disorders, immunofluorescence appears to be more senitive and more speific than immunohistochemistry.

Cell Transformation, Neoplastic↗