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Biomedical subjects

K C Gatter

Publications and source records attributed to K C Gatter.

At least 217 records · Page 12Linked to original sources

The use of monoclonal antibody Y1/82A in the identification of acute myeloblastic and monocytic leukemias.

A newly developed monoclonal antibody (Y1/82A), which binds a cytoplasmic antigen in peripheral blood monocytes and tissue macrophages, was tested for its ability to detect monocytic differentiation in acute myeloid leukemia, i.e., to distinguish French-American-British (FAB) groups M4 and M5 from FAB groups M1, M2, M3, M6 and M7. Staining was performed by the alkaline phosphatase-antialkaline phosphatase (APAAP) immunocytochemical technic on bone marrow smears from 29 cases of acute myeloid leukemia, on 17 normal peripheral blood and/or bone marrow smears, on bone marrows from 10 cases of lymphoid leukemia, and on lymph nodes of 13 patients with lymphoma. Neoplastic cells from 11 of 11 patients with either M4 or M5 leukemia had positive results, whereas only 2 out of 18 cases of M1, M2, M3, M6, and M7 leukemia had positive results. In normal samples, only peripheral blood monocytes, bone marrow macrophages, and megakaryocytes stained. Lymphoid neoplasms were unreactive. These results suggest that monoclonal antibody Y1/82A may be a useful reagent in detecting cases of M4 and M5 acute myeloid leukemia and that it offers a valuable alternative to nonspecific esterase cytochemistry.

Antibodies, Monoclonal↗

Granular cell tumours revisited. An immunohistological and ultrastructural study.

Twenty-five granular cell tumours were stained with a panel of antibodies to histiocytic, muscle, neural, neural crest, epithelial and endothelial markers. Electron microscopy was also performed in six cases. Twenty-four of the cases were similar morphologically and immunocytochemically. One case with features of an endothelial origin is described. The present study strongly supports the viewpoint that granular cell tumours are a distinct entity rather than being the common appearance of a group of lesions of differing histogenesis. Origin from a neural crest-derived peripheral nerve-related cell is favoured.

Humans↗

Epithelial membrane antigen expression by the perineurium of peripheral nerve and in peripheral nerve tumours.

Specimens of normal peripheral nerve and a series of peripheral nerve lesions have been immunostained with three different anti-epithelial membrane antigen (EMA) monoclonal antibodies. Sites of EMA immunoreactivity have been confirmed within perineurial cells of peripheral nerve, noted within the capsule of Schwannomas and palisaded encapsulated neuromas, and also detected with traumatic neuromas and plexiform neurofibromas. No expression was detected within simple neurofibromas, diffuse neurofibromas or within malignant Schwannomas. These sites of EMA expression concur with the suggested involvement of perineurial cells in the formation of the particular lesions. The relationship between EMA expression by the perineurium and the piaarachnoid membrane is discussed.

Antibodies, Monoclonal↗

The immunohistological detection of platelets, megakaryocytes and thrombi in routinely processed specimens.

The production and characterization of a new monoclonal antibody, Y2/51, against platelet glycoprotein IIIa is described. A useful feature of this antibody is its ability to recognize platelets and megakaryocytes in formalin-fixed routinely processed material. It could also be used to reveal platelets both in thrombi in large vessels and in microthrombi too small to be readily apparent on conventional microscopic examination. For this purpose it was helpful to use the antibody in conjunction with a new monoclonal reagent (Ret40f) against red cell sialoglycoprotein beta which detects red cells and their precursors in routinely processed tissue. The use of these antibodies should be valuable for the detection of thrombi in a variety of situations such as renal transplant rejection, coronary artery disease and vasculitis.

Animals↗

Immunohistochemistry of cytokeratin proteins in squamous and transitional cell lesions of the urinary tract.

Expression of low and high molecular weight cytokeratin proteins was investigated immunohistochemically in a variety of transitional and squamous epithelial lesions of the urinary tract with and without schistosomiasis. The monoclonal antibodies used were CAM 5.2 and NCL5D3 for low, PK 63 and 121 for high, and MAK 6 for a broad range of intermediate molecular weight cytokeratins. On staining with CAM 5.2 and NCL5D3, urothelial hyperplasias (n = 12) and grades 1 (n = 5) and 2 (n = 10) papillary transitional cell carcinomas showed labelling patterns quite distinct from carcinoma in situ (n = 4) and non-papillary grades 2 (n = 6) and 3 tumours (n = 3). Among squamous lesions only focal positivity was obtained in 14 of 22 moderate to poorly differentiated squamous cell carcinomas. By contrast, PK 63 and 121 stained squamous lesions exclusively. MAK 6 stained the whole range of urothelial and squamous lesions with the exception of squamous metaplasias. Polyclonal antikeratin adequately labelled spindle cell areas of high grade tumours. The distinctive staining patterns given by these or similar antibodies may help in the identification of squamous metaplasia and in diagnosing tumours of the urothelium.

Carcinoma, Squamous Cell↗

EBM/11 reactivity in malignant histiocytosis.

A patient presented initially with a testicular mass, which on biopsy had morphological features consistent with malignant histiocytosis. The tumour cells labelled strongly with EBM/11, a murine monoclonal antibody with high specificity for cells of the human mononuclear phagocyte system. Subsequent clinical and laboratory studies confirmed the diagnosis. As poorly differentiated tumour cells reacted with EBM/11, this antibody may be useful in positively identifying malignant tumours with histiocytic differentiation from malignancies of other types where morphological detail alone is inconclusive in tumour classification.

Aged↗

Antisera against epitopes resistant to denaturation on T3 (CD3) antigen can detect reactive and neoplastic T cells in paraffin embedded tissue biopsy specimens.

Polyclonal rat antisera, raised against affinity purified CD3 antigen, gave strong immunoenzymatic labelling of T cells in routine paraffin embedded sections, with negligible background staining. The specificity of these reactions was confirmed by staining biopsy specimens from 21 previously phenotyped non-Hodgkin's lymphomas (including 14 of T cell origin and six of B cell origin). It is suggested that the ability of the polyclonal anti-CD3 antisera to detect T cells in paraffin sections is due to the presence in these sera of antibodies against fixation resistant epitopes on CD3 antigen, and that immunisation with purified denatured preparations of other white cell associated antigens may broaden the range of antibodies suitable for the phenotypic analysis of leucocytes in routine histological samples.

Antigens, Differentiation, T-Lymphocyte↗

Monoclonal antibody (Y1/82A) with specificity towards peripheral blood monocytes and tissue macrophages.

A new monoclonal antibody, Y1/82A, was raised against phytohaemagglutinin activated peripheral blood mononuclear cells. Using an immunohistochemical technique it was shown that Y1/82A reacts against peripheral blood and bone marrow monocytes and resident macrophages from essentially all human tissues. Y1/82A bound to determinants present in leukaemic cells from patients with acute myelomonocytic leukaemia and acute monocytic leukaemia, but not to neoplastic cells from patients with malignant lymphoproliferative disorders or malignant epithelial tumours. Y1/82A failed to react with other cell types, with the exception of osteoclasts and megakaryocytes. Analysis by Western blotting showed that the antigen detected by antibody Y1/82A was associated with intracellular granules in macrophages. Monoclonal antibody Y1/82A may be useful in the diagnosis of monocytic leukaemias and histiocytic neoplasms and in the identification of macrophages in tissues from various inflammatory and neoplastic conditions.

Antibodies, Monoclonal↗

Use of monoclonal antibody against human neutrophil elastase in normal and leukaemic myeloid cells.

A monoclonal antibody, NP57, was produced and used against the neutrophil granule protein elastase, which selectively stain neutrophils in cryostat and paraffin wax sections. The antibody stains neutrophils and a subpopulation of monocytes in blood smears and neutrophil precursors in bone marrow smears, and gives positive reactions with the cell lines HL60 and U-937. It labelled the blast cells in 68% of cases of acute myeloid leukaemia (M1-M5) but was unreactive with all cases of lymphoid leukaemias. Most of the elastase negative myeloid leukaemias were labelled by monoclonal anti-myeloperoxidase (antibody MPO-7) as were cells from the promyelocytic line HL60. No cases of myeloid leukaemia showed the opposite pattern--that is elastase positive, myeloperoxidase negative, suggesting that the production of myeloperoxidase precedes the onset of elastase synthesis during myeloid maturation. The anti-elastase antibody NP57 is a useful addition to the range of monoclonal antibodies available for the differential diagnosis of acute leukaemia by alkaline phosphatase-antialkaline phosphatase (APAAP) labelling of cell smears; it may also be of value for the histopathological diagnosis of tumour deposits in myeloid leukaemia and for the detection of neutrophils in paraffin sections.

Antibodies, Monoclonal↗

Biochemical evidence that cytokeratins are present in smooth muscle.

Recent immunocytochemical studies have revealed that cytokeratin intermediate filaments, previously thought to be restricted to epithelial tissues, are present in muscle. In view of the implications of these reports for diagnostic pathology it is important to investigate by biochemical means whether these findings represent the presence of true cytokeratin proteins or an unexpected antigenic cross-reaction. In the present study intermediate filament proteins have been extracted from samples of human myometrium and identified by immunoblotting techniques using well characterized monoclonal antibodies, two against cytokeratins and two against desmin. The results show that the proteins of the appropriate molecular weight for cytokeratin were labelled by anti-cytokeratin antibodies and were quite distinct from those recognized by anti-desmin antibodies. This study therefore confirms previous immunocytochemical findings and emphasizes the need for caution when using anti-intermediate filament antibodies for diagnostic purposes.

Antibodies, Monoclonal↗

Coexpression of epithelial membrane antigen (EMA), Ki-1, and interleukin-2 receptor by anaplastic large cell lymphomas. Diagnostic value in so-called malignant histiocytosis.

A group of 63 cases of anaplastic large cell lymphomas (variants of diffuse large cell lymphomas often diagnosed as "malignant histiocytosis") was characterized on both morphologic criteria and expression of epithelial membrane antigen (EMA) and Ki-1 antigen (CD30). On the basis of the reactivity of these tumors with anti-EMA and anti-Ki-1 antibodies, four subtypes could be distinguished. In the majority of cases (n = 49), neoplastic cells coexpressed EMA and Ki-1 antigens. Nineteen of these cases were tested for IL-2R, and all were positive (Type I, EMA+, Ki-1+, IL-2R+). In the second group (n = 5), the neoplastic cells expressed EMA but not the Ki-1 antigen. These cases were not tested for the presence of IL-2R (Type II, EMA+, Ki-1-, IL-2R?). There were tumors with similar morphology expressing only Ki-1 antigen (Type III, EMA-, Ki-1+, IL-2R-) or negative for both EMA and Ki-1 antigens (Type IV, EMA-, Ki-1-, IL-2R-). EMA appeared to occur predominantly on activated cells, as has been previously shown for Ki-1 antigen. Analysis using monoclonal antibodies to T-cell, B-cell, or macrophage-associated differentiation antigens showed that these tumors were heterogeneous in terms of cell lineage. Tumors coexpressing EMA, Ki-1, and IL-2R (Type I), were most commonly of T-cell origin (n = 12); the remainder in this type expressed B-cell markers (n = 4), a mixed B/T phenotype (n = 2), or no clear phenotype (n = 9). By contrast, tumors of Types II, III, and IV were mainly from B-cell origin (n = 6) or showed a mixed B/T phenotype (n = 1). Despite the fact that a significant proportion of these cases were initially classified morphologically as "malignant histiocytosis," only 3 of the 63 cases were possibly of histiocytic origin. These results confirm that true malignant histiocytosis is rare and that most tumors with histologic features currently regarded as being consistent with this diagnosis are lymphocytic in origin and express activation antigens such as EMA, Ki-1 antigen, and IL-2R.

Antibodies↗

Immunophenotyping of acute myeloid leukemia by immuno-alkaline phosphatase (APAAP) labeling with a panel of antibodies.

A panel of eight antibodies was used by the alkaline-phosphatase/anti-alkaline phosphatase (APAAP) method to stain peripheral blood films, bone marrow smears, and cytocentrifuge preparations from 29 cases of acute myeloid leukemia. These findings were correlated with the French-American-British (FAB) classification. Leukemic cells from six cases of myeloblastic leukemia (FAB;M1) were predominantly labeled by the antimyeloperoxidase monoclonal antibody (MPO-7). Leukemic cells from the majority of eight cases of myeloblastic leukemia with maturation (FAB;M2) and progranulocytic leukemia (FAB;M3) stained with monoclonal antibodies MPO-7, NP57 (anti-elastase), and EBM11 (antimonocyte/macrophage). Leukemic cells from six cases of myelomonocytic (FAB;M4) and five cases of monocytic (FAB;M5) leukemia were most often labeled with antibodies MPO-7, NP57, and EBM11 as well as monoclonal antibodies Y1/82A (anti-monocyte) and KB90 (against the p150, 95 molecule, CD11c; a monocyte/granulocyte marker), but not with monoclonal antibody C17 (antiglycoprotein IIb/IIIa) and/or monoclonal antibody Y2/51 (antiglycoprotein IIIa). Erythroblasts from a single case of erythroleukemia (FAB;M6) were not labeled with any of the antibodies from this panel. Leukemic cells from two cases of acute megakaryocytic leukemia (FAB;M7) stained strongly with the monoclonal antiglycoprotein IIIa/IIb antibody (C17) and antiglycoprotein IIIa antibody (Y2/51). Staining by the APAAP method with this panel of antibodies was easy to perform, required no expensive instrumentation, and provided useful information in the classification of acute myeloid leukemia.

Alkaline Phosphatase↗

Expression of a Hodgkin and Reed-Sternberg cell associated antigen (Ki-1) in cutaneous lymphoid infiltrates.

Skin biopsy specimens from normal skin and from 115 patients with benign dermatoses, pre- or pseudo-malignant disorders or malignant cutaneous lymphomas have been examined immunohistologically for expression of the Reed-Sternberg cell associated antigen CD30 detected by monoclonal antibodies Ki-1 and Ber-H2. The antibodies stained the atypical cells in lymphomatoid papulosis, a proportion of the neoplastic cells in some cases of mycosis fungoides and most of the neoplastic cells in six large cell anaplastic/pleomorphic non-Hodgkin's lymphomas. The lymphoid cells in all other specimens were Ki-1- and Ber-H2-negative. In all cases, expression of the Ki-1/Ber-H2 antigen was accompanied by expression of activation and proliferation associated markers (i.e., HLA-DR, IL-2 receptor, transferrin receptor and the Ki-67 nuclear antigen). These data indicate the value of antibodies Ki-1 and Ber-H2 in distinguishing between lymphomatoid papulosis and other types of pre- or pseudo-malignant disorders and support the view that lymphomatoid papulosis, Hodgkin's disease and some types of non-Hodgkin's lymphoma constitute a spectrum of related disorders, originated from activated lymphoid cells.

Antibodies, Monoclonal↗

Immunohistological analysis of the lymphoid infiltrate in cutaneous malignant melanomas.

The immunological phenotypes of the lymphoid cells in 39 cutaneous malignant melanomas have been investigated by staining cryostat sections with a panel of 20 monoclonal antibodies against lymphoid cells and their subsets. Staining was performed by the alkaline phosphatase: anti-alkaline phosphatase (APAAP) method in which the substrate label (red) is easily distinguishable from melanin. The lymphoid infiltrates had an essentially identical composition in all cases, consisting of T-lymphocytes associated with both Langerhans cells and HLA-DR-positive tissue macrophages. B-lymphocytes and natural killer cells were either absent or only present in low numbers. The ratio between T8 (suppressor/cytotoxic) and T4 (helper/inducer) lymphocytes varied and showed no correlation with melanoma subtype, level of invasion or magnitude of lymphocytic response. Examination for markers associated with T-cell activation and/or with cell proliferation revealed that all lesions contained HLA-DR-positive T-lymphocytes, whereas expression of the transferrin receptor and the interleukin-2 receptor (Tac-antigen) occurred mainly in melanomas with a significant inflammatory infiltrate. These data support the concept that malignant melanomas are capable of evoking autologous T-cell immune reactions.

Alkaline Phosphatase↗

Is it necessary to embed bone marrow biopsies in plastic for haematological diagnosis?

With the increase in the use of bone marrow trephines for diagnosis have come numerous reports that traditional methods of preparation (by decalcification and embedding in paraffin wax) should be replaced by plastic embedding to avoid decalcification. It has been argued that only by this means can the high quality preparations needed for accurate haematopathological diagnosis be achieved. The present study challenges this viewpoint and argues that with a little extra care and attention conventional paraffin embedding techniques can give equally high quality preparations. Sections prepared in this way meet the diagnostic needs of the haematologist, without requiring a separate technique to be established in the pathology laboratory solely for bone marrow trephines.

Biopsy↗

An immunohistochemical study of differentiation in malignant fibrous histiocytoma.

Immunohistochemistry was used to examine 10 cases of malignant fibrous histiocytoma. Malignant cells in all cases expressed vimentin and in eight there was co-expression of either desmin or neurofilament, both of these being present in four cases. In addition, cytokeratin was found in one case. In each tumour, a population of small cells was identified which had the staining characteristics of benign macrophages, and this was distinct from the tumour cells. This study supports the concept that malignant fibrous histiocytoma is a tumour of mesenchymal cells rather than of histiocytes and emphasizes the diversity of its cytostructure.

Antibodies, Monoclonal↗

Cytokeratin expression in smooth muscle and smooth muscle tumours.

The expression of cytokeratin intermediate filaments by a tumour has been accepted as evidence of an epithelial origin. Although there have been anecdotal reports of cytokeratin expression within tissues and neoplasms of non-epithelial origin, particularly muscle, there have been no comprehensive studies of its frequency and distribution. In order to investigate this we have studied 51 cases of normal smooth muscle and benign and malignant smooth muscle tumours using a panel of monoclonal antibodies against a range of intermediate filaments (cytokeratins, desmin and vimentin). Cytokeratin expression was noted overall in 50% of normal, benign and malignant smooth muscle tissues. Such expression tended to have a focal or patchy distribution. No case expressed cytokeratins in the absence of both desmin and vimentin. The implication of these findings for diagnostic immunocytochemistry is that intermediate filaments alone are not completely reliable markers of tumour histogenesis and should be used as part of a larger panel of monoclonal antibodies.

Desmin↗