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Biomedical subjects

G F Burns

Publications and source records attributed to G F Burns.

At least 19 recordsLinked to original sources

Chronic myelomonocytic leukemia with paraproteinemia but no detectable plasmacytosis: a detailed cytological and immunological study.

A patient with chronic myelomonocytic leukemia with IgG K paraproteinemia, but no detectable plasmacytosis, is described. The patient was entering a blastic phase at the time of the most detailed studies. Cytological, cytochemical, and ultrastructural studies revealed a mixed myeloid proliferation with granulocytic forms predominating over monocytic elements. A variety of ultrastructural abnormalities, including defective granulation, was observed but no cells with highly developed rough endoplasmic reticulum were observed. Immunological marker studies showed that the mature myeloid cells possessed receptors for the Fc of IgG and weakly expressed the Ia-like P29/34 antigen. The mature myeloid cells also expressed both surface and intracytoplasmic Ig restricted to IgG K, and this IgG K persisted after 4 weeks in culture. A reverse plaque assay showed that the myeloid cells were capable of releasing IgG K in vitro, but studies involving the incorporation of radio-labeled amino acids showed no detectable Ig production by the myeloid cells. The possible interpretations of these data are discussed in some detail in relation to previous reports of paraproteinemia in myeloid proliferative disorders.

Aged

The detection of membrane-associated complement components (C 3 and C 4) on circulating human normal and leukemic leukocytes and on cultured cells with monkey erythrocytes.

Monkey erythrocyte (Mk) rosette formation is described as an exquisitely sensitive method for the detection of complement (C) components on the membrane of human leukocytes. Blocking of the immune adherence receptor on Mk blocked subsequent rosette formation as did pretreatment of leukocytes with antiserum to the C components C 3 and C 4. In vitro C deposition by immune complex formation with normal human lymphocytes enhanced Mk rosette formation, and this could be inhibited with antiserum to C 3. The use of Mk rosette formation revealed that cells from a wide variety of human lymphoid and myeloid leukemias carry membrane-bound C. It was also shown that several lymphoblastoid cell lines, including a T cell line, probably synthesize both C 3 and C 4. Mk rosette formation is not dependent on metabolic activity of the rosetting leukocyte, and it is suggested that this technique will be of value in detecting C deposition in a variety of situations.

Animals

Membrane receptors of human leukaemic myeloid cells: sequential expression of the gamma Fc receptor.

An immunological surface marker study was performed on 13 patients with a variety of myeloid leukaemias. It was shown that expression of the receptor for the Fc of IgG (gamma FcR) starts to take place at the promyelocyte stage, and that the receptor is present on more mature granulocytic cells, but is absent from myeloblasts. Myeloblasts and promyelocytes are negative for the complement receptor CR2. Monoblasts, unlike myelobasts, were shown to express a gamma FcR and, to a lesser extent, CR2. Receptor expression therefore appears to be an earlier event in monocytic development. The possible diagnostic value of immunological marker studies in myeloid disorders is considered.

Cell Membrane

Typical hairy-cell leukaemia with IgGk paraproteinaemia.

A case of hairy-cell leukaemia (HCL) with IgG(k) paraprotein is described. The typical clinico-pathological features of the patient are stressed, and it is shown that the hairy cells (HCs) were producing and secreting IgGk. The case is placed in a more general context by the demonstration that HCs from other typical cases of HCL produce and secrete IgG. These findings conclusively demonstrate that HCL is a B-cell disease.

Aged

A re-examination of the alleged monocytic features of hairy-cell leukaemia.

A number of the 'monocytic' features of the hairy cells (HCs) of hairy-cell leukemia (HCL) are studied in detail and discussed in relation to the now established B-cell nature of the disease. By means of a rosette assay employing erythrocytes coated with IgG (EAG), a receptor for the Fc of IgG is shown to be strongly expressed on all HCs, whether in suspension or in monolayers. This receptor is shed and re-expressed over a period of some 6 h. In EAG rosette formation the indicator erythrocytes are deformed and the receptor is not blocked by an antiserum to the Ia-like antigen. By ultrastructural acid-phosphatase cytochemistry, it is established that HCs phagocytose latex particles, but do not phagocytose a variety of other particles to a significant extent. These, and other features, are discussed in relation to the literature and it is shown that all are compatible with the current view that HCL is a form of B-cell lympholiferative.

Cells, Cultured

Hairy-cell leukaemia: an immunoperoxidase study of paraffin-embedded tissues.

Paraffin sections of a variety of tissues from 12 patients with typical hairy-cell leukaemia (HCL) were stained for immunoglobulin heavy and light chains by the peroxidase-antiperoxidase (PAP) technique. Plasma cells were frequent, particularly in a lymph node from a severely infected patient. The reactive nature of the plasma cells of HCL was suggested by the fact that there was no restriction of light-chain expression, although viable hairy cells were shown to express monoclonal surface immunoglobulin. This, together with the absence by both light and electron microscopy of forms intermediate between hairy cells and plasma cells and the lack of ribosome-lamella complexes in the plasma cells, suggested that hairy cells do not differentiate into plasma cells. Although hairy cells are known to contain immunoglobulin, this was not demonstrable in hairy cells in the paraffin-embedded tissue. The PAP technique was also useful for demonstrating abundant splenic macrophages in HCL.

Humans

Platelet function in hairy-cell leukaemia.

A quantitative study of various aspects of platelet function was carried out in eight patients with typical hairy-cell leukaemia (HCL). In at least two patients platelet aggregation was convincingly reduced to more than one aggregating agent (ADP, adrenaline, collagen, thrombin, and ristocetin). Granular storage capacity for {(14)C} 5-HT was reduced in five of the six patients tested. The two patients with definitely abnormal aggregation had the greatest reduction in granular storage pool and the longest bleeding times of those tested but, like the other patients, they did not have a clinical haemostatic defect. It was concluded that a granular storage pool defect (SPD) was at least partly responsible for aggregation abnormalities in HCL since the platelet release reaction in response to thrombin appeared to be normal. All our patients ran a chronic course uncomplicated by any of the factors known to predispose to a platelet SPD acquired in the circulation. Although in the one patient tested before and after splenectomy there was some improvement in platelet aggregation after operation, there was no clear general relationship between defective platelet function and either previous splenectomy or platelet count. Since a direct involvement of the megakaryocytic series in the underlying cell proliferation of HCL seems unlikely, it is concluded that the platelet defect can most reasonably be attributed to the production of abnormal platelets as a result of marrow fibrosis and/or infiltration by hairy cells.

Bleeding Time

Characterization of the receptor for IgM present on human B lymphocytes.

The presence of a receptor for the Fc of IgM (muFcR) was demonstrated on the pathological B cells of all of sixteen patients with hairy-cell leukaemia and most, but not all, of twenty-four cases of chronic lymphocytic leukaemia, by a rosette method employing ox erythrocytes sensitized with purified IgM (EAm). This muFcR was also demonstrated on a small population of normal human mononuclear cells from peripheral blood. Pathological B cells with this receptor (Bm) simultaneously expressed a different and distinct receptor for the Fc of IgG, and were detectable without preincubation in medium containing foetal calf serum (FCS). The muFcR on B cells was blocked by Fc5mu and IgM, but not by F(ab')2mu fragments, or by IgG, whether monomeric or aggregated. Monomeric IgM and IgM bound to its antigen blocked much more effectively than pentameric IgM. B cells also possessed surface immunoglobulin and the Ia-like P29, 34 antigen, and an antiserum to this antigen blocked the muFcR. The muFcR on B cells differs in a number of ways from the muFcR reported on T cells, and these differential characteristics are discussed in some detail. The muFcR was rapidly shed and resynthesized when washed Bm cells were maintained in medium not containing FCS and the general importance of this phenomenon in any study of muFcR is considered. It is suggested that Bm cells are memory cells and that the muFcR plays a part in the immune response.

B-Lymphocytes

Cytochemical, ultrastructural and immunological studies of circulating Reed-Sternberg cells.

Reed-Sternberg (R-S) cells in the circulating blood of a patient with Hodgkin's disease were cytochemically peroxidase and Sudan black negative, devoid of alkaline phosphatase and non-specific esterase, mostly PAS negative but occasionally showing positivity, and nearly always showing moderately strong granular positivity for acid phosphatase. Electron microscopy showed irregular nuclear profiles, conspicuous nucleoli, a moderate development of cytoplasmic organelles but absence of structures resembling monocytic granules. The R-S cells frequently possessed receptors for the Fc region of IgG and were mostly positive for SmIg, but did not form rosettes with sheep or mouse erythrocytes nor have receptors for the Fc region of IgM or the C3 component of complement. The combined results suggest that R-S cells are of B-cell lineage.

Acid Phosphatase

Identification of the hairy cells of leukaemic reticuloendotheliosis by an esterase method.

A distinctive pattern of alpha-naphthyl butyrate esterase positivity was observed in all of a series of 14 patients with HCL. This pattern was not observed in a range of other haematological malignancies including nine cases of CLL, two cases of Sézary's syndrome, six cases of null cell ALL, two cases of Schilling-type monocytic leukaemia and one case of lymphosarcoma cell leukaemia. The potential diagnostic value of this simple cytochemical test is discussed in relation to existing methods.

Acid Phosphatase

Morphological and immunological similarity of the monocytes from pure and mixed monocytic leukaemias.

Morphological and immunological marker data on a patient with 'pure' monocytic leukaemia are presented and compared with those of 6 cases of clearly mixed myelomonocytic leukaemia with a variable monocytic component. In all patients studied, the leukaemic monocytes expressed a receptor for the Fc of IgG, and IgG sensitization markedly enhanced phagocytosis of ox erythrocytes. A variable, but lower, percentage of the leukaemic monocytes had a receptor for mouse C3, but the cells uniformly lacked surface immunoglobulin and receptors for the Fc of IgM and for unsensitised mouse erythrocytes. Cytochemical and ultrastructural study also showed no clear difference between the monocytes of the 'pure' and mixed monocytic leukaemias. This report therefore lends no support to the concept of distinct types of monocytic leukaemia.

Binding Sites, Antibody

Evidence for the presence of a receptor for IgM on the pathological cells of Sézary's syndrome.

It has been demonstrated that in two patients with T-cell Sézary syndrome the pathological cells express a receptor for EA(IgM) when cultured in a medium with foetal calf or autologous serum. A study of the time-course of this rosette formation revealed that a large proportion, but not all, of E-rosetting cells progressively expressed this receptor. In agreement with previous reports by others on the normal T-cell population bearing the IgM receptor, incubation at 37 degrees C in the presence of serum was shown to be a necessary condition. The implications of this pathological subpopulation of T-cells are discussed.

Binding Sites