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Biomedical subjects

A E Dewar

Publications and source records attributed to A E Dewar.

At least 37 records · Page 2Linked to original sources

Expression of MHC class II antigens in human B-cell leukaemia, and increased levels of class II antigens and DR-specific mRNA after stimulation with 12-O-tetradecanoyl phorbol-13-acetate.

Cells from the peripheral blood of B-cell chronic lymphocytic leukaemia (CLL) patients were examined serologically for the expression of cell surface MHC class II antigens with monoclonal antibodies (mAbs) specific for the products of HLA-DP, -DQ and -DR genes, and mRNAs from the cells of three patients were analysed with a cDNA probe specific for DR beta chain genes. In 12 cases of CLL studied by indirect immunofluorescence and FACS analysis, a variable proportion of cells failed to express detectable levels of HLA-DP and HLA-DQ antigens at the cell surface, although greater than 90% of the cells had detectable expression of HLA-DR antigens. In all cases, greater than 90% of the cells expressed MHC class I antigens and the majority of cells reacted with the Leu-1 (CD5) mAb. Cells from different patients expressed variable levels of MHC class II antigens, and this was reflected in the finding of variable levels of mRNA detectable with the cDNA probe. Culture of cells with the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA) induced much increased levels of expression of MHC class II antigens. HLA-DP and -DQ antigens were expressed on greater than 90% of the cells in all cases studied after culture of the cells with TPA, and MHC class II specific mRNA transcripts were correspondingly increased. In a single case of plasma cell leukaemia studied, MHC class II antigens were not detectable at the cell surface and their expression was not induced after culture of the cells with TPA.

Antibodies, Monoclonal↗

Immunohistochemical analysis of human MHC class II antigens in B-cell non-Hodgkin's lymphomas.

Twenty cases of B-cell non-Hodgkin's lymphoma (NHL) were evaluated by immunohistochemical staining of frozen sections with a panel of anti MHC class II monoclonal antibodies (MCA). These studies showed marked differences in the expression of class II antigens both between different cases and within the population of cells of individual cases. In all of the cases studied the majority of the tumour cells reacted with MCAs directed against determinants common to the products of SB and DR loci. However, MCAs specific for DC determinants failed to react with 3/20 cases and in several other cases stained only a minority of cells. Absent or reduced expression of DC antigens was most marked in lymphocytic lymphoma; however, in centroblastic-centrocytic and centroblastic lymphomas, DC antigens could be detected on the majority of cells.

Antibodies, Monoclonal↗

Immunohistochemical staining of non-Hodgkin's lymphoma with monoclonal antibodies specific for the leucocyte common antigen.

Forty cases of non-Hodgkin's lymphoma (NHL) have been stained with monoclonal antibodies (F8-11-13, F-10-89-4 and Dako LC) to the Leucocyte Common Antigen (LC) in both cryostat and paraffin sections with an immunoperoxidase technique. In cryostat sections all B-cell lymphomas (25/25) reacted with F10-89-4 and Dako LC, whilst the majority (23/25) stained with F8-11-13; of the T-cell lymphomas studied, all reacted with F10-89-4 (6/60 and Dako LC (4/4), however 2/6 did not react with F8-11-13. Similar variability in reaction was observed in malignant histiocytosis where 1/3 did not react with F8-11-13 whilst all three reacted with F10-89-4 and Dako LC. In paraffin sections (using the two MCabs F8-11-13 and Dako LC) three of the 25 B-cell lymphomas failed to stain with either F8-11-13 or Dako LC (one lymphocytic lymphoma and two lymphomas showing plasmacytic differentiation). The remainder of the B-cell lymphomas reacted with both antibodies. Six out of 12 T-cell lymphomas did not stain with either F8-11-13 or Dako LC, using our standard immunoperoxidase procedure. Staining with Dako LC was however detected in all cases of T-cell lymphoma when incubation with primary antibody was extended from thirty minutes (standard) to overnight. This study confirmed that LC can be detected in all NHL in cryostat sections, and that in the majority of B-cell NHL the higher molecular weight component of LC was demonstrable using F8-11-13. Difficulty in detecting LC determinants after tissue processing for paraffin sections in a number of cases of NHL, especially those of T-cell type or showing plasmacytic differentiation, suggests that lack of reaction with these antibodies does not always preclude the diagnosis of lymphoma.

Antibodies, Monoclonal↗

Abnormalities in the expression of the leucocyte-common antigen in chronic lymphocytic leukaemia.

The surface glycoproteins of lymphocytes isolated from patients suffering from B cell chronic lymphocytic leukaemia (B-CLL) have been studied by radioactive labelling with impermeable probes and with MoAb. Several features not found in normal B cells have been observed. The abnormalities found in the expression of polypeptides of the leucocyte common (L-C) antigen, identified by appropriate MoAb, have been examined in detail. It has been shown by both biochemical analysis and MoAb binding that this group of polypeptides can, within a panel of B-CLL patients, range from a typical B cell pattern to the pattern resembling that normally found in T cells. The T lymphocyte profile is correlated with a poor prognosis (MVA C rating) and in the one patient where a change in the glycoprotein profile towards that of the T cell was observed, the change coincided with a clinical deterioration. The biological significance of the molecular diversity is discussed.

Antigen-Antibody Reactions↗

Surface glycoproteins as markers of the cellular status of B chronic lymphocytic leukaemia lymphocytes.

The phenotype of B CLL cells is investigated with respect to their surface glycoproteins. These glycoproteins are identified by vectorial tritiation followed by 1 and 2 dimensional gel electrophoresis, and by lectin and MoAb binding using immunoprecipitation and flow cytometry. The profiles of the CLL cells are compared with those of normal B cells, prepared from tonsils, and T cells from peripheral blood. The CLL cells show many similarities with T cells, particularly the expression of glycoproteins which bind the MoAbs gpL 115, F10-44-2 and EZB 52, and a complex set of binding sites for Helix pomatia lectin. The significance of these observations in terms of the cellular origins of the leukaemic lymphocytes is discussed.

Antibodies, Monoclonal↗

Histocompatibility antigen frequencies in patients with chronic lymphocytic leukaemia: possible identification of a subgroup with relatively benign disease.

A series of 57 patients with chronic lymphocytic leukaemia was typed for HLA-A, B and DR antigens and compared with a control population of equal size. There was an increased frequency of HLA-A1 and B8 in the patient group, although it was not statistically significant after allowance for the number of specificities tested. A subgroup of patients lacking both A1 and B8 differed from the others in sex ratio, degree of lymphocytosis and incidence of hypogammaglobulinaemia at presentation. This subgroup also had less need for treatment within 6 months of presentation. While these findings must be considered preliminary, it is possible that tissue typing may help to identify patients with a relatively benign form of the disease.

Aged↗

Cell marker studies in patients with newly diagnosed chronic lymphatic leukaemia.

Cell marker analysis including mouse red cell rosetting ability was carried out on 24 newly diagnosed patients with chronic lymphatic leukaemia. Using a technique not employing neuraminidase a significant difference in mouse red cell rosetting ability was noted between male and female patients. It is well accepted that females often have a milder form of disease and better longterm survival than it is suggested this might be a reflection of the difference found in mouse red cell rosetting ability between the sexes in this condition.

Female↗

Correlation of lysosomal enzyme abnormalities in various forms of adult leukaemia.

Lysosomal enzyme activities were studied in cells derived from the following types of leukaemia: chronic myeloid, acute myeloid, acute myelomonocytic, acute monocytic, non-T, non-B cell acute lymphoblastic, T-cell acute lymphoblastic, B-cell chronic lymphocytic and T-cell chronic lymphocytic. Activities of beta-hexosaminidase and alpha-mannosidase were significantly higher in cells from acute monocytic and acute myelomonocytic leukaemias, and somewhat higher in the other myeloid leukaemias, when compared with control granulocytes. Activities of beta-hexosaminidase, alpha-mannosidase, alpha-fucosidase, beta-glucuronidase and acid phosphatase were markedly lower in B cells of chronic lymphocytic leukaemia when compared with control or other leukaemic lymphoid cells. On isoelectric focusing abnormal patterns of beta-hexosaminidase, alpha-mannosidase and beta-glucuronidase activities were commonly found in myeloid and non-T, non-B cell leukaemias. All patients with acute myeloid leukaemia exhibited a relative decrease in the B form of beta-hexosaminidase activity. The results described show that studies on lysosomal enzymes may assist in the classification of different types of leukaemia.

Adult↗

Colony formation and interleukin 2 production by leukaemic human T cells.

PHA-induced colony formation and interleukin 2 (IL-2) production were studied in four patients with T cell leukaemia (three cases OKT4+/T helper and one case OKT8+/T cytotoxic suppressor). Cases of T helper cell leukaemia showed colony formation that was comparable to normal purified blood T cells and was not dependent on the addition of conditioned medium, containing IL-2 activity, to cultures. In contrast the T suppressor cell leukaemia formed colonies only when cultures were supplemented with IL-2 containing medium. When IL-2 production by PHA stimulated cells was measured culture supernatants from the three T helper cell leukaemias all showed normal or high levels of activity, when compared to normal blood mononuclear cells, whereas the T suppressor cell leukaemia showed no activity.

Aged↗

T and B lymphocyte markers in effusions of patients with non-Hodgkin's lymphoma.

T and B cells were sought in effusion fluids of 13 patients with lymphoma. In T cell lymphomas (four cases) morphologically abnormal cells that formed E rosettes were present. In B cell lymphomas (nine cases) morphologically abnormal cells were present in only two cases, however immunological studies showed a reduction in T cells and monoclonal light chain immunoglobulin expression in six of nine cases.

Ascitic Fluid↗

Preparation and properties of antisera to Mph-1, the mouse macrophage alloantigen.

Mph-1 is an alloantigen demonstrable on mouse peritoneal macrophages. Two lines, B10M.I and C.I, have been bred for use with strains I/StDa or BALB/c to produce appropriate alloantisera. Optimal immunization procedures for production of anti-Mph-1.2 (the common antigen) are described. Antisera against Mph-1.1 have so far been obtained only erratically. Antisera show complement dependent cytotoxicity against normal peritoneal macrophages and cultured blood monocytes but have no obvious effect on peritoneal lymphocytes or cultured blood neutrophils. Absorption studies show that cell for cell normal peritoneum has about fifteen times more antigen than lymph node, spleen, liver or bone marrow and at least eighty times more than thymus. We were unable to use the antiserum to cause passive enhancement of skin grafts in mice.

Animals↗

Studies on blood lymphocytes of patients with nodular poorly differentiated lymphocytic lymphoma.

T and B lymphocytes were measured in pretreatment blood samples from patients wih nodular poorly differentiated lymphocytic lymphoma (NPDLL). There were significant differences in T cell values between control groups and patients with NPDLL. In 13 out of 20 cases of NPDLL blood lymphocytes showed abnormalities of immunoglobulin light chain expression and were considered to show an abnormal clonal expansion of B lymphocytes. The abnormal clone of B cells in the blood reflected that found in lymph nodes and could be detected in the absence of bone marrow involvement or blood lymphocytosis.

B-Lymphocytes↗

T-cell lymphoma in children and young adults: clinical, immunological and pathological features.

The clinical, pathological and immunological features in 5 cases of T-cell lymphoma without overt marrow involvement are described. Classification of this distinct sub-group of lymphoma on morphological and clinical criteria alone has been shown to be unreliable, and precise recognitionr equires additional information from cytochemical and immunological marker studies of peripheral blood and lymph nodes. Valuable information may also be obtained from analysis of pleural fluid. The accurate identification of this sub-group assumes new clinical relevance in the light of the considerable improvement in prognosis reported with treatment schedules that are effective in acute lymphoblastic leukaemia.

Adolescent↗

Properties of anti-hairy cell serum.

An antiserum was prepared in rabbits against hairy leukaemic cells. After absorption with human erythrocytes, thymus and liver powder, the serum was passed through immunoabsorbent columns to remove extensive anti-plasma protein activity. Following these procedures, sensitive techniques failed to reveal residual activity against alpha-macroglobulins, beta2-microglobulin and other human plasma proteins. The antiserum reacted with normal B lymphocytes but not with T lymphocytes or monocytes. Positive reactions were seen in B cell lymphomas, chronic lymphocytic leukaemia, hairy-cell leukaemia and uninucleated Reed-Sternberg cells.

B-Lymphocytes↗