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Biomedical subjects

M F Greaves

Publications and source records attributed to M F Greaves.

At least 181 records · Page 10Linked to original sources
PubMed1981

Analysis of the clinical and biological significance of lymphoid phenotypes in acute leukemia.

Analysis of leukemic cell phenotypes using cell surface antigens and various enzymes indicates that acute lymphoblastic leukemia (ALL) is a biologically heterogeneous disease consisting of four major subclasses with additional subsets existing within these subclasses. These different types of ALL appear to reflect sequential stages of early lymphocyte ontogeny. There is a strong association between cell phenotype and first remission duration in ALL (p trend less than 0.0001) and an equally strong correlation between remission duration and white blood cell count at presentation. If common ALL and thymic ALL (T-ALL) are compared after adjustment of white blood cell counts, then the prognostic differences between these two major subclasses almost disappear (p = 0.38). It is suggested, therefore, that an immunological (and enzymatic) phenotype of ALL subclasses may not be an independent correlate of prognosis but nevertheless is linked to other differentiation-linked features, especially growth rate and sites of clonal expansion (e.g., marrow versus thymus), which critically influence the size of the clonogenic leukemic population and its associated evolutionary status with respect to drug resistant mutants at the time of diagnosis and introduction of therapy. An extensive library of monoclonal antibodies has been used to further define the phenotypic heterogeneity of T-and non-T All. Several of the antigenic structures identified by these monoclonal antibodies have been isolated and characterized. T-ALL can be dissected into several subsets corresponding to stages of intrathymic differentiation. Non-T ALL (null-ALL, common ALL, and B-ALL) all have a phenotype indicative of B-lineage affiliation indicating that "non-T, non-B" ALL may originate from B-cell precursors in bone marrow. A cell type is identified in normal bone marrow which has the same identical monoclonal antibody-defined phenotype as common ALL and may provide the target cell for this disease.

Acute Disease↗
PubMed1980

Restricted expression of a human T cell lineage membrane antigen.

An antiserum raised against human fetal and childhood thymocytes (anti-Thy) and absorbed with peripheral lymphocytes (tonsil) detected an antigen(s) shared by thymocytes, T cell-acute leukemias, activated peripheral T cells and a subset of peripheral T cells. The antigen was expressed by the negative circulating T cell subset after mitogen activation of that separated population. The antigen was shown to be separate from the E rosette receptor, another anti-T cell serum detected antigen, and beta 2-microglobulin; its expression was not related to a particular phase of the cell cycle. The results suggest that the antigen is expressed by T cells only under certain maturational and proliferative conditions.

Absorption↗
PubMed1980

Terminal transferase enzyme assay and immunological membrane markers in the diagnosis of leukaemia: a multiparameter analysis of 300 cases.

Multiparameter analyses have been carried out with recently developed enzyme and membrane markers in 300 patients with various leukaemias including ALL, AML, but excluding Ph1 positive leukaemias. TdT enzyme levels were particularly valuable in the differential diagnosis of adult acute lymphoid and myeloid leukaemias. The levels were raised in 108 (94%) of the 115 patients who were considered to be non-T, non-B ALL on membrane marker and morphological analysis; all seven cases giving negative TdT results in this group were young children. Unexpectedly high levels were seen only in three (4.1%) of 73 cases of acute myeloid leukaemia verified by histochemistry and membrane markers. Anti-ALL serum was a most useful reagent in childhood leukaemias but blasts from 19 patients (10% of childhood ALL cases and 29% of adult ALL cases) failed to react with the serum in spite of TdT positivity. Strongly ALL+ blasts were seen only in non-T, non-B ALL and some undifferentiated leukaemias. Weakly ALL+ blasts were seen in seven of 32 cases of thymic ALL (Thy-ALL) but in other respects these blasts expressed Thy-ALL features, such as strong reactivity with anti-T cell (HuTLA) serum, negativity with anti-Ia-like serum and raised TdT. The combination of tests was particularly useful in 32 cases of undifferentiated leukaemia: in 10 of these cases TdT positivity indicated the probable 'lymphoblast', nature of blast cells: the remaining 22 cases remained unclassifiable with the markers used. The analysis revealed other interesting variant forms of leukaemias.

Acute Disease↗
PubMed1980

Lymphocyte antigens in systemic lupus erythematosus: studies with heterologous antisera.

Rabbit antisera were produced against pooled living lymphocytes from 25 patients with active systemic lupus erythematosus (SLE). Lymphocytes collected at plasmapheresis or venipuncture were frozen in liquid nitrogen and later coated with rabbit antibody to normal human tonsils and normal thymocytes immediately before intravenous immunization of rabbits. Antisera were subsequently extensively absorbed with normal human tonsillar cells, thymocytes, peripheral blood lymphocytes, erythrocytes, and leukocytes from patients with myelogeneous and lymphatic leukemia until residual base-line immunofluorescent staining of normal human lymphocytes using F(ab)2' of whole antisera averaged less than 5%. Absorbed pepsin-digested antisera detected membrane antigens which were markedly increased (mean 32%) on lymphocytes from patients with active SLE (P less than 0.05). Membrane antigens reacting with absorbed, pepsin-digested antisera were present on both T and B cells but, in most instances, predominated on T cells. Control observations using absorbed pepsin-digested antisera to normal human lymphocytes or peripheral blood lymphocytes from patients with rheumatoid arthritis showed no similar specificity. SLE patients treated with moderate or high dose corticosteroids or immunosuppressive agents (cytoxan or azathioprine) appeared to lose lymphocyte antigens detected by these reagents. Control studies with other connective tissue disease patients, miscellaneous hospitalized subjects, or normal controls showed low levels of reactivity (2-5%). SLE lymphocyte membrane antigens uniquely increased during active disease; this may represent neoantigens or alterations associated with the disease itself.

Adult↗
PubMed1980

Differentiation-linked expression of cell surface markers on HL-60 leukemic cells.

The cell surface antigenic phenotype of HL-60, a human acute promyelocytic leukemia cell line, has been analyzed before and after maturation induction with dimethylsulfoxide (DMSO) using a panel of markers including a "library" of monoclonal antibodies and "conventional" antisera in conjunction with the fluorescene-activated cell sorter. HL-60 cells express granulocyte and "leukocyte" differentiation antigens but not antigens of the lymphoid, platelet, and erythroid lineages. DMSO-induced morphological maturation was found to be associated with a decrease in the proportion of cells in mitotic cycle, induction of C3d receptors, increased expression of granulocytic and leukocyte antigens, and diminished expression of HLA-A,B,C and beta 2-microglobulin determinants. HL-60 cells have no detectable expression of HLA-DR-associated determinants as assayed by rabbit anti-p28,33 monoclonal anti-HLA-DR (monomorphic determinant), and HLA-DRw typing alloantisera. The relationship of these changes in cell surface properties to normal granulocytic differentiation is discussed.

Animals↗
PubMed1980

A monoclonal antibody identifying a cell surface antigen shared by common acute lymphoblastic leukemias and B lineage cells.

A monoclonal antibody designated PI153/3, which reacts with neuroblastoma and fetal brain, is shown to identify also a cell surface determinant shared by pre-B and mature B cells and their corresponding leukemias including chronic lymphocytic leukemia, non-Hodgkin's lymphoma, B acute lymphoblastic leukemia, and hairy cell leukemia, but not plasmacytoma. Almost all non-T, non-B acute "lymphoid" leukemias bind PI153/3. The latter includes 71 of 74 common ALL tested, most but not all "unclassified" or "null" ALL and cases of both acute undifferentiated leukemia and Ph1 positive chronic myeloid leukemia in blast crisis with common ALL phenotypes. The antigen is absent or present at very low density on normal and leukemic T lymphocyte, myeloid and erythroid cells. The determinant appears to co-redistribute with cell surface immunoglobulin in B lymphocytes and segregates independently of other cell surface antigens associated with B cells and/or cALL including HLA-DR (Ia-like antigens) and the cALL (gp 100) antigen.

Antibodies↗
PubMed1980

T lymphocyte subpopulations and Ia-positive T cells in patients with immunodeficiency.

T lymphocyte subpopulations (T gamma and Tmu) were studied in a group of 36 adult patients with immunodeficiency. Proportions and numbers of Ia(+) T cells were also studied in comparison to 46 normal adult controls. Values for per cent and total numbers of T gamma and Tmu cells indicated no uniform abnormality. Mean normal percentage of Ia(+) T cells was 2.4% whereas 16 to 29 immunodeficient patients showed elevated proportions and absolute numbers of Ia(+) T cells. Striking fluctuation in proportions of Ia(+) T cells was noted in serial studies of five immunodeficient subjects in contrast to similar analyses of normal controls. A correlation (P less than 0.01) was recorded between absolute numbers of Ia(+) T cells in immune deficiency patients and numbers of T mu cells. Depletion of T gamma cells by EA rosetting in patients with late-onset primary acquired hypogammaglobulinaemia did not result in significant change in IgG or IgM synthesis with T gamma-depleted T cells were co-cultured with normal B cells. Depletion of Ia(+) T cells likewise did not significantly influence Ig synthesis in co-culture with normal or immune-deficient B cells. These studies emphasize the complexity of defects present among any large group of patients with immune deficiency.

Adult↗
PubMed1980

Identification of cells expressing T and p28,33 (Ia-like) antigens in sections of human lymphoid tissue.

A method has been developed for identifying human lymphocyte populations in tissue sections using hetero-antisera to T cells and to the B cell associated Ia-like, p28,33 polypeptide complex. The differential topographical localisation of T and B cells is revealed by simultaneous staining with antibodies tagged with different fluorochromes; this approach also identifies a small population of T cells bearing Ia-like antigens. Preliminary studies on lymphomatous tissue suggests this approach will be of value in the study of malignancy and cellular infiltration in disease.

Antigens, Surface↗
PubMed1980

The presence of HLA-DR antigens on lactating human breast epithelium and milk fat globule membranes.

HLA-DR antigens have been demonstrated on the secretory epithelia of lactating breast using rabbit anti-p28,33 ('Ia-like') and mouse monoclonal anti-HLA-DR 'framework'. Normal non-lactating breast, benign or malignant tumours, epithelial cells from normal breast or isolated from milk and a presumptive breast carcinoma cell line (MCF-7) were all HLA-DR-negative. HLA-DR, HLA (ABC 'framework') and beta 2-microglobulin determinants were also demonstrated on the surface of milk fat globules (MFG) which were unreactive with monoclonal antibodies to thymus cells or leucocytes. A monoclonal antibody detecting allelic HLA-DR determinants (HLA-DRw 1,2,6) was positive on 40% of MFG samples tested, positive reactions being concordant, when tested, with blood B lymphocytes. Antisera raised against MFG membranes also contain anti-HLA-DR activity. Whether the breast epithelial cells synthesize HLA-DR molecules or acquire these passively from mononuclear cells which infiltrate during lactation is not yet resolved.

Breast↗
PubMed1979

Relation of "lymphoid" phenotype and response to chemotherapy incorporating vincristine-prednisolone in the acute phase of Ph1 positive leukemia.

Forty-four patients with Ph positive leukemia (36 developing blast crisis after chronic phase and eight presenting in acute leukemia) were classified into subgroups on the basis of reactivity of blasts with an anti-serum made against non-T,non-B acute lymphoid leukemia (ALL+), levels of terminal transferase enzyme (TdT+) and morphology. Positivity with anti-ALL serum was the most sensitive and reliable marker, and TdT was an important aid. The presence of "lymphoid" blasts in blast crisis of CML was related to the response to chemotherapy incorporating Vincristine and Prednisolone (VP). Patients with ALL+ blasts frequently (14 of 15 cases) responded to therapy while 21 of 25 patients who had no ALL+ blasts failed to respond. The clinical course of the ALL+ patients was variable: eight patients remitted with return to the appearances of the chronic phase; four patients demonstrated elimination of the Ph1 positive clone with hypoplasia and this was followed by normal (Ph1 negative) marrow regeneration in two. Subsequent relapse was of either the ALL+ "lymphoid" or the ALL-myeloid type. A regimen incorporating VP should be the treatment of choice in "lymphoid" blast crisis of CML.

Antigens, Neoplasm↗
PubMed1979

"Ia-like" antigens on human T cells.

Human T lymphocytes have been tested for cell surface p. 28,33 "Ia-like" heteroantigen and DRw alloantigens. Small numbers (1--5%) of sheep (E) rosette or T antigen-positive, surface immunoglobulin-negative (E+, T+, smIg-) T cells were Ia+; these cells appeared to be restricted to the TG subset. Following activation by allogeneic lymphocytes or sperm, or by purified protein derivative of tuberculin (PPD), the proportion of positive T cells increased substantially. DRw typing indicated that Ia specificities on activated T cells were not acquired passively from the stimulator cells, suggesting therefore that either "selection" of a small DRw+ cell subset or derepression and/or exposure of DR locus gene products occurs during T cell activation.

Antigens, Surface↗
PubMed1979

Immunological analysis of human microglia: lack of monocytic and lymphoid membrane differentiation antigens.

While it is certain that reactive microglia (phagocytes in damaged brain tissue) originate from monocytes, the derivation of resting microglia (argentophilic cells in undamaged brain tissue) is not clear. In order to examine a possible lymphocytic and/or monocytic origin for resting microglia, cryostat sections of presumably normal human brain tissue were treated with anti-lymphocyte, anti-monocyte and anti-beta 2-microglobulin sera and then stained with the immunoperoxidase technique. No positive reaction was obtained. It must be concluded that resting microglia are not derived from mononuclear blood cells.

Antigens, Surface↗