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Biomedical subjects

M F Greaves

Publications and source records attributed to M F Greaves.

At least 91 records · Page 5Linked to original sources
PubMed1988

Terminal deoxynucleotidyl transferase and HLA-DR expression appear unrelated to prognosis of acute myeloid leukaemia.

Mononuclear cells from peripheral blood or bone marrow from 314 patients with acute myeloid leukaemia were examined for the presence of nuclear terminal deoxynucleotidyl transferase (304 patients), surface membrane expression of HLA-DR (314 patients) and the common acute lymphoblastic leukaemia antigen (281 patients). All patients were treated with identical remission induction chemotherapy, and morphological diagnosis was carried out in a central laboratory. The overall complete remission rate was 70%. There were no significant correlations between the immunological markers and complete remission rate, duration of remission, or survival.

Adolescent↗
PubMed1988

Structural and partial amino acid sequence analysis of the human hemopoietic progenitor cell antigen CD34.

Monoclonal antibodies of the CD34 class all recognize a monomeric cell surface antigen of approximately Mr 110,000 which is selectively expressed on human hemopoietic progenitor cells. This structure can be readily surface-labeled with [125I]actoperoxidase and by periodate-[3H]borohydride, but it labels only weakly with [35S]methionine, [35Sl]cysteine, 3H-amino acids, or 3H-mannose, even after prolonged labeling periods. However, the antigen is more efficiently labeled by [3H]glucosamine. Lectin binding studies, sensitivity to certain glycosidases, and gel filtration analysis of glycans released by alkaline hydrolysis indicate that this glycoprotein contains several complex-type N-linked glycans as well as several highly sialylated O-linked glycans. Western blotting experiments show that various CD34 antibodies fail to efficiently detect desialylated and/or de-N-glycosylated forms of the antigen. Experiments involving the use of tunicamycin, together with metabolic labeling studies, strongly suggest that this structure "turns over" very slowly in vivo. The CD34 antigen is not detectably labeled by 32P-phosphate in vivo, nor are immune complexes containing it associated with phosphokinase activity in vitro. Sequential immunoprecipitation and Western blotting studies indicate that this antigen is not a member of the leukosialin/sialophorin family despite the fact that these molecules share several structural similarities. Partial amino acid analysis of highly purified CD34 antigen revealed no significant sequence similarity with any previously described structures.

Amino Acid Sequence↗
PubMed1987

Characterisation of stroma-dependent blast colony-forming cells in human marrow.

Human bone marrow contains a population of haemopoietic progenitor cells that can be distinguished by their ability to adhere to preformed stromal layers (cultured in the presence of methylprednisolone [MP+] and form blast cell colonies. The stromal layers function in the colony assay after they have been heavily irradiated but not after they have been passaged. The binding of the progenitor cells to the stromal cells is complete after 2 hours of coincubation, and stromal layers of 9.6 cm2 can provide adhesion sites for at least 2,000 blast colony-forming cells. The blast colony-forming cells were shown by micromanipulation to self-renew as well as to give rise to multipotential and lineage-committed colony-forming progenitor cells.

Bone Marrow Cells↗
PubMed1987

Cloning of human thymic subcapsular cortex epithelial cells with T-lymphocyte binding sites and hemopoietic growth factor activity.

The thymic microenvironment involves complex cell interactions among different types of epithelial cells, macrophages, tissue histiocytes, and immature and maturing T cells. We describe the isolation of a subset of thymic epithelial cells by selective primary culture followed by cotransfection with a simian virus 40 replication-origin-defective mutant and pSV2neo plasmid. The cloned cells have the composite immunophenotype that is unique to thymic subcapsular epithelial cells, suggesting that they may provide a model system in vitro for analyzing the earliest steps in T-cell differentiation. This possibility is supported by the finding that these epithelial cells express LFA-3-associated binding sites for T cells, secrete a macrophage hemopoietic growth factor, and synergize with macrophages in the production of interleukin 1.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

Expression of HPCA-1 and HLA-DR antigens on growth factor- and stroma-dependent colony forming cells.

The expression of HLA-DR and HPCA-1 antigens (recognized by the L243 and BI.3C5 antibodies respectively) on adult human bone marrow cells was examined by fluorescence activated cell sorting and colony assays. Nearly all the (day 14) lineage restricted and multipotential colony forming cells analysed in methylcellulose cultures in the presence of added growth factors express HLA-DR and HPCA-1 determinants. Two colour cell sorting reveals that the lineage restricted HLA-DR positive progenitors express variable levels of BI.3C5 positivity whereas most of the multipotential progenitors, the multi-CFC or CFU-GEMM, are highly BI.3C5 positive. The isolated HLA-DR and BI.3C5 positive populations also contain haemopoietic precursors which adhere to and form colonies on pre-formed stromal layers. Thus, haemopoietic progenitors assayed in both types of culture system can be analysed and enriched by simultaneous two-colour sorting using anti-HLA-DR and BI.3C5 monoclonal antibodies. Similarities in the antigenic phenotype of such cells, however, precludes the use of these reagents for segregating growth factor-dependent from stroma-dependent progenitors.

Adult↗
PubMed1987

Polycythaemia rubra vera transforming to acute lymphoblastic leukaemia.

Two patients who developed acute lymphoblastic leukaemia following polycythaemia rubra vera (PRV) are described. In both cases the diagnosis was made using cytochemistry and immunological markers. One patient's cells marked as T-cell acute lymphoblastic leukaemia (T-ALL), the other as unclassified (null) ALL. These cases support the concept that PRV is a stem cell disorder.

Acute Disease↗
PubMed1987

Molecular lesion in chronic granulocytic leukemia is highly conserved despite ethnic and geographical variation.

Leukemic cell DNA from patients with Philadelphia chromosome positive chronic granulocytic leukemia in the United Kingdom, Taiwan, and South Africa and of diverse ethnic origins all have identifiable molecular rearrangements of the breakpoint cluster region on chromosome 22 band q11 when screened with an appropriate DNA probe. This result reinforces the highly conserved nature of the molecular lesion in chronic granulocytic leukemia and its suitability as a diagnostic marker for the disease. Since the assay can be performed by sample referral on relatively small numbers of nondividing frozen or dead cells, it is ideally suited for large scale epidemiological and clinical studies, particularly in developing countries where karyotyping services are not readily available.

Chromosome Mapping↗
PubMed1987

Lineage specificity of rearrangement and expression of genes encoding the T cell receptor-T3 complex and immunoglobulin heavy chain in leukemia.

In acute lymphoblastic leukemia (ALL) diagnostic samples and cell lines with unequivocal B cell precursor (common) or T cell precursor immunophenotypes, there is inappropriate or cross-lineage IgH or T cell receptor beta gene (TCR beta) rearrangement in approximately 25% of the cases. The frequency of such rearrangements is lower in mature lymphoid neoplasms and acute myeloblastic leukemia. The most immature B lineage ALL ('null' ALL) has a much lower frequency of TCR gene rearrangement than the common variant of B cell precursor ALL and also has a high frequency of oligoclonal rearrangements of IgH genes. Non-T leukemic cells with inappropriately rearranged TCR beta gene did not necessarily have a rearranged TCR gamma gene. Inappropriately rearranged IgH or TCR genes are usually not expressed at the mRNA level, and the gene for the TCR associated protein T3 delta is not detectably expressed at the mRNA or protein level in leukemias classified unambiguously as non-T. Five cases of acute leukemia with ambiguous or mixed lineage immunophenotypes (myeloid + T or myeloid + B) are described. These five had diverse patterns of IgH, TCR beta, and TCR gamma rearrangement, and all expressed terminal transferase concomitantly with MY9 (CD33). The T3 delta gene was expressed in two cases, which also expressed other T cell markers indicating that coordinated lymphoid lineage programs had been initiated. The implications of these observations for lineage-associated regulation of genes during normal differentiation and leukemogenesis are discussed.

Adult↗
PubMed1987

A computer program for interpreting immunophenotypic data as an aid to the diagnosis of leukemia.

A computer program has been developed for interpreting the immunophenotypic data obtained in cases of leukemia. It has been designed as a logic program, and its reasoning is based entirely on that used by one experienced immunologist. For each case the program gives a conclusion (qualified if necessary), a summary of the underlying reasoning, and suggestions for any further investigations that may be of benefit. Its performance has been considered acceptable for every one of 400 past cases, and these include various uncommon and atypical conditions.

Adult↗
PubMed1987

Plastic-adherent progenitor cells in human bone marrow.

Human bone marrow contains plastic-adherent hemopoietic progenitor cells whose plating efficiency is increased by brief (2 h) exposure to methylprednisolone (MP). When subsequently covered with methylcellulose medium, they form colonies of monoblastoid cells. Colony size, but not number, and mature cell production are increased by erythropoietin (epo) and granulocyte-macrophage colony-stimulating factor (GM-CSF). However, colonies do not grow under serum-free conditions. The resistance of plastic-adherent progenitors to treatment with 5-fluorouracil (5FU), their growth pattern, and their capacity to produce granulocytic and erythroid colonies on replating, suggest that they may be similar to the primitive, 5FU-resistant, plastic-adherent progenitor cells (HPP-CFC) in murine marrow.

Bone Marrow Cells↗
PubMed1986

Rearrangement of immunoglobulin heavy chain genes in human T leukaemic cells shows preferential utilization of the D segment (DQ52) nearest to the J region.

The DNA rearrangements leading to the assembly of genes coding for the immunoglobulin heavy chain (IgH) in B cells and the T cell receptor for antigen in T cells are not completely lineage specific. This probably reflects the use of a common recombinase by IgH and the T cell receptor. This paper describes novel observations on the nature of these cross-lineage rearrangements. A high proportion (though not all) IgH rearrangements in human T leukaemic cells involve the D segment nearest to the J region (DQ52). This same D segment is not involved in B cell IgH rearrangements with one important exception, namely a proportion of B cell leukaemic clones with the most primitive B cell precursor phenotype. These observations have potentially important implications for early lymphoid cell differentiation and in particular support the idea that the 3' D plus J region might lie within a limited window of accessibility of the IgH gene in precursor lymphocytes.

DNA Restriction Enzymes↗
PubMed1986

Ethnic composition, age and sex, together with location and standard of housing as determinants of HLTV-I infection in an urban Trinidadian community.

The presence of antibody to human T-cell leukaemia virus (HLTV-I) has been assessed in 2,143 men and women who represent 83% of all adults aged 35 to 69 years resident in a defined urban community in Trinidad. Individuals of African descent had a higher sero-positivity rate (7.0%) than those originating from India (1.4%), Europe (0%) or of mixed descent (2.7%). Women were infected more frequently than men, and the prevalence of infection increased with age in both sexes. Sero-positivity rates were significantly increased in adults who lived in housing of poor quality (p less than 0.001) or close to water courses (p less than 0.025). These data and others raise the possibility that one route of HLTV-I transmission may be via insect vectors under particular domestic circumstances.

Adult↗
PubMed1986

Differentiation-linked leukemogenesis in lymphocytes.

Most human lymphoid malignancies preserve a pattern of gene expression reflecting their proliferative activity and the development level of clonal expansion and maturation arrest. Characteristics of leukemia and other cancer cells frequently considered to reflect aberrant differentiation may more often reflect clonal selection of cell types that are normally infrequent and transitory. The differentiation status of progenitor or mature lymphoid cells influences which genetic elements are at risk of being exploited, via mutation, recombination, or deletion, for clonal advantage. These alterations may frequently arise spontaneously as a consequence of the unique developmental and functional programs of lymphoid cells and have as a major phenotypic consequence the stabilization of transitory cellular phenotypes.

Antigens, Surface↗