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A M Ford

Publications and source records attributed to A M Ford.

49 records · Page 3Linked to original sources
PubMed1989

Molecular evidence for a single clonal origin in biphenotypic concomitant chronic lymphocytic leukemia and multiple myeloma.

To establish the clonal origin of a case of concomitant B-cell chronic lymphocytic leukemia (IgM kappa) and multiple myeloma (IGA lambda), we analyzed the immunoglobulin (Ig) gene rearrangements in the patient's blood and bone marrow. Despite the different isotypes, pretreatment investigation of the heavy chain gene (JH) revealed a germline fragment and two identical rearrangements in the blood and marrow. Both kappa and lambda light-chain genes were rearranged in the blood, suggesting peripheral blood lymphocyte involvement in the myeloma. Analysis of the Ig genes after chemotherapy demonstrated no change in the JH or CK rearrangements; however, the lambda genes were now in a germline configuration. Our results suggest that in this patient both chronic lymphocytic leukemia and myeloma originated from the same B-cell progenitor.

Antigens, Neoplasm↗
PubMed1988

Cell lineage specificity of chromatin configuration around the immunoglobulin heavy chain enhancer.

As tested by DNase I hypersensitivity, the chromatin structure of the IgH enhancer region in human B cell precursor cell lines is in an open or accessible conformation. All T cell lines, with either germline or rearranged IgH genes, were also hypersensitive to DNase I but in contrast to B cell precursors showed no detectable Cmu expression. Normal thymocytes similarly had a hypersensitive IgH enhancer site. In contrast to lymphoid cells, all myeloid cell lines tested, as well as normal granulocytes, were not DNase I hypersensitive and did not express Cmu. A putative lymphomyeloid progenitor cell line KG1, although having a germline configuration of Ig genes, produced Cmu transcripts and was hypersensitive to DNase I in the IgH enhancer region. After induction of myeloid differentiation the Ig enhancer region of KG1 cells is no longer hypersensitive or transcriptionally active. Two HhaI restriction sites on either side of the IgH enhancer were not methylated in all Cmu-expressing lines but methylated in non-expressing cell lines. These results show that an open chromatin structure around the heavy chain enhancer is necessary but insufficient for initiating transcription from unrearranged IgH genes and further suggests this region may be in an open or accessible configuration prior to lineage commitment and closed following adoption of the myeloid lineage.

Blotting, Northern↗
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↗
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

Developmentally regulated rearrangement and expression of genes encoding the T cell receptor-T3 complex.

Human leukemic cells corresponding to the earliest identifiable stages of intrathymic T cell differentiation lack cell surface expression of the T cell receptor(TCR alpha/beta)-T3 complex but transcribe TCR beta mRNA from either germ-line configuration (1/13) or partially (DJ) or fully (VDJ) rearranged (12/13) genes. These cells do not produce TCR alpha mRNA, but do contain T3 delta and T3 epsilon mRNA and accumulate T3 polypeptides, primarily in the perinuclear envelope. Equivalent normal T cells isolated from thymus have a predominantly germ-line configuration of TCR beta but contain intracellular T3 proteins. T3 gene expression is therefore a very early event in T cell differentiation. TCR alpha chain production appears to be the limiting maturation-linked event in the transport, assembly, and cell surface membrane insertion of the TCR alpha/beta-T3 complex.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1986

Clonal rearrangement and expression of the T cell receptor beta gene and involvement of the breakpoint cluster region in blast crisis of CGL.

A case of lymphoid blast crisis of Ph1-positive CGL is described in which the blast cells had an immature T cell phenotype, clonal rearrangement and expression of the T cell receptor beta gene, and a rearrangement of the breakpoint cluster region (bcr) on chromosome 22. This case therefore provides definite evidence for transformation involving a common myeloid-T lineage progenitor, penetrance of the Ph1 molecular alteration into the T cell lineage, and clonal selection in blast crisis at the level of a committed T lineage precursor.

Chromosome Mapping↗
PubMed1983

Immunoglobulin gene organisation and expression in haemopoietic stem cell leukaemia.

We have analysed the organisation and expression of mu genes in the granulocytic phase and in the lymphoid and myeloid blast crises of Philadelphia chromosome (Ph1) chronic granulocytic leukaemia (CGL), a leukaemia which is known to arise in multipotential stem cells. We find that mu chain gene rearrangement occurs exclusively in lymphoid blast crisis leading in some, but not all, cases to the synthesis of small amounts of cytoplasmic mu chains characteristic of early pre-B lymphocytes. In Southern blots, only one or two rearranged mu chain genes are seen, suggesting that a clonal event leading to blast crisis can occur in a committed B cell precursor rather than in the multipotential stem cell precursor, in which the Ph1 chromosome originated. The pattern of mu gene rearrangement observed in Ph1 CGL blast crisis is compared with that in normal B cells, other B lineage malignancies, myeloid leukaemias and T cell leukaemias.

B-Lymphocytes↗
PubMed1983

Measurement of IgG antibody and airborne antigen to control an industrial outbreak of hypersensitivity pneumonitis.

An outbreak of hypersensitivity pneumonitis in a textile plant was attributed on epidemiological grounds to a chilled water air-conditioning system where a slime was growing in the chilled water sump and on demister vanes. All of the patients and about 80% of their asymptomatic co-workers had strongly positive precipitin tests to extracts of the slime. An adaptation of a radioiodinated staphylococcal protein A solid-phase radioimmunoassay was applied to monitor antigen and specific antibody. To control the outbreak, a variety of cleaning and water treatment measures were taken between 1977 and 1979 to reduce the amount of antigen in the water and in the air. The amount of slime in the water was greatly reduced though the antigen content per gram of slime did not change. Airborne antigen in the affected work areas decreased progressively.

Air Conditioning↗
PubMed1982

Influence of salinomycin on antimicrobial resistance of coliforms and streptococci from broiler chickens.

An experiment was conducted to evaluate antimicrobial resistance of coliforms and streptococci isolated from feces of chickens fed salinomycin. Two groups of 20 chickens were fed either a control feed or feed supplemented with 80 g/ton salinomycin. Chicken fecal coliforms and streptococci were isolated at 5, 15, 19, 22, 26, 33, 40, and 47 days of age and their resistance to 11 or 12 antibacterial agents (coliforms and streptococci, respectively) were determined in both groups of chickens. Salinomycin significantly reduced the number of coliforms resistant to sulfadiazine and reduced the number of streptococci resistant to erythromycin and lincomycin. Streptococci from birds fed salinomycin had lower minimum inhibitory concentrations for streptomycin. No streptococci isolates developed resistance to salinomycin. Coliforms from birds fed salinomycin had more (P less than .05) resistance patterns involving two, five, and six drugs. Numbers of coliforms resistant to streptomycin, ampicillin, carbenicillin, and cephalothin were greater (P less than .05) from birds fed salinomycin.

Animals↗
PubMed1981

Influence of salinomycin on incidence, shedding, and antimicrobial resistance of Salmonella typhimurium in experimentally infected broiler chicks.

Twenty broiler chickens were fed 80 g/T salinomycin, an antibiotic produced by Streptomyces albus, and 20 birds were fed a control, unmedicated feed. The birds were experimentally infected with Salmonella typhimurium. The study evaluated the effects of salinomycin on Salmonella incidence, shedding, and antimicrobial resistance. Salinomycin had no effect on body weights, length of time salmonellae were shed, number of salmonellae shed on postdosing day 3, salmonellae tissue recoverability, or on the total number of resistance patterns. Salinomycin caused the decline of salmonellae to be more gradual; however, both treatments were comparable at the end of the study. The majority of isolated from birds receiving salinomycin maintained the original S. typhimurium antibiogram of streptomycin, sulfadiazine, and nalidixic acid. The salinomycin salmonellae were more susceptible to tetracycline, amikacin, carbenicillin, gentamicin, and cephalothin. The multiple resistance patterns of eight and nine drugs tended to be more prevalent among salmonellae from control birds than salinomycin treated birds. The antibiotic salinomycin appears to be an acceptable feed additive in broilers at the level of 80 g/T based on these results of its effects on salmonellae shedding and antimicrobial resistance.

Animals↗
PubMedDate not supplied

DNase I hypersensitive sites in the chromatin of human mu immunoglobulin heavy-chain genes.

An immunoglobulin polypeptide chain is encoded by multiple gene segments that lie far apart in germ-line DNA and must be brought together to allow expression of an immunoglobulin gene active in B lymphocytes. For the immunoglobulin heavy chain genes, one of many variable (V) region genes becomes joined to one of several diversity (D) segments which are fused to one of several joining (J) segments lying 5' of the constant region (C) genes. Here we show that the rearranged mu genes of an IgM-producing human B-lymphocyte cell line exhibit pancreatic deoxyribonuclease (DNase I) hypersensitive sites in the JH-C mu intron that are absent in naked DNA or the chromatin of other differentiated cell types. DNA sequence analysis reveals that the major hypersensitive site maps to a conserved region of the JH-C mu intron recently shown to function as a tissue-specific enhancer of heavy-chain gene expression. A similar association of an enhancer-like element with a DNase I hypersensitive site has been reported for the mouse immunoglobulin light-chain J kappa-C kappa intron. These results implicate disruption of local chromatin structure in the mechanism of immunoglobulin enhancer function.

B-Lymphocytes↗