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Biomedical subjects

D Catovsky

Publications and source records attributed to D Catovsky.

At least 379 records · Page 21Linked to original sources

The human leucocyte P30 antigen: properties and assessment of value as a clonal marker.

FMC3 and FMC29 are monoclonal antibodies which react with a 30,000 Dalton molecule expressed on the lymphocyte surface membrane. The molecule is a protein which does not appear to be N-glycosylated. The antigen, which is also expressed intracellularly, does not appear to be a marker of differentiation or maturation. Polyclonal cell populations, such as peripheral blood lymphocytes, show a bimodal distribution of surface antigen density, whilst monoclonal cell populations analysed quantitatively showed unimodal antigen density distributions. This suggests the antigen may be a clonal marker.

Antibodies, Monoclonal↗

Phenotypic conversion of TdT+ adult AML to CALLA+ ALL.

A case of acute leukaemia is described in which the blast cells showed Sudan Black and terminal deoxynucleotidyl transferase (TdT) positivity at presentation and did not react with the monoclonal antibodies (McAb) My9 (anti-myeloid) and J5 (anti-CALL antigen). The myeloid lineage of these cells was confirmed by the myeloperoxidase (MPO) reaction at electron microscopic level. The patient entered complete remission but relapsed one year later with blasts showing negative Sudan Black and MPO reactions. These cells were still TdT+ but J5 was now positive. This case points to the existence of a clonogenic leukaemic cell with potential for evolution in both myeloid and lymphoid lineages. This is also suggested by the reactivity of both types of blast cells with the McAb 3C5 which recognises an antigen present both on early myeloid and lymphoid precursors. It is possible that patients with such leukaemias may benefit from combined therapy directed against cells of both myeloid and lymphoid lineages.

Adult↗

Biphenotypic leukaemia: a case of mixed T lymphoblastic and myeloblastic leukaemia.

A case of mixed acute leukaemia with T lymphoblastic, myeloblastic, and monocytic components is described. The use of immunological markers, ultrastructural morphology, cytochemistry, immunochemistry, and combined techniques, simultaneously detecting two markers in individual cells, made it possible to define the different blast cell populations.

Aged↗

Intracytoplasmic inclusions in B prolymphocytic leukaemia: ultrastructural, cytochemical, and immunological studies.

The intracytoplasmic inclusions seen in most cells from a patient with B prolymphocytic leukaemia were analysed using both light and electron microscopy. They consisted of a dense homogeneous structure and were surrounded by a membrane, which had no continuity with the Golgi cisternae or the endoplasmic reticulum; some inclusions had a clear association with small lysosomal granules. Immunofluorescence and immunoperoxidase studies using light microscopy failed to elucidate completely the nature of the inclusions, but immunocytochemical reactions performed using electron microscopy suggested an immunoglobulin nature. All inclusions were negative for acid phosphatase and periodic acid Schiff. The nature of the inclusions described in the prolymphocytes of this patient were compared with those previously recorded in B prolymphocytic leukaemia.

Aged↗

Analysis of helper activity on pokeweed mitogen- and interleukin 2-driven immunoglobulin synthesis by neoplastic T4+ cells.

The neoplastic T cells of a series of seven patients with chronic T-cell neoplasia were tested for helper activity on pokeweed mitogen (PWM)-induced and interleukin 2 (IL-2)-induced Ig synthesis. The neoplastic T cells of all patients had a T3+4+8-11+I1- phenotype but differed in expression of the 3A1 antigen. The neoplastic T cells of three patients had helper activity on both PWM- and IL-2-driven Ig synthesis, and in addition produced IL-2 in response to PWM stimulation. Two of these patients had hypergammaglobulinemia. In contrast, the neoplastic T cells in the remaining four patients did not produce IL-2 and did not support PWM-driven Ig synthesis. The T4+ cells of these four patients, however, provided excellent helper activity on IL-2-driven Ig synthesis. These findings emphasize the role of IL-2 in T cell-dependent Ig synthesis and clearly show that IL-2 production is required for helper activity in the PWM-driven system. It is concluded that the combined use of PWM- and IL-2-driven Ig synthesis systems allows separate analysis of IL-2 production and T-helper activity in health and disease.

Aged↗

Criteria for the diagnosis of acute leukemia of megakaryocyte lineage (M7). A report of the French-American-British Cooperative Group.

For the diagnosis of M7, the bone marrow aspirate shows a leukemic cell infiltrate that comprises 30% or more of all cells. These cells are identified as being of megakaryocyte lineage by the platelet peroxidase reaction on electron microscopy or by tests with monoclonal or polyclonal platelet-specific antibodies. Myelofibrosis or increased bone marrow reticulin are a prominent aspect in most patients with M7. In patients with increased reticulin, the bone marrow sample may be difficult to obtain and the counts done on the marrow films may be misleading. In these patients, the diagnosis of M7 should be based on excellent bone marrow biopsy sections that show an excess of blasts and, at times, increased numbers of maturing megakaryocytes; and on the presence of unequivocal megakaryoblasts in the peripheral blood or bone marrow (or both) as shown by immunologic techniques.

Acute Disease↗

Prolymphocytic leukemia of B cell type: rearranged immunoglobulin (Ig) genes with defective Ig production.

An unusual case of prolymphocytic leukemia of the B cell type (B-PLL) in a 79-year-old patient is reported. The clinical and cytomorphological features of the disease were typical of B-PLL, but membrane and cytoplasmic immunoglobulins (Ig) could not be demonstrated by immunofluorescence techniques; 3% to 4% of the cells were shown to have IgG kappa in the cytoplasm by a more sensitive immunoperoxidase method. The cells were unreactive with a panel of monoclonal antibodies against T cell antigens but they were positive with B cell lineage reagents: FMC4, anti-HLA-Dr determinants; FMC7, which reacts with most B-PLL; anti-B1 and anti-B4, which react with most B cell leukemias. Analysis of Ig genes at the DNA level demonstrated that both heavy-chain alleles and one kappa chain allele were rearranged, confirming that the patient's cells were of B lineage. Chromosome analysis revealed a consistent abnormality, t(17;21)(p11;p11), in all cells and, in addition, a 14q+ marker in 10% of the cells. This study highlights the value of DNA analysis techniques for the characterization of neoplastic B cells. The low rate of expression of Ig genes, despite their rearrangement, suggests that a specific transcriptional or posttranscriptional defect must exist in these cells.

Aged↗

Neoplastic kappa and lambda cells in a B-PLL with chromosome translocations of both light chain gene regions.

We describe a chromosome translocation t(2;13) (p11-12;p11) involving the kappa (kappa) light chain gene region (2p11-12), and a subsequent translocation t(11;22) (q23;11) involving the lambda (lambda) light chain gene region (22q11) within the same clone, in a patient with B-cell prolymphocytic leukaemia (B-PLL), of whose peripheral mononuclear cells 82% expressed (kappa) chains and 8% expressed (lambda) chains. Electron microscope (EM) studies using the immunogold method showed that both kappa- and lambda-producing cells were prolymphocytes. Immunoglobulin (Ig) gene analysis by Southern blotting demonstrated rearrangement of both Ig heavy (H) chain genes and one kappa gene. Although a lambda gene rearrangement corresponding to the minor lambda-positive population was not detected, a small monoclonal (M) band of IgM-lambda was present in the serum. The chromosome translocations and the pattern of light chain expression, particularly the lambda-producing cells, are discussed in the light of the restricted light chain expression observed in Burkitt's lymphomas with variant translocations involving the light chain genes.

B-Lymphocytes↗

The effect of vitamin D3 metabolites on normal and leukemic bone marrow cells in vitro.

We studied the effects of 1,25-dihydroxyvitamin D3 and other metabolites of vitamin D3 on the maturation in liquid culture and on colony formation in semisolid media of marrow and buffy coat cells from patients with myeloid leukemias and from normal individuals. After incubation with 1,25-dihydroxy-vitamin D3, a proportion of both normal and leukemic myeloid cells resembled cells of the monocyte-macrophage lineage; these cells expressed alpha-naphthylacetate esterase and were able to phagocytize and kill candida organisms. When granulocyte-macrophage progenitor cells (CFU-GM) were incubated with 1,25-dihydroxyvitamin D3, the number of monocyte-macrophage colonies was increased and the number of granulocyte colonies was reduced; megakaryocyte colony formation (CFU-Mk) was inhibited substantially; and there was no effect on erythroid (BFU-E) or multilineage (CFU-GEMM) progenitor cell colony formation. We propose that 1,25-dihydroxyvitamin D3 may induce cells that are normally committed to differentiate along the granulocytic pathways to differentiate instead along the monocyte-macrophage pathway. If these in vitro observations reflect the in vivo activity of 1,25-dihydroxyvitamin D3, it may be involved in the modulation of collagen deposits in the bone marrow.

24,25-Dihydroxyvitamin D 3↗

Changes in surface antigens of HL-60 cells during differentiation in vitro.

We have examined the pattern of binding of monoclonal antibodies OKM 1, FMC 10, FMC 12, FMC 13, FMC 17 and FMC 33 to human promyelocytic leukaemia (HL-60) cells. We found that the expression of antigens detectable with FMC 17 and FMC 33 (specific for monocytes and macrophages) was increased by exposure of HL-60 cells to 1,25-dihydroxyvitamin D3 but not by exposure of HL-60 cells to 12-tetradecanoyl phorbol-13-acetate (TPA). The antigen detected with the OKM 1 antibody was highly induced by TPA. The expression of granulocyte-specific antigens detected by FMC 10 and FMC 13 was increased during induction of granulocytic maturation; these antigens were retained during monocyte-macrophage differentiation of HL-60 cells. We conclude that in some cases the expression of particular antigens during maturation of malignant cells proceeds normally while in other cases antigenic differences between leukaemic and normal cells at equivalent levels of maturation can be detected.

Antibodies, Monoclonal↗

Adult T-cell lymphoma/leukemia in a Caribbean patient: cytogenetic, immunologic, and ultrastructural findings.

Cytogenetic findings on immunologically and morphologically characterized leukemic cells from a Caribbean patient with adult T-cell lymphoma/leukemia (ATLL) (HTLV+) are reported. Marker studies on peripheral blood lymphoid cells showed a mature postthymic phenotype: TdT-, OKT3+, OKT4+, OKT6-, OKT8-, 3A1-, anti-HLA-DR-. Light and electron microscopic analysis revealed a great cellular pleomorphism with respect to nuclear features. Three main types of leukemic cell were observed: typical multilobed ATLL lymphocytes, Sézary's syndrome (SS) cells, and cells intermediate between those two. Chromosome studies on PHA-stimulated cultures revealed three clones. The predominant clone was hyperdiploid; significant abnormalities were 1q+, 14q+, and 6q- (breakpoint q21), which are known to occur in lymphoid malignancies, together with trisomy 7q and i(17q), which have been reported previously in Japanese ATLL and the small variant of SS, respectively. The 14q+ marker was t(11;14)(q13;q22-24). The incidence of 6q-, trisomy 7q, and i(17q) varied within the main clone, and it is speculated that these chromosome abnormalities might be related to the variation observed in the cell types of this patient. Two minor clones had 6q- (breakpoint q25) and 13q+ markers, respectively. It was not possible to unequivocally establish the relationship between these three clones. The chromosomal, morphologic, and immunologic findings in this case support a close relationship between ATLL in Japan and in the Caribbean basin, as well as between the proliferating cells of ATLL and SS.

Antigens, Surface↗

Oral ketoconazole and amphotericin B for the prevention of yeast colonization in patients with acute leukaemia.

Forty-eight neutropenic patients with acute leukaemia were randomly allocated to receive, as antifungal prophylaxis, either ketoconazole, 400 mg once daily (K), or amphotericin B tablets and lozenges (A), or both ketoconazole and amphotericin B together (K + A). Antifungal prophylaxis was considered to have failed if (1) there was evidence of increasing colonization of the oropharynx or faeces with Candida spp. or other yeasts, or (2) if systemic antifungal therapy was begun empirically. Prophylaxis failed in nine of 17 patients given K, in four of 19 given A, and in four of 12 given K + A. The differences between the three regimens were not statistically significant, neither was there any significant difference in the mean duration of neutropenia before prophylaxis failed. The absorption of ketoconazole was impaired when patients were neutropenic. We conclude that ketoconazole was neither more nor less effective than amphotericin B in the prevention of yeast colonization in neutropenic patients.

Adolescent↗