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Biomedical subjects

D Delia

Publications and source records attributed to D Delia.

At least 91 records · Page 5Linked to original sources
PubMed1985

Large granular lymphocytes from murine blood and intestinal epithelium: comparison of surface antigens, natural killer activity, and morphology.

Large granular lymphocytes obtained from murine blood (B-LGL) and intestinal epithelium (IE-LGL) are cells associated with natural killer (NK) activity and thought to be a first line of defense against tumors and/or infectious organisms. Since B-LGL and IE-LGL represent circulating and mucosal NK effectors, respectively, we compared their surface markers, NK activity and morphology to define possible differences between NK cells in different anatomical compartments. B-LGL and IE-LGL were purified by Percoll gradient centrifugation from nude, normal, and beige C57BL/6 mice. We have defined the following surface phenotypes. B-LGL: In nude mice most of them expressed T-200 (89%), asialo-GM1 (71%), and NK-1.1 (72%); 15% possessed the Thy-1.2 antigen, few cells expressed Ly-2, and none showed Ly-1 positivity. Beige mouse B-LGL were positive for T-200 and NK-1.1. IE-LGL; Nude IE-LGL compared to nude B-LGL showed a similar expression of T-200 and Thy-1.2. Ly-1+ and Ly-2+ cells were more numerous than in B-LGL, whereas NK-1.1+ and asialo-GM1+ cells were less numerous. Interestingly, Ly-2+ IE-LGL were at least partially Thy-1.2-. In euthymic mice IE-LGL had a phenotype comparable to that of nude IE-LGL. The NK activity of B-LGL from nude and normal mice was considerably higher than that of IE-LGL from the corresponding mice. IE-LGL from nude mice possessed larger cytoplasms, and more numerous and bigger azurophilic granules than B-LGL. Similar findings were obtained in normal mice. In beige mice 95% of B-LGL showed a single granule whereas 80% of IE-LGL contained multiple granules (mean 3/cell). Giant granules were frequently found in beige IE-LGL while they were rare in beige B-LGL. Thus, clear differences exist between B-LGL and IE-LGL and they may reflect either different homing patterns of subpopulations of LGL or different stages of maturation of the same lineage of cells.

Animals↗
PubMed1985

Allostimulation of patients' lymphocytes generates both T and NK-like cells cytotoxic for autologous melanoma.

Killing of autologous melanoma (auto-Me) was obtained with pooled allostimulated peripheral blood lymphocytes (PBL) in 34/42 cases and found not to be due to a cross-reactivity between melanoma and allogeneic normal antigens. To see whether generation of tumour cytotoxic PBL by allostimulation was due to release of IL-2, PBL from 34 patients were divided into two aliquots and stimulated either by alloantigens or IL-2. Allostimulated PBL were cytotoxic for auto-Me in 30/34 cases (85%) whereas IL-2 generated tumour cytotoxic cells in 22/34 cases (64%). Lysis of K562, a target for monitoring NK-like activity, was obtained in 95-100% of cases with both stimuli. A similar frequency of OKT3+, OKT4+, OKT8+ and HNK1+ cells was found in PBL activated by allostimulation and IL-2, whereas a higher frequency of OKM1+ cells was evident in IL-2-stimulated PBL. Cold-target competition studies indicated that allostimulation generated at least two different types of effectors, one lytic to auto-Me but not to K562, and the other which lysed both targets. Allostimulated, FACS-separated T3- cells killed both auto-Me and K562 cells whereas T3+ cells lysed only auto-Me. It is concluded that allostimulation generated two subpopulations of auto-Me killer cells, one of the T lineage and the other NK-like, which both can destroy auto-Me targets.

Antibodies, Monoclonal↗
PubMed1985

Detection of the common acute lymphoblastic leukaemia antigen (CALLA) on B cells from human fetal tissues. A multiple phenotypic characterization.

Fetal bone marrow liver and spleen of gestational age 15-20 weeks contain CALLA+, HLA-DR+ lymphoid cells. We show that a proportion of them expresses surface membrane immunoglobulins (SIg) as well as B cell differentiation antigens. A multiple phenotypic analysis reveals that CALLA+ fetal B cells are: HLA-DR+, SIg+, FMC8+, BA1+, Y29.55+ or Y29.55-, B2+, TdT-. Tissue specific phenotypic differences concern the expression of B7 and HLA-DC on spleen but not on bone marrow B cells. This study indicates that the distribution of the CALL antigen across the B cell committed lineage is much wider in fetal than neonatal life since CALLA+B cells have not yet been detected in bone marrow and peripheral blood of normal infants and adults. In addition, the interpretation of our phenotypic data suggest that fetal bone marrow B cells are more immature than those present in the spleen, thus, further supporting the evidence that the bone marrow is the organ of B cell lymphopoiesis.

Antigens, Neoplasm↗
PubMed1984

Monoclonal gammopathy (IgM-k) in a patient with Burkitt's type lymphoblastic lymphoma.

We report a Burkitt's type lymphoblastic lymphoma (B-LL) case characterized by an abnormal IgMk immunoglobulin secretion and referred to us on February 12, 1982. The diagnosis has been histologically documented and the pathological stage of the disease (IV B) was determined according to the diagnostic criteria usually employed for the non-Hodgkin's lymphoma (NHL). Serum proteins were determined by electrophoresis and immunodiffusion. The review of the literature has allowed us to ascertain that the presence of a monoclonal IgM peak can be associated with NHL, particularly with those of B cell type and in adult subjects. Up to now, only six IgM B-LL secreting cases have been described. The biological and prognostic significance of this elevated Ig secretion is uncertain; therefore it may be important for the future to evaluate, in B-LL this immunological parameter.

Adolescent↗
PubMed1984

A computer algorithm for the analysis of protein distribution in budding yeast.

Flow cytometry gives relevant data on cellular parameters such as DNA, RNA, and protein contents of individual cells and is therefore a powerful tool for analyzing microbial population dynamics. Relevant information about growth dynamics may be obtained from protein distribution. In fact, protein distribution is related to age distribution and depends on the law of growth of the population and the law of growth of the single cell. To extract the available information from protein distribution, we developed a computer algorithm starting from a model for growth of Saccharomyces cerevisiae. This algorithm quantitatively fits experimental protein distributions, allows a deconvolution of these distributions, and thus yields information about temporal parameters of the cell cycle and structure of yeast populations.

Cell Cycle↗
PubMed1984

Characterization of the response of human thymocytes and blood lymphocytes to the synergistic mitogenicity of 12-O-tetradecanoylphorbol-13-acetate (TPA)-ionomycin.

The combination of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) and the calcium ionophore ionomycin is synergistically mitogenic for human fetal and infant thymocytes as well as peripheral blood lymphocytes. Optimal mitogenic stimulation is achieved when TPA and ionomycin are used at doses of 0.5-1 ng/ml and 0.5-1 microgram/ml, respectively. Phenotypic analysis and cell sorting show that the thymocytes responsive to the mitogen have a mature or medullary phenotype (T1+, T3+, T11+, T6-, HLA-A,B++, [TdT]-); similarly in blood the T cell subsets (T11+, T4+ and T11+, T8+) are selectively responsive to TPA-ionomycin. Both activated lymphocytes and thymocytes express HLA-DR antigens as well as activation antigens such as T9, T10 and T cell activation antigen. T cells activated by TPA-ionomycin can be grown for periods of up to 50 days without addition of exogeneous interleukin 2. The observations may have implications for the membrane-associated signals involved in T cell growth and proliferation.

Cell Division↗
PubMed1984

Monoclonal antibody-defined surface markers of effector cells involved in human monocyte cytotoxicity.

Human adherent peripheral blood mononuclear cells were cytotoxic in vitro against the murine TU5 line in a 48-hr [3H]thymidine-release assay. Monocyte-enriched adherent cell preparations contain a small and variable (usually less than 5%) contamination with large granular lymphocytes as assessed by morphology and staining with monoclonal antibody markers B73.1 and HNK1. To assess whether killing was in fact mediated by monocytes, mononuclear cells or monocyte-enriched preparations were separated using monoclonal antibodies directed against mononuclear phagocytes (Mo2, UCHM1, B44.1) or natural killer (NK) cells (B73.1 and HNK1), and a fluorescence-activated cell sorter. Cells positive for monocyte markers were highly cytotoxic against TU5, whereas negative cells were not. B73.1+ or HNK1+ cells had little or no activity. Cytotoxicity of cells positive for monocyte markers (Mo2, UCHM1, B44.1) was augmented by in vitro exposure to lymphokines or less frequently to interferon (IFN). However, cells negative for these monocytes markers were also stimulated to kill TU5 by lymphokine or IFN to an extent similar or greater than that of positive ones. IFN or lymphokines induced killing of TU5 by monocyte-depleted, B73.1-positive, lymphoid cells. These observations demonstrate that human monocytes do kill tumor cells, either in the absence of deliberate stimulation or after exposure to agents such as lymphokines. However, the possible contribution to "monocyte" cytotoxicity of minor NK cell contaminants must be taken into account particularly when agents such as IFN and lymphokines are applied, even when a relatively NK-cell-resistant target such as TU5 is used.

Antibodies, Monoclonal↗
PubMed1984

Lineage relationship of chronic lymphocytic leukemia and hairy cell leukemia: studies with TPA.

The tumor promoting agent TPA (phorbol ester; 1.6 X 10(-8)M) was used to induce the differentiation in vitro of B-chronic lymphocytic leukemia (B-CLL) cells from 14 untreated patients. The uninduced phenotype was SIg+, Mrbc+, RFT-1+, RFA-4-, FMC7-. After 72 h incubation with TPA, B-CLL cells became RFA-4+, FMC7+ and lost the capability of Mrbc rosetting. Large proportions of the "induced" cells also showed morphological and ultrastructural changes, such as undulating membranes and bleblike protusions and became strongly positive for tartrate resistant acid phosphatase (TRAP+) and also contained cytoplasmic immunoglobulins. These features are very similar to the features of hairy cell leukemia (HCL). These observations confirm previous clinical findings that B-CLL and HCL are related disorders of the B lineage. The development of "hairy" features in induced B-CLL and in HCL seems to be a malignancy-associated feature because the Mrbc+ normal B cells (B-CLL-equivalent cells) isolated from tonsil also develop TRAP positivity but no membrane aberrations.

B-Lymphocytes↗
PubMed1984

Phenotype of the terminal transferase-positive cells in human foetal liver and bone-marrow: analysis with monoclonal antibodies.

Liver and bone-marrow of 20 human foetuses between 15th and 20th week of gestational age were examined. Mononuclear cells were labelled with murine monoclonal antibodies to reveal surface antigens and with a rabbit antiserum to TdT for the detection of the nuclear enzyme, using a double colour indirect immunofluorescence technique. The results have revealed that TdT+ cells express the phenotype of B cell precursors HLA-DR+, CALLA+, FMC8+, LEU-1-, LEU-5-, LEU-9-. It suggests that foetal liver and bone-marrow have an active function in B-lymphopoiesis in humans. The involvement of TdT in the process of B-cell immunological acquisition is uncertain because only humans and Xenopus embryos, among the species examined, express TdT outside the thymus during ontogenesis.

Adolescent↗
PubMed1983

Differential expression of HLA-DR and DR-linked determinants on human leukemias and lymphoid cells.

Leukemic and normal hemopoietic cells were examined with the monoclonal anti-bodies DA2 and Genox 353 for the presence of HLA-DR and DR-linked (DC/MB) determinants, respectively. Although most non-T acute leukemias and leukemic cell lines expressed the monomorphic DR determinant detected by DA2, fewer than expected expressed the DR-linked polymorphic specificity detected by Genox 353. TdT+ lymphoid precursors from normal bone marrow were also DA2+ but Genox 353-. T cells and thymocytes which were DA2-, Genox 353- became DA2+, Genox 353+ after activation in vitro. Immunoprecipitation using DA2 and Genox 353 gave bands on polyacrylamide gel-electrophoresis which were of different molecular weights. In addition, DA2 could absorb out Genox 353 determinants from a cell lysate whereas Genox 353 could not absorb out DA2 determinants. It is concluded that DA2 and Genox 353 detect HLA-DR and DR-linked (DC1/MB1) determinants, respectively, and that these are differentially expressed on hemopoietic cells during differentiation.

Antibodies, Monoclonal↗
PubMed1983

Human Thy-1 antigen: cell surface expression on early T and B lymphocytes.

Human Thy-1 is present on the surface of only a small proportion of haemopoietic cells (thymus--0.2-10%; bone marrow--0.1-0.5%). We have analysed these Thy-1+ cells in more detail using immunofluorescence on a wide range of human haemopoietic cell lines and fresh leukaemic blasts; both situations where rare cells can become clonally expanded. The data demonstrate that Thy-1 is confined to the early stages of T- and B-lymphocyte development, and is absent from all myeloid cells. The Thy-1+ B cells represent late pre-B (c mu+)/early sIgM+ B cells. The Thy-1+ T cells are situated in the outer thymic cortex. Dual immunofluorescence analysis of FACS separated Thy-1+ thymocytes shows them to have the antigenic phenotype and morphology of prothymocytes/early thymocytes (some overlap seen with CALLA, TdT, OKT6 and OKT1).

Adult↗
PubMed1983

Analysis of the binding of peanut agglutinin (PNA) to leukaemic cells and its relationship to T-cell differentiation.

Several leukaemias have been screened with a panel of monoclonal antibodies as well as fluoresceinated peanut lectin (FITC-PNA). Approximately 25% of T-acute lymphoblastic leukaemias (T-ALLs) were strongly positive with FITC-PNA. The staining distribution pattern did not correlate with any other monoclonal antibody used, although the phenotypes of the PNA+ T-ALLs were similar to those found on cortical thymocytes and probably reflect a more mature cellular phenotype within the T-ALL group. Some myeloid leukaemias were also PNA+ although the staining was generally weak. Several T-cell lines were examined and generally the TdT- lines showed strongest fluorescence after incubation with FITC-PNA. If these lines were induced to differentiate with 12-O-tetradecanoyl phorbol 13-acetate (TPA) they became PNA-. This was accompanied by an increase in cellular sialyl transferase activity, suggesting that one step in the differentiation process of "early' T cells is the terminal sialylation of existing oligosaccharide chains. Metabolic labelling of PNA+ T-cell lines with [35S]-methionine followed by detergent lysis and affinity chromatography on PNA-agarose showed that several bands of molecular weights 40-100,000 were bound to the column when examined by sodium dodecyl sulphate polyacrylamide gel electrophoresis. If TPA-treated cells were examined these bands were absent.

Cell Differentiation↗
PubMed1982

Modulation of T leukaemic cell phenotype with phorbol ester.

A panel of monoclonal antibodies and other markers (e.g., terminal deoxynucleotidyl transferase, sheep erythrocyte rosettes, peanut agglutinin) have been used in conjunction with flow cytometry and biochemical analysis to monitor the induction of maturation in human thymic (T) leukaemic cell lines by phorbol ester (TPA). Seven cell lines underwent multiple phenotypic alterations in response to TPA but were unresponsive to synthetic thymic hormones (TP5, FTS) or to other compounds (e.g. DMSO, retinoic acid) which induce maturation in other types of leukaemia. The changes parallel those observed in normal T-cell differentiation and partly reflect alterations in glycosyl transferase activity, altered synthesis of proteins and regulation of cell surface receptors (for transferrin) associated with rapid growth and metabolism. These studies further illustrate the reversibility of maturation arrest in human leukaemia and provide support for the view that leukaemia may involve regulatory defects in the coupling of proliferation and maturation. Induction of promotion of terminal differentiation in leukaemic equivalents of T-cell precursors may provide a convenient system for the study of biochemical and molecular events involved in T-cell development and diversification.

Antibodies, Monoclonal↗
PubMed1981

Expression of cell-surface HLA-DR, HLA-ABC and glycophorin during erythroid differentiation.

The unexpected discovery that Ia-like (HLA-DR) antigens in humans were present on blast cells from acute myeloblastic leukaemia led to the finding that normal granulocytic progenitors, in contrast to their mature descendents, also expressed HLA-DR antigens. Thus, anti-Ia sera stain a proportion of myeloblasts in normal bone marrow, inhibit myeloid progenitor (CFU-GM) colony formation in the presence of complement and can be used to label and separate CFU-GM on a fluorescence-activated cell sorter (FACS). Winchester et al. subsequently reported that erythroid progenitors (BFU-E and CFU-E) were also inhibited or killed by anti-Ia (p28,37) and complement. These observations raised the possibility that HLA-DR (or presumptive I-region equivalent) products might have a regulatory role in early haematopoiesis. We have now analysed HLA-DR and HLA-ABC antigen expression on normal erythroid progenitors using monoclonal antibodies to non-polymorphic determinants and fluorescence-activated cell sorting. In parallel experiments, we tested a monoclonal antibody to glycophorin, a well defined erythroid-specific cell-surface membrane glycoprotein. We report that HLA-DR, HLA-ABC and glycophorin are all expressed at various stages during erythroid differentiation.

Bone Marrow↗
PubMed1981

Mapping cell surface antigen expression of haemopoietic progenitor cells using monoclonal antibodies.

A library of monoclonal antibodies which show selective reactivity with particular cells or gene products (e.g. HLA-DR, glycophorin) of different cell lineages in the haemopoietic system has been compiled. Using these probes in conjunction with the fluorescence-activated cell sorter (FACS) the pattern and sequence of cell surface antigenic expression on haemopoietic progenitor cells have been mapped. A cell is identified in bone marrow which has a unique membrane phenotype and the nuclear enzyme terminal deoxynucleotidyl transferase. Its composite phenotype is identical to that seen in the common variant of acute lymphoblastic leukaemia (ALL). It is suggested that this cell is a putative B lineage progenitor which provides the major target for ALL. Detailed analysis of erythroid differentiation with monoclonal antibodies on the FACS reveals an intriguing pattern of antigenic expression in which HLA-DR, glycophorin and band III appear in sequence. HLA-DR (Ia-like antigen) may be present on all or most committed haemopoietic progenitor cells and could play an important role in cell interactions regulating early haemopoiesis.

Animals↗