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Biomedical subjects

E Ruud

Publications and source records attributed to E Ruud.

36 records · Page 2Linked to original sources
PubMed1985

The specific induction of myc protooncogene expression in normal human B cells is not a sufficient event for acquisition of competence to proliferate.

Resting human B cells can be activated to proliferate in the presence of both polyclonal antibodies to immunoglobulin mu heavy chains and B-cell growth factor (BCGF). This process appears to be temporally controlled in that the initial activation of the B cells and their responsiveness to BCGF is carried out by polyclonal anti-mu-chain antibodies alone. We have used this system to investigate the role of the c-myc gene in the cell cycle of normal human peripheral blood B cells. Our results show that the polyclonal anti-mu-chain antibody-induced B-cell activation is accompanied by a specific induction of c-myc gene expression without promoting subsequent entry into the S phase unless BCGF is added. Monoclonal antibodies to either mu chain or the pan-B-cell antigen Bp35 also revealed a similar G0-to-G1 transition and activation of c-myc gene expression. However, unlike activation with polyclonal anti-mu-chain antibodies, cells stimulated with these monoclonal antibodies do not acquire responsiveness to BCGF. The results imply that additional inducible functions must be present to potentiate the myc-specific function in order for the B cells to acquire the capacity to proliferate in response to BCGF. These findings are discussed in relation to the origin of B-cell malignancies.

Antibodies, Anti-Idiotypic↗
PubMed1985

Characterization of two murine monoclonal antibodies reactive with human B cells. Their use in a high-yield, high-purity method for isolation of B cells and utilization of such cells in an assay for B-cell stimulating factor.

We describe two monoclonal antibodies, HH1 and HH2. Both reacted selectively with surface immunoglobulin (sIg)-positive human B cells. Both antibodies stained on average 7-8% of peripheral blood mononuclear cells. They have not been found to react with cells or cell lines of other haematopoietic cell lineages, except that HH2 was positive on a small percentage of cells of the erythroid cell line K562. The molecular weight of the HH1 antigen was 95 kD, as established by Western blotting. Neither of these two antibodies reacted with Ig determinants, Fc receptors, complement receptors, or known class-I or class-II molecules. A combination of these antibodies was used in a direct panning technique for high-yield enrichment of normal B lymphocytes from peripheral blood. The enriched B cells could be further purified by lysis of T cells (final yield, on average 72 +/- 8% of initial B cells) or by a second panning (yield, 35 +/- 11%). The purified B cells contained less than 1% contaminating T cells and less than 0.5% monocytes and were used in an assay for B-cell-stimulating factor which they showed a normal and very reproducible proliferative response.

Animals↗
PubMed1985

Distinct effects of gamma interferon on human B-lymphocyte precursor cell lines.

The effect of gamma interferon (IFN-gamma) on proliferation and antigenic characteristics of cell lines belonging to the B-cell progenitor compartment was studied. We observed a selective effect of recombinant IFN-gamma but not IFN-alpha on proliferation of the B-precursor cell lines Reh and KM3. On day 4, after addition of 400 mu/ml IFN-gamma the [3H]thymidine uptake in these cells was reduced to 60% and 45% respectively, while no effect of IFN-gamma was evident on the proliferation of the more mature B-cell lines Raji, Ramos, B85, and Daudi. On the other hand, both Reh and Ramos showed induction of major histocompatibility complex (MHC) class I antigen expression in response to 400 mu/ml IFN-gamma. In contrast to 12-O-tetradecanoyl-phorbol-13-acetate (TPA), IFN-gamma did not induce increased MHC class II antigen expression on Reh cells. Taken together, our results indicate that IFN-gamma fulfils distinct functions at different levels in the development of B cells.

B-Lymphocytes↗
PubMed1985

Differences in modifications of cytoplasmic free Ca2+ concentration and 86Rb+ influx in human neoplastic B cells by antibodies to mu- relative to delta-Ig heavy chains.

Cytoplasmic free Ca2+ concentration and influx of 86Rb+ (K+ analogue) were determined during the first minutes after stimulation of neoplastic human B cells and B cell lines by antibodies to surface Ig. The Ca2+ concentration increased in the great majority of samples (41 of 48). All of four B cell lines also responded, providing formal evidence that accessory cells are not required for this early, surface Ig-mediated event. Antibodies to delta as well as mu, heavy chains (anti-delta and anti-mu) could induce both Ca2+ and 86Rb+ responses. 86Rb+ responders were found within the group of Ca2+ responders, but no quantitative relation was observed between the two responses. In cells expressing both sIgM and sIgD, antibodies to delta heavy chains were more potent than those to mu heavy chains in inducing Ca2+ responses, whereas the opposite pattern was seen with regard to 86Rb+ responses. These results demonstrate that sIgM and sIgD can deliver different biochemical signals to the cell.

Antibodies, Neoplasm↗
PubMed1984

Different fate of antibodies to surface IgM and IgD in germinal centre cell-associated lymphomas.

In all of four human germinal centre cell-associated B lymphomas carrying sIgM + sIgD F(ab')2 fragments of rabbit antibodies to human mu-chain were accumulated intracellularly, whereas the accumulation of antibodies to delta-chain was considerably less abundant. The accumulation of antibodies to light chain was intermediate between antibodies to mu- and delta-chain. These results could be explained by the following observations: (i) the difference in the level of reexpression of sIgM and sIgD and (ii) the discovery that antibodies to delta-chain bound to reexpressed sIgD were degraded at a higher rate than those bound to primary sIgD and at a higher rate than antibodies to mu-chain, whether bound to primary or reexpressed sIgM.

Absorption↗
PubMed1984

Induction of maturation in different types of B-cell lymphomas in vitro with TPA and antibodies to surface immunoglobulin.

Cells from eight selected cases of human non-Hodgkin lymphomas of various histological types (lymphocytic, centrocytic, centrocytic/centroblastic, and immunocytomas) were stimulated in vitro with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and anti-immunoglobulins (anti-Ig) against the surface immunoglobulin (sIg) on the tumour cells. Six of these cases responded by intracellular Ig accumulation as measured by flow cytofluorometry and direct phenotypical change into immunoblasts/plasmablasts as detected by light microscopic immunocytochemistry. However, the response to TPA alone varied considerably from case to case. These findings suggest that many, if not all, B-cell subsets have the capacity to develop directly into Ig-synthesizing cells (immunoblasts and plasmablasts). However, conditions for eliciting such events may vary, depending on the phenotypical properties and differentiation stage.

Antibodies, Anti-Idiotypic↗
PubMed1984

Induction of maturation of human B-cell lymphomas in vitro. Morphologic changes in relation to immunoglobulin and DNA synthesis.

In vitro stimulation of cells from 8 non-Hodgkin's lymphomas comprising several histologic types with a tumor promotor (TPA) and with or without anti-immunoglobulins directed against the surface immunoglobulin of the tumor cells is reported. Morphologic transformation to immunoblastic and plasmablastic cells, but not to plasma cells, and induction of Ig and DNA synthesis were observed. A comparative analysis, including flow cytofluorometry, light microscopy combined with immunocytochemistry, and electron microscopy, suggests that the three events may not always be associated phenomena at the single-cell level even in monoclonal cell populations.

B-Lymphocytes↗
PubMed1983

Different responses elicited in vitro by antibodies to IgM and IgD in cells from a surface IgM + D-positive human follicular lymphoma.

The effect of anti-Igs in combination with the tumour promotor TPA on DNA and Ig synthesis in a human follicular germinal centre cell lymphoma carrying sIgM and sIgD was investigated. The lymphoma cells responded to both anti-mu and anti-delta chains and to anti-lambda light chains by DNA synthesis, as measured by methyl-(3H)-thymidine incorporation. Flow cytofluorometric measurements, however, showed that only anti-mu chains induced marked increase in cytoplasmic Ig content. This result suggests that in certain B-cell subsets the signals elicited via sIgM and sIgD are different.

Antibodies, Anti-Idiotypic↗
PubMed1983

Delineation of subsets in human B-cell lymphomas by a set of monoclonal antibodies raised against B lymphoma cells.

Murine hybridoma antibodies to a human B-cell lymphoma were developed. After screening against normal T cells, monocytes, and granulocytes 11 antibodies that reacted with cells from other B-cell lymphomas remained, of which 10 showed individually distinct staining patterns, as tested by indirect fluorescence. When tested against lymphomas or cell lines, none of these antibodies revealed staining patterns suggesting reactivity with conventional B-cell surface markers, such as immunoglobulin, complement factor 3 receptors, or HLA-DR antigens. Only one of the antibodies (GB1) reacted with human serum, as determined by a blocking assay. The antibodies were found to belong to different immunoglobulin isotypes. Two antibodies (GB13 and GB14) reacted with greater than 5% of normal peripheral blood mononuclear cells. These reactions were mainly due to reactivity with B cells. The antibodies reacted only in a few cases with acute leukaemias, B-cell lines, and follicular lymphomas. On the other hand, distinct patterns of reactivity in different histological groups of diffuse lymphomas were obtained, suggesting that the antibodies may be useful in delineating phenotypic subsets among human B-cell lymphomas.

Animals↗
PubMed1983

One hundred and twenty visually handicapped children below 7 years of age.

120 visually handicapped pre-school children are evaluated according to eye disease and its etiology, and the associated handicap, all related to the different levels of functioning. One third of the children fulfil the expectations on visually handicapped children. The group consists mainly of children suffering from hereditary ocular disorders and some children with retrolental fibroplasia. One third of the children are moderately or severely intellectually impaired, bearing a heavy burden of additional handicaps; many are born premature or dysmature, having suffered perinatal complications. The final third are children who fall outside the other 2 groups, some with a brain damage syndrome, some with light or moderate behavioural and emotional disturbance. The moderate and severe emotional disturbance and its relation to a brain dysfunctional syndrome are discussed.

Affective Symptoms↗
PubMed1983

Triggering of monoclonal human lymphoma B cells with antibodies to IgM heavy chains: differences of response obtained with monoclonal as compared to polyclonal antibodies.

A comparative study of human B lymphoma cells activation by monoclonal (murine hybridoma) antibodies to mu heavy chains (Ma-mu) as compared to polyclonal (rabbit) antibodies to mu heavy chains (Ra-mu) has been carried out. Early events related to calmodulin activation such as 86Rb influx and changes in cell volume at 4 h could be induced by Ma-mu. One antibody (AF6) approached Ra-mu with regard to the strength of response obtained. However, Ma-mus including AF6 were deficient in inducing DNA synthesis under conditions where this was achieved with Ra-mu. Studies in one lymphoma, where stimulation of re-expressed surface IgM could be studied, revealed that Ma-mu was deficient in stimulating re-expressed sIgM. These findings raise questions with regard to polyclonal antibody to surface Ig as a model for B cell triggering by antigen and suggest that antigen-induced B cell triggering may be more complex than indicated by previous studies with polyclonal antibody.

Antibodies, Monoclonal↗
PubMed1982

Monoclonal human B lymphoma cells respond to DNA synthesis to anti-immunoglobulins in the presence of the tumour promotor TPA.

Monoclonal human B lymphoma cells were triggered in vitro to DNA synthesis with F(ab')2 fragments of rabbit IgG antibodies specific for different human immunoglobulin (Ig) light and heavy chains. The specificity of the responses corresponded to surface Ig (sIg) present on tumour cells. Anti-mu chain, anti-delta chain, and antibodies to light chains were found to mediate this effect. However, to induce DNA synthesis, the tumour promotor 12-O-tetradecanoyl-phorbol-13-acetate (TPA) was usually required. TPA alone induced cytoplasmic protrusions and increases in cellular volume. These observations should provide new opportunities to study the triggering of B cells with anti-Ig in well-defined cell populations.

Antibodies, Anti-Idiotypic↗
PubMed1981

On the importance of substrate adhesion and cell aggregation in the Con A-induced blastogenesis of lymphocytes.

The importance of substrate adhesion and cell aggregation for the Con A-induced blastogenesis of human peripheral lymphocytes was studied by flow cytometric methods. The percentage of lymphocytes responding to the mitogen by growth and DNA synthesis was approximately the same among non-adherent, single cells as among substrate-adherent and aggregated cells. However, the response of the former cells was delayed by about 10 h as compared with that of adherent and aggregated cells. This delay increased to about 20 h in monocyte-depleted cultures. Stimulation with succinyl-Con A, which caused negligible aggregation, produced a significant response. Blast cells appeared to be largely non-adherent. It is concluded that neither substrate adhesion nor cell aggregation are prerequisites for Con A-induced blastogenesis, although substrate adhesion seems to have a significant promotive effect that is probably associated with a direct contact of the lymphocytes with monocytes.

Cell Adhesion↗