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Biomedical subjects

W J Koopman

Publications and source records attributed to W J Koopman.

211 records · Page 12Linked to original sources
PubMed1978

Biochemical relationship of thymocyte mitogenic factor and factors enhancing humoral and cell-mediated immune responses.

Supernatants from concanavalin A-induced mouse spleen cells contain soluble factors which: 1) augment the anti-sheep erythrocyte hemolytic plaque-forming cell response of nude mouse spleen cells, 2) facilitate the generation of antigen-specific cytotoxic cells by alloantigen-stimulated thymocytes, and 3) enhance the mitogenic response of thymocytes in the presence or absence of phytohemagglutinin. The uninduced control spleen cell supernatants contained variable but significantly less biologic activity within the difference assay systems. The principle enhancing activity (apparent m.w. 35,000 to 38,000) in each of the assay systems was found to be inseparable after a multiple step purification scheme involving ammonium sulfate precipitation, two-cycle gel filtration, hydroxylapatite chromatography, and hydrophobic chromatography on Phenyl Sepharose. These results indicate that either a single factor (designated thymocyte mitogenic factor) augments both humoral and cell-mediated immune responses or, alternatively, the different biologic activities are mediated by different factors that share a common core structure.

Ammonium Sulfate↗
PubMed1977

Association of a low molecular weight helper factor(s) with thymocyte proliferative activity.

Human mixed leukocyte supernatants contain thymocyte proliferative activity (TPA) and a low m.w. helper factor, designated HP-1, which is capable of partially restoring the antibody response of T-cell-deficient adherent murine spleen cells to the thymic-dependent antigen, SRC. TPA and HP-1 appear to have a comparable m.w. (14,000 to 14,500 daltons) by Sephadex gel filtration column chromatography. Furthermore, HP-1 and TPA exhibit similar patterns of heterogeneity on DEAE-cellulose chromatography, elute together on CM-cellulose chromatography, and manifest identical patterns of migration on polyacrylamide gel electrophoresis. These data suggest that the TPA and HP-1 activities reside in either the same molecule(s) or in different molecules with identical charge/mass ratios. Furthermore, the results support the hypothesis that the helper activity of HP-1 is derived from its capacity to activate T and/or pre-T cells.

Animals↗
PubMed1976

Interaction of soluble C3 fragments with guinea pig lymphocytes. Comparison of effects of C3a, C3b, C3c, and C3d on lymphokine production and lymphocyte proliferation.

C3a, C3b, C3c, and C3d were generated from purified guinea pig C3 by trypsin treatment. These fragments were characterized immunochemically and functionally by rosette inhibition. C3b is capable of binding to both C3b and C3d receptors on lymphocytes whereas C3d binds only to C3D receptors. C3b stimulates guinea pig spleen cells to elaborate a macrophage chemotactic factor which is similar in m.w. to that generated in response to PHA or LPS and is antigenically unrelated to C3 or C5. In contrast, neither C3a, C3c, or C3d stimulate guinea pig lymphocytes. Neither C3 nor any of its major fragments induce cellular proliferation. These data are compatible with the hypothesis that C3b triggers spleen cells to release a macrophage chemotactic factor by cross-linking C3b and C3d receptors.

Animals↗
PubMedDate not supplied

Evidence that Ca2+-waves in Xenopus melanotropes depend on calcium-induced calcium release: a fluorescence correlation microscopy and linescanning study.

The neuroendocrine melanotrope cell displays Ca2+ oscillations that are build up by several discrete Ca2+ rises ('steps'). Each step is linked to Ca2+-entry across the plasma membrane via voltage-operated calcium channels and associated with a fast Ca2+-wave travelling from the plasma membrane to the central parts of the cell. Previously, linescanning with confocal laser scanning microscopy (CLSM) supported that these waves have high speeds (between 30 and 80 microm/s), which is considered indicative of the involvement of a calcium-induced calcium release (CICR) mechanism in fast-wave propagation. However, to firmly establish the presence of a CICR mechanism one must rule out the possibility that the Ca2+ signal is artifactually accelerated by the presence of a highly mobile Ca2+ probe and also eliminate imaging artifacts inherent to single wavelength imaging. In the present study both problems are addressed. Mobility and intracellular distribution of a generally used Ca2+ probe, Oregon-green 488 BAPTA-1 (O-green-1), were established using fluorescence correlation microscopy. We then used the ratio signal of co-loaded O-green-1 and Fura-Red to quantify the relative [Ca2+]i during linescanning. It was found that O-green-1 displays different diffusion times when regions near the plasma membrane and in the center of the cell are compared. However, the calculated diffusion constant of the probe was too low to account for the observed high speed of the Ca2+ wave. In conclusion, we established the authenticity of the high speed of Ca2+-waves in Xenopus melanotropes, providing evidence for the involvement of a CICR mechanism in wave propagation.

Animals↗
PubMedDate not supplied

Rheumatoid factor diversity.

Rheumatoid factors, antibodies directed against the Fc portion of IgG, exhibit considerable isotypic and idiotypic diversity. Differential expression of IgM and IgA rheumatoid factors suggests that isotype-specific regulatory pathways are operative in man. The physical characteristics of IgA rheumatoid factor in rheumatoid arthritis have also been investigated. Although the polymeric form of IgA rheumatoid factor generally predominates in sera and synovial fluids of rheumatoid arthritis patients, wide variations in the ratio of monomeric to polymeric IgA rheumatoid factor are observed. Both forms are elaborated by synovial plasma cells. That differences in the proportions of monomeric and polymeric IgA RF present in sera may be of pathogenetic significance is suggested by evidence that complexes of polymeric IgA rheumatoid factor and IgG are potent inducers of lysosomal release by RMN whereas monomeric IgA rheumatoid factor-IgG complexes are essentially inactive in this regard. The idiotypic diversity of rheumatoid factors has also been under intensive investigation. A monoclonal antibody designated 6B6.6 recognizes a Vk-associated idiotype present on approximately one-third of IgMk rheumatoid factor paraproteins, but only a small fraction of polyclonal IgM 6B6.6-defined idiotype is distinct from previously described rheumatoid factor cross-reactive idiotypes. Taken together, these studies underline the extensive diversity of rheumatoid factors present in various conditions. Application of molecular genetic approaches to the study of rheumatoid factors should provide explanations for the molecular basis of this diversity and serve to clarify the relationship among rheumatoid factors expressed in both physiologic and pathologic states.

Antibody Diversity↗
PubMedDate not supplied

Experience with a chimeric monoclonal anti-CD4 antibody in the treatment of refractory rheumatoid arthritis.

We have used a chimeric monoclonal anti-CD4 antibody (cM-T412) in a phase I trial involving patients with refractory RA. The objectives of this initial study were to evaluate the safety, immunogenicity, and biologic effects of cM-T412. Twenty-five patients with active refractory RA (all taking methotrexate concomitantly) were treated with incremental doses (10 to 700 mg) of cM-T412 in an open-label, escalating dose phase I trial. Levels of circulating CD4+ T-cells decreased rapidly post-infusion and remained significantly depressed even at 18 months following treatment. Repopulation of CD4+ T cells consisting of increased CD45RA+ (naive) and CD45RO+ (memory) CD4+ T-cells was observed in approximately 1/3 of the patients between day 14 and 6 months post-infusion. Proliferative responses of peripheral blood lymphocytes to mitogens and recall antigens were generally diminished following cM-T412 infusion, with mitogen responses normalizing more rapidly than responses to recall antigens. Adverse events during the first 6 months of follow-up included fever, often associated with myalgias, malaise, and asymptomatic hypotension; these symptoms were self-limited and appeared to correlate with transient elevations of interleukin-6. Negligible human antibody responses to the cM-T412 variable region were observed; indeed, only 2 patients developed transient low levels of antibodies reactive with cM-T412. Non-blinded assessment indicated that 43% of patients exhibited > or = 50% improvement in tender joint counts at 5 weeks, and 33% at 6 months post-infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Antifolates in rheumatoid arthritis: a hypothetical mechanism of action.

The antifolates, methotrexate, aminopterin, 10-deazaaminopterin and sulfasalazine are clinically useful in the treatment of rheumatoid arthritis. Toxicity, rather than efficacy, appears to the the major factor limiting the usefulness of the classical antifolates (i.e., methotrexate and 10-deazaaminopterin). The fact that folate supplementation of methotrexate-treated rheumatoid arthritis patients reduces toxicity without altering efficacy also suggests that inhibition of the drug's target enzyme, dihydrofolate reductase, is not complete and not essential for efficacy. Since polyglutamates of methotrexate are direct inhibitors of thymidylate synthase and folate dependent enzymes of purine biosynthesis, the efficacy of this agent may involve blockade of these pathways. We hypothesize that blockage of aminoimidazole carboxamide ribotide transformylase, the folate dependent enzyme responsible for the insertion of carbon 2 into the purine ring, produces an immunosuppression mediated by secondary inhibition of adenosine deaminase, and S-adenosyl homocystein hydrolase by aminoimidazolecarboxamide metabolites. This mechanism of immunosuppression may explain the clinical effect of methotrexate, 10-deazaaminopterin, and possibly sulfasalazine. Since purine biosynthesis is a fundamental process, blockading this pathway may also decrease leukotriene production and interleukin-1 expression, which also could contribute to the efficacy of methotrexate.

Acyltransferases↗