Specific intracellular signals mediated by interleukin-6 (IL-6) receptor complexes, such as signal transducer and activator of transcription 3 (STAT 3) and extracellu-lar signal-regulated kinase (ERK) 1/2, are considered to be responsible for inducing a variety of cellular responses. In multiple myeloma, IL-6 only enhanced the proliferation of CD45 tumor cells that harbored the IL-6-independent activation of src family kinases even though STAT3 and ERK1/2 could be activated in response to IL-6 in both CD45 and CD45 cells. Furthermore, the IL-6-induced proliferation of CD45 U266 myeloma cells was significantly suppressed by Lyn-specific antisense oligodeoxynucleo-tides or a selective src kinase inhibitor. These results indicate that the activation of both STAT3 and ERK1/2 is not enough for IL-6-induced proliferation of myeloma cell lines that require src family kinase activation independent of IL-6 stimulation. Thus, the activation of the src family kinases associated with CD45 expression is a prerequisite for the proliferation of myeloma cell lines by IL-6. We propose a mechanism for IL-6-induced cell proliferation that is strictly dependent upon the cellular context in myelomas. (Blood. 2002;99:2172-2178)
Dendritic cells (DCs) are believed to be the most potent antigen-presenting cells and may be important in the induction of anti-leukemia specific T cell responses. In this preliminary clinical study, a patient with chronic phase chronic myelogenous leukemia (CML) was vaccinated with autologous leukemic DCs following autologous peripheral blood stem cell transplantation (PBSCT). In an in vitro study, leukemic DCs were generated using granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-α α α α, and interleukin-4 from granulocyte colony-stimulating factor (G-CSF)-mobilized PBSC fraction of this patient, and were found to be Ph1
A case of Klinefelter's syndrome associated with progressive systemic sclerosis (PSS) is described. The patient had been infertile for 20 years after marriage and was diagnosed as PSS with Klinefelter's syndrome at the age of 43. In reviewing the literature, we observed that five cases with PSS within the range of 41 to 61 years of age, and seventeen cases with systemic lupus erythematosus (SLE), but only few cases with other connective tissue diseases were reported in association with Klinefelter's syndrome. Possible involvement of male hypogonadism in the pathogenesis of PSS was suggested.
Ly-1-B cells have been shown to be elevated in autoimmune mice, especially NZB, and to secrete IgM autoantibody, suggesting that Ly-1 B cells may participate in autoimmune diseases. In this study, B-cell populations carrying Leu-1, a human T-cell surface molecule homologous to mouse Ly-1 (Leu-1 B), were examined by dual fluorescence flow cytometry, in peripheral blood lymphocytes taken from patients suffering from various autoimmune disease. These B cells were shown to be present at a significantly high percentage in rheumatoid arthritis (RA) patients. There was no significant correlation among the incidence of Leu-1 B cells, rheumatoid factor (RF) titers, and the amount of IgM production in vitro. There was, however, a significantly high incidence of Leu-1 B cells in RA patients with a high RF titer (greater than 5 X 2(13), suggesting that these B cells in RA may play an important role in IgM RF production in vivo.
Rat monoclonal antibodies were constructed by fusion of immunized rat spleen cells with a non-secreting mouse myeloma cell. Two monoclonal antibodies (6HD5 and HMK-12) were selected for further study. Both reacted with various IgE molecules of different specificities and different allotypes, but did not react with immunoglobulins of other isotypes and with light chains. These antibodies were therefore anti-isotypic (IgE) and not anti-allotypic or anti-idiotypic. It was shown by competition studies that these antibodies recognize different epitopes on the FcRε fragment. A sensitive ELISA for the quantitation of murine IgE was developed with these monoclonal antibodies; the sensitivity was between 2 and 250 ng/ml for detection of serum IgE levels. Good correlation was obtained with protein amounts as determined by enzyme-linked immunosorbent assay (ELISA) and passive cutaneous anaphylaxis (PCA) activities. Both monoclonal antibodies were used to study anaphylactic reactions elicited by IgE antibodies. Both could inhibit PCA reactions and both could elicit reverse PCA reactions.
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