Receptor-mediated immediate and sustained anti-ss-adrenergic effects of melatonin were demonstrated in contractile function. A role for NO in the response was indicated, while a role for PKC was not verified.
The initial novel observation of this study was that most B cells of male BXSB lupus mice bear surface IgG2a b of extrinsic origin. To define the surface antigen, we here examine three (NZBxBXSB)F1-derived IgG2a b monoclonal antibodies (mAbs) selected for binding to cell surfaces. Surprisingly, all three mAbs bound the nucleosome (nuc) particle, the fundamental unit of chromatin and an early target of autoimmunity in systemic lupus erythematosus. Their tentative dissociation constant (K d ) for soluble nuc particles was approximately 7 Â 10The mAbs bound more weakly to both H2A-H2B-DNA and H3-H4-DNA complexes, and in immunoblot they stained all four core histones. The mAbs detected a surface antigen on all cell lines examined, present on viable cells. When stripped of nuc , and in the presence of DNase I, their binding to cell lines improved. Heparin displaced the antigen from the cell surface. In vivo, the three mAbs stained B cells of several BALB/c mice clearly stronger than the isotype control; this differential staining was significantly reduced in FcgRIIBdeficient mice. The results indicate that the three mAbs recognize (a) planted antigen on viable cultured cells and (b) soluble autoantigen in vivo, leading to immune complexes that bind to FcgRIIB. Further experiments demonstrated that antinuc IgG2a could be eluted from splenocytes of a male BXSB lupus mouse. Hence, at least part of the extrinsic IgG2a b found on BXSB B cells may represent FcgRIIB-bound nuc-IgG2a b complexes.
Multiple myeloma (MM) is considered an incurable B cell malignancy, although many patients can benefit from high-dose therapy with autologous stem cell transplantation (ASCT) as a first-line treatment. In non-Hodgkin lymphoma (NHL), ASCT is usually performed after relapse with curative intent. Disease progression is often associated with increased angiogenesis, in which endothelial progenitor cells (EPC) may have a central role. Here, we investigated the clinical impact of EPC levels in peripheral blood stem cell (PBSC) autografts for MM and NHL patients who received ASCT. EPC were identified by flow cytometry as aldehyde dehydrogenase(hi) CD34(+) vascular endothelial growth factor receptor 2(+) CD133(+) cells in both MM and NHL autografts. In MM, there was a positive correlation between EPC percentage and serum (s)-β2-microglobulin levels (r(2) = .371, P = .002). Unlike for NHL patients, MM patients with high numbers of infused EPC (EPC cells per kilogram) during ASCT had significant shorter progression-free survival (PFS) (P = .035), overall survival (P = .044) and time to next treatment (P = .009). In multivariate analysis, EPC cells per kilogram was a significant independent negative prognostic indicator of PFS (P = .03). In conclusion, the presence of high number of EPC in PBSC grafts is associated with adverse prognosis after ASCT in MM.
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