HIV-1/HCV co-infection is a significant health problem. Highly active antiretroviral treatment (HAART) against HIV-1 has proved to be fairly successful. On the other hand, direct acting antiviral drugs against HCV have improved cure rates but high cost and development of drug resistance are important concerns.
View Article and Find Full Text PDFMonoclonal antibodies (mAbs) are widely used in anti-inflammatory and tumor therapy. Although effective, mAbs can cause a variety of adverse effects. An important toxicity seen with a few mAbs is cytokine-release syndrome (CRS).
View Article and Find Full Text PDFAnalysis of multicolor flow cytometric data is traditionally based on the judgment of an expert, generally time consuming, sometimes incomplete and often subjective in nature. In this article, we investigate another statistical method using a Sequential Univariate Gating (SUG) algorithm to identify regions of interest between two groups of multivariate flow cytometric data. The metric used to differentiate between the groups of univariate distributions in SUG is the Kolmogorov-Smirnov distance (D) statistic.
View Article and Find Full Text PDFTNF-alpha is a pleitropic cytokine that expresses both pro- and anti-inflammatory activity and transgenic mice expressing human tumor necrosis factor-alpha (TNF-alpha) exhibit a progressive polyarthritis that models rheumatoid arthritis (RA). One of the common comorbidities of RA is anemia of chronic disease (ACD). The purpose of these experiments was to study the changes in the bone marrow and peripheral blood that accompany polyarthritis in TNF-alpha transgenic mice in an effort to better understand the pathogenesis of myelodysplasia and ACD.
View Article and Find Full Text PDFPurpose: Originally approved for three times/week dosing, recombinant human erythropoietin (rhEPO) is now often used at weekly intervals. We have studied rhEPO in mice to better understand why the extended dosing interval retains efficacy.
Methods: C57Bl/6 mice received a single sc.
Bone marrow-derived immunomodulatory cytokines impart a critical function in the regulation of innate immune responses and hemopoiesis. However, the source of immunomodulatory cytokines in murine bone marrow and the cellular immune mechanisms that control local cytokine secretion remain poorly defined. Herein, we identified a population of resident murine bone marrow myeloid DEC205(+)CD11c(-)B220(-)Gr1(+)CD8alpha(-)CD11b(+) cells that respond to TLR2, TLR4, TLR7, TLR8, and TLR9 agonists as measured by the secretion of proinflammatory and anti-inflammatory cytokines in vitro.
View Article and Find Full Text PDFBackground: Cellular binding of annexin V and membrane permeability to 7-aminoactinomycin D (7AAD) are important tools for studying apoptosis and cell death by flow cytometry. Combining viability markers with cell surface marker expression is routinely used to study various cell lineages. Current classification methods using strict thresholds, or "gates," on the fluorescent intensity of these markers are subjective in nature and may not fully describe the phenotypes of interest.
View Article and Find Full Text PDFAlthough it has been shown that functions of immunoglobulin G (IgG) antibodies (Abs) that depend on binding to certain Fc gamma receptors (Fc gamma R) can be influenced by Fc glycan fucosylation, quantitative in vivo analyses comparing the effects of different levels of fucose are still lacking. We used a simple mouse model to compare Fc gamma R-dependent T cell activation induced by different fucosylation variants of a hamster/human IgG1 chimeric version of anti-mouse CD3 monoclonal Ab, 145-2C11 (2C11). Initial studies supported the expectation that this agonist activity by 2C11 was a reflection of Fc gamma R binding, including comparisons of human IgG1 and IgG4 variants of 2C11 that showed the IgG4 to be dramatically less active at inducing T cell activation.
View Article and Find Full Text PDFArch Immunol Ther Exp (Warsz)
February 2003
Peripheral blood lymphocytes from patients with Sezary syndrome (SzS) frequently demonstrate decreased surface expression of transforming growth factor beta receptor II (TGFbetaRII). The mechanism of this low TGFbetaRII expression remains unknown. Because mutations within the poly-A tract of the TGFbetaRII sequence (nucleotides 709-718) were shown to result in diminished TGFbetaRII expression in other types of malignant tumors, we examined the sequence of the TGFbetaRII poly-A tract in two SzS-derived cell lines and in peripheral blood SzS cells from 17 SzS patients and 4 control, healthy individuals using DNA sequencing and single-stranded conformation polymorphism (SSCP) analysis.
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