Synthetic small interfering RNA (siRNA) can suppress the expression of endogenous mRNA through RNA interference. It has been reported that siRNA can induce type I IFN production from plasmacytoid dendritic cells, leading to off-target effects. To separate immunostimulation from the desired gene-specific inhibitory activity, we designed RNA strands with chemical modifications at strategic positi...

Findings from molecular genetic and cytogenetic investigations suggest that mutations in suppressor genes play a key role in osteosarcoma pathogenesis. RB and p53 are frequently involved and are speculated to be indispensable components. Alterations in putative suppressor genes on chromosomes 18q and 3q additionally may be involved in various patterns. The high resolution of magnetic resonance ...

Naturally occurring nucleotide modifications within RNA have been proposed to be structural determinants for innate immune recognition. We tested this hypothesis in the context of native nonself-RNAs. Isolated, fully modified native bacterial transfer RNAs (tRNAs) induced significant secretion of IFN-α from human peripheral blood mononuclear cells in a manner dependent on TLR7 and plasmacytoid ...

An extensive Phase I evaluation of human lymphoblastoid interferon has been completed which, in addition to describing its clinical and pharmacological effects, emphasized a broad-scale evaluation of the immune response as a function of interferon dosage. Dose-limiting toxicity was generally due to constitutional symptoms which are remarkably similar to those produced by influenza, although tra...

background: nonspecific symptoms are common in all areas of medicine. patients and caregivers can be frustrated when an illness cannot be reduced to a discrete pathophysiological process that corresponds with the symptoms. we therefore asked the following questions: 1) which demographic factors and psychological comorbidities are associated with change from an initial diagnosis of nonspecific a...

Chyawanprash is an ayurvedic formulation used in Indian traditional medicinal system for its beneficial effect on human health. We investigated the immunostimulatory effects of Chyawanprash (CHY) using in vitro assays evaluating the secretion of cytokines such as Tumor Necrosis Factor-alpha (TNF-α), Interleukin-1beta (IL-1β) and Macrophage Inflammatory Protein-1-alpha (MIP-1-α) from murine bone...

Mononuclear phagocytes are essential for adjuvant activity and polyclonal immunoglobulin synthesis induced by endotoxin-associated protein (EP) from Salmonella spp. To define the mechanisms of EP-mediated immunostimulation, we evaluated monocyte functions central to adjuvanticity following exposure to Salmonella typhimurium EP. In this study, we show that EP promotes the survival of monocytes b...

Using murine macrophage-like J774.1 cells and fecal precipitates prepared from the feces of elderly volunteers whose acute inflammation had been inhibited by LKM512 yogurt consumption, we investigated the likelihood that immunostimulation by altered intestinal bacterial cell components contribute to the antiinflammatory benefits of this yogurt. Tumor necrosis factor-a production due to stimulat...