Effects of an anion channel blocker, 4, 4'-diisothiocyano-2,2'-disulfonic acid stilbene (DIDS), on human neutrophil function

We investigated the capacity of DIDS to influence degranulation and superoxide anion (O-2) generation by human neutrophils exposed to soluble, surface-active stimuli. DIDS caused a concentration-related (25-200 microM) inhibition of myeloperoxidase (MPO) release from N-formyl-methionyl-leucyl-phenylalanine (FMLP), 5(S), 12(R)-dihydroxy-6, 14-cis-8, 10-trans-eicosatetraenoic acid (LTB4), 1-0-hexadecyl/octadecyl-2-0-acetyl-sn-glyceryl-3-phosphorylcholine (AGEPC) and phorbol myristate acetate (PMA)-stimulated neutrophils. In contrast, DIDS had no effect on O-2 production by FMLP and PMA activated cells, whereas it enhanced LTB4 and AGEPC-elicited O-2 generation. The respective effects of DIDS on these neutrophil activities were reversed by washing the cells prior to exposure to stimulus. Thus, DIDS represents a useful pharmacologic probe for investigating the role(s) of anions in the mechanisms of neutrophil activation with structurally and chemically dissimilar stimuli.     

Nitrogen budget of a shortgrass prairie ecosystem

Summary A N budget is presented for a shortgrass prairie ecosystem. The grassland was ungrazed by domestic herbivores. The quantities of N in various plant, animal, microorganism, and soil components of the ecosystem are estimated for the date when aboveground living biomass was at its maximum for the growing season of 1973. Annual transfers of N between the various compartments were also estimated.Of the total N, 99.5% was in organic forms. The relatively inert heteropolycondensate fraction of the organic matter in the soils contained 88.8% of the N. Living organisms contained 4.2% and dead but recognizable organisms or part thereof contained 6.5% of the total N. Belowground animals contained more than 10 times as much N as abovegroud animals, but combined, animals contained less than 0.1% of the total in the system. Living plant material contained 2.5% of the total N. Seventy-two percent of the living plant N was below ground. Microorganisms contained 1.4% of the total N.Total N uptake by plants from soil solution was 2.9 g·m^-2·yr^-1. Aerial portions of plants were allocated 1.9 N·m^-2·yr^-1 although apparently 26% of this amount came from internally recycled sources. The heteropolycondensate fraction of the soil contributed 0.7 g N·m^-2·yr^-1 to mineral forms, but these components of the system were assumed to be in steady state; thus an equal amount of mineral N was allocated back to the source. Mineralization of N from plant residues was sufficient to account for all of the N taken up by plants from soil solution. Soil animals immobilized about 0.4 g N·m^-2·yr^-1 while the amount shunted to aboveground animals was trivial.     

Cyanidin-3-glucoside, a natural product derived from blackberry, exhibits chemopreventive and chemotherapeutic activity

Epidemiological data suggest that consumption of fruits and vegetables has been associated with a lower incidence of cancer. Cyanidin-3-glucoside (C3G), a compound found in blackberry and other food products, was shown to possess chemopreventive and chemotherapeutic activity in the present study. In cultured JB6 cells, C3G was able to scavenge ultraviolet B-induced *OH and O2-* radicals. In vivo studies indicated that C3G treatment decreased the number of non-malignant and malignant skin tumors per mouse induced by 12-O-tetradecanolyphorbol-13-acetate (TPA) in 7,12-dimethylbenz[a]anthracene-initiated mouse skin. Pretreatment of JB6 cells with C3G inhibited UVB- and TPA-induced transactivation of NF-kappaB and AP-1 and expression of cyclooxygenase-2 and tumor necrosis factor-alpha. These inhibitory effects appear to be mediated through the inhibition of MAPK activity. C3G also blocked TPA-induced neoplastic transformation in JB6 cells. In addition, C3G inhibited proliferation of a human lung carcinoma cell line, A549. Animal studies showed that C3G reduced the size of A549 tumor xenograft growth and significantly inhibited metastasis in nude mice. Mechanistic studies indicated that C3G inhibited migration and invasion of A549 tumor cells. These finding demonstrate for the first time that a purified compound of anthocyanin inhibits tumor promoter-induced carcinogenesis and tumor metastasis in vivo.     

Immune regulation of bone loss by Th17 cells

A significant macrophage and T-cell infiltrate commonly occurs in inflammatory joint conditions such as rheumatoid arthritis that have significant bone destruction. Cytokines produced by activated macrophages and T cells are implicated in arthritis pathogenesis and are involved in osteoclast-mediated bone resorption. The scope of the present review is to analyze current knowledge and to provide a better understanding of how macrophage-derived factors promote the differentiation of a novel T-helper subset (Th17) that promotes osteoclast formation and activation.     

Molecular classification of scrapie strains in mice using gene expression profiling

Transmissible spongiform encephalopathy strains demonstrate specific prion characteristics, each with specific incubation times, and strain-specific patterns of deposition of the misfolded isoform of prion, PrPSc, in the brains of infected individuals. Different biochemical properties, including glycosylation profiles and the degree of proteinase resistance, have been shown to be strain-specific. However, no relationship between these properties and the phenotypic differences in the subsequent diseases has as yet been determined. Here we explore the utility of gene expression profiles to identify differences in the host response to different strains of prion agent. We identify 114 genes that exhibit significantly different levels of expression in mice infected with three strains of scrapie. These genes represent a pool of genes involved in a strain-specific response to prion disease. We have identified the most discriminatory genes from this list utilizing a wrapper-based feature selection algorithm with external cross-validation.     

Ascorbic acid, cognitive function, and Alzheimer's disease: a current review and future direction

This narrative review appraises the human and animal studies implicating ascorbic acid (AA) in normal cognitive function and Alzheimer's disease. A research framework for how nutrition affects brain aging is proposed with emphasis on AA intake, status, metabolism, and transport into brain tissue. A final synopsis highlights areas for future research regarding AA nourishment and healthy brain aging.     

Aging of human fibroblasts in vitro. Correlations between DNA synthetic ability and cell size.

In tobacco cell suspensions, protein synthesis and mitotic activity were inhibited by amino acid analogues: p-fluorophenylalanine (pFPA) or 5-methyltryptophan (5MT). After inhibition by pFPA, when the mitotic activity recovered in the presence of phenylalanine and casein hydrolysate, the time table of the mitotic phases was permanently altered. The inhibiting effects of 5MT were effectively reversed by tryptophan addition to the medium. Therefore 5MT was selected for reversible protein synthesis inhibition in partially synchronized cell suspensions. When cytokinin was added in a culture where protein synthesis was inhibited by 5MT, no mitosis was observed after the cells were transferred to a hormone-free medium and protein synthesis restored by tryptophan. Cytokinin must again be added in order to restore mitosis. Thus, the hormone effectiveness of cytokinins required that protein synthesis remained undisturbed. The effect of the protein synthesis inhibition by 5MT upon the metabolism of N⁶-benzyladenine was investigated: the intracellular concentration of this cytokinin was not altered, whereas the metabolic pool of its derivatives was quantitatively reduced.