Polymorphism of the tumor necrosis factor beta gene in systemic lupus erythematosus

We investigated the Nco I restriction fragment length polymorphism (RFLP) of the tumor necrosis factor beta (TNFB) gene in 173 patients with systemic lupus erythematosus (SLE), 192 unrelated healthy controls, and eleven panel families, all of German origin. The phenotype frequency of the TNFB*I allele was significantly increased in patients compared to controls (63.6% vs 47.1%, RR = 1.96, p <0.002). The results of a two-point haplotype statistical analysis between TNFB and HLA alleles show that there is linkage disequilibrium between TNFB*I and HLA-A1, Cw7, B8, DR3, DQ2, and C4A DE. The frequency of TNFB*I was compared in SLE patients and controls in the presence or absence of each of these alleles. TNFB*I is increased in patients over controls only in the presence of the mentioned alleles. Therefore, the whole haplotypeA1, Cw7, B8, TNFB* I, C4A DE, DR3, DQ2 is increased in patients and it cannot be determined which of the genes carried by this haplotype is responsible for the susceptibility to SLE. In addition, two-locus associations were analyzed in 192 unrelated healthy controls for TNFB and class I alleles typed by serology, and for TNFB and class II alleles typed by polymerase chain reaction/oligonucleotide probes. We found positive linkage disequilibrium between TNFB*I and the following alleles: HLA-A24, HLA-B8, DRBI*0301, DRBI*ll04, DRBI*1302, DQAI*0501, DQBI*0201, DQBI*0604, and DPBI*OIO1. TNFB*2 is associated with HLA-B7, DRBI*1501, and DQB I *0602

Identification of Ag-acceptors in 111 ⁣^{111}\!Ag 111 ⁣^{111}\!Cd doped ZnTe and CdTe

Nominally undoped ZnTe and CdTe crystals were implanted with radioactive $^{111}\!$Ag, which decays to $^{111}\!$Cd, and investigated by photoluminescence spectroscopy (PL). In ZnTe, the PL lines caused by an acceptor level at 121 meV are observed: the principal bound exciton (PBE) line, the donor-acceptor pair (DAP) band, and the two-hole transition lines. In CdTe, the PBE line and the DAP band that correspond to an acceptor level at 108 meV appear. Since the intensities of all these PL lines decrease in good agreement with the half-life of $^{111}\!$Ag of 178.8 h, both acceptor levels are concluded to be associated with defects containing a single Ag atom. Therefore, the earlier assignments to substitutional Ag on Zn- and Cd-lattice sites in the respective II-VI semiconductors are confirmed. The assignments in the literature of the S$_1$, S$_2$, and S$_3$ lines in ZnTe and the X$\scriptstyle^\textrm{Ag}_{1}\,\,,$ X$\scriptstyle^\textrm{Ag}_{2}$/ C$\scriptstyle^\textrm{Ag}_{1}\,$ and C$\scriptstyle^\textrm{Ag}_{2}\,$ lines in CdTe to Ag-related defect complexes are not confirmed

Effect of different intravenous iron preparations on lymphocyte intracellular reactive oxygen species generation and subpopulation survival

<p>Abstract</p> <p>Background</p> <p>Infections in hemodialysis (HD) patients lead to high morbidity and mortality rates and are associated with early cardiovascular mortality, possibly related to chronic inflammation. Intravenous (IV) iron is widely administered to HD patients and has been associated with increased oxidative stress and dysfunctional cellular immunity. The purpose of this study was to examine the effect of three commercially available IV iron preparations on intracellular reactive oxygen species generation and lymphocyte subpopulation survival.</p> <p>Methods</p> <p>Peripheral blood mononuclear cells (PBMC) were isolated from healthy donor buffy coat. PBMC were cultured and incubated with 100 μg/mL of sodium ferric gluconate (SFG), iron sucrose (IS) or iron dextran (ID) for 24 hours. Cells were then probed for reactive oxygen species (ROS) with dichlorofluorescein-diacetate. In separate studies, isolated PBMCs were incubated with the 25, 50 or 100 μg/mL iron concentrations for 72 hours and then stained with fluorescein conjugated monoclonal antibodies for lymphocyte subpopulation identification. Untreated PBMCs at 24 hours and 72 hours served as controls for each experiment.</p> <p>Results</p> <p>All three IV iron preparations induced time dependent increases in intracellular ROS with SFG and IS having a greater maximal effect than ID. The CD4+ lymphocytes were most affected by IV iron exposure, with statistically significant reduction in survival after incubation with all three doses (10, 25 and 100 μg/mL) of SFG, IS and ID.</p> <p>Conclusion</p> <p>These data indicate IV iron products induce differential deleterious effects on CD4+ and CD16+ human lymphocytes cell populations that may be mediated by intracellular reactive oxygen species generation. Further studies are warranted to determine the potential clinical relevance of these findings.</p

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference