Background Rosacea is a common chronic light-sensitive inflammatory skin disease of unknown origin. The purpose of this work was to determine the parameters of oxidative stress, antioxidative ...capacity, and the pathophysiologic role of ferritin expression in skin cells of patients with rosacea. Objectives The investigation consisted of measurements of serum peroxide levels, serum total antioxidative potential levels, and immunohistochemical analyses of ferritin in skin tissue samples. Results Serum peroxide levels were significantly higher and serum total antioxidative potential levels were significantly lower in patients with rosacea than in healthy control subjects ( P < .05). Compared with control subjects, the number of ferritin-positive cells was significantly higher ( P < .001) in skin samples from patients with rosacea, especially those with severe disease. Limitations Patients with rosacea in the study were aged 30 to 70 years (average age was 56 years). Younger patients with flushing only were not included according to the request of the ethics committee, limiting the use of diagnostic biopsies only to the necessary cases. Conclusion The statistically significant differences in the expression of ferritin, higher peroxide levels, and lower antioxidative potential support the onset of systemic oxidative stress in patients with rosacea.
The interaction of bovine cells with lipopolysaccharide (LPS) was explored using human embryo kidney (HEK) 293 cell line stably transduced with bovine toll-like receptor-4 (TLR4) alone or in ...combination with bovine MD-2. These lines and mock-transduced HEK293 cells were tested by flow cytometry for LPS-fluorescein isothiocyanate (LPS-FITC) binding, nuclear factor kappa B (NFκB) activation, interleukin-8 (IL-8) production and interferon-β mRNA expression/interferon (IFN) type I production. Whereas bovine TLR4 was sufficient to promote binding of high concentrations of LPS-FITC, both bovine TLR4 and MD-2 were required for activation by LPS, as assessed by NFκB activation and IL-8 production. Induction of IFN bioactivity was not observed in doubly transduced HEK293 cells, and no evidence for IFN-β mRNA induction in response to LPS was obtained, although cells responded by IFN-β mRNA expression to stimulation by Sendai virus and poly-inosinic acid-poly-cytidylic acid (poly(I:C)). Cells stably transduced with both bovine TLR4 and bovine MD-2 responded to LPS by IL-8 production, in decreasing order, in the presence of fetal bovine serum (FCS), of human serum, and of human serum albumin (HSA). The reduced activity in the presence of HSA could be restored by the addition of soluble CD14 (sCD14) but not of LPS binding protein (LBP). This is in contrast to macrophages which show a superior response to LPS in the presence of HSA when compared with macrophages stimulated by LPS in the presence of FCS. This suggests that macrophages but not HEK293 cells express factors rendering LPS stimulation serum-independent. Stably double-transduced cells reacted, in decreasing order, to LPS from Rhodobacter sphaeroides, to LPS from Escherichia coli, to synthetic lipd-IVa (compound 406), to diphosphoryl-lipid-A (S. minnesota) and to monophosphoryl-lipid-A (S. minnesota). They failed to react to the murine MD-2/TLR4 ligand taxol. This resembles the reactivity of bovine macrophages with regard to sensitivity (ED50) and order of potency but is distinct from the reactivity pattern of other species. This formally establishes that in order to react to LPS, cattle cells require serum factors (e.g. sCD14) and cell-expressed factors such as MD-2 and TLR4. The cell lines described are the first of a series expressing defined pattern recognition receptors (PRR) of bovine origin. They will be useful in the study of the interaction of the bovine TLR4-MD-2 complex and Gram-negative bovine pathogens, e.g. the agents causing Gram-negative bovine mastitis.
Fracture behaviour of two steels, AISI 420 and ASTM A618, was numerically investigated using a newly developed algorithm for the J-integral calculation. The algorithm is based on the results of the ...finite element (FE) simulation of single specimen test method, commonly used in experimental determination of J-integral. FE stress analysis results are used as an input for the algorithm which calculates J values on three different paths around the crack tip, taking their average value as final. The obtained J-integral values are plotted against specimen crack growth steps ( Delta a). In that way, valuable measures of J-integral acting as a crack driving force are available. Research was done using a FE model of compact type (CT) specimen with three initial crack lengths, a/W=0.25, 0.5, 0.75.
It has recently been suggested that immunotactoid glomerulopathy be separated from much more common fibrillary glomerulonephritis by ultrastructural features of highly organized immune deposits ...containing tubules of more than 30 nm in diameter. We report and discuss the results of a light, immunofluorescence and electron microscopic study of a needle renal biopsy from a 75-year-old, non-insulin dependant diabetic female presented with nephrotic syndrome, hypertension and a progressive renal failure. A unique coexistence of nodular glomerulosclerosis, as traditionally ascribed to diabetes with a peculiar type of immunotactoid glomerulopathy was confirmed by the exclusion of amyloidosis, monoclonal gammopathies, systemic autoimmune diseases and cryoglobulinemia. Mesangial, scattered subepithelial and segmentally prominent subendothelial immune deposits were found highly organized in mostly parallel arrays of 40 to 91 nm thick tubules. The average thickness of 67 nm exceeds the average diameter of tubules in all other 11 published cases of immunotactoid glomerulopathy to date. By immunofluorescence, predominantly capillary wall, thick, ribbon-like glomerular deposits contained IgG, IgM, kappa and lambda light chains of equal intensity, C3, C4 and fibrin related antigens. Mild to moderate glomerular cell proliferation associated with nodular sclerosis has been assumed to be causally related to immunotactoid deposits.
SUMMARY
Polyspecific IgG given intravenously at high doses (IVIG) is used for immunomodulatory therapy in autoimmune diseases such as idiopathic thrombocytopenic purpura and myasthenia gravis. It is ...assumed that the clinical effect is brought about in part by a modulation of mononuclear phagocyte function, in particular by an inhibition of Fc receptor (FcR) mediated phagocytosis. In the present study, the effect of IVIG on FcR‐mediated phagocytosis by monocytes was analysed in vitro. Since monocytes exposed to minute amounts of surface‐bound IgG displayed impaired phagocytosis of IgG‐coated erythrocytes (EA), the effect of IVIG was studied with mononuclear cells suspended in teflon bags in medium containing 10% autologous serum and IVIG 2–10 mg/ml). Monocytes pre‐exposed to IVIG and then washed, displayed impaired ingestion of EA when compared with control cells cultured in 10% autologous serum only. The decrease in phagocytosis was observed with sheep erythrocytes treated with either rabbit IgG or bovine IgGl and with anti‐D‐treated human erythrocytes. This suggests that phagocytosis via both FcR type I (FcRI) and type II (FcRII) was decreased. The impairment of phagocytosis was dependent on the presence of intact IgG and was mediated by IVIG from nulliparous donors and from multigravidae to the same extent, suggesting that alloantibodies contained in IVIG have a minor role in modulating FcR‐mediated phagocytosis by monocytes. A flow cytometric analysis using anti‐FcRI, FcRII and FcRIII monoclonal antibodies showed that IVIG treatment upregulated FcRI expression but did not significantly alter the expression of FcRII and FcRIII.
In this paper a theory of multi-walled carbon nanotubes and a suitable way for modelling them using the finite element method is presented. A brief reference to FE modelling of a single-walled carbon ...nanotube (SWNT) is given as an introduction to modelling of multi-walled carbon nanotubes, consisting of several layers of SWNT. Also, a theory of the connection interface between nanotube layers and its influence on the loading is given. A SWNT finite element model is used to model a multi-walled carbon nanotube (MWNT). A brief theory concerning MWNT is given, as well as a theory of modelling a connecting interface between layers, as a result of van der Waals interactions. Different loading conditions are used as examples of multi-walled carbon nanotubes under specific loads. Results are compared with those given by other authors.
Mononuclear phagocytes in distinct differentiation stages and cultured under different conditions were tested for their sensitivity towards lipopolysaccharide (LPS), using procoagulant activity (PCA) ...expression and tumor necrosis factor (TNF) production as indices. The response of mature monocyte-derived macrophages differed from that of freshly isolated monocytes 1) by higher levels of constitutive PCA, 2) by responding to approximately 1,000-fold lower concentrations of LPS with PCA and TNF production, and 3) by a faster rise in PCA and TNF production. Due to the high constitutive level of PCA expression, the PCA stimulation index for LPS was low in macrophages when compared with that in monocytes. Thus, during differentiation to macrophages, human monocytes acquire increased sensitivity to LPS (2 orders of magnitude more sensitive than a sensitive turbidimetric Limulus amoebocyte lysate assay). This exquisite sensitivity to LPS is expressed regardless of whether LPS is offered in the presence or absence of lipopolysaccharide binding protein-containing serum. This points to as yet uncharacterized pathways of high affinity interaction between LPS and macrophages.
Software systems continuously grow in size and code complexity, the latter most evident through greater component interconnectedness. This leaves more space for bugs which introduce risks such as ...exposure to security threats. Combinatorial testing looks for interaction failures in order to improve the system security and effectiveness guarantees. One of the most effective test selection approaches under combinatorial testing are experimental design extensions for software testing. Covering array test sets are compact while maintaining at the same time complete combinatorial coverage up to the desired level. Smaller test sets with customizable level of assurance can drive testing costs down substantially. The paper presents a survey of research into combinatorial testing suite factors while also identifying possible future research ideas.
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