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91.
Dimitrios Daoussis Vasileios Panoulas Tracey Toms Holly John Ioannis Antonopoulos Peter Nightingale Karen MJ Douglas Rainer Klocke George D Kitas 《Arthritis research & therapy》2009,11(4):R116-8
Introduction
Recent evidence suggests that uric acid (UA), regardless of crystal deposition, may play a direct pathogenic role in renal disease. We have shown that UA is an independent predictor of hypertension and cardiovascular disease (CVD), and that CVD risk factors associate with renal dysfunction, in patients with rheumatoid arthritis (RA). In this study we investigated whether UA associates with renal dysfunction in patients with RA and whether such an association is independent or mediated through other comorbidities or risk factors for renal impairment. 相似文献92.
Arno Wegkamp Astrid E Mars Magda Faijes Douwe Molenaar Ric CH de Vos Sebastian MJ Klaus Andrew D Hanson Willem M de Vos Eddy J Smid 《Microbial cell factories》2010,9(1):100
Background
Using a functional genomics approach we addressed the impact of folate overproduction on metabolite formation and gene expression in Lactobacillus plantarum WCFS1. We focused specifically on the mechanism that reduces growth rates in folate-overproducing cells. 相似文献93.
nalD encodes a second repressor of the mexAB-oprM multidrug efflux operon of Pseudomonas aeruginosa 总被引:1,自引:0,他引:1
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The Pseudomonas aeruginosa nalD gene encodes a TetR family repressor with homology to the SmeT and TtgR repressors of the smeDEF and ttgABC multidrug efflux systems of Stenotrophomonas maltophilia and Pseudomonas putida, respectively. A sequence upstream of mexAB-oprM and overlapping a second promoter for this efflux system was very similar to the SmeT and TtgR operator sequences, and NalD binding to this region was, in fact, demonstrated. Moreover, increased expression from this promoter was seen in a nalD mutant, consistent with NalD directly controlling mexAB-oprM expression from a second promoter. 相似文献
94.
95.
Sadagopal S Lorey SL Barnett L Basham R Lebo L Erdem H Haman K Avison M Waddell K Haas DW Kalams SA 《Journal of virology》2008,82(21):10418-10428
During untreated human immunodeficiency virus type 1 (HIV-1) infection, virus-specific CD8+ T cells partially control HIV replication in peripheral lymphoid tissues, but host mechanisms of HIV control in the central nervous system (CNS) are incompletely understood. We characterized HIV-specific CD8+ T cells in cerebrospinal fluid (CSF) and peripheral blood among seven HIV-positive antiretroviral therapy-naïve subjects. All had grossly normal brain magnetic resonance imaging and spectroscopy and normal neuropsychometric testing. Frequencies of epitope-specific CD8+ T cells by direct tetramer staining were on average 2.4-fold higher in CSF than in blood (P = 0.0004), while HIV RNA concentrations were lower. Cells from CSF were readily expanded ex vivo and responded to a broader range of HIV-specific human leukocyte antigen class I restricted optimal peptides than did expanded cells from blood. HIV-specific CD8+ T cells, in contrast to total CD8+ T cells, in CSF and blood were at comparable maturation states, as assessed by CD45RO and CCR7 staining. The strong relationship between higher T-cell frequencies and lower levels of viral antigen in CSF could be the result of increased migration to and/or preferential expansion of HIV-specific T cells within the CNS. This suggests an important role for HIV-specific CD8+ T cells in control of intrathecal viral replication.Human immunodeficiency virus type 1 (HIV-1) invades the central nervous system (CNS) early during primary infection (21, 30, 35), and proviral DNA persists in the brain throughout the course of HIV-1 disease (7, 25, 29, 47, 77, 83). Limited data from human and nonhuman primate studies suggest that little or no viral replication occurs in the brain during chronic, asymptomatic infection, based on the absence of demonstrable viral RNA or proteins (8, 85). In contrast, cognitive impairment affects approximately 40% of patients who progress to advanced AIDS without highly active antiretroviral therapy (21, 30, 35, 65). During HIV-associated dementia, there is active HIV-1 replication in the brain (23, 52, 61, 81), and viral sequence differences between cerebrospinal fluid (CSF) and peripheral tissues suggest distinct anatomic compartments of replication (18, 19, 22, 53, 75, 76, 78). Host mechanisms that control viral replication in the CNS during chronic, asymptomatic HIV-1 infection are incompletely understood.Anti-HIV CD8+ T cells are present in blood and peripheral tissues throughout the course of chronic HIV-1 infection (2, 14). Multiple lines of evidence support a critical role for these cells in controlling HIV-1 replication. During acute HIV-1 infection, the appearance of CD8+ T-cell responses correlates temporally with a decline in viremia (11, 43), and a greater proliferative capacity of peripheral blood HIV-specific CD8+ T cells correlates with better control of viremia (36, 54). In addition, the presence of certain major histocompatibility complex class I human leukocyte antigen (HLA) alleles, notably HLA-B*57, predicts slower progression to AIDS and death during chronic, untreated HIV-1 infection (55, 62). Finally, in the simian immunodeficiency virus (SIV) model, macaques depleted of CD8+ T cells experience increased viremia and rapid disease progression (39, 51, 67).Little is known regarding the role of intrathecal anti-HIV CD8+ T cells in HIV neuropathogenesis. Nonhuman primate studies have identified SIV-specific CD8+ T cells in the CNS early after infection (16, 80). Increased infiltration of SIV antigen-specific CD8+ T cells and cytotoxic T lymphocytes has been detected only in CSF of slow progressors without neurological symptoms (72). In chronically infected macaques with little or no SIV replication in the brain, the frequency of HIV-specific T cells was higher in CSF than in peripheral blood but did not correlate with the level of plasma viremia or CD4+ T-cell counts (56). Although intrathecal anti-HIV CD8+ T cells may help control viral replication, a detrimental role in the neuropathogenesis of HIV-1 has also been postulated (38). Immune responses contribute to neuropathogenesis in models of other infectious diseases, and during other viral infections cytotoxic T lymphocytes can worsen disease through direct cytotoxicity or release of inflammatory cytokines such as gamma interferon (IFN-γ) (3, 17, 31, 37, 42, 44, 71).We tested the hypothesis that quantitative and/or qualitative differences in HIV-specific CD8+ T-cell responses are present in CSF compared to blood during chronic, untreated HIV-1 infection. We characterized HIV-specific CD8+ T-cell responses in CSF among seven antiretroviral therapy-naïve adults with chronic HIV-1 infection, relatively high peripheral blood CD4+ T-cell counts, and low plasma HIV-1 RNA concentrations. We show that among these HIV-positive individuals with no neurological symptoms and with little or no HIV-1 RNA in CSF, frequencies of HIV-specific T cells are significantly higher in CSF than in blood. These CSF cells are at a state of differentiation similar to that of T cells in blood and are functionally competent for expansion and IFN-γ production. The higher frequency of functional HIV-specific CD8+ T cells in CSF, in the context of low or undetectable virus in CSF, suggests that these cells play a role in the control of intrathecal viral replication. 相似文献
96.
Heidi J. Silver Kevin D. Niswender Joel Kullberg Johan Berglund Lars Johansson Morten Bruvold Malcolm J. Avison E.Brian Welch 《Obesity (Silver Spring, Md.)》2013,21(4):765-774
Objective:
Improved understanding of how depot‐specific adipose tissue mass predisposes to obesity‐related comorbidities could yield new insights into the pathogenesis and treatment of obesity as well as metabolic benefits of weight loss. We hypothesized that three‐dimensional (3D) contiguous “fat‐water” MR imaging (FWMRI) covering the majority of a whole‐body field of view (FOV) acquired at 3 Tesla (3T) and coupled with automated segmentation and quantification of amount, type, and distribution of adipose and lean soft tissue would show great promise in body composition methodology.Design and Methods:
Precision of adipose and lean soft tissue measurements in body and trunk regions were assessed for 3T FWMRI and compared to dual‐energy X‐ray absorptiometry (DXA). Anthropometric, FWMRI, and DXA measurements were obtained in 12 women with BMI 30‐39.9 kg/m2.Results:
Test–retest results found coefficients of variation (CV) for FWMRI that were all under 3%: gross body adipose tissue (GBAT) 0.80%, total trunk adipose tissue (TTAT) 2.08%, visceral adipose tissue (VAT) 2.62%, subcutaneous adipose tissue (SAT) 2.11%, gross body lean soft tissue (GBLST) 0.60%, and total trunk lean soft tissue (TTLST) 2.43%. Concordance correlation coefficients between FWMRI and DXA were 0.978, 0.802, 0.629, and 0.400 for GBAT, TTAT, GBLST, and TTLST, respectively.Conclusions:
While Bland–Altman plots demonstrated agreement between FWMRI and DXA for GBAT and TTAT, a negative bias existed for GBLST and TTLST measurements. Differences may be explained by the FWMRI FOV length and potential for DXA to overestimate lean soft tissue. While more development is necessary, the described 3T FWMRI method combined with fully‐automated segmentation is fast (<30‐min total scan and post‐processing time), noninvasive, repeatable, and cost‐effective. 相似文献97.
I Prieto-Potín JA Roman-Blas MJ Martínez-Calatrava R Gómez R Largo Gabriel Herrero-Beaumont 《Arthritis research & therapy》2013,15(4):R81
Objective
The aim of this study was to determine whether hypercholesterolemia increases articular damage in a rabbit model of chronic arthritis.Methods
Hypercholesterolemia was induced in 18 rabbits by administrating a high-fat diet (HFD). Fifteen rabbits were fed normal chow as controls. Chronic antigen-induced arthritis (AIA) was induced in half of the HFD and control rabbits, previously immunized, by intra-articular injections of ovalbumin. After sacrifice, lipid and systemic inflammation markers were analyzed in blood serum. Synovium was analyzed by Krenn score, multinucleated cell counting, immunohistochemistry of RAM11 and CD31, and TNF-α and macrophage chemoattractant protein-1 (MCP-1) gene expression. Active bone resorption was assessed by protein expression of receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG) and quantification of cathepsin K, contact surface and the invasive area of pannus into bone.Results
Rabbits receiving the HFD showed higher total serum cholesterol, HDL, triglycerides and CRP levels than rabbits fed a normal diet. Synovitis score was increased in HFD, and particularly in AIA and AIA + HFD groups. AIA + HFD synovium was characterized by a massive infiltration of RAM11+ cells, higher presence of multinucleated foam cells and bigger vascularization than AIA. Cathepsin K+ osteoclasts and the contact surface of bone resorbing pannus were also increased in rabbits with AIA + HFD compared with AIA alone. Synovial TNF-α and MCP-1 gene expression was increased in AIA and HFD rabbits compared with healthy animals. RANKL protein expression in AIA and AIA + HFD groups was higher compared with either HFD or normal groups.Conclusions
This experimental model demonstrates that hypercholesterolemia increments joint tissue damage in chronic arthritis, with foam macrophages being key players in this process. 相似文献98.
99.
Impacts of yeast metabolic network structure on enzyme evolution 总被引:1,自引:1,他引:0
A comment on D Vitkup, P Kharchenko and A Wagner: Influence of metabolic network structure and function on enzyme evolution. Genome Biol 2006, 7:R39. 相似文献
100.
BD Pascal MJ Chalmers SA Busby CC Mader MR Southern NF Tsinoremas PR Griffin 《BMC bioinformatics》2007,8(1):156