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91.
Urine levels of HMGB1 in Systemic Lupus Erythematosus patients with and without renal manifestations
Deena A Abdulahad Johanna Westra Johannes Bijzet Sebastian Dolff Marcory C van Dijk Pieter C Limburg Cees GM Kallenberg Marc Bijl 《Arthritis research & therapy》2012,14(4):R184
Introduction
Lupus nephritis (LN) is a severe and frequent manifestation of systemic lupus erythematosus (SLE). Its pathogenesis has not been fully elucidated but immune complexes are considered to contribute to the inflammatory pathology in LN. High Mobility Group Box 1 (HMGB1) is a nuclear non-histone protein which is secreted from different types of cells during activation and/or cell death and may act as a pro-inflammatory mediator, alone or as part of DNA-containing immune complexes in SLE. Urinary excretion of HMGB1 might reflect renal inflammatory injury. To assess whether urinary HMGB1 reflects renal inflammation we determined serum levels of HMGB1 simultaneously with its urinary levels in SLE patients with and without LN in comparison to healthy controls (HC). We also analyzed urinary HMGB1 levels in relation with clinical and serological disease activity.Methods
The study population consisted of 69 SLE patients and 17 HC. Twenty-one patients had biopsy proven active LN, 15 patients had a history of LN without current activity, and 33 patients had non-renal SLE. Serum and urine levels of HMGB1 were both measured by western blotting. Clinical and serological parameters were assessed according to routine procedures. In 17 patients with active LN a parallel analysis was performed on the expression of HMGB1 in renal biopsies.Results
Serum and urinary levels of HMGB1 were significantly increased in patients with active LN compared to patients without active LN and HC. Similarly, renal tissue of active LN patients showed strong expression of HMGB1 at cytoplasmic and extracellular sites suggesting active release of HMGB1. Serum and urinary levels in patients without active LN were also significantly higher compared to HC. Urinary HMGB1 levels correlated with SLEDAI, and showed a negative correlation with complement C3 and C4.Conclusion
Levels of HMGB1 in urine of SLE patients, in particular in those with active LN, are increased and correlate with SLEDAI scores. Renal tissue of LN patients shows increased release of nuclear HMGB1 compared to control renal tissue. HMGB1, although at lower levels, is, however, also present in the urine of patients without active LN. These data suggest that urinary HMGB1 might reflect both local renal inflammation as well as systemic inflammation. 相似文献92.
Suzanne Arends Anneke Spoorenberg Pieternella M Houtman Martha K Leijsma Reinhard Bos Cees GM Kallenberg Henk Groen Elisabeth Brouwer Eveline van der Veer 《Arthritis research & therapy》2012,14(2):R98
Introduction
The aim of this study was to investigate the effect of three years of tumor necrosis factor-alpha (TNF-α) blocking therapy on bone turnover as well as to analyze the predictive value of early changes in bone turnover markers (BTM) for treatment discontinuation in patients with ankylosing spondylitis (AS).Methods
This is a prospective cohort study of 111 consecutive AS outpatients who started TNF-α blocking therapy. Clinical assessments and BTM were assessed at baseline, three and six months, as well as at one, two, and three years. Z-scores of BTM were calculated to correct for age and gender. Bone mineral density (BMD) was assessed yearly.Results
After three years, 72 patients (65%) were still using their first TNF-α blocking agent. In these patients, TNF-α blocking therapy resulted in significantly increased bone-specific alkaline phosphatase, a marker of bone formation; decreased serum collagen-telopeptide (sCTX), a marker of bone resorption; and increased lumbar spine and hip BMD compared to baseline. Baseline to three months decrease in sCTX Z-score (HR: 0.394, 95% CI: 0.263 to 0.591), AS disease activity score (ASDAS; HR: 0.488, 95% CI: 0.317 to 0.752), and physician''s global disease activity (HR: 0.739, 95% CI: 0.600 to 0.909) were independent inversely related predictors of time to treatment discontinuation because of inefficacy or intolerance. Early decrease in sCTX Z-score correlated significantly with good long-term response regarding disease activity, physical function and quality of life.Conclusions
Three years of TNF-α blocking therapy results in a bone turnover balance that favors bone formation, especially mineralization, in combination with continuous improvement of lumbar spine BMD. Early change in sCTX can serve as an objective measure in the evaluation of TNF-α blocking therapy in AS, in addition to the currently used more subjective measures. 相似文献93.
The interaction of hemoglobin with phospholipid bilayer vesicles (liposomes) has been analyzed in several studies to better understand membrane-protein interactions. However, not much is known on hemoglobin interactions with the aminophospholipids, predominantly localized in the inner leaflet of erythrocytes, e.g., phosphatidylserine (PS), phosphatidylethanolamine (PE) in membranes containing phosphatidylcholine (PC). Effects of cholesterol, largely abundant in erythrocytes, have also not been studied in great details in earlier studies. This work therefore describes the study of the interactions of different hemoglobin variants HbA, HbE and HbF and the globin subunits of HbA with the two aminophospholipids in the presence and absence of cholesterol. Absorption measurements indicate preferential oxidative interaction of HbE and alpha-globin subunit with unilamellar vesicles containing PE and PS compared to normal HbA. Cholesterol was found to stabilize such oxidative interactions in membranes containing both the aminophospholipids. HbE and alpha-globin subunits were also found to induce greater leakage of membrane entrapped carboxyfluorescein (CF) using fluorescence measurements. HbE was found to induce fusion of membrane vesicles containing cholesterol and PE when observed under electron microscope. Taken together, these findings might be helpful in understanding the oxidative stress-related mechanism(s) involved in the premature destruction of erythrocytes in peripheral blood, implicated in the hemoglobin disorder, HbE/beta-thalassemia. 相似文献
94.
Girling RD Madison R Hassall M Poppy GM Turner JG 《Journal of experimental botany》2008,59(11):3077-3085
Feeding damage to plants by insect herbivores induces the production of plant volatiles, which are attractive to the herbivores natural enemies. Little is understood about the plant biochemical pathways involved in aphid-induced plant volatile production. The aphid parasitoid Diaeretiella rapae can detect and respond to aphid-induced volatiles produced by Arabidopsis thaliana. When given experience of those volatiles, it can learn those cues and can therefore be used as a novel biosensor to detect them. The pathways involved in aphid-induced volatile production were investigated by comparing the responses of D. rapae to volatiles from a number of different transgenic mutants of A. thaliana, mutated in their octadecanoid, ethylene or salicylic acid wound-response pathways and also from wild-type plants. Plants were either undamaged or infested by the peach-potato aphid, Myzus persicae. It is demonstrated that the octadecanoid pathway and specifically the COI1 gene are required for aphid-induced volatile production. The presence of salicylic acid is also involved in volatile production. Using this model system, in combination with A. thaliana plants with single point gene mutations, has potential for the precise dissection of biochemical pathways involved in the production of aphid-induced volatiles. 相似文献
95.
Lukoye Atwoli Abdullah H. Baqui Thomas Benfield Raffaella Bosurgi Fiona Godlee Stephen Hancocks Richard Horton Laurie Laybourn-Langton Carlos Augusto Monteiro Ian Norman Kirsten Patrick Nigel Praities Marcel GM Olde Rikkert Eric J. Rubin Peush Sahni Richard Smith Nick Talley Sue Turale Damin Vzquez 《PLoS medicine》2021,18(9)
96.
Poppy J. Lambert Alexandra Stiegler Theresa Rssler Megan L. Lambert Alice M. I. Auersperg 《Biology letters》2021,17(9)
Paying attention to weight is important when deciding upon an object''s efficacy or value in various contexts (e.g. tool use, foraging). Proprioceptive discrimination learning, with objects that differ only in weight, has so far been investigated almost exclusively in primate species. Here, we show that while Goffin''s cockatoos learn faster when additional colour cues are used, they can also quickly learn to discriminate between objects on the basis of their weight alone. Ultimately, the birds learned to discriminate between visually identical objects on the basis of weight much faster than primates, although methodological differences between tasks should be considered. 相似文献
97.
Hettema ME Zhang D de Leeuw K Stienstra Y Smit AJ Kallenberg CG Bootsma H 《Arthritis research & therapy》2008,10(2):R49
Introduction
Several systemic autoimmune diseases are associated with an increased prevalence of atherosclerosis which could not be explained by traditional risk factors alone. In systemic sclerosis (SSc), microvascular abnormalities are well recognized. Previous studies have suggested an increased prevalence of macrovascular disease as well. We compared patients with SSc to healthy controls for signs of early atherosclerosis by measuring intima-media thickness (IMT) of the common carotid artery in relation to traditional risk factors and markers of endothelial activation. 相似文献98.
Can biological control benefit from genetically‐modified crops? Tritrophic interactions on insect‐resistant transgenic plants 总被引:4,自引:0,他引:4
Abstract. The use of recombinant DNA technology to develop genetically‐modified crops is considered as a major breakthrough for agriculture by many scientists. However, some scientists, and an even larger proportion of the general public, are sceptical about the advantages and are even more concerned about the potential risk of this new technology. To evaluate this novel technology, cost‐benefit analyses are needed in which the real risks are measured and judged against the benefits. A tiered risk assessment scheme is described herein. This allows comparisons to be made with other insect‐control technologies (e.g. insecticides) and risks to be determined, rather than only hazards being identified. Recombinant DNA technology could allow plants to be designed that are well suited for use alongside biological control programmes. Unfortunately, plant breeders have continued to attempt to breed for total resistance, and biocontrol specialists have ignored the role of the plant in ensuring successful foraging behaviour by insect natural enemies. Although some scientists have highlighted the need to consider both the bottom‐up (plant defence) and top‐down (biocontrol) control of insect pests, there have been few serious attempts to combine these approaches. As more is understood about the proximate and ultimate causes of direct and indirect defences, the potential exists for engineering plants that combine both strategies. This new possibility for controlling insect pests, which will combine both ‘nature’s' own defences with man's ingenuity, may stack the odds in our favour in the continual struggle against insect pests. 相似文献
99.
Abraham EC Huaqian J Aziz A Kumarasamy A Datta P 《Molecular and cellular biochemistry》2008,310(1-2):235-239
Earlier studies have shown significant loss of chaperone activity in α-crystallin from diabetic lenses. In vitro glycation
studies have suggested that glycation of α-crystallin could be the major cause of chaperone activity loss. The following lysine
(K) residues in α-crystallin have been identified as the major glycation sites: K11, K78, and K166 in αA-crystallin and K90,
K92, and K166 in αB-crystallin. The present study was aimed to assess the contribution of each of the above glycation site
in the overall glycation and loss of chaperone activity by mutating them to threonine followed by in vitro glycation with
fructose. Level of glycated protein (GP) was determined by phenylboronate affinity chromatography, advanced glycation end
products (AGEs) by direct ELISA using anti-AGE polyclonal antibody, and chaperone activity by using alcohol dehydrogenase
as the target protein. K11T, K78, and K166T mutants of αA showed 33, 17, and 27% decrease in GP and 32, 18, and 21% decrease
in AGEs, respectively, as compared to αA-wt. Likewise, K90T, K92T, K90T/K92T, and K166T mutants of αB showed 18, 21, 29, and
12% decrease in GP and 22, 24, 32, and 16% decrease in AGEs, respectively. Chaperone activity also showed concomitant increase
with decreasing glycation and AGEs formation. αA-K11T and αB-K90T/K92T mutants showed the largest decrease in glycation and
increase in chaperone activity. 相似文献
100.
Anton?C?van de Vusse Suzanne?GM?Stomp-van den Berg Alfons?HF?Kessels Wim?EJ?WeberEmail author 《BMC neurology》2004,4(1):13