Abstract:
BACKGROUND:Proteinase 3 is the major autoantigen in Wegener's granulomatosis (WG). Membrane PR3 expression is bimodal; low expressing cells (mPR3(low)) can be distinguished from cells with high expression (mPR3(high)) within a given individual. High mPR3 expression is a WG risk factor and is associated with relapse. However, no mechanisms for this important clinical observation have been provided. We tested the hypothesis that mPR3 expression, rather than the expression of other membrane molecules implicated in anti-neutrophil cytoplasmic autoantibodies (ANCA) activation, determines the robustness of the PR3-ANCA-mediated response. METHODS:mPR3(low) and mPR3(high) neutrophils from a given individual were separated by magnetic cell sorting. Superoxide was measured by the ferricytochrome assay, and Akt phosphorylation by Western blotting. Double staining and flow cytometry were used to assay Fc gamma-receptor and beta 2-integrin expression with respect to the mPR3 phenotype. Degranulation was measured via beta-glucuronidase activity, migration with fibronectin-coated transwells, and cell quantification by the myeloperoxidase (MPO) assay. RESULTS:PR3-ANCA-treated mPR3(high) versus mPR3(low) neutrophils showed more superoxide generation (33.7 +/- 15.2 nmol O(2) (-) to 14.6 +/- 8.4, P < 0.01), more degranulation (29%+/- 5 to 22%+/- 3, P < 0.05), and more PI3-K/Akt activation. In contrast, all responses in both mPR3 subsets were similar after other stimuli. We observed no differences in the beta 2-integrin, Fc gamma R IIa, and III expression with respect to the mPR3 subtype. Furthermore, we found no differences in the mobilization of PR3-containing granules and no differences in migration through fibronectin. CONCLUSION:The degree of neutrophil mPR3 expression has definitive functional consequences.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Schreiber A,Luft FC,Kettritz Rdoi
10.1111/j.1523-1755.2004.00640.xsubject
Has Abstractpub_date
2004-06-01 00:00:00pages
2172-83issue
6eissn
0085-2538issn
1523-1755pii
S0085-2538(15)49962-4journal_volume
65pub_type
杂志文章abstract::Cyclosporine A (CsA) is a potent immunosuppressive drug that inhibits the transcription of several proinflammatory cytokines including interleukin-2. In contrast, CsA stimulates transcription of the pleuripotent cytokine, transforming growth factor-beta (TGF beta). Since the effect of CsA in transplant recipients is u...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1038/ki.1996.479
更新日期:1996-11-01 00:00:00
abstract::We studied in 32 patients on maintenance hemodialysis (duration of treatment 6 to 133 months) whether duration of dialysis treatment affects blood pressure, plasma noradrenaline levels and alpha 2-adrenoceptor density (assessed in platelet membranes by 3H-yohimbine binding). Plasma noradrenaline levels were a signific...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1987.267
更新日期:1987-11-01 00:00:00
abstract::Murine double minute (MDM)-2, an E3 ubiquitin ligase, promotes cancer cell survival and growth, by degrading the cell cycle regulator p53. Antagonism of MDM2 by the small-molecule cis-imidazoline nutlin analogs is under current study for cancer therapy. To test whether MDM2 also promotes regenerative cell growth, we d...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2011.482
更新日期:2012-06-01 00:00:00
abstract::The presence of nitric oxide (NO) in the kidney has been implicated in the pathogenesis of human glomerulonephritis. However, the exact type of glomerular cells that express NO synthase (NOS) and the NOS isoform involved in the local production of NO has not been identified in the human diseased kidney. We examined th...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00907.x
更新日期:1998-06-01 00:00:00
abstract::Heterozygous mutations of the tissue-specific transcription factor hepatocyte nuclear factor (HNF)1beta, cause maturity onset diabetes of the young (MODY5) and kidney anomalies including agenesis, hypoplasia, dysplasia and cysts. Because of these renal anomalies, HNF1beta is classified as a CAKUT (congenital anomalies...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.149
更新日期:2008-07-01 00:00:00
abstract::Short-term correction of metabolic acidosis in normal and uremic subjects has been shown to decrease protein degradation, but the long-term effects of better correction of acidosis on nutrition in ESRF are unknown. The aim of this study was to assess the possible benefits, in the nutritional state and morbidity, of im...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1038/ki.1997.433
更新日期:1997-10-01 00:00:00
abstract::These studies were undertaken to examine effects of elevated glucose levels on glycolysis, sorbitol pathway activity, and the cytosolic redox state of NADH/NAD+ in isolated glomeruli. Blood-free glomeruli were isolated from kidneys of male, Sprague-Dawley rats using standard sieving techniques, then incubated for one ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.121
更新日期:1992-04-01 00:00:00
abstract::Recent studies suggest that postnatal neovascularization relies not exclusively on sprouting of preexisting vessels ("angiogenesis"), but also involves the contribution of bone marrow-derived circulating endothelial progenitor cells (EPCs). EPCs can be isolated from peripheral blood or bone marrow mononuclear cells, C...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1111/j.1523-1755.2005.00261.x
更新日期:2005-05-01 00:00:00
abstract::Gene expression differs substantially among individual cells of the same type. We speculate that genes that are expressed in all but a portion of cells of a given cell type would be likely essential and required for either the cell survival (housekeeping) or for the cell type's unique structure and function, enabling ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2017.04.022
更新日期:2017-11-01 00:00:00
abstract:BACKGROUND:While metabolically generated oxidants are produced locally in experimental glomerular diseases, little is still known of their significance and the respective scavenger systems in human glomerular diseases. METHODS:Here we studied kidneys from patients with congenital nephrotic syndrome of the Finnish type...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.059002481.x
更新日期:2001-02-01 00:00:00
abstract::We studied the glomerular architecture in renal biopsies of 95 patients undergoing bariatric surgery for extreme obesity but whose renal function was normal. The comparison group was 40 control patients having protocol biopsies. These latter patients had normal weight and renal function, were non-diabetic, non-hyperte...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5002796
更新日期:2008-04-01 00:00:00
abstract::During the heterologous phase of experimental anti-glomerular basement membrane (anti-GBM) nephritis, leukocyte influx peaks within hours, whereas albuminuria occurs within 1 day. In the subsequent autologous phase, endogenous anti-GBM IgG develops and albuminuria persists. Heparan sulfate (HS) proteoglycans like synd...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5002514
更新日期:2007-11-01 00:00:00
abstract::This study was undertaken to test the hypothesis that, given equal arterial pressure reductions, the combination of an angiotensin converting enzyme (ACE) inhibitor and calcium antagonist slows declines in renal function and yields greater reductions in albuminuria over either agent alone. This hypothesis was evaluate...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1038/ki.1992.139
更新日期:1992-04-01 00:00:00
abstract::Many subjects nowadays present with end-stage renal failure and its attendant cardiovascular complications without known prior renal damage. In this report we review the evidence available to strongly suggest that the present practice of secondary prevention in those with known prior renal disease should be extended t...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1111/j.1523-1755.2004.66001.x
更新日期:2004-12-01 00:00:00
abstract::Major features of a long-standing inflammation in the kidney are vascular proliferation, glomerulosclerosis, interstitial fibrosis and tubular atrophy, leading to a gradual deterioration of the renal function. In this study we have investigated the expression of B-type receptors for platelet-derived growth factor (PDG...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1989.306
更新日期:1989-12-01 00:00:00
abstract::In 38 conscious rats divided into seven groups, acute unilateral ischemic renal failure was induced by 1 hour of complete occlusion of the left renal artery while the contralateral kidney remained intact. Renal excretory function of the left kidney was monitored up to 144 hours after ischemia and revealed a typical co...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1980.53
更新日期:1980-04-01 00:00:00
abstract::In April 2006, Japan's health insurance system instituted a bundling policy that included recombinant human erythropoietin (rHuEPO) in outpatient hemodialysis therapy. To evaluate outcomes of this, we analyzed a prospective cohort of hemodialysis patients in the Japan Dialysis Outcomes and Practice Patterns Study, in ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2010.382
更新日期:2011-02-01 00:00:00
abstract::The cardiorenal safety database from the Celecoxib Long-term Arthritis Safety Study (CLASS) was analyzed to examine whether supratherapeutic doses of celecoxib are associated with decreased renal function and blood pressure (BP) effects compared with standard doses of diclofenac and ibuprofen in osteoarthritis (OA) an...
journal_title:Kidney international
pub_type: 杂志文章,随机对照试验
doi:10.1038/sj.ki.5001766
更新日期:2006-10-01 00:00:00
abstract::Cisplatin is a platinum-containing antitumor agent whose usefulness is limited by nephrotoxicity. We examined the effects of cisplatin on a representative, transporting epithelium--the frog skin. Cisplatin (10(-3)M) from the mucosal surface increased the active transport of sodium by 35 to 40%, as monitored by short-c...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1981.2
更新日期:1981-01-01 00:00:00
abstract::The pathologic and clinical features of 16 patients with dense intramembranous deposit disease are described. By light microscopy nine patients had membranoproliferative glomerulonephritis, five had focal segmental necrotizing glomerulonephritis with segmental epithelial crescents, four of whom also had a prominent tu...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1984.71
更新日期:1984-04-01 00:00:00
abstract:BACKGROUND:The next phase of the molecular revolution will bring functional genomics down to the level of individual cells in a tissue. Laser capture microdissection (LCM) coupled with reverse transcription-polymerase chain reaction (RT-PCR) can measure gene expression in normal, cancerous, injured, or fibrotic tissue....
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00295.x
更新日期:2000-09-01 00:00:00
abstract::The homocysteine hypothesis states that circulating homocysteine is a vascular toxin in concentrations that occur in the general population and in renal failure. This hypothesis is currently being tested in the Kidney and End State Renal Disease Study (HOST), but data have emerged since the HOST began that suggest its...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000279
更新日期:2006-05-01 00:00:00
abstract:BACKGROUND:Variant forms of lysozyme, a ubiquitous bacteriolytic enzyme, are known to lead to hereditary non-neuropathic renal amyloidosis and, so far, three different mutations of the lysozyme gene have been reported. In this study, we report a novel lysozyme variant, Phe57Ile, associated with renal amyloidosis in thr...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00904.x
更新日期:2003-05-01 00:00:00
abstract:BACKGROUND:Primary collapsing glomerulopathy recurs postransplant, raising the possibility of circulating factors implicated in the pathogenesis of the disease. METHODS:To determine the presence of circulating factors in collapsing glomerulopathy patients, we tested serum from those patients in an in vivo assay. Eleve...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00715.x
更新日期:2004-07-01 00:00:00
abstract:BACKGROUND:Advanced glycation of proteins and their attendant advanced glycation end products (AGEs) contribute to the complications associated with diabetes mellitus or uremia. Regulatory mechanisms of AGE formation in vivo remain an issue of particular interest. We investigated a role of the glyoxalase detoxification...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.00051.x
更新日期:2001-12-01 00:00:00
abstract::Chronic metabolic acidosis (CMA) is a major cause of growth defect, implying disturbances of protein metabolism. Previously, in vivo studies performed in the fasting state showed enhanced whole body protein turnover, whereas in vitro studies showed unchanged muscle protein synthesis. The present study is the first to ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.472
更新日期:1994-12-01 00:00:00
abstract::Levels of components of the classical and alternative complement pathways and the activity of the C3 nephritic factor (C3NeF) were measured in serum specimens from patients with type I (subendothelial deposits) and type II (intramembranous dense deposits) membranoproliferative glomerulonephritis (MPGN) and the results...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1976.6
更新日期:1976-01-01 00:00:00
abstract:BACKGROUND:The use of renal Kt/V (r-Kt/V) as an indicator for the need of dialysis initiation has been recommended in the NKF-DOQI guidelines. In analogy to clinical practice in peritoneal dialysis, a fall of r-Kt/V below a threshold of 2.0 per week may indicate inadequate renal toxin elimination. However, there are no...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.00957.x
更新日期:2001-10-01 00:00:00
abstract::The candidacidal activity of kidneys, liver, and spleen's phagocytic systems was studied in mouse. Different strains of mice were inoculated intravenously (i.v.) with 1 to 2.6 x 10(4) viable Candida albicans. Elimination of the microorganisms from the kidneys, liver, and spleen were evaluated by enumeration of colony ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.225
更新日期:1991-09-01 00:00:00
abstract::Our genetic hypercalciuric (GH) rats have been selected and inbred for 29 generations to maximize urine calcium (UCa) excretion compared to identical gender controls (Ctl). To determine the effect of the increased UCa on urinary supersaturation and stone formation, we pair fed 15 GH and 15 Ctl rats a standard 1.2% cal...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.468
更新日期:1995-12-01 00:00:00