C5a receptor mediates neutrophil activation and ANCA-induced glomerulonephritis.

Anti-neutrophil cytoplasmic autoantibody (ANCA)-induced necrotizing crescentic glomerulonephritis (NCGN) requires complement participation in its pathogenesis. We tested the hypothesis that the anaphylatoxin C5a is pivotal to disease induction via the neutrophil C5a receptor (C5aR). Supernatants from ANCA-activated neutrophils activated the complement cascade in normal serum, producing C5a.

Autoimmunity in kidney diseases.

Renal involvement in autoimmunity has many facets. Glomerular, tubular and vascular structures are targeted and damaged as a consequence of autoimmune processes. Most dramatic and life-threatening causes are observed with diseases that result in rapidly progressive glomerulonephritis (GN), frequently accompanied by involvement of additional non-renal organs.

Neutrophil surface presentation of the anti-neutrophil cytoplasmic antibody-antigen proteinase 3 depends on N-terminal processing.

The neutrophil serine protease proteinase 3 (PR3) is a main autoantigen in anti-neutrophil cytoplasmic antibody-associated vasculitis. PR3 surface presentation on neutrophilic granulocytes, the main effector cells, is pathogenically important. PR3 is presented by the NB1 (CD177) glycoprotein, but how the presentation develops during neutrophil differentiation is not known.

The life-extending gene Indy encodes an exchanger for Krebs-cycle intermediates.

A longevity gene called Indy (for 'I'm not dead yet'), with similarity to mammalian genes encoding sodium-dicarboxylate cotransporters, was identified in Drosophila melanogaster. Functional studies in Xenopus oocytes showed that INDY mediates the flux of dicarboxylates and citrate across the plasma membrane, but the specific transport mechanism mediated by INDY was not identified. To test whether INDY functions as an anion exchanger, we examined whether substrate efflux is stimulated by transportable substrates added to the external medium.

Fever-like temperatures affect neutrophil NF-kappaB signaling, apoptosis, and ANCA-antigen expression.

The neutrophil is pivotal to ANCA vasculitis pathogenesis. Fever frequently complicates ANCA diseases. This study investigated the effects of short-term heat exposure on apoptosis in neutrophils that were treated with LPS, GM-CSF, IL-8, and dexamethasone.

Lectin-like oxidized low-density lipoprotein (LDL) receptor (LOX-1)-mediated pathway and vascular oxidative injury in older-age rat renal transplants.

Background: Older-age renal allografts are associated with inferior survival; however, the mechanisms are unclear. Reactive oxygen species participate in aging and in chronic vascular disease. We investigated how mediators of oxidative stress may increase allograft susceptibility to vascular injury.

The effect of fever-like temperatures on neutrophil signaling.

The effect of fever on neutrophils has not been explored. We tested the hypothesis that fever-like temperature spikes affect neutrophil signaling and function. Prior 60 min, 42 degrees C heat exposure inhibited p38 MAPK, ERK, PI3-Kinase/Akt, and NF-kappaB activation in TNF-alpha-challenged suspended neutrophils.

Growth arrest specific protein 6/Axl signaling in human inflammatory renal diseases.

Background: Growth arrest-specific gene 6 (Gas6) and its binding partner, the receptor tyrosine kinase Axl, are important mediators in experimental nephritis. The authors tested whether the Gas6/Axl signaling pathway participates in human renal diseases.

Methods: The authors compared 26 human renal specimens from patients with IgA nephritis, acute diffuse immune complex glomerulonephritis, acute lupus nephritis, antineutrophil cytoplasmic antibody--associated glomerulonephritis, acute transplant rejection, and normal renal tissue.

Cardiovascular magnetic resonance of acute myocardial infarction at a very early stage.

Objectives: Very early changes in myocardial tissue composition during acute myocardial infarction (AMI) are difficult to assess in vivo. Cardiovascular magnetic resonance (CMR) imaging provides techniques for visualizing tissue pathology.

Background: The diagnostic role of CMR in very acute stages of myocardial infarction is uncertain.

Hydroxymethylglutaryl coenzyme A reductase inhibition reduces Chlamydia pneumoniae-induced cell interaction and activation.

Background: Chlamydia pneumoniae stimulates chronic inflammation in vascular cells. Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) may have an ameliorating effect. We investigated possible mechanisms.

Endothelial cell specific molecule-1--a newly identified protein in adipocytes.

Expression of the endothelial cell-specific molecule (ESM)-1 was originally identified in lung and kidney endothelial cells, where its expression is regulated by cytokines. In vitro, ESM-1 interferes with the molecular mechanisms of immune cell migration by binding to adhesion molecules. In this study, we have explored the expression of ESM-1 in isolated human adipocytes and in rat adipose tissue depots.

Patterns of oxidized epitopes, but not NF-kappa B expression, change during atherogenesis in WHHL rabbits.

Oxidative modification of lipoproteins plays an important role in atherogenesis. We investigated a variety of different oxidatively modified epitopes (malondialdehyde (MDA)-2, hydroxynonenal (HNE)-7, peroxynitrite, hypochlorite, EO-6) in parallel and compared normal vessel wall, early and advanced atherosclerotic lesions in WHHL rabbits. Early atherosclerotic lesions showed abundant intracellular staining in macrophages for all ox-epitopes, apo B and apo E; advanced lesions showed a more prominent peri- and extracellular staining for ox-epitopes, which tended to colocalize more with apo B than apo E.

Comparison of the effects of alpha-tocopherol, ubiquinone-10 and probucol at therapeutic doses on atherosclerosis in WHHL rabbits.

Oxidative modification of lipoproteins may trigger and maintain atherogenesis. We compared the effects of different antioxidants (alpha-tocopherol, probucol, ubiquinone-10) at doses similar to those used in humans in Watanabe Heritable Hyperlipidemic (WHHL) rabbits for 12 months. Aortic lesions were analyzed for their extent and cellular composition of lesions, mean thickness of fibrous caps and density of smooth muscle cells therein, content of antioxidants, non-oxidized and oxidized lipids.

Characterization of structure and mechanism of transfection-active peptide-DNA complexes.

We studied a number of physicochemical parameters of transfection-active peptide-DNA complexes including size, aggregation behaviour and circular dichroism (CD) spectra. These data were brought in relationship to the transfection activity of these peptides in order to better understand the mechanism of peptide-mediated gene transfer. A DNA binding oligolysine (K(16)) and a peptide comprising K(16) with an added peptide loop containing the arbitrary sequence RAD not known as a receptor ligand were used.

Histone H1-mediated transfection: role of calcium in the cellular uptake and intracellular fate of H1-DNA complexes.

Previously, we have shown that the transgene expression in the endothelial cell line ECV 304 strongly depends on the presence of low concentrations of Ca2+. However, it remained unclear, which transfection steps are controlled by Ca2+ ions. In the present study, we constructed transfection complexes of digoxigenin-labelled DNA and FITC-labelled histone H1.

Increased importin alpha protein expression in diabetic nephropathy.

Background: Importins transport kinases, transcription factors, and viral proteins into the nucleus. Since the expression of several genes is increased in diabetic nephropathy, we tested the hypothesis that importin protein expression is increased in diabetic kidneys.

Methods: Immunohistochemistry and Western blotting were used in kidneys from streptozotocin-treated diabetic rats and from spontaneously diabetic Goto-Kakizaki rats.

Prolonged cold preservation augments vascular injury independent of renal transplant immunogenicity and function.

Background: While prolonged cold ischemia has detrimental effects on graft survival, the mechanisms remain unclear. We tested whether or not cold preservation enhances intragraft inflammatory responses and vascular injury.

Methods: Rat renal grafts were cold preserved in University of Wisconsin solution for 2, 4, 6, 12, 24, and 48 hours, and then transplanted into syngeneic recipients and harvested after 24 hours.

Carotid Artery Stent Placement Prior to Coronary Angioplasty or Coronary Bypass Graft Surgery.

Patients with concomitant carotid and coronary artery disease are at high risk of both cardiac and cerebrovascular complications when they undergo revascularization procedures. The best management strategies for patients with concomitant disease have not been determined for certain. Staged surgical procedures with either coronary artery bypass grafting prior to carotid endarterectomy or vice versa appear to be associated with an increased risk of ischemic complications compared to separate procedures.

Identification and characterization of novel smoothelin isoforms in vascular smooth muscle.

Smoothelin is a cytoskeletal protein specifically expressed in differentiated smooth muscle cells and has been shown to colocalize with smooth muscle alpha actin. In addition to the small smoothelin isoform of 59 kD, we recently identified a large smoothelin isoform of 117 kD. The aim of this study was to identify and characterize novel smoothelin isoforms.

Twins in cardiovascular genetic research.

Twin studies have been largely responsible for showing the effects of genetic variance on a quantitative trait. The model is based on the fact that monozygotic twins share all genes in common, whereas dizygotic twins are related as siblings and share "on average" half their genes. Environmental confounders are minimized because twin children are usually exposed to similar environments.

Sustained ERK phosphorylation is necessary but not sufficient for MMP-9 regulation in endothelial cells: involvement of Ras-dependent and -independent pathways.

Endothelial expression of matrix metalloproteinase-9 (MMP-9), which degrades native type IV collagen, was implicated as a prerequisite for angiogenesis. Therefore, the aim of this study was to determine signaling requirements that regulate MMP-9 expression in endothelial cells. Both, primary and permanent human umbilical vein endothelial cells (HUVEC and ECV304, respectively) were stimulated with phorbol 12-myristate 13-acetate (PMA) and the cytokine tumor necrosis factor-(alpha) (TNF(alpha)) to induce MMP-9 expression.