Frequency of disease-associated and other nuclear autoantibodies in patients of the German Network for Systemic Scleroderma: correlation with characteristic clinical features.

Introduction: In the present study, we analysed in detail nuclear autoantibodies and their associations in systemic sclerosis (SSc) patients included in the German Network for Systemic Scleroderma Registry.

Methods: Sera of 863 patients were analysed according to a standardised protocol including immunofluorescence, immunoprecipitation, line immunoassay and immunodiffusion.

Results: Antinuclear antibodies (ANA) were detected in 94.

Effect of different synthetic membranes on laboratory parameters and survival in chronic haemodialysis patients.

A number of studies suggested that the type of dialysis membrane is associated with differences in long-term outcome of patients undergoing haemodialysis, both in terms of morbidity and mortality. In the majority of dialysis units, synthetic membranes are being used. However, no studies are available so far for comparison between different biocompatible membranes.

High frequency of corticosteroid and immunosuppressive therapy in patients with systemic sclerosis despite limited evidence for efficacy.

Introduction: In systemic sclerosis (SSc) little evidence for the effectiveness of anti-inflammatory and immunosuppressive therapy exists. The objective of this study was to determine the extent to which SSc patients are treated with corticosteroids and immunosuppressive agents.

Methods: Data on duration and dosage of corticosteroids and on the type of immunosuppressive agent were analyzed from 1,729 patients who were registered in the German Network for Systemic Scleroderma (DNSS).

mTOR regulates vascular smooth muscle cell differentiation from human bone marrow-derived mesenchymal progenitors.

Objective: Vascular smooth muscle cells (VSMCs) and circulating mesenchymal progenitor cells (MSCs) with a VSMC phenotype contribute to neointima formation and lumen loss after angioplasty and during allograft arteriosclerosis. We hypothesized that phosphoinositol-Akt-mammalian target of rapamycin-p70S6 kinase (PI3K/Akt/mTOR/p70S6K) pathway activation regulates VSMC differentiation from MSCs.

Methods And Results: We studied effects of PI3K/Akt/mTOR signaling on phenotypic modulation of MSC and VSMC marker expression, including L-type Ca(2+) channels.

Nephroprotective effect of the HMG-CoA-reductase inhibitor cerivastatin in a mouse model of progressive renal fibrosis in Alport syndrome.

Background: Alport syndrome is caused by mutations in genes encoding for the alpha3, alpha4 or alpha5 chain of type IV collagen leading to excessive production of fibrotic tissue and end-stage renal failure. HMG-CoA-reductase-inhibitors exhibit pleiotropic effects by which they modulate the production of connective tissue. The aim of this study was to examine the anti-fibrotic effect of the HMG-CoA-reductase-inhibitor, cerivastatin, in COL4A3 knockout mice, an animal model of Alport syndrome with progressive renal fibrosis.

Rho/Rho kinase pathway regulates maintenance of the differentiated tubular epithelial cell phenotype on laminin-1.

Background: Maintenance of a polarized tubular epithelium by appropriate intracellular signaling and extracellular matrix is critical both in normal renal function as well as in acute and chronic tubular injury. We examined the hypothesis that maintenance of a differentiated epithelial phenotype on the basement membrane glycoprotein laminin-1 is controlled by the Rho/Rho kinase pathway.

Methods: Using the tubular epithelial cell lines LLC-PK1 and MDCK which were cultured on laminin-1 vs.

Nephroprotection by antifibrotic and anti-inflammatory effects of the vasopeptidase inhibitor AVE7688.

Background: Chronic renal disease substantially increases the risk of cardiovascular events and death. Vasopeptidase inhibitors are known to show a strong antihypertensive effect. In the present study, we investigated the nephroprotective potential of the vasopeptidase inhibitor AVE7688 beyond its antihypertensive effects in a mouse model of progressive renal fibrosis.

[Successful treatment of a severe case of idiopathic pulmonary fibrosis with rapamycin].

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive chronic disorder of the lower respiratory tract. The main clinical feature is a progressive shortness of breath, particularly on exercise. An overproduction and deposition of collagen and a proliferation of mesenchymal cells are the histopathologic characteristics.

[The Jo-1 Syndrome--immunological findings and clinical manifestations].

El The Jo-1 syndrome is an autoimmune disease which is characterized by the presence of autoantibodies against the Jo-1 antigen. The designation Jo-1 is derived from the name of the first patient (John P.) who was tested positive for this antibody.

Differential regulation of smooth muscle markers in human bone marrow-derived mesenchymal stem cells.

Objective: To study smooth-muscle differentiation and de-differentiation of human bone marrow-derived mesenchymal stem cells (MSCs), which have been shown to enter the circulation and to contribute to vascular repair and atherosclerosis.

Design: Human MSCs from bone marrow were cultured with 20% fetal calf serum (FCS) or with 10% FCS and various concentrations of dimethyl sulfoxide (DMSO). Expression of smooth muscle markers was determined by Western blot analysis and immunofluorescence.

[Glomerular-type proteinuria in hantavirus nephritis].

Background: Infection with hantavirus of the Puumala type is known to cause severe illness, fever, loin pain and impaired vision. Tubulointerstitial nephritis leads to acute renal failure.

Case Reports: In four patients presenting with hantavirus infection and acute renal failure, proteinuria was analyzed by microelectrophoresis to explore possible causes of renal protein loss in hantavirus nephritis.

Antifibrotic, nephroprotective potential of ACE inhibitor vs AT1 antagonist in a murine model of renal fibrosis.

Background: Several studies have shown antifibrotic effects of angiotensin converting enzyme (ACE) inhibitors as well as of angiotensin receptor 1 (AT1) antagonists, however, prospective trials with clinical end points comparing these effects do not exist. COL4A3-/- mice develop a non-hypertensive progressive renal fibrosis. We used this animal model to compare the potential of ACE inhibitor vs AT1 antagonist to prevent renal fibrosis irrespective of blood pressure-dependent involvement by the renin system.

Preemptive ramipril therapy delays renal failure and reduces renal fibrosis in COL4A3-knockout mice with Alport syndrome.

Background: Alport syndrome (AS) is a common hereditary cause of end-stage renal failure in adolescence due to defects in type IV collagen genes. Molecular genetics allows early diagnosis, however, no preventive strategy can be offered. Using the COL4A3 -/- mouse, an animal model for human AS, we evaluated therapy with ramipril in mice.

P2 receptor antagonist PPADS inhibits mesangial cell proliferation in experimental mesangial proliferative glomerulonephritis.

Background: Although extracellular nucleotides have been shown to confer mitogenic effects in cultured rat mesangial cells through activation of purinergic P2 receptors (P2Y receptors), thus far the in vivo relevance of these findings is unclear. Virtually all cells and in particular the dense granules of platelets contain high levels of nucleotides that are released upon cell injury or platelet aggregation. In experimental mesangial proliferative glomerulonephritis in the rat (anti-Thy1 model), mesangiolysis and glomerular platelet aggregation are followed by a pronounced mesangial cell (MC) proliferative response leading to glomerular hypercellularity.