Identification of a cis-acting element which assists in the recruitment of alternative transcription start sites/promoters.

The transcription start sites (TSSs) of the human plasma prekallikrein gene (KLKB1) determined in RNA from kidney are mostly localized within intron 1 and exon 2, suggesting that the region encompassing exon 1, intron 1, and exon 2 comprises an alternative promoter. Reporter gene analyses in HepG2 and immortalized human kidney epithelial cells confirmed a significant transcriptional activity of this putative promoter region. However, when the TSSs recruited for transcription of the reporter gene were determined, only a few transcripts starting within the insert were detected, whereas the majority of TSSs were located in the vector backbone up to about 2000 bp upstream of the insert.

Cellular expression of plasma prekallikrein in human tissues.

Plasma prekallikrein (PPK) is synthesised in hepatocytes and secreted into the blood, where it participates in the surface-dependent activation of blood coagulation, fibrinolysis, kinin generation and inflammation. Recently we demonstrated by quantitative RT-PCR that the human PPK gene is transcribed not only in the liver, but also in various non-hepatic human tissues at significant levels. However, up to now no reliable information is available concerning protein synthesis in the corresponding human tissues.

Kinin receptors in stimulated and characterized decidua tissue-derived cells.

Bradykinin and its kinin B(2) receptor are autocrine and paracrine mediators in foetal membranes and decidua. As a first step we characterized the intracellular morphology of decidual cells. Cultured decidua tissue-derived cells immunolabel for vimentin fibrils, and are considered to be of mesenchymal origin.

Expression of the plasma prekallikrein gene: utilization of multiple transcription start sites and alternative promoter regions.

The plasma prekallikrein gene is expressed in many different human tissues at distinctly different levels and therefore tissue-specific control of the gene transcription is likely. In this study we demonstrate that transcription of the plasma prekallikrein gene can be initiated at multiple sites, for which at least four different promoters are utilized. A comparison of the genomic and mRNA sequences of mouse plasma prekallikrein revealed that the sequence segment that was formerly regarded as the first exon of the mouse plasma prekallikrein gene consists of three exons, with the first exon localized 14.

Contact activation in low-density lipoprotein apheresis systems.

Background: Anaphylactoid reactions due to contact activation have been observed in patients on ACE inhibitor therapy and hemodialysis with negatively charged dialysis membranes. Negatively charged surfaces are functional constituents of different LDL apheresis systems. Therefore, contact activation was investigated during LDL apheresis with three different systems: (i) heparin-induced extracorporeal LDL precipitation (HELP); (ii) dextran sulfate cellulose (DSC) columns; and (iii) modified polyacrylate gels (DALI) in a clinical setting.

Mechanism of kinin release during experimental acute pancreatitis in rats: evidence for pro- as well as anti-inflammatory roles of oedema formation.

1 Kinin B(2) receptor antagonists or tissue kallikrein (t-KK) inhibitors prevent oedema formation and associated sequelae in caerulein-induced pancreatitis in the rat. We have now further investigated the mechanism of kinin generation in the pancreas. 2 Kinins were elevated in the pancreatic tissue already before oedema formation became manifest.

Eluate derived by extracorporal antibody-based immunoadsorption elevates the cytosolic Ca2+ concentration in podocytes via B2 kinin receptors.

Background/aim: Patients with idiopathic focal segmental glomerulosclerosis (FSGS) often develop a recurrence of the disease after kidney transplantation. In a number of FSGS patients, plasmapheresis and immunoadsorption procedures have been shown to transiently reduce proteinuria and are thought to do this by eliminating a circulating factor. Direct cellular effects of eluates from immunoadsorption procedures on podocytes, the primary target of injury in FSGS, have not yet been reported.

The hyaluronan-binding serine protease from human plasma cleaves HMW and LMW kininogen and releases bradykinin.

The influence of the hyaluronan-binding protease (PHBSP), a plasma enzyme with FVII- and pro-urokinase-activating potency, on components of the contact phase (kallikrein/kinin) system was investigated. No activation or cleavage of the proenzymes involved in the contact phase system was observed. The pro-cofactor high molecular weight kininogen (HK), however, was cleaved in vitro by PHBSP in the absence of any charged surface, releasing the activated cofactor and the vasoactive nonapeptide bradykinin.