A5083908687- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Protease and Inhibitor Mechanisms
- Blood Coagulation and Thrombosis Mechanisms
- Peptidase Inhibition and Analysis
- Hemophilia Treatment and Research
- Enzyme Production and Characterization
- Complement system in diseases
- Enzyme function and inhibition
- Signaling Pathways in Disease
- Cell Adhesion Molecules Research
- Blood properties and coagulation
- Sepsis Diagnosis and Treatment
- Bone and Dental Protein Studies
- Bone Metabolism and Diseases
- Vitamin K Research Studies
- Autoimmune Bullous Skin Diseases
- Organ Transplantation Techniques and Outcomes
- Polysaccharides and Plant Cell Walls
- Biochemical and Structural Characterization
- Electrolyte and hormonal disorders
- Potassium and Related Disorders
- Calpain Protease Function and Regulation
- S100 Proteins and Annexins
- Immune Response and Inflammation
- Mast cells and histamine
University of Oslo
2013-2024
Oslo University Hospital
1992-2014
Norges Blindeforbund
2011
National Hospital for Neurology and Neurosurgery
2001
University College London
2001
Norwegian Cancer Society
2001
Babraham Institute
1999
Nordland Hospital
1996
Dutch Blood Transfusion Society
1996
University of Amsterdam
1996
The cysteine protease legumain is involved in several biological and pathological processes, the has been found over-expressed associated with an invasive metastatic phenotype a number of solid tumors. Consequently, proposed as prognostic marker for certain cancers, potential therapeutic target. Nevertheless, details on how advances malignant progression along regulation its proteolytic activity are unclear. In present work, expression was examined colorectal cancer cell lines. Substantial...
Abstract Background High activity of cysteine proteases such as legumain and the cathepsins have been shown to facilitate growth invasion a variety tumor types. In breast cancer, several recent studies indicated that loss protease inhibitor cystatin E/M leads increased metastasis. Although is normally expressed in skin, its role regulation progression malignant melanoma has not studied. Methods A panel various non-melanoma cell lines was used. Cystatin C were analyzed media by immunoblotting...
Sepsis is a severe infection-induced systemic inflammatory syndrome. Inhibition of downstream mediators sepsis, e.g., TNF-α, has failed in clinical trials. The aim this study was to investigate the effects inhibiting CD14, key upstream innate immunity molecule, on early and hemostatic responses pig model gram-negative sepsis. comprised two arms, whole live Escherichia coli bacteria E. lipopolysaccharide (LPS) (n=25 n=9 animals, respectively). animals were allocated into treatment (antiCD14)...
Objectives. To study clinical and laboratory manifestations of hereditary angio‐oedema (HAE). Subjects. Thirty‐three affected members a kindred 63. Results. Oedematous attacks in the skin, mucous membranes gastrointestinal tract with fluid displacement were elicited by mental physical stress, minor traumas, dental surgical procedures, eruption teeth, tonsillitis, pregnancies, use oestrogen‐containing pills including menopausal substitution. Every adult woman symptomatic HAE ( n =11) showed...
Five patients with hereditary angioedema (HAE) were studied during attacks and remission as healthy controls. The high levels of C1/C1-INH complexes, low C4 ratio activation products (C4bc)/C4 also differed significantly compared to During C4bc/C4 increased (922-2007; P = 0.022, versus attacks, median values throughout), C2 CH50 dropped (111-31%; 0.043 110-36%; 0.016, respectively), TCC (C5b-9) (0.88-1.23 AU/ml; 0.028). Cleavage HK be almost complete (20-90%; 0.009). While factor...
Abstract Macrophages express several lysosomal cysteine proteases such as cathepsins and legumain. In this study, we assessed the expression, activity secretion of legumain in cellular models monocytes/macrophages. were derived from M-CSF- or GM-CSF/IFNγ-stimulated human primary monocytes (M2 M1, respectively), PMA-treated THP-1 cells, murine RAW264.7 macrophages. both monocyte-to-macrophage differentiation caused highly increased expression Also, macrophages, but not monocytes, was...
We developed a live Escherichia coli model of acute sepsis in pigs with emphasize on biomarkers reflecting the early inflammatory response sepsis. Healthy pigs, 25-35 kg, were challenged intravenously (IV) (n = 12) or intrapulmonary 6) E. and observed for 3 5 h respectively. Control received culture medium 6 + 3). Haemodynamic parameters broad panel mediators measured. The dose bacteria was carefully titrated to obtain condition resembling phase human septic shock. IV group displayed...
Bradykinin (BK) is regarded as an important mediator of edema, shock, and inflammation during sepsis. In this study, we evaluated the contribution BK in porcine sepsis by blocking measuring stable metabolite, BK1-5, using anesthetized pigs. The effect alone, efficacy icatibant to block effect, recovery measured plasma BK1-5 were first investigated. Purified injected intravenously induced abrupt fall blood pressure, which was completely prevented pretreatment with icatibant. detected...
Simvastatin, a HMG-CoA reductase inhibitor, is prescribed worldwide to patients with hypercholesterolemia. Although simvastatin well tolerated, side effects like myotoxicity are reported. The mechanism for statin-induced still poorly understood. Reports have suggested impaired mitochondrial dysfunction as contributor the observed myotoxicity. In this regard, we wanted study of on glucose metabolism and activity legumain, cysteine protease. Legumain, being only known asparaginyl...
The cysteine protease legumain is involved in several biological and pathological processes, the has been found over-expressed associated with an invasive metastatic phenotype a number of solid tumors.Consequently, proposed as prognostic marker for certain cancers, potential therapeutic target.Nevertheless, details on how advances malignant progression along regulation its proteolytic activity are unclear.In present work, expression was examined colorectal cancer cell lines.Substantial...
Introduction Right ventricular (RV) myocardial dysfunction is a common feature in septic shock. It can worsen outcome, but the etiology poorly understood. Pulmonary artery hypertension (PAH) plays part pathogenesis of right heart sepsis its importance unknown. In pigs, PAH substantial and translational value porcine models therefore questioned. We hypothesized that causes inflammatory response which leads to independent PAH. Materials methods Sepsis was induced by Escherichia coli-infusion...
Both the coagulation and fibrinolytic cascades generate proteolytic enzymes which appear to be essential for tumor invasion. In present investigation adenocarcinomas normal colon from 14 patients with colorectal cancer were studied by immunohistochemistry. The most striking observation was an enrichment of plasminogen activator inhibitor in tissue, whereas no such immunoreactivity detected biopsies colon. tumor‐host interface characterized a massive accumulation inflammatory cells,...
To investigate the stepwise autophagic-lysosomal processing of hepatocellular proteins, abundant cytosolic enzyme, betaine:homocysteine methyltransferase (BHMT) was used as a probe. Full-length (45 kDa) endogenous BHMT found to be cleaved in an autophagy-dependent (3-methyladenine-sensitive) manner isolated rat hepatocytes generate novel N-terminal 10-kDa fragment (p10) identified and characterized by mass spectrometry. The cleavage site consistent with asparaginyl proteinase, legumain...
Background and aimsWe have previously found increased levels of the cysteine protease legumain in plasma plaques from patients with carotid atherosclerosis. This study further investigated during acute cardiovascular events.MethodsCirculating released platelets were assessed by enzyme-linked-immunosorbent assay. Quantitative PCR immunoblotting used to expression, while localization was visualized immunohistochemistry.ResultsIn SUMMIT Malmö cohort (n = 339 or without type 2 diabetes and/or...
This work investigates the effect of cell-collagen I interactions on synthesis and activation MMP-2, as well MT1-MMP TIMP-1, by using an in vitro model with 3D fibrillar 2D monomeric collagen. In order to reveal whether metastasis-associated protein S100A4 can influence cell's response two forms collagen, osteosarcoma cell lines high low endogenous levels were used. Attachment cells collagen resulted opposite effects MMP-2 activation. decreased proMMP-2, a corresponding reduction MT1-MMP. By...