EXPLORATION AND PREFERENTIAL RANKING OF PATIENT BENEFITS OF MEDICAL DEVICES: A NEW AND GENERIC INSTRUMENT FOR HEALTH ECONOMIC ASSESSMENTS.

Objectives: For medical devices, benefits other than direct clinical effects may have a large impact on the patients' well-being, but a standardized method for measuring these benefits is unavailable. The objective was to explore potential patient benefits provided by medical devices, and to assess the relative preferences of these benefits in the general Swedish population.

Methods: To identify attributes of patient benefit, healthcare personnel within a wide range of disease areas were interviewed.

Association between high-sensitive troponin I and coronary artery calcification in a Danish general population.

Background: High-sensitive troponin I (hs-TnI) is an individual predictor of future cardiovascular disease (CVD). However, the relationship between hs-TnI and coronary artery calcification (CAC) as determined by computed tomography (CT) has not previously been investigated in a general population.

Methods: 1173 randomized, middle-aged subjects without known CVD underwent a non-contrast cardiac-CT scan for CAC determination.

Increased vascularization of shoulder regions of carotid atherosclerotic plaques from patients with diabetes.

Objective: Increased vascularization is considered an important contributing factor for plaque vulnerability. Microvascular proliferative disease in patients with diabetes results in renal damage and visual loss. We assessed the hypothesis that vascularization in carotid atherosclerotic tissue is increased in diabetic patients, especially in the critical shoulder regions of the plaque.

Consistent differences in protein distribution along the longitudinal axis in symptomatic carotid atherosclerotic plaques.

Identifying proteins associated with a complicated atherosclerotic plaque phenotype would provide potential biomarkers for detection of patients at elevated risk for clinically overt disease. We hypothesized that the protein content of carotid atherosclerotic tissue differs between complicated segments located in the internal carotid artery (ICA) and more stable segments in the common carotid artery (CCA). Using differential proteomics, we aimed to identify proteins differentially expressed between these segments of symptomatic carotid plaques.

Erythrocyte sodium-lithium countertransport activity is inversely correlated to adiponectin, retinol binding protein 4 and body height.

Background: We have previously described that the sodium/lithium countertransport (SLC) in the erythrocyte cell membrane is closely linked to obesity and insulin resistance. Adiponectin and retinol-binding protein 4 (RBP-4) are believed to affect obesity and insulin resistance. In the present study, we aimed to further characterize the relationship between SLC, inflammatory markers, adiponectin and RBP-4.

The haptoglobin 2-2 genotype is associated with carotid atherosclerosis in 64-year old women with established diabetes.

Background: Haptoglobin polymorphism generates three common human genotypes: Hp1-1, Hp2-1 and Hp2-2. Among subjects with diabetes, Hp2-2 is associated with an elevated risk to develop cardiovascular disease. The impact of haptoglobin genotype on subclinical carotid atherosclerosis is not known.

Differences in lesion severity and cellular composition between in vivo assessed upstream and downstream sides of human symptomatic carotid atherosclerotic plaques.

Background: The heterogeneous structure of carotid atherosclerotic plaques may be better understood if it is related to blood flow variations, influencing gene expression and cellular functions. Upstream of the maximum stenosis there is laminar blood flow and high shear stress, downstream there is turbulence and low shear stress. We studied if these variations were associated with differences in plaque morphology and composition between sites located up- and downstream of the maximum stenosis in symptomatic carotid plaques.

Soluble urokinase-type plasminogen activator receptor forms in plasma as markers of atherosclerotic plaque vulnerability.

Objectives: : To test if circulating forms of the soluble urokinase-type plasminogen activator receptor (suPAR) are potential biomarkers of plaque vulnerability.

Design And Methods: : Plasma concentrations of suPAR(I-III), suPAR(II-III) and uPAR(I) were measured by time-resolved fluorescence immunoassays in Caucasian patients operated for symptomatic carotid atherosclerosis (n=255). Local suPAR release from plaques into the circulation was assessed in plasma passing retrogradely over the plaque in the carotid artery, collected during surgery (n=7).

Adipose tissue is not an important source for matrix metalloproteinase-9 in the circulation.

Objectives: Matrix metalloproteinase 9 (MMP-9) is overexpressed in atherosclerotic plaques and in many cancers, and has emerged as a potential circulating biomarker for such diseases. However, adipose tissue (AT) might also produce circulating MMP-9, thereby reducing the value of MMP-9 as a biomarker. The aim of this study was to evaluate the impact of AT on circulating MMP-9, and if the metabolic syndrome might have a modifying effect.

Discovery and identification of serine and threonine phosphorylated proteins in activated mast cells: implications for regulation of protein synthesis in the rat basophilic leukemia mast cell line RBL-2H3.

Mast cells are important in allergic inflammation and innate immunity. Antigen-induced activation via cell-surface receptors initiates a series of intracellular signaling events, leading to the secretion of inflammatory mediators. While many of the kinases involved in this process have been defined, their substrates are generally unknown.

Expression of chemokine (C-C motif) ligand 18 in human macrophages and atherosclerotic plaques.

Objective: Using gene expression profiling, we aimed to identify genes that are predominantly expressed in human carotid atherosclerotic plaques. Such genes may be important in atherogenesis and pathophysiology of the plaque, and genes that encode for secreted proteins may be potential biomarkers for atherosclerosis and cardiovascular disease.

Methods: DNA microarray generated expression profiles of human carotid atherosclerotic plaques were compared to expression profiles of 80 different human tissues and cell types, to identify plaque-specific genes.

Urokinase-type plasminogen activator receptor is associated with macrophages and plaque rupture in symptomatic carotid atherosclerosis.

There is a strong correlation between macrophage infiltration and plaque instability in recently symptomatic carotid atherosclerotic plaques, and it is hypothesised that mechanisms related to macrophages may be involved in plaque vulnerability and rupture. We previously found high expression of urokinase-type plasminogen activator receptor (UPAR) in human macrophages. The aim of this study was to investigate whether UPAR co-localises with macrophages in symptomatic carotid plaques, and whether UPAR expression is associated with plaque rupture.

A MUC1 tandem repeat reporter protein produced in CHO-K1 cells has sialylated core 1 O-glycans and becomes more densely glycosylated if coexpressed with polypeptide-GalNAc-T4 transferase.

A recombinant mucin O-glycosylation reporter protein, containing 1.7 tandem repeats (TRs) from the transmembrane mucin MUC1, was constructed. The reporter protein, MUC1(1.

Recombinant MUC1 mucin with a breast cancer-like O-glycosylation produced in large amounts in Chinese-hamster ovary cells.

We have developed an expression system for the production of large quantities of recombinant MUC1 mucin in CHO-K1 (Chinese-hamster ovary K1) cells. The extracellular part of human MUC1, including 16 MUC1 tandem repeats, was produced as a fusion protein with murine IgG Fc, with an intervening enterokinase cleavage site for the removal of the Fc tail. Stable MUC1-IgG-producing CHO-K1 clones were generated and were found to secrete MUC1-IgG into the culture medium.

Two glycosylation alterations of mouse intestinal mucins due to infection caused by the parasite Nippostrongylus brasiliensis.

The glycosylation alterations of mouse small intestinal mucins during a 12-day infectious cycle caused by the parasite Nippostrongylus brasiliensis have been studied. The guanidinium chloride insoluble mucins were isolated at day 0 to 12 from the small intestine of infected and non-infected C57BL/6 mice. The O-linked oligosaccharides were released by reductive beta-elimination from the mucins and separated into neutral, sialylated and sulfated fractions.

The N terminus of the MUC2 mucin forms trimers that are held together within a trypsin-resistant core fragment.

The N terminus of the human MUC2 mucin (amino acids 1-1397) has been expressed as a recombinant tagged protein in Chinese hamster ovary cells. The intracellular form was found to be an endoglycosidase H-sensitive monomer, whereas the secreted form was an oligomer that gave monomers upon disulfide bond reduction. The secreted MUC2 N terminus contained a trypsin-resistant core fragment.

Blood group A glycosyltransferase occurring as alleles with high sequence difference is transiently induced during a Nippostrongylus brasiliensis parasite infection.

Neutral mucin oligosaccharides from the small intestine of control rats and rats infected with the parasite Nippostrongylus brasiliensis were released and analyzed by gas chromatography-mass spectrometry. Infected animals expressed seven blood group A-like structures that were all absent in the control animals. The blood group A nature of these epitopes was confirmed by blood group A reactivity of the prepared mucins, of which Muc2 was one.