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Evaluation of original and modified APC-resistance tests in unselected outpatients with clinically suspected thrombosis and in healthy controls

APC-resistance is the most common hereditary condition associated with venous thrombosis. It is in a majority of cases due to a single point mutation in the factor V gene (FVR506Q). Currently used functional APC-resistance tests have 85-90% sensitivity and specificity for the FVR506Q mutation. A modified test which includes predilution of patient plasma in factor V depleted plasma has increased th

The role of cocaine- and amphetamine-regulated transcript in endocrine cells

Type 2 diabetes (T2D) is a metabolic disease characterized by insufficient insulin secretion and insulin resistance. Disturbed beta-cell function is the final culprit that leads to the development of T2D. In addition, impaired incretin effect is likely a part of the pathogenesis of T2D. The aim of this thesis was to study the role of CART in beta-cells and incretin producing L- and K-cells.Endogen

Structural determinants in ApoA-I amyloidogenic variants explain improved cholesterol metabolism despite low HDL levels

Twenty Apolipoprotein A-I (ApoA-I) variants are responsible for a systemic hereditary amyloidosis in which protein fibrils can accumulate in different organs, leading to their failure. Several ApoA-I amyloidogenic mutations are also associated with hypoalphalipoproteinemia, low ApoA-I and high-density lipoprotein (HDL)-cholesterol plasma levels; however, subjects affected by ApoA-I-related amyloid

HpaA is essential for Helicobacter pylori colonization in mice

Infection with the human gastric pathogen Helicobacter pylori can give rise to chronic gastritis, peptic ulcer, and gastric cancer. All H. pylori strains express the surface-localized protein HpaA, a promising candidate for a vaccine against H. pylori infection. To study the physiological importance of HpaA, a mutation of the hpaA gene was introduced into a mouse-adapted H. pylori strain. To justi

The slippery slope of hematopoietic stem cell aging

The late stages of life, in most species including humans, are associated with a decline in the overall maintenance and health of the organism. This applies also to the hematopoietic system, where aging is not only associated with an increased predisposition for hematological malignancies, but also identified as a strong comorbidity factor for other diseases. Research during the last two decades h

A future for facility management

Purpose: This paper aims to discuss the current debates in facility management to understand where the research community is working and where the facility management sector and discipline might be heading. Design/methodology/approach: A review of research outputs has been undertaken to identify research themes. The discussion is based on developments that are already shaping how one should view f

TCP transcription factors link the regulation of genes encoding mitochondrial proteins with the circadian clock in Arabidopsis thaliana

Diurnal regulation of transcripts encoding proteins located in mitochondria, plastids, and peroxisomes is important for adaptation of organelle biogenesis and metabolism to meet cellular requirements. We show this regulation is related to diurnal changes in promoter activities and the presence of specific cis-acting regulatory elements in the proximal promoter region [TGGGC(C/T)], previously defin

Quantitative proteomic analysis of microdissected breast cancer tissues : comparison of label-free and SILAC-based quantification with shotgun, directed, and targeted MS approaches

Quantitative proteomics plays an important role in validation of breast-cancer-related biomarkers. In this study, we systematically compared the performance of label-free quantification (LFQ) and SILAC with shotgun and directed methods for quantifying breast-cancer-related markers in microdissected tissues. We show that LFQ leads to slightly higher coefficient of variation (CV) for protein quantif

Tumour necrosis factor-α/etanercept complexes in serum predict long-term efficacy of etanercept treatment in seronegative rheumatoid arthritis

Objective: To study whether serum levels of tumour necrosis factor-α (TNF-α), free or bound to etanercept, in biological-naïve adults with rheumatoid arthritis (RA) could predict the long-term efficacy of etanercept, measured as drug survival. Method: We identified 145 biological-naïve patients with RA starting treatment with etanercept at the Department of Rheumatology, Skåne University Hospital

Action sequencing in the spontaneous swimming behavior of zebrafish larvae - implications for drug development

All motile organisms need to organize their motor output to obtain functional goals. In vertebrates, natural behaviors are generally composed of a relatively large set of motor components which in turn are combined into a rich repertoire of complex actions. It is therefore an experimental challenge to investigate the organizational principles of natural behaviors. Using the relatively simple locom

Joint modeling of longitudinal autoantibody patterns and progression to type 1 diabetes : results from the TEDDY study

AIMS: The onset of clinical type 1 diabetes (T1D) is preceded by the occurrence of disease-specific autoantibodies. The level of autoantibody titers is known to be associated with progression time from the first emergence of autoantibodies to the onset of clinical symptoms, but detailed analyses of this complex relationship are lacking. We aimed to fill this gap by applying advanced statistical mo

Sex differences in coeliac disease risk: A Swedish sibling design study.

BACKGROUND: For unknown reasons girls are at an increased risk of coeliac disease compared to boys. However, the observed association might be confounded, since maternal coeliac disease is associated with both an increased risk of the disease in first-degree relatives as well as an increased ratio of girls to boys in offspring. AIMS: We investigate the effect of sex on the risk of coeliac dise

Neighborhood deprivation and mortality in individuals with cancer: a multilevel analysis from Sweden.

Little information is available on the effect of neighborhood deprivation on mortality in individuals with cancer. The aim of this study was to investigate the effect of level of neighborhood deprivation on mortality after a wide range of cancer diagnoses. This 1990-2004 follow-up study included all individuals in Sweden aged 25-74 years and used multilevel logistic regression with individual-leve

Challenge-induced plasma exudation and mucinous secretion in human airways

Secretion of mucins and exudation of plasma are distinct processes of importance to innate immunity and inflammatory disease. Yet, little is known about their relation in human airways. The objective of the present study was to use the human nasal airway to determine mucinous secretion and plasma exudation in response to common challenge agents and mediators. Ten healthy volunteers were subjected

Prediction of glaucomatous visual field loss by extrapolation of linear trends.

OBJECTIVE: To investigate how well short-term progression rates can predict long-term visual field outcomes in patients with glaucoma. METHODS: We calculated visual field rates of progression using linear regression analysis of the Visual Field Index (VFI) for 100 consecutive patients with glaucoma having 10 or more Swedish Interactive Thresholding Algorithm standard field tests. Final VFI was pre

Epidermal growth factor receptor status and persistent activation of Akt and p44/42 MAPK pathways correlate with the effect of cetuximab in head and neck and colon cancer cell lines.

OBJECTIVE: The aim of this study was to investigate the effect of epidermal growth factor receptor (EGFR) blockade on cell survival and on downstream signalling pathways using the monoclonal antibody cetuximab. METHODS: We used three colon cancer cell lines, of which one was EGFR-negative, and two head and neck squamous cell carcinoma (HNSCC) lines. EGFR expression and gene copy number were measur

God vård på lika villkor vid hjärtinfarkt i dagens Sverige. Geografiska skillnader i dödlighet utan betyd

I TV-programmet »Uppdrag granskning« påstods nyligen (16 mars 2004) att det är livsviktigt för patienter med akut hjärtinfarkt att bo i närheten av rätt sjukhus. Frågan är när geografiska skillnader i dödlighet blir så pass stora och säkra att de har betydelse för den enskilda patienten. När man studerar skillnader i dödlighet mellan olika sjukhus bör man om möjligt också beakta landstingens roll.It is a known fact that the 1990s brought a decrease in mortality after myocardial infarction in Sweden but that differences in mortality rates following myocardial infarction still remain between the Swedish counties. Unresolved, however, are questions as to what these inter-county differences mean for the individual patient and what role hospital care plays in this context. We analysed all patie

Glutathione peroxidase activity, and content of total and soluble selenium in five bovine and porcine organs used in meat production

Glutathione peroxidase (GSHPx) activity, and total and soluble selenium content were compared in five bovine and porcine organs. The highest GSHPx activity in porcine tissues was found in the liver (35.0 U/g), spleen (29.3 U/g) and kidney (27.3 U/g) with much lower values in the heart (1.8 U/g) and diaphragm (0.8 U/g). A different pattern with lower inter-organ variation in GSHPx activity was obse

Functional studies of human intestinal alkaline sphingomyelinase by deglycosylation and mutagenesis

Intestinal alk-SMase (alkaline sphingomyelinase) is an ectoenzyme related to the NPP (nucleotide phosphodiesterase) family. It has five potential N-glycosylation sites and predicated transmembrane domains at both the N- and C-termini. The amino acid residues forming the two metal-binding sites in NPP are conserved, and those of the active core are modified. We examined the functional changes of th

Ultrathin ZrO2 films on Si-rich SiC(0001)-(3x3): Growth and thermal stability

The growth and thermal stability of ultrathin ZrO2 films on the Si-rich Si(0001)-(3 x 3) surface have been explored using photoelectron spectroscopy (PES) and X-ray absorption spectroscopy (XAS). The films were grown in situ by chemical vapor deposition using the zirconium tetra tert-butoxide (ZTB) precursor. The O 1s XAS results show that growth at 400 degrees C yields tetragonal ZrO2. An interfa